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Sample records for reproductive toxicity risk

  1. VARIATIONS IN REPRODUCTIVE TOXICANT IDENTIFICATION

    Energy Technology Data Exchange (ETDEWEB)

    Simmons, F

    2008-05-13

    Reproductive toxicants are a very important class of compounds. They present unique hazards to those of child bearing ages, perform their 'dirty work' using a wide variety of mechanisms on a number of different organs, and are regulatorily important. Because of all of this, properly identifying reproductive toxicants is important, but fraught with difficulty. In this paper we will describe types or reproductive toxicants, their importance, and both mistakes and good practices that people who are not experts in reproductive toxicology may use in their attempts to identify them. Additionally, this paper will focus on chemical reproductive toxicants and will not address biological agents that could affect reproductive toxicity although many principles outlined here could be applied to that endeavor.

  2. Test systems to identify reproductive toxicants.

    Science.gov (United States)

    Riecke, K; Stahlmann, R

    2000-09-01

    Experience with drugs and other xenobiotics indicates that both animal testing and epidemiological studies are necessary to provide adequate data for an estimation of risks that might be associated with exposure to a chemical substance. In this review, the pros and cons of test systems for reproductive toxicity are discussed. Usually, several studies are performed to cover the different phases of the reproductive cycle. In the preclinical development of drugs, the three so-called 'segment testing protocols' have been used for several decades now. More recently, new testing concepts have been accepted internationally which include more flexibility in implementation. Several examples of compounds with the potential for reproductive toxicity are presented in more detail in a discussion of some pitfalls of the tests for fertility (phthalates and fluoroquinolones), teratogenicity (acyclovir and protease inhibitors) and postnatal developmental toxicity (fluoroquinolones). In addition, important aspects of kinetics and metabolism as a prerequisite for a rational interpretation of results from toxicological studies are briefly discussed. In vitro assays are useful for supplementing the routinely used in vivo approaches or for studying an expected or defined effect, but they are not suitable for revealing an unknown effect of a chemical on the complex reproductive process.

  3. Use of genomic data in risk assessment case study: I. Evaluation of the dibutyl phthalate male reproductive development toxicity data set

    Energy Technology Data Exchange (ETDEWEB)

    Makris, Susan L., E-mail: makris.susan@epa.gov [U.S. Environmental Protection Agency, National Center for Environmental Assessment, Office of Research and Development, (Mail code 8623P), 1200 Pennsylvania Ave., NW, Washington, DC 20460 (United States); Euling, Susan Y. [U.S. Environmental Protection Agency, National Center for Environmental Assessment, Office of Research and Development, (Mail code 8623P), 1200 Pennsylvania Ave., NW, Washington, DC 20460 (United States); Gray, L. Earl [U.S. Environmental Protection Agency, National Health and Environmental Effects Research Laboratory, Office of Research and Development, (MD-72), Highway 54, Research Triangle Park, NC 27711 (United States); Benson, Robert [U.S. Environmental Protection Agency, Region 8, (Mail code 8P-W), 1595 Wynkoop Street, Denver, CO 80202 (United States); Foster, Paul M.D. [National Toxicology Program, National Institute of Environmental Health Sciences, P.O. Box 12233 (MD K2-12), Research Triangle Park, NC 27709 (United States)

    2013-09-15

    A case study was conducted, using dibutyl phthalate (DBP), to explore an approach to using toxicogenomic data in risk assessment. The toxicity and toxicogenomic data sets relative to DBP-related male reproductive developmental outcomes were considered conjointly to derive information about mode and mechanism of action. In this manuscript, we describe the case study evaluation of the toxicological database for DBP, focusing on identifying the full spectrum of male reproductive developmental effects. The data were assessed to 1) evaluate low dose and low incidence findings and 2) identify male reproductive toxicity endpoints without well-established modes of action (MOAs). These efforts led to the characterization of data gaps and research needs for the toxicity and toxicogenomic studies in a risk assessment context. Further, the identification of endpoints with unexplained MOAs in the toxicity data set was useful in the subsequent evaluation of the mechanistic information that the toxicogenomic data set evaluation could provide. The extensive analysis of the toxicology data set within the MOA context provided a resource of information for DBP in attempts to hypothesize MOAs (for endpoints without a well-established MOA) and to phenotypically anchor toxicogenomic and other mechanistic data both to toxicity endpoints and to available toxicogenomic data. This case study serves as an example of the steps that can be taken to develop a toxicological data source for a risk assessment, both in general and especially for risk assessments that include toxicogenomic data.

  4. Reproductive and developmental toxicity of hydrofluorocarbons used as refrigerants.

    Science.gov (United States)

    Ema, Makoto; Naya, Masato; Yoshida, Kikuo; Nagaosa, Ryuichi

    2010-04-01

    The present paper summarizes data on the reproductive and developmental toxicity of hydrofluorocarbons (HFCs), including pentafluoroethane (HFC-125), 1,1,1,2-tetrafluoroethane (HFC-134a), 1,1,1-trifluoroethane (HFC-143a), 1,1-difluoroethane (HFC-152a), difluoromethane (HFC-32) and 1,1,1,3,3-pentafluoropropane (HFC-245fa), used as refrigerants, published in openly available scientific literature. No developmental toxicity of HFC-125 was found even at 50,000 ppm in rats or rabbits. Although HFC-134a exhibited no dominant lethal effect or reproductive toxicity in rats, it caused low body weight in pre- and postnatal offspring and slightly retarded skeletal ossification in fetuses at 50,000 ppm in rats. No maternal or developmental toxicity was noted after exposure to HFC-143a even at 40,000 ppm in rats or rabbits or HFC-152a even at 50,000 ppm in rats. HFC-32 is slightly maternally and developmentally toxic at 50,000 ppm in rats, but not in rabbits. HFC-245fa caused decreases in maternal body weight and food consumption at 10,000 and 50,000 ppm and fetal weight at 50 000ppm. No evidence of teratogenicity for these HFCs was noted in rats or rabbits. There is limited information about the reproductive toxicity of these HFCs. Animal studies remain necessary for risk assessments of chemicals because it is difficult to find alternative methods to determine the toxic effects of chemicals. It is required to reduce emissions of organic vapors containing HFCs to reduce the risk of exposure. Copyright 2009 Elsevier Inc. All rights reserved.

  5. QSAR models for reproductive toxicity and endocrine disruption in regulatory use – a preliminary investigation

    DEFF Research Database (Denmark)

    Jensen, Gunde Egeskov; Niemelä, Jay Russell; Wedebye, Eva Bay

    2008-01-01

    the new legislation. This article focuses on a screening exercise by use of our own and commercial QSAR models for identification of possible reproductive toxicants. Three QSAR models were used for reproductive toxicity for the endpoints teratogenic risk to humans (based on animal tests, clinical data...... for humans owing to possible developmental toxic effects: Xn (Harmful) and R63 (Possible risk of harm to the unborn child). The chemicals were also screened in three models for endocrine disruption....

  6. Male reproductive organs are at risk from environmental hazards

    DEFF Research Database (Denmark)

    Bonde, Jens Peter

    2010-01-01

    Male reproductive disorders that are of interest from an environmental point of view include sexual dysfunction, infertility, cryptorchidism, hypospadias and testicular cancer. Several reports suggest declining sperm counts and increase of these reproductive disorders in some areas during some time...... are the best documented risk factors for impaired male reproductive function and include physical exposures (radiant heat, ionizing radiation, high frequency electromagnetic radiation), chemical exposures (some solvents as carbon disulfide and ethylene glycol ethers, some pesticides as dibromochloropropane...... reproductive toxicants. New data show that environmental low-level exposure to biopersistent pollutants in the diet may pose a risk to people in all parts of the world. For other toxicants the evidence is only suggestive and further evaluation is needed before conclusions can be drawn. Whether compounds...

  7. Toxicity of compounds with endocrine activity in the OECD 421 reproductive toxicity screening test

    NARCIS (Netherlands)

    Piersma AH; Verhoef A; Elvers LH; Wester PW; LEO; LPI

    1998-01-01

    The issue of endocrine disruption has, in view of human risk assessment, raised the question on whether more sensitive test methods are needed to detect the reproductive toxic properties of xenobiotic compounds with endocrine properties. We studied six known and alleged endocrine disruptors in an

  8. A review of reproductive toxicity of microcystins

    International Nuclear Information System (INIS)

    Chen, Liang; Chen, Jun; Zhang, Xuezhen; Xie, Ping

    2016-01-01

    Highlights: • Reproductive toxicity of MCs on mammals, fishes, amphibians, and birds is reviewed. • PP1/2A inhibition and oxidative stress are important toxic mechanisms of MCs. • Reproductive toxicity of MCs may be closely related to endocrine-disrupting effects. • The trans-generational toxicity of microcystins is a matter of concern. • Data concerning female reproductive and sex-specific effects of MCs are lacking. - Abstract: Animal studies provide strong evidence of positive associations between microcystins (MCs) exposure and reproductive toxicity, representing a threat to human reproductive health and the biodiversity of wild life. This paper reviews current knowledge of the reproductive toxicity of MCs, with regard to mammals, fishes, amphibians, and birds, mostly in males. Toxicity of MCs is primarily governed by the inhibition of protein phosphatases 1 and 2A (PP1 and PP2A) and disturbance of cellular phosphorylation balance. MCs exposure is related to excessive production of reactive oxygen species (ROS) and oxidative stress, leading to cytoskeleton disruption, mitochondria dysfunction, endoplasmic reticulum (ER) stress, and DNA damage. MCs induce cell apoptosis mediated by the mitochondrial and ROS and ER pathways. Through PP1/2A inhibition and oxidative stress, MCs lead to differential expression/activity of transcriptional factors and proteins involved in the pathways of cellular differentiation, proliferation, and tumor promotion. MC-induced DNA damage is also involved in carcinogenicity. Apart from a direct effect on testes and ovaries, MCs indirectly affect sex hormones by damaging the hypothalamic-pituitary-gonad (HPG) axis and liver. Parental exposure to MCs may result in hepatotoxicity and neurotoxicity of offspring. We also summarize the current research gaps which should be addressed by further studies.

  9. A review of reproductive toxicity of microcystins

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Liang, E-mail: chan91@yeah.net [Donghu Experimental Station of Lake Ecosystems, State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072 (China); University of Chinese Academy of Sciences, Beijing 100049 (China); Chen, Jun, E-mail: chenjun@ihb.ac.cn [Donghu Experimental Station of Lake Ecosystems, State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072 (China); Zhang, Xuezhen, E-mail: xuezhen@mail.hzau.edu.cn [College of Fisheries, Huazhong Agricultural University, Freshwater Aquaculture Collaborative Innovation Center of Hubei Province, Wuhan 430070 (China); Xie, Ping, E-mail: xieping@ihb.ac.cn [Donghu Experimental Station of Lake Ecosystems, State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072 (China)

    2016-01-15

    Highlights: • Reproductive toxicity of MCs on mammals, fishes, amphibians, and birds is reviewed. • PP1/2A inhibition and oxidative stress are important toxic mechanisms of MCs. • Reproductive toxicity of MCs may be closely related to endocrine-disrupting effects. • The trans-generational toxicity of microcystins is a matter of concern. • Data concerning female reproductive and sex-specific effects of MCs are lacking. - Abstract: Animal studies provide strong evidence of positive associations between microcystins (MCs) exposure and reproductive toxicity, representing a threat to human reproductive health and the biodiversity of wild life. This paper reviews current knowledge of the reproductive toxicity of MCs, with regard to mammals, fishes, amphibians, and birds, mostly in males. Toxicity of MCs is primarily governed by the inhibition of protein phosphatases 1 and 2A (PP1 and PP2A) and disturbance of cellular phosphorylation balance. MCs exposure is related to excessive production of reactive oxygen species (ROS) and oxidative stress, leading to cytoskeleton disruption, mitochondria dysfunction, endoplasmic reticulum (ER) stress, and DNA damage. MCs induce cell apoptosis mediated by the mitochondrial and ROS and ER pathways. Through PP1/2A inhibition and oxidative stress, MCs lead to differential expression/activity of transcriptional factors and proteins involved in the pathways of cellular differentiation, proliferation, and tumor promotion. MC-induced DNA damage is also involved in carcinogenicity. Apart from a direct effect on testes and ovaries, MCs indirectly affect sex hormones by damaging the hypothalamic-pituitary-gonad (HPG) axis and liver. Parental exposure to MCs may result in hepatotoxicity and neurotoxicity of offspring. We also summarize the current research gaps which should be addressed by further studies.

  10. Development of QSAR models using artificial neural network analysis for risk assessment of repeated-dose, reproductive, and developmental toxicities of cosmetic ingredients.

    Science.gov (United States)

    Hisaki, Tomoka; Aiba Née Kaneko, Maki; Yamaguchi, Masahiko; Sasa, Hitoshi; Kouzuki, Hirokazu

    2015-04-01

    Use of laboratory animals for systemic toxicity testing is subject to strong ethical and regulatory constraints, but few alternatives are yet available. One possible approach to predict systemic toxicity of chemicals in the absence of experimental data is quantitative structure-activity relationship (QSAR) analysis. Here, we present QSAR models for prediction of maximum "no observed effect level" (NOEL) for repeated-dose, developmental and reproductive toxicities. NOEL values of 421 chemicals for repeated-dose toxicity, 315 for reproductive toxicity, and 156 for developmental toxicity were collected from Japan Existing Chemical Data Base (JECDB). Descriptors to predict toxicity were selected based on molecular orbital (MO) calculations, and QSAR models employing multiple independent descriptors as the input layer of an artificial neural network (ANN) were constructed to predict NOEL values. Robustness of the models was indicated by the root-mean-square (RMS) errors after 10-fold cross-validation (0.529 for repeated-dose, 0.508 for reproductive, and 0.558 for developmental toxicity). Evaluation of the models in terms of the percentages of predicted NOELs falling within factors of 2, 5 and 10 of the in-vivo-determined NOELs suggested that the model is applicable to both general chemicals and the subset of chemicals listed in International Nomenclature of Cosmetic Ingredients (INCI). Our results indicate that ANN models using in silico parameters have useful predictive performance, and should contribute to integrated risk assessment of systemic toxicity using a weight-of-evidence approach. Availability of predicted NOELs will allow calculation of the margin of safety, as recommended by the Scientific Committee on Consumer Safety (SCCS).

  11. Reproductive toxicity of carbon nanomaterials: a review

    Science.gov (United States)

    Vasyukova, I.; Gusev, A.; Tkachev, A.

    2015-11-01

    In the current review, we assembled the experimental evidences of an association between carbon nanomaterials including carbon black, graphite nanoplatelets, graphene, single- and multi-walled carbon nanotubes, and fullerene exposure and adverse reproductive and developmental effects, in vitro and in vivo studies. It is shown that carbon nanomaterials reveal toxic effect on reproductive system and offspring development of the animals of various system groups to a certain degree depending on carbon crystal structure. Although this paper provides initial information about the potential male and female reproductive toxicity of carbon nanomaterials, further studies, using characterized nanoparticles, relevant routes of administration, and doses closely reflecting all the expected levels of exposure are needed.

  12. Reproductive toxicity in boron exposed workers in Bandirma, Turkey.

    Science.gov (United States)

    Başaran, Nurşen; Duydu, Yalçin; Bolt, Hermann M

    2012-06-01

    Boric acid and sodium borates have been considered as being "toxic to reproduction and development", following results of animal studies with high doses. However unfavorable effects of boron exposure on reproduction and development have not been proved in epidemiological studies so far. The aim of the present study was to investigate the reproductive toxicity indicators in highly exposed workers employed in a boric acid production plant in Bandırma, Turkey. Two hundred and four workers participated in this study. The mean blood boron concentration of the high exposure group of workers was 223.89 ± 69.49 (152.82-454.02)ng/g. Unfavorable effects of boron exposure on the reproductive toxicity indicators were not observed. Copyright © 2012 Elsevier GmbH. All rights reserved.

  13. Herbs of interest to the Brazilian Federal Government: female reproductive and developmental toxicity studies

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    Luiz Fernando Verissimo

    2011-12-01

    Full Text Available In 2009 the Brazilian Ministry of Health published a document named RENISUS that lists 71 herbs traditionally used in Brazil that could result in phytomedicines to be dispensed by the governmental health care program. This manuscript reviews female reproductive and/or developmental toxicity information of these herbs. More than half (35 of the herbs lack information regarding female reproductive and/or developmental effects. From the fourteen herbs used traditionally to disturb female reproduction, five present experimental data corroborating their actions as abortifacients (Maytenus ilicifolia, Momordica charantia, Plectranthus barbatus, Ruta graveolens or labour facilitator (Bidens pilosa. For 23 of the herbs evaluated experimentally for any type of female reproductive endpoint, only a single study was retrieved and at least twelve of these studies were conducted with a single dose. This scenario suggests that the scientific power of the published information is very low and that a scientifically-based risk/benefit analysis about the use of these herbs during pregnancy is not possible. Considering the appeal that phytomedicines have for pregnant women, usually aware and afraid of the risks that synthetic drugs may have in their pregnancy and progeny, well designed studies evaluating reproductive and/or developmental toxicity of these herbs urge.

  14. Herbs of interest to the Brazilian Federal Government: female reproductive and developmental toxicity studies

    Directory of Open Access Journals (Sweden)

    Luiz Fernando Verissimo

    2011-08-01

    Full Text Available In 2009 the Brazilian Ministry of Health published a document named RENISUS that lists 71 herbs traditionally used in Brazil that could result in phytomedicines to be dispensed by the governmental health care program. This manuscript reviews female reproductive and/or developmental toxicity information of these herbs. More than half (35 of the herbs lack information regarding female reproductive and/or developmental effects. From the fourteen herbs used traditionally to disturb female reproduction, five present experimental data corroborating their actions as abortifacients (Maytenus ilicifolia, Momordica charantia, Plectranthus barbatus, Ruta graveolens or labour facilitator (Bidens pilosa. For 23 of the herbs evaluated experimentally for any type of female reproductive endpoint, only a single study was retrieved and at least twelve of these studies were conducted with a single dose. This scenario suggests that the scientific power of the published information is very low and that a scientifically-based risk/benefit analysis about the use of these herbs during pregnancy is not possible. Considering the appeal that phytomedicines have for pregnant women, usually aware and afraid of the risks that synthetic drugs may have in their pregnancy and progeny, well designed studies evaluating reproductive and/or developmental toxicity of these herbs urge.

  15. Is Boric Acid Toxic to Reproduction in Humans? Assessment of the Animal Reproductive Toxicity Data and Epidemiological Study Results.

    Science.gov (United States)

    Duydu, Yalçın; Başaran, Nurşen; Ustündağ, Aylin; Aydın, Sevtap; Undeğer, Ulkü; Ataman, Osman Yavuz; Aydos, Kaan; Düker, Yalçın; Ickstadt, Katja; Waltrup, Brita Schulze; Golka, Klaus; Bolt, Hermann Maximilian

    2016-01-01

    Boric acid and sodium borates are classified as toxic to reproduction in the CLP Regulation under "Category 1B" with the hazard statement of "H360FD". This classification is based on the reprotoxic effects of boric acid and sodium borates in animal experiments at high doses. However, boron mediated reprotoxic effects have not been proven in epidemiological studies so far. The epidemiological study performed in Bandırma boric acid production plant is the most comprehensive published study in this field with 204 voluntarily participated male workers. Sperm quality parameters (sperm morphology, concentration and motility parameters), FSH, LH and testosterone levels were determined in all participated employees as the reproductive toxicity biomarkers of males. However, boron mediated unfavorable effects on reproduction in male workers have not been determined even in the workers under very high daily boron exposure (0.21 mg B/kg-bw/day) conditions. The NOAEL for rat reproductive toxicity is equivalent to a blood boron level of 2020 ng/g. This level is higher than the mean blood boron concentration (223.89 ± 69.49 ng/g) of the high exposure group workers in Bandırma boric acid production plant (Turkey) by a factor of 9. Accordingly, classifying boric acid and sodium borates under "Category 1B" as "presumed reproductive human toxicant in the CLP regulation seems scientifically not reasonable. The results of the epidemiological studies (including the study performed in China) support for a down-classification of boric acid from the category 1B, H360FD to category 2, H361d, (suspected of damaging the unborn child).

  16. REPRODUCTIVE TOXICITY OF PHTHALATE ESTERS

    Science.gov (United States)

    Phthalate esters display several modes of toxicity in mammalian species. In the rat, in utero exposure at relatively low dosage levels disrupts development of the reproductive system of the male rat by altering fetal testis hormone production. This presentation is a review of t...

  17. QSAR Models for Reproductive Toxicity and Endocrine Disruption Activity

    Directory of Open Access Journals (Sweden)

    Marjan Vračko

    2010-03-01

    Full Text Available Reproductive toxicity is an important regulatory endpoint, which is required in registration procedures of chemicals used for different purposes (for example pesticides. The in vivo tests are expensive, time consuming and require large numbers of animals, which must be sacrificed. Therefore an effort is ongoing to develop alternative In vitro and in silico methods to evaluate reproductive toxicity. In this review we describe some modeling approaches. In the first example we describe the CAESAR model for prediction of reproductive toxicity; the second example shows a classification model for endocrine disruption potential based on counter propagation artificial neural networks; the third example shows a modeling of relative binding affinity to rat estrogen receptor, and the fourth one shows a receptor dependent modeling experiment.

  18. Nickel nanoparticles exposure and reproductive toxicity in healthy adult rats.

    Science.gov (United States)

    Kong, Lu; Tang, Meng; Zhang, Ting; Wang, Dayong; Hu, Ke; Lu, Weiqi; Wei, Chao; Liang, Geyu; Pu, Yuepu

    2014-11-17

    Nickel is associated with reproductive toxicity. However, the reproductive toxicity of nickel nanoparticles (Ni NPs) is unclear. Our goal was to determine the association between nickel nanoparticle exposure and reproductive toxicity. According to the one-generation reproductive toxicity standard, rats were exposed to nickel nanoparticles by gavage and we selected indicators including sex hormone levels, sperm motility, histopathology, and reproductive outcome etc. Experimental results showed nickel nanoparticles increased follicle stimulating hormone (FSH) and luteinizing hormone (LH), and lowered etradiol (E2) serum levels at a dose of 15 and 45 mg/kg in female rats. Ovarian lymphocytosis, vascular dilatation and congestion, inflammatory cell infiltration, and increase in apoptotic cells were found in ovary tissues in exposure groups. For male rats, the weights decreased gradually, the ratio of epididymis weight over body weight increased, the motility of rat sperm changed, and the levels of FSH and testosterone (T) diminished. Pathological results showed the shedding of epithelial cells of raw seminiferous tubule, disordered arrangement of cells in the tube, and the appearance of cell apoptosis and death in the exposure group. At the same time, Ni NPs resulted in a change of the reproductive index and the offspring development of rats. Further research is needed to elucidate exposure to human populations and mechanism of actions.

  19. Nickel Nanoparticles Exposure and Reproductive Toxicity in Healthy Adult Rats

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    Lu Kong

    2014-11-01

    Full Text Available Nickel is associated with reproductive toxicity. However, the reproductive toxicity of nickel nanoparticles (Ni NPs is unclear. Our goal was to determine the association between nickel nanoparticle exposure and reproductive toxicity. According to the one-generation reproductive toxicity standard, rats were exposed to nickel nanoparticles by gavage and we selected indicators including sex hormone levels, sperm motility, histopathology, and reproductive outcome etc. Experimental results showed nickel nanoparticles increased follicle stimulating hormone (FSH and luteinizing hormone (LH, and lowered etradiol (E2 serum levels at a dose of 15 and 45 mg/kg in female rats. Ovarian lymphocytosis, vascular dilatation and congestion, inflammatory cell infiltration, and increase in apoptotic cells were found in ovary tissues in exposure groups. For male rats, the weights decreased gradually, the ratio of epididymis weight over body weight increased, the motility of rat sperm changed, and the levels of FSH and testosterone (T diminished. Pathological results showed the shedding of epithelial cells of raw seminiferous tubule, disordered arrangement of cells in the tube, and the appearance of cell apoptosis and death in the exposure group. At the same time, Ni NPs resulted in a change of the reproductive index and the offspring development of rats. Further research is needed to elucidate exposure to human populations and mechanism of actions.

  20. Reproductive Health Risks Associated with Occupational Exposures to Antineoplastic Drugs in Health Care Settings: A Review of the Evidence

    Science.gov (United States)

    Connor, Thomas H.; Lawson, Christina C.; Polovich, Martha; McDiarmid, Melissa A.

    2015-01-01

    Objectives Antineoplastic drugs are known reproductive and developmental toxicants. Our objective was to review the existing literature of reproductive health risks to workers who handle antineoplastic drugs. Methods A structured literature review of 18 peer-reviewed, English language publications of occupational exposure and reproductive outcomes was performed. Results While effect sizes varied with study size and population, occupational exposure to antineoplastic drugs appears to raise the risk of both congenital malformations and miscarriage. Studies of infertility and time-to-pregnancy also suggested an increased risk for sub-fertility. Conclusions Antineoplastic drugs are highly toxic in patients receiving treatment and adverse reproductive effects have been well documented in these patients. Healthcare workers with chronic, low level occupational exposure to these drugs also appear to have an increased risk of adverse reproductive outcomes. Additional precautions to prevent exposure should be considered. PMID:25153300

  1. Phthalate Esters and Reproductive Toxicity** Presentation requested by State of Mass Use Reductions Committee-TURI

    Science.gov (United States)

    Phthalate esters and reproductive toxicity the presentation described the uses of phthalates, the toxicity to mammals with a focus on reproductive toxicity and the potency of these chemicals to disrupt mammalian reproductive development in utero

  2. Assessment in rats of the reproductive toxicity of gasoline from a gasoline vapor recovery unit.

    Science.gov (United States)

    McKee, R H; Trimmer, G W; Whitman, F T; Nessel, C S; Mackerer, C R; Hagemann, R; Priston, R A; Riley, A J; Cruzan, G; Simpson, B J; Urbanus, J H

    2000-01-01

    Gasoline (CAS 86290-81-5) is one of the world's largest volume commercial products. Although numerous toxicology studies have been conducted, the potential for reproductive toxicity has not been directly assessed. Accordingly, a two-generation reproductive toxicity study in rats was conducted to provide base data for hazard assessment and risk characterization. The test material, vapor recovery unit gasoline (68514-15-8), is the volatile fraction of formulated gasoline and the material with which humans are most likely to come in contact. The study was of standard design. Exposures were by inhalation at target concentrations of 5000, 10 000, and 20 000 mg/m(3). The highest exposure concentration was approximately 50% of the lower explosive limit and several orders of magnitude above anticipated exposure during refueling. There were no treatment-related clinical or systemic effects in the parental animals, and no microscopic changes other than hyaline droplet nephropathy in the kidneys of the male rats. None of the reproductive parameters were affected, and there were no deleterious effects on offspring survival and growth. The potential for endocrine modulation was also assessed by analysis of sperm count and quality as well as time to onset of developmental landmarks. No toxicologically important differences were found. Therefore, the NOAEL for reproductive toxicity in this study was > or =20 000 mg/m(3). The only systemic effects, in the kidneys of the male rats, were consistent with an alpha-2 u-globulin-mediated process. This is a male rat-specific effect and not relevant to human health risk assessment.

  3. Multigeneration reproduction and male developmental toxicity studies on atrazine in rats.

    Science.gov (United States)

    DeSesso, John M; Scialli, Anthony R; White, Tacey E K; Breckenridge, Charles B

    2014-06-01

    Reproductive toxicity of Atrazine (ATR) was evaluated in two rat multigenerational studies. Development of male reproductive parameters was evaluated in separate studies after prenatal or postnatal exposure. In multigenerational studies, rats received dietary concentrations of 0, 10, 50, 100 or 500 ppm ATR. In separate studies in female rats, ATR was administered by gavage at 0, 1, 5, 25 or 125 mg/kg/day during pregnancy (GD6-21) or lactation (LD2-21). Plasma testosterone concentration, testicular and epididymal weights, and sperm counts were measured in male offspring on PND70 and 170. In the multigenerational studies, parental systemic toxicity occurred at 500 ppm (38.7 mg/kg/day), but reproductive endpoints were unaffected. In the prenatal study, maternal toxicity and embryo-fetal mortality occurred at 125 mg/kg/day. In male offspring, testosterone levels and sperm counts were unaffected, although the percentage of abnormal sperm increased at 125 mg/kg/day (PND 70) and 25 mg/kg/day (PND170). In the postnatal study, maternal toxicity and reduced body weights of male offspring occurred at 125 mg/kg/day. Additionally, reduced testicular (PND70, PND170) and epididymal (PND70) weights and increased numbers of abnormal sperm (PND70, PND170) were seen, but no changes in plasma testosterone or sperm counts. Dietary administration of ATR did not affect rat reproduction up to a parentally toxic dose of 38.7 mg/kg/day. Some effects on male reproductive system development occurred after high dose, bolus administration to dams, but doses were much higher than expected under normal use conditions. Thus, oral RfDs for ATR would be protective for reproductive effects. © 2014 Wiley Periodicals, Inc.

  4. Reproductive toxicity assessment of surface water of the Tai section of the Yangtze River, China by in vitro bioassays coupled with chemical analysis

    International Nuclear Information System (INIS)

    Wang Xiaoyi; Wu Jiang; Hao Yingqun; Zhu Bingqing; Shi Wei; Hu Guanjiu; Han Xiaodong; Giesy, John P.; Yu Hongxia

    2011-01-01

    Reproductive toxicity of organic extracts of the surface water from the Tai section of the Yangtze River was assessed by in vitro cytotoxity assays and selected persistent organic pollutants including PCBs, OCPs and PAHs were quantified by instrumental analysis. Eleven of the US EPA priority PAHs were detected. Individual PAHs were found to range from 0.7 to 20 ng/L. Concentrations of BaP did not exceed the national drinking water source quality standard of China. However, a 286-fold concentrated organic extract induced significant reproductive toxicity in adult male rats. The morphology of cells, MTT assay and LDH release assay were all affected by exposure to the organic extracts of water. The results of the reproductive toxicity indicated that PAHs posed the greatest risk of the chemicals studied. The compounds present in the water could be bioconcentrated and result in adverse effects. - Highlights: → Only 11 PAHs of US EPA priority PAHs were detected in surface water the Yangtze River. → Level of BaP didn't exceed national drinking water source quality standard of China. → 286-fold concentrated organic extracts induced great reproductive toxicity in rats. → PAHs posed the greatest risk of the chemicals studied. → The compounds in the water could be bioconcentrated and result in adverse effects. - In vitro bioassay responses observed in Yangtze River source water extracts showed great reproductive toxicity, and PAHs were responsible.

  5. Acute toxicity of Fenvalerate Induced Alteration in Metabolic and Reproductive Hormones of Rats

    International Nuclear Information System (INIS)

    Aly, M.A.S.; El Arab, E.A.

    1999-01-01

    The acute toxic effect of fenvalerate-a synthetic pyrethroid insecticide currently used in agriculture practice-on metabolic and reproductive hormones of rats had been studied. Intragastric administration of fen valerate (45 mg/kg) to male rats provoked a statistically significant decrease in T 3 and T 4 concentration during the setup regimen; the maximum decrease was recorded at 6 h. On the other hand, the reproductive hormones; LH, FSH and prolactin showed progressive increase in their values associated with a decrease in testosterone levels. The highest effect of fenvalerate on reproductive hormones was recorded at 24 h, followed by slight recovery at 48 h. In the future, measurement of such hormones might be included in any toxicology program for the risk assessment of synthetic pyrethroid insecticides if they should be mitigated or avoided

  6. Development and validation of an OECD reproductive toxicity test guideline with the mudsnail Potamopyrgus antipodarum (Mollusca, Gastropoda)

    DEFF Research Database (Denmark)

    Ruppert, Katharina; Geiß, Cornelia; Askem, Clare

    2017-01-01

    Mollusks are known to be uniquely sensitive to a number of reproductive toxicants including some vertebrate endocrine disrupting chemicals. However, they have widely been ignored in environmental risk assessment procedures for chemicals. This study describes the validation of the Potamopyrgus ant...

  7. Assessing reproductive toxicity of two environmental toxicants with a novel in vitro human spermatogenic model

    Directory of Open Access Journals (Sweden)

    Charles A. Easley, IV

    2015-05-01

    Full Text Available Environmental influences and insults by reproductive toxicant exposure can lead to impaired spermatogenesis or infertility. Understanding how toxicants disrupt spermatogenesis is critical for determining how environmental factors contribute to impaired fertility. While current animal models are available, understanding of the reproductive toxic effects on human fertility requires a more robust model system. We recently demonstrated that human pluripotent stem cells can differentiate into spermatogonial stem cells/spermatogonia, primary and secondary spermatocytes, and haploid spermatids; a model that mimics many aspects of human spermatogenesis. Here, using this model system, we examine the effects of 2-bromopropane (2-BP and 1,2,dibromo-3-chloropropane (DBCP on in vitro human spermatogenesis. 2-BP and DBCP are non-endocrine disrupting toxicants that are known to impact male fertility. We show that acute treatment with either 2-BP or DBCP induces a reduction in germ cell viability through apoptosis. 2-BP and DBCP affect viability of different cell populations as 2-BP primarily reduces spermatocyte viability, whereas DBCP exerts a much greater effect on spermatogonia. Acute treatment with 2-BP or DBCP also reduces the percentage of haploid spermatids. Both 2-BP and DBCP induce reactive oxygen species (ROS formation leading to an oxidized cellular environment. Taken together, these results suggest that acute exposure with 2-BP or DBCP causes human germ cell death in vitro by inducing ROS formation. This system represents a unique platform for assessing human reproductive toxicity potential of various environmental toxicants in a rapid, efficient, and unbiased format.

  8. Reproductive toxicity: Male and female reproductive systems as targets for chemical injury

    Energy Technology Data Exchange (ETDEWEB)

    Mattison, D.R.; Plowchalk, D.R.; Meadows, M.J.; Al-Juburi, A.Z.; Gandy, J.; Malek, A. (Univ. of Arkansas for Medical Sciences, Little Rock (USA))

    1990-03-01

    On the basis of current knowledge of reproductive biology and toxicology, it is apparent that chemicals affecting reproduction may elicit their effects at a number of sites in both the male and the female reproductive system. This multiplicity of targets is attributable to the dynamic nature of the reproductive system, in which the hypothalamic-pituitary-gonadal axis is controlled by precise positive and negative feedback mechanisms among its components. Interference by a xenobiotic at any level in either the male or the female reproductive system may ultimately impair hypothalamic or pituitary function. Normal gonadal processes such as spermatogenesis or oogenesis, ejaculation or ovulation, hormone production by Leydig or granulosa cells, and the structure or function of the accessory reproductive structures (e.g., epididymis, fallopian tube) also appear vulnerable to xenobiotics. The reproductive system is a complex one that requires local and circulating hormones for control. This brief review illustrates a system for characterizing the mechanism of action of reproductive toxicants, as well as for defining the sites available for disruption of reproduction. Unfortunately, at present, data addressing the actual vulnerability of reproduction are sorely lacking. However, when experiments have been conducted and combined with epidemiologic data or clinical observation, it has been possible to demonstrate impairment of reproductive processes by xenobiotics. The role of environmental exposure to xenobiotics in the increase in infertility that has been observed remains to be defined. 87 references.

  9. Oral repeated-dose systemic and reproductive toxicity of 6:2 fluorotelomer alcohol in mice

    Directory of Open Access Journals (Sweden)

    Pushkor Mukerji

    2015-01-01

    Full Text Available 6:2 fluorotelomer alcohol (6:2 FTOH was evaluated for potential systemic repeated-dose and reproductive toxicity in mice. 6:2 FTOH was administered by oral gavage to CD-1 mice as a suspension in 0.5% aqueous methylcellulose with 0.1% Tween-80 at dosages of 1, 5, 25, or 100 mg/kg/day. The no-observed-adverse-effect level (NOAEL for systemic toxicity was 25 mg/kg/day (males and 5 mg/kg/day (females, based on effects at higher doses on mortality, clinical observations, body weight, nutritional parameters, hematology (red and white blood cell, clinical chemistry (liver-related, liver weights, and histopathology (liver, teeth, reproductive tract, and mammary gland. However, 6:2 FTOH was not a selective reproductive toxicant. The NOAEL for reproductive toxicity was >100 mg/kg/day; no effects on reproductive outcome were observed at any dosage. The NOAEL for viability and growth of the offspring was 25 mg/kg/day, based on clinical signs of delayed maturation in pups, and reductions in pup survival and pup body weight during lactation at 100 mg/kg/day. While the severity of the effects was generally greater in mice than previously reported in CD rats, the overall NOAELs were identical in both species, 5 mg/kg/day for systemic toxicity and 25 mg/kg/day for offspring viability/growth. 6:2 FTOH was not a selective reproductive toxicant in either species; no effects on reproductive outcome occurred at any dose level, and any effects observed in offspring occurred at dose levels that induced mortality and severe toxicity in maternal animals.

  10. Development and validation of OECD test guidelines on mollusc reproductive toxicity tests

    DEFF Research Database (Denmark)

    Lagadic, Laurent; Holbech, Henrik; hutchinson, tom

    the comparison of endpoints relevant for reproduction in invertebrates often shows a much higher sensitivity in molluscs vs. e.g. daphnids. The OECD test guideline programme has thus been extended to cover reproduction effects of chemicals in molluscs. Existing mollusc toxicity test protocols have been reviewed...... in an OECD Detailed Review Paper that identifies two relevant candidate species for developing freshwater tests: Potamopyrgus antipodarum and Lymnaea stagnalis. However, this review did not clarify which toxicity test design/conditions are the most appropriate for chemicals assessment. Therefore, a mollusc...... reproduction test guideline will be developed describing partial- and full- life-cycle test protocols in these species, so as to propose a balanced suite of apical mollusc toxicity tests applicable for the assessment of any type of chemical, including endocrine disruptors, as level 4 and 5 assays of the EDTA...

  11. Developmental and reproductive toxicity of inorganic arsenic: animal studies and human concerns.

    Science.gov (United States)

    Golub, M S; Macintosh, M S; Baumrind, N

    1998-01-01

    Information on the reproductive and developmental toxicity of inorganic arsenic is available primarily from studies in animals using arsenite and arsenate salts and arsenic trioxide. Inorganic arsenic has been extensively studied as a teratogen in animals. Data from animal studies demonstrate that arsenic can produce developmental toxicity, including malformation, death, and growth retardation, in four species (hamsters, mice, rats, rabbits). A characteristic pattern of malformations is produced, and the developmental toxicity effects are dependent on dose, route, and the day of gestation when exposure occurs. Studies with gavage and diet administration indicate that death and growth retardation are produced by oral arsenic exposure. Arsenic is readily transferred to the fetus and produces developmental toxicity in embryo culture. Animal studies have not identified an effect of arsenic on fertility in males or females. When females were dosed chronically for periods that included pregnancy, the primary effect of arsenic on reproduction was a dose-dependent increase in conceptus mortality and in postnatal growth retardation. Human data are limited to a few studies of populations exposed to arsenic from drinking water or from working at or living near smelters. Associations with spontaneous abortion and stillbirth have been reported in more than one of these studies, but interpretation of these studies is complicated because study populations were exposed to multiple chemicals. Thus, animal studies suggest that environmental arsenic exposures are primarily a risk to the developing fetus. In order to understand the implications for humans, attention must be given to comparative pharmacokinetics and metabolism, likely exposure scenarios, possible mechanisms of action, and the potential role of arsenic as an essential nutrient.

  12. Perspective on a Modified Developmental and Reproductive Toxicity Testing Strategy for Cancer Immunotherapy.

    Science.gov (United States)

    Prell, Rodney A; Halpern, Wendy G; Rao, Gautham K

    2016-05-01

    The intent of cancer immunotherapy (CIT) is to generate and enhance T-cell responses against tumors. The tumor microenvironment establishes several inhibitory pathways that lead to suppression of the local immune response, which is permissive for tumor growth. The efficacy of different CITs, alone and in combination, stems from reinvigorating the tumor immune response via several mechanisms, including costimulatory agonists, checkpoint inhibitors, and vaccines. However, immune responses to other antigens (self and foreign) may also be enhanced, resulting in potentially undesired effects. In outbred mammalian pregnancies, the fetus expresses paternally derived alloantigens that are recognized as foreign by the maternal immune system. If unchecked or enhanced, maternal immunity to these alloantigens represents a developmental and reproductive risk and thus is a general liability for cancer immunotherapeutic molecules. We propose a tiered approach to confirm this mechanistic reproductive liability for CIT molecules. A rodent allopregnancy model is based on breeding 2 different strains of mice so that paternally derived alloantigens are expressed by the fetus. When tested with a cross-reactive biotherapeutic, small molecule drug, or surrogate molecule, this model should reveal on-target reproductive liabilities if the pathway is involved in maintaining pregnancy. Alternatively, allopregnancy models with genetically modified mice can be interrogated for exquisitely specific biotherapeutics with restricted species reactivity. The allopregnancy model represents a relatively straightforward approach to confirm an expected on-target reproductive risk for CIT molecules. For biotherapeutics, it could potentially replace more complex developmental and reproductive toxicity testing in nonhuman primates when a pregnancy hazard is confirmed or expected. © The Author(s) 2016.

  13. 40 CFR 799.9355 - TSCA reproduction/developmental toxicity screening test.

    Science.gov (United States)

    2010-07-01

    ... developmental defects should not be used. Healthy virgin animals, not subjected to previous experimental..., except legal holidays. (1) OECD (1995). Reproduction/Developmental Toxicity Screening Test, OECD 421...

  14. Development of a male reproductive toxicity assay for evaluating the success of bioremediation

    International Nuclear Information System (INIS)

    Schrock, E.J.; Bantle, J.A.

    1995-01-01

    The Eglin Air Force Base was contaminated with JP-4 over 10 years ago. The project goal was to develop and evaluate male reproductive toxicity testing procedures and endpoints using the gametes of the South African clawed frog Xenopus laevis with particular emphasis on assessing the toxicity of contaminated soil from Eglin Air Force Base in Florida. Reproductive toxicity tests were done to evaluate several different locations within the original spill area. Specific sites were selected based on their location to the spill site. The site was evaluated before and after remediation. Before remediation, the males were exposed to the JP-4 orally for 73 days, with the contaminant injected into the food source. After remediation, the males were directly exposed to the contaminated soil samples for 60 days. The endpoints measured in both studies were: change in body weight, organ to body weight ratios, sperm counts, number of malformed sperm, and sperm motility. In both the pre and post remediation studies, there were no significant effects on body weight or organ weight data at the p ≤ 0.05 level. However, there were effects seen in sperm count and morphology. The male reproductive toxicity assay under development has given useful information in initially determining the reproductive toxicity of JP-4. Significant effects were seen in both the pre and post remediation direct exposure tests, indicating that the direct exposure route may be the most promising for future testing

  15. Reproductive and developmental toxicology

    National Research Council Canada - National Science Library

    Gupta, Ramesh C

    2011-01-01

    .... With a special focus on placental toxicity, this book is the only available reference to connect the three key risk stages, and is the only resource to include reproductive and developmental toxicity in domestic animals, fish, and wildlife.

  16. Toxicity of Nanoparticles on the Reproductive System in Animal Models: A Review.

    Science.gov (United States)

    Brohi, Rahim Dad; Wang, Li; Talpur, Hira Sajjad; Wu, Di; Khan, Farhan Anwar; Bhattarai, Dinesh; Rehman, Zia-Ur; Farmanullah, F; Huo, Li-Jun

    2017-01-01

    In the last two decades, nanotechnologies demonstrated various applications in different fields, including detection, sensing, catalysis, electronics, and biomedical sciences. However, public concerns regarding the well-being of human may hinder the wide utilization of this promising innovation. Although, humans are exposed to airborne nanosized particles from an early age, exposure to such particles has risen dramatically within the last century due to anthropogenic sources of nanoparticles. The wide application of nanomaterials in industry, consumer products, and medicine has raised concerns regarding the potential toxicity of nanoparticles in humans. In this review, the effects of nanomaterials on the reproductive system in animal models are discussed. Females are particularly more vulnerable to nanoparticle toxicity, and toxicity in this population may affect reproductivity and fetal development. Moreover, various types of nanoparticles have negative impacts on male germ cells, fetal development, and the female reproductive system. These impacts are associated with nanoparticle modification, composition, concentration, route of administration, and the species of the animal. Therefore, understanding the impacts of nanoparticles on animal growth and reproduction is essential. Many studies have examined the effects of nanoparticles on primary and secondary target organs, with a concentration on the in vivo and in vitro effects of nanoparticles on the male and female reproductive systems at the clinical, cellular, and molecular levels. This review provides important information regarding organism safety and the potential hazards of nanoparticle use and supports the application of nanotechnologies by minimizing the adverse effects of nanoparticles in vulnerable populations.

  17. Review of reproductive and developmental toxicity induced by organotins in aquatic organisms and experimental animals

    Energy Technology Data Exchange (ETDEWEB)

    Hirose, A.; Takagi, A.; Nishimura, T.; Kanno, J.; Ema, M. [National Inst. of Health Sciences, Tokyo (Japan)

    2004-09-15

    Widespread use of organotins has caused increasing amounts to be released into the environment. The most important non-pesticidal route of entry of organotins into the environment is through leaching of organotin-stabilized PVC in water, and the use in antifouling agents, resulting in the introduction of organotin into the aquatic environment. Data are available regarding the detection of butyltins and phenyltins in aquatic marine organisms and marine products. Food chain bioamplification of butyltin in oysters, mud crabs, marine mussels, chinook salmons, dolphins, tunas, and sharks and of phenyltin in carps and horseshoe crabs has been reported. These findings indicate that organotins accumulate in the food chain and are bioconcentrated, and that humans can be exposed to organotins via seafood. The levels of organotin compounds in seafood are not considered to be sufficiently high to affect human health. However, Belfroid et al. (2000) noted that more research on residual TBT levels in seafood was needed before a definitive conclusion on possible health risks could be drawn. Although the toxicity of organotins has been extensively reviewed, the reproductive and developmental toxicity of organotins is not well understood. We summarized the data of the studies on reproductive and developmental toxicity of organotins in aquatic organisms and experimental animals.

  18. Analysis of reproductive toxicity and classification of glufosinate-ammonium.

    Science.gov (United States)

    Schulte-Hermann, Rolf; Wogan, Gerald N; Berry, Colin; Brown, Nigel A; Czeizel, Andrew; Giavini, Erminio; Holmes, Lewis B; Kroes, Robert; Nau, Heinz; Neubert, Diether; Oesch, Franz; Ott, Tilmann; Pelkonen, Olavi; Robert-Gnansia, Elisabeth; Sullivan, Frank M

    2006-04-01

    CONCLUSION REGARDING CLASSIFICATION OF GLUFOSINATE-AMMONIUM: Science Partners' Evaluation Group (Evaluation Group) has conducted an independent analysis of the herbicide glufosinate-ammonium (GA) relative to its potential to cause reproductive toxicity in humans. Further, the Evaluation Group has evaluated the implementation of Annex 6 of Commission Directive 2001/59/EC (28th ATP of Council Directive 67/548/EEC) and Council Directive 91/414/EEC, with respect to classification of chemicals posing potential reproductive hazards. After consideration of all information available to us relevant to the potential of glufosinate-ammonium (GA) to cause reproductive toxicity, the Science Partners Evaluation Group concludes that no classification of GA is justified. The following form the basis of this conclusion. There are no human data to suggest that GA causes reproductive toxicity in women or in their conceptus. The issue concerning possible reproductive hazard to humans is raised solely on the basis of positive animal test results that show GA to cause preimplantation or implantation losses in rats. SPECIFICALLY: a. Daily treatment with GA had no detectable effect on the earliest stages of the reproductive sequence including gametogenesis, ovulation, mating and conception; b. Treatment with GA interfered with rat gestation before and at the stage when the conceptus implants into the uterus. This effect occurred at doses of 360 ppm in the feed (corresponding to daily doses of 27.8 mg/kg bw) and above; and c. After implantation, no further effect of GA on prenatal and post-natal development was recognized. Previous concerns that GA might be toxic to embryonic stages after implantation were not supported by the data. Abortions and stillbirth seen were associated with, and regarded as secondary to, maternal toxicity. There was no evidence suggesting the induction of malformations in the offspring. The mechanism underlying this adverse effect in experimental laboratory

  19. A high-throughput method for assessing chemical toxicity using a Caenorhabditis elegans reproduction assay

    International Nuclear Information System (INIS)

    Boyd, Windy A.; McBride, Sandra J.; Rice, Julie R.; Snyder, Daniel W.; Freedman, Jonathan H.

    2010-01-01

    The National Research Council has outlined the need for non-mammalian toxicological models to test the potential health effects of a large number of chemicals while also reducing the use of traditional animal models. The nematode Caenorhabditis elegans is an attractive alternative model because of its well-characterized and evolutionarily conserved biology, low cost, and ability to be used in high-throughput screening. A high-throughput method is described for quantifying the reproductive capacity of C. elegans exposed to chemicals for 48 h from the last larval stage (L4) to adulthood using a COPAS Biosort. Initially, the effects of exposure conditions that could influence reproduction were defined. Concentrations of DMSO vehicle ≤ 1% did not affect reproduction. Previous studies indicated that C. elegans may be influenced by exposure to low pH conditions. At pHs greater than 4.5, C. elegans reproduction was not affected; however below this pH there was a significant decrease in the number of offspring. Cadmium chloride was chosen as a model toxicant to verify that automated measurements were comparable to those of traditional observational studies. EC 50 values for cadmium for automated measurements (176-192 μM) were comparable to those previously reported for a 72-h exposure using manual counting (151 μM). The toxicity of seven test toxicants on C. elegans reproduction was highly correlative with rodent lethality suggesting that this assay may be useful in predicting the potential toxicity of chemicals in other organisms.

  20. Toxicity of Nanoparticles on the Reproductive System in Animal Models: A Review

    Science.gov (United States)

    Brohi, Rahim Dad; Wang, Li; Talpur, Hira Sajjad; Wu, Di; Khan, Farhan Anwar; Bhattarai, Dinesh; Rehman, Zia-Ur; Farmanullah, F.; Huo, Li-Jun

    2017-01-01

    In the last two decades, nanotechnologies demonstrated various applications in different fields, including detection, sensing, catalysis, electronics, and biomedical sciences. However, public concerns regarding the well-being of human may hinder the wide utilization of this promising innovation. Although, humans are exposed to airborne nanosized particles from an early age, exposure to such particles has risen dramatically within the last century due to anthropogenic sources of nanoparticles. The wide application of nanomaterials in industry, consumer products, and medicine has raised concerns regarding the potential toxicity of nanoparticles in humans. In this review, the effects of nanomaterials on the reproductive system in animal models are discussed. Females are particularly more vulnerable to nanoparticle toxicity, and toxicity in this population may affect reproductivity and fetal development. Moreover, various types of nanoparticles have negative impacts on male germ cells, fetal development, and the female reproductive system. These impacts are associated with nanoparticle modification, composition, concentration, route of administration, and the species of the animal. Therefore, understanding the impacts of nanoparticles on animal growth and reproduction is essential. Many studies have examined the effects of nanoparticles on primary and secondary target organs, with a concentration on the in vivo and in vitro effects of nanoparticles on the male and female reproductive systems at the clinical, cellular, and molecular levels. This review provides important information regarding organism safety and the potential hazards of nanoparticle use and supports the application of nanotechnologies by minimizing the adverse effects of nanoparticles in vulnerable populations. PMID:28928662

  1. Toxicity of Nanoparticles on the Reproductive System in Animal Models: A Review

    Directory of Open Access Journals (Sweden)

    Rahim Dad Brohi

    2017-09-01

    Full Text Available In the last two decades, nanotechnologies demonstrated various applications in different fields, including detection, sensing, catalysis, electronics, and biomedical sciences. However, public concerns regarding the well-being of human may hinder the wide utilization of this promising innovation. Although, humans are exposed to airborne nanosized particles from an early age, exposure to such particles has risen dramatically within the last century due to anthropogenic sources of nanoparticles. The wide application of nanomaterials in industry, consumer products, and medicine has raised concerns regarding the potential toxicity of nanoparticles in humans. In this review, the effects of nanomaterials on the reproductive system in animal models are discussed. Females are particularly more vulnerable to nanoparticle toxicity, and toxicity in this population may affect reproductivity and fetal development. Moreover, various types of nanoparticles have negative impacts on male germ cells, fetal development, and the female reproductive system. These impacts are associated with nanoparticle modification, composition, concentration, route of administration, and the species of the animal. Therefore, understanding the impacts of nanoparticles on animal growth and reproduction is essential. Many studies have examined the effects of nanoparticles on primary and secondary target organs, with a concentration on the in vivo and in vitro effects of nanoparticles on the male and female reproductive systems at the clinical, cellular, and molecular levels. This review provides important information regarding organism safety and the potential hazards of nanoparticle use and supports the application of nanotechnologies by minimizing the adverse effects of nanoparticles in vulnerable populations.

  2. Toxicity testing of human assisted reproduction devices using the mouse embryo assay.

    NARCIS (Netherlands)

    Punt-Van der Zalm, J.P.; Hendriks, J.C.M.; Westphal, J.R.; Kremer, J.A.M.; Teerenstra, S.; Wetzels, A.M.M.

    2009-01-01

    Systems to assess the toxicity of materials used in human assisted reproduction currently lack efficiency and/or sufficient discriminatory power. The development of 1-cell CBA/B6 F1 hybrid mouse embryos to blastocysts, expressed as blastocyst rate (BR), is used to measure toxicity. The embryos were

  3. Evaluating chemical and other agent exposures for reproductive and developmental toxicity

    National Research Council Canada - National Science Library

    Subcommittee on Reproductive and Developmental Toxicity, Committee on Toxicology, Board on Environmental Studies and Toxicology, National Research Council

    2001-01-01

    .... As part of its efforts to reduce or eliminate exposure of Naval personnel and their families to reproductive and developmental toxicants, the Navy requested that the National Research Council (NRC...

  4. Cancer and reproductive risks in the semiconductor industry.

    Science.gov (United States)

    LaDou, Joseph; Bailar, John C

    2007-01-01

    Although many reproductive toxicants and carcinogens are used in the manufacture of semiconductor chips, and worrisome findings have been reported, no broad epidemiologic study has been conducted to define possible risks in a comprehensive way. With few exceptions, the American semiconductor industry has not supported access for independent studies. Older technologies are exported to newly industrialized countries as newer technologies are installed in Japan, the United States, and Europe. Thus there is particular concern about the many workers, mostly in countries that are still industrializing, who have jobs that use chemicals, technologies, and equipment that are no longer in use in developed countries. Since most countries lack cancer registries and have inadequate reproductive and cancer reporting mechanisms, industry efforts to control exposures to carcinogens are of particular importance. Government agencies, the courts, industry, publishers, and academia, on occasion, collude to ignore or to downplay the importance of occupational diseases. Examples of how this happens in the semiconductor industry are presented.

  5. Sodium arsenite-induced reproductive toxicities in male Wistar rats ...

    African Journals Online (AJOL)

    Sodium arsenite-induced reproductive toxicities in male Wistar rats: role of Tridax procumbens leaf extract. ... Bulletin of Animal Health and Production in Africa ... In the present study, the effects of ethanol leaf extract of Tridax procumbens ... in Groups B to D as compared to Group A was significantly reduced (p<0.05).

  6. NTP-CERHR expert panel report on the reproductive anddevelopmental toxicity of hydroxyurea

    Energy Technology Data Exchange (ETDEWEB)

    Liebelt, E.L.; Balk, S.J.; Faber, W.; Fisher, J.W.; Hughes, C.L.; Lanzkron, S.M.; Lewis, K.M.; Marchetti, F.; Mehendale, H.M.; Rogers,J.M.; Shad, A.T.; Skalko, R.G.; Stanek, E.J.

    2007-01-01

    The National Toxicology Program (NTP) and the National Institute of Environmental Health Sciences (NIEHS) established the NTP Center for the Evaluation of Risks to Human Reproduction (CERHR) in June 1998. The purpose of CERHR is to provide timely, unbiased, scientifically sound evaluations of human and experimental evidence for adverse effects on reproduction and development caused by agents to which humans may be exposed. Hydroxyurea was selected for evaluation by a CERHR expert panel because of (1) its increasing use in the treatment of sickle cell disease in children and adults, (2) knowledge that it inhibits DNA synthesis and is cytotoxic, and (3) published evidence of its reproductive and developmental toxicity in rodents. Hydroxyurea is FDA-approved for reducing the frequency of painful crises and the need for blood transfusions in adults with sickle cell anemia who experience recurrent moderate-to-severe crises. Hydroxyurea is used in the treatment of cancer, sickle cell disease, and thalassemia. It is the only treatment for sickle cell disease aside from blood transfusion used in children. Hydroxyurea may be used in the treatment of children and adults with sickle cell disease for an extended period of time or for repeated cycles of therapy. Treatment with hydroxyurea may be associated with cytotoxic and myelosuppressive effects, and hydroxyurea is mutagenic.

  7. Optimizing the design of a reproduction toxicity test with the pond snail Lymnaea stagnalis.

    Science.gov (United States)

    Charles, Sandrine; Ducrot, Virginie; Azam, Didier; Benstead, Rachel; Brettschneider, Denise; De Schamphelaere, Karel; Filipe Goncalves, Sandra; Green, John W; Holbech, Henrik; Hutchinson, Thomas H; Faber, Daniel; Laranjeiro, Filipe; Matthiessen, Peter; Norrgren, Leif; Oehlmann, Jörg; Reategui-Zirena, Evelyn; Seeland-Fremer, Anne; Teigeler, Matthias; Thome, Jean-Pierre; Tobor Kaplon, Marysia; Weltje, Lennart; Lagadic, Laurent

    2016-11-01

    This paper presents the results from two ring-tests addressing the feasibility, robustness and reproducibility of a reproduction toxicity test with the freshwater gastropod Lymnaea stagnalis (RENILYS strain). Sixteen laboratories (from inexperienced to expert laboratories in mollusc testing) from nine countries participated in these ring-tests. Survival and reproduction were evaluated in L. stagnalis exposed to cadmium, tributyltin, prochloraz and trenbolone according to an OECD draft Test Guideline. In total, 49 datasets were analysed to assess the practicability of the proposed experimental protocol, and to estimate the between-laboratory reproducibility of toxicity endpoint values. The statistical analysis of count data (number of clutches or eggs per individual-day) leading to ECx estimation was specifically developed and automated through a free web-interface. Based on a complementary statistical analysis, the optimal test duration was established and the most sensitive and cost-effective reproduction toxicity endpoint was identified, to be used as the core endpoint. This validation process and the resulting optimized protocol were used to consolidate the OECD Test Guideline for the evaluation of reproductive effects of chemicals in L. stagnalis. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Vitamin E modulates reproductive toxicity of pyrethroid lambda-cyhalothrin in male rabbits.

    Science.gov (United States)

    Yousef, Mokhtar I

    2010-05-01

    The objective of the current study was to analyze the reproductive toxicity caused by lambda-cyhalothrin (LCT) in male rabbits, and to evaluate the possible protective effect of vitamin E (Vit. E) as antioxidant. Animals were orally administered their respective doses of LCT every other day and given drinking water supplemented with vitamin E for 16 weeks. Results showed that semen quality was deteriorated following treatment with LCT. Also, testosterone levels, body weight (BW), feed intake (FI), and relative testes (RTW) and epididymis (REW) weights were significantly decreased. Concentrations of thiobarbituric acid-reactive substances (TBARS) were significantly increased in seminal plasma of rabbits treated with LCT compared with control. While, activities of glutathione S-transferase (GST), transaminases and acid phosphatase (AcP) were significantly decreased. Vitamin E alone significantly increased testosterone levels, BW, FI, RTW, REW, semen characteristics and seminal plasma enzymes, and decreased the levels of TBARS. Also, the present study showed that vitamin E might be effective against LCT-induced reproductive toxicity. It was suggested that LCT exerted a significant adverse effect on reproductive performance of male rabbits. Furthermore, vitamin E antagonized the toxic effects of LCT and improved semen quality of male rabbit. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  9. Reproductive Toxicity Screen of Trifluoroiodomethane (CF31) in Sprague-Dawley Rats

    National Research Council Canada - National Science Library

    Dodd, Darol

    1998-01-01

    .... The purpose of this study was to determine and evaluate the potential for CF3I to produce reproductive toxicity and to provide additional information on the effect of CF3I exposure on the thyroid...

  10. Predicting the risk of developmental toxicity from in vitro assays

    International Nuclear Information System (INIS)

    Spielmann, Horst

    2005-01-01

    Reproductive toxicity refers to the adverse effects of a substance on any aspect of the reproductive cycle, including the impairment of reproductive function, the induction of adverse effects in the embryo, such as growth retardation, malformations, and death. Due to the complexity of the mammalian reproductive cycle, it is impossible to model the whole cycle in a single in vitro system in order to detect chemical effects on mammalian reproduction. However, the cycle can be broken down in its biological components which may be studied individually or in combination. This approach has the advantage that the target tissue/organ of a developmental toxicant can be identified. In specific areas of developmental toxicity, a number of useful and promising in vitro models are already available. The individual tests may be used as building blocks of a tiered testing strategy. So far, research has focused on developing and validating tests covering only a few components of the reproductive cycle, in particular organogenesis of the embryo, reflecting important concerns for teratogenic chemicals. During the last three decades, a number of established models and promising new developments have emerged that will be discussed, e.g. culture of mammalian embryos and embryonic cells and tissues and the use of embryonic stem cells

  11. Mollusc reproductive toxicity tests - Development and validation of test guidelines

    DEFF Research Database (Denmark)

    Ducrot, Virginie; Holbech, Henrik; Kinnberg, Karin Lund

    . Draft standard operating procedures (SOPs) have been designed based upon literature and expert knowledge from project partners. Pre-validation studies have been implemented to validate the proposed test conditions and identify issues in performing the SOPs and analyzing test results. Pre-validation work......The Organisation for Economic Cooperation and Development is promoting the development and validation of mollusc toxicity tests within its test guidelines programme, eventually aiming for the standardization of mollusc apical toxicity tests. Through collaborative work between academia, industry...... and stakeholders, this study aims to develop innovative partial life-cycle tests on the reproduction of the freshwater gastropods Potamopyrgus antipodarum and Lymnaea stagnalis, which are relevant candidate species for the standardization of mollusc apical toxicity tests assessing reprotoxic effects of chemicals...

  12. NATURAL PLANT TOXICANT – CYANOGENIC GLYCOSIDE AMYGDALIN: CHARACTERISTIC, METABOLISM AND THE EFFECT ON ANIMAL REPRODUCTION

    Directory of Open Access Journals (Sweden)

    Eduard Kolesár

    2015-02-01

    Full Text Available The amount of cyanogenic glycosides, as natural plant toxicants, in plants varies with plant species and environmental effects. Cyanogenic glycoside as an amygdalin was detected in apricot kernels, bitter almonds and peach, plum, pear and apple seeds. Amygdalin itself is non-toxic, but its HCN production decomposed by some enzymes is toxic substance. Target of this review was to describe the characteristic, metabolism and possible effects of amygdalin on reproductive processes. Previous studies describe the effects of natural compound amygdalin on female and male reproductive systems focused on process of steroidogenesis, spermatozoa motility and morphological abnormalities of spermatozoa. In accordance to the previous studies on amygdalin its benefit is controversial.

  13. In vitro assessment of reproductive toxicity of cigarette smoke and deleterious consequences of maternal exposure to its constituents

    Directory of Open Access Journals (Sweden)

    Shao-Chin Wu

    2012-01-01

    Full Text Available Cigarette smoke is known to be a serious health risk factor and considered reproductively toxic. In the current study, we investigated whether constituents of cigarette smoke, pyrazine, 2-ethylpyridine, and 3-ethylpyridine, adversely affect reproductive functioning such as oocyte maturation and sperm capacitation. Our findings indicated that three smoke components were involved in retardation of oocyte maturation in a dose-dependent manner and the lowest-observed-adverse-effect level (LOAEL was determined to be 10-10M. However, individual smoke components administrated at the LOAEL did not attenuate oocyte maturation, demonstrating that all three toxicants were equally required for the observed growth impairment. When exposed to all three components at 10-10M during in vitro capacitation, murine sperm lost forward progression and were unable to show adequate hyperactivation, which is indicative of the incompletion of the capacitation process. Only sperm administrated with 3-ethylpyridine alone showed significant reduction in capacitation status, suggesting the chemical is the one responsible for disrupting sperm capacitation. Taken together, this is the first report that documents the effect of cigarette smoke components on oocyte maturation and sperm capacitation. The present findings demonstrate the adverse effects of smoke constituents of mammalian reproduction and the differences in sensitivity to smoke components between male and female gametes. Since both processes take place in the female reproductive system, our data provide new insights into deleterious consequences of maternal exposure to cigarette smoke.

  14. The reproductive and developmental toxicity of High Flash Aromatic Naphtha.

    Science.gov (United States)

    McKee, R H; Wong, Z A; Schmitt, S; Beatty, P; Swanson, M; Schreiner, C A; Schardein, J L

    1990-01-01

    Catalytic reforming is a refining process that converts naphthenes to aromatics by dehydrogenation to make higher octane gasoline blending components. A portion of this wide boiling range hydrocarbon stream can be separated by distillation and used for other purposes. One such application is a mixture of predominantly 9-carbon aromatic molecules (C9 aromatics, primarily isomers of ethyltoluene and trimethylbenzene), which is removed and used as a solvent--High Flash Aromatic Naphtha. A program was initiated to assess the toxicological properties of High Flash Aromatic Naphtha since there may be human exposure through inhalation or external body contact. The current study was conducted to assess the potential for developmental toxicity in the mouse and for reproductive toxicity in the rat. In the developmental toxicity study in CD-1 mice, exposure of dams by inhalation to near lethal levels (1500 ppm) resulted in fetal mortality, reduced weight, delayed ossification, and an increased incidence of cleft palate. At 500 ppm, a level at which maternal weight gain was slightly reduced, fetal weight gain was also reduced, but there was no other evidence of developmental effects. The lowest exposure level (100 ppm) did not cause any maternal or developmental toxicity. There was no consistent evidence of reproductive toxicity in rats, even at exposure levels which resulted in significantly reduced parental weight gain. In addition, when parental exposure was stopped on GD (gestation day) 20, birth weights as well as postnatal survival were generally similar to control values, even in the 1500 ppm exposure group. Postnatal weight gain was also similar to controls early in weaning, but, if maternal exposure was reinitiated, weight gain was reduced in the high exposure group. However, when exposure was continued until delivery, pups in the high exposure group exhibited reduced litter size, birth weight and poor survival. Thus it was likely that the reduction in fetal weight

  15. One-generation reproductive toxicity study of DHA-rich oil in rats

    NARCIS (Netherlands)

    Blum, R.; Kiy, T.; Waalkens-Berendsen, I.; Wong, A.W.; Roberts, A.

    2007-01-01

    Polyunsaturated fatty acids, including docosahexaenoic acid (DHA), are natural constituents of the human diet. DHA-algal oil is produced through the use of the marine protist, Ulkenia sp. The reproductive toxicity of DHA-algal oil was assessed in a one-generation study. Rats were provided diets

  16. Toxicity of copper nanoparticles and CuCl2 salt to Enchytraeus albidus worms: Survival, reproduction and avoidance responses

    International Nuclear Information System (INIS)

    Amorim, Mónica João Barros; Scott-Fordsmand, Janeck James

    2012-01-01

    Environmental effects of copper nanoparticles are little studied in terrestrial ecosystems. In the present article, the toxicity of copper nanoparticles (Cu-NP) on the enchytraeid Enchytraeus albidus is compared to the toxicity of a copper-salt (CuCl 2 ). The effect parameters studied were survival, reproductive output and avoidance behaviour. The results show that Cu-NP were more toxic to E. albidus than the same concentrations of the CuCl 2 -salt. The physic-chemical analysis of the particles indicated that only a small fraction was released as ions. Hence, the results indicated a nanoparticle-specific effect – lower reproductive output and higher avoidance. This was observed as 2–8 fold (significant) lower ECx values for Cu-NP (EC 50-reprod = 95 mg Cu/kg; EC 50-avoid = 241 mg Cu/kg) exposed organisms compared to CuCl 2 (EC 50-reprod = 251 mg Cu/kg; EC 50-avoid = 475 mg Cu/kg) exposed organisms. These results corroborate with a nanoparticle-specific effect. - Highlights: ► Enchytraeus albidus were exposed to Cu-salt and Cu nanoparticles (80 nm) in soil. ► Survival, reproduction and avoidance behaviour were assessed. ► Particles characterization indicated very small ion release. ► Cu nanoparticles toxicity was higher than Cu-salt for reproduction and avoidance. - Toxicity of Cu chloride salt and Cu nanoparticles to Enchytraeus albidus indicated higher toxicity of Cu-NP.

  17. Assessment of mechanisms of metal-induced reproductive toxicity in aquatic species as a biomarker of exposure

    International Nuclear Information System (INIS)

    Anderson, M.; George, W.; Sikka, S.; Kamath, B.; Preslan, J.; Agrawal, K.; Rege, A.

    1993-01-01

    This project is designed to identify heavy metals and organic contaminants of concern which could impact on the biota in the Louisiana wetlands by assessment of uptake and bioaccumulation of contaminants and their effects on reproductive processes as biomarkers of exposure. Heavy metals (lead, cadmium, cobalt, and mercury) have been demonstrated to have toxic effects on reproduction in mammals and several aquatic species. Hexachlorobenzene (HCB) is an persistent environmental contaminant which has been measured in human serum, fat, semen, and follicular fluid. HCB has been shown to be a reproductive toxin in rats and primates. Polychlorinated biphenyls (PCBs) are prevalent chlorinated hydrocarbons currently contaminating our environment. PCBs resist degradation and are insoluble in water; however, they bioaccumulate in aquatic species. Disturbances of the reproductive systems are not only sensitive indicators of toxicity but threatens the propagation of a species

  18. Contents of toxic elements in biological environment of pregnant women of all reproductive age give birth first time

    Directory of Open Access Journals (Sweden)

    Markevych V.V.

    2016-09-01

    Full Text Available Purpose — to investigate the toxic contents of microelements in serum and erythrocytes of pregnant women in the early, middle and old reproductive age in the case of the first delivery. Patients and methods. The study was conducted in the third trimester of pregnancy on 36.08±0.59 weeks of gestation. Reproductive age of pregnant women was 16.33±0.21, 24.67±0.37 and 36.14±0.77 years respectively. The content of toxic ME (chromium, nickel, lead and cobalt in the biological substrates was determined by atomic absorption spectrophotometer C — 115 MI. Results. We found that pregnant women regardless of reproductive age who gave birth for the first time had high level of nickel both in serum and in red blood cells. With the growth of reproductive age we saw accumulation of toxic chromium in serum. Much less content of cadmium in red blood cells and possibly other tissues in pregnant women of older reproductive age apparently linked to the more conscious and responsible attitude to their health condition, the process of pregnancy and a healthy lifestyle and above except the main source of cadmium — smoking. The lowest content of lead in red blood cells is determined in the women of middle reproductive age. At the same time serum and erythrocytic content of lead in any group was not higher its level in healthy pregnant women. Conclusion. Nowadays very actual is researching of placenta as a body that provides trace element balance in system «mother—placenta—fetus». To determine the role of placenta in protecting the fetus from exposure of toxic elements reasonable is investigation of their content in the placenta and its functions — barrier penetration, depositing of essential and toxic elements.

  19. Reproductive toxicity parameters and biological monitoring in occupationally and environmentally boron-exposed persons in Bandirma, Turkey.

    Science.gov (United States)

    Duydu, Yalçın; Başaran, Nurşen; Üstündağ, Aylin; Aydin, Sevtap; Ündeğer, Ülkü; Ataman, Osman Yavuz; Aydos, Kaan; Düker, Yalçın; Ickstadt, Katja; Waltrup, Britta Schulze; Golka, Klaus; Bolt, Hermann M

    2011-06-01

    Boric acid and sodium borates have been considered as being "toxic to reproduction and development", following results of animal studies with high doses. Experimentally, a NOAEL (no observed adverse effect level) of 17.5 mg B/kg-bw/day has been identified for the (male) reproductive effects of boron in a multigeneration study of rats, and a NOAEL for the developmental effects in rats was identified at 9.6 mg B/kg-bw/day. These values are being taken as the basis of current EU safety assessments. The present study was conducted to investigate the reproductive effects of boron exposure in workers employed in boric acid production plant in Bandirma, Turkey. In order to characterize the external and internal boron exposures, boron was determined in biological samples (blood, urine, semen), in workplace air, in food, and in water sources. Unfavorable effects of boron exposure on the reproductive toxicity indicators (concentration, motility, morphology of the sperm cells and blood levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and total testosterone) were not observed. The mean calculated daily boron exposure (DBE) of the highly exposed group was 14.45 ± 6.57 (3.32-35.62) mg/day. These human exposures represent worst-case exposure conditions to boric acid/borates in Turkey. These exposure levels are considerably lower than exposures, which have previously led to reproductive effects in experimental animals. In conclusion, this means that dose levels of boron associated with developmental and reproductive toxic effects in animals are by far not reachable for humans under conditions of normal handling and use.

  20. On the impact of second generation mating and offspring in multi-generation reproductive toxicity studies on classification and labelling of substances in Europe

    DEFF Research Database (Denmark)

    Rorije, Emiel; Muller, André; Beekhuijzen, Manon E.W.

    2011-01-01

    The possible impact on classification and labelling decisions of effects observed in second generation parental (P1) and offspring (F2) parameters in multi-generation studies was investigated. This was done for 50 substances classified as reproductive toxicants in Europe, for which a multi-genera...... and reduced animal use, provide strong further support for replacement of the classical two-generation reproductive toxicity study by the EOGRTS in regulatory reproductive toxicity assessment....

  1. An epigenetic signal encoded protection mechanism is activated by graphene oxide to inhibit its induced reproductive toxicity in Caenorhabditis elegans.

    Science.gov (United States)

    Zhao, Yunli; Wu, Qiuli; Wang, Dayong

    2016-02-01

    Although many studies have suggested the adverse effects of engineered nanomaterials (ENMs), the self-protection mechanisms for organisms against ENMs toxicity are still largely unclear. Using Caenorhabditis elegans as an in vivo assay system, our results suggest the toxicity of graphene oxide in reducing reproductive capacity by inducing damage on gonad development. The observed reproductive toxicity of GO on gonad development was due to the combinational effect of germline apoptosis and cell cycle arrest, and DNA damage activation might act as an inducer for this combinational effect. For the underlying molecular mechanism of reproductive toxicity of GO, we raised a signaling cascade of HUS-1/CLK-2-CEP-1-EGL-1-CED-4-CED-3 to explain the roles of core apoptosis signaling pathway and DNA damage checkpoints. Moreover, we identified a miRNA regulation mechanism activated by GO to suppress its induced reproductive toxicity. A mir-360 regulation mechanism was activated by GO to suppress its induced DNA damage-apoptosis signaling cascade through affecting component of CEP-1. Our identified epigenetic signal encoded protection mechanism activated by GO suggests a novel self-protection mechanism for organisms against the ENMs toxicity. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Reproductive Toxicity of Triptolide in Male House Rat, Rattus rattus

    Directory of Open Access Journals (Sweden)

    Neena Singla

    2014-01-01

    Full Text Available The aim of study was to investigate the toxic effect of triptolide fed in bait on reproduction of male house rat, Rattus rattus. Feeding of cereal based bait containing 0.2% triptolide to male R. rattus for 5 days in no-choice feeding test, leading to mean daily ingestion of 20.45 mg/kg bw of triptolide, was found effective in significantly (P≤0.05 reducing sperm motility and viability in cauda epididymal fluid by 80.65 and 75.14%, respectively, from that of untreated rats. Pregnancy rates were decreased by 100% in untreated cyclic female rats paired with male rats treated with 0.2% triptolide. Present studies suggest the potential of 0.2% triptolide bait in regulating reproductive output of R. rattus.

  3. Optimizing the design of a reproduction toxicity test with the pond snail Lymnaea stagnalis

    DEFF Research Database (Denmark)

    Charles, Sandrine; Ducrot, Virginie; Azam, Didier

    2016-01-01

    This paper presents the results from two ring-tests addressing the feasibility, robustness and reproducibility of a reproduction toxicity test with the freshwater gastropod Lymnaea stagnalis (RENILYS strain). Sixteen laboratories (from inexperienced to expert laboratories in mollusc testing) from...... nine countries participated in these ring-tests. Survival and reproduction were evaluated in L. stagnalis exposed to cadmium, tributyltin, prochloraz and trenbolone according to an OECD draft Test Guideline. In total, 49 datasets were analysed to assess the practicability of the proposed experimental...... protocol, and to estimate the between-laboratory reproducibility of toxicity endpoint values. The statistical analysis of count data (number of clutches or eggs per individual-day) leading to ECx estimation was specifically developed and automated through a free web-interface. Based on a complementary...

  4. Effectivity of advanced wastewater treatment: reduction of in vitro endocrine activity and mutagenicity but not of in vivo reproductive toxicity.

    Science.gov (United States)

    Giebner, Sabrina; Ostermann, Sina; Straskraba, Susanne; Oetken, Matthias; Oehlmann, Jörg; Wagner, Martin

    2018-02-01

    Conventional wastewater treatment plants (WWTPs) have a limited capacity to eliminate micropollutants. One option to improve this is tertiary treatment. Accordingly, the WWTP Eriskirch at the German river Schussen has been upgraded with different combinations of ozonation, sand, and granulated activated carbon filtration. In this study, the removal of endocrine and genotoxic effects in vitro and reproductive toxicity in vivo was assessed in a 2-year long-term monitoring. All experiments were performed with aqueous and solid-phase extracted water samples. Untreated wastewater affected several endocrine endpoints in reporter gene assays. The conventional treatment removed the estrogenic and androgenic activity by 77 and 95 %, respectively. Nevertheless, high anti-estrogenic activities and reproductive toxicity persisted. All advanced treatment technologies further reduced the estrogenic activities by additional 69-86 % compared to conventional treatment, resulting in a complete removal of up to 97 %. In the Ames assay, we detected an ozone-induced mutagenicity, which was removed by subsequent filtration. This demonstrates that a post treatment to ozonation is needed to minimize toxic oxidative transformation products. In the reproduction test with the mudsnail Potamopyrgus antipodarum, a decreased number of embryos was observed for all wastewater samples. This indicates that reproductive toxicants were eliminated by neither the conventional nor the advanced treatment. Furthermore, aqueous samples showed higher anti-estrogenic and reproductive toxicity than extracted samples, indicating that the causative compounds are not extractable or were lost during extraction. This underlines the importance of the adequate handling of wastewater samples. Taken together, this study demonstrates that combinations of multiple advanced technologies reduce endocrine effects in vitro. However, they did not remove in vitro anti-estrogenicity and in vivo reproductive toxicity. This

  5. Neuro-endocrine effects of aqueous extract of Amaranthus viridis (Linn. leaf in male Wistar rat model of cyclophosphamide-induced reproductive toxicity

    Directory of Open Access Journals (Sweden)

    Oladele Abiodun Ayoka

    Full Text Available Cyclophosphamide (CP is a widely used cytotoxic alkylating agent with antitumor and immunosuppressant properties that is associated with various forms of reproductive toxicity. The significance of natural antioxidants of plant origin should be explored, especially in a world with increasing incidence of patients in need of chemotherapy. The neuro-endocrine effects of aqueous extract of Amaranthus viridis (Linn. leaf (AEAVL in Wistar rats with CP-induced reproductive toxicity was determined. Forty rats were used for this study such that graded doses of the extract were administered following CP-induced reproductive toxicity and comparisons were made against control, toxic and standard (vitamin E groups at p < 0.05. The synthetic drugs (CP, 65 mg/kg i.p. for 5 days; Vitamin E, 100 mg/kg p.o. for 30 days as well as the extract (100, 200 and 400 mg/kg p.o. for 30 days were administered to the rats at 0.2 mL/100 g. CP induced reproductive toxicity as evidenced by significantly lowered levels of FSH, LH and testosterone, perturbation of sperm characterization, deleterious disruptions of the antioxidant system as evidenced by decreased levels of GSH as well as elevation of TBARS activity. Histopathological examination showed hemorrhagic lesions with scanty and hypertrophied parenchymal cells in the pituitary while the testis showed ballooned seminiferous tubules with loosed connective tissues and vacuolation of testicular interstitium. These conditions were significantly reversed (p < 0.05 following administration of the graded doses of the extract. It was, therefore, concluded that AEAVL could potentially be a therapeutic choice in patients with CP-induced neuro-endocrine dysfunction and reproductive toxicity. Keywords: Cyclophosphamide, Neuro-endocrine dysfunction, Reproductive toxicity, Rats, Amaranthus viridis

  6. Workplace standards for exposure to toxicants during pregnancy.

    Science.gov (United States)

    Till, Christine; Koren, Gideon; Rovet, Joanne F

    2008-01-01

    Many women of childbearing age are exposed to reproductive toxicants in the workplace. This article highlights the need for an evaluation of current occupational exposure guidelines for pregnant women working with hazardous agents that have the potential of being reproductive toxins. Limited information regarding reproductive risks associated with many chemicals in the workplace presents challenges in the establishment of standards that are 'safe' for vulnerable populations, such as the fetus. The management of these risks must take into consideration the limitations of available knowledge as well as individual risk factors that may amplify the likelihood of adverse outcomes. In 1981, Quebec adopted a policy that provides "precautionary leave" or reassignment of pregnant workers to other jobs if they are exposed to a factor suspected to compromise their health or that of their fetus during pregnancy. The advantages and disadvantages of this approach to managing reproductive hazards are discussed. The existence of a regulatory safety net at the level of the workplace for minimizing the impact of toxicant exposure on reproductive health outcomes is stressed. Management options that can be implemented early to provide added protection when a hazard cannot be reduced or eliminated are recommended.

  7. Endosulfan is toxic to the reproductive health of male freshwater fish, Cyprinion watsoni

    Science.gov (United States)

    Islam, Fakhar ul; Jalali, Samina; Shafqat, Mustafa Nawaz; Shah, Syed Tahir Abbas

    2017-12-01

    Endosulfan is an organochlorine pesticide that is toxic to aquatic life. Endosulfan might hamper the reproductive health of indigenous fish in agricultural areas of Pakistan where this pesticide is sprayed widely. The aim of the current study is to investigate the toxic effects of endosulfan on selected reproductive parameters of male freshwater fish, Cyprinion watsoni. Two concentrations of endosulfan (0.5 and 1 ppb for 30 days exposure) were tested for their effects on body weight, body length, and testicular weight, length, and width. Testicular testosterone was assayed from tissue extracts using enzyme immunoassay (EIA). A significant increase in the mortality rate was observed in both treated groups during both spawning and quiescent seasons. The overall behavior of fish in the aquarium was normal in all control and treated groups. However, the treated fish exhibited anxiety after treatment with endosulfan. The body weight and length, and testicular weight, length and width were not significantly different to the control group. The testicular testosterone concentrations were significantly lower in both endosulfan-treated groups compared to the control. The decrease was dose-dependent, with a significant difference between the two treated groups. The histomorphological results demonstrated various testicular alterations in the treated groups. These alterations included an increase in interlobular areas and clumping patterns in spermatocytes/spermatids. Because spermatids eventually differentiate into sperms, their low count will directly result in lower sperm count. Taken together, these results suggest that endosulfan is a toxicant that at least disturbs testosterone levels (possibly others) and negatively impacts the reproductive health of male freshwater fish.

  8. QSAR models for reproductive toxicity and endocrine disruption in regulatory use - a preliminary investigation

    DEFF Research Database (Denmark)

    Jensen, Gunde Egeskov; Niemela, J.R.; Wedebye, Eva Bay

    2008-01-01

    A special challenge in the new European Union chemicals legislation, Registration, Evaluation and Authorisation of Chemicals, will be the toxicological evaluation of chemicals for reproductive toxicity. Use of valid quantitative structure-activity relationships (QSARs) is a possibility under...

  9. Reproductive profiles and risk of breast cancer subtypes

    DEFF Research Database (Denmark)

    Brouckaert, Olivier; Rudolph, Anja; Laenen, Annouschka

    2017-01-01

    Background: Previous studies have shown that reproductive factors are differentially associated with breast cancer (BC) risk by subtypes. The aim of this study was to investigate associations between reproductive factors and BC subtypes, and whether these vary by age at diagnosis. Methods: We used...... pooled data on tumor markers (estrogen and progesterone receptor, human epidermal growth factor receptor-2 (HER2)) and reproductive risk factors (parity, age at first full-time pregnancy (FFTP) and age at menarche) from 28,095 patients with invasive BC from 34 studies participating in the Breast Cancer...... the risk for TNBC (OR = 0.78, CI 0.70-0.88, p diagnosis, whereas the association with luminal HER2-like BC was present only for early onset BC....

  10. Aphid reproductive investment in response to mortality risks

    Science.gov (United States)

    2010-01-01

    Background Aphids are striking in their prodigious reproductive capacity and reliance on microbial endosymbionts, which provision their hosts with necessary amino acids and provide protection against parasites and heat stress. Perhaps as a result of this bacterial dependence, aphids have limited immune function that may leave them vulnerable to bacterial pathogens. An alternative, non-immunological response that may be available to infected aphids is to increase reproduction, thereby ameliorating fitness loss from infection. Such a response would reduce the need to mount a potentially energetically costly immune response, and would parallel that of other hosts that alter life-history traits when there is a risk of infection. Here we examined whether pea aphids (Acyrthosiphon pisum) respond to immunological challenges by increasing reproduction. As a comparison to the response to the internal cue of risk elicited by immunological challenge, we also exposed pea aphids to an external cue of risk - the aphid alarm pheromone (E)-β-farnesene (EBF), which is released in the presence of predators. For each challenge, we also examined whether the presence of symbionts modified the host response, as maintaining host fitness in the face of challenge would benefit both the host and its dependent bacteria. Results We found that aphids stabbed abdominally with a sterile needle had reduced fecundity relative to control aphids but that aphids stabbed with a needle bearing heat-killed bacteria had reproduction intermediate, and statistically indistinguishable, to the aphids stabbed with a sterile needle and the controls. Aphids with different species of facultative symbiotic bacteria had different reproductive patterns overall, but symbionts in general did not alter aphid reproduction in response to bacterial exposure. However, in response to exposure to alarm pheromone, aphids with Hamiltonella defensa or Serratia symbiotica symbiotic infections increased reproduction but those

  11. Reproductive activities of Heliotropium indicum isolate against Helopeltis theivora and toxicity evaluation in mice.

    Science.gov (United States)

    Dolui, A K; Debnath, Manabendra; De, B; Kumar, Atul

    2012-05-01

    A new compound E was isolated from the methanolic extract of the leaves of Heliotropium indicum by chromatographic fractionation. In the present study, the effect of the compound E on reproduction of Helopeltis theivora has been evaluated. The acute toxicity study (LD50) and sub-acute toxicity studies (haematological, biochemical and histopathological parameters) in albino Swiss mice were carried out to evaluate the safety aspect of the compound E. The compound showed significant inhibitory effect on the reproductive life of H. theivora. The oviposition period, fecundity and hatching percentage of H. theivora were found to be 15.67 days, 39.33 and 28.00% respectively after treatment with 2% compound E, whereas the control value were found to be 20.33 days, 77.67 and 77.33% respectively. The LD50 of the compound was found to be 780 mg kg(-1) in Swiss albino female mice. The compound did not show any toxicity in mice at sub-lethal dose treatment (78 mg kg(-1) b. wt., once daily) for 21 days as evident from different haematological, biochemical and histopathological parameters in compound E treated group when compared with control.

  12. Two-generation reproductive toxicity study of tributyltin chloride in female rats.

    Science.gov (United States)

    Ogata, R; Omura, M; Shimasaki, Y; Kubo, K; Oshima, Y; Aou, S; Inoue, N

    2001-05-25

    A two-generation reproductive toxicity study of the effects of tributyltin chloride (TBTCl) was conducted in female rats using dietary concentrations of 5, 25, and 125 ppm TBTCl. Reproductive outcomes of dams (number and body weight of pups and the percentage of live pups) and the growth of female pups (the day of eye opening and body weight gain) were significantly decreased in the 125 ppm TBTCl group. A delay in vaginal opening and impaired estrous cyclicity were also observed in the 125 ppm TBTCl group. However, an increase in anogenital distance was found in all TBTCl groups on postnatal d 1. A dose-effect relationship was observed in TBTCl-induced changes in anogenital distance. These results indicate that the whole-life exposure to TBTCl affects the sexual development and reproductive function of female rats. In addition, the TBTCl-induced increase in anogenital distance seems to suggest it may exert a masculinizing effect on female neonates. However, the concentrations of TBTCl used in this study are not environmentally relevant.

  13. Revision of the ICH guideline on detection of toxicity to reproduction for medicinal products: SWOT analysis.

    Science.gov (United States)

    Barrow, Paul

    2016-09-01

    SWOT analysis was used to gain insights and perspectives into the revision of the ICH S5(R2) guideline on detection of toxicity to reproduction for medicinal products. The current ICH guideline was rapidly adopted worldwide and has an excellent safety record for more than 20 years. The revised guideline should aim to further improve reproductive and developmental (DART) safety testing for new drugs. Alternative methods to animal experiments should be used whenever possible. Modern technology should be used to obtain high quality data from fewer animals. Additions to the guideline should include considerations on the following: limit dose setting, maternal toxicity, biopharmaceuticals, vaccines, testing strategies by indication, developmental immunotoxicity, and male-mediated developmental toxicity. Emerging issues, such as epigenetics and the microbiome, will most likely pose challenges to DART testing in the future. It is hoped that the new guideline will be adopted even outside the ICH regions. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Health assessment of gasoline and fuel oxygenate vapors: reproductive toxicity assessment.

    Science.gov (United States)

    Gray, Thomas M; Steup, David; Roberts, Linda G; O'Callaghan, James P; Hoffman, Gary; Schreiner, Ceinwen A; Clark, Charles R

    2014-11-01

    Vapor condensates of baseline gasoline (BGVC), or gasoline-blended with methyl tertiary butyl ether (G/MTBE), ethyl t-butyl ether (G/ETBE), t-amyl methyl ether (G/TAME), diisopropyl ether (G/DIPE), ethanol (G/EtOH), or t-butyl alcohol (G/TBA) were evaluated for reproductive toxicity in rats at target concentrations of 2000, 10,000, or 20,000mg/m(3), 6h/day, 7days/week. BGVC and G/MTBE were assessed over two generations, the others for one generation. BGVC and G/MTBE F1 offspring were evaluated for neuropathology and changes in regional brain glial fibrillary acidic protein content. No neurotoxicity was observed. Male kidney weight was increased consistent with light hydrocarbon nephropathy. In adult rats, decreased body weight gain and increased liver weight were seen. Spleen weight decreased in adults and pups exposed to G/TBA. No pathological changes to reproductive organs occurred in any study. Decreased food consumption was seen in G/TAME lactating females. Transient decreases in G/TAME offspring weights were observed during lactation. Except for a minor increase in time to mating in G/TBA which did not affect other reproductive parameters, there were no adverse reproductive findings. The NOAEL for reproductive and offspring parameters was 20,000mg/m(3) for all vapor condensates except for lower offspring NOAELs of 10,000mg/m(3) for G/TBA and 2000mg/m(3) for G/TAME. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Toxicity reference values for methylmercury effects on avian reproduction: Critical review and analysis.

    Science.gov (United States)

    Fuchsman, Phyllis C; Brown, Lauren E; Henning, Miranda H; Bock, Michael J; Magar, Victor S

    2017-02-01

    Effects of mercury (Hg) on birds have been studied extensively and with increasing frequency in recent years. The authors conducted a comprehensive review of methylmercury (MeHg) effects on bird reproduction, evaluating laboratory and field studies in which observed effects could be attributed primarily to Hg. The review focuses on exposures via diet and maternal transfer in which observed effects (or lack thereof) were reported relative to Hg concentrations in diet, eggs, or adult blood. Applicable data were identified for 23 species. From this data set, the authors identified ranges of toxicity reference values suitable for risk-assessment applications. Typical ranges of Hg effect thresholds are approximately 0.2 mg/kg to >1.4 mg/kg in diet, 0.05 mg/kg/d to 0.5 mg/kg/d on a dose basis, 0.6 mg/kg to 2.7 mg/kg in eggs, and 2.1 mg/kg to >6.7 mg/kg in parental blood (all concentrations on a wet wt basis). For Hg in avian blood, the review represents the first broad compilation of relevant toxicity data. For dietary exposures, the current data support TRVs that are greater than older, commonly used TRVs. The older diet-based TRVs incorporate conservative assumptions and uncertainty factors that are no longer justified, although they generally were appropriate when originally derived, because of past data limitations. The egg-based TRVs identified from the review are more similar to other previously derived TRVs but have been updated to incorporate new information from recent studies. While important research needs remain, a key recommendation is that species not yet tested for MeHg toxicity should be evaluated using toxicity data from tested species with similar body weights. Environ Toxicol Chem 2017;36:294-319. © 2016 SETAC. © 2016 SETAC.

  16. Reproductive health education and sexual risk among high-risk female adolescents and young adults.

    Science.gov (United States)

    Ancheta, Rosedelia; Hynes, Colin; Shrier, Lydia A

    2005-04-01

    The objective of this study was to explore the associations of sources, content, and timing of reproductive health education with cognitive and behavioral sexual risk in a sample of high-risk female adolescents and young adults. Female adolescents and young adults (n=113, median age 17 years) receiving treatment for a sexually transmitted disease (STD) reported sources of reproductive health education, topics covered, and when first formal education occurred. Dependent variables included sexual risk knowledge; condom attitudes, negotiation skills, and use (consistent and at last sex); and number of sexual partners. Most participants reported receiving reproductive health education from both parental (80%) and formal sources (92%). Parents discussed the menstrual cycle (94%) more frequently than other sex education topics, while formal sources focused most on teaching about STDs (91%). Although median age of first formal instruction was 12 years, 26% of girls received their first formal education during or after the year they initiated coitus. Girls with a parental source of education and those receiving formal instruction on pregnancy reported greater ability to negotiate condom use. Girls who received education later in relation to the onset of sexual activity and those with a parental source of education reported more sexual partners. Early reproductive health education and education from both parental and formal sources is associated with reduced sexual risk among high-risk adolescent girls. Interestingly, receiving parental education is also associated with more sexual partners, suggesting that parental educational efforts may be reactive to their daughters' increasing sexual risk behavior. Future research should examine multiple sources of reproductive health education and the timing of education from these sources to enhance understanding the dynamic interactions between reproductive health education and adolescent sexual risk.

  17. Protective Effect of Vitamins E and C on Endosulfan-Induced Reproductive Toxicity in Male Rats

    Directory of Open Access Journals (Sweden)

    Hussain Kargar

    2012-09-01

    Full Text Available Background: The role of oxidative stress in endosulfan-induced reproductive toxicity has been implicated. This study was performed to evaluate the possible protective effect of vitamins E and C, against endosulfan-induced reproductive toxicity in rats.Methods: Fifty adult male Sprague–Dawley rats were randomly divided into five groups (n=10 each. The groups included a control receiving vehicle, a group treated with endosulfan (10 mg/kg/day alone, and three endosulfan-treated group receiving vitamin C (20 mg/kg/day, vitamin E (200 mg/kg/day, or vitamine C+vitamin E at the same doses. After 10 days of treatment, sperm parameters, plasma lactate dehydrogenase (LDH, plasma testosterone and malondialdehyde (MDA levels in the testis were determined. Results: Oral administration of endosulfan caused a reduction in the sperm motility, viability, daily sperm production (DSP and increased the number of sperm with abnormal chromatin condensation. Endosulfan administration increased testis MDA and plasma LDH. Supplementation of vitamin C and vitamin E to endosulfan-treated rats reduced the toxic effect of endosulfan on sperm parameters and lipid peroxidation in the testis. Vitamin E was more protective than vitamin C in reducing the adverse effects of the endosulfan.Conclusion: The findings data suggest that administration of vitamins C and E ameliorated the endosulfan-induced oxidative stress and sperm toxicity in rat. The effect of vitamin E in preventing endosulfan-induced sperm toxicity was superior to that of vitamin C.

  18. Protective effect of vitamins e and C on endosulfan-induced reproductive toxicity in male rats.

    Science.gov (United States)

    Takhshid, Mohammad Ali; Tavasuli, Ali Reza; Heidary, Yazdan; Keshavarz, Mojtaba; Kargar, Hussain

    2012-09-01

    The role of oxidative stress in endosulfan-induced reproductive toxicity has been implicated. This study was performed to evaluate the possible protective effect of vitamins E and C, against endosulfan-induced reproductive toxicity in rats. Fifty adult male Sprague-Dawley rats were randomly divided into five groups (n=10 each). The groups included a control receiving vehicle, a group treated with endosulfan (10 mg/kg/day) alone, and three endosulfan-treated group receiving vitamin C (20 mg/kg/day), vitamin E (200 mg/kg/day), or vitamine C+vitamin E at the same doses. After 10 days of treatment, sperm parameters, plasma lactate dehydrogenase (LDH), plasma testosterone and malondialdehyde (MDA) levels in the testis were determined. Oral administration of endosulfan caused a reduction in the sperm motility, viability, daily sperm production (DSP) and increased the number of sperm with abnormal chromatin condensation. Endosulfan administration increased testis MDA and plasma LDH. Supplementation of vitamin C and vitamin E to endosulfan-treated rats reduced the toxic effect of endosulfan on sperm parameters and lipid peroxidation in the testis. Vitamin E was more protective than vitamin C in reducing the adverse effects of the endosulfan. The findings data suggest that administration of vitamins C and E ameliorated the endosulfan-induced oxidative stress and sperm toxicity in rat. The effect of vitamin E in preventing endosulfan-induced sperm toxicity was superior to that of vitamin C.

  19. In vitro functional screening as a means to identify new plasticizers devoid of reproductive toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Boisvert, Annie; Jones, Steven; Issop, Leeyah [The Research Institute of the McGill University Health Centre, McGill University, Montreal, Quebec, Canada H4A 3J1 (Canada); Department of Medicine, McGill University, Montreal, Quebec, Canada H4A 3J1 (Canada); Erythropel, Hanno C. [Department of Chemical Engineering, McGill University, Montreal, Quebec, Canada H4A 3J1 (Canada); Papadopoulos, Vassilios [The Research Institute of the McGill University Health Centre, McGill University, Montreal, Quebec, Canada H4A 3J1 (Canada); Department of Medicine, McGill University, Montreal, Quebec, Canada H4A 3J1 (Canada); Department of Pharmacology & Therapeutics, McGill University, Montreal, Quebec, Canada H4A 3J1 (Canada); Culty, Martine, E-mail: martine.culty@mcgill.ca [The Research Institute of the McGill University Health Centre, McGill University, Montreal, Quebec, Canada H4A 3J1 (Canada); Department of Medicine, McGill University, Montreal, Quebec, Canada H4A 3J1 (Canada); Department of Pharmacology & Therapeutics, McGill University, Montreal, Quebec, Canada H4A 3J1 (Canada)

    2016-10-15

    Plasticizers are indispensable additives providing flexibility and malleability to plastics. Among them, several phthalates, including di (2-ethylhexyl) phthalate (DEHP), have emerged as endocrine disruptors, leading to their restriction in consumer products and creating a need for new, safer plasticizers. The goal of this project was to use in vitro functional screening tools to select novel non-toxic plasticizers suitable for further in vivo evaluation. A panel of novel compounds with satisfactory plasticizer properties and biodegradability were tested, along with several commercial plasticizers, such as diisononyl-cyclohexane-1,2-dicarboxylate (DINCH®). MEHP, the monoester metabolite of DEHP was also included as reference compound. Because phthalates target mainly testicular function, including androgen production and spermatogenesis, we used the mouse MA-10 Leydig and C18-4 spermatogonial cell lines as surrogates to examine cell survival, proliferation, steroidogenesis and mitochondrial integrity. The most promising compounds were further assessed on organ cultures of rat fetal and neonatal testes, corresponding to sensitive developmental windows. Dose-response studies revealed the toxicity of most maleates and fumarates, while identifying several dibenzoate and succinate plasticizers as innocuous on Leydig and germ cells. Interestingly, DINCH®, a plasticizer marketed as a safe alternative to phthalates, exerted a biphasic effect on steroid production in MA-10 and fetal Leydig cells. MEHP was the only plasticizer inducing the formation of multinucleated germ cells (MNG) in organ culture. Overall, organ cultures corroborated the cell line data, identifying one dibenzoate and one succinate as the most promising candidates. The adoption of such collaborative approaches for developing new chemicals should help prevent the development of compounds potentially harmful to human health. - Highlights: • Phthalate plasticizers exert toxic effects on male reproduction

  20. In vitro functional screening as a means to identify new plasticizers devoid of reproductive toxicity

    International Nuclear Information System (INIS)

    Boisvert, Annie; Jones, Steven; Issop, Leeyah; Erythropel, Hanno C.; Papadopoulos, Vassilios; Culty, Martine

    2016-01-01

    Plasticizers are indispensable additives providing flexibility and malleability to plastics. Among them, several phthalates, including di (2-ethylhexyl) phthalate (DEHP), have emerged as endocrine disruptors, leading to their restriction in consumer products and creating a need for new, safer plasticizers. The goal of this project was to use in vitro functional screening tools to select novel non-toxic plasticizers suitable for further in vivo evaluation. A panel of novel compounds with satisfactory plasticizer properties and biodegradability were tested, along with several commercial plasticizers, such as diisononyl-cyclohexane-1,2-dicarboxylate (DINCH®). MEHP, the monoester metabolite of DEHP was also included as reference compound. Because phthalates target mainly testicular function, including androgen production and spermatogenesis, we used the mouse MA-10 Leydig and C18-4 spermatogonial cell lines as surrogates to examine cell survival, proliferation, steroidogenesis and mitochondrial integrity. The most promising compounds were further assessed on organ cultures of rat fetal and neonatal testes, corresponding to sensitive developmental windows. Dose-response studies revealed the toxicity of most maleates and fumarates, while identifying several dibenzoate and succinate plasticizers as innocuous on Leydig and germ cells. Interestingly, DINCH®, a plasticizer marketed as a safe alternative to phthalates, exerted a biphasic effect on steroid production in MA-10 and fetal Leydig cells. MEHP was the only plasticizer inducing the formation of multinucleated germ cells (MNG) in organ culture. Overall, organ cultures corroborated the cell line data, identifying one dibenzoate and one succinate as the most promising candidates. The adoption of such collaborative approaches for developing new chemicals should help prevent the development of compounds potentially harmful to human health. - Highlights: • Phthalate plasticizers exert toxic effects on male reproduction

  1. Ethylene glycol and propylene glycol ethers – Reproductive and developmental toxicity

    Directory of Open Access Journals (Sweden)

    Beata Starek-Świechowicz

    2015-10-01

    Full Text Available Both ethylene and propylene glycol alkyl ethers (EGAEs and PGAEs, respectively are widely used, mainly as solvents, in industrial and household products. Some EGAEs demonstrate gonadotoxic, embriotoxic, fetotoxic and teratogenic effects in both humans and experimental animals. Due to the noxious impact of these ethers on reproduction and development of organisms EGAEs are replaced for considerably less toxic PGAEs. The data on the mechanisms of testicular, embriotoxic, fetotoxic and teratogenic effects of EGAEs are presented in this paper. Our particular attention was focused on the metabolism of some EGAEs and their organ-specific toxicities, apoptosis of spermatocytes associated with changes in the expression of various genes that code for oxidative stress factors, protein kinases and nuclear hormone receptors. Med Pr 2015;66(5:725–737

  2. Development and validation of an OECD reproductive toxicity test guideline with the mudsnail Potamopyrgus antipodarum (Mollusca, Gastropoda).

    Science.gov (United States)

    Ruppert, Katharina; Geiß, Cornelia; Askem, Clare; Benstead, Rachel; Brown, Rebecca; Coke, Maira; Ducrot, Virginie; Egeler, Philipp; Holbech, Henrik; Hutchinson, Thomas H; Kinnberg, Karin L; Lagadic, Laurent; Le Page, Gareth; Macken, Ailbhe; Matthiessen, Peter; Ostermann, Sina; Schimera, Agnes; Schmitt, Claudia; Seeland-Fremer, Anne; Smith, Andy J; Weltje, Lennart; Oehlmann, Jörg

    2017-08-01

    Mollusks are known to be uniquely sensitive to a number of reproductive toxicants including some vertebrate endocrine disrupting chemicals. However, they have widely been ignored in environmental risk assessment procedures for chemicals. This study describes the validation of the Potamopyrgus antipodarum reproduction test within the OECD Conceptual Framework for Endocrine Disrupters Testing and Assessment. The number of embryos in the brood pouch and adult mortality serve as main endpoints. The experiments are conducted as static systems in beakers filled with artificial medium, which is aerated trough glass pipettes. The test chemical is dispersed into the medium, and adult snails are subsequently introduced into the beakers. After 28 days the reproductive success is determined by opening the brood pouch and embryo counting. This study presents the results of two validation studies of the reproduction test with eleven laboratories and the chemicals tributyltin (TBT) with nominal concentrations ranging from 10 to 1000 ng TBT-Sn/L and cadmium with concentrations from 1.56 to 25 μg/L. The test design could be implemented by all laboratories resulting in comparable effect concentrations for the endpoint number of embryos in the brood pouch. After TBT exposure mean EC 10 , EC 50 , NOEC and LOEC were 35.6, 127, 39.2 and 75.7 ng Sn/L, respectively. Mean effect concentrations in cadmium exposed snails were, respectively, 6.53, 14.2, 6.45 and 12.6 μg/L. The effect concentrations are in good accordance with already published data. Both validation studies show that the reproduction test with P. antipodarum is a well-suited tool to assess reproductive effects of chemicals. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Parasite dispersal risk tolerance is mediated by its reproductive value.

    Science.gov (United States)

    Nolan, Maxcy P; Delaplane, Keith S

    2017-10-01

    Parasite dispersal theory draws heavily upon epidemiological SIR models in which host status (susceptible (S), infected (I), or recovered (R)) is used to study parasite dispersal evolution. In contrast to these extrinsically host-centric drivers, in this study we focus on an intrinsic driver, the parasite's reproductive value (predicted future offspring) as a regulator of the extent to which the individual will engage in risky dispersal behaviour. As a model system we use the honeybee Apis mellifera and its ectoparasite, the mite Varroa destructor . Mite reproduction happens exclusively inside cells of bee brood, and newly emerged fecund mites may parasitize either a homocolonial brood cell (low risk dispersal) or emigrate to a new bee colony via phoretic attachment to mature forager bees (high risk dispersal). In an empirical bioassay, prepartum mites (high reproductive value) and postpartum mites (low reproductive value) were offered a choice of newly emerged homocolonial worker bees (low risk), homocolonial pollen forager bees (high risk), or heterocolonial pollen foragers (high risk). A preference for newly emerged bees was earlier and more strongly sustained among prepartum mites. This suggests comparatively greater dispersal risk tolerance among postpartum mites with lower reproductive value. A dangerous bid for dispersal may be adaptive if the individual has already successfully reproduced and the rewards for successful dispersal are sufficiently large.

  4. Evaluation of sublethal toxicity of zinc and chromium in Eudrilus eugeniae using biochemical and reproductive parameters.

    Science.gov (United States)

    Basha, P Mahaboob; Latha, V

    2016-05-01

    Zinc (Zn) and chromium (Cr) act as essential nutrients; however, they can be toxic at higher concentrations. In this study, earthworm species Eudrilus eugeniae was studied for its sensitivity to sublethal doses of Cr (8 ppm) and Zn (350 ppm) in terms of alterations occurred in oxidative stress indices and reproductive parameters in the testis. A significant (p food intake was observed on 7, 14 and 21 days of Cr toxicity; while increased rate was evident upon 7 days of Zn exposure. Changes evident in the rate of cocoon production (-39.54 and +38.63 %), hatchability (-77.85 and +30.0 %) highlight higher toxic potential of Cr than Zn, respectively. Moderate to severe vacuolization in spermatic follicles and higher incidence of tailless (+52.6 % in Cr and 20.8 % in Zn), and head bent (+18.8 % in Cr and 0 % in Zn) sperms were evident in Cr(VI) exposed worms emphasizing the higher vulnerability of E. eugeniae to Cr toxicity. A significant (p implied from results that excessive free radical production and inadequate antioxidant defenses have lead to morphological alterations in sperms which sequentially reduced the reproductive rate.

  5. 76 FR 59142 - Guidance for Industry on Reproductive and Developmental Toxicities-Integrating Study Results To...

    Science.gov (United States)

    2011-09-23

    ... of study results to assess concerns about human reproductive and developmental toxicities. It does... assist that office in processing your requests. See the SUPPLEMENTARY INFORMATION section for electronic access to the guidance document. Submit electronic comments on the guidance to http://www.regulations.gov...

  6. Toxicity of four veterinary pharmaceuticals on the survival and reproduction of Folsomia candida in tropical soils.

    Science.gov (United States)

    Zortéa, Talyta; Segat, Julia C; Maccari, Ana Paula; Sousa, José Paulo; Da Silva, Aleksandro S; Baretta, Dilmar

    2017-04-01

    This study aimed to evaluate the effect of veterinary pharmaceuticals (VPs) used to control endo- and ectoparasites in ruminants, on the survival and reproduction of the collembolan species Folsomia candida. Standard ecotoxicological tests were conducted in Tropical Artificial Soil and the treatments consisted of increasing dosages of four commercial products with different active ingredients: ivermectin, fipronil, fluazuron and closantel. Ecotoxicological effects were related to the class and mode of action of the different compounds. Fipronil and ivermectin were the most toxic compounds causing a significant reduction in the number of juveniles at the lowest doses tested (LOEC reprod values of 0.3 and 0.2 mg kg -1 of dry soil, respectively) and similar low EC 50 values (fipronil: 0.19 mg kg -1 dry soil, CL 95% 0.16-0.22; ivermectin: 0.43 mg kg -1 dry soil, CL 95% 0.09-0.77), although the effects observed in the former compound were possibly related to a low adult survival (LC 50 of 0.62 mg kg -1 dry soil; CL 95% : 0.25-1.06). For the latter compound no significant lethal effects were observed. Fluazuron caused an intermediate toxicity (EC 50 of 3.07 mg kg -1 dry soil, CL 95% : 2.26-3.87), and also here a decrease in adult survival could explain the effects observed at reproduction. Closantel, despite showing a significant reduction on the number of juveniles produced, no dose-response relationship nor effects higher than 50% were observed. Overall, all tested compounds, especially ivermectin, when present in soil even at sub-lethal concentrations, can impair the reproduction of collembolans and possibly other arthropods. However, the actual risk to arthropod communities should be further investigated performing tests under a more realistic exposure (e.g., by testing the dung itself as the contaminated matrix) and by deriving ecotoxicologically relevant exposure concentration in soil derived from the presence of cattle dung. Copyright © 2017 Elsevier

  7. Oral two-generation reproduction toxicity study with NM-200 synthetic amorphous silica in Wistar rats

    NARCIS (Netherlands)

    Wolterbeek, A.; Oosterwijk, T.; Schneider, S.; Landsiedel, R.; Groot, D. de; Ee, R. van; Wouters, M.; Sandt, H. van de

    2015-01-01

    Synthetic amorphous silica (SAS) like NM-200 is used in a wide variety of technological applications and consumer products. Although SAS has been widely investigated the available reproductive toxicity studies are old and do not cover all requirements of current OECD Guidelines. As part of a

  8. Three-generation reproduction toxicity study of genetically modified rice with insect resistant genes.

    Science.gov (United States)

    Hu, Yichun; Zhuo, Qin; Gong, Zhaolong; Piao, Jianhua; Yang, Xiaoguang

    2017-01-01

    In the present work, we evaluated the three generation reproductive toxicity of the genetically modified rice with insectresistant cry1Ac and sck genes. 120 Sprague-Dawley (SD) rats were divided into three groups which were fed with genetically modified rice diet (GM group), parental control rice diet (PR group) and AIN-93 control diet (both used as negative control) respectively. Bodyweight, food consumption, reproductive data, hematological parameters, serum chemistry, relative organ weights and histopathology for each generation were examined respectively. All the hematology and serum chemistry parameters, organ/body weight indicators were within the normal range or no change to the adverse direction was observed, although several differences in hematology and serum chemistry parameters (WBC, BUN, LDH of male rat, PLT, PCT, MPV of female rats), reproductive data (rate of morphologically abnormal sperm) were observed between GM rice group and two control groups. No macroscopic or histological adverse effects were found or considered as treatment-related, either. Overall, the three generation study of genetically modified rice with cry1Ac and sck genes at a high level showed no unintended adverse effects on rats's reproductive system. Copyright © 2016. Published by Elsevier Ltd.

  9. Reproductive Toxicity of Zishen Yutai Pill in Rats: The Fertility and Early Embryonic Development Study (Segment I

    Directory of Open Access Journals (Sweden)

    Li Zhou

    2016-01-01

    Full Text Available Purpose. This study was aimed to investigate the reproductive toxicity of Zishen Yutai Pill (ZYP on fertility and early embryonic development in rats. Methods. SD rats were randomly divided into 5 groups: vehicle control group (distilled water, i.g., positive control group (80 mg/kg of cyclophosphamide, i.p., and three ZYP-treated groups (3, 6, and 12 g/kg/d, i.e., 12x, 24x, and 48x clinical doses, i.g.. The high dose was set as the maximum gavage dosage. Results. Cyclophosphamide showed diverse hazards, such as decreased weight of male reproductive organs and sperm density (P<0.05. However, there were no obvious effects of ZYP on physical signs, animal behavior, and survival rate, as well as on weight and food intake during the premating and gestation periods. Importantly, there were no significant adverse effects of ZYP on indexes of copulation, fecundity and fertility indexes, weights and coefficients of male reproductive organs, epididymal sperm number and motility, estrous cycle, preimplantation loss rate, and implantation rate. Besides, the numbers of live and resorbed fetuses per litter were not significantly altered. Conclusions. ZYP had no reproductive toxicities on fertility and early embryonic development in rats at 48x equivalent clinical doses.

  10. Reproductive toxicity testing of vaccines

    International Nuclear Information System (INIS)

    Verdier, Francois; Barrow, Paul C.; Burge, Joeelle

    2003-01-01

    Vaccines play a major role in the prevention of human birth defects by protecting the pregnant woman from teratogenic or otherwise harmful infections. Until now, it has not been common practice to perform preclinical developmental toxicity tests for new vaccines. Despite the excellent safety record of vaccines, increased attention is now being given to the feasibility of screening new vaccines for developmental hazards in animals before their use in humans. Contrary to previous assumptions, many vaccines are now given to potentially pregnant women. Any new components of the vaccine formulation (adjuvants, excipients, stabilisers, preservatives, etc...) could also be tested for influences on development, although based on past experience the risks are limited by the very low dosages used. The conferred immunity following vaccination lasts for several years. Therefore, the developing conceptus may theoretically be exposed to the induced antibodies and/or sensitised T-cells, even if the pregnant woman was last vaccinated during childhood (particularly if she encounters the antigen during pregnancy through exposure to infection). However, it should be kept in mind that viral or bacterial infections represent a higher risk for a pregnant woman than the potential adverse effects related to vaccination or the associated immune response. Non-clinical safety studies may be employed as an aid for hazard identification. In these studies interactions of the vaccine with the maternal immune system or with the developmental systems of the offspring are considered. Post-natal examinations are necessary to detect all possible manifestations of developmental toxicity, such as effects on the immune system. Species selection for the preclinical studies is based on immunogenicity to the vaccine and the relative timing and rate of transfer of maternal antibodies to the offspring. A single study design is proposed for the pre- and post-natal developmental assessments of vaccines in

  11. Reproductive toxicity after levetiracetam administration in male rats: Evidence for role of hormonal status and oxidative stress.

    Directory of Open Access Journals (Sweden)

    Merve Baysal

    Full Text Available Levetiracetam (LEV is an antiepileptic drug commonly used in the treatment of epilepsy because of its excellent safety profile in all age groups. It is remarkable that there are no studies evaluating the toxic effects of this drug on the male reproductive system, as it is commonly used in male patients of reproductive age. From this point of view, our aim was to evaluate the possible toxic effects of LEV on the male reproductive system. Therefore, LEV was administered to male rats orally at 50, 150, and 300 mg/kg for 70 consecutive days. At the end of this period, alterations to body and organ weights were calculated, and sperm concentration, motility, and morphology were investigated by a computer-assisted sperm analysis system. Sperm DNA damage was determined by comet assay and histopathological examination of the testes was carried out. Serum testosterone, follicle-stimulating hormone (FSH, and luteinizing hormone (LH levels were measured by ELISAs to determine the effects of hormonal status, while glutathione, superoxide dismutase, catalase, and malondialdehyde levels in the testes were measured by colorimetric assay kits to determine the role of oxidative status in potential toxicity. According to the results, sperm quality was decreased by LEV treatment in a dose-dependent manner. LEV induced significant DNA damage in the 150 and 300 mg/kg LEV-administered groups. Histopathology of the testes showed that LEV resulted in testicular injury in the 300 mg/kg LEV-administered group. Serum testosterone, FSH, and LH levels were significantly decreased in the 300 mg/kg LEV-administered group. Glutathione, superoxide dismutase, and catalase levels were significantly decreased in all experimental groups while malondialdehyde levels were significantly increased in 150 and 300 mg/kg LEV-administered groups. According to these results, it was determined that LEV administration decreased sperm quality and it was alleged that hormonal alteration and

  12. Evaluation of the toxic effect of endocrine disruptor Bisphenol A (BPA) in the acute and chronic toxicity tests with Pomacea lineata gastropod.

    Science.gov (United States)

    de Andrade, André Lucas Correa; Soares, Priscila Rafaela Leão; da Silva, Stephannie Caroline Barros Lucas; da Silva, Marília Cordeiro Galvão; Santos, Thamiris Pinheiro; Cadena, Marilia Ribeiro Sales; Soares, Pierre Castro; Cadena, Pabyton Gonçalves

    2017-07-01

    Bisphenol A (BPA) is a plasticizer and a risk when it interacts with organisms, and can cause changes in the development and reproduction of them. This study aimed to evaluate the effects of BPA, by acute and chronic toxicity tests with neonates and adults of Pomacea lineata. Adults and neonates were divided into groups exposed to BPA (1-20mg/L), or 17β-estradiol (1mg/L) and control in the acute and chronic toxicity tests. Behavior, heart rate, reproduction and hemolymph biochemical analysis were measured. In the acute toxicity test, the 96-h LC 50 with adults was 11.09 and with neonates was 3.14mg/L. In this test, it was observed lethargic behavior and an increase of 77.6% of aspartate aminotransferase in the adults' hemolymph (ptest, it was observed behaviors associated with reproduction, as Copulate, in the groups exposed to BPA. The results that were found in this study proved that BPA is a potentially toxic agent to Pomacea lineata according to biological parameters evaluated. These data contribute to the understanding of BPA toxic effects' in the aquatic invertebrates. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. A category approach for reproductive effects of phthalates.

    NARCIS (Netherlands)

    Fabjan, Evelin; Hulzebos, Etje; Mennes, W; Piersma, Aldert H

    2006-01-01

    In regulatory toxicology, the experimental assessment of reproductive toxicity is one of the most costly endpoints to perform. Categorizing chemicals is an approach that can be used to reduce animal tests in risk assessments of chemicals, for example, via REACH (Registration, Evaluation, and

  14. Tavaborole, a Novel Boron-Containing Small Molecule Pharmaceutical Agent for Topical Treatment of Onychomycosis: I. Reproductive and Developmental Toxicity Studies.

    Science.gov (United States)

    Ciaravino, Vic; Coronado, Dina; Lanphear, Cheryl; Hoberman, Alan; Chanda, Sanjay

    2016-09-01

    Tavaborole is a topical antifungal agent approved by the US Food and Drug Administration for the treatment of toenail onychomycosis. As part of the nonclinical development program, reproductive and developmental toxicity studies were conducted (rat oral fertility and early embryonic development, rat (oral) and rabbit (dermal) embryo-fetal development). There were no effects on fertility or reproductive performance at doses up to 300 mg/kg/d (107 times the maximum recommended human dose [MRHD] based on mean area under the plasma concentration-time curve comparisons). In the rat embryo-fetal development toxicity studies, teratogenicity was not observed at doses up to 100 mg/kg/d (29 times the MRHD). However, several treatment-related skeletal malformations and variations were observed at 300 mg/kg/d (570 times the MRHD). In rabbit embryo-fetal development toxicity studies dosed via oral or dermal administration, the no observable adverse effect level for maternal toxicity and embryo-fetal toxicity was 50 mg/kg/d (16 times the MRHD) and 5% (26 times the MRHD), respectively. © The Author(s) 2016.

  15. Endocrine-disrupting effects and reproductive toxicity of low dose MCLR on male frogs (Rana nigromaculata) in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Jia, Xiuying; Cai, Chenchen; Wang, Jia; Gao, Nana; Zhang, Hangjun, E-mail: zhanghangjun@gmail.com

    2014-10-15

    Highlights: • Low-dose MCLR (1 μg/L) elicits a potential ecological effect on amphibian populations. • MCLR can induce abnormal sperm morphologies and activities on male frogs. • MCLR can induce a decrease in serum testosterone and an increase in serum estradiol of male frogs. • MCLR can increase SF-1 protein levels and decrease P450 aromatase levels in the gonads of frogs. - Abstract: Toxic cyanobacterial blooms are potential global threats to aquatic ecosystems and human health. The World Health Organization has set a provisional guideline limit of 1 μg/L microcystin-LR (MCLR) in freshwater. However, MCLR concentrations in several water bodies have exceeded this level. Despite this recommended human safety standard, MCLR-induced endocrine-disrupting effects and reproductive toxicity on male frog (Rana nigromaculata) were demonstrated in this study. Results showed that sperm motility and sperm count were significantly and negatively correlated with exposure time and concentration. By contrast, abnormal sperm rate was positively correlated with both parameters. Ultrastructural observation results revealed abnormal sperm morphologies, vacuoles in spermatogenic cells, cell dispersion, incomplete cell structures, and deformed nucleoli. These results indicated that MCLR could induce toxic effects on the reproductive system of frogs, significantly decrease testosterone content, and rapidly increase estradiol content. Prolonged exposure and increased concentration enhanced the relative expression levels of P450 aromatase and steroidogenic factor 1; thus, endocrine function in frogs was disrupted. This study is the first to demonstrate in vivo MCLR toxicity in the reproductive system of male R. nigromaculata. This study provided a scientific basis of the global decline in amphibian populations.

  16. Endocrine-disrupting effects and reproductive toxicity of low dose MCLR on male frogs (Rana nigromaculata) in vivo

    International Nuclear Information System (INIS)

    Jia, Xiuying; Cai, Chenchen; Wang, Jia; Gao, Nana; Zhang, Hangjun

    2014-01-01

    Highlights: • Low-dose MCLR (1 μg/L) elicits a potential ecological effect on amphibian populations. • MCLR can induce abnormal sperm morphologies and activities on male frogs. • MCLR can induce a decrease in serum testosterone and an increase in serum estradiol of male frogs. • MCLR can increase SF-1 protein levels and decrease P450 aromatase levels in the gonads of frogs. - Abstract: Toxic cyanobacterial blooms are potential global threats to aquatic ecosystems and human health. The World Health Organization has set a provisional guideline limit of 1 μg/L microcystin-LR (MCLR) in freshwater. However, MCLR concentrations in several water bodies have exceeded this level. Despite this recommended human safety standard, MCLR-induced endocrine-disrupting effects and reproductive toxicity on male frog (Rana nigromaculata) were demonstrated in this study. Results showed that sperm motility and sperm count were significantly and negatively correlated with exposure time and concentration. By contrast, abnormal sperm rate was positively correlated with both parameters. Ultrastructural observation results revealed abnormal sperm morphologies, vacuoles in spermatogenic cells, cell dispersion, incomplete cell structures, and deformed nucleoli. These results indicated that MCLR could induce toxic effects on the reproductive system of frogs, significantly decrease testosterone content, and rapidly increase estradiol content. Prolonged exposure and increased concentration enhanced the relative expression levels of P450 aromatase and steroidogenic factor 1; thus, endocrine function in frogs was disrupted. This study is the first to demonstrate in vivo MCLR toxicity in the reproductive system of male R. nigromaculata. This study provided a scientific basis of the global decline in amphibian populations

  17. Standardized toxicity testing may underestimate ecotoxicity: Environmentally relevant food rations increase the toxicity of silver nanoparticles to Daphnia.

    Science.gov (United States)

    Stevenson, Louise M; Krattenmaker, Katherine E; Johnson, Erica; Bowers, Alexandra J; Adeleye, Adeyemi S; McCauley, Edward; Nisbet, Roger M

    2017-11-01

    Daphnia in the natural environment experience fluctuations in algal food supply, with periods when algal populations bloom and seasons when Daphnia have very little algal food. Standardized chronic toxicity tests, used for ecological risk assessment, dictate that Daphnia must be fed up to 400 times more food than they would experience in the natural environment (outside of algal blooms) for a toxicity test to be valid. This disconnect can lead to underestimating the toxicity of a contaminant. We followed the growth, reproduction, and survival of Daphnia exposed to 75 and 200 µg/L silver nanoparticles (AgNPs) at 4 food rations for up to 99 d and found that AgNP exposure at low, environmentally relevant food rations increased the toxicity of AgNPs. Exposure to AgNP at low food rations decreased the survival and/or reproduction of individuals, with potential consequences for Daphnia populations (based on calculated specific population growth rates). We also found tentative evidence that a sublethal concentration of AgNPs (75 µg/L) caused Daphnia to alter energy allocation away from reproduction and toward survival and growth. The present findings emphasize the need to consider resource availability, and not just exposure, in the environment when estimating the effect of a toxicant. Environ Toxicol Chem 2017;36:3008-3018. © 2017 SETAC. © 2017 SETAC.

  18. Reproductive toxicity of Samanea tubulosa on rats

    Directory of Open Access Journals (Sweden)

    Maria Rafaella Luz de Araújo

    2015-12-01

    Full Text Available Samanea tubulosa is a plant used for medicinal and feeding purposes. However, ingestion of S. tubulosa pods has been associated with bovine abortion. Thus, the aim of this work was to investigate the effects of diet containing 5% of S. tubulosa pod meal on male and female Wistar rats. Diet was administered to male rats (n = 10 for 60 days before mating. Female rats (n = 10 received the treatment for 30 days, during cohabitation and from gestational day (GD 0 to GD20. Treated animals were mated with untreated rats. In male rats, plant consumption caused decreased food consumption and 20% fertility index reduction. Litters from treated males presented lower body weight and crown–rump length. Female rats treated with the plant increased water and food intake and body weight. Decreases in fertility, fecundity and gestation indices and increase of placenta weight and mean number of corpora lutea were found. Thus, owing to the possible general and reproductive toxic effects, long-term consumption of S. tubulosa is not recommended for phytotherapic or food purposes.

  19. An integrated omic analysis of hepatic alteration in medaka fish chronically exposed to cyanotoxins with possible mechanisms of reproductive toxicity.

    Science.gov (United States)

    Qiao, Qin; Le Manach, Séverine; Huet, Hélène; Duvernois-Berthet, Evelyne; Chaouch, Soraya; Duval, Charlotte; Sotton, Benoit; Ponger, Loïc; Marie, Arul; Mathéron, Lucrèce; Lennon, Sarah; Bolbach, Gérard; Djediat, Chakib; Bernard, Cécile; Edery, Marc; Marie, Benjamin

    2016-12-01

    Cyanobacterial blooms threaten human health as well as the population of other living organisms in the aquatic environment, particularly due to the production of natural toxic components, the cyanotoxin. So far, the most studied cyanotoxins are microcystins (MCs). In this study, the hepatic alterations at histological, proteome and transcriptome levels were evaluated in female and male medaka fish chronically exposed to 1 and 5 μg L -1 microcystin-LR (MC-LR) and to the extract of MC-producing Microcystis aeruginosa PCC 7820 (5 μg L -1 of equivalent MC-LR) by balneation for 28 days, aiming at enhancing our understanding of the potential reproductive toxicity of cyanotoxins in aquatic vertebrate models. Indeed, both MC and Microcystis extract adversely affect reproductive parameters including fecundity and egg hatchability. The liver of toxin treated female fish present glycogen storage loss and cellular damages. The quantitative proteomics analysis revealed that the quantities of 225 hepatic proteins are dysregulated. In particular, a notable decrease in protein quantities of vitellogenin and choriogenin was observed, which could explain the decrease in reproductive output. Liver transcriptome analysis through Illumina RNA-seq reveals that over 100-400 genes are differentially expressed under 5 μg L -1  MC-LR and Microcystis extract treatments, respectively. Ingenuity pathway analysis of the omic data attests that various metabolic pathways, such as energy production, protein biosynthesis and lipid metabolism, are disturbed by both MC-LR and the Microcystis extract, which could provoke the observed reproductive impairment. The transcriptomics analysis also constitutes the first report of the impairment of circadian rhythm-related gene induced by MCs. This study contributes to a better understanding of the potential consequences of chronic exposure of fish to environmental concentrations of cyanotoxins, suggesting that Microcystis extract could impact a

  20. Reproductive toxicity of a mixture of regulated drinking-water disinfection by-products in a multigenerational rat bioassay

    Science.gov (United States)

    BACKGROUND:Trihalomethanes (THMs) and haloaretic acids (HAAs) are regulated disinfection by-products (DBPs); their joint reproductive toxicity in drinking water is unknown.OBJECTIVE: We aimed to evaluate a drinking water mixture of the four regulated THMs and five regulated HAAs ...

  1. THE RISK FACTORS FOR INITIAL REPRODUCTIVE LOSS

    Directory of Open Access Journals (Sweden)

    Екатерина Игоревна Лебедева

    2017-09-01

    Conclusion. Mixed somatic and gynecological pathology, abnormalities in hemostasis, combination of inherited and acquired thrombogenic risk factors dominates in women with initial reproductive loss, though only 37,3 % such pregnancies have favorable outcome.

  2. Occupational reproductive health risks.

    Science.gov (United States)

    Filkins, K; Kerr, M J

    1993-01-01

    The potentially harmful effects on women of certain workplace exposures are widely appreciated, and steps to control these have included legislative efforts such as right-to-know laws of well as corporate policies mandating selective restriction of fertile women, which are illegal under federal civil rights laws. This chapter reviews the various occupational health risks reproductive women face in the workplace but also considers the effects of other genetic, medical, social, infectious, and environmental factors which may be of even greater concern than most occupational factors.

  3. Evaluation of the Reproductive and Developmental Risks of Caffeine

    Science.gov (United States)

    Brent, Robert L; Christian, Mildred S; Diener, Robert M

    2011-01-01

    A risk analysis of in utero caffeine exposure is presented utilizing epidemiological studies and animal studies dealing with congenital malformation, pregnancy loss, and weight reduction. These effects are of interest to teratologists, because animal studies are useful in their evaluation. Many of the epidemiology studies did not evaluate the impact of the “pregnancy signal,” which identifies healthy pregnancies and permits investigators to identify subjects with low pregnancy risks. The spontaneous abortion epidemiology studies were inconsistent and the majority did not consider the confounding introduced by not considering the pregnancy signal. The animal studies do not support the concept that caffeine is an abortafacient for the wide range of human caffeine exposures. Almost all the congenital malformation epidemiology studies were negative. Animal pharmacokinetic studies indicate that the teratogenic plasma level of caffeine has to reach or exceed 60 µg/ml, which is not attainable from ingesting large amounts of caffeine in foods and beverages. No epidemiological study described the “caffeine teratogenic syndrome.” Six of the 17 recent epidemiology studies dealing with the risk of caffeine and fetal weight reduction were negative. Seven of the positive studies had growth reductions that were clinically insignificant and none of the studies cited the animal literature. Analysis of caffeine's reproductive toxicity considers reproducibility and plausibility of clinical, epidemiological, and animal data. Moderate or even high amounts of beverages and foods containing caffeine do not increase the risks of congenital malformations, miscarriage or growth retardation. Pharmacokinetic studies markedly improve the ability to perform the risk analyses. Birth Defects Res (Part B) 92:152–187, 2011. © 2011 Wiley-Liss, Inc. PMID:21370398

  4. The associations between a polygenic score, reproductive and menstrual risk factors and breast cancer risk.

    Science.gov (United States)

    Warren Andersen, Shaneda; Trentham-Dietz, Amy; Gangnon, Ronald E; Hampton, John M; Figueroa, Jonine D; Skinner, Halcyon G; Engelman, Corinne D; Klein, Barbara E; Titus, Linda J; Newcomb, Polly A

    2013-07-01

    We evaluated whether 13 single nucleotide polymorphisms (SNPs) identified in genome-wide association studies interact with one another and with reproductive and menstrual risk factors in association with breast cancer risk. DNA samples and information on parity, breastfeeding, age at menarche, age at first birth, and age at menopause were collected through structured interviews from 1,484 breast cancer cases and 1,307 controls who participated in a population-based case-control study conducted in three US states. A polygenic score was created as the sum of risk allele copies multiplied by the corresponding log odds estimate. Logistic regression was used to test the associations between SNPs, the score, reproductive and menstrual factors, and breast cancer risk. Nonlinearity of the score was assessed by the inclusion of a quadratic term for polygenic score. Interactions between the aforementioned variables were tested by including a cross-product term in models. We confirmed associations between rs13387042 (2q35), rs4973768 (SLC4A7), rs10941679 (5p12), rs2981582 (FGFR2), rs3817198 (LSP1), rs3803662 (TOX3), and rs6504950 (STXBP4) with breast cancer. Women in the score's highest quintile had 2.2-fold increased risk when compared to women in the lowest quintile (95 % confidence interval: 1.67-2.88). The quadratic polygenic score term was not significant in the model (p = 0.85), suggesting that the established breast cancer loci are not associated with increased risk more than the sum of risk alleles. Modifications of menstrual and reproductive risk factors associations with breast cancer risk by polygenic score were not observed. Our results suggest that the interactions between breast cancer susceptibility loci and reproductive factors are not strong contributors to breast cancer risk.

  5. Reproductive History and Risk of Multiple Sclerosis

    DEFF Research Database (Denmark)

    Nielsen, N. M.; Jorgensen, K. T.; Stenager, E.

    2011-01-01

    Background: It has been suggested that reproductive factors may be involved in the etiology of multiple sclerosis (MS). We studied associations of reproductive history with MS risk in a population-based setting. Methods: Using national databases, we established a cohort comprising 4.4 million...... Danish men and women born between 1935 and 1989 and alive in 1968 or later. We obtained information about their live-born children, pregnancy losses, pregnancy complications, and infertility diagnoses. MS cases in the cohort were identified through 2004 in the Danish Register of Multiple Sclerosis...

  6. Genetic Counselors' Experiences Regarding Communication of Reproductive Risks with Autosomal Recessive Conditions found on Cancer Panels.

    Science.gov (United States)

    Mets, Sarah; Tryon, Rebecca; Veach, Patricia McCarthy; Zierhut, Heather A

    2016-04-01

    The development of hereditary cancer genetic testing panels has altered genetic counseling practice. Mutations within certain genes on cancer panels pose not only a cancer risk, but also a reproductive risk for autosomal recessive conditions such as Fanconi anemia, constitutional mismatch repair deficiency syndrome, and ataxia telangiectasia. This study aimed to determine if genetic counselors discuss reproductive risks for autosomal recessive conditions associated with genes included on cancer panels, and if so, under what circumstances these risks are discussed. An on-line survey was emailed through the NSGC list-serv. The survey assessed 189 cancer genetic counselors' experiences discussing reproductive risks with patients at risk to carry a mutation or variant of uncertain significance (VUS) in a gene associated with both an autosomal dominant cancer risk and an autosomal recessive syndrome. Over half (n = 82, 55 %) reported having discussed reproductive risks; the remainder (n = 66, 45 %) had not. Genetic counselors who reported discussing reproductive risks primarily did so when patients had a positive result and were of reproductive age. Reasons for not discussing these risks included when a patient had completed childbearing or when a VUS was identified. Most counselors discussed reproductive risk after obtaining results and not during the informed consent process. There is inconsistency as to if and when the discussion of reproductive risks is taking place. The wide variation in responses suggests a need to develop professional guidelines for when and how discussions of reproductive risk for autosomal recessive conditions identified through cancer panels should occur with patients.

  7. Pharmacokinetics and expert systems as aids for risk assessment in reproductive toxicology.

    OpenAIRE

    Mattison, D R; Jelovsek, F R

    1987-01-01

    A minimal approach to risk assessment in reproductive toxicology involves four components: hazard identification, hazard characterization, exposure characterization, and risk characterization. In practice, risk assessment in reproductive toxicology has been reduced to arbitrary safety factors or mathematical models of the dose-response relationship. These approaches obscure biological differences across species rather than using this important and frequently accessible information. Two approa...

  8. Cardiometabolic Risk in PCOS: More than a Reproductive Disorder.

    Science.gov (United States)

    Torchen, Laura C

    2017-11-11

    Polycystic ovary syndrome (PCOS) is diagnosed by its characteristic reproductive features. However, PCOS is also associated with metabolic abnormalities, including insulin resistance and β-cell dysfunction. The severity of these abnormalities varies according to the reproductive phenotype, with the so-called NIH or classic phenotype conferring the greatest metabolic risk. The increased risk for type 2 diabetes (T2D) is well established among affected women with the NIH phenotype, but whether PCOS also confers an increased risk for cardiovascular events remains unknown. Recent studies in daughters of affected women have found evidence for pancreatic β-cell dysfunction prior to menarche. Further, genetic analyses have provided evidence that metabolic abnormalities such as obesity and insulin resistance contribute to the pathogenesis of PCOS. PCOS increases the risk for T2D. However, the risk for cardiovascular disease has not been quantified, and prospective, longitudinal studies are still critically needed.

  9. Health risks associated with inhaled nasal toxicants

    NARCIS (Netherlands)

    Feron, VJ; Arts, JHE; Kuper, CF; Slootweg, PJ; Woutersen, RA

    2001-01-01

    Health risks of inhaled nasal toxicants were reviewed with emphasis on chemically induced nasal lesions in humans, sensory irritation, olfactory and trigeminal nerve toxicity, nasal immunopathology and carcinogenesis, nasal responses to chemical mixtures, in vitro models, and nasal dosimetry- and

  10. Cyanotoxins: producing organisms, occurrence, toxicity, mechanism of action and human health toxicological risk evaluation.

    Science.gov (United States)

    Buratti, Franca M; Manganelli, Maura; Vichi, Susanna; Stefanelli, Mara; Scardala, Simona; Testai, Emanuela; Funari, Enzo

    2017-03-01

    Cyanobacteria were present on the earth 3.5 billion years ago; since then they have colonized almost all terrestrial and aquatic ecosystems. They produce a high number of bioactive molecules, among which some are cyanotoxins. Cyanobacterial growth at high densities, forming blooms, is increasing in extension and frequency, following anthropogenic activities and climate changes, giving rise to some concern for human health and animal life exposed to cyanotoxins. Numerous cases of lethal poisonings have been associated with cyanotoxins ingestion in wild animal and livestock. In humans few episodes of lethal or severe human poisonings have been recorded after acute or short-term exposure, but the repeated/chronic exposure to low cyanotoxin levels remains a critical issue. The properties of the most frequently detected cyanotoxins (namely, microcystins, nodularins, cylindrospermopsin and neurotoxins) are here critically reviewed, describing for each toxin the available information on producing organisms, biosynthesis/genetic and occurrence, with a focus on the toxicological profile (including kinetics, acute systemic toxicity, mechanism and mode of action, local effects, repeated toxicity, genotoxicity, carcinogenicity, reproductive toxicity; human health effects and epidemiological studies; animal poisoning) with the derivation of health-based values and considerations on the risks for human health.

  11. Cardiometabolic Risk in PCOS: More than a Reproductive Disorder

    Science.gov (United States)

    Torchen, Laura C.

    2018-01-01

    Purpose of Review Polycystic ovary syndrome (PCOS) is diagnosed by its characteristic reproductive features. However, PCOS is also associated with metabolic abnormalities, including insulin resistance and β-cell dysfunction. The severity of these abnormalities varies according to the reproductive phenotype, with the so-called NIH or classic phenotype conferring the greatest metabolic risk. The increased risk for type 2 diabetes (T2D) is well-established among affected women with the NIH phenotype, but whether PCOS also confers an increased risk for cardiovascular events remains unknown. Recent Findings Recent studies in daughters of affected women have found evidence for pancreatic β-cell dysfunction prior to menarche. Further, genetic analyses have provided evidence that metabolic abnormalities such as obesity and insulin resistance contribute to the pathogenesis of PCOS. Summary PCOS increases the risk for T2D. However, the risk for cardiovascular disease has not been quantified, and prospective, longitudinal studies are still critically needed. PMID:29128916

  12. Risk of hypertensive disorders in pregnancies following assisted reproductive technology

    DEFF Research Database (Denmark)

    Opdahl, S; Henningsen, A A; Tiitinen, A

    2015-01-01

    STUDY QUESTION: Is the risk of hypertensive disorders in pregnancies conceived following specific assisted reproductive technology (ART) procedures different from the risk in spontaneously conceived (SC) pregnancies? SUMMARY ANSWER: ART pregnancies had a higher risk of hypertensive disorders, in ...

  13. Health, equity, and reproductive risks in the workplace.

    Science.gov (United States)

    Daniels, C R; Paul, M; Rosofsky, R

    1990-01-01

    Potential exposure to occupational reproductive hazards raises complex questions regarding health and gender discrimination in the workplace. On the one hand, growing scientific evidence suggests that workplace exposures to either sex can cause a wide range of disorders ranging from infertility to adverse pregnancy outcomes. On the other hand, policies alleging to protect workers from reproductive risks have often reinforced gender inequalities in the workplace. This article sheds new light on this continuing debate through an examination of the policy insights suggested by a recent study of reproductive hazard policies in Massachusetts. In what ways do policies evidenced in this study reflect or differ from historical patterns of protectionism? The article presents a political-legal review of reproductive hazard policies in the workplace, then examines the policy implications of the Massachusetts study, and finally presents the prescriptions for change that are implied by both the historical and contemporary evidence.

  14. Effects of functionalized fullerenes on bifenthrin and tribufos toxicity to Daphnia magna: Survival, reproduction, and growth rate.

    Science.gov (United States)

    Brausch, Kathryn A; Anderson, Todd A; Smith, Philip N; Maul, Jonathan D

    2010-11-01

    Incorporation of carbon nanomaterials into industrial and consumer products is increasing, yet their impact on aquatic ecosystems alone and in chemical mixtures is largely unknown. Carbon nanomaterials may be found in the aquatic environment as mixtures with pesticides because of their proposed use in agriculture as smart delivery systems and nanosensors. The interaction effects of a functionalized fullerene ([1,2-methanofullerene C₆₀]-61-carboxylic acid) (fC₆₀) at 52.8 µg/L and the hydrophobic pesticides bifenthrin and tribufos were examined. The test organism was Daphnia magna, and response variables included 48-h survival, reproduction (bifenthrin, 70-d; tribufos, 21-d), and 10-d growth. Both pesticides reduced D. magna survival and reproduction (p bifenthrin acute toxicity but did not significantly affect chronic endpoints or growth (p > 0.05). Median lethal concentrations (LC50s), median inhibition concentrations (IC50s) for days surviving, and IC50s for reproduction were 0.86, 0.55, and 0.49 µg/L for bifenthrin; 0.22, 0.39, and 0.77 µg/L for fC₆₀-bifenthrin mix; 6.63, 9.89, and 5.79 µg/L for tribufos; and 9.17, 8.17, and 6.59 µg/L for fC₆₀-tribufos mix. Mixtures did not affect instantaneous growth rate (p > 0.05). These results suggest that fC₆₀ had little effect on pesticide chronic toxicity but influenced acute toxicity. Given the widespread application of nanotechnology, the influence of nanomaterials on environmental contaminants is an important consideration. Thus, our results may be useful in the development and use of nanotechnology in agricultural practices. © 2010 SETAC.

  15. Emerging Fusarium and Alternaria Mycotoxins: Occurrence, Toxicity and Toxicokinetics

    Directory of Open Access Journals (Sweden)

    Sophie Fraeyman

    2017-07-01

    Full Text Available Emerging Fusarium and Alternaria mycotoxins gain more and more interest due to their frequent contamination of food and feed, although in vivo toxicity and toxicokinetic data are limited. Whereas the Fusarium mycotoxins beauvericin, moniliformin and enniatins particularly contaminate grain and grain-based products, Alternaria mycotoxins are also detected in fruits, vegetables and wines. Although contamination levels are usually low (µg/kg range, higher contamination levels of enniatins and tenuazonic acid may occasionally occur. In vitro studies suggest genotoxic effects of enniatins A, A1 and B1, beauvericin, moniliformin, alternariol, alternariol monomethyl ether, altertoxins and stemphyltoxin-III. Furthermore, in vitro studies suggest immunomodulating effects of most emerging toxins and a reproductive health hazard of alternariol, beauvericin and enniatin B. More in vivo toxicity data on the individual and combined effects of these contaminants on reproductive and immune system in both humans and animals is needed to update the risk evaluation by the European Food Safety Authority. Taking into account new occurrence data for tenuazonic acid, the complete oral bioavailability, the low total body clearance in pigs and broiler chickens and the limited toxicity data, a health risk cannot be completely excluded. Besides, some less known Alternaria toxins, especially the genotoxic altertoxins and stemphyltoxin III, should be incorporated in risk evaluation as well.

  16. Understanding Pesticide Risks: Toxicity and Formulation

    OpenAIRE

    Muntz, Helen; Miller, Rhonda; Alston, Diane

    2016-01-01

    This fact sheet provides information about pesticide risks to human health, primary means of pesticide exposure, standardized measures of pesticide toxicity, pesticide signal words and type of pesticide formulations.

  17. Effects of toxic chemicals on the reproductive system. Council on Scientific Affairs.

    Science.gov (United States)

    1985-06-21

    In an effort to make physicians more aware of the hazards of the workplace to pregnant workers, the Council on Scientific Affairs' Advisory Panel on Reproductive Hazards in the Workplace prepared this third and final report reviewing the effects of chemical exposure. A total of 120 chemicals were considered for reviews based on an estimation of their imminent hazard, ie, widespread use and/or inherent toxicity. Following a brief introduction, which sets out general principles, clinical applications, and aids to the recognition of a human teratogen, the report presents reviews and opinions for three representative chemicals. Information concerning the remaining 117 compounds is available upon request.

  18. Association between duration of reproductive lifespan and Framingham risk score in postmenopausal women.

    Science.gov (United States)

    Kim, Soo Hyun; Sim, Mu Yul; Park, Sat Byul

    2015-12-01

    The benefit of estrogen therapy in postmenopausal women is still uncertain. Based upon extensive observational data, it was believed that estrogen was cardioprotective. The relationship between the period of exposure to endogenous estrogens and the risk of cardiovascular disease (CVD) has not been studied in Korean women. To assess associations between reproductive lifespan and CVD by using the Framingham risk score (FRS) in postmenopausal Korean women. This cross-sectional, population-based study used data from the Korea National Health and Nutrition Examination Survey (KNHANES) for the five years 2008-2012,after adjustment for relevant variables using complex sample analysis and data weighting. Among 25,534 women, 1973 women were enrolled, after excluding those 80 years of age (n=6194), those with diabetes, CVD or cancer (n=491), those with unrecorded physical measurements (n=7335), those with menarche age ≤8 years or ≥20 years (n=6194), and premenopausal women (n=3347). The FRS tended to show a significant negative correlation with the reproductive lifespan (preproductive lifespan and FRS (adjusted relative risk [RR] for reproductive years [shortest lifespan group] compared with 28-33 reproductive years [moderate lifespan group], 1.2, p33 reproductive years [longest lifespan group] compared with 28-33 reproductive years [moderate lifespan group], -0.42, p=0.011). A longer reproductive lifespan is associated with a lower estimated risk of CVD in the next 10 years in postmenopausal women. This result suggests that estrogen has a long-term protective effect against CVD. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  19. Fertility drugs, reproductive strategies and ovarian cancer risk

    OpenAIRE

    Tomao, Federica; Lo Russo, Giuseppe; Spinelli, Gian Paolo; Stati, Valeria; Prete, Alessandra Anna; Prinzi, Natalie; Sinjari, Marsela; Vici, Patrizia; Papa, Anselmo; Chiotti, Maria Stefania; Benedetti Panici, Pierluigi; Tomao, Silverio

    2014-01-01

    Several adverse effects have been related to infertility treatments, such as cancer development. In particular, the relationship between infertility, reproductive strategies, and risk of gynecological cancers has aroused much interest in recent years. The evaluation of cancer risk among women treated for infertility is very complex, mainly because of many factors that can contribute to occurrence of cancer in these patients (including parity status). This article addresses the possible associ...

  20. Review of hazards to female reproductive health in veterinary practice.

    Science.gov (United States)

    Scheftel, Joni M; Elchos, Brigid L; Rubin, Carol S; Decker, John A

    2017-04-15

    OBJECTIVE To review publications that address female reproductive health hazards in veterinary practice, summarize best practices to mitigate reproductive risks, and identify current knowledge gaps. DESIGN Systematized review. SAMPLE English-language articles describing chemical, biological, and physical hazards present in the veterinary workplace and associations with adverse reproductive outcomes or recommendations for minimizing risks to female reproductive health. PROCEDURES Searches of the CAB abstracts database were performed in July 2012 and in May 2015 with the following search terms: veterinarians AND occupational hazards and vets.id AND occupational hazards.sh. Searches of the PubMed database were conducted in November 2012 and in May 2015 with the following medical subject heading terms: occupational exposure AND veterinarians; anesthetics, inhalation/adverse effects AND veterinarians; risk factors AND pregnancy AND veterinarians; pregnancy outcome AND veterinarians; and animal technicians AND occupational exposure. Two additional PubMed searches were completed in January 2016 with the terms disinfectants/toxicity AND female AND fertility/drug effects and veterinarians/psychology AND stress, psychological. No date limits were applied to searches. RESULTS 4 sources supporting demographic trends in veterinary medicine and 118 resources reporting potential hazards to female reproductive health were identified. Reported hazards included exposure to anesthetic gases, radiation, antineoplastic drugs, and reproductive hormones; physically demanding work; prolonged standing; and zoonoses. CONCLUSIONS AND CLINICAL RELEVANCE Demographic information suggested that an increasing number of women of reproductive age will be exposed to chemical, biological, and physical hazards in veterinary practice. Information on reproductive health hazards and minimizing risk, with emphasis on developing a safety-focused work culture for all personnel, should be discussed starting

  1. Food plant toxicants and safety - Risk assessment and regulation of inherent toxicants in plant foods

    DEFF Research Database (Denmark)

    Essers, A.J.A.; Alink, G.M.; Speijers, G.J.A.

    1998-01-01

    The ADI as a tool for risk management and regulation of food additives and pesticide residues is not readily applicable to inherent food plant toxicants: The margin between actual intake and potentially toxic levels is often small; application of the default uncertainty factors used to derive ADI...... values, particularly when extrapolating from animal data, would prohibit the utilisation of the food, which may have an overall beneficial health effect. Levels of inherent toxicants are difficult to control; their complete removal is not always wanted, due to their function for the plant or for human...... health. The health impact of the inherent toxicant is often modified by factors in the food, e.g. the bioavailability from the matrix and interaction with other inherent constituents. Risk-benefit analysis should be made for different consumption scenarios, without the use of uncertainty factors. Crucial...

  2. Reproductive factors and Parkinson's disease risk in Danish women

    DEFF Research Database (Denmark)

    Greene, N; Lassen, C F; Rugbjerg, K

    2014-01-01

    and lifestyle factors. RESULTS: After adjusting for smoking, caffeine and alcohol use, education, age, and family Parkinson's disease history, inverse associations between Parkinson's disease and early menarche (first period at ≤11 years), oral contraceptives, high parity (≥4 children) and bilateral...... and fertile life length, age at menopause or post-menopausal hormone treatment was found. CONCLUSIONS: Reproductive factors related to women's early- to mid-reproductive lives appear to be predictive of subsequent Parkinson's disease risk whereas factors occurring later in life seem less important....

  3. Raphanus sativus extract protects against Zearalenone induced reproductive toxicity, oxidative stress and mutagenic alterations in male Balb/c mice.

    Science.gov (United States)

    Ben Salah-Abbès, Jalila; Abbès, Samir; Abdel-Wahhab, Mosaad A; Oueslati, Ridha

    2009-04-01

    Zearalenone (ZEN) is a non-steroidal estrogenic mycotoxin produced by several species of Fusarium in cereals and agricultural products. It has been implicated in several mycotoxicosis in farm animals and in humans. There is unequivocal evidence of reproductive toxicity of ZEN in male mice although the mechanism of action is unknown. Several reports suggest that exposure to ZEN resulted in oxidative stress, genotoxicity and perturbation of reproductive parameters. Therefore, the aim of the current study was to evaluate the protective effects of aqueous extract of Raphanus sativus growing in Tunisia against ZEN-induced reproductive toxicity and oxidative stress. Fifty male Balb/c mice were divided into five groups and treated for 28 days as follows: the control group, olive oil-treated groups, another treated with ZEN (40 mg/kg b.w), the last one treated with R. sativus extract alone (15 mg/kg b.w) and the other with ZEN + R. sativus extract. Testis samples were collected for the epididymal sperm count, testosterone concentration, and MDA level, GPx, CAT and SOD activities. Blood samples were collected for different biochemical analyses. Also, RAPD-PCR method was performed to assess the antigenotoxic effect of the extract in germ cells. The results indicated that ZEN-induced toxicological effects in accordance to those reported in the literature: decreasing in the sperm number, testosterone level and antioxidant enzyme status. The RAPD-PCR analysis revealed an alteration in the DNA bands patterns between control and ZEN-treated mice. The extract alone, rich in many antioxidant compounds, was safe and succeeded in counteracting the oxidative stress and protect against the toxicity resulting from ZEN.

  4. NTP-CERHR Expert Panel Report on the reproductive and developmental toxicity of hydroxyurea

    Science.gov (United States)

    The National Toxicology Program (NTP) and the National Institute of Environmental Health Sciences (NIEHS) established the NTP Center for the Evaluation of Risks to Human Reproduction (CERHR) in June 1998. The purpose of CERHR is to provide timely, unbiased, scientifically sound e...

  5. Reproductive Toxic Chemicals at Work and Efforts to Protect Workers' Health: A Literature Review

    Directory of Open Access Journals (Sweden)

    Kyung-Taek Rim

    2017-06-01

    Full Text Available A huge number of chemicals are produced and used in the world, and some of them can have negative effects on the reproductive health of workers. To date, most chemicals and work environments have not been studied for their potential to have damaging effects on the workers' reproductive system. Because of the lack of information, many workers may not be aware that such problems can be related to occupational exposures. Newly industrialized countries such as Republic of Korea have rapidly amassed chemicals and other toxicants that pose health hazards, especially to the reproductive systems of workers. This literature review provides an overview of peer-reviewed literature regarding the teratogenic impact and need for safe handling of chemicals. Literature searches were performed using PubMed, Google Scholar, and ScienceDirect. Search strategies were narrowed based on author expertise and 100 articles were chosen for detailed analysis. A total of 47 articles met prespecified inclusion criteria. The majority of papers contained studies that were descriptive in nature with respect to the Medical Subject Headings (MeSH terms and keywords: “reproductive and heath or hazard and/or workplace or workers or occupations.” In the absence of complete information about the safe occupational handling of chemicals in Republic of Korea (other than a material safety data sheet, this review serves as a valuable reference for identifying and remedying potential gaps in relevant regulations. The review also proposes other public health actions including hazard surveillance and primary prevention activities such as reduction, substitution, ventilation, as well as protective equipment.

  6. Reproductive Toxic Chemicals at Work and Efforts to Protect Workers' Health: A Literature Review.

    Science.gov (United States)

    Rim, Kyung-Taek

    2017-06-01

    A huge number of chemicals are produced and used in the world, and some of them can have negative effects on the reproductive health of workers. To date, most chemicals and work environments have not been studied for their potential to have damaging effects on the workers' reproductive system. Because of the lack of information, many workers may not be aware that such problems can be related to occupational exposures. Newly industrialized countries such as Republic of Korea have rapidly amassed chemicals and other toxicants that pose health hazards, especially to the reproductive systems of workers. This literature review provides an overview of peer-reviewed literature regarding the teratogenic impact and need for safe handling of chemicals. Literature searches were performed using PubMed, Google Scholar, and ScienceDirect. Search strategies were narrowed based on author expertise and 100 articles were chosen for detailed analysis. A total of 47 articles met prespecified inclusion criteria. The majority of papers contained studies that were descriptive in nature with respect to the Medical Subject Headings (MeSH) terms and keywords: "reproductive and heath or hazard and/or workplace or workers or occupations." In the absence of complete information about the safe occupational handling of chemicals in Republic of Korea (other than a material safety data sheet), this review serves as a valuable reference for identifying and remedying potential gaps in relevant regulations. The review also proposes other public health actions including hazard surveillance and primary prevention activities such as reduction, substitution, ventilation, as well as protective equipment.

  7. The era of 3Rs implementation in developmental and reproductive toxicity (DART) testing: Current overview and future perspectives.

    Science.gov (United States)

    Beekhuijzen, Manon

    2017-09-01

    Since adoption of the first globally implemented guidelines for developmental and reproductive toxicity (DART) testing for pharmaceuticals, industrial chemicals and agrochemicals, many years passed without major updates. However in recent years, significant changes in these guidelines have been made or are being implemented. These changes have been guided by the ethical drive to reduce, refine and replace (3R) animal testing, as well as the addition of endocrine disruptor relevant endpoints. Recent applied improvements have focused on reduction and refinement. Ongoing scientific and technical innovations will provide the means for replacement of animal testing in the future and will improve predictivity in humans. The aim of this review is to provide an overview of ongoing global DART endeavors in respect to the 3Rs, with an outlook towards future advances in DART testing aspiring to reduce animal testing to a minimum and the supreme ambition towards animal-free hazard and risk assessment. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Food plant toxicants and safety: risk assessment and regulation of inherent toxicants in plant foods.

    NARCIS (Netherlands)

    Essers, A.J.; Alink, G.M.; Speijers, G.J.A.; Alexander, J.; Bouwmeister, P.J.; Brandt, van den P.A.; Ciere, S.; Gry, J.; Herrman, J.; Kuiper, H.A.; Mortby, E.; Renwickn, A.G.

    1998-01-01

    The ADI as a tool for risk management and regulation of food additives and pesticide residues is not readily applicable to inherent food plant toxicants: The margin between actual intake and potentially toxic levels is often small; application of the default uncertainty factors used to derive ADI

  9. Acute, reproductive toxicity and two-generation teratology studies of a standardized quassinoid-rich extract of Eurycoma longifolia Jack in Sprague-Dawley rats.

    Science.gov (United States)

    Low, Bin-Seng; Das, Prashanta Kumar; Chan, Kit-Lam

    2014-07-01

    The roots of Eurycoma longifolia Jack are popularly sought as herbal medicinal supplements to improve libido and general health amongst the local ethnic population. The major quassinoids of E. longifolia improved spermatogenesis and fertility but toxicity studies have not been well documented. The reproductive toxicity, two generation of foetus teratology and the up-and-down acute toxicity were investigated in Sprague-Dawley rats orally treated with quassinoid-rich E. longifolia extract (TAF273). The results showed that the median lethal dose (LD50 ) of TAF273 for female and male rats was 1293 and >2000 mg/kg, respectively. Fertility index and litter size of the TAF273 treated were significantly increased when compared with those of the non-treated animals. The TAF273-treated dams decreased in percentage of pre-implantation loss, post-implantation loss and late resorption. No toxic symptoms were observed on the TAF273-treated pregnant female rats and their foetuses were normal. The no-observed adverse effect level (NOAEL) obtained from reproductive toxicity and teratology studies of TAF273 in rats was 100 mg/kg body weight/day, being more than 10-fold lower than the LD50 value. Thus, any human dose derived from converting the rat doses of 100 mg/kg and below may be considered as safe for further clinical studies. Copyright © 2013 John Wiley & Sons, Ltd.

  10. Reproductive toxicity in rats after chronic oral exposure to low dose of depleted uranium

    International Nuclear Information System (INIS)

    Li Rong; Ai Guoping; Xu Hui; Su Yongping; Cheng Tianmin; Leng Yanbing

    2007-01-01

    Objective: To study the reproductive toxicity in rats induced by low dose of depleted uranium (DU). Methods: Male and female rats(F 0 generation) were exposed to DU in food at doses of 0, 0.4, 4 and 40 mg·kg -1 ·d -1 for 160 days, respectively. Then the activities of enzymes in testis and sexual hormone contents in serum were detected. Mature male rats were mated with female rats exposed to the same doses for 14 days. Pregnant rate and normal labor rate in F 0 rats were detected, as well as the survival rate and weight of F 1 rats within 21 d after birth. Results: No adverse effects of DU on fertility were evident at any dose in F 0 rats. Compared with control group, the rate of pregnancy, normal labor, survival of offspring birth and offspring nurture in F 1 generation of high-dose group reduced to 40.0%, 33.3%, 33.3%, and 33.3%, respectively. The sexual hormone contents in F 0 generation exposed increased, but those in Fl rats decreased significantly. The activities of lactate dehydrogenase-X (LDH-X) decreased in F 1 rats exposed to high-dose of DU, and those of sorbitol dehydrogenase (SDH), LDH and Na + -K + -ATPase decreased in F 1 rats exposed to DU. Conclusions: Reproduction function, growth and development of F 0 rats are not obviously affected after chronic oral exposure to DU, while the toxicity effects in F 1 generation was observed at any dose. (authors)

  11. Caenorhabditis elegans as a Model for Toxic Effects of Nanoparticles: Lethality, Growth, and Reproduction.

    Science.gov (United States)

    Maurer, Laura L; Ryde, Ian T; Yang, Xinyu; Meyer, Joel N

    2015-11-02

    The nematode Caenorhabditis elegans is extensively utilized in toxicity studies. C. elegans offers a high degree of homology with higher organisms, and its ease of use and relatively inexpensive maintenance have made it an attractive complement to mammalian and ecotoxicological models. C. elegans provides multiple benefits, including the opportunity to perform relatively high-throughput assays on whole organisms, a wide range of genetic tools permitting investigation of mechanisms and genetic sensitivity, and transparent bodies that facilitate toxicokinetic studies. This unit describes protocols for three nanotoxicity assays in C. elegans: lethality, growth, and reproduction. This unit focuses on how to use these well-established assays with nanoparticles, which are being produced in ever-increasing volume and exhibit physicochemical properties that require alteration of standard toxicity assays. These assays permit a broad phenotypic assessment of nanotoxicity in C. elegans, and, when used in combination with genetic tools and other assays, also permit mechanistic insight. Copyright © 2015 John Wiley & Sons, Inc.

  12. Reproductive disorders associated with pesticide exposure.

    Science.gov (United States)

    Frazier, Linda M

    2007-01-01

    Exposure of men or women to certain pesticides at sufficient doses may increase the risk for sperm abnormalities, decreased fertility, a deficit of male children, spontaneous abortion, birth defects or fetal growth retardation. Pesticides from workplace or environmental exposures enter breast milk. Certain pesticides have been linked to developmental neurobehavioral problems, altered function of immune cells and possibly childhood leukemia. In well-designed epidemiologic studies, adverse reproductive or developmental effects have been associated with mixed pesticide exposure in occupational settings, particularly when personal protective equipment is not used. Every class of pesticides has at least one agent capable of affecting a reproductive or developmental endpoint in laboratory animals or people, including organophosphates, carbamates, pyrethroids, herbicides, fungicides, fumigants and especially organochlorines. Many of the most toxic pesticides have been banned or restricted in developed nations, but high exposures to these agents are still occurring in the most impoverished countries around the globe. Protective clothing, masks and gloves are more difficult to tolerate in hot, humid weather, or may be unavailable or unaffordable. Counseling patients who are concerned about reproductive and developmental effects of pesticides often involves helping them assess their exposure levels, weigh risks and benefits, and adopt practices to reduce or eliminate their absorbed dose. Patients may not realize that by the first prenatal care visit, most disruptions of organogenesis have already occurred. Planning ahead provides the best chance of lowering risk from pesticides and remediating other risk factors before conception.

  13. Mixtures of toxic agents and attributable risk calculations

    International Nuclear Information System (INIS)

    Seiler, F.A.; Scott, B.R.

    1987-01-01

    Calculations of attributable risks have attracted increasing interest recently. However, these efforts have been limited to mostly one agent, radiation, and no interactions with effects of other toxic agents have been taken into account. This paper outlines a generic approach to the calculation of attributable risks for an exposure to several toxic agents and interaction effects associated with them. In this calculation, the partition of interaction terms between the agents responsible is of particular importance. At present, there are no rules on how to assign equitable shares, so one methodology will be proposed and others discussed briefly. For one example of an assignment, the standard errors of the attributable risks are determined in terms of the uncertainties of the input parameters, thus setting the stage for a comparison of the different shares of responsibility

  14. Toxicity assessment strategies, data requirements, and risk assessment approaches to derive health based guidance values for non-relevant metabolites of plant protection products.

    Science.gov (United States)

    Dekant, Wolfgang; Melching-Kollmuss, Stephanie; Kalberlah, Fritz

    2010-03-01

    In Europe, limits for tolerable concentrations of "non-relevant metabolites" for active ingredients (AI) of plant protection products in drinking water between 0.1 and 10 microg/L are discussed depending on the toxicological information available. "Non-relevant metabolites" are degradation products of AIs, which do not or only partially retain the targeted toxicities of AIs. For "non-relevant metabolites" without genotoxicity (to be confirmed by testing in vitro), the application of the concept of "thresholds of toxicological concern" results in a health-based drinking water limit of 4.5 microg/L even for Cramer class III compounds, using the TTC threshold of 90 microg/person/day (divided by 10 and 2). Taking into account the thresholds derived from two reproduction toxicity data bases a drinking water limit of 3.0 microg/L is proposed. Therefore, for "non-relevant metabolites" whose drinking water concentration is below 3.0 microg/L, no toxicity testing is necessary. This work develops a toxicity assessment strategy as a basis to delineate health-based limits for "non-relevant metabolites" in ground and drinking water. Toxicological testing is recommended to investigate, whether the metabolites are relevant or not, based on the hazard properties of the parent AIs, as outlined in the SANCO Guidance document. Also, genotoxicity testing of the water metabolites is clearly recommended. In this publication, tiered testing strategies are proposed for non-relevant metabolites, when drinking water concentrations >3.0 microg/L will occur. Conclusions based on structure-activity relationships and the detailed toxicity database on the parent AI should be included. When testing in animals is required for risk assessment, key aspects are studies along OECD-testing guidelines with "enhanced" study designs addressing additional endpoints such as reproductive toxicity and a developmental screening test to derive health-based tolerable drinking water limits with a limited number

  15. Costs of Reproduction in Breeding Female Mallards: Predation Risk during Incubation Drives Annual Mortality

    Directory of Open Access Journals (Sweden)

    Todd W. Arnold

    2012-06-01

    Full Text Available The effort expended on reproduction may entail future costs, such as reduced survival or fecundity, and these costs can have an important influence on life-history optimization. For birds with precocial offspring, hypothesized costs of reproduction have typically emphasized nutritional and energetic investments in egg formation and incubation. We measured seasonal survival of 3856 radio-marked female Mallards (Anas platyrhynchos from arrival on the breeding grounds through brood-rearing or cessation of breeding. There was a 2.5-fold direct increase in mortality risk associated with incubating nests in terrestrial habitats, whereas during brood-rearing when breeding females occupy aquatic habitats, mortality risk reached seasonal lows. Mortality risk also varied with calendar date and was highest during periods when large numbers of Mallards were nesting, suggesting that prey-switching behaviors by common predators may exacerbate risks to adults in all breeding stages. Although prior investments in egg laying and incubation affected mortality risk, most relationships were not consistent with the cost of reproduction hypothesis; birds with extensive prior investments in egg production or incubation typically survived better, suggesting that variation in individual quality drove both relationships. We conclude that for breeding female Mallards, the primary cost of reproduction is a fixed cost associated with placing oneself at risk to predators while incubating nests in terrestrial habitats.

  16. Toxicity of abamectin and doramectin to soil invertebrates

    Energy Technology Data Exchange (ETDEWEB)

    Kolar, Lucija [Laboratory of Forensic Toxicology and Ecotoxicology, Veterinary Faculty, University of Ljubljana, Gerbiceva 60, SI-1000 Ljubljana (Slovenia); Institute of Ecological Science, Vrije Universiteit, De Boelelaan 1085, 1081 HV Amsterdam (Netherlands)], E-mail: lucija.kolar@vf.uni-lj.si; Kozuh Erzen, Nevenka [Laboratory of Forensic Toxicology and Ecotoxicology, Veterinary Faculty, University of Ljubljana, Gerbiceva 60, SI-1000 Ljubljana (Slovenia)], E-mail: nevenka.kozuh@vf.uni-lj.si; Hogerwerf, Lenny [Institute of Ecological Science, Vrije Universiteit, De Boelelaan 1085, 1081 HV Amsterdam (Netherlands)], E-mail: l.hogerwerf@students.uu.nl; Gestel, Cornelis A.M. van [Institute of Ecological Science, Vrije Universiteit, De Boelelaan 1085, 1081 HV Amsterdam (Netherlands)], E-mail: kees.van.gestel@ecology.falw.vu.nl

    2008-01-15

    This study aimed at determining the toxicity of avermectins to soil invertebrates in soil and in faeces from recently treated sheep. Abamectin was more toxic than doramectin. In soil, earthworms (Eisenia andrei) were most affected with LC50s of 18 and 228 mg/kg dry soil, respectively, while LC50s were 67-111 and >300 mg/kg for springtails (Folsomia candida), isopods (Porcellio scaber) and enchytraeids (Enchytraeus crypticus). EC50s for the effect on reproduction of springtails and enchytraeids were 13 and 38 mg/kg, respectively for abamectin, and 42 and 170 mg/kg for doramectin. For earthworms, NOEC was 10 and 8.4 mg/kg for abamectin and doramectin effects on body weight. When exposed in faeces, springtails and enchytraeids gave LC50s and EC50s of 1.0-1.4 and 0.94-1.1 mg/kg dry faeces for abamectin and 2.2->2.4 mg/kg for doramectin. Earthworm reproduction was not affected. This study indicates a potential risk of avermectins for soil invertebrates colonizing faeces from recently treated sheep. - Avermectins may pose a risk to soil invertebrates colonizing faeces from recently treated sheep.

  17. Toxicity of abamectin and doramectin to soil invertebrates

    International Nuclear Information System (INIS)

    Kolar, Lucija; Kozuh Erzen, Nevenka; Hogerwerf, Lenny; Gestel, Cornelis A.M. van

    2008-01-01

    This study aimed at determining the toxicity of avermectins to soil invertebrates in soil and in faeces from recently treated sheep. Abamectin was more toxic than doramectin. In soil, earthworms (Eisenia andrei) were most affected with LC50s of 18 and 228 mg/kg dry soil, respectively, while LC50s were 67-111 and >300 mg/kg for springtails (Folsomia candida), isopods (Porcellio scaber) and enchytraeids (Enchytraeus crypticus). EC50s for the effect on reproduction of springtails and enchytraeids were 13 and 38 mg/kg, respectively for abamectin, and 42 and 170 mg/kg for doramectin. For earthworms, NOEC was 10 and 8.4 mg/kg for abamectin and doramectin effects on body weight. When exposed in faeces, springtails and enchytraeids gave LC50s and EC50s of 1.0-1.4 and 0.94-1.1 mg/kg dry faeces for abamectin and 2.2->2.4 mg/kg for doramectin. Earthworm reproduction was not affected. This study indicates a potential risk of avermectins for soil invertebrates colonizing faeces from recently treated sheep. - Avermectins may pose a risk to soil invertebrates colonizing faeces from recently treated sheep

  18. Genetic and epigenetic risks of assisted reproduction.

    Science.gov (United States)

    Jiang, Ziru; Wang, Yinyu; Lin, Jing; Xu, Jingjing; Ding, Guolian; Huang, Hefeng

    2017-10-01

    Assisted reproductive technology (ART) is used primarily for infertility treatments to achieve pregnancy and involves procedures such as in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), and cryopreservation. Moreover, preimplantation genetic diagnosis (PGD) of ART is used in couples for genetic reasons. In ART treatments, gametes and zygotes are exposed to a series of non-physiological processes and culture media. Although the majority of children born with this treatment are healthy, some concerns remain regarding the safety of this technology. Animal studies and follow-up studies of ART-borne children suggested that ART was associated with an increased incidence of genetic, physical, or developmental abnormalities, although there are also observations that contradict these findings. As IVF, ICSI, frozen-thawed embryo transfer, and PGD manipulate gametes and embryo at a time that is important for reprogramming, they may affect epigenetic stability, leading to gamete/embryo origins of adult diseases. In fact, ART offspring have been reported to have an increased risk of gamete/embryo origins of adult diseases, such as early-onset diabetes, cardiovascular disease, and so on. In this review, we will discuss evidence related to genetic, especially epigenetic, risks of assisted reproduction. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. [Risk assessment and risk control for occupational exposure to chemical toxicants from an isophorone nitrile device].

    Science.gov (United States)

    Wang, Dejun; Fu, Xiaokuan; Kong, Fanling; Sui, Shaofeng; Jiang, Yuanyuan; Du, Yinglin; Zhou, Jingyang

    2014-06-01

    Risk assessment and risk control for occupational exposure to chemical toxicants were performed on an isophorone nitrile device with an annual production of 5,000 tons, based on improved Singaporean semi-quantitative risk assessment method, with consideration of actual situation in China and in the present project. With the use of engineering analysis and identification of occupational hazards in the improved Singaporean semi-quantitative risk assessment method, hazard rating (HR) and risk assessment were performed on chemical toxicants from an isophorone nitrile device with an annual production of 5,000 tons. The chemical toxicants in the isophorone nitrile device were mainly isophorone, hydrocyanic acid, methanol, phosphoric acid, sodium hydroxide, and sodium cyanide; the HR values were mild hazard (2), extreme hazard (5), mild hazard (2), mild hazard (2), moderate hazard (3), and extreme hazard (5), respectively, and the corresponding exposure rating (ER) values were 2.09, 2.72, 2.76, 1.68, 2.0, and 1.59, respectively. The risk of chemical toxicants in this project was assessed according to the formula Risk = [HR×ER](1/2). Hydrocyanic acid was determined as high risk, sodium hydroxide and sodium cyanide as medium risk, and isophorone, methanol, and phosphoric acid as low risk. Priority in handling of risks was determined by risk rating. The table of risk control measure was established for pre-assessment of occupational hazards. With risk assessment in this study, we concluded that the isophorone nitrile device with 5,000 ton annual production was a high-occupational hazard device. This device is a project of extreme occupational hazard. The improved Singaporean semi-quantitative risk assessment method is a scientific and applicable method, and is especially suitable for pre-evaluation of on-site project with no analogy.

  20. Use of environmental health-risk analysis for managing toxic substances

    International Nuclear Information System (INIS)

    McKone, T.E.

    1985-03-01

    This paper presents a set of simple models used to assess health risks based on toxicity, environmental mobility and persistence. These models use a representative landscape in order to describe the steady-state distribution of arsenic, tritiated water, and TCDD as a result of continuous additions to soil. This information is used to assess potential exposures. Application of the screening model to three chemically different carcinogens reveals that the environmental health risk does not scale with direct measures of toxicity. As estimated here, the environmental health risk of TCDD relative to tritiated water and arsenic is roughly an order of magnitude less than its cancer potency relative to these compounds. The difference is attributable in large part to the immobility of TCDD relative to tritium and the lower persistence of TCDD compared to arsenic. The purpose is to present a simple procedure for using the relative behavior of toxic species under prototype conditions as a basis for risk management. 21 refs., 4 tabs

  1. Age at menopause, reproductive history and venous thromboembolism risk among postmenopausal women

    Science.gov (United States)

    Canonico, Marianne; Plu-Bureau, Geneviève; O’Sullivan, Mary Jo; Stefanick, Marcia L.; Cochrane, Barbara; Scarabin, Pierre-Yves; Manson, JoAnn E.

    2013-01-01

    Objectives To investigate VTE risk in relation to age at menopause, age at menarche, parity, bilateral oophorectomy and time since menopause, as well as any interaction with randomized HT assignment among postmenopausal women. Methods Using pooled data from the Women’s Health Initiative HT clinical trials including 27,035 postmenopausal women ages 50 to 79 years with no history of VTE, we assessed the risk of VTE in relation to age at menopause, age at menarche, parity, bilateral oophorectomy and time since menopause by Cox proportional hazard models. Linear trends, quadratic relationships and interactions of reproductive life characteristics with HT on VTE risk were systematically tested. Results During the follow-up, 426 women reported a first VTE, including 294 nonprocedure-related events. No apparent interaction of reproductive life characteristics with HT assignment on VTE risk was detected and there was any significant association of VTE with age at menarche, age at menopause, parity, oophorectomy or time since menopause. However, analyses restricted to nonprocedure-related VTE showed a U-shaped relationship between age at menopause and thrombotic risk that persisted after multivariable analysis (pmenopause, those with early menopause (agemenopause (age>55 years) had a significant increased VTE risk (HR=1.8;95%CI:1.2–2.7 and HR=1.5;95%CI:1.0–2.4, respectively). Conclusion Reproductive life characteristics have little association with VTE and do not seem to influence the effect of HT on thrombotic risk among postmenopausal women. Nevertheless, early and late onset of menopause might be newly identified risk factors for nonprocedure-related VTE. PMID:23760439

  2. The combined toxicity of dibutyl phthalate and benzo(a)pyrene on the reproductive system of male Sprague Dawley rats in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Chen Xuemei [Laboratory of Reproductive Biology, Chongqing Medical University, Chongqing 400016 (China); An Hui; Ao Lin; Sun Lei; Liu Wenbin; Zhou Ziyuan [Department of Hygenic Toxicology, College of Military Preventive Medicine, Key Lab of Medical Protection for Electromagnetic Radiation, Ministry of Education of China, Third Military Medical University, Chongqing 400038 (China); Wang Yingxiong, E-mail: wyx61221@yahoo.com.cn [Laboratory of Reproductive Biology, Chongqing Medical University, Chongqing 400016 (China); Cao Jia, E-mail: caojia1962@126.com [Department of Hygenic Toxicology, College of Military Preventive Medicine, Key Lab of Medical Protection for Electromagnetic Radiation, Ministry of Education of China, Third Military Medical University, Chongqing 400038 (China)

    2011-02-15

    Our previous studies revealed more than 100 pollutants, most of which were endocrine disruptors (EDs) in two Chinese rivers, the Jialing and the Yangtze near Chongqing. Most EDs, such as dibutyl phthalate (DBP) and benzo(a)pyrene (BaP), are known to act individually as reproductive toxicants. However, little is known about the combined toxicity of DBP and BaP. In the current study, male Sprague Dawley rats were subchronically exposed to single doses of DBP (250 mg/kg), single doses of BaP (5 mg/kg) and combined doses of DBP and BaP. Significant adverse effects were observed on the reproductive system, including decreased sperm count, increased production of abnormal sperm, changes in serum testosterone levels and irregular arrangements of the seminiferous epithelium. Biochemical analyses showed that the activities of superoxide dismutase and glutathione peroxidase decreased after exposure to these EDs. Therefore, our data suggest that exposure to DBP and BaP, in either separate or combined doses, can affect the reproductive system of male rats adversely via oxidative stress-related mechanisms. No significant additive effect was observed after combined exposure. These results indicate that exposure to mixtures of EDs have unexpected and elusive effects. Our findings provide preliminary but important data for assessing water safety in China.

  3. The combined toxicity of dibutyl phthalate and benzo(a)pyrene on the reproductive system of male Sprague Dawley rats in vivo

    International Nuclear Information System (INIS)

    Chen Xuemei; An Hui; Ao Lin; Sun Lei; Liu Wenbin; Zhou Ziyuan; Wang Yingxiong; Cao Jia

    2011-01-01

    Our previous studies revealed more than 100 pollutants, most of which were endocrine disruptors (EDs) in two Chinese rivers, the Jialing and the Yangtze near Chongqing. Most EDs, such as dibutyl phthalate (DBP) and benzo(a)pyrene (BaP), are known to act individually as reproductive toxicants. However, little is known about the combined toxicity of DBP and BaP. In the current study, male Sprague Dawley rats were subchronically exposed to single doses of DBP (250 mg/kg), single doses of BaP (5 mg/kg) and combined doses of DBP and BaP. Significant adverse effects were observed on the reproductive system, including decreased sperm count, increased production of abnormal sperm, changes in serum testosterone levels and irregular arrangements of the seminiferous epithelium. Biochemical analyses showed that the activities of superoxide dismutase and glutathione peroxidase decreased after exposure to these EDs. Therefore, our data suggest that exposure to DBP and BaP, in either separate or combined doses, can affect the reproductive system of male rats adversely via oxidative stress-related mechanisms. No significant additive effect was observed after combined exposure. These results indicate that exposure to mixtures of EDs have unexpected and elusive effects. Our findings provide preliminary but important data for assessing water safety in China.

  4. Reproductive toxicity of bisphenol A and cadmium in Potamopyrgus antipodarum and modulation of bisphenol A effects by different test temperature

    International Nuclear Information System (INIS)

    Sieratowicz, Agnes; Stange, Daniela; Schulte-Oehlmann, Ulrike; Oehlmann, Joerg

    2011-01-01

    An OECD initiative for the development of mollusc-based toxicity tests for endocrine disrupters and other chemicals has recommended three test species with respective test designs for further standardisation. Preparing a subsequent pre-validation study we performed a reproduction test with Potamopyrgus antipodarum, determining the concentration range of the selected test substances, bisphenol A (BPA) and cadmium (Cd). At 16 deg. C, the recommended test temperature, the number of embryos in the brood pouch was increased by BPA and decreased by Cd (NOEC: 20 μg BPA/L and 1 μg Cd/L). Coinstantaneous BPA tests at 7 deg. C and 25 deg. C demonstrated a temperature dependency of the response, resulting in lower NOECs (5 μg/L respectively). As expected, reproduction in control groups significantly varied depending on temperature. Additional observations of the brood stock showed seasonal fluctuations in reproduction under constant laboratory conditions. The recommended temperature range and test conditions have to be further investigated. - Highlights: → We performed a reproduction test with the mollusc Potamopyrgus antipodarum. → We defined the test substance concentration range for a pre-validation study. → The bisphenol A effect (increased reproduction) depends on the test temperature. → Reproduction of control groups significantly varies depending on temperature. → The brood stock shows seasonal fluctuations in reproduction at constant conditions. - A reproduction test with Potamopyrgus antipodarum with 2 substances for subsequent pre-validation is presented and bisphenol A effects show a temperature dependency.

  5. Application of bioassays with Enchytraeus crypticus and Folsomia candida to evaluate the toxicity of a metal-contaminated soil, before and after remediation

    Energy Technology Data Exchange (ETDEWEB)

    Gonzalez, Veronica; Simon, Mariano [Univ. de Almeria (Spain). Dept. de Edafologia y Quimica Agricola; Dietz-Ortiz, Maria; Gestel, Cornelis A.M. van [VU Univ., Amsterdam (Netherlands). Dept. of Animal Ecology

    2011-10-15

    A contaminated soil was amended to reduce bioavailability of metals (As, Cd, Cu, Pb, and Zn) and to modify its potential environmental impacts. Reproduction toxicity tests using two different soil invertebrates, Enchytraeus crypticus and Folsomia candida, were used to evaluate efficiency of soil amendments to reduce metal availability. This study has been carried out on a very contaminated soil from El Arteal mining district (SE Spain). The amendments used were marble sludge from the cutting and polishing of marble, compost from greenhouse wastes, and synthetic iron oxides. Soils were analyzed for cation exchange capacity, organic carbon and calcium carbonate content, particle size distribution, pH, electrical conductivity, and total metal content. Porewater and 0.01 M CaCl{sub 2}-extractable concentrations were measured in unamended and amended soils. Soil organisms were exposed to all treatments and to untreated soil. The parameters evaluated in both bioassays were survival and reproduction. All treatments decreased the porewater and CaCl{sub 2}-extractable concentrations of Zn, Pb, Cd, and Cu. The amendments increased survival and reproduction of E. crypticus, reducing toxicity. Survival of F. candida was also increased by the treatments; its reproduction did, however, not improve. These differences may be due to other factors that may affect collembolan reproduction. The different sensitivity of each test organism to some soil properties such as pH and electrical conductivity, which can affect reproduction, should be considered before interpreting results from bioassays focussed on toxicity due to pollutants. Reproduction toxicity bioassays with soil invertebrates are a good complement of chemical analysis to properly assess the ecological risk of remediation processes. Organisms with different exposure routes and different sensitivities to soil properties should be used simultaneously to assess the environmental risk of metal-contaminated sites and to evaluate

  6. A critical evaluation of developmental and reproductive toxicology in nonhuman primates.

    Science.gov (United States)

    Faqi, Ali S

    2012-02-01

    The nonhuman primates (NHPs) are used in many areas of biomedical research where their similarities to humans make them exclusively valuable animal models. The use of NHPs in pre-clinical testing is expected to increase due to the increase in the development of biological compounds for therapeutic uses. The regulatory agencies around the world including Food and Drug Administration (FDA) generally requires developmental and reproductive toxicity (DART) testing of all new drugs to be used by women of childbearing age or men of reproductive potential. NHPs are most frequently used for DART testing when commonly used rodents and/or rabbits are not pharmacologically relevant species. Animal studies are unique in that assessment of reproduction and development as DART studies are not performed in controlled clinical trials; therefore, pre-clinical safety assessment forms the basis for risk assessment for marketed drug products. This paper provides a critical evaluation of developmental and reproductive toxicity studies in NHPs. The manuscript will focus on species selection, limitation of International Conference for Harmonization stages (A-F) using NHPs as a test system, study designs, logistical/technical challenges, and strength, and limitations. It will also pinpoint confounding factors inherent to the test system that may complicate the interpretation of the NHP DART data.

  7. Acute and subacute toxicity of 18F-FDG

    International Nuclear Information System (INIS)

    Dantas, Danielle Maia

    2013-01-01

    Before starting clinical trials of a new drug, it is necessary to perform a battery of safety tests for assessing human risk. Radiopharmaceuticals like any new drug must be tested taking into account its specificity, duration of treatment and especially the toxicity of both parties, the unlabeled molecule and its radionuclide, apart from impurities emanating from radiolysis. Regulatory agencies like the Food and Drug Administration - USA (FDA) and the European Medicine Agency (EMEA), establish guidelines for the regulation of production and research of radiopharmaceuticals. In Brazil the production of radiopharmaceuticals was not regulated until the end of 2009, when were established by the National Agency for Sanitary Surveillance (ANVISA) resolutions No. 63, which refers to the Good Manufacturing Practices of Radiopharmaceuticals and No. 64 which seeks the registration of record radiopharmaceuticals. To obtain registration of radiopharmaceuticals are necessary to prove the quality, safety, efficacy and specificity of the drug . For the safety of radiopharmaceuticals must be presented studies of acute toxicity, subacute and chronic toxicity as well as reproductive, mutagenic and carcinogenic. Nowadays IPEN-CNEN/SP produces one of the most important radiopharmaceutical of nuclear medicine, the 18 F-FDG, which is used in many clinical applications, particularly in the diagnosis and staging of tumors. The objective of this study was to evaluate the systemic toxicity (acute/ subacute) radiopharmaceutical 18 F-FDG in an in vivo test system, as recommended by the RDC No. 64, which will serve as a model for protocols toxicity of radiopharmaceuticals produced at IPEN. The following tests were performed: tests of acute and subacute toxicity, biodistribution studies of 18 F-FDG, comet assay and reproductive toxicity. In acute toxicity, healthy rats were injected . (author)

  8. Dependency of cardiovascular risk on reproductive stages and on age among middle-aged Chinese women.

    Science.gov (United States)

    Sun, Y; Ruan, X; Mueck, A O

    2017-10-01

    To assess the 10-year cardiovascular risk in middle-aged Chinese women living in the same community and the impact of reproductive aging and age. This was a cross-sectional study in the Yuetan Community of Beijing. Data on lifestyle habits, prevalence and treatment of chronic diseases with significance for cardiovascular disease (CVD) development were collected by interview. CVD risk factors were assessed by physical examination and laboratory tests. The 10-year cardiovascular risk was calculated using the Framingham 10-year risk score. STRAW +10 criteria were used for the stages of reproductive aging. A total of 536 women, aged 40-60 years, were enrolled. The incidences of hypertension, dyslipidemia, abdominal obesity, glucose intolerance and diabetes were 32.6%, 45.7%, 65.5%, 37.9% and 10.1%, respectively. After adjustment, the incidence of hypertension and diabetes increased with age and with reproductive aging. Dyslipidemia and glucose intolerance were only associated with age. Abdominal obesity was related neither to age nor to reproductive aging. The 10-year cardiovascular risk ranged from 1% to 24.8%; 11.6% of women had a moderate or high Framingham 10-year risk score. CVD risk factors were frequent and more than 10% of the women were at moderate or high risk of developing cardiovascular disease within the next 10 years. To our knowledge, this was demonstrated for the first time in middle-aged Chinese women. Thus, women should maintain a healthy lifestyle and physicians should monitor them to prevent CVD.

  9. Consolidating Risk Estimates for Radiation-Induced Complications in Individual Patient: Late Rectal Toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Prior, Phillip; Devisetty, Kiran [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI (United States); Tarima, Sergey S. [Division of Biostatistics, Institute for Health and Society, Medical College of Wisconsin, Milwaukee, WI (United States); Lawton, Colleen A.F. [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI (United States); Semenenko, Vladimir A., E-mail: vsemenenko@mcw.edu [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI (United States)

    2012-05-01

    Purpose: To test the feasibility of a new approach to synthesize published normal tissue complication data using late rectal toxicity in prostate cancer as an example. Methods and Materials: A data survey was performed to identify the published reports on the dose-response relationships for late rectal toxicity. The risk estimates for Grade 1 or greater, Grade 2 or greater, and Grade 3 or greater toxicity were obtained for a test cohort of patients treated at our institution. The influence of the potential factors that might have affected the reported toxicity levels was investigated. The studies that did not conform to the general data trends were excluded, and single, combined risk estimates were derived for each patient and toxicity level. Results: A total of 21 studies of nonoverlapping patient populations were identified. Three studies provided dose-response models for more than one level of toxicity. Of these 21 studies, 6, 14, and 5 were used to derive the initial risk estimates for Grade 1, 2, and 3 or greater toxicity, respectively. A comparison of risk estimates between the studies reporting rectal bleeding and rectal toxicity (bleeding plus other symptoms) or between studies with follow-up <36 months and {>=}36 months did not reveal significant differences (p {>=} .29 for all comparisons). After excluding three reports that did not conform to the general data trends, the combined risk estimates were derived from 5 reports (647 patients), 11 reports (3,369 patients), and 5 reports (1,330 patients) for Grade 1, 2, and 3 or greater toxicity, respectively. Conclusions: The proposed approach is feasible and allows for more systematic use of published dose-response data to estimate the complication risks for the individual patient.

  10. Consolidating Risk Estimates for Radiation-Induced Complications in Individual Patient: Late Rectal Toxicity

    International Nuclear Information System (INIS)

    Prior, Phillip; Devisetty, Kiran; Tarima, Sergey S.; Lawton, Colleen A.F.; Semenenko, Vladimir A.

    2012-01-01

    Purpose: To test the feasibility of a new approach to synthesize published normal tissue complication data using late rectal toxicity in prostate cancer as an example. Methods and Materials: A data survey was performed to identify the published reports on the dose–response relationships for late rectal toxicity. The risk estimates for Grade 1 or greater, Grade 2 or greater, and Grade 3 or greater toxicity were obtained for a test cohort of patients treated at our institution. The influence of the potential factors that might have affected the reported toxicity levels was investigated. The studies that did not conform to the general data trends were excluded, and single, combined risk estimates were derived for each patient and toxicity level. Results: A total of 21 studies of nonoverlapping patient populations were identified. Three studies provided dose–response models for more than one level of toxicity. Of these 21 studies, 6, 14, and 5 were used to derive the initial risk estimates for Grade 1, 2, and 3 or greater toxicity, respectively. A comparison of risk estimates between the studies reporting rectal bleeding and rectal toxicity (bleeding plus other symptoms) or between studies with follow-up <36 months and ≥36 months did not reveal significant differences (p ≥ .29 for all comparisons). After excluding three reports that did not conform to the general data trends, the combined risk estimates were derived from 5 reports (647 patients), 11 reports (3,369 patients), and 5 reports (1,330 patients) for Grade 1, 2, and 3 or greater toxicity, respectively. Conclusions: The proposed approach is feasible and allows for more systematic use of published dose–response data to estimate the complication risks for the individual patient.

  11. A two-generation inhalation reproductive toxicity study upon the exposure to manganese chloride.

    Science.gov (United States)

    McGough, Doreen; Jardine, Lynne

    2017-01-01

    A number of published studies have suggested that high levels of exposure to manganese, especially those found in occupational settings, can adversely affect the reproductive system. The objective of this study was therefore to investigate if these findings can be replicated using the Sprague Dawley rat and, if so, to identify those parts of the reproductive system are more susceptible. Male and female rats were exposed to manganese dichloride (MnCl 2 ) via inhalation at concentrations of 0 (air-control); 5, 10 and 20μg/L air over 10 weeks (F0) and over 11 weeks (F1) prior to mating, and then throughout mating, gestation and lactation until termination after the F1 and F2 generation had reached Day 21 of lactation respectively. Animals were monitored for clinical signs of toxicity and for effects on body weight, food consumption, effects on the entire reproductive system including maternal care. The offspring were monitored for survival and growth up to weaning. Blood samples were taken from all adult animals for bioanalytical of manganese analysis prior to dosing, prior to mating and prior to weaning/necropsy. There were no deaths related to treatment, though respiratory tract effects were observed in F0 animals in the mid and high dose animals. Body weight and food consumption were affected at high dose in both generation. There were no treatment-related effects on the oestrous cycles, mating performance, sexual maturity, fertility or duration of gestation or litter size, the sperm motility, count of morphology (sperm) or the ovary follicle scoring in either generation. The No Observed Effect Level (NOEL) for reproductive performance was considered to be the target dose level of 20μg/L. Based on these findings, manganese chloride could not be considered a reprotoxicant under these conditions of exposure. Therefore, soluble and insoluble forms of inorganic manganese compounds by extrapolation cannot be considered as reprotoxicants. Copyright © 2016 Elsevier B

  12. Bisphenol A in Reproduction: Epigenetic Effects.

    Science.gov (United States)

    Chianese, Rosanna; Troisi, Jacopo; Richards, Sean; Scafuro, Marika; Fasano, Silvia; Guida, Maurizio; Pierantoni, Riccardo; Meccariello, Rosaria

    2018-02-21

    Bisphenol A (BPA) is an endocrine disrupting chemical widely used in the manufacture of polycarbonate plastic and epoxy resin to produce a multitude of consumer products, food and drink containers, and medical devices. BPA is similar to estradiol in structure and thus interferes in steroid signalling with different outcomes on reproductive health depending on doses, life stage, mode, and timing of exposure. In this respect, it has an emerging and controversial role as a "reproductive toxicant" capable of inducing short and long-term effects including the modulation of gene expression through epigenetic modification (i.e. methylation of CpG islands, histone modifications and production of non-coding RNA) with direct and trans-generational effects on exposed organisms and their offspring, respectively. This review provides an overview about BPA effects on reproductive health and aims to summarize the epigenetic effects of BPA in male and female reproduction. BPA exerts epigenetic effects in both male and female reproduction. In males, BPA affects spermatogenesis and sperm quality and possible trans-generational effects on the reproductive ability of the offspring. In females, BPA affects ovary, embryo development, and gamete quality for successful in vivo and in vitro fertilization (IVF). The exact mechanisms of BPA-mediated effects in reproduction are not fully understood; however, the environmental exposure to BPA - especially in fetal and neonatal period - deserves attention to preserve the reproductive ability in both sexes and to reduce the epigenetic risk for the offspring. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  13. Curcumin mitigates fenthion-induced testicular toxicity in rats ...

    African Journals Online (AJOL)

    Fenthion is a widely used organophosphorus pesticide in agriculture that induces different cytotoxic effects, including male reproductive toxicity. The present work aimed to study the ameliorative effects of curcumin, a potential therapeutic agent against several chronic diseases, on reproductive toxicity induced by the ...

  14. Human Health Toxicity Values in Superfund Risk Assessments

    Science.gov (United States)

    This memorandum revises the hierarchy of human health toxicity values generally recommended for use inr isk assessments, originally presented in Risk Assessment Guidance for Superfund Volume I, Part A.

  15. Reproductive history and risk of type 2 diabetes mellitus in postmenopausal women: findings from the Women's Health Initiative.

    Science.gov (United States)

    LeBlanc, Erin S; Kapphahn, Kristopher; Hedlin, Haley; Desai, Manisha; Parikh, Nisha I; Liu, Simin; Parker, Donna R; Anderson, Matthew; Aroda, Vanita; Sullivan, Shannon; Woods, Nancy F; Waring, Molly E; Lewis, Cora E; Stefanick, Marcia

    2017-01-01

    The aim of the study was to understand the association between women's reproductive history and their risk of developing type 2 diabetes. We hypothesized that characteristics signifying lower cumulative endogenous estrogen exposure would be associated with increased risk. Prospective cohort analysis of 124,379 postmenopausal women aged 50 to 79 years from the Women's Health Initiative (WHI). We determined age of menarche and final menstrual period, and history of irregular menses from questionnaires at baseline, and calculated reproductive length from age of menarche and final menstrual period. Presence of new onset type 2 diabetes was from self-report. Using multivariable Cox proportional hazards models, we assessed associations between reproductive variables and incidence of type 2 diabetes. In age-adjusted models, women with the shortest (<30 y) reproductive periods had a 37% (95% CI, 30-45) greater risk of developing type 2 diabetes than women with medium-length reproductive periods (36-40 y). Women with the longest (45+ y) reproductive periods had a 23% (95% CI, 12-37) higher risk than women with medium-length periods. These associations were attenuated after full adjustment (HR 1.07 [1.01, 1.14] for shortest and HR 1.09 [0.99, 1.22] for longest, compared with medium duration). Those with a final menstrual period before age 45 and after age 55 had an increased risk of diabetes (HR 1.04; 95% CI, 0.99-1.09 and HR 1.08; 95% CI, 1.01-1.14, respectively) compared to those with age of final menstrual period between 46 and 55 years. Timing of menarche and cycle regularity was not associated with risk after full adjustment. Reproductive history may be associated with type 2 diabetes risk. Women with shorter and longer reproductive periods may benefit from lifestyle counseling to prevent type 2 diabetes.

  16. The ChemScreen project to design a pragmatic alternative approach to predict reproductive toxicity of chemicals

    DEFF Research Database (Denmark)

    van der Burg, Bart; Wedebye, Eva Bay; Dietrich, Daniel R.

    2015-01-01

    to validate the test panel using mechanistic approaches. We are actively engaged in promoting regulatory acceptance of the tools developed as an essential step towards practical application, including case studies for read-across purposes. With this approach, a significant saving in animal use and associated......There is a great need for rapid testing strategies for reproductive toxicity testing, avoiding animal use. The EU Framework program 7 project ChemScreen aimed to fill this gap in a pragmatic manner preferably using validated existing tools and place them in an innovative alternative testing...

  17. Fertility drugs, reproductive strategies and ovarian cancer risk.

    Science.gov (United States)

    Tomao, Federica; Lo Russo, Giuseppe; Spinelli, Gian Paolo; Stati, Valeria; Prete, Alessandra Anna; Prinzi, Natalie; Sinjari, Marsela; Vici, Patrizia; Papa, Anselmo; Chiotti, Maria Stefania; Benedetti Panici, Pierluigi; Tomao, Silverio

    2014-01-01

    Several adverse effects have been related to infertility treatments, such as cancer development. In particular, the relationship between infertility, reproductive strategies, and risk of gynecological cancers has aroused much interest in recent years. The evaluation of cancer risk among women treated for infertility is very complex, mainly because of many factors that can contribute to occurrence of cancer in these patients (including parity status). This article addresses the possible association between the use of fertility treatments and the risk of ovarian cancer, through a scrupulous search of the literature published thus far in this field. Our principal objective was to give more conclusive answers on the question whether the use of fertility drug significantly increases ovarian cancer risk. Our analysis focused on the different types of drugs and different treatment schedules used. This study provides additional insights regarding the long-term relationships between fertility drugs and risk of ovarian cancer.

  18. Crataegus monogyna fruit aqueous extract as a protective agent against doxorubicin-induced reproductive toxicity in male rats

    Directory of Open Access Journals (Sweden)

    Ali Shalizar Jalali

    2013-04-01

    Full Text Available Objective: Doxorubicin (DOX is a broad spectrum chemotherapeutic agent used in the treatment of several malignancies. The use of DOX in clinical chemotherapy has been restricted due to its diverse toxicities, including reproductive toxicity. Crataegus monogyna (C. monogyna is one of the oldest medicinal plants that have been shown to be cytoprotective because of scavenging free radicals. The present study was undertaken to determine whether C. monogyna fruits aqueous extract could serve as a protective agent against reproductive toxicity during DOX treatment in a rat model through antioxidant-mediated mechanisms. Materials and Methods: Male Wistar rats were allocated to four groups. Two groups of rats were treated with DOX at a dose of 4 mg/kg intraperitoneally on days 1, 7, 14, 21, and 28 (accumulated dose of 20 mg/kg. One of the groups received C. monogyna fruits aqueous extract at a dose of 20 mg/kg per day orally for 28 days along with DOX. A vehicle-treated control group and a C. monogyna control group were also included. Results: The DOX-treated group showed significant decreases in the body and organ weights and spermatogenic activities as well as many histological alterations. DOX treatment also caused a significant decrease in sperm count and motility with an increase in dead and abnormal sperms. Moreover, significant decrease in serum levels of testosterone and increased serum concentrations of FSH, LH, LDH, CPK, and SGOT were observed in DOX-treated rats. Notably, Crataegus co-administration caused a partial recovery in above-mentioned parameters. Conclusion: These findings indicated that doxorubicin can adversely damage the testicular tissue, while Crataegus co-administrationcould effectively prevent these adverse effects by effective inhibiting oxidative processes and restoration of antioxidant defense system.

  19. NTP-CERHR EXPERT PANEL REPORT ON THE REPRODUCTIVE AND DEVELOPMENTAL TOXICITY OF AMPHETAMINE AND METHAMPHETAMINE.

    Science.gov (United States)

    A manuscript describes the results of an expert panel meeting of the NTP Center for the Evaluation of Risks to Human Reproduction (CERHR). The purpose CERHR is to provide timely, unbiased, scientifically sound evaluations of human and experimental evidence for adverse effects ...

  20. Toxic chemical risk acceptance criteria

    International Nuclear Information System (INIS)

    Craig, D.K.; Davis, J.; Lee, L.; Lein, P.; Omberg, S.

    1992-01-01

    This paper presents recommendations of a subcommittee of the Westinghouse M ampersand 0 Nuclear Facility Safety Committee concerning toxic chemical risk acceptance criteria. Two sets of criteria have been developed, one for use in the hazard classification of facilities, and the second for use in comparing risks in DOE non-reactor nuclear facility Safety Analysis Reports. The Emergency Response Planning Guideline (ERPG) values are intended to provide estimates of concentration ranges for specific chemicals above which exposure would be expected to lead to adverse heath effects of increasing severity for ERPG-1, -2, and -3s. The subcommittee recommends that criteria for hazard class or risk range be based on ERPGs for all chemicals. Probability-based Incremental Cancer Risk (ICR) criteria are recommended for additional analyses of risks from all known or suspected human carcinogens. Criteria are given for both on-site and off-site exposure. The subcommittee also recommends that the 5-minute peak concentration be compared with the relevant criterion with no adjustment for exposure time. Since ERPGs are available for only a limited number of chemicals, the subcommittee has developed a proposed hierarchy of concentration limit parameters for the different criteria

  1. Effects of Pesticides on the Growth and Reproduction of Earthworm: A Review

    International Nuclear Information System (INIS)

    Yasmin, S.; Doris D'Souza, D.

    2010-01-01

    Scientific literature addressing the influence of pesticides on the growth and reproduction of earthworm is reviewed. Earthworms are considered as important bio indicators of chemical toxicity in the soil ecosystem. Studies on this aspect are important because earthworms are the common prey of many terrestrial vertebrate species such as birds and small mammals, and thus they play a key role in the bio magnification process of several soil pollutants. Majority of the studies have used mortality as an endpoint rather than subtler endpoints such as reproductive output. It is now emphasized that, whereas higher concentrations of a pollutant can easily be assessed with the acute (mortality) test, contaminated soils with lower (sublethal) pollutant concentrations require more sensitive test methods such as reproduction test in their risk assessment.

  2. Reproductive and Developmental Toxicity of Phthalates

    NARCIS (Netherlands)

    Lyche, J.L.; Gutleb, A.C.; Bergman, A.; Eriksen, G.S.; Murk, A.J.; Ropstad, E.; Saunders, M.; Skaare, J.U.

    2009-01-01

    The purposes of this review are to (1) evaluate human and experimental evidence for adverse effects on reproduction and development in humans, produced by exposure to phthalates, and (2) identify knowledge gaps as for future studies. The widespread use of phthalates in consumer products leads to

  3. Innovative non-animal testing strategies for reproductive toxicology: the contribution of Italian partners within the EU project ReProTect

    Directory of Open Access Journals (Sweden)

    Stefano Lorenzetti

    2011-12-01

    Full Text Available Reproductive toxicity, with its many targets and mechanisms, is a complex area of toxicology; thus, the screening and identification of reproductive toxicants is a main scientific challenge for the safety assessment of chemicals, including the European Regulation on Chemicals (REACH. Regulatory agencies recommend the implementation of the 3Rs principle (refinement, reduction, replacement as well as of intelligent testing strategies, through the development of in vitro methods and the use of mechanistic information in the hazard identification and characterization steps of the risk assessment process. The EU Integrated Project ReProTect (6th Framework Programme implemented an array of in vitro tests to study different building blocks of the mammalian reproductive cycle: methodological developments and results on male and female germ cells, prostate and placenta are presented.

  4. Petroleum Hydrocarbon Mixture Toxicity and a Trait Based Approach to Soil Invertebrate Species for Site Specific Risk Assessments.

    Science.gov (United States)

    Gainer, Amy; Cousins, Mark; Hogan, Natacha; Siciliano, Steven D

    2018-05-05

    Although petroleum hydrocarbons (PHCs) released to the environment typically occur as mixtures, PHC remediation guidelines often reflect individual substance toxicity. It is well documented that groups of aliphatic PHCs act via the same mechanism of action, nonpolar narcosis and, theoretically, concentration addition mixture toxicity principles apply. To assess this theory, ten standardized acute and chronic soil invertebrate toxicity tests on a range of organisms (Eisenia fetida, Lumbricus terrestris, Enchytraeus crypticus, Folsomia candida, Oppia nitens and Hypoaspis aculeifer) were conducted with a refined PHC binary mixture. Reference models for concentration addition and independent action were applied to the mixture toxicity data with consideration of synergism, antagonism and dose level toxicity. Both concentration addition and independent action, without further interactions, provided the best fit with observed response to the mixture. Individual fraction effective concentration values were predicted from optimized, fitted reference models. Concentration addition provided a better estimate than independent action of individual fraction effective concentrations based on comparison with available literature and species trends observed in toxic responses to the mixture. Interspecies differences in standardized laboratory soil invertebrate species responses to PHC contaminated soil was reflected in unique traits. Diets that included soil, large body size, permeable cuticle, low lipid content, lack of ability to molt and no maternal transfer were traits linked to a sensitive survival response to PHC contaminated soil in laboratory tests. Traits linked to sensitive reproduction response in organisms tested were long life spans with small clutch sizes. By deriving single fraction toxicity endpoints considerate of mixtures, we reduce resources and time required in conducting site specific risk assessments for the protection of soil organism's exposure pathway. This

  5. Systems Toxicology of Male Reproductive Development ...

    Science.gov (United States)

    Adverse trends in male reproductive health have been reported for increased rates of testicular germ cell tumor, low semen quality, cryptorchidism, and hypospadias. An association with prenatal environmental exposure has been inferred from human and animal studies underlying male reproductive developmental defects. The present study established the links between environmental chemicals, molecular targets, and adverse outcomes using U.S. EPA animal study (ToxRefDB) and high-throughput screening (ToxCast) databases. This systems-based approach revealed a phenotypic hierarchy across 63 chemicals and a pleiotropic in vitro bioactivity profile. Although estrogenic and anti-androgenic activities have been extensively studied in male reproductive developmental toxicity, the present study showed these receptor targets to be only a subset of the potential landscape of molecular targets. A variety of chemical (e.g. phthalates, conazoles, carbamates, and phenol compounds) and bioactivity (e.g. nuclear receptors, vascular remodeling proteins, and cytochrome-P450 reductases) clusters further suggested multiple pathways leading to the adverse outcomes. This points to the need for multi-scale systems models to predict whether the occurrence of one adverse outcome may predict the risk of another. Imbalances in androgen and estrogen signaling have been a general focus in male reproductive toxicology research. While a number of recent studies have demonstrated that both hormonal

  6. Development of an in vitro test system for assessment of male, reproductive toxicity.

    Science.gov (United States)

    Habas, Khaled; Anderson, Diana; Brinkworth, Martin

    2014-02-10

    There is a need for improved reproductive toxicology assays that do not require large numbers of animals but are sensitive and informative. Therefore, Staput velocity-sedimentation separation followed by culture of specific mouse testicular cells was used as such a system. The specificity of separation was assessed using immunocytochemistry to identify spermatids, spermatocytes and spermatogonia. The efficacy of the system to detect toxicity was then evaluated by analysing the effects of hydrogen peroxide (H2O2) by the terminal uridine-deoxynucleotide end-labelling (TUNEL) assay to show the rate of apoptosis induced among the different types of germ cells. We found that 2 h of treatment at both 1 and 10 μM induced increases of over ∼10-fold in the percentage of apoptotic cells (p≤0.001), confirming that testicular germ cells are prone to apoptosis at very low concentrations of H2O2. It was also demonstrated for the first time for this compound that spermatogonia are significantly more susceptible than spermatocytes, which are more affected than spermatids. This reflects the proportion of actively dividing cells in these cell types, suggesting a mechanism for the differential sensitivity. The approach should thus form the basis of a useful test system for reproductive and genetic toxicology in the future. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  7. Development and Evaluation of Reproductive and Developmental Toxicity Tests for Assessing the Hazards of Environmental Contaminants

    Science.gov (United States)

    1997-08-01

    diet of the animals, their dret was supplemented wtth Poly Vt vitamins by injecting the worms with vitamins three tunes a week. The weight of the...No Kl K2 K3 Bl B2 B3 Male 18 44 23 26 56 34 Clutch Weight (g) 2.64 14.07 5.07 5.72 14.50 8.94 % Normal 46.00 54.50 75.00 66.50 59.50 70.50...107. FEMALE REPRODUCTIVE TOXICITY EXPERIMENT: FINAL BREEDING AND EGG CLUTCH DATA AFTER DIRECT EXPOSURE TO EGLIN AFB SOIL Frog No. Kl K2 K3 Bl B2 B3

  8. In utero exposure to toxic air pollutants and risk of childhood autism.

    Science.gov (United States)

    von Ehrenstein, Ondine S; Aralis, Hilary; Cockburn, Myles; Ritz, Beate

    2014-11-01

    Genetic and environmental factors are believed to contribute to the development of autism, but relatively few studies have considered potential environmental risks. Here, we examine risks for autism in children related to in utero exposure to monitored ambient air toxics from urban emissions. Among the cohort of children born in Los Angeles County, California, 1995-2006, those whose mothers resided during pregnancy in a 5-km buffer around air toxics monitoring stations were included (n = 148,722). To identify autism cases in this cohort, birth records were linked to records of children diagnosed with primary autistic disorder at the California Department of Developmental Services between 1998 and 2009 (n = 768). We calculated monthly average exposures during pregnancy for 24 air toxics selected based on suspected or known neurotoxicity or neurodevelopmental toxicity. Factor analysis helped us identify the correlational structure among air toxics, and we estimated odds ratios (ORs) for autism from logistic regression analyses. Autism risks were increased per interquartile range increase in average concentrations during pregnancy of several correlated toxics mostly loading on 1 factor, including 1,3-butadiene (OR = 1.59 [95% confidence interval = 1.18-2.15]), meta/para-xylene (1.51 [1.26-1.82]), other aromatic solvents, lead (1.49 [1.23-1.81]), perchloroethylene (1.40 [1.09-1.80]), and formaldehyde (1.34 [1.17-1.52]), adjusting for maternal age, race/ethnicity, nativity, education, insurance type, parity, child sex, and birth year. Risks for autism in children may increase following in utero exposure to ambient air toxics from urban traffic and industry emissions, as measured by community-based air-monitoring stations.

  9. Toxicological Considerations, Toxicity Assessment, and Risk Management of Inhaled Nanoparticles.

    Science.gov (United States)

    Bakand, Shahnaz; Hayes, Amanda

    2016-06-14

    Novel engineered nanoparticles (NPs), nanomaterial (NM) products and composites, are continually emerging worldwide. Many potential benefits are expected from their commercial applications; however, these benefits should always be balanced against risks. Potential toxic effects of NM exposure have been highlighted, but, as there is a lack of understanding about potential interactions of nanomaterials (NMs) with biological systems, these side effects are often ignored. NPs are able to translocate to the bloodstream, cross body membrane barriers effectively, and affect organs and tissues at cellular and molecular levels. NPs may pass the blood-brain barrier (BBB) and gain access to the brain. The interactions of NPs with biological milieu and resulted toxic effects are significantly associated with their small size distribution, large surface area to mass ratio (SA/MR), and surface characteristics. NMs are able to cross tissue and cell membranes, enter into cellular compartments, and cause cellular injury as well as toxicity. The extremely large SA/MR of NPs is also available to undergo reactions. An increased surface area of the identical chemical will increase surface reactivity, adsorption properties, and potential toxicity. This review explores biological pathways of NPs, their toxic potential, and underlying mechanisms responsible for such toxic effects. The necessity of toxicological risk assessment to human health should be emphasised as an integral part of NM design and manufacture.

  10. Toxicological Considerations, Toxicity Assessment, and Risk Management of Inhaled Nanoparticles

    Directory of Open Access Journals (Sweden)

    Shahnaz Bakand

    2016-06-01

    Full Text Available Novel engineered nanoparticles (NPs, nanomaterial (NM products and composites, are continually emerging worldwide. Many potential benefits are expected from their commercial applications; however, these benefits should always be balanced against risks. Potential toxic effects of NM exposure have been highlighted, but, as there is a lack of understanding about potential interactions of nanomaterials (NMs with biological systems, these side effects are often ignored. NPs are able to translocate to the bloodstream, cross body membrane barriers effectively, and affect organs and tissues at cellular and molecular levels. NPs may pass the blood–brain barrier (BBB and gain access to the brain. The interactions of NPs with biological milieu and resulted toxic effects are significantly associated with their small size distribution, large surface area to mass ratio (SA/MR, and surface characteristics. NMs are able to cross tissue and cell membranes, enter into cellular compartments, and cause cellular injury as well as toxicity. The extremely large SA/MR of NPs is also available to undergo reactions. An increased surface area of the identical chemical will increase surface reactivity, adsorption properties, and potential toxicity. This review explores biological pathways of NPs, their toxic potential, and underlying mechanisms responsible for such toxic effects. The necessity of toxicological risk assessment to human health should be emphasised as an integral part of NM design and manufacture.

  11. Cluster analysis of cardiovascular and metabolic risk factors in women of reproductive age.

    Science.gov (United States)

    Tzeng, Chii-Ruey; Chang, Yuan-chin Ivan; Chang, Yu-chia; Wang, Chia-Woei; Chen, Chi-Huang; Hsu, Ming-I

    2014-05-01

    To study the association between endocrine disturbances and metabolic complications in women seeking gynecologic care. Retrospective study, cluster analysis. Outpatient clinic, university medical center. 573 women, including 384 at low risk and 189 at high risk of cardiometabolic disease. None. Cardiovascular and metabolic parameters and clinical and biochemical characteristics. Risk factors for metabolic disease are associated with a low age of menarche, high levels of high-sensitivity C-reactive protein and liver enzymes, and low levels of sex hormone-binding globulin. Overweight/obese status, polycystic ovary syndrome, oligo/amenorrhea, and hyperandrogenism were found to increase the risk of cardiometabolic disease. However, hyperprolactinemia and premature ovarian failure were not associated with the risk of cardiometabolic disease. In terms of androgens, the serum total testosterone level and free androgen index but not androstenedione or dehydroepiandrosterone sulfate (DHEAS) were associated with cardiometabolic risk. Although polycystic ovary syndrome is associated with metabolic risk, obesity was the major determinant of cardiometabolic disturbances in reproductive-aged women. Hyperprolactinemia and premature ovarian failure were not associated with the risk of cardiovascular and metabolic diseases. NCT01826357. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  12. Toxicity ratios: Their use and abuse in predicting the risk from induced cancer

    International Nuclear Information System (INIS)

    Mays, C.W.; Taylor, G.N.; Lloyd, R.D.

    1986-01-01

    The toxicity ratio concept assumes the validity of certain relationships. In some examples for bone sarcoma induction, the approximate toxicity of 239 Pu in man can be calculated algebraically from the observed toxicity in the radium-dial painters and the ratio of 239 Pu/ 226 Ra toxicities in suitable laboratory mammals. In a species highly susceptible to bone sarcoma induction, the risk coefficients for both 239 Pu and 226 Ra are elevated, but the toxicity ratio of 239 Pu to 226 Ra tends to be similar to the ratio in resistant species. Among the tested species the toxicity ratio of 239 Pu to 226 Ra ranged from 6 to 22 (a fourfold range), whereas their relative sensitivities to 239 Pu varied by a factor of 150. The toxicity ratio approach can also be used to estimate the actinide risk to man from liver cancer, by comparing to the Thorotrast patients; from lung cancer, by comparing to the uranium miners and the atomic-bomb survivors; and from neutron-induced cancers, by comparing to cancers induced by gamma rays. The toxicity ratio can be used to predict the risk to man from a specific type of cancer that has been reliably induced by a reference radiation in humans and that can be induced by both the reference and the investigated radiation in suitable laboratory animals. 26 refs., 3 figs., 1 tab

  13. Hazard classification or risk assessment

    DEFF Research Database (Denmark)

    Hass, Ulla

    2013-01-01

    The EU classification of substances for e.g. reproductive toxicants is hazard based and does not to address the risk suchsubstances may pose through normal, or extreme, use. Such hazard classification complies with the consumer's right to know. It is also an incentive to careful use and storage...

  14. Joint associations between genetic variants and reproductive factors in glioma risk among women.

    Science.gov (United States)

    Wang, Sophia S; Hartge, Patricia; Yeager, Meredith; Carreón, Tania; Ruder, Avima M; Linet, Martha; Inskip, Peter D; Black, Amanda; Hsing, Ann W; Alavanja, Michael; Beane-Freeman, Laura; Safaiean, Mahboobeh; Chanock, Stephen J; Rajaraman, Preetha

    2011-10-15

    In a pooled analysis of 4 US epidemiologic studies (1993-2001), the authors evaluated the role of 5 female reproductive factors in 357 women with glioma and 822 controls. The authors further evaluated the independent association between 5 implicated gene variants and glioma risk among the study population, as well as the joint associations of female reproductive factors (ages at menarche and menopause, menopausal status, use of oral contraceptives, and menopausal hormone therapy) and these gene variants on glioma risk. Risk estimates were calculated as odds ratios and 95% confidence intervals that were adjusted for age, race, and study. Three of the gene variants (rs4295627, a variant of CCDC26; rs4977756, a variant of CDKN2A and CDKN2B; and rs6010620, a variant of RTEL1) were statistically significantly associated with glioma risk in the present population. Compared with women who had an early age at menarche (<12 years of age), those who reported menarche at 12-13 years of age or at 14 years of age or older had a 1.7-fold higher risk and a 1.9-fold higher risk of glioma, respectively (P for trend = 0.009). Postmenopausal women and women who reported ever having used oral contraceptives had a decreased risk of glioma. The authors did not observe joint associations between these reproductive characteristics and the implicated glioma gene variants. These results require replication, but if confirmed, they would suggest that the gene variants that have previously been implicated in the development of glioma are unlikely to act through the same hormonal mechanisms in women.

  15. Multi-Toxic Endpoints of the Foodborne Mycotoxins in Nematode Caenorhabditis elegans

    Directory of Open Access Journals (Sweden)

    Zhendong Yang

    2015-12-01

    Full Text Available Aflatoxins B1 (AFB1, deoxynivalenol (DON, fumonisin B1 (FB1, T-2 toxin (T-2, and zearalenone (ZEA are the major foodborne mycotoxins of public health concerns. In the present study, the multiple toxic endpoints of these naturally-occurring mycotoxins were evaluated in Caenorhabditis elegans model for their lethality, toxic effects on growth and reproduction, as well as influence on lifespan. We found that the lethality endpoint was more sensitive for T-2 toxicity with the EC50 at 1.38 mg/L, the growth endpoint was relatively sensitive for AFB1 toxic effects, and the reproduction endpoint was more sensitive for toxicities of AFB1, FB1, and ZEA. Moreover, the lifespan endpoint was sensitive to toxic effects of all five tested mycotoxins. Data obtained from this study may serve as an important contribution to knowledge on assessment of mycotoxin toxic effects, especially for assessing developmental and reproductive toxic effects, using the C. elegans model.

  16. Launch Area Toxic Risk Analysis Program (LATRA) Toxicology Review

    National Research Council Canada - National Science Library

    Prince, Joseph

    1996-01-01

    .... Therefore, a literature search of three species of rocket emissions was performed to identify health effects information useful to HQ Space Command for managing the risk from these toxic clouds...

  17. Risk factors that affect reproductive target achievement in fertile dairy cows.

    Science.gov (United States)

    Aungier, S P M; Roche, J F; Diskin, M G; Crowe, M A

    2014-01-01

    The aims of the present study were to investigate (1) the risk factors that influence the achievement of reproductive targets postpartum (pp) and (2) the key factors that influence pregnancy rate following first artificial insemination (AI) in dairy cows. Ninety-eight Holstein-Friesian pp cows were blood sampled from wk 1 to 4 pp for hematology and biochemistry. Reproductive tract health was assessed weekly by ultrasonography and vaginal mucus scoring. Body condition score (BCS), lameness score, and milk yield were assessed every 2 wk. Milk samples for progesterone assay were collected twice weekly and on d 4, 5, and 7 after AI. Risk factors associated with achieving reproductive targets depended on (1) increased metabolic activity of the liver (increased glutamate dehydrogenase at calving and increased γ-glutamyl transpeptidase in wk 4), (2) a competent immune system (increased neutrophils in wk 1; decreased α1-acid glycoprotein in wk 1, 2, and 3), (3) an endocrine system that was capable of responding by producing sufficient triiodothyronine in wk 2 and increased insulin-like growth factor I in wk 3 and 4, (4) a lower negative energy balance status (decreased nonesterified fatty acid concentration in wk 1; decreased β-hydroxybutyrate concentration in wk 2; BCS loss between calving and d 28 pp mucus discharge at first ovulation and at d 45 pp; resumed ovarian cyclicity by the end of the voluntary waiting period (≥ d 35 pp)], and (6) adequate diet (to ensure increased glutathione peroxidase in wk 2 and 3 and increased magnesium in wk 4). Risk factors that increased the odds of a successful first AI were previous ovulation(s) (odds ratio=3.17 per ovulation), BCS >2.5 at AI (odds ratio=3.01), and clear vaginal mucus (score=0) compared with purulent mucus (score >0) 4 d after first AI (odds ratio=2.99). In conclusion, this study identified key risk factors in the early pp period that give a higher probability of cows achieving their reproductive targets and of

  18. Reproductive factors and risk of mortality in the European Prospective Investigation into Cancer and Nutrition; a cohort study

    NARCIS (Netherlands)

    Merritt, Melissa A.; Riboli, Elio; Murphy, Neil; Kadi, Mai; Tjønneland, Anne; Olsen, Anja; Overvad, Kim; Dossus, Laure; Dartois, Laureen; Clavel-Chapelon, Françoise; Fortner, Renée T.; Katzke, Verena A.; Boeing, Heiner; Trichopoulou, Antonia; Lagiou, Pagona; Trichopoulos, Dimitrios; Palli, Domenico; Sieri, Sabina; Tumino, Rosario; Sacerdote, Carlotta; Panico, Salvatore; Bueno-de-Mesquita, H. Bas; Peeters, Petra H.; Lund, Eiliv; Nakamura, Aurelie; Weiderpass, Elisabete; Quirós, J. Ramón; Agudo, Antonio; Molina-Montes, Esther; Larrañaga, Nerea; Dorronsoro, Miren; Cirera, Lluís; Barricarte, Aurelio; Olsson, Åsa; Butt, Salma; Idahl, Annika; Lundin, Eva; Wareham, Nicholas J.; Key, Timothy J.; Brennan, Paul; Ferrari, Pietro; Wark, Petra A.; Norat, Teresa; Cross, Amanda J.; Gunter, Marc J.

    2015-01-01

    Background: Reproductive events are associated with important physiologic changes, yet little is known about how reproductive factors influence long-term health in women. Our objective was to assess the relation of reproductive characteristics with all-cause and cause-specific mortality risk.

  19. Developmental and Reproductive Toxicology of Methanol

    Science.gov (United States)

    Methanol is a high production volume chemical used as a feedstock for chemical syntheses and as a solvent and fuel additive. Methanol is acutely toxic to humans, causing acidosis, blindness in death at high dosages, but its developmental and reproductive toxicity in humans is poo...

  20. Predation risk affects growth and reproduction of an invasive snail and its lethal effect depends on prey size

    Science.gov (United States)

    Guo, Jing; Martín, Pablo R.; Zhang, Chunxia

    2017-01-01

    The behavior of invasive species under predation risk has been studied extensively, but their growth and reproductive responses have rarely been investigated. We conducted experiments with juveniles and adults of the invasive freshwater snail Pomacea canaliculata, and we observed changes in growth and reproduction in response to predation risk from a caged predator (Trachemys scripta elegans). P. canaliculata produced eggs earlier in the presence of predators and injured conspecifics compared with the control group (no risk), although the total number of egg masses laid by per female was exceeded by that of the controls after 15 days. Egg hatching success noticeably decreased under predation risk, and the incubation period was significantly prolonged; however, the oviposition height of the snails was not affected. A lethal effect of predation risk was detected in juvenile snails but not in adults. The growth of juvenile P. canaliculata was inhibited under predation risk, probably due to a reduction in food intake. Adult females exhibited a greater reduction in growth under predation risk than males, which likely resulted in part from the high reproductive investment of females in egg laying. These results indicate that P. canaliculata snails under predation risk face a trade-off between predator avoidance and growth and reproduction, where the lethal effect of predation risk is linked to the size of the prey. PMID:29136660

  1. Predation risk affects growth and reproduction of an invasive snail and its lethal effect depends on prey size.

    Directory of Open Access Journals (Sweden)

    Jing Guo

    Full Text Available The behavior of invasive species under predation risk has been studied extensively, but their growth and reproductive responses have rarely been investigated. We conducted experiments with juveniles and adults of the invasive freshwater snail Pomacea canaliculata, and we observed changes in growth and reproduction in response to predation risk from a caged predator (Trachemys scripta elegans. P. canaliculata produced eggs earlier in the presence of predators and injured conspecifics compared with the control group (no risk, although the total number of egg masses laid by per female was exceeded by that of the controls after 15 days. Egg hatching success noticeably decreased under predation risk, and the incubation period was significantly prolonged; however, the oviposition height of the snails was not affected. A lethal effect of predation risk was detected in juvenile snails but not in adults. The growth of juvenile P. canaliculata was inhibited under predation risk, probably due to a reduction in food intake. Adult females exhibited a greater reduction in growth under predation risk than males, which likely resulted in part from the high reproductive investment of females in egg laying. These results indicate that P. canaliculata snails under predation risk face a trade-off between predator avoidance and growth and reproduction, where the lethal effect of predation risk is linked to the size of the prey.

  2. Cypermethrin induced reproductive toxicity in male Wistar rats: protective role of Tribulus terrestris.

    Science.gov (United States)

    Sharma, Poonam; Huq, Amir Ul; Singh, Rambir

    2013-09-01

    The present study was designed to investigate role of ethanolic extract of Tribulus terrestris (EETT) against alpha-cypermethrin induced reproductive toxicity in male Wistar rats. 24 male Wistar rats weighing about 250-300g were divided in four groups. Group-I was control. alpha-cypermethrin (3.38 mg kg-1b.wt.) was given to group-IlI for 28 days. In Group-Ill, alpha-cypermethrin and EETT (100 mg kg -1b.wt.) were administered in combination for 28 days. Rats in group-IV were given EETT for 28 days. At the end of the experiment, rats were sacrificed, testes and epididymis were removed and sperm characteristics, sex hormones and various biochemical parameters were studied. Decrease in weight of testes and epididymis, testicular sperm head count, sperm motility, live sperm count, serum testosterone (T), follicle stimulating hormone (FSH), leutinizing hormone (LH), catalase (CAT), superoxide dismutase (SOD), glutathione S transferase (GST), glutathione reductase (GR), glutathione peroxidase (GPx), total protein content and increase in sperm abnormalities and lipid peroxidation (LPO) level was observed in rats exposed to cypermethrin. In combination group-Ill, EETT treatment ameliorated alpha-cypermethrin induced damage. EETT treatment in group-IV increased testes and epididymis weight, sperm head counts, sperm motility, live sperm counts, testosterone, FSH, LH, GSH, CAT, SOD, GST, GR, GPx and total protein content. The study suggested that Tribulus terrestris plant possess reproductive system enhancement and antioxidant activity.

  3. Undetected Toxicity Risk in Pharmacogenetic Testing for Dihydropyrimidine Dehydrogenase

    Directory of Open Access Journals (Sweden)

    Felicia Stefania Falvella

    2015-04-01

    Full Text Available Fluoropyrimidines, the mainstay agents for the treatment of colorectal cancer, alone or as a part of combination therapies, cause severe adverse reactions in about 10%–30% of patients. Dihydropyrimidine dehydrogenase (DPD, a key enzyme in the catabolism of 5-fluorouracil, has been intensively investigated in relation to fluoropyrimidine toxicity, and several DPD gene (DPYD polymorphisms are associated with decreased enzyme activity and increased risk of fluoropyrimidine-related toxicity. In patients carrying non-functional DPYD variants (c.1905+1G>A, c.1679T>G, c.2846A>T, fluoropyrimidines should be avoided or reduced according to the patients’ homozygous or heterozygous status, respectively. For other common DPYD variants (c.496A>G, c.1129-5923C>G, c.1896T>C, conflicting data are reported and their use in clinical practice still needs to be validated. The high frequency of DPYD polymorphism and the lack of large prospective trials may explain differences in studies’ results. The epigenetic regulation of DPD expression has been recently investigated to explain the variable activity of the enzyme. DPYD promoter methylation and its regulation by microRNAs may affect the toxicity risk of fluoropyrimidines. The studies we reviewed indicate that pharmacogenetic testing is promising to direct personalised dosing of fluoropyrimidines, although further investigations are needed to establish the role of DPD in severe toxicity in patients treated for colorectal cancer.

  4. Use of toxicity assessment to develop site specific remediation criteria for oil and gas facilities : guidance manual

    International Nuclear Information System (INIS)

    1996-01-01

    The results of a two year study into the evaluation of toxicity-based methods to develop site-specific, risk-based cleanup objectives for the decommissioning of oil and gas facilities were compiled into a manual of guidance. The two basic approaches used in determining remediation criteria for contaminated sites are: (1) comparison of the concentrations of chemicals found on-site with broad regional or national soil and water quality objectives developed for the chemicals involved, and (2) site-specific risk assessment. Toxicity tests are used to test organisms such as earthworms, lettuce seeds, or larval fish directly in the soil, water or sediment suspected of being contaminated. The effects of any contamination on the survival, growth, reproduction, and behaviour of the test organisms are then evaluated. The manual provides guidance in: (1) using toxicity assessments within the regulatory framework of site decommissioning, (2) performing a toxicity assessment, and (3) developing site-specific criteria for a risk assessment. 18 refs., 3 tabs., 5 figs

  5. Workgroup Report: Implementing a National Occupational Reproductive Research Agenda—Decade One and Beyond

    Science.gov (United States)

    Lawson, Christina C.; Grajewski, Barbara; Daston, George P.; Frazier, Linda M.; Lynch, Dennis; McDiarmid, Melissa; Murono, Eisuke; Perreault, Sally D.; Robbins, Wendie A.; Ryan, Megan A.K.; Shelby, Michael; Whelan, Elizabeth A.

    2006-01-01

    The initial goal of occupational reproductive health research is to effectively study the many toxicants, physical agents, and biomechanical and psychosocial stressors that may constitute reproductive hazards in the workplace. Although the main objective of occupational reproductive researchers and clinicians is to prevent recognized adverse reproductive outcomes, research has expanded to include a broader spectrum of chronic health outcomes potentially affected by reproductive toxicants. To aid in achieving these goals, the National Institute for Occupational Safety and Health, along with its university, federal, industry, and labor colleagues, formed the National Occupational Research Agenda (NORA) in 1996. NORA resulted in 21 research teams, including the Reproductive Health Research Team (RHRT). In this report, we describe progress made in the last decade by the RHRT and by others in this field, including prioritizing reproductive toxicants for further study; facilitating collaboration among epidemiologists, biologists, and toxicologists; promoting quality exposure assessment in field studies and surveillance; and encouraging the design and conduct of priority occupational reproductive studies. We also describe new tools for screening reproductive toxicants and for analyzing mode of action. We recommend considering outcomes such as menopause and latent adverse effects for further study, as well as including exposures such as shift work and nanomaterials. We describe a broad domain of scholarship activities where a cohesive system of organized and aligned work activities integrates 10 years of team efforts and provides guidance for future research. PMID:16507468

  6. Risk Levels of Toxic Cyanobacteria in Portuguese Recreational Freshwaters

    Directory of Open Access Journals (Sweden)

    Carina Menezes

    2017-10-01

    Full Text Available Portuguese freshwater reservoirs are important socio-economic resources, namely for recreational use. National legislation concerning bathing waters does not include mandatory levels or guidelines for cyanobacteria and cyanotoxins. This is an issue of concern since cyanotoxin-based evidence is insufficient to change the law, and the collection of scientific evidence has been hampered by the lack of regulatory levels for cyanotoxins in bathing waters. In this work, we evaluate the profile of cyanobacteria and microcystins (MC in eight freshwater reservoirs from the center of Portugal, used for bathing/recreation, in order to determine the risk levels concerning toxic cyanobacteria occurrence. Three of the reservoirs did not pose a risk of MC contamination. However, two reservoirs presented a high risk in 7% of the samples according to the World Health Organization (WHO guidelines for MC in bathing waters (above 20 µg/L. In the remaining three reservoirs, the risk concerning microcystins occurrence was low. However, they exhibited recurrent blooms and persistent contamination with MC up to 4 µg/L. Thus, the risk of exposure to MC and potential acute and/or chronic health outcomes should not be disregarded in these reservoirs. These results contribute to characterize the cyanobacterial blooms profile and to map the risk of toxic cyanobacteria and microcystins occurrence in Portuguese inland waters.

  7. Male reproductive organs are at risk from environmental hazards

    DEFF Research Database (Denmark)

    Bonde, Jens Peter

    2010-01-01

    are the best documented risk factors for impaired male reproductive function and include physical exposures (radiant heat, ionizing radiation, high frequency electromagnetic radiation), chemical exposures (some solvents as carbon disulfide and ethylene glycol ethers, some pesticides as dibromochloropropane......, ethylendibromide and DDT/DDE, some heavy metals as inorganic lead and mercury) and work processes such as metal welding. Improved working conditions in affluent countries have dramatically decreased known hazardous workplace exposures, but millions of workers in less affluent countries are at risk from...... as phthalates, bisphenol A and boron that are present in a large number of industrial and consumer products entails a risk remains to be established. The same applies to psychosocial stressors and use of mobile phones. Finally, there are data indicating a particular vulnerability of the fetal testis...

  8. Chapter 11.18 - Neuroendocrine Control of Female Reproduction.

    Science.gov (United States)

    The hypothalamus and pituitary are known to play roles in reproductive function. A growing body of evidence indicates that environmental toxicants can alter female reproductive function by disrupting hypothalamic control of the pituitary and subsequently the endocrine control of ...

  9. The risk of toxic retinopathy in patients on long-term hydroxychloroquine therapy.

    Science.gov (United States)

    Melles, Ronald B; Marmor, Michael F

    2014-12-01

    Hydroxychloroquine sulfate is widely used for the long-term treatment of autoimmune conditions but can cause irreversible toxic retinopathy. Prior estimations of risk were low but were based largely on short-term users or severe retinal toxicity (bull's eye maculopathy). The risk may be much higher because retinopathy can be detected earlier when using more sensitive screening techniques. To reassess the prevalence of and risk factors for hydroxychloroquine retinal toxicity and to determine dosage levels that facilitate safe use of the drug. Retrospective case-control study in an integrated health organization of approximately 3.4 million members among 2361 patients who had used hydroxychloroquine continuously for at least 5 years according to pharmacy records and who were evaluated with visual field testing or spectral-domain optical coherence tomography. Hydroxychloroquine use for at least 5 years. Retinal toxicity as determined by characteristic visual field loss or retinal thinning and photoreceptor damage, as well as statistical measures of risk factors and prevalence. Real body weight predicted risk better than ideal body weight and was used for all calculations. The overall prevalence of hydroxychloroquine retinopathy was 7.5% but varied with daily consumption (odds ratio, 5.67; 95% CI, 4.14-7.79 for >5.0 mg/kg) and with duration of use (odds ratio, 3.22; 95% CI, 2.20-4.70 for >10 years). For daily consumption of 4.0 to 5.0 mg/kg, the prevalence of retinal toxicity remained less than 2% within the first 10 years of use but rose to almost 20% after 20 years of use. Other major risk factors include kidney disease (odds ratio, 2.08; 95% CI, 1.44-3.01) and concurrent tamoxifen citrate therapy (odds ratio, 4.59; 95% CI, 2.05-10.27). These data suggest that hydroxychloroquine retinopathy is more common than previously recognized, especially at high dosages and long duration of use. While no completely safe dosage is identified from this study, daily consumption of

  10. Development and validation of an OECD reproductive toxicity test guideline with the pond snail Lymnaea stagnalis (Mollusca, Gastropoda).

    Science.gov (United States)

    Ducrot, Virginie; Askem, Clare; Azam, Didier; Brettschneider, Denise; Brown, Rebecca; Charles, Sandrine; Coke, Maïra; Collinet, Marc; Delignette-Muller, Marie-Laure; Forfait-Dubuc, Carole; Holbech, Henrik; Hutchinson, Thomas; Jach, Arne; Kinnberg, Karin L; Lacoste, Cédric; Le Page, Gareth; Matthiessen, Peter; Oehlmann, Jörg; Rice, Lynsey; Roberts, Edward; Ruppert, Katharina; Davis, Jessica Elphinstone; Veauvy, Clemence; Weltje, Lennart; Wortham, Ruth; Lagadic, Laurent

    2014-12-01

    The OECD test guideline development program has been extended in 2011 to establish a partial life-cycle protocol for assessing the reproductive toxicity of chemicals to several mollusk species, including the great pond snail Lymnaea stagnalis. In this paper, we summarize the standard draft protocol for a reproduction test with this species, and present inter-comparison results obtained in a 56-day prevalidation ring-test using this protocol. Seven European laboratories performed semi-static tests with cultured snails of the strain Renilys® exposed to nominal concentrations of cadmium chloride (from 53 to 608μgCdL(-1)). Cd concentrations in test solutions were analytically determined to confirm accuracy in the metal exposure concentrations in all laboratories. Physico-chemical and biological validity criteria (namely dissolved oxygen content >60% ASV, water temperature 20±1°C, control snail survival >80% and control snail fecundity >8 egg-masses per snail over the test period) were met in all laboratories which consistently demonstrated the reproductive toxicity of Cd in snails using the proposed draft protocol. Effect concentrations for fecundity after 56days were reproducible between laboratories (68

  11. Metritis in dairy cows: risk factors and reproductive performance.

    Science.gov (United States)

    Giuliodori, M J; Magnasco, R P; Becu-Villalobos, D; Lacau-Mengido, I M; Risco, C A; de la Sota, R L

    2013-06-01

    The objectives of this study were to assess the risk factors for metritis, its effects on milk yield and on reproductive performance, and the efficacy of ceftiofur therapy in Holstein dairy cows. Cows (n=303) from a commercial dairy herd in Argentina were studied. Cows were scored for body condition, and blood samples were collected on d -14, 7, 21, 31, 41, and 50 relative to parturition. Cows having a watery, purulent, or brown, and fetid vaginal discharge (VD) and rectal temperature ≤ 39.2°C were diagnosed as having clinical metritis, and those having a similar VD and rectal temperature >39.2°C were diagnosed as having puerperal metritis. Both clinical and puerperal metritis cows were randomly assigned to control (no treatment) or ceftiofur group (2.2mg/kg×3 consecutive days). Cure was declared if clear VD was observed at 21 d in milk (DIM). Blood samples were analyzed for nonesterified fatty acids, β-hydroxybutyrate, and blood urea nitrogen using commercial kits, and for insulin-like growth factor-1, insulin, and leptin by RIA. Data were analyzed with PROC MIXED, GENMOD, PHREG, and LIFETEST from SAS (SAS Institute Inc., Cary, NC). The risk for metritis increased with dystocia, retained fetal membranes, and dead calf [AOR (adjusted odds ratio)=2.58, 95% CI: 1.189-5.559], and as prepartum nonesterified fatty acids levels increased (AOR=1.001, 95% CI: 0.999-1.002). Conversely, risk decreased as prepartum insulin-like growth factor-1 increased (AOR=0.65, 95% CI: 0.349-1.219). Cows having either clinical or puerperal metritis produced less milk by 90 DIM than did healthy cows (2,236 ± 172 vs. 2,367 ± 77 vs. 2,647 ± 82 kg, respectively). Cows with puerperal metritis had lower risk for pregnancy by 100 DIM (AOR=0.189, 95% CI: 0.070-0.479) and a lower hazard rate for pregnancy by 150 DIM (hazard rate: 0.753, 95% CI: 0.621-0.911), and took longer to get pregnant (129 vs. 111 vs. 109 d, for puerperal metritis, clinical metritis, and healthy cows, respectively

  12. Triorganotin as a compound with potential reproductive toxicity in mammals

    Directory of Open Access Journals (Sweden)

    V.S. Delgado Filho

    2011-09-01

    Full Text Available Organotin compounds are typical environmental contaminants and suspected endocrine-disrupting substances, which cause irreversible sexual abnormality in female mollusks, called "imposex". However, little is known about the capability of triorganotin compounds, such as tributyltin and triphenyltin, to cause disorders in the sexual development and reproductive functions of mammals, including humans and rodents. Moreover, these compounds can act as potential competitive inhibitors of aromatase enzyme and other steroidogenic enzymes, affecting the reproductive capacity of male and female mammals. In this review, we discuss the cellular, biochemical, and molecular mechanisms by which triorganotin compounds induce adverse effects in the mammalian reproductive function.

  13. The regulation of cellular apoptosis by the ROS-triggered PERK/EIF2α/chop pathway plays a vital role in bisphenol A-induced male reproductive toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Yin, Li [Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing 400038 (China); Dai, Yanlin [Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing 400038 (China); Medical Laboratory Technology Department, Chuxiong Medical College, Yunnan 675005 (China); Cui, Zhihong; Jiang, Xiao; Liu, Wenbin; Han, Fei; Lin, Ao; Cao, Jia [Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing 400038 (China); Liu, Jinyi, E-mail: jinyiliutmmu@163.com [Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing 400038 (China)

    2017-01-01

    Bisphenol A (2,2-bis(4-hydroxyphenyl)propane, BPA) is ubiquitous in the environment, wildlife, and humans. Evidence from past studies suggests that BPA is associated with decreased semen quality. However, the molecular basis for the adverse effect of BPA on male reproductive toxicity remains unclear. We evaluated the effect of BPA on mouse spermatocytes GC-2 cells and adult mice, and we explored the potential mechanism of its action. The results showed that BPA inhibited cell proliferation and increased the apoptosis rate. The testes from BPA-treated mice showed fewer spermatogenic cells and sperm in the seminiferous tubules. In addition, BPA caused reactive oxygen species (ROS) accumulation. Previous study has verified that mitochondrion was the organelle affected by the BPA-triggered ROS accumulation. We found that BPA induced damage to the endoplasmic reticulum (ER) in addition to mitochondria, and most ER stress-related proteins were activated in cellular and animal models. Knocking down of the PERK/EIF2α/chop pathway, one of the ER stress pathways, partially recovered the BPA-induced cell apoptosis. In addition, an ROS scavenger attenuated the expression of the PERK/EIF2α/chop pathway-related proteins. Taken together, these data suggested that the ROS regulated PERK/EIF2α/chop pathway played a vital role in BPA-induced male reproductive toxicity. - Highlights: • BPA exposure caused the damage of the endoplasmic reticulum. • BPA exposure activated ER stress related proteins in male reproductive system. • ROS regulated PERK/EIF2α/chop pathway played a vital role in BPA-induced toxicity.

  14. Bioavailability and toxicity of pyrene in soils upon biochar and compost addition.

    Science.gov (United States)

    Bielská, Lucie; Kah, Melanie; Sigmund, Gabriel; Hofmann, Thilo; Höss, Sebastian

    2017-10-01

    The study investigates the role of biochar and/or compost in mitigating the toxic effects of pyrene in soils using reproduction of nematodes and porewater concentration as measures of pyrene toxicity and bioavailability, respectively. Two soils were spiked with increasing levels of pyrene to achieve a concentration-response relationship for the reproduction of Caenorhabditis elegans. The observed EC50 values (pyrene concentration causing 50% inhibition of reproduction) were 14mg/kg and 31mg/kg (dry mass) for these soils, corresponding to equilibrium porewater concentrations of 37μg/L and 47μg/L, respectively. Differences in organic carbon content were not sufficient to explain the variability in toxicity between the different soils. Soils causing a significant inhibition of reproduction were further amended with 10%-compost, 5%-biochar, or both, and the effects on reproduction and porewater concentration determined. Combined addition of compost and biochar was identified as the most effective strategy in reducing pyrene concentration in soil porewater, which was also partly reflected in soil toxicity. However, porewater concentrations predicted only 52% of pyrene toxicity to nematodes, pointing to particle-bound or dietary exposure pathways. Capsule: Amending pyrene-spiked soil with biochar and compost effectively reduced pyrene porewater concentrations and toxicity to nematodes, which were significantly related. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Toxic effects of di(2-ethylhexyl)phthalate on mortality, growth, reproduction and stress-related gene expression in the soil nematode Caenorhabditis elegans.

    Science.gov (United States)

    Roh, Ji-Yeon; Jung, In-Ho; Lee, Jai-Young; Choi, Jinhee

    2007-07-31

    In this study, di(2-ethylhexyl)phthalate (DEHP) toxicities to Caenorhabditis elegans were investigated using multiple toxic endpoints, such as mortality, growth, reproduction and stress-related gene expression, focusing on the identification of chemical-induced gene expression as a sensitive biomarker for DEHP monitoring. The possible use of C. elegans as a sentinel organism in the monitoring of soil ecosystem health was also tested by conducting the experiment on the exposure of nematode to field soil. Twenty-four-hour median lethal concentration (LC50) data suggest that DEHP has a relatively high potential of acute toxicity to C. elegans. Decreases in body length and egg number per worm observed after 24h of DEHP exposure may induce long-term alteration in the growth and reproduction of the nematode population. Based on the result from the C. elegans genome array and indicated in the literatures, stress proteins, metallothionein, vitellogenin, xenobiotic metabolism enzymes, apoptosis-related proteins, and antioxidant enzyme genes were selected as stress-related genes and their expression in C. elegans by DEHP exposure was analyzed semi-quantitatively. Expression of heat shock protein (hsp)-16.1 and hsp-16.2 genes was decreased by DEHP exposure. Expression of cytochrome P450 (cyp) 35a2 and glutathione-S-transferease (gst)-4, phase I and phase II of xenobiotic metabolism enzymes, was increased by DEHP exposure in a concentration-dependent manner. An increase in stress-related gene expressions occurred concomitantly with the deterioration on the physiological level, which suggests an increase in expression of those genes may not be considered as a homeostatic response but as a toxicity that might have physiological consequences. The experiment with the soil from the landfill site suggests that the potential of the C. elegans biomarker identified in laboratory conditions should be calibrated and validated for its use in situ.

  16. Tributyltin impairs the reproductive cycle in female rats.

    Science.gov (United States)

    Lang Podratz, Priscila; Delgado Filho, Vicente Sathler; Lopes, Pedro Francisco Iguatemy; Cavati Sena, Gabriela; Matsumoto, Silvia Tamie; Samoto, Vivian Yochiko; Takiya, Christina Maeda; de Castro Miguel, Emilio; Silva, Ian Victor; Graceli, Jones Bernardes

    2012-01-01

    Triorganotins are environmental contaminants, commonly used in antifouling agents for boats, that bioaccumulate and thus are found in mammals and humans due to ingestion of contaminated seafood diets. The importance of triorganotins as environmental endocrine disruptors and consequent reproductive toxicity in different animal models is well known; however, the adverse effects on reproductive cycle are less well understood. The potential reproductive toxicity of tributyltin (TBT) on regular reproductive cycling of female rats was examined. Wistar female rats (12 wk old, weighing approximately 230 g) were divided into two groups: control (vehicle, ethanol 0.4%) and tributyltin (100 ng/kg/d, 7 d/wk, for 16 d by gavage). Tributyltin significantly decreased the cycle regularity (%), duration of the reproductive cycle, the proestrus and diestrus phases, and number of epithelial cell in proestrus phase. TBT also increased the duration of metestrus and the number of cornified cells in this phase. Ovary weight and serum 17β-estradiol levels decreased markedly, accompanied by a significant increase in progesterone levels. Histological analysis showed apoptotic cells in corpus luteum and granulosa cells layer, with cystic follicles after TBT exposure. Tributyltin also elevated number of atretic follicles and corpoa lutea. The micronucleus (MN) test, using Chinese hamster ovary cells, demonstrated a concentration-dependent mutagenic effect of TBT, and at 2.0 × 10(-2)ng/ml most of the cells were nonviable. The toxic potential of TBT over the reproductive cycle may be attributed to changes found in the ovarian weight, unbalanced levels of sexual female hormones, and number of ovarian follicles and corpora lutea.

  17. Sertraline-induced reproductive toxicity in male rats: evaluation of possible underlying mechanisms

    Directory of Open Access Journals (Sweden)

    Ozlem Atli

    2017-01-01

    Full Text Available This study was conducted to clarify the toxic effects of sertraline (SRT on the reproductive system of male rats and to elucidate the underlying mechanisms. Rats were treated orally with SRT at doses of 5, 10, and 20 mg kg−1 for 28 consecutive days. At the end of the treatment period, sperm concentration, sperm motility, and sperm morphology were investigated by computer-assisted sperm analysis system whereas sperm DNA damage was detected by comet assay. The oxidative status of the testes was investigated, and a histopathological examination was conducted. Serum testosterone, follicle-stimulating hormone (FSH, and luteinizing hormone (LH levels were measured to determine the effects of SRT on the spermatogenesis process. One-way ANOVA, post-hoc Dunnett′s T3 test for the sperm comet assay, and post-hoc Tukey′s test for the others were performed for statistical analysis. The results showed that SRT caused an increase in sperm DNA damage and induced histopathological lesions in all groups treated with SRT. There was abnormal sperm morphology and increased malondialdehyde (MDA in the 10 mg kg−1 treatment group. More dramatic changes were observed in the 20 mg kg−1 treatment group. Decreased sperm count was accompanied by a significant increase in abnormal sperm morphology, DNA damage, and degeneration in cellular-tubular structures. Serum LH and testosterone levels were elevated in the 20 mg kg−1 treatment group. Decreased glutathione (GSH and increased MDA were signs of enhanced oxidative stress (OS. In conclusion, SRT induced testicular toxicity in a dose-dependent manner and OS is suggested as a crucial mechanism.

  18. Preliminary analysis of risk factors for late rectal toxicity after helical tomotherapy for prostate cancer

    International Nuclear Information System (INIS)

    Tomita, Natsuo; Soga, Norihito; Ogura, Yuji

    2013-01-01

    The purpose of this study is to examine risk factors for late rectal toxicity for localized prostate cancer patients treated with helical tomotherapy (HT). The patient cohort of this retrospective study was composed of 241 patients treated with HT and followed up regularly. Toxicity levels were scored according to the Radiation Therapy Oncology Group grading scale. The clinical and dosimetric potential factors increasing the risk of late rectal toxicity, such as age, diabetes, anticoagulants, prior abdominal surgery, prescribed dose, maximum dose of the rectum, and the percentage of the rectum covered by 70 Gy (V70), 60 Gy (V60), 40 Gy (V40) and 20 Gy (V20) were compared between ≤ Grade 1 and ≥ Grade 2 toxicity groups using the Student's t-test. Multivariable logistic regression analysis of the factors that appeared to be associated with the risk of late rectal toxicity (as determined by the Student's t-test) was performed. The median follow-up time was 35 months. Late Grade 2-3 rectal toxicity was observed in 18 patients (7.4%). Age, the maximum dose of the rectum, V70 and V60 of the ≥ Grade 2 toxicity group were significantly higher than in those of the ≤ Grade 1 toxicity group (P=0.00093, 0.048, 0.0030 and 0.0021, respectively). No factor was significant in the multivariable analysis. The result of this study indicates that the risk of late rectal toxicity correlates with the rectal volume exposed to high doses of HT for localized prostate cancer. Further follow-up and data accumulation may establish dose-volume modeling to predict rectal complications after HT. (author)

  19. Assessing PAHs pollution in Shandong coastal area (China) by combination of chemical analysis and responses of reproductive toxicity in crab Portunus trituberculatus.

    Science.gov (United States)

    Pan, Luqing; Xu, Ruiyi; Wen, Jianmin; Guo, Ruiming

    2017-06-01

    The concentrations of PAHs in seawater and sediments were measured at three selected sites (S1, S2, and S3) along the coastal area of Shandong (China) in April, May, and June, 2015, which ranged from 29.72 to 123.88 ng/L and 82.62 to 232.63 ng/g, respectively. Meanwhile, the reproductive toxicity responses in crab Portunus trituberculatus were also evaluated to assess the pollution of PAHs during the sampling period. Chemical analysis showed that S3 was the most PAH-contaminated area while S1 was the least, and the biochemical parameters concerned with reproduction were efficiently responded to the three sites, especially in S3 (p coastal area of Shandong, China.

  20. Maternal risk of breeding failure remained low throughout the demographic transitions in fertility and age at first reproduction in Finland.

    Directory of Open Access Journals (Sweden)

    Jianghua Liu

    Full Text Available Radical declines in fertility and postponement of first reproduction during the recent human demographic transitions have posed a challenge to interpreting human behaviour in evolutionary terms. This challenge has stemmed from insufficient evolutionary insight into individual reproductive decision-making and the rarity of datasets recording individual long-term reproductive success throughout the transitions. We use such data from about 2,000 Finnish mothers (first births: 1880s to 1970s to show that changes in the maternal risk of breeding failure (no offspring raised to adulthood underlay shifts in both fertility and first reproduction. With steady improvements in offspring survival, the expected fertility required to satisfy a low risk of breeding failure became lower and observed maternal fertility subsequently declined through an earlier age at last reproduction. Postponement of the age at first reproduction began when this risk approximated zero-even for mothers starting reproduction late. Interestingly, despite vastly differing fertility rates at different stages of the transitions, the number of offspring successfully raised to breeding per mother remained relatively constant over the period. Our results stress the importance of assessing the long-term success of reproductive strategies by including measures of offspring quality and suggest that avoidance of breeding failure may explain several key features of recent life-history shifts in industrialized societies.

  1. Maternal Risk of Breeding Failure Remained Low throughout the Demographic Transitions in Fertility and Age at First Reproduction in Finland

    Science.gov (United States)

    Liu, Jianghua; Rotkirch, Anna; Lummaa, Virpi

    2012-01-01

    Radical declines in fertility and postponement of first reproduction during the recent human demographic transitions have posed a challenge to interpreting human behaviour in evolutionary terms. This challenge has stemmed from insufficient evolutionary insight into individual reproductive decision-making and the rarity of datasets recording individual long-term reproductive success throughout the transitions. We use such data from about 2,000 Finnish mothers (first births: 1880s to 1970s) to show that changes in the maternal risk of breeding failure (no offspring raised to adulthood) underlay shifts in both fertility and first reproduction. With steady improvements in offspring survival, the expected fertility required to satisfy a low risk of breeding failure became lower and observed maternal fertility subsequently declined through an earlier age at last reproduction. Postponement of the age at first reproduction began when this risk approximated zero–even for mothers starting reproduction late. Interestingly, despite vastly differing fertility rates at different stages of the transitions, the number of offspring successfully raised to breeding per mother remained relatively constant over the period. Our results stress the importance of assessing the long-term success of reproductive strategies by including measures of offspring quality and suggest that avoidance of breeding failure may explain several key features of recent life-history shifts in industrialized societies. PMID:22529952

  2. Reproductive risk factors assessment for anaemia among pregnant women in India using a multinomial logistic regression model.

    Science.gov (United States)

    Perumal, Vanamail

    2014-07-01

    To assess reproductive risk factors for anaemia among pregnant women in urban and rural areas of India. The International Institute of Population Sciences, India, carried out third National Family Health Survey in 2005-2006 to estimate a key indicator from a sample of ever-married women in the reproductive age group 15-49 years. Data on various dimensions were collected using a structured questionnaire, and anaemia was measured using a portable HemoCue instrument. Anaemia prevalence among pregnant women was compared between rural and urban areas using chi-square test and odds ratio. Multinomial logistic regression analysis was used to determine risk factors. Anaemia prevalence was assessed among 3355 pregnant women from rural areas and 1962 pregnant women from urban areas. Moderate-to-severe anaemia in rural areas (32.4%) is significantly more common than in urban areas (27.3%) with an excess risk of 30%. Gestational age specific prevalence of anaemia significantly increases in rural areas after 6 months. Pregnancy duration is a significant risk factor in both urban and rural areas. In rural areas, increasing age at marriage and mass media exposure are significant protective factors of anaemia. However, more births in the last five years, alcohol consumption and smoking habits are significant risk factors. In rural areas, various reproductive factors and lifestyle characteristics constitute significant risk factors for moderate-to-severe anaemia. Therefore, intensive health education on reproductive practices and the impact of lifestyle characteristics are warranted to reduce anaemia prevalence. © 2014 John Wiley & Sons Ltd.

  3. Protective Effect of Vitamin E on Nicotine Induced Reproductive ...

    African Journals Online (AJOL)

    Protective Effect of Vitamin E on Nicotine Induced Reproductive Toxicity in ... The health implications of cigarette smoking and ..... toxic byproducts of many metabolic processes in ... Male infertility, clinical ... rats: A possible role of cessation.

  4. The toxic and radiological risk equivalence approach in UF6 transport

    International Nuclear Information System (INIS)

    Ringot, C.; Hamard, J.

    1988-12-01

    After a brief description of the safety in transport of UF 6 , we discuss the equivalence of the radioactive and chemical risks in UF 6 transport regulations. As the concept of low specific activity appears to be ill-suited for a toxic gas, we propose a quantity of material limit designated T 2 (equivalent to A 2 for radioactive substances) for packagings unable to withstand accident conditions (9 m drop, 800 0 C fire environment for 30 minutes). It is proposed that this limit be chosen for the amount of release acceptable after AIEA tests. Different possible scenarios are described, with fire assumed to be the most severe toxic risk situation

  5. A review of acrylamide toxicity and its mechanism

    Directory of Open Access Journals (Sweden)

    Ehsan Zamani

    2017-05-01

    Full Text Available Acrylamide (AA is an important industrial chemical agent that is mainly used in the production of polymers and copolymers. Recently it has been attention because of its production in the diet at high-temperature (>120 ºC processes such as cooking, frying, toasting, roasting or baking of high carbohydrate foods. According to high exposure to acrylamide, recognition of its toxic effect is necessary. Neurotoxicity, reproductive toxicity and immunotoxicity of AA were observed in several studies. There isn’t a clear mechanism that justifies this toxicity. In this study we reviewed the mechanisms of AA toxicity especially oxidative stress and apoptosis. AA can cause neurotoxicity, reproductive toxicity and genotoxicity on animal models. It showed neurotoxicity in human. We suggested the oxidative stress is the main factor for inducing of acrylamide toxicities. We advised that modifying of food processing methods can be as a good way for decreasing of AA production in foods.

  6. Vector-borne diseases: the basic reproduction number R0 and risk maps

    NARCIS (Netherlands)

    Hartemink, N.A.|info:eu-repo/dai/nl/304836699

    2009-01-01

    This thesis deals with the derivation of the basic reproduction number (R0) for vector-borne diseases, in the context of studying the effect of climate change on the risk of emergence diseases. Vector-borne diseases are transmitted from an infected individual to another individual by vectors,

  7. Risk of poor neonatal outcome at term after medically assisted reproduction: a propensity score-matched study.

    Science.gov (United States)

    Ensing, Sabine; Abu-Hanna, Ameen; Roseboom, Tessa J; Repping, Sjoerd; van der Veen, Fulco; Mol, Ben Willem J; Ravelli, Anita C J

    2015-08-01

    To study risk of birth asphyxia and related morbidity among term singletons born after medically assisted reproduction (MAR). Population cohort study. Not applicable. A total of 1,953,932 term singleton pregnancies selected from a national registry for 1999-2011. None. Primary outcome Apgar score score score matching analysis was performed with matching on multiple maternal baseline covariates (maternal age, ethnicity, socioeconomic status, parity, year of birth, and preexistent diseases). Each MAR pregnancy was matched to three SC controls. Relative to SC, the MAR singletons had an increased risk of adverse neonatal outcomes including Apgar score score matching, the risk of an Apgar score Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  8. Assessment of female reproductive endpoints in Sprague-Dawley rats developmentally exposed to Diuron: potential ovary toxicity.

    Science.gov (United States)

    Grassi, Tony Fernando; Guerra, Marina Trevisan; Perobelli, Juliana Elaine; de Toledo, Fabíola Choqueta; da Silva, Denise Salioni; De Grava Kempinas, Wilma; Barbisan, Luís Fernando

    2011-10-01

    Diuron is widely used in agriculture but its deleterious effects on the reproductive system and mammary gland are still poorly understood. This study evaluated whether early-life-stage exposure to Diuron alters puberty onset or susceptibility to mammary carcinogenesis in female Sprague-Dawley rats. Pregnant rats received basal diet or diet containing Diuron at 500, 750, and 1,250 ppm, from gestational day 12 to the end of lactation (postnatal day 21 [PND21]). After weaning, female offspring continued receiving basal diet or diet containing Diuron until PND 51. At PND 51, female Sprague-Dawley offspring received a single dose of 50 mg/kg b.w. of 7,12-dimethylbenz(a)anthracene (DMBA) for initiation of mammary carcinogenesis. The animals were sacrificed on PND 51, 75, and 226 to 233 (week 25) for mammary gland morphology, reproductive organs and tumor analysis, respectively. There were no significant differences among groups on vaginal opening, estrous cycle, mammary morphology, or carcinogenesis. However, reductions in ovary weight and corpora lutea were observed at PND 75 in the group treated with Diuron at 1,250 ppm. The findings suggesting that Diuron exposure (1,250 ppm) may have been potentially toxic to the ovaries. © 2011 Wiley Periodicals, Inc.

  9. Signatures of reproductive events on blood counts and biomarkers of inflammation: Implications for chronic disease risk.

    Directory of Open Access Journals (Sweden)

    Daniel W Cramer

    Full Text Available Whether inflammation mediates how reproductive events affect chronic-disease risk is unclear. We studied inflammatory biomarkers in the context of reproductive events using National Health and Nutrition Examination Survey (NHANES data. From 15,986 eligible women from the 1999-2011 data cycles, we accessed information on reproductive events, blood counts, C-reactive protein (CRP, and total homocysteine (tHCY. We calculated blood-count ratios including: platelet-lymphocyte (PLR, lymphocyte-monocyte (LMR, platelet-monocyte (PMR, and neutrophil-monocyte (NMR. Using sampling weights per NHANES guidelines, means for counts, ratios, or biomarkers by reproductive events were compared using linear regression. We performed trend tests and calculated p-values with partial sum of squares F-tests. Higher PLR and lower LMR were associated with nulliparity. In postmenopausal women, lower PMR was associated with early age at first birth and higher NMR with later age at and shorter interval since last birth. Lower PNR and higher neutrophils and tHCY were associated with early natural menopause. In all women, the neutrophil count correlated positively with CRP; but, in premenopausal women, correlated inversely with tHCY. Reproductive events leave residual signatures on blood counts and inflammatory biomarkers that could underlie their links to chronic disease risk.

  10. Low-technology assisted reproduction and the risk of preterm birth in a hospital-based cohort.

    Science.gov (United States)

    Messerlian, Carmen; Platt, Robert W; Tan, Seang-Lin; Gagnon, Robert; Basso, Olga

    2015-01-01

    To estimate the risk of preterm birth in singleton infants conceived through low-technology assisted reproduction (intrauterine insemination and/or ovulation induction/stimulation). Hospital-based cohort study. University-affiliated hospital. Singleton babies born between 2001 and 2007 to 16,712 couples with no reported infertility (reference category), 378 babies conceived with low-technology treatment; 437 conceived with high-technology treatment; and 620 conceived naturally after a period of infertility. None. Treatment data were obtained from couples undergoing standard infertility investigation and care. Preterm birth, defined at three clinical endpoints: assisted reproduction appeared to be a moderately strong predictor of preterm birth, with similar associations observed in the high-technology treatment group. After adjusting for confounders, as well as the shared characteristics of infertile couples, associations were attenuated but remained significant, suggesting that part of the risk is likely attributable to the treatment. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  11. Toxic plants: Effects on reproduction and fetal and embryonic development in livestock

    Science.gov (United States)

    Reproductive success is dependent on a large number of carefully orchestrated biological events that must occur in a specifically timed sequence. The interference with one of more of these sequences or events may result in total reproductive failure or a more subtle reduction in reproductive potent...

  12. Toxicity of middle distillates from dermal exposure.

    Science.gov (United States)

    Koschier, F J

    1999-02-01

    This report focuses on recent studies that investigated the effects of kerosine dermal exposure on neurotoxicity and reproductive/developmental toxicity. Background toxicity information will also be reviewed for kerosine range mid distillates. The kerosine range mid distillates have a carbon range of C9-C16 and have a boiling range of 302-554 degrees F (150-290 degrees C). This category includes kerosine, aviation fuels (e.g., Jet A, JP-5 and JP-8), no. 1 fuel oil and diesel fuel oil. In general, the kerosine range mid distillates demonstrate relatively low acute toxicity by any route of exposure. High inhalation exposures can induce central nervous system depression characterized by ataxia, hypoactivity and prostration. Kerosines are known to cause skin irritation and inflammation under conditions of acute and repeated exposure in animals and humans, but are only slightly irritating to the eye and are not skin sensitizers. In addition, the absorption of kerosine range mid distillates through the skin has been demonstrated to be fairly rapid, but limited to approximately 10-15% of the applied dose after 24 hours. The kerosine range mid distillates are generally inactive in genetic toxicity tests although positive studies have been reported. Positive results, while at times equivocal, have been reported for straight run kerosine and jet fuel A in the mouse lymphoma assay with metabolic activation, and hydrodesulfurized kerosine (mouse) and jet fuel A (rat) in the bone marrow cytogenetic assay. Effects on the nervous and reproductive systems have been reported in humans and experimental animals under conditions where inhalation and dermal exposure to specific kerosine type fuels are sometimes difficult to separate. Recent laboratory studies have addressed this point and examined the effects of dermal exposure. In these studies, rats were exposed to hydrodesulfurized kerosine by skin application to determine the potential of dermal contact to cause reproductive

  13. Impact of the environment on reproductive health.

    Science.gov (United States)

    1991-01-01

    The WHO workshop on the impact of the environment on reproductive health is summarized. Topics include the nature of environmental factors affecting reproductive health, environmental factors blamed for declining sperm quantity and quality, the effects of natural and man-made disasters on reproductive health, chemical pollutants, how the environment damages reproductive health, and research needs for better research methodologies and surveillance data. Recommendations are made to: 1) promote international research collaboration with an emphasis on consistency of methodological approaches for assessing developmental and reproductive toxicity, on development of improved surveillance systems and data bases, an strengthening international disaster alert and evaluation systems; 2) promote research capabilities for multidisciplinary studies, for interactive studies of the environment and cellular processes, and for expansion of training and education; and 3) take action on priority problems of exposure to chemical, physical, and biological agents, of exposure to pesticides among specific populations, and of inadequate screening methods for identification of environmental chemicals. The costs of environmental injury to reproduction include subfertility, intrauterine growth retardation, spontaneous abortion, and various birth defects. Developed country's primary threats are from chemical pollution, radiation, and stress. There is a large gap in knowledge. Caution is urged in understanding the direct relationship between environmental causes and infertility. Sexual health is difficult to assess and research is suggested. Exposure to excessive vitamin A and toxic chemicals are cited as agents probably having serious effects on malformations. Sperm quality has declined over the decades; there is speculation about the potential causes. The effects of radiation such as at Chernobyl are described. Toxic chemical exposure such as in Bhopal, India killed thousands. Neurological

  14. Glyphosate: environmental contamination, toxicity and potential risks to human health via food contamination.

    Science.gov (United States)

    Bai, Shahla Hosseini; Ogbourne, Steven M

    2016-10-01

    Glyphosate has been the most widely used herbicide during the past three decades. The US Environmental Protection Agency (EPA) classifies glyphosate as 'practically non-toxic and not an irritant' under the acute toxicity classification system. This classification is based primarily on toxicity data and due to its unique mode of action via a biochemical pathway that only exists in a small number of organisms that utilise the shikimic acid pathway to produce amino acids, most of which are green plants. This classification is supported by the majority of scientific literature on the toxic effects of glyphosate. However, in 2005, the Food and Agriculture Organisation (FAO) reported that glyphosate and its major metabolite, aminomethylphosphonic acid (AMPA), are of potential toxicological concern, mainly as a result of accumulation of residues in the food chain. The FAO further states that the dietary risk of glyphosate and AMPA is unlikely if the maximum daily intake of 1 mg kg(-1) body weight (bw) is not exceeded. Research has now established that glyphosate can persist in the environment, and therefore, assessments of the health risks associated with glyphosate are more complicated than suggested by acute toxicity data that relate primarily to accidental high-rate exposure. We have used recent literature to assess the possible risks associated with the presence of glyphosate residues in food and the environment.

  15. Human health risk assessment database, "the NHSRC toxicity value database": supporting the risk assessment process at US EPA's National Homeland Security Research Center.

    Science.gov (United States)

    Moudgal, Chandrika J; Garrahan, Kevin; Brady-Roberts, Eletha; Gavrelis, Naida; Arbogast, Michelle; Dun, Sarah

    2008-11-15

    The toxicity value database of the United States Environmental Protection Agency's (EPA) National Homeland Security Research Center has been in development since 2004. The toxicity value database includes a compilation of agent property, toxicity, dose-response, and health effects data for 96 agents: 84 chemical and radiological agents and 12 biotoxins. The database is populated with multiple toxicity benchmark values and agent property information from secondary sources, with web links to the secondary sources, where available. A selected set of primary literature citations and associated dose-response data are also included. The toxicity value database offers a powerful means to quickly and efficiently gather pertinent toxicity and dose-response data for a number of agents that are of concern to the nation's security. This database, in conjunction with other tools, will play an important role in understanding human health risks, and will provide a means for risk assessors and managers to make quick and informed decisions on the potential health risks and determine appropriate responses (e.g., cleanup) to agent release. A final, stand alone MS ACESSS working version of the toxicity value database was completed in November, 2007.

  16. Human health risk assessment database, 'the NHSRC toxicity value database': Supporting the risk assessment process at US EPA's National Homeland Security Research Center

    International Nuclear Information System (INIS)

    Moudgal, Chandrika J.; Garrahan, Kevin; Brady-Roberts, Eletha; Gavrelis, Naida; Arbogast, Michelle; Dun, Sarah

    2008-01-01

    The toxicity value database of the United States Environmental Protection Agency's (EPA) National Homeland Security Research Center has been in development since 2004. The toxicity value database includes a compilation of agent property, toxicity, dose-response, and health effects data for 96 agents: 84 chemical and radiological agents and 12 biotoxins. The database is populated with multiple toxicity benchmark values and agent property information from secondary sources, with web links to the secondary sources, where available. A selected set of primary literature citations and associated dose-response data are also included. The toxicity value database offers a powerful means to quickly and efficiently gather pertinent toxicity and dose-response data for a number of agents that are of concern to the nation's security. This database, in conjunction with other tools, will play an important role in understanding human health risks, and will provide a means for risk assessors and managers to make quick and informed decisions on the potential health risks and determine appropriate responses (e.g., cleanup) to agent release. A final, stand alone MS ACESSS working version of the toxicity value database was completed in November, 2007

  17. The contribution of reproductive factors and family history towards premenopausal breast cancer risk in Kuala Lumpur, Malaysia.

    Science.gov (United States)

    Razif, S Mohd; Sulaiman, S; Hanie, S Soraya; Aina, E Nor; Rohaizak, M; Fuad, I; Nurismah, M I; Sharifah, N A

    2011-08-01

    Breast cancer is the most common cancer among Malaysian women. This study aimed to determine the reproductive for premenopausal breast cancer risk in Kuala Lumpur, Malaysia. A case-control study was conducted in 216 histopathologically confirmed cases of premenopausal breast cancer and 216 community-based controls that were matched by age within a 5-year period and ethnicity. The results of this study showed that premenopausal breast cancer risks were strongly related to parity, number of live births and family history of breast cancer. Premenopausal women with these known reproductive and family history risk factors should take extra measures to undergo appropriate screening method for early detection of breast cancer.

  18. Medicinal plants used in Lesotho for treatment of reproductive and post reproductive problems.

    Science.gov (United States)

    Moteetee, A; Seleteng Kose, L

    2016-12-24

    Reproductive healthcare has been highlighted as a major challenge in Lesotho mainly due to the high prevalence of HIV/AIDS and sexually transmitted infections. As a result other reproductive ailments have not received much attention, particularly because healthcare facilities are already limited and many of them are inaccessible. For these reasons, medicinal plants play a major role in primary healthcare system in the country, in addition the plants are easily accessible, more affordable, and their use forms part of the cultural heritage. However, documentation of medicinal plants used for reproductive ailments is scattered, more importantly the biological and pharmacological properties, as well as toxicity of many of these plants are not yet known. To document the plants used by both male and female Basotho (residing in Lesotho) for the treatment of reproductive ailments, to explore their recorded biological and pharmacological effects as well as their toxicity, and to establish if these plants are used for similar purposes in other southern African cultures. The results stem from published findings of recent interviews of traditional medicinal practitioners in the Maseru District of Lesotho, first author's own experiences and observations from the Qacha's Nek District as well as comprehensive literature survey including numerous books and unpublished data. Electronic databases such as Google, Google Scholar, PubMed, and ScienceDirect were also used to search for the chemical compounds, pharmacological activity, and toxicity of the plants. A total of 87 plant species are reported to be used for the treatment of several reproductive problems such as infertility, complications associated with pregnancy (twelve plants are used to treat conditions such as colic, heartburn, nausea, and constipation), cleansing and/ or toning of the uterus (with a purpose either to induce pregnancy or to get rid of the placenta, for example Withania somnifera and Zantedeschia

  19. Toxicity of noradrenaline, a novel anti-biofouling component, to two non-target zooplankton species, Daphnia magna and Ceriodaphnia dubia.

    Science.gov (United States)

    Overturf, C L; Wormington, A M; Blythe, K N; Gohad, N V; Mount, A S; Roberts, A P

    2015-05-01

    Noradrenaline (NA) is the active component of novel antifouling agents and acts by preventing attachment of fouling organisms. The goal of this study was to examine the toxicity of NA to the non-target zooplankton D. magna and C. dubia. Neonates were exposed to one of five concentrations of NA and effects on survival, reproduction and molting were determined. Calculated LC50 values were determined to be 46 and 38 μM in C. dubia and D. magna, respectively. A 10-day C. dubia study found that reproduction metrics were significantly impacted at non-lethal concentrations. In D. magna, concentrations greater than 40 μM significantly impacted molting. A toxicity test was conducted with D. magna using oxidized NA, which yielded similar results. These data indicate that both NA and oxidized NA are toxic to non-target zooplankton. Results obtained from this study can be used to guide future ecological risk assessments of catecholamine-based antifouling agents. Copyright © 2015. Published by Elsevier Inc.

  20. Differential reconstructed gene interaction networks for deriving toxicity threshold in chemical risk assessment

    OpenAIRE

    Yang, Yi; Maxwell, Andrew; Zhang, Xiaowei; Wang, Nan; Perkins, Edward J; Zhang, Chaoyang; Gong, Ping

    2013-01-01

    Background Pathway alterations reflected as changes in gene expression regulation and gene interaction can result from cellular exposure to toxicants. Such information is often used to elucidate toxicological modes of action. From a risk assessment perspective, alterations in biological pathways are a rich resource for setting toxicant thresholds, which may be more sensitive and mechanism-informed than traditional toxicity endpoints. Here we developed a novel differential networks (DNs) appro...

  1. High-risk populations identified in Childhood Cancer Survivor Study investigations: implications for risk-based surveillance.

    Science.gov (United States)

    Hudson, Melissa M; Mulrooney, Daniel A; Bowers, Daniel C; Sklar, Charles A; Green, Daniel M; Donaldson, Sarah S; Oeffinger, Kevin C; Neglia, Joseph P; Meadows, Anna T; Robison, Leslie L

    2009-05-10

    Childhood cancer survivors often experience complications related to cancer and its treatment that may adversely affect quality of life and increase the risk of premature death. The purpose of this manuscript is to review how data derived from Childhood Cancer Survivor Study (CCSS) investigations have facilitated identification of childhood cancer survivor populations at high risk for specific organ toxicity and secondary carcinogenesis and how this has informed clinical screening practices. Articles previously published that used the resource of the CCSS to identify risk factors for specific organ toxicity and subsequent cancers were reviewed and results summarized. CCSS investigations have characterized specific groups to be at highest risk of morbidity related to endocrine and reproductive dysfunction, pulmonary toxicity, cerebrovascular injury, neurologic and neurosensory sequelae, and subsequent neoplasms. Factors influencing risk for specific outcomes related to the individual survivor (eg, sex, race/ethnicity, age at diagnosis, attained age), sociodemographic status (eg, education, household income, health insurance) and cancer history (eg, diagnosis, treatment, time from diagnosis) have been consistently identified. These CCSS investigations that clarify risk for treatment complications related to specific treatment modalities, cumulative dose exposures, and sociodemographic factors identify profiles of survivors at high risk for cancer-related morbidity who deserve heightened surveillance to optimize outcomes after treatment for childhood cancer.

  2. Acute and Chronic Toxicity of Soluble Fractions of Industrial Solid Wastes on Daphnia magna and Vibrio fischeri

    Directory of Open Access Journals (Sweden)

    Letícia Flohr

    2012-01-01

    Full Text Available Industrial wastes may produce leachates that can contaminate the aquatic ecosystem. Toxicity testing in acute and chronic levels is essential to assess environmental risks from the soluble fractions of these wastes, since only chemical analysis may not be adequate to classify the hazard of an industrial waste. In this study, ten samples of solid wastes from textile, metal-mechanic, and pulp and paper industries were analyzed by acute and chronic toxicity tests with Daphnia magna and Vibrio fischeri. A metal-mechanic waste (sample MM3 induced the highest toxicity level to Daphnia magna(CE50,48 h=2.21%. A textile waste induced the highest toxicity level to Vibrio fischeri (sample TX2, CE50,30 min=12.08%. All samples of pulp and paper wastes, and a textile waste (sample TX2 induced chronic effects on reproduction, length, and longevity of Daphnia magna. These results could serve as an alert about the environmental risks of an inadequate waste classification method.

  3. 1997 Toxic Hazards Research Annual Report

    Science.gov (United States)

    1998-05-01

    evaluate the potential for CF 3I to produce reproductive toxicity and to provide additional information on the effect of CF 3I exposure on the...questions raised on the effects of CF 3I exposure following the recently completed acute and subchronic inhalation toxicity studies (Dodd et al., 1997a...individuals from potential toxic consequences resulting from exposure to combustion products of advanced composite materials (ACM), this laboratory has

  4. Menstrual and reproductive factors and risk of breast cancer: A case-control study in the Fez region, Morocco.

    Directory of Open Access Journals (Sweden)

    Mohamed Khalis

    Full Text Available Breast cancer is the most common cancer in women worldwide. In the Moroccan context, the role of well-known reproductive factors in breast cancer remains poorly documented. The aim of this study was to explore the relationship between menstrual and reproductive factors and breast cancer risk in Moroccan women in the Fez region.A case-control study was conducted at the Hassan II University Hospital of Fez between January 2014 and April 2015. A total of 237 cases of breast cancer and 237 age-matched controls were included. Information on sociodemographic characteristics, menstrual and reproductive history, family history of breast cancer, and lifestyle factors was obtained through a structured questionnaire. Conditional logistic regression models were used to estimate odds ratios and 95% confidence intervals for breast cancer by menstrual and reproductive factors adjusted for potential confounders.Early menarche (OR = 1.60, 95% CI: 1.08-2.38 and nulliparity (OR = 3.77, 95% CI: 1.98-7.30 were significantly related to an increased risk of breast cancer, whereas an early age at first full-term pregnancy was associated with a decreased risk of breast cancer (OR = 0.41, 95% CI: 0.25-0.65.The results of this study confirm the role of established reproductive factors for breast cancer in Moroccan women. It identified some susceptible groups at high risk of breast cancer. Preventive interventions and screening should focus on these groups as a priority. These results should be confirmed in a larger, multicenter study.

  5. Introduction to Toxicity and Risk Assessment for Project Chemists

    Science.gov (United States)

    2012-03-27

    Toxicity of Hexavalent Chromium  External review complete  EPA will wait until studies underway on carcinogenic mode of action are complete to...finalize the assessment  NJ and Cal values for hex chrome 16 Risk-Based Screening Levels Resident Soil (mg/kg) Resident Water Use (µg/L) DRAFT 0.04

  6. Protective influence of healthful nutrition on mechanisms of environmental pollutant toxicity and disease risks.

    Science.gov (United States)

    Hoffman, Jessie B; Hennig, Bernhard

    2017-06-01

    Human exposures to environmental contaminants around the world contribute to the global burden of disease and thus require urgent attention. Exploring preventive measures against environmental exposure and disease risk is essential. While a sedentary lifestyle and/or poor dietary habits can exacerbate the deleterious effects resulting from exposure to toxic chemicals, much emerging evidence suggests that positive lifestyle changes (e.g., healthful nutrition) can modulate and/or reduce the toxicity of environmental pollutants. Our work has shown that diets high in anti-inflammatory bioactive food components (e.g., phytochemicals or polyphenols) are possible strategies for modulating and reducing the disease risks associated with exposure to toxic pollutants in the environment. Thus, consuming healthy diets rich in plant-derived bioactive nutrients may reduce the vulnerability to diseases linked to environmental toxic insults. This nutritional paradigm in environmental toxicology requires further study in order to improve our understanding of the relationships between nutrition and other lifestyle modifications and toxicant-induced diseases. © 2017 New York Academy of Sciences.

  7. Assisted reproductive techniques and risk of exstrophy-epispadias complex: a German case-control study.

    Science.gov (United States)

    Zwink, Nadine; Jenetzky, Ekkehart; Hirsch, Karin; Reifferscheid, Peter; Schmiedeke, Eberhard; Schmidt, Dominik; Reckin, Sabrina; Obermayr, Florian; Boemers, Thomas M; Stein, Raimund; Reutter, Heiko; Rösch, Wolfgang H; Brenner, Hermann; Ebert, Anne-Karoline

    2013-04-01

    We assessed the risk of exstrophy-epispadias complex in children conceived by in vitro fertilization or intracytoplasmic sperm injection. Data from the German Network for Congenital Uro-REctal malformations were compared to nationwide data from the German In Vitro Fertilization Register and the German Federal Statistical Office. Odds ratios (95% CI) were determined to quantify associations using logistic regression. A total of 123 patients with exstrophy-epispadias complex born in Germany between 1997 and 2011 were recruited through participating departments of pediatric urology and pediatric surgery throughout the country as well as the German self-help organizations Blasenekstrophie/Epispadie e.V. and Kloakenekstrophie. All German live births (10,069,986) between 1997 and 2010 comprised the controls. Overall, 12 subjects (10%) and 129,982 controls (1%) were conceived by in vitro fertilization or intracytoplasmic sperm injection. Conception by assisted reproductive technique was associated with a more than eightfold increased risk of exstrophy-epispadias complex compared to spontaneous conception (OR 8.3, 95% CI 4.6-15.0, p risk of exstrophy-epispadias complex in children conceived by in vitro fertilization (OR 14.0, 95% CI 6.5-30.0, p study provides evidence that assisted reproductive techniques such as in vitro fertilization and intracytoplasmic sperm injection are associated with a markedly increased risk of having a child born with exstrophy-epispadias complex. However, it remains unclear whether this finding may be due to assisted reproduction per se and/or underlying infertility/subfertility etiology or parent characteristics. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  8. Financial "risk-sharing" or refund programs in assisted reproduction: an Ethics Committee opinion.

    Science.gov (United States)

    2016-10-01

    Financial "risk-sharing" fee structures in assisted reproduction programs charge patients a higher initial fee but provide reduced fees for subsequent cycles and often a partial or complete refund if treatment fails. This opinion of the ASRM Ethics Committee analyzes the ethical issues raised by these fee structures, including patient selection criteria, conflicts of interest, success rate transparency, and patient informed consent. This document replaces the document of the same name, last published in 2013 (Fertil Steril 2013;100:334-6). Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  9. QSAR screening of 70,983 REACH substances for genotoxic carcinogenicity, mutagenicity and developmental toxicity in the ChemScreen project

    DEFF Research Database (Denmark)

    Wedebye, Eva Bay; Dybdahl, Marianne; Nikolov, Nikolai Georgiev

    2015-01-01

    The ChemScreen project aimed to develop a screening system for reproductive toxicity based on alternative methods. QSARs can, if adequate, contribute to the evaluation of chemical substances under REACH and may in some cases be applied instead of experimental testing to fill data gaps...... for information requirements. As no testing for reproductive effects should be performed in REACH on known genotoxic carcinogens or germ cell mutagens with appropriate risk management measures implemented, a QSAR pre-screen for 70,983 REACH substances was performed. Sixteen models and three decision algorithms...... were used to reach overall predictions of substances with potential effects with the following result: 6.5% genotoxic carcinogens, 16.3% mutagens, 11.5% developmental toxicants. These results are similar to findings in earlier QSAR and experimental studies of chemical inventories, and illustrate how...

  10. Chapter 22: Female Reproductive Toxicology

    Science.gov (United States)

    The female reproductive system provides multiple targets for environmental toxicants with the hypothalamic-pituitary-ovarian axis. Moreover, the functional impact of a chemical can differ, depending on the species involved and the parameters of exposure. While cross-species compa...

  11. BMI, diet and female reproductive factors as risks for thyroid cancer: a systematic review.

    Directory of Open Access Journals (Sweden)

    Emily Peterson

    Full Text Available BACKGROUND: Thyroid cancer incidence rates have been increasing worldwide but the reason behind this is unclear. Both the increasing use of diagnostic technologies allowing the detection of thyroid cancer and a true increase in thyroid cancer incidence have been proposed. This review assesses the role of body mass index (BMI, diet, and reproductive factors on the thyroid cancer trend. METHODS: Epidemiologic studies of the selected risk factors up to June 2010 were reviewed and critically assessed. RESULTS: Among the thirty-seven studies reviewed and despite variation in the risk estimates, most papers supported a small but positive association for BMI (risk estimate range: 1.1-2.3 in males and 1.0-7.4 in females.. Among specific dietary components, there was no consistent association of thyroid cancer risk with iodine intake through fortification (risk estimate range: 0.49-1.6 or fish consumption (risk estimate range 0.6-2.2, nor with diets high in cruciferous vegetables (risk estimate range 0.6-1.9. A small number of studies showed a consistent protective effect of diets high in non-cruciferous vegetable (risk estimate range: 0.71-0.92. Among reproductive factors (pregnancy, parity, number of live births, use of prescription hormones, menstrual cycle regularity, and menopausal status, none were consistently associated with higher thyroid cancer risk. CONCLUSIONS: BMI had the strongest link to thyroid cancer risk among those examined. Detailed examinations of population-level risk factors can help identify and support prevention efforts to reduce the burden of thyroid cancer.

  12. Cypermethrin-induced reproductive toxicity in the rat is prevented by resveratrol

    Directory of Open Access Journals (Sweden)

    Poonam Sharma

    2014-01-01

    Full Text Available Aims : The current study was to assess the protective role of resveratrol in cypermethrin-induced reproductive toxicity in male Wistar rats. Materials and Methods : Rats were exposed to cypermethrin (3.83 mg/kg bw for 14 days. Pre- and post-treatment of resveratrol (20 mg/kg bw for 14 days was given to cypermethrin exposed rats. At the end of the experiment, rats were sacrificed, testis and epididymis were removed, sperm characteristics, sex hormones, and various biochemical parameters were studied. Results : Cypermethrin exposure resulted in a significant decrease in weight of testis and epididymis, testicular sperm head counts, sperm motility and live sperm counts and increase in sperm abnormalities. Serum testosterone (T, follicle stimulating hormone (FSH, luteinizing hormone (LH, reduced glutathione (GSH, catalase (CAT, superoxide dismutase (SOD, glutathione S-transferase (GST, glutathione reductase (GR, glutathione peroxidase (GPx and total protein (TP content were decreased and lipid peroxidation (LPO level was increased on cypermethrin exposure. Pre- and post-treatment of resveratrol increased sperm head counts, sperm motility, live sperm counts, T, FSH, LH, GSH, CAT, SOD, GST, GR, GPx and TP contents and decreased LPO. Treatment with resveratrol alone has improved sperm parameters and testicular antioxidant defence system. Conclusion : The study concluded that resveratrol ameliorated cypermethrin-induced testicular damage by reducing oxidative stress and by enhancing the level of sex hormones.

  13. Distribution and Biological Effects of Nanoparticles in the Reproductive System.

    Science.gov (United States)

    Liu, Ying; Li, Hongxia; Xiao, Kai

    2016-01-01

    Nanoparticles have shown great potential in biomedical applications such as imaging probes and drug delivery. However, the increasing use of nanoparticles has raised concerns about their adverse effects on human health and environment. Reproductive tissues and gametes represent highly delicate biological systems with the essential function of transmitting genetic information to the offspring, which is highly sensitive to environmental toxicants. This review aims to summarzie the penetration of physiological barriers (blood-testis barrier and placental barrier), distribution and biological effects of nanoparticles in the reproductive system, which is essential to control the beneficial effects of nanoparticles applications and to avoid their adverse effects on the reproductive system. We referred to a large number of relevant peer-reviewed research articles about the reproductive toxicity of nanoparticles. The comprehensive information was summarized into two parts: physiological barrier penetration and biological effects of nanoparticles in male or female reproductive system; distribution and metabolism of nanoparticles in the reproductive system. The representative examples were also presented in four tables. The in vitro and in vivo studies imply that some nanoparticles are able to cross the blood-testis barrier or placental barrier, and their penetration depends on the physicochemical characteristics of nanoparticles (e.g., composition, shape, particle size and surface coating). The toxicity assays indicate that nanoparticles might induce adverse physiological effects and impede fertility or embryogenesis. The barrier penetration, adverse physiological effects, distribution and metabolism are closely related to physicochemical characteristics of nanoparticles. Further systematic and mechanistic studies using well-characterized nanoparticles, relevant administration routes, and doses relevant to the expected exposure level are required to improve our

  14. NTP-CERHR Monograph on the Potential Human Reproductive and Developmental Effects of Di-n-Butyl Phthalate (DBP).

    Science.gov (United States)

    2003-04-01

    TThe National Toxicology Program (NTP) Center for the Evaluation of Risks to Human Reproduction (CERHR) conducted an evaluation of the potential for di-n-butyl phthalate (DBP) to cause adverse effects on reproduction and development in humans. DBP is one of 7 phthalate chemicals evaluated by the NTP CERHR Phthalates Expert Panel. These phthalates were selected for evaluation because of high production volume, extent of human exposures, use in children's products, and/or published evidence of reproductive or developmental toxicity. Unlike many phthalates, DBP is not currently used as a plasticizer in polyvinyl chloride plastics. DBP is a component of latex adhesives and is used in cosmetics and other personal care products, as a plasticizer in cellulose plastics, and as a solvent for dyes. The results of this evaluation on DBP are published in a NTP-CERHR monograph which includes: 1) the NTP Brief, 2) the Expert Panel Report on the Reproductive and Developmental Toxicity of Di-n-Butyl Phthalate, and 3) public comments received on the Expert Panel Report. As stated in the NTP Brief, the NTP reached the following conclusions regarding the possible effects of exposure to DBP on human development and reproduction. First, although DBP could possibly affect human reproduction and development if exposures are sufficiently high, the NTP concludes that there is negligible concern for reproductive toxicity in exposed adults. Second, the NTP concludes that there is minimal concern for developmental effects when pregnant women are exposed to DBP levels estimated by the panel (2-10 mug/kg body weight/day). There is no direct evidence that exposure of people to DBP adversely affects reproduction or development, but studies reviewed by the expert panel show that oral exposure to high doses of DBP (>/=100 mg/kg body weight/day) may adversely affect the prenatal and early postnatal development in rodents. Finally, based on exposure estimates in women of reproductive age, the NTP

  15. Factors associated with monozygosity in assisted reproductive technology pregnancies and the risk of recurrence using linked cycles.

    Science.gov (United States)

    Luke, Barbara; Brown, Morton B; Wantman, Ethan; Stern, Judy E

    2014-03-01

    To evaluate factors associated with monozygosity (MZ) (number of fetal heartbeats on early ultrasound greater than the number of embryos transferred) and the risk of recurrence in subsequent pregnancies using a national assisted reproduction database. Historical cohort study. Clinic-based data. 197,327 pregnancies (including 2,824 with evidence of MZ) from cycles reported to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) between 2004 and 2010. None. Evidence of MZ, adjusted odds ratios and their 95% confidence intervals computed from logistic regression models. In the univariate analysis, the risk of MZ was increased with ovulation disorders, donor oocytes, gonadotropin-releasing hormone agonist (GnRH-a) suppression, assisted hatching (AZH), and day 5-6 transfer, and was decreased with higher follicle-stimulating hormone (FSH) doses (≥3,000 IU). In the multivariate analysis, the risk of MZ was increased with GnRH-a suppression, AZH, and decreased with intracytoplasmic sperm injection (ICSI) and higher FSH dose. The interaction showed that although MZ was more likely with day 5-6 embryos, AZH had a minimal nonsignificant effect, whereas in day 2-3 embryos, AZH had a substantial statistically significant effect. Only one woman had a recurrence of MZ in a subsequent assisted reproduction pregnancy, which is consistent with randomness. The risk of MZ was higher with fresh day 5-6 embryos, donor oocytes, GnRH-a suppression, lower FSH doses, and AZH (particularly with day 2-3 embryos). Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  16. Rat two-generation reproductive toxicity study of bisphenol A.

    Science.gov (United States)

    Ema, M; Fujii, S; Furukawa, M; Kiguchi, M; Ikka, T; Harazono, A

    2001-01-01

    This study was conducted to determine the low-dose effects of bisphenol A (BPA) in a rat two-generation reproduction study. Groups of 25 male and 25 female Crj: CD (SD) IGS rats were given BPA at 0.2, 2, 20, or 200 microg/kg/day by gastric intubation throughout the study beginning at the onset of a 10- and 2-week premating period, in F0 males and females, respectively, and continuing through the mating, gestation, and lactation periods, for two generations. There were adult (F0, F1, F2) and postnatal day (PND) 22 (F1, F2) necropsies: the oldest F2 males and females being killed at postnatal weeks 7 and 14, respectively. No compound-related clinical signs or effects on body weight or food consumption were observed in any generation. There were no compound-related changes in surface righting reflex, negative geotaxis reflex, mid-air righting reflex, pinna detachment, incisor eruption, eye opening, testes descent, preputial separation, or vaginal opening in F1 and F2 generations, or behavior in the open field or water filled multiple T-maze in the F1 generation. No test compound-related changes in estrous cyclicity, copulation index, fertility index, number of implantations, gestation length, litter size, pup weight, pup sex ratio, pup viability, or other functional reproductive measures were noted in any generation. A few significant changes in the anogenital distance (AGD) per cube root of body weight ratio were found at 0.2 and 20 microg/kg in F1 males, at 2, 20, and 200 microg/kg in F1 females, and at 20 and 200 microg/kg in F2 females. However, the changes in the AGD were consistently small (within 5% of control values), and no continuous changes in the AGD or AGD/cube root of body weight ratio were detected. There were no compound-related changes in epididymal sperm counts or motility in F0 and F1 males. No compound-related necropsy findings or effects on organ weight including the reproductive organs were found in any generation. Histopathologic examinations

  17. Risk disparities in the globalisation of assisted reproductive technology: the case of Asia.

    Science.gov (United States)

    Ha, Jung-Ok

    2013-01-01

    This paper analyses the disparities in risks associated with biomedical technology focusing on the results of assisted reproductive technology (ART). ART among biomedical technologies transferred to Asia is a representative case that reveals in its clinical use and related scientific research the global politics of technology. This study notes the global politics at work in the recognition of and reaction to such risks. While many Asian countries aggressively pursue technological development, weak legislative and administrative regulations have created various problems and controversial cases. This study asserts that risks associated with technology are characterised as social facts not natural ones or mere 'side effects', since technological development and risk are closely intertwined.

  18. Toxic action of Acmella oleracea extract on the male reproductive system of Amblyomma cajennense ticks.

    Science.gov (United States)

    Anholeto, Luís Adriano; Oliveira, Patrícia Rosa de; Rodrigues, Rodney Alexandre Ferreira; Yamane, Lais Thiemi; Castro, Karina Neoob de Carvalho; Ferreira, Allan Roberto Fernandes; Camargo-Mathias, Maria Izabel

    2017-09-15

    The present study evaluated through morphohistological and histochemical techniques the effects of different concentrations of crude ethanolic extract of A. oleracea (EEAO) (Jambu) on the male reproductive system of Amblyomma cajennense sensu stricto (s.s.) ticks. The toxicity of this natural chemical was stablished, signalizing the promising potential of the compound as a strategy to control ectoparasites in the near future. For the experiment, 100 males fed on host rabbits with homogeneous weight (p>0.05) were used. The ticks were divided into five groups (10 animals each): Control 1-exposed to distilled water; Control 2-exposed to ethanol 50% and DMSO 1%; Treatment 1-3-exposed to the concentrations of 6.2, 12.5 and 25mg/mL of the EEAO, respectively, diluted in ethanol 50% and DMSO 1%, with exposure by immersion. After exposure, the males were dissected for the removal of the reproductive system and subjected to routine histological analysis with HE staining and histochemical techniques (PAS for the detection of neutral polysaccharides and Bromophenol blue to detect total proteins). The exposed individuals showed alterations in the glandular complex cells; however, the testes remained intact. The secretory cells of the multilobulated accessory glands presented intense cytoplasmic vacuolation. Additionally, the synthesis and secretion were reduced in the secretion granules, mainly concerning the polysaccharides, glyco- and lipoprotein elements, substances that will constitute the seminal fluid and enable the capacitation of spermatozoa in the female genital tract and also necessary for the formation of the spermatophore, which will encapsulate the mature spermatids. The alterations were dose-dependent, i.e., more intense and severe as the concentration of the product increased. .This experiment confirmed the cytotoxic potential of A. oleracea ethanolic extract in the concentrations of 6.2, 12.5 and 25mg/mL on the reproductive system of A. cajennense s.s. male

  19. Reproductive health of male radiographers

    International Nuclear Information System (INIS)

    Shakhatreh, Farouk M.

    2001-01-01

    To compare certain reproductive health problems reported in 2 groups of males, one of which was exposed to x-ray radiation (radiographers) and the other group that was not exposed to x-ray radiation. The reproductive health problems were miscarriage, congenital anomalies, still births and infertility. Two groups of men were selected (90 in each group). The first group consisted of radiographers and the other groups consisted of men not exposed to x-ray radiation. The 2 groups were matched for age and source. Relative risk, attributable risk percentage and level of significance were calculated. Incidence rate of reproductive health problems was increasing with the increase in duration of exposure to x-ray radiation ranging between 17% (for those exposed for 1-5 years) to 91% (for those exposed for more than 15 years). There were significant associations between exposure to radiation and miscarriage (relative risk = 1.67, attributable risk percentage = 40%), congenital anomalies (relative risk = 10, attributable risk percentage 90%), still birth (relative risk = 7, attributable risk percentage = 86%), and infertility (relative risk = 4.5, attributable risk = 78%). The incidence rates of reproductive health problems reported by male radiographers were significantly higher than that reported by the non exposed group and higher than the incidence rates reported in community-based studies in Jordan. The incidence rates of fetal death (miscarriage and stillbirth together) and infertility reported by our radiographers were higher than had been reported by the British radiographers. An immediate plan of action is needed to protect our radiographers. Further studies are needed in this field taking into account all extraneous variables that may affect the reproductive health of radiographers. (author)

  20. Predation risk affects reproductive physiology and demography of elk.

    Science.gov (United States)

    Creel, Scott; Christianson, David; Liley, Stewart; Winnie, John A

    2007-02-16

    Elk (Cervus elaphus) in the Greater Yellowstone Ecosystem alter patterns of aggregation, habitat selection, vigilance, and foraging in the presence of wolves (Canis lupus). Antipredator behaviors like these can reduce predation risk but are also likely to carry costs. Data from five elk populations studied for 16 site years showed that progesterone concentrations (from 1489 fecal samples) declined with the ratio of elk to wolves. In turn, progesterone concentrations were a good predictor of calf recruitment in the subsequent year. Together, these data suggest that wolves indirectly affect the reproductive physiology and the demography of elk through the costs of antipredator behavior.

  1. Two-generation reproductive toxicity study of implanted depleted uranium (DU) in CD rats.

    Science.gov (United States)

    Arfsten, D P; Still, K R; Wilfong, E R; Johnson, E W; McInturf, S M; Eggers, J S; Schaeffer, D J; Bekkedal, M Y-V

    2009-01-01

    Depleted uranium (DU) munitions and armor plating have been used in several conflicts over the last 17 yr, including the Persian Gulf War and the Iraq War. Because of its effectiveness and availability, DU will continue to be used in military applications into the foreseeable future. There is much controversy over the use of DU in weapons and equipment because of its potential radiological and toxic hazards, and there is concern over the chronic adverse health effects of embedded DU shrapnel in war veterans and bystanders. This study evaluated the effects of long-term implantation of DU on the reproductive success of F0 generation adults and development and survival of subsequent F1 and F2 generations in a two-generation reproductive toxicity study. F0 generation Sprague-Dawley rats, 8 wk of age, were surgically implanted with 0, 4, 8, 12, or 20 DU pellets (1 x 2 mm). Inert implant control animals were implanted with 12 or 20 tantallum (Ta) pellets. The F0 generation was then mated at 120 d post DU implantation. In the F0 generation, when measured on postimplantation d 27 and 117, uranium was present in the urine of DU-implanted animals in a dose-dependent manner. F0 reproductive success was similar across treatment groups and the maternal retrieval test revealed no changes in maternal behavior. DU implantation exerted no effect on the survival, health, or well-being of the F0 generation. Necropsy results of F0 animals were negative with the exception of a marked inflammatory response surrounding the implanted DU pellets. For the F1 generation, measures of F1 development through postnatal day (PND) 20 were unremarkable and no gross abnormalities were observed in F1 offspring. No uranium was detected in whole-body homogenates of PND 4 or PND 20 pups. Necropsy findings of F1 PND 20 pups were negative and no instances of ribcage malformation were observed in F1 PND 20 pups. Body weight and body weight gain of F1 rats through PND 120 were similar across treatment

  2. Toxicity testing in the 21 century: defining new risk assessment approaches based on perturbation of intracellular toxicity pathways.

    Directory of Open Access Journals (Sweden)

    Sudin Bhattacharya

    Full Text Available The approaches to quantitatively assessing the health risks of chemical exposure have not changed appreciably in the past 50 to 80 years, the focus remaining on high-dose studies that measure adverse outcomes in homogeneous animal populations. This expensive, low-throughput approach relies on conservative extrapolations to relate animal studies to much lower-dose human exposures and is of questionable relevance to predicting risks to humans at their typical low exposures. It makes little use of a mechanistic understanding of the mode of action by which chemicals perturb biological processes in human cells and tissues. An alternative vision, proposed by the U.S. National Research Council (NRC report Toxicity Testing in the 21(st Century: A Vision and a Strategy, called for moving away from traditional high-dose animal studies to an approach based on perturbation of cellular responses using well-designed in vitro assays. Central to this vision are (a "toxicity pathways" (the innate cellular pathways that may be perturbed by chemicals and (b the determination of chemical concentration ranges where those perturbations are likely to be excessive, thereby leading to adverse health effects if present for a prolonged duration in an intact organism. In this paper we briefly review the original NRC report and responses to that report over the past 3 years, and discuss how the change in testing might be achieved in the U.S. and in the European Union (EU. EU initiatives in developing alternatives to animal testing of cosmetic ingredients have run very much in parallel with the NRC report. Moving from current practice to the NRC vision would require using prototype toxicity pathways to develop case studies showing the new vision in action. In this vein, we also discuss how the proposed strategy for toxicity testing might be applied to the toxicity pathways associated with DNA damage and repair.

  3. [Protection of reproductive functions in patients with tumors].

    Science.gov (United States)

    Snajderová, M; Mardesić, T; Ganevová, M; Malinová, B

    2002-08-16

    Survival from cancer continues to improve. Antimitotic therapy can induce failure of spermatogenesis and oogenesis, gonadal disturbances and infertility. Recent advances in reproductive medicine have opened opportunities for the preservation of reproductive potential of patients with cancer. The aim of our study was to analyse by a multidisciplinary team the contemporary state of art and proposal of the Czech model of fertility preservation starting in childhood and continuing through the whole reproductive period. This paper highlights the problems associated with gonadal failure as a consequence of therapy for malignancy in childhood, adolescence and adulthood. Analysis of these problems served as a principle for the management strategy for fertility preservation. Patients undergoing treatment for malignancy are at the high risk of gonadal damage and infertility. Therefore, alternative treatments with less gonadal toxicity and different treatment protocols were evaluated. Fertility can be preserved with the freezing and banking of spermatozoa, embryos, and oocytes obtained prior to the cancer treatment. In female patients (starting in puberty) pharmacological preservation of gonads with gonadoliberin analogues is also possible. Chance for the future fertility preservation for children offers freezing and thawing of primordial follicles and spermatozoa obtained during the gonadal biopsies. Long-term follow-up study by a multidisciplinary medical team is necessary.

  4. Consensus report on the future of animal-free systemic toxicity testing.

    Science.gov (United States)

    Leist, Marcel; Hasiwa, Nina; Rovida, Costanza; Daneshian, Mardas; Basketter, David; Kimber, Ian; Clewell, Harvey; Gocht, Tilman; Goldberg, Alan; Busquet, Francois; Rossi, Anna-Maria; Schwarz, Michael; Stephens, Martin; Taalman, Rob; Knudsen, Thomas B; McKim, James; Harris, Georgina; Pamies, David; Hartung, Thomas

    2014-01-01

    Since March 2013, animal use for cosmetics testing for the European market has been banned. This requires a renewed view on risk assessment in this field. However, in other fields as well, traditional animal experimentation does not always satisfy requirements in safety testing, as the need for human-relevant information is ever increasing. A general strategy for animal-free test approaches was outlined by the US National Research Council`s vision document for Toxicity Testing in the 21st Century in 2007. It is now possible to provide a more defined roadmap on how to implement this vision for the four principal areas of systemic toxicity evaluation: repeat dose organ toxicity, carcinogenicity, reproductive toxicity and allergy induction (skin sensitization), as well as for the evaluation of toxicant metabolism (toxicokinetics) (Fig. 1). CAAT-Europe assembled experts from Europe, America and Asia to design a scientific roadmap for future risk assessment approaches and the outcome was then further discussed and refined in two consensus meetings with over 200 stakeholders. The key recommendations include: focusing on improving existing methods rather than favoring de novo design; combining hazard testing with toxicokinetics predictions; developing integrated test strategies; incorporating new high content endpoints to classical assays; evolving test validation procedures; promoting collaboration and data-sharing of different industrial sectors; integrating new disciplines, such as systems biology and high throughput screening; and involving regulators early on in the test development process. A focus on data quality, combined with increased attention to the scientific background of a test method, will be important drivers. Information from each test system should be mapped along adverse outcome pathways. Finally, quantitative information on all factors and key events will be fed into systems biology models that allow a probabilistic risk assessment with flexible

  5. Toxic releases and risk disparity: a spatiotemporal model of industrial ecology and social empowerment.

    Science.gov (United States)

    Aoyagi, Hannah; Ogunseitan, Oladele A

    2015-06-02

    Information-based regulations (IBRs) are founded on the theoretical premise that public participation in accomplishing policy goals is empowered by open access to information. Since its inception in 1988, the Toxics Release Inventory (TRI) has provided the framework and regulatory impetus for the compilation and distribution of data on toxic releases associated with industrial development, following the tenets of IBR. As TRI emissions are reputed to disproportionately affect low-income communities, we investigated how demographic characteristics are related to change in TRI emissions and toxicity risks between 1989 and 2002, and we sought to identify factors that predict these changes. We used local indicators of spatial association (LISA) maps and spatial regression techniques to study risk disparity in the Los Angeles urban area. We also surveyed 203 individuals in eight communities in the same region to measure the levels of awareness of TRI, attitudes towards air pollution, and general environmental risk. We discovered, through spatial lag models, that changes in gross and toxic emissions are related to community ethnic composition, poverty level, home ownership, and base 1989 emissions (R-square=0.034-0.083). We generated a structural equation model to explain the determinants of social empowerment to act on the basis of environmental information. Hierarchical confirmatory factor analysis (HCFA) supports the theoretical model that individual empowerment is predicted by risk perception, worry, and awareness (Chi-square=63.315, p=0.022, df=42). This study provides strong evidence that spatiotemporal changes in regional-scale environmental risks are influenced by individual-scale empowerment mediated by IBRs.

  6. Toxic Releases and Risk Disparity: A Spatiotemporal Model of Industrial Ecology and Social Empowerment

    Directory of Open Access Journals (Sweden)

    Hannah Aoyagi

    2015-06-01

    Full Text Available Information-based regulations (IBRs are founded on the theoretical premise that public participation in accomplishing policy goals is empowered by open access to information. Since its inception in 1988, the Toxics Release Inventory (TRI has provided the framework and regulatory impetus for the compilation and distribution of data on toxic releases associated with industrial development, following the tenets of IBR. As TRI emissions are reputed to disproportionately affect low-income communities, we investigated how demographic characteristics are related to change in TRI emissions and toxicity risks between 1989 and 2002, and we sought to identify factors that predict these changes. We used local indicators of spatial association (LISA maps and spatial regression techniques to study risk disparity in the Los Angeles urban area. We also surveyed 203 individuals in eight communities in the same region to measure the levels of awareness of TRI, attitudes towards air pollution, and general environmental risk. We discovered, through spatial lag models, that changes in gross and toxic emissions are related to community ethnic composition, poverty level, home ownership, and base 1989 emissions (R-square = 0.034–0.083. We generated a structural equation model to explain the determinants of social empowerment to act on the basis of environmental information. Hierarchical confirmatory factor analysis (HCFA supports the theoretical model that individual empowerment is predicted by risk perception, worry, and awareness (Chi-square = 63.315, p = 0.022, df = 42. This study provides strong evidence that spatiotemporal changes in regional-scale environmental risks are influenced by individual-scale empowerment mediated by IBRs.

  7. Contraceptive behavior as risk factor for reproductive health of junior students attending a medical university

    Directory of Open Access Journals (Sweden)

    T.N. Govyazina

    2017-06-01

    Full Text Available 1–3 year students attending medical and preventive faculty of a medical university were our research object. Our research had many stages, and at the first one our goal was to examine and to assess basic behavioral risks for reproductive health of students attending medical and preventive faculty of a medical university. We conducted a sociological examination via questioning. 428 students were questioned as per materials collecting program which included 74 parameters; they accounted for 91.6 % out of the overall official number of students, 45.0 % male students and 40.0 % female students combined work and studies. We detected that, as per questioning results, the specific weight of students who took care of their health amounted to 79.2 % boys and 95.2 % girls. However, the students tended to have bad habits, i.e. constant alcohol intake or smoking. And although information on diseases prevention and on how to pursue healthy lifestyle was perfectly available to them, students didn't try to use it and preserve their health. All the respondents said they were against abortion. Girls were likely to adopt a complex approach when choosing a contraceptive, they resorted to hormonal agents, and, with their partners' consent, to condoms. But they often took hormonal agents without any consultations with a gynecologist or an endocrinologist. Contraceptives were rather rarely applied, and students appeared to have no knowledge on risk factors causing reproductive health deterioration. They also tended to be negligent and too self-confident when it came to reproductive health protection. A risk of abortions was very high for girls who didn't use contraceptives, and also all students ran rather high risk of catching sexual diseases. Sexual education is needed to correct contraceptive behavior; medical workers are a main source of information on reproductive health of young people in 7–10 % cases only. We need to create interactive educational programs

  8. High concentrations of protein test substances may have non-toxic effects on Daphnia magna: implications for regulatory study designs and ecological risk assessments for GM crops.

    Science.gov (United States)

    Raybould, Alan; Burns, Andrea; Hamer, Mick

    2014-01-01

    Laboratory testing for possible adverse effects of insecticidal proteins on non-target organisms (NTOs) is an important part of many ecological risk assessments for regulatory decision-making about the cultivation of insect-resistant genetically modified (IRGM) crops. To increase confidence in the risk assessments, regulatory guidelines for effects testing specify that representative surrogate species for NTOs are exposed to concentrations of insecticidal proteins that are in excess of worst-case predicted exposures in the field. High concentrations in effects tests are achieved by using protein test substances produced in microbes, such as Escherichia coli. In a study that exposed Daphnia magna to a single high concentration of a microbial test substance containing Vip3Aa20, the insecticidal protein in MIR162 maize, small reductions in growth were observed. These effects were surprising as many other studies strongly suggest that the activity of Vip3Aa20 is limited to Lepidoptera. A plausible explanation for the effect on growth is that high concentrations of test substance have a non-toxic effect on Daphnia, perhaps by reducing its feeding rate. A follow-up study tested that hypothesis by exposing D. magna to several concentrations of Vip3Aa20, and a high concentration of a non-toxic protein, bovine serum albumin (BSA). Vip3Aa20 and BSA had sporadic effects on the reproduction and growth of D. magna. The pattern of the effects suggests that they result from non-toxic effects of high concentrations of protein, and not from toxicity. The implications of these results for regulatory NTO effects testing and ERA of IRGM crops are discussed.

  9. Observed and predicted reproduction of Ceriodaphnia dubia exposed to chloride, sulfate, and bicarbonate

    Science.gov (United States)

    Lasier, Peter J.; Hardin, Ian R.

    2010-01-01

    Chronic toxicities of Cl-, SO42-, and HCO3- to Ceriodaphnia dubia were evaluated in low- and moderate-hardness waters using a three-brood reproduction test method. Toxicity tests of anion mixtures were used to determine interaction effects and to produce models predicting C. dubia reproduction. Effluents diluted with low- and moderate-hardness waters were tested with animals acclimated to low- and moderate-hardness conditions to evaluate the models and to assess the effects of hardness and acclimation. Sulfate was significantly less toxic than Cl- and HCO3- in both types of water. Chloride and HCO3- toxicities were similar in low-hardness water, but HCO3- was the most toxic in moderate-hardness water. Low acute-to-chronic ratios indicate that toxicities of these anions will decrease quickly with dilution. Hardness significantly reduced Cl- and SO42- toxicity but had little effect on HCO3-. Chloride toxicity decreased with an increase in Na+ concentration, and CO3- toxicity may have been reduced by the dissolved organic carbon in effluent. Multivariate models using measured anion concentrations in effluents with low to moderate hardness levels provided fairly accurate predictions of reproduction. Determinations of toxicity for several effluents differed significantly depending on the hardness of the dilution water and the hardness of the water used to culture test animals. These results can be used to predict the contribution of elevated anion concentrations to the chronic toxicity of effluents; to identify effluents that are toxic due to contaminants other than Cl-, SO42-, and HCO3-; and to provide a basis for chemical substitutions in manufacturing processes.

  10. Ginger attenuated di (n-butyl phthalate-induced reproductive toxicity in pubertal male rabbits

    Directory of Open Access Journals (Sweden)

    S. S. Oda

    2017-12-01

    Full Text Available This study was conducted to investigate the toxic effects of di (n-butyl phthalate (DBP on reproductive functions in male rabbits and the probable protective role of ginger. Twenty rabbits were divided equally into 4 groups: control group; DBP group (520 mg/kg body weight [BW] DBP orally, DBP+ginger group (520 mg/kg BW DBP and 400 mg/kg BW ginger and ginger group (400 mg/kg BW ginger orally. Treatments were given three-times/week. After 7 wk of the experiment, DBP induced significant reduction in testis and prostate weights, serum and intratesticular testosterone concentrations, sperm counts both mass and progressive sperm motility and live sperms percentage as well as significant elevation of testicular malondialdehyde compared to control group. No significant changes were detected in epididymal weights, serum FSH and serum LH concentrations and testicular total superoxide dismutase and glutathione peroxidase activities in all treated groups. DBP induced considerable histopathological alterations in testis and to minimal extent in epididymis and prostates. Ginger treatment attenuated the significant changes to a certain extent induced by DBP intoxication in male rabbits probably due to its potential to scavenge free radicals.

  11. Assessment of the Developmental Toxicity of Epidermal Growth ...

    African Journals Online (AJOL)

    Purpose: To determine whether epidermal growth factor (EGF) is involved in reproductive developmental toxicity, using the embryonic stem cell test (EST), as well as ascertain how EGF influences embryonic development. Methods: To predict developmental toxicity on the basis of reducing cell viability and inhibition of ...

  12. Potentials and limitations of hazard indices for the determination of risk potentials of disposed toxic wastes

    International Nuclear Information System (INIS)

    Kirchner, Gerald

    1989-01-01

    Hazard indices are often used for the determination of risk potentials arising from the geological disposal of toxic wastes. They are based on simplified models for the calculation of potential health effects caused by the wastes. The attractiveness of hazard indices lies in their simplicity which nevertheless results in reliable data on necessary isolation times and the most toxic nuclides of a waste. They also make possible comparisons of the potential risks of different wastes. After a discussion of the processes that control the behavior of toxic wastes in the environment after a failure of the geological barriers, a new hazard index is presented. Originally developed for nuclear wastes, it is the first which involves the joint consideration of the composition of a waste, the probability for transport of waste nuclides to man, their toxicity, and the time-dependent changes of the risk potentials which are caused by radioactive buildup and decay processes after the waste has entered the biosphere. The new hazard index makes possible the calculation of risk potentials at a given time of release and time period of concern thereafter. Sample calculations for different nuclear wastes show the importance of the model improvements on resulting time-dependent risk potentials. Applicability of the new hazard index to non-nuclear wastes is described. Potentials and limitations of comparative risk assessments using hazard indices are discussed. (author)

  13. Severe Pulmonary Toxicity After Myeloablative Conditioning Using Total Body Irradiation: An Assessment of Risk Factors

    International Nuclear Information System (INIS)

    Kelsey, Chris R.; Horwitz, Mitchell E.; Chino, Junzo P.; Craciunescu, Oana; Steffey, Beverly; Folz, Rodney J.; Chao, Nelson J.; Rizzieri, David A.; Marks, Lawrence B.

    2011-01-01

    Purpose: To assess factors associated with severe pulmonary toxicity after myeloablative conditioning using total body irradiation (TBI) followed by allogeneic stem cell transplantation. Methods and Materials: A total of 101 adult patients who underwent TBI-based myeloablative conditioning for hematologic malignancies at Duke University between 1998 and 2008 were reviewed. TBI was combined with high-dose cyclophosphamide, melphalan, fludarabine, or etoposide, depending on the underlying disease. Acute pulmonary toxicity, occurring within 90 days of transplantation, was scored using Common Terminology Criteria for Adverse Events version 3.0. Actuarial overall survival and the cumulative incidence of acute pulmonary toxicity were calculated via the Kaplan-Meier method and compared using a log-rank test. A binary logistic regression analysis was performed to assess factors independently associated with acute severe pulmonary toxicity. Results: The 90-day actuarial risk of developing severe (Grade 3-5) pulmonary toxicity was 33%. Actuarial survival at 90 days was 49% in patients with severe pulmonary toxicity vs. 94% in patients without (p < 0.001). On multivariate analysis, the number of prior chemotherapy regimens was the only factor independently associated with development of severe pulmonary toxicity (odds ratio, 2.7 per regimen). Conclusions: Severe acute pulmonary toxicity is prevalent after TBI-based myeloablative conditioning regimens, occurring in approximately 33% of patients. The number of prior chemotherapy regimens appears to be an important risk factor.

  14. Predicted risks of radiogenic cardiac toxicity in two pediatric patients undergoing photon or proton radiotherapy

    International Nuclear Information System (INIS)

    Zhang, Rui; Howell, Rebecca M; Homann, Kenneth; Giebeler, Annelise; Taddei, Phillip J; Mahajan, Anita; Newhauser, Wayne D

    2013-01-01

    Hodgkin disease (HD) and medulloblastoma (MB) are common malignancies found in children and young adults, and radiotherapy is part of the standard treatment. It was reported that these patients who received radiation therapy have an increased risk of cardiovascular late effects. We compared the predicted risk of developing radiogenic cardiac toxicity after photon versus proton radiotherapies for a pediatric patient with HD and a pediatric patient with MB. In the treatment plans, each patient’s heart was contoured in fine detail, including substructures of the pericardium and myocardium. Risk calculations took into account both therapeutic and stray radiation doses. We calculated the relative risk (RR) of cardiac toxicity using a linear risk model and the normal tissue complication probability (NTCP) values using relative seriality and Lyman models. Uncertainty analyses were also performed. The RR values of cardiac toxicity for the HD patient were 7.27 (proton) and 8.37 (photon), respectively; the RR values for the MB patient were 1.28 (proton) and 8.39 (photon), respectively. The predicted NTCP values for the HD patient were 2.17% (proton) and 2.67% (photon) for the myocardium, and were 2.11% (proton) and 1.92% (photon) for the whole heart. The predicted ratios of NTCP values (proton/photon) for the MB patient were much less than unity. Uncertainty analyses revealed that the predicted ratio of risk between proton and photon therapies was sensitive to uncertainties in the NTCP model parameters and the mean radiation weighting factor for neutrons, but was not sensitive to heart structure contours. The qualitative findings of the study were not sensitive to uncertainties in these factors. We conclude that proton and photon radiotherapies confer similar predicted risks of cardiac toxicity for the HD patient in this study, and that proton therapy reduced the predicted risk for the MB patient in this study

  15. Imprinting disorders after assisted reproductive technologies

    DEFF Research Database (Denmark)

    Lidegaard, Øjvind; Pinborg, Anja; Andersen, Anders Nyboe

    2006-01-01

    To assess the evidence of an increased risk of imprinting diseases in children born after use of assisted reproductive technologies.......To assess the evidence of an increased risk of imprinting diseases in children born after use of assisted reproductive technologies....

  16. Polycystic ovary syndrome and early-onset preeclampsia: reproductive manifestations of increased cardiovascular risk.

    Science.gov (United States)

    Veltman-Verhulst, Susanne M; van Rijn, Bas B; Westerveld, H Egbertine; Franx, Arie; Bruinse, Hein W; Fauser, Bart C J M; Goverde, Angelique J

    2010-01-01

    Primary prevention of cardiovascular disease (CVD) in women is a major healthcare issue. Detection of premenopausal women with increased risk of CVD could enhance prevention strategies and reduce first event-related morbidity and mortality. In this study, we argue that an unfavorable metabolic constitution in women may present itself early in life as a reproductive complication, such as polycystic ovary syndrome (PCOS) and preeclampsia. We evaluated the cardiovascular risk of women with a history of early-onset preeclampsia and women with PCOS and assessed their need for implementation of early risk factor-reduction strategies. We performed a standardized evaluation of 240 women with a history of early-onset preeclampsia and 456 women diagnosed with PCOS for established major CVD risk factors. Metabolic syndrome characteristics were analyzed per body mass index category. Mean age was 30.6 and 29.0 years for women with preeclampsia and PCOS, respectively. High percentages of metabolic syndrome were found in both groups (preeclampsia group, 14.6%; and PCOS group, 18.4%), with an incidence of greater than 50% in both groups of women if body mass index was greater than 30 kg/m. Overall, more than 90% of the women qualified for either lifestyle or medical intervention according to the American Heart Association guideline for CVD prevention in women. Women with PCOS and early-onset preeclampsia already show an unfavorable cardiovascular risk profile with high need for lifestyle or medical intervention at a young age. We therefore recommend an active role of the gynecologist in routine screening and follow-up of women with reproductive conditions linked to future cardiovascular risk.

  17. Dose- dependent ameliorative effects of quercetin and l-Carnitine against atrazine- induced reproductive toxicity in adult male Albino rats.

    Science.gov (United States)

    Abdel Aziz, Rabie L; Abdel-Wahab, Ahmed; Abo El-Ela, Fatma I; Hassan, Nour El-Houda Y; El-Nahass, El-Shaymaa; Ibrahim, Marwa A; Khalil, Abdel-Tawab A Y

    2018-06-01

    This study aimed to determine the protective effects of co-administration of Quercetin (QT) or l-Carnitine (LC) against the oxidative stress induced by Atrazine (ATZ) in the reproductive system of intact male Albino rats. 36 rats were divided equally into 6 groups. Rats in the control negative "CNT" group received 1.5 ml distilled water for 21 days. All rats in the other groups received ATZ (120 mg/kg bw) through gavage. Groups 3 and 4 were co-administered with either low or high dose of QT (10 "ATZLQT" and 50 "ATZHQT" mg/kg bw, respectively). Groups 5 and 6 were co-administered with either low or high dose of LC (200 "ATZLLC" and 400 "ATZHLC" mg/kg bw, respectively). At the end of the experiment, animals were sacrificed and all samples were collected. ATZ significantly increased serum level of malondialdehyde (MDA) and decreased total antioxidant capacity (TAC). Also, ATZ increased significantly the sperm cell abnormalities and reduced both testicular IgA and serum testosterone levels. Testicular DNA laddering % and CYP17A1 mRNA expression were significantly reduced in ATZ group. Interestingly, co-administration with low dose QT or different doses of LC succeeded to counteract the negative toxic effects of ATZ on serum oxidative stress indicators, serum testosterone levels, testicular IgA level and improved testicular CYP17A1 mRNA expression. In conclusion, QT in low dose and LC in both low and high doses exerted a significant protective action against the reproductive toxicity of ATZ, while higher dose of QT failed induce immune-stimulant effect against ATZ in adult male Albino rats. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  18. Risk associated with toxic blooms of marine phytoplankton functional groups on Artemia franciscana

    Directory of Open Access Journals (Sweden)

    Ana D’ors

    2014-08-01

    Full Text Available Objective: To study mortality of copepod Artemia franciscana against the occurrence of harmful marine algae and possible toxicological changes exhibited by binary and tertiary combinations of these harmful algae toxins. Methods: Tweenty four hours acute toxicity assays were performed with selected concentrations of Alexandrium minutum, Prorocentrum lima and Nitzschia N1c1 living cells. Additionally, the results were analyzed using the median-effect/combination index (CI-isobologram equation to assess possible changes in the toxic effect induced by phytoplankton functional groups. Results: Biotoxin equivalent values obtained by immunodetection were (2.12±0.10, (8.60±1.30 and (4.32±1.67 pg/cell for saxitoxin, okadaic acid and domoic acid, respectively. The 24-h LC50 values estimated to saxitoxin and okadaic acid equivalents were 4.06 and 6.27 µg/L, significantly below the value obtained for Nitzschia N1c1, which was established at 467.33 µg/L. CI analysis applied on phytoplankton assemblages showed that both ternary mixture as the binary combinations exhibited antagonic action on toxic effects in Artemia nauplii, which were significantly lower than the toxic effect exhibited by each species studied. Conclusions: These results show that, although these harmful algae represent a serious risk to estuarine zooplankton community, the presence of phytoplankton functional groups within the same bloom can reduce the potential risk compared to the expected risk when each of the phytoplankton groups are evaluated individually.

  19. Lead Toxicity in the Pediatric Patient with Sickle Cell Disease: Unique Risks and Management.

    Science.gov (United States)

    Jung, Josephine Misun; Peddinti, Radhika

    2018-01-01

    Lead toxicity is the result of lead ingestion, one of the most common ingestions in the pediatric population. Nationwide and statewide efforts to recognize and curtail this epidemic have led to declining rates of toxicity. In patients with sickle cell disease (SCD), lead toxicity can be an elusive diagnosis due to overlapping symptom profiles, and inconsistent follow-up with a primary care physician can make the diagnosis even more difficult. In this article, two illustrative cases of lead toxicity in patients with SCD are described. The discussion reviews the current risk factors, screening, and inpatient management of lead toxicity, as well as describing the unique and sometimes confounding presentations of lead toxicity versus sickle cell crisis. [Pediatr Ann. 2018;47(1):e36-e40.]. Copyright 2018, SLACK Incorporated.

  20. Comparison of Birth-and Conception-Based Definitions of Postnatal Age in Developmental and Reproductive Rodent Toxicity Studies: lnfluence of Gestation Length on Measurements of Offspring Body Weight and Puberty in Controls

    Science.gov (United States)

    Most laboratories conducting developmental and reproductive toxicity studies in rodents assign age by defining postnatal day (PND) 0 or 1 as the day of birth (DOB); i.e., gestation length affects PND and the timing of postnatal measurements. Some laboratories, however, define age...

  1. Multivariate Analysis of Reproductive Risk Factors for Ovarian Cancer in Alexandria, Egypt

    International Nuclear Information System (INIS)

    El-Khwsky, F.S.; Maghraby, H.K.; Rostom, Y.A.; Abdel-Rahman, A.H.

    2006-01-01

    Background: Ovarian cancer is the eighth leading cancer in women, as it accounts for 4% of all malignant tumors in females. The incidence of ovarian cancer is up to 10 times higher in western countries than in rural Asian and Africa ones. Different reproductive characteristics, life styles and specific medical conditions are responsible for different pattern and incidence of ovarian cancer worldwide. Material and Methods: A case control study was conducted during the time period from 2000 to 2003 including 172 cases of epithelial ovarian cancer, recently diagnosed and confirmed by histopathology. The patients were accessed at the hospitals currently covered by Alexandria Cancer Registry. In addition, 441 control subjects, comparable by age and address, were randomly selected from patients admitted to the same hospitals for non gynecological, non endocrinal acute diseases. Both cases and controls were subjected to a specific predesigned questionnaire to cover menstrual, reproductive and lifestyle indicators. Univariate and multivariate analysis were conducted and 5% level of significance was adopted. Results: Significantly increased risks were reported with increased number of abortions and increased number of ovarian cycles (OR=1.8, 95% CI (1.7-2.8), and 2.8, 95% CI 2.8 (1.5-5.2), respectively. Similarly, high risks were also reported for increased number of pregnancies, OR= 1.6, 95% CI 1.1-2.4) for I to three pregnancies and 4.2,95% CI 1.2-15.9) for more than four pregnancies On the other hand, decreased risks were reported for those with increased parity compared to nulliparous. Conclusion: Although ovarian cancer is less frequent in our community, yet the significant positive and negative associations between risk factors and ovarian cancer were similar to the results of other studies, apart from the primary prevention program that should be outlined according to prevalence of significant risk factors in the studied local community

  2. Assessing single and joint effects of chemicals on the survival and reproduction of Folsomia candida (Collembola) in soil

    International Nuclear Information System (INIS)

    Amorim, M.J.B.; Pereira, C.; Menezes-Oliveira, V.B.; Campos, B.; Soares, A.M.V.M.; Loureiro, S.

    2012-01-01

    Chemicals are often found in the environment as complex mixtures. There has been a large effort in the last decade to assess the combined effect of chemicals, using the conceptual models of Concentration Addition and Independent Action, but also including synergistic, antagonistic, dose-level and dose–ratio dependent deviations from these models. In the present study, single and mixture toxicity of atrazine, dimethoate, lindane, zinc and cadmium were studied in Folsomia candida, assessing survival and reproduction. Different response patterns were observed for the different endpoints and synergistic patterns were observed when pesticides were present. Compared with the previously tested Enchytraeus albidus and Porcellionides pruinosus, the mixture toxicity pattern for F. candida was species specific. The present study highlights the importance of studying toxicity of chemicals mixtures due to the observed potentiation of effects and confirms that for an adequate ecologically relevant risk assessment different organisms and endpoints should be included. - Highlights: ► Folsomia candida (Collembola) were exposed to binary mixtures of atrazine, dimethoate, lindane, zinc and cadmium. ► Synergistic response patterns were often observed when pesticides were present in the mixtures. ► Response patterns upon mixture exposure differed within endpoints (survival vs. reproduction) in some cases. ► As to single chemical toxicity, response patterns for mixture exposures seem to be also species specific. - Exposure to chemical mixtures in Folsomia candida showed potentiation of effects. Mixture toxicity patterns differ among species and endpoint measured.

  3. Incidence and risk of hematologic toxicities in cancer patients treated with regorafenib.

    Science.gov (United States)

    Zhao, Bin; Zhao, Hong

    2017-11-07

    Regorafenib, an oral vascular endothelial growth factor receptor tyrosine-kinase inhibitor, has been approved for the treatment of several malignancies. As a non-traditional cytotoxic chemotherapeutic agent, regorafenib is often associated with hematologic toxicities. Here we searched PubMed and Embase up to June 2017 for relevant clinical trials. Eligible studies include trials in which subjects treated with 160 mg of regorafenib daily during the first 21 days of each 28-day cycle, and adequate safety data profile reporting thrombocytopenia, anemia, neutropenia and leucopenia. Statistical analyses were conducted to calculate the overall incidences, relative risks (RRs) and their 95% confidence intervals (CIs). A total of 2,341 subjects from 16 trials were included in the present studies. The incidences of regorafenib associated all-grade and high-grade hematologic toxicities were: thrombocytopenia, 22% and 3%; anemia, 20% and 3%; neutropenia, 10% and 2%, and leucopenia, 13% and 2%, respectively. Regorafenib-treated subjects had a significant increased risk of all-grade (RR=6.35; 95% CI, 3.19-12.64) and high-grade (RR=6.27; 95% CI, 1.69-23.26) thrombocytopenia, all-grade (RR=2.76; 95% CI, 1.63-4.68) and high-grade (RR=5.38; 95% CI, 1.60-18.06) anemia. Our results suggested that regorafenib therapy was associated with significantly increased risks of hematological toxicities, and hematologic monitoring at regular intervals should be advised to clinician.

  4. Impact of heavy metals on the female reproductive system

    Directory of Open Access Journals (Sweden)

    Piotr Rzymski

    2015-05-01

    Full Text Available Introduction. It has been recognized that environmental pollution can affect the quality of health of the human population. Heavy metals are among the group of highly emitted contaminants and their adverse effect of living organisms has been widely studied in recent decades. Lifestyle and quality of the ambient environment are among these factors which can mainly contribute to the heavy metals exposure in humans. Objective. A review of literature linking heavy metals and the female reproductive system and description of the possible associations with emission and exposure of heavy metals and impairments of female reproductive system according to current knowledge. Results. The potential health disorders caused by chronic or acute heavy metals toxicity include immunodeficiency, osteoporosis, neurodegeneration and organ failures. Potential linkages of heavy metals concentration found in different human organs and blood with oestrogen-dependent diseases such as breast cancer, endometrial cancer, endometriosis and spontaneous abortions, as well as pre-term deliveries, stillbirths and hypotrophy, have also been reported. Conclusions. Environmental deterioration can lead to the elevated risk of human exposure to heavy metals, and consequently, health implications including disturbances in reproduction. It is therefore important to continue the investigations on metal-induced mechanisms of fertility impairment on the genetic, epigenetic and biochemical level.

  5. Urinary bisphenol A concentrations are associated with reproductive parameters in young men

    DEFF Research Database (Denmark)

    Adoamnei, Evdochia; Mendiola, Jaime; Vela-Soria, Fernando

    2018-01-01

    Bisphenol A (BPA) is a pervasive environmental toxicant with known reproductive effects on sperm parameters and hormone levels. Several observational studies have investigated the associations between BPA exposure and male reproductive function, but findings are inconsistent. The objective of thi...

  6. Particle size: a missing factor in risk assessment of human exposure to toxic chemicals in settled indoor dust.

    Science.gov (United States)

    Cao, Zhi-Guo; Yu, Gang; Chen, Yong-Shan; Cao, Qi-Ming; Fiedler, Heidelore; Deng, Shu-Bo; Huang, Jun; Wang, Bin

    2012-11-15

    For researches on toxic chemicals in settled indoor dust, selection of dust fraction is a critical influencing factor to the accuracy of human exposure risk assessment results. However, analysis of the selection of dust fraction in recent studies revealed that there is no consensus. This study classified and presented researches on distribution of toxic chemicals according to dust particle size and on relationship between dust particle size and human exposure possibility. According to the literature, beyond the fact that there were no consistent conclusions on particle size distribution of adherent fraction, dust with particle size less than 100 μm should be paid more attention and that larger than 250 μm is neither adherent nor proper for human exposure risk assessment. Calculation results based on literature data show that with different selections of dust fractions, analytical results of toxic chemicals would vary up to 10-fold, which means that selecting dust fractions arbitrarily will lead to large errors in risk assessment of human exposure to toxic chemicals in settled dust. Taking into account the influence of dust particle size on risk assessment of human exposure to toxic chemicals, a new methodology for risk assessment of human exposure to toxic chemicals in settled indoor dust is proposed and human exposure parameter systems to settled indoor dust are advised to be established at national and regional scales all over the world. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. Assessment of genetic risk of exposure resulted from X-ray examination of women of the reproductive age

    International Nuclear Information System (INIS)

    Strel'nikova, N.K.

    1989-01-01

    On the basis of the available data an evaluation of genetic radiation risk during roentgenologic examination of women of the reproductive age is presented. It is demonstrated that the degree of genetic risk depends on woman's age at the moment of the roentgenologic examination and the amount of the gonadal dose. Identification of the high-risk exposed populations has been substantiated

  8. Adverse Effect of Antifouling Compounds on the Reproductive Mechanisms of the Ascidian Ciona intestinalis

    Directory of Open Access Journals (Sweden)

    Alessandra Gallo

    2013-09-01

    Full Text Available Fertilization and embryo development that occur in sea water are sensitive to xenobiotics from anthropogenic sources. In this work, we evaluated the influence of two antifouling biocides, tributyltin (TBT and diuron, on the reproductive mechanisms of the marine invertebrate Ciona intestinalis. By using electrophysiological techniques, we examined the impact of these compounds on the electrical properties of the mature oocytes and of events occurring at fertilization. With different toxicity assays, we studied the effect of the two biocides on the gametes by evaluating fertilization rate and embryo development. Results show that sodium (Na+ currents were significantly reduced by either of the two biocides, whereas conductance was significantly increased. The fertilization current frequency and amplitude, fertilization rate and larval development were affected only by TBT. This study suggests that: (i the two biocides affect either the electrical properties of the oocyte plasma membrane and the reproductive success representing a risk factor for the survival of the species exposed to environmental pollution; (ii the ascidian Ciona intestinalis may represent a good model organism to test toxicity of marine pollutants. Possible mechanisms of action of the two biocides are discussed.

  9. Adverse Effect of Antifouling Compounds on the Reproductive Mechanisms of the Ascidian Ciona intestinalis

    Science.gov (United States)

    Gallo, Alessandra; Tosti, Elisabetta

    2013-01-01

    Fertilization and embryo development that occur in sea water are sensitive to xenobiotics from anthropogenic sources. In this work, we evaluated the influence of two antifouling biocides, tributyltin (TBT) and diuron, on the reproductive mechanisms of the marine invertebrate Ciona intestinalis. By using electrophysiological techniques, we examined the impact of these compounds on the electrical properties of the mature oocytes and of events occurring at fertilization. With different toxicity assays, we studied the effect of the two biocides on the gametes by evaluating fertilization rate and embryo development. Results show that sodium (Na+) currents were significantly reduced by either of the two biocides, whereas conductance was significantly increased. The fertilization current frequency and amplitude, fertilization rate and larval development were affected only by TBT. This study suggests that: (i) the two biocides affect either the electrical properties of the oocyte plasma membrane and the reproductive success representing a risk factor for the survival of the species exposed to environmental pollution; (ii) the ascidian Ciona intestinalis may represent a good model organism to test toxicity of marine pollutants. Possible mechanisms of action of the two biocides are discussed. PMID:24065165

  10. Adverse effect of antifouling compounds on the reproductive mechanisms of the ascidian Ciona intestinalis.

    Science.gov (United States)

    Gallo, Alessandra; Tosti, Elisabetta

    2013-09-20

    Fertilization and embryo development that occur in sea water are sensitive to xenobiotics from anthropogenic sources. In this work, we evaluated the influence of two antifouling biocides, tributyltin (TBT) and diuron, on the reproductive mechanisms of the marine invertebrate Ciona intestinalis. By using electrophysiological techniques, we examined the impact of these compounds on the electrical properties of the mature oocytes and of events occurring at fertilization. With different toxicity assays, we studied the effect of the two biocides on the gametes by evaluating fertilization rate and embryo development. Results show that sodium (Na⁺) currents were significantly reduced by either of the two biocides, whereas conductance was significantly increased. The fertilization current frequency and amplitude, fertilization rate and larval development were affected only by TBT. This study suggests that: (i) the two biocides affect either the electrical properties of the oocyte plasma membrane and the reproductive success representing a risk factor for the survival of the species exposed to environmental pollution; (ii) the ascidian Ciona intestinalis may represent a good model organism to test toxicity of marine pollutants. Possible mechanisms of action of the two biocides are discussed.

  11. Mode of Action Frameworks in Toxicity Testing and Chemical Risk Assessment

    NARCIS (Netherlands)

    Meek, B.

    2009-01-01

    Recently, legislative mandates worldwide are requiring systematic consideration of much larger numbers of chemicals. This necessitates more efficient and effective toxicity testing, as a basis to be more predictive in a risk assessment context. This in turn requires much more emphasis early in the

  12. Effects of nanotoxicity on female reproductivity and fetal development in animal models.

    Science.gov (United States)

    Sun, Jianling; Zhang, Qiu; Wang, Zhiping; Yan, Bing

    2013-04-29

    The extensive application of nanomaterials in industry, medicine and consumer products has raised concerns about their potential toxicity. The female population is particularly vulnerable and deserves special attention because toxicity in this group may impact both female reproductivity and fetal development. Mouse and zebrafish models each have their own unique features and studies using these models to examine the potential toxicity of various nanoparticles are compared and summarized in this review. Several nanoparticles exhibit detrimental effects on female reproductivity as well as fetal development, and these adverse effects are related to nanoparticle composition, surface modification, dose, exposure route and animal species. Limited studies on the mechanisms of nanotoxicity are also documented and reviewed herein.

  13. Effects of Nanotoxicity on Female Reproductivity and Fetal Development in Animal Models

    Directory of Open Access Journals (Sweden)

    Jianling Sun

    2013-04-01

    Full Text Available The extensive application of nanomaterials in industry, medicine and consumer products has raised concerns about their potential toxicity. The female population is particularly vulnerable and deserves special attention because toxicity in this group may impact both female reproductivity and fetal development. Mouse and zebrafish models each have their own unique features and studies using these models to examine the potential toxicity of various nanoparticles are compared and summarized in this review. Several nanoparticles exhibit detrimental effects on female reproductivity as well as fetal development, and these adverse effects are related to nanoparticle composition, surface modification, dose, exposure route and animal species. Limited studies on the mechanisms of nanotoxicity are also documented and reviewed herein.

  14. Reproductive and behavioral effects of diisononyl phthalate (DINP) in perinatally exposed rats

    DEFF Research Database (Denmark)

    Boberg, Julie; Christiansen, Sofie; Petersen, Marta Axelstad

    2011-01-01

    Diisononyl phthalate (DINP) is a plasticizer abundantly used in consumer products as a substitute for other plasticizers prohibited in certain products due to reproductive toxicity. As anti-androgenic effects of DINP are suspected, DINP effects on reproduction and sexually dimorphic behavior were...

  15. Roles of piRNAs in microcystin-leucine-arginine (MC-LR) induced reproductive toxicity in testis on male offspring.

    Science.gov (United States)

    Zhang, Ling; Zhang, Hui; Zhang, Huan; Benson, Mikael; Han, Xiaodong; Li, Dongmei

    2017-07-01

    In the present study, we evaluated the toxic effects on the testis of the male offspring of MC-LR exposure during fetal and lactational periods. Pregnant females were distributed into two experimental groups: control group and MC-LR group which were exposed to 0 and 10 μg/L of MC-LR, respectively, through drinking water separately during fetal and lactational periods. At the age of 30 days after birth, the male offspring were euthanized. The body weight, testis index, and histomorphology change were observed and the global changes of piwi-interacting RNA (piRNA) expression were evaluated. The results revealed that MC-LR was found in the testis of male offspring, body weight and testis index decreased significantly, and testicular tissue structure was damaged in the MC-LR group. In addition, the exposure to MC-LR resulted in an altered piRNA expression profile and an increase of the cell apoptosis and a decrease of the cell proliferation in the testis of the male offspring. It was reasonable to speculate that the toxic effects on reproductive system of the male offspring in MC-LR group might be mediated by piRNAs through the regulation of the target genes. As far as we are aware, this is the first report showing that MC-LR could play a role in disorder of proliferative and cell apoptosis in the testis of the male offspring by the maternal transmission effect of toxicity. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Calculating background levels for ecological risk parameters in toxic harbor sediment

    Science.gov (United States)

    Leadon, C.J.; McDonnell, T.R.; Lear, J.; Barclift, D.

    2007-01-01

    Establishing background levels for biological parameters is necessary in assessing the ecological risks from harbor sediment contaminated with toxic chemicals. For chemicals in sediment, the term contaminated is defined as having concentrations above background and significant human health or ecological risk levels. For biological parameters, a site could be considered contaminated if levels of the parameter are either more or less than the background level, depending on the specific parameter. Biological parameters can include tissue chemical concentrations in ecological receptors, bioassay responses, bioaccumulation levels, and benthic community metrics. Chemical parameters can include sediment concentrations of a variety of potentially toxic chemicals. Indirectly, contaminated harbor sediment can impact shellfish, fish, birds, and marine mammals, and human populations. This paper summarizes the methods used to define background levels for chemical and biological parameters from a survey of ecological risk investigations of marine harbor sediment at California Navy bases. Background levels for regional biological indices used to quantify ecological risks for benthic communities are also described. Generally, background stations are positioned in relatively clean areas exhibiting the same physical and general chemical characteristics as nearby areas with contaminated harbor sediment. The number of background stations and the number of sample replicates per background station depend on the statistical design of the sediment ecological risk investigation, developed through the data quality objective (DQO) process. Biological data from the background stations can be compared to data from a contaminated site by using minimum or maximum background levels or comparative statistics. In Navy ecological risk assessments (ERA's), calculated background levels and appropriate ecological risk screening criteria are used to identify sampling stations and sites with contaminated

  17. Reproductive and developmental hazards in the workplace.

    Science.gov (United States)

    McElgunn, B

    1998-05-01

    Toxic exposures to both the father and the mother before conception and to the mother during pregnancy can affect fertility, the course of pregnancy, and fetal development. The present focus on cancer-causing chemicals in toxicity evaluations has overshadowed other important health endpoints, such as reproductive and developmental toxicity, that may occur at much lower levels of exposure. Environmental tobacco smoke, video display terminals, and indoor air quality are three of the most common concerns of pregnant women in their places of work. The controversies and uncertainties about these and the lack of data on other potential hazards make toxic exposure both a delicate and a necessary issue when counseling women about their workplace health during pregnancy.

  18. Melatonin and male reproductive health: relevance of darkness and antioxidant properties.

    Science.gov (United States)

    Rocha, C S; Rato, L; Martins, A D; Alves, M G; Oliveira, P F

    2015-01-01

    The pineal hormone melatonin controls several physiological functions that reach far beyond the regulation of the circadian rhythm. Moreover, it can be produced in extra-pineal organs such as reproductive organs. The role of melatonin in the mammalian seasonal and circadian rhythm is well known. Nevertheless, its overall effect in male reproductive physiology remains largely unknown. Melatonin is a very powerful endogenous antioxidant that can also be exogenously taken safely. Interestingly, its antioxidant properties have been consistently reported to improve the male reproductive dysfunctions associated with pathological conditions and also with the exposure to toxicants. Nevertheless, the exact molecular mechanisms by which melatonin exerts its action in the male reproductive system remain a matter of debate. Herein, we propose to present an up-to-date overview of the melatonin effects in the male reproductive health and debate future directions to disclose possible sites of melatonin action in male reproductive system. We will discuss not only the role of melatonin during darkness and sleep but also the importance of the antioxidant properties of this hormone to male fertility. Since melatonin readily crosses the physiological barriers, such as the blood-testis barrier, and has a very low toxicity, it appears as an excellent candidate in the prevention and/or treatment of the multiple male reproductive dysfunctions associated with various pathologies.

  19. Bisphenol A and Reproductive Health: Update of Experimental and Human Evidence, 2007–2013

    Science.gov (United States)

    Peretz, Jackye; Vrooman, Lisa; Ricke, William A.; Hunt, Patricia A.; Ehrlich, Shelley; Hauser, Russ; Padmanabhan, Vasantha; Taylor, Hugh S.; Swan, Shanna H.; VandeVoort, Catherine A.

    2014-01-01

    Background: In 2007, an expert panel reviewed associations between bisphenol A (BPA) exposure and reproductive health outcomes. Since then, new studies have been conducted on the impact of BPA on reproduction. Objective: In this review, we summarize data obtained since 2007, focusing on a) findings from human and animal studies, b) the effects of BPA on a variety of reproductive end points, and c) mechanisms of BPA action. Methods: We reviewed the literature published from 2007 to 2013 using a PubMed search based on keywords related to BPA and male and female reproduction. Discussion: Because BPA has been reported to affect the onset of meiosis in both animal and in vitro models, interfere with germ cell nest breakdown in animal models, accelerate follicle transition in several animal species, alter steroidogenesis in multiple animal models and women, and reduce oocyte quality in animal models and women undergoing in vitro fertilization (IVF), we consider it an ovarian toxicant. In addition, strong evidence suggests that BPA is a uterine toxicant because it impaired uterine endometrial proliferation, decreased uterine receptivity, and increased implantation failure in animal models. BPA exposure may be associated with adverse birth outcomes, hyperandrogenism, sexual dysfunction, and impaired implantation in humans, but additional studies are required to confirm these associations. Studies also suggest that BPA may be a testicular toxicant in animal models, but the data in humans are equivocal. Finally, insufficient evidence exists regarding effects of BPA on the oviduct, the placenta, and pubertal development. Conclusion: Based on reports that BPA impacts female reproduction and has the potential to affect male reproductive systems in humans and animals, we conclude that BPA is a reproductive toxicant. Citation: Peretz J, Vrooman L, Ricke WA, Hunt PA, Ehrlich S, Hauser R, Padmanabhan V, Taylor HS, Swan SH, VandeVoort CA, Flaws JA. 2014. Bisphenol A and reproductive

  20. Zika virus and assisted reproduction.

    Science.gov (United States)

    Cordeiro, Christina N; Bano, Rashda; Washington Cross, Chantel I; Segars, James H

    2017-06-01

    Due to the fact that the Zika virus can be sexually transmitted, there is a potential risk for disease transmission at several stages of assisted reproduction. Such a possibility poses a serious challenge to couples pursing fertility with reproductive technologies. Here, we discuss what is known regarding Zika virus infection with respect to sexual transmission and correlate this knowledge with recent recommendations in the realm of infertility treatment. Zika virus can be transmitted from infected men and women through vaginal, oral or anal intercourse. Zika virus RNA has been detected in blood, semen, cervical mucus and vaginal fluid. Currently, the Centers for Disease Control recommends that infected men wait 6 months, and infected women 8 weeks, prior to attempting pregnancy. Reproductive tissue donors should wait 6 months before giving a specimen. Further study of Zika virus transmission in different reproductive tissues and establishment of validated testing methods for viral disease transmissibility are urgently needed. Reproductive technologists need to establish screening, testing and laboratory protocols aimed to reduce the risk of Zika virus transmission during assisted reproduction.

  1. 78 FR 69414 - Toxic Substances Control Act Chemical Testing; Receipt of Test Data

    Science.gov (United States)

    2013-11-19

    ...; Acute emulsion polymerization in Inhalation Toxicity in paper, textile, fiber, and Rats; Bacterial.../ Reproduction Development Toxicity. Note: CAS No. = Chemical Abstracts Service Registry Number. Authority: 15 U...

  2. Concentrations, sources and human health risk of inhalation exposure to air toxics in Edmonton, Canada.

    Science.gov (United States)

    Bari, Md Aynul; Kindzierski, Warren B

    2017-04-01

    With concern about levels of air pollutants in recent years in the Capital Region of Alberta, an investigation of ambient concentrations, sources and potential human health risk of hazardous air pollutants (HAPs) or air toxics was undertaken in the City of Edmonton over a 5-year period (2009-2013). Mean concentrations of individual HAPs in ambient air including volatile organic compounds (VOCs), polycyclic aromatic hydrocarbons (PAHs) and trace metals ranged from 0.04 to 1.73 μg/m 3 , 0.01-0.54 ng/m 3 , and 0.05-3.58 ng/m 3 , respectively. Concentrations of benzene, naphthalene, benzo(a)pyrene (BaP), arsenic, manganese and nickel were far below respective annual Alberta Ambient Air Quality Objectives. Carcinogenic and non-carcinogenic risk of air toxics were also compared with risk levels recommended by regulatory agencies. Positive matrix factorization identified six air toxics sources with traffic as the dominant contributor to total HAPs (4.33 μg/m 3 , 42%), followed by background/secondary organic aerosol (SOA) (1.92 μg/m 3 , 25%), fossil fuel combustion (0.92 μg/m 3 , 11%). On high particulate air pollution event days, local traffic was identified as the major contributor to total HAPs compared to background/SOA and fossil fuel combustion. Carcinogenic risk values of traffic, background/SOA and metals industry emissions were above the USEPA acceptable level (1 × 10 -6 ), but below a tolerable risk (1 × 10 -4 ) and Alberta benchmark (1 × 10 -5 ). These findings offer useful preliminary information about current ambient air toxics levels, dominant sources and their potential risk to public health; and this information can support policy makers in the development of appropriate control strategies if required. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Atopic diseases in twins born after assisted reproduction

    DEFF Research Database (Denmark)

    Jäderberg, Ida; Thomsen, Simon F; Kyvik, Kirsten Ohm

    2012-01-01

    Jäderberg I, Thomsen SF, Kyvik KO, Skytthe A, Backer V. Atopic diseases in twins born after assisted reproduction. Paediatric and Perinatal Epidemiology 2012; 26: 140-145. We examined the risk of atopic diseases in twins born after assisted reproduction. Data on atopic diseases and assisted...... reproduction in 9694 twin pairs, 3-20 years of age, from the Danish Twin Registry were collected via multidisciplinary questionnaires. The risk of atopic diseases in twins born after assisted reproduction was compared with the risk in twins born after spontaneous conception using logistic regression...... and variance components analysis. Children born after assisted reproduction did not have a different risk of atopic outcomes (adjusted odds ratios [95% confidence intervals] for asthma: 0.95 [0.85, 1.07], P = 0.403; hay fever: 1.01 [0.86, 1.18], P = 0.918; and atopic dermatitis: 1.02 [0.81, 1.11], P = 0...

  4. Perceptions of environmental health risks among residents in the "Toxic Doughnut": opportunities for risk screening and community mobilization.

    Science.gov (United States)

    White, Brandi M; Hall, Eric S

    2015-12-10

    Surrounded by landfills, and toxic and hazardous facilities, Altgeld Gardens is located in a "toxic doughnut". With high rates of environmentally-related conditions, residents have called for a community-based environmental health assessment to improve overall health in their community. The purpose of this study was to investigate the attitudes and beliefs of environmental health risks of Altgeld's residents which would assist community organizing efforts and provide the groundwork for a community-based environmental health assessment. A questionnaire was designed and administered to 42 Altgeld residents who also participated in focus groups to assess their perceptions of environmental health risks. All participants were Altgeld residents for at least two years and were fairly representative of the broader community. Physical and social hazards were primarily identified as posing risks to participants' family and the broader community. Physical hazards included the dumping of hazardous waste and landfills; social hazards were crime and drugs. These findings have been useful in community organizing efforts and in program planning for local community-based organizations and public health agencies. The results have also been used to prioritize health and environmental risk issues impacting the community.

  5. Atopic diseases in twins born after assisted reproduction.

    Science.gov (United States)

    Jäderberg, Ida; Thomsen, Simon F; Kyvik, Kirsten O; Skytthe, Axel; Backer, Vibeke

    2012-03-01

    We examined the risk of atopic diseases in twins born after assisted reproduction. Data on atopic diseases and assisted reproduction in 9694 twin pairs, 3-20 years of age, from the Danish Twin Registry were collected via multidisciplinary questionnaires. The risk of atopic diseases in twins born after assisted reproduction was compared with the risk in twins born after spontaneous conception using logistic regression and variance components analysis. Children born after assisted reproduction did not have a different risk of atopic outcomes (adjusted odds ratios [95% confidence intervals] for asthma: 0.95 [0.85, 1.07], P = 0.403; hay fever: 1.01 [0.86, 1.18], P = 0.918; and atopic dermatitis: 1.02 [0.81, 1.11], P = 0.773 respectively) compared with children born after spontaneous conception. Assisted reproduction did not modify the heritability of atopic diseases. This study does not support an association between assisted reproduction and development of atopic diseases. This result must be confirmed in subsequent studies, preferably of singleton populations. © 2011 Blackwell Publishing Ltd.

  6. Systemic Lupus Erythematosus, Radiotherapy, and the Risk of Acute and Chronic Toxicity: The Mayo Clinic Experience

    International Nuclear Information System (INIS)

    Pinn, Melva E.; Gold, Douglas G. M.; Petersen, Ivy A.; Osborn, Thomas G.; Brown, Paul D.; Miller, Robert C.

    2008-01-01

    Purpose: To determine the acute and chronic toxic effects of radiotherapy in patients with systemic lupus erythematosus (SLE). Methods and Materials: Medical records of 21 consecutive patients with SLE, who had received 34 courses of external beam radiotherapy and one low-dose-rate prostate implant, were retrospectively reviewed. Patients with discoid lupus erythematosus were excluded. Results: Median survival was 2.3 years and median follow-up 5.6 years. Eight (42%) of 19 patients evaluable for acute toxicity during radiotherapy experienced acute toxicity of Grade 1 or greater, and 4 (21%) had acute toxicity of Grade 3 or greater. The 5- and 10-year incidence of chronic toxicity of Grade 1 or greater was 45% (95% confidence interval [CI], 22-72%) and 56% (95% CI, 28-81%), respectively. The 5- and 10-year incidence of chronic toxicity of Grade 3 or greater was 28% (95% CI, 18-60%) and 40% (95% CI, 16-72%), respectively. Univariate analysis showed that chronic toxicity of Grade 1 or greater correlated with SLE renal involvement (p < 0.006) and possibly with the presence of five or more American Rheumatism Association criteria (p < 0.053). Chronic toxicity of Grade 3 or greater correlated with an absence of photosensitivity (p < 0.02), absence of arthritis (p < 0.03), and presence of a malar rash (p < 0.04). Conclusions: The risk of acute and chronic toxicity in patients with SLE who received radiotherapy was moderate but was not prohibitive of the use of radiotherapy. Patients with more advanced SLE may be at increased risk for chronic toxicity

  7. Subchronic immunotoxicity and screening of reproductive toxicity and developmental immunotoxicity following single instillation of HIPCO-single-walled carbon nanotubes: purity-based comparison.

    Science.gov (United States)

    Park, Eun-Jung; Choi, Je; Kim, Jae-Ho; Lee, Byoung-Seok; Yoon, Cheolho; Jeong, Uiseok; Kim, Younghun

    2016-10-01

    Impurity has been suggested as an important factor determining toxicity following exposure to single-walled carbon nanotubes (SWCNTs). In this study, we first compared immunotoxicity based on iron content on day 90 after a single intratracheal instillation of SWCNTs in male and female mice. The inflammatory responses were generally stronger in mice exposed to acid-purified (P)-SWCNTs compared to raw (R)-SWCNTs. In addition, both R- and P-SWCNTs induced Th1-polarized immune responses with apoptotic death of BAL cells and systemically impaired the function of antigen-presenting cells (APC). We also screened reproductive and developmental toxicity by cohabitating male and female mice on day 14 after instillation. Interestingly, the pregnancy rate rapidly decreased following exposure to both types of SWCNTs, especially R-SWCNTs. In addition, we investigated developmental immunotoxicity of the offspring on day 28 after exposure to both types of SWCNTs. Their hematological changes were clearer relative to those of the parents and a significant decrease in the alkaline phosphatase and potassium levels was observed in mice of both sexes exposed to the higher dose of R- and P-SWCNTs. In conclusion, we suggest that SWCNTs may induce Th1-polarized immune responses accompanied by suppression of APC function on day 90 after a single instillation without significant iron content dependance. In addition, the consecutive exposure of SWCNTs to the subsequent generation may exacerbate metabolic and hematological disturbance. Furthermore, our results underscore the need to clarify the reproductive and developmental health effects of SWCNTs.

  8. Longevity and reproduction of Ceriodaphnia dubia in receiving waters

    International Nuclear Information System (INIS)

    Stewart, A.J.; Konetsky, B.K.

    1998-01-01

    Seven-day tests with Ceriodaphnia dubia are commonly used to estimate toxicity of effluents or receiving waters but can sometimes yield no toxicity outcomes even if pollutants are present. The authors conducted two sets of full life-cycle tests with C. dubia to (1) determine whether tests with longer exposure periods to low concentrations of contaminants in ambient water might reveal evidence of toxicity that could not be discerned from 7-d tests and (2) determine the relative importance of water quality versus food as factors influencing C. dubia longevity and reproduction. In the first set of tests, C. dubia was reared in diluted mineral water (a negative control), water from a stream impacted by coal fly-ash, or water from a retention basin containing sediments contaminated with mercury, other metals, and polychlorinated biphenyls. The second set of tests used water from the retention basin only. Before testing, though, water in the second set of tests was either filtered or not filtered, and food was either added or not added. Ceriodaphnia dubia longevity and reproduction did not differ much among the three water types in the first set of tests, but both longevity and reproduction were strongly affected by the filtering and food-addition treatments in the second set of tests. Thus, C. dubia appeared to be relatively insensitive to general water quality factors but sensitive to food-related factors. In five of the six full life-cycle tests, lifetime reproduction by C. dubia could not be reliably predicted from reproduction data from the first 7 d of testing. The increase in predictability of lifetime reproduction of C. dubia as a function of test duration also differed among water types in the first set of tests and among treatments in the second set of tests. This, it may not be possible to reliably extrapolate the results of 7-d tests with C. dubia to longer time scales

  9. Impact of globalization under the ICH guidelines on the conduct of reproductive toxicity studies--report on current status in Japan, Europe and the U.S. by questionnaire survey.

    Science.gov (United States)

    Mineshima, Hiroshi; Endo, Yoshihiko; Ogasawara, Hiroyuki; Nishigaki, Keiji; Numa, Toshiaki; Hirano, Fumiya; Matsuzawa, Toshiaki

    2004-08-01

    We surveyed interpretation of the ICH guidelines concerning reproductive toxicology. Valid responses were obtained from Japan (JPN), Europe (EUR) and the U.S. The results obtained were compared to those at the time of a previous survey targeted at JPN facilities in 1995-1996 as well as compared among all three regions. Compared to the previous survey in Japan, the number of facilities performing toxicokinetics (TK) in rats has slightly increased. This result was considered to represent changes of attitude toward TK in reproductive toxicity studies. Differences in interpretation of the guidelines between JPN, EUR and the US were widely seen. Clear differences were noted in sperm examinations, postnatal tests, fetal examinations, some examinations for F1 animals after culling and TK. Researchers in the West seemed to be interpreting the ICH guidelines more flexibly from the scientific point of view. JPN researchers appeared to interpret the guidelines, including notes, as rigid requirements. Most of the parts which produced different interpretations were the notes in the guidelines. The force of mention in the notes should be defined in the future. In addition, there were doubts about some parts, including notes, which had been found to have become unsuitable for the implementation of studies because of scientific progress or from long experience in using the guidelines. Therefore, updates of the guidelines may be needed in the future as well as the remedy of interpretation by JPN researchers. In JPN, the number of reproductive toxicity studies has decreased. The scanty experience in JPN therefore raises apprehension of appropriate selection and stagnating development of methodology, and might hinder the maintenance of the guidelines. In the future, the cooperation of CROs as well as global collaboration will be essential not only to scientific developments of reproductive toxicology but also updates of the guidelines.

  10. How endangered is sexual reproduction of high-mountain plants by summer frosts? Frost resistance, frequency of frost events and risk assessment.

    Science.gov (United States)

    Ladinig, Ursula; Hacker, Jürgen; Neuner, Gilbert; Wagner, Johanna

    2013-03-01

    In temperate-zone mountains, summer frosts usually occur during unpredictable cold spells with snow-falls. Earlier studies have shown that vegetative aboveground organs of most high-mountain plants tolerate extracellular ice in the active state. However, little is known about the impact of frost on reproductive development and reproductive success. In common plant species from the European Alps (Cerastium uniflorum, Loiseleuria procumbens, Ranunculus glacialis, Rhododendron ferrugineum, Saxifraga bryoides, S. moschata, S. caesia), differing in growth form, altitudinal distribution and phenology, frost resistance of reproductive and vegetative shoots was assessed in different reproductive stages. Intact plants were exposed to simulated night frosts between -2 and -14 °C in temperature-controlled freezers. Nucleation temperatures, freezing damage and subsequent reproductive success (fruit and seed set, seed germination) were determined. During all reproductive stages, reproductive shoots were significantly less frost resistant than vegetative shoots (mean difference for LT50 -4.2 ± 2.7 K). In most species, reproductive shoots were ice tolerant before bolting and during fruiting (mean LT50 -7 and -5.7 °C), but were ice sensitive during bolting and anthesis (mean LT50 around -4 °C). Only R. glacialis remained ice tolerant during all reproductive stages. Frost injury in reproductive shoots usually led to full fruit loss. Reproductive success of frost-treated but undamaged shoots did not differ significantly from control values. Assessing the frost damage risk on the basis of summer frost frequency and frost resistance shows that, in the alpine zone, low-statured species are rarely endangered as long as they are protected by snow. The situation is different in the subnival and nival zone, where frost-sensitive reproductive shoots may become frost damaged even when covered by snow. Unprotected individuals are at high risk of suffering from frost damage, particularly

  11. Effects of soil organic matter content on cadmium toxicity in Eisenia fetida: implications for the use of biomarkers and standard toxicity tests.

    Science.gov (United States)

    Irizar, A; Rodríguez, M P; Izquierdo, A; Cancio, I; Marigómez, I; Soto, M

    2015-01-01

    Bioavailability is affected by soil physicochemical characteristics such as pH and organic matter (OM) content. In addition, OM constitutes the energy source of Eisenia fetida, a well established model species for soil toxicity assessment. The present work aimed at assessing the effects of changes in OM content on the toxicity of Cd in E. fetida through the measurement of neutral red uptake (NRU) and mortality, growth, and reproduction (Organisation for Economic Co-operation and Development [OECD] Nos. 207 and 222). Complementarily, metallothionein (MT) and catalase transcription levels were measured. To decrease variability inherent to natural soils, artificial soils (Organization for Economic Cooperation and Development 1984) with different OM content (6, 10, and 14%) and spiked with Cd solutions at increasing concentrations were used. Low OM in soil decreased soil ingestion and Cd bioaccumulation but also increased Cd toxicity causing lower NRU of coelomocytes, 100 % mortality, and stronger reproduction impairment, probably due to the lack of energy to maintain protection mechanisms (production of MT).Cd bioaccumulation did not reflect toxicity, and OM played a pivotal role in Cd toxicity. Thus, OM content should be taken into account when using E. fetida in in vivo exposures for soil health assessment.

  12. Sperm as an indicator of reproductive risk among petroleum refinery workers

    Energy Technology Data Exchange (ETDEWEB)

    Rosenberg, M.J.; Wyrobek, A.J.; Ratcliffe, J.; Gordon, L.A.; Watchmaker, G.; Fox, S.H.; Moore, D.H.; Hornung, R.W.

    1985-02-01

    A questionnaire study of men in a wastewater treatment plant of a petroleum refinery showed twice the rate of fetal loss in the period during employment in the plant compared with the periods before and after. Questions regarding the interpretation of that study and continuing concern about reproductive risk prompted us to perform a cross sectional evaluation of sperm concentration and morphology. After adjustment for an abstinence period, the mean sperm concentration of the 74 unexposed men did not differ significantly from that of the 34 exposed men (79.9 million/cm/sup 3/ v 68.2 million/cm/sup 3/, p(1) . 0.16). The two groups also had a similar proportion of sperm with abnormal morphology (49.1% v 44.5%, p(1) . 0.94). This lack of association remained when degree of exposure, age, use of alcohol and marijuana, past illness or fever, use of baths or sauna, and history of urological problems were considered. These results are most consistent with the absence of sperm mediated reproductive problems.

  13. Toxicity of contaminants in lagoons and pannes of the Indiana Dunes National Lakeshore

    International Nuclear Information System (INIS)

    Gillespie, R.; Speelman, J.; Stewart, P.M.

    1995-01-01

    Contaminants in water and sediments of lagoons and pannes were 2--90 times greater at sites adjacent to slag and coal piles than those at reference sites. One site (Lagoon-US5) had sediments with very high concentrations of toxic organics (e.g. naphthalene, phenanthrene, dibenzofuran). Although analyses indicated a gradient of contaminant concentration with distance from their sources, toxicity assays were somewhat equivocal. With the exception of less reproduction in Ceriodaphnia at one lagoon site (US3 = 0.55 of reference), survival of fathead minnows and reproduction in Ceriodaphnia in lagoon and panne waters varied independently of the contaminant concentration. In fact, there was better Ceriodaphnia reproduction in water from two contaminated sites (Lagoon-US5, Panne-WP1) than in water from reference sites. Fathead minnow survival, Ceriodaphnia survival, Ceriodaphnia reproduction, amphipod survival, and amphipod growth varied among sites in toxicity assays with sediments, 100% mortality of fatheads at Lagoon-US5, 100% mortality of Ceriodaphnia at Lagoon-US3, and less survival of fathead minnows at Lagoon-US3 indicate possible toxicity from contaminants in sediments at these sites. Of all organisms and end-points tested, Ceriodaphnia survival seemed to be most closely associated with concentrations of contaminants in lagoon water and sediments. Amphipod survival also varied with contaminants in sediments, however, survival in sediments of contaminated sites ranged only from 0.90--0.93 of reference sites. Although the results are not consistent among organisms, toxicity assays indicate that sediments from the lagoon site with the highest contaminants (Lagoon-US5) and possibly those from another contaminated lagoon site (Lagoon-US3) could be toxic to aquatic organisms. Water and sediments from contaminated panne sites do not appear to be toxic to aquatic test organisms

  14. Corrosion protection products as a source of bisphenol A and toxicity to the aquatic environment.

    Science.gov (United States)

    Vermeirssen, Etiënne L M; Dietschweiler, Conrad; Werner, Inge; Burkhardt, Michael

    2017-10-15

    Steel components are typically treated with anti-corrosion coatings like epoxy or polyurethane resins to protect the integrity and functioning of steel. Such resins may contain substances, such as bisphenol A (BPA), that have caused concern in a human and environmental toxicological context. We investigated the release of toxicity from four anti-corrosion coatings used in hydraulic and civil engineering. Resins were applied onto glass plates and leachate samples produced by horizontally shaking the plates in water for 7 days. Two experiments were conducted, one with a 1 day and one with a 7 day curing period. Using a suite of bioassays, we tested samples for: agonistic and antagonistic effects on various mammalian nuclear receptors; inhibition of photosynthesis and growth in algae; inhibition of bacterial bioluminescence; and inhibition of water flea reproduction. Concentrations of BPA, bisphenol F and various BPA transformation products were determined by chemical analysis (LC-MS/MS). Bioassay results were evaluated using a scheme developed by DIBt (Centre of Competence for Construction, Berlin, Germany). Three products induced responses in one or more of the measured endpoints and toxicity profiles varied markedly in intensity across products. One product released high amounts of BPA which was associated with effects on nuclear receptor transactivation, requiring a more than 700-fold dilution for effect induction to fall below 20%. The same product was also the most toxic to water flea reproduction, requiring ca. 70-fold dilution for effects to fall below 20%. Another product was highly toxic in terms of bacterial bioluminescence, particularly after a shorter curing time, requiring a ca. 1'300-fold dilution for effects to fall below 20%. The third product required a 22-fold dilution for inhibition of water flea reproduction to drop below 20%. Results show that anti-corrosion coatings based on epoxy resins can be a source of toxicity to the aquatic environment

  15. Personal care product preservatives: risk assessment and mixture toxicities with an industrial wastewater.

    Science.gov (United States)

    Carbajo, Jose B; Perdigón-Melón, Jose A; Petre, Alice L; Rosal, Roberto; Letón, Pedro; García-Calvo, Eloy

    2015-04-01

    The aquatic toxicity of eight preservatives frequently used in personal care products (PCPs) (iodopropynyl butylcarbamate, bronopol, diazolidinyl urea, benzalkonium chloride, zinc pyrithione, propylparaben, triclosan and a mixture of methylchloroisothiazolinone and methylisothiazolinone) was assessed by means of two different approaches: a battery of bioassays composed of single species tests of bacteria (Vibrio fischeri and Pseudomonas putida) and protozoa (Tetrahymena thermophila), and a whole biological community resazurin-based assay using activated sludge. The tested preservatives showed considerable toxicity in the studied bioassays, but with a marked difference in potency. In fact, all biocides except propylparaben and diazolidinyl urea had EC50 values lower than 1 mg L(-1) in at least one assay. Risk quotients for zinc pyrithione, benzalkonium chloride, iodopropynyl butylcarbamate and triclosan as well as the mixture of the studied preservatives exceeded 1, indicating a potential risk for the process performance and efficiency of municipal sewage treatment plants (STPs). These four single biocides explained more than 95% of the preservative mixture risk in all bioassays. Each individual preservative was also tested in combination with an industrial wastewater (IWW) from a cosmetics manufacturing facility. The toxicity assessment was performed on binary mixtures (preservative + IWW) and carried out using the median-effect principle, which is a special case of the concept of Concentration Addition (CA). Almost 70% of all experiments resulted in EC50 values within a factor of 2 of the values predicted by the median-effect principle (CI values between 0.5 and 2). The rest of the mixtures whose toxicity was mispredicted by CA were assessed with the alternative concept of Independent Action (IA), which showed higher predictive power for the biological community assay. Therefore, the concept used to accurately predict the toxicity of mixtures of a preservative

  16. Toxicological risk assessment of complex mixtures through the Wtox model

    Directory of Open Access Journals (Sweden)

    William Gerson Matias

    2015-01-01

    Full Text Available Mathematical models are important tools for environmental management and risk assessment. Predictions about the toxicity of chemical mixtures must be enhanced due to the complexity of eects that can be caused to the living species. In this work, the environmental risk was accessed addressing the need to study the relationship between the organism and xenobiotics. Therefore, ve toxicological endpoints were applied through the WTox Model, and with this methodology we obtained the risk classication of potentially toxic substances. Acute and chronic toxicity, citotoxicity and genotoxicity were observed in the organisms Daphnia magna, Vibrio scheri and Oreochromis niloticus. A case study was conducted with solid wastes from textile, metal-mechanic and pulp and paper industries. The results have shown that several industrial wastes induced mortality, reproductive eects, micronucleus formation and increases in the rate of lipid peroxidation and DNA methylation of the organisms tested. These results, analyzed together through the WTox Model, allowed the classication of the environmental risk of industrial wastes. The evaluation showed that the toxicological environmental risk of the samples analyzed can be classied as signicant or critical.

  17. "Incorporating epigenetic data into the risk assessment process for the toxic metals arsenic, cadmium, chromium, lead, and mercury: strategies and challenges."

    Directory of Open Access Journals (Sweden)

    Paul eRay

    2014-07-01

    Full Text Available Exposure to toxic metals poses a serious human health hazard based on ubiquitous environmental presence, the extent of exposure, and the toxicity and disease states associated with exposure. This global health issue warrants accurate and reliable models derived from the risk assessment process to predict disease risk in populations. There has been considerable interest recently in the impact of environmental toxicants such as toxic metals on the epigenome. Epigenetic modifications are somatically inherited alterations to an individual’s genome without a change in the DNA sequence, and include, but are not limited to, three commonly studied alterations: DNA methylation, histone modification, and non-coding RNA expression. Given the role of epigenetic alterations in regulating gene and thus protein expression, there is the potential for the integration of toxic metal-induced epigenetic alterations as informative factors in the risk assessment process. In the present review, epigenetic alterations induced by five high priority toxic metals/metalloids are prioritized for analysis and their possible inclusion into the risk assessment process is discussed.

  18. Rethink potential risks of toxic emissions from natural gas and oil mining.

    Science.gov (United States)

    Meng, Qingmin

    2018-09-01

    Studies have showed the increasing environmental and public health risks of toxic emissions from natural gas and oil mining, which have become even worse as fracking is becoming a dominant approach in current natural gas extraction. However, governments and communities often overlook the serious air pollutants from oil and gas mining, which are often quantified lower than the significant levels of adverse health effects. Therefore, we are facing a challenging dilemma: how could we clearly understand the potential risks of air toxics from natural gas and oil mining. This short study aims at the design and application of simple and robust methods to enhance and improve current understanding of the becoming worse toxic air emissions from natural gas and oil mining as fracking is becoming the major approach. Two simple ratios, the min-to-national-average and the max-to-national-average, are designed and applied to each type of air pollutants in a natural gas and oil mining region. The two ratios directly indicate how significantly high a type of air pollutant could be due to natural gas and oil mining by comparing it to the national average records, although it may not reach the significant risks of adverse health effects according to current risk screening methods. The min-to-national-average and the max-to-national-average ratios can be used as a direct and powerful method to describe the significance of air pollution by comparing it to the national average. The two ratios are easy to use for governments, stakeholders, and the public to pay enough attention on the air pollutants from natural gas and oil mining. The two ratios can also be thematically mapped at sampled sites for spatial monitoring, but spatial mitigation and analysis of environmental and health risks need other measurements of environmental and demographic characteristics across a natural gas and oil mining area. Copyright © 2018 Elsevier Ltd. All rights reserved.

  19. Influence of temperature on the toxicity of zinc to the earthworm Eisenia fetida

    Energy Technology Data Exchange (ETDEWEB)

    Spurgeon, D.J.; Tomlin, M.A.; Hopkin, S.P. [Univ. of Reading (United Kingdom)

    1997-02-01

    A range of toxicity tests have been proposed to assess the potential hazards of pollutants to earthworms. Of these, the two acute toxicity tests using Eisenia fetida recommended by the OECD and EEC have become routinely used in the risk assessment and regulation of new and existing chemicals. In addition to the acute tests, procedures have also been proposed for measuring the sub-lethal effects of chemicals on parameter such as reproduction and weight change. In both the lethal and sub-lethal toxicity tests developed with worms, attempts have been made to standardise test conditions to allow results from different laboratories to be directly compared. However, variability in exposure conditions and responses are fundamental to determine the effects of pollutants under natural conditions. In the field, conditions such as light, moisture availability, pH, temperature and humidity all fluctuate over time. Such variations affect both the sensitivity and exposure of individuals to toxic chemicals. Hence when evaluating the potential effects of pollutants, it may be important to known how changes in test conditions influence toxicity. This study assessed the effects of different temperatures on the lethal and sub-lethal toxicity of zinc for the earthworm Eisenia fetida. 23 refs., 1 fig., 1 tab.

  20. Assessing plant protection practices using pressure indicator and toxicity risk indicators: analysis of therelationship between these indicators for improved risk management, application in viticulture.

    Science.gov (United States)

    Oussama, Mghirbi; Kamel, Ellefi; Philippe, Le Grusse; Elisabeth, Mandart; Jacques, Fabre; Habiba, Ayadi; Jean-Paul, Bord

    2015-06-01

    The excessive use of plant protection products (PPPs) has given rise to issues of public and environmental health because of their toxicity. Reducing the use of toxic PPPs and replacing them with products that are less toxic for human health and the environment have become socially, environmentally and economically indispensable. In this article, we assess the plant protection practices of a small group of winegrowers practicing "integrated agriculture" in the south of France, in order to measure the benefit of using toxicity risk indicators as a decision-support tool for different players in land management. An analysis of plant protection practices using indicators of the risk to operator health and the environment (IRSA, IRTE), together with a frequency-of-treatment indicator (TFI), enabled us to (i) show the variability of these indicators depending on the production system and farmers' pesticide use strategies and (ii) calculate correlations between these indicators. This analysis of plant protection practices at different scales (farm, field), carried out in collaboration with the growers, enabled us to perform an initial validation of decision-support tools for determining risk management strategies regarding the use of pesticides.

  1. Toxicities and risk assessment of heavy metals in sediments of Taihu Lake, China, based on sediment quality guidelines.

    Science.gov (United States)

    Zhang, Yanfeng; Han, Yuwei; Yang, Jinxi; Zhu, Lingyan; Zhong, Wenjue

    2017-12-01

    The occurrence, toxicities, and ecological risks of five heavy metals (Pb, Cu, Cd, Zn and Ni) in the sediment of Taihu Lake were investigated in this study. To evaluate the toxicities caused by the heavy metals, the toxicities induced by organic contaminants and ammonia in the sediments were screened out with activated carbon and zeolite. The toxicities of heavy metals in sediments were tested with benthic invertebrates (tubificid and chironomid). The correlations between toxicity of sediment and the sediment quality guidelines (SQGs) derived previously were evaluated. There were significant correlations (pheavy metals based on SQGs, indicating that threshold effect level (TEL) and probable effect level (PEL) were reliable to predict the toxicities of heavy metals in the sediments of Taihu Lake. By contrast, the method based on acid volatile sulfides (AVS) and simultaneously extracted metals (SEM), such as ∑SEM/AVS and ∑SEM-AVS, did not show correlations with the toxicities. Moreover, the predictive ability of SQGs was confirmed by a total predicting accuracy of 77%. Ecological risk assessment based on TELs and PELs showed that the contaminations of Pb, Cu, Cd and Zn in the sediments of Taihu Lake were at relatively low or medium levels. The risks caused by heavy metals in the sediments of northern bay of the lake, which received more wastewater discharge from upper stream, were higher than other area of the lake. Copyright © 2017. Published by Elsevier B.V.

  2. Risk factors for postpartum endometritis and the effect of endometritis on reproductive performance in dairy cows in Korea.

    Science.gov (United States)

    Kim, Ill-Hwa; Kang, Hyun-Gu

    2003-12-01

    The objectives of this study were to determine the risk factors for postpartum endometritis by evaluating several reproductive factors in individual cows, and to determine the effect of endometritis on the subsequent reproductive performance in dairy herds in Korea. The data, including health status, parity and body condition score (BCS) of cows, and calving date, were collected from 320 cows in eight dairy herds calving from January 2001 to October 2002. We used logistic regression to evaluate the effects of these factors on endometritis. A stepwise procedure, used to obtain the appropriate model with alpha=0.05, revealed that retained placenta, metabolic disorders and parity are the important risk factors for endometritis. The mean intervals from calving to first service and conception were prolonged (Pconception rate was lower (Pconception was higher (P<0.05) in the endometritis group (1.9) than in the non-endometritis group (1.6). We conclude that retained placenta, metabolic disorders and cow parity are strongly correlated with the development of postpartum endometritis, which decreases reproductive performance in dairy herds in Korea.

  3. Hazard identification and risk characterization of bisphenols A, F and AF to aquatic organisms.

    Science.gov (United States)

    Tišler, Tatjana; Krel, Alja; Gerželj, Urška; Erjavec, Boštjan; Dolenc, Marija Sollner; Pintar, Albin

    2016-05-01

    Production of bisphenol A (BPA) analogues such as bisphenol F (BPF) and bisphenol AF (BPAF) has recently increased, due to clear evidence of adverse effects of BPA on humans and wildlife. Bisphenols (BPs) have already been released into aquatic environment without previous available information about potential adverse effects of BPs and their potential risk to aquatic ecosystems. In this study, lethal and sublethal effects of BPF and BPAF to bacteria, algae, crustacea and fish embryos were investigated and the results were compared to the adverse effects obtained for BPA. We found that BPAF was the most toxic compound to Daphnia magna, Danio rerio and Desmodesmus subspicatus; the lowest 72 h EC50 (median effective concentration) and 21 d NOEC (no observed effect concentration) values were determined at 2.2 mg/L regarding zebrafish hatching success and 0.23 mg/L of BPAF obtained for growth and reproduction of water fleas, respectively. In most cases, BPA was more toxic to D. magna, D. rerio and D. subspicatus in comparison to BPF, but pigmentation of zebrafish embryos after 48 h of exposure and reproduction of water fleas after 21-day D. magna reproductive test exposure to BPF were much more impaired. Risk quotients (measured environmental concentration/21 d NOEC) showed that BPA, BPF and BPAF are recently not chronically hazardous to the survival, reproduction and growth of water fleas in surface waters. On the other hand, we importantly show that currently present BPAF concentrations in surface waters could cause a potential ecological risk to aquatic organisms. In the near future, higher concentrations of BPF and BPAF in surface waters are anticipated and for this reason further testing using test systems with various aquatic species and endpoints are needed to provide additional information about toxic impacts of BPF and BPAF on aquatic biota. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. The approach of toxic and radiological risk equivalence in UF6 transport

    International Nuclear Information System (INIS)

    Ringot, C.; Hamard, J.

    1989-01-01

    After a brief description of the present situation concerning the safety of the transport of UF6 and the new regulation project which is being developed under the behalf of IAEA, the equivalence of radioactive and chemical risks is considered for UF6 transport regulations. The concept of low specific activity appearing misfitting to toxic gas, it is proposed a quantity limit of material, T 2 (equivalent to A 2 for radioactive materials), for packagings which do not resist to accidental conditions, (9 m drop, 800 0 C, 30 minutes fire environment). It is proposed that this limit is chosen as the release rate which is acceptable after the IAEA tests for packages having a capacity higher than T 2 kilograms. The fire being considered as the most severe situation for the toxic risk, different possible scenarios are described. This approach of risk equivalence leads to impose that the packaging resists a 800 0 C - 30 minutes fire and that in this condition the release is less than T 2 . The problem of the behaviour of the shell and the openings (in particular the valve) is raised in this context [fr

  5. Toxic agent and radiation control: meeting the 1990 objectives for the nation

    International Nuclear Information System (INIS)

    Rall, D.P.

    1984-01-01

    Toxic agent and radiation control is 1 of the 15 health priority areas addressed through the Public Health Service's Objectives for the Nation. Several gains in moving toward the 1990 goals for toxic agent and radiation control have been recorded. Research and technical assistance, combined with legislation to reduce the amount of lead in gasoline, have contributed to a decrease in the mean blood lead level of the general population. New testing procedures have been developed to evaluate both reproductive and developmental toxicities of chemicals. Educational implementation of pelvimetry referral criteria in a multiyear study involving approximately 200 U.S. hospitals has resulted in a 50 percent reduction in the number of pelvimetries performed. Health-related responses have been given to environmental problems such as exposures to polychlorinated biphenyls (PCBs) in Massachusetts and Florida and exposures to dioxin in Missouri and New Jersey. Chemical records for some 1000 compounds likely to occur in chemical dumps or in bulk transit are being either created or updated to enhance online data retrieval services. For the foreseeable future, however, improvement of knowledge of the potential health risk posed by toxic chemicals and radiation must remain one of the most important priorities. To control toxic agents, development of surveillance systems and data bases are equally important

  6. Genetic variations, reproductive aging, and breast cancer risk in African American and European American women: The Women's Circle of Health Study.

    Science.gov (United States)

    Coignet, Marie V; Zirpoli, Gary Robert; Roberts, Michelle R; Khoury, Thaer; Bandera, Elisa V; Zhu, Qianqian; Yao, Song

    2017-01-01

    Reproductive aging phenotypes, including age at menarche (AM) and age at natural menopause (ANM), are well-established risk factors for breast cancer. In recent years, many genetic variants have been identified in association with AM and ANM in genome-wide association studies among European populations. Using data from the Women's Circle of Health Study (WCHS) of 1,307 European-American (EA) and 1,365 African-American (AA) breast cancer cases and controls, we aimed to replicate 53 earlier GWAS variants for AM and ANM in AA and EA groups and to perform analyses on total and net reproductive lifespan (TRLS; NRLS). Breast cancer risk was also examined in relation to a polygenic risk score (PRS) for each of the reproductive aging phenotypes. We replicated a number of variants in EA women, including rs7759938 in LIN28B for AM and rs16991615 in MCM8 for ANM; whereas in the AA group, only one SNP (rs2947411 in TMEM18) for AM was directionally consistent and nominally significant. In analysis of TRLS and NRLS, several SNPs were significant, including rs466639 in RXRG that was associated with both phenotypes in both AA and EA groups. None of the PRS was associated with breast cancer risk. Given the paucity of data available among AA populations, our study contributes to the literature of genetics of reproductive aging in AA women and highlights the importance of cross population replication of GWAS variants.

  7. Does the risk of sperm competition help explain cooperation between reproductive competitors? A study in the ocellated wrasse (Symphodus ocellatus).

    Science.gov (United States)

    Stiver, Kelly A; Alonzo, Suzanne H

    2013-03-01

    Although cooperating individuals may gain benefits, they risk being cheated by their allies. Therefore, to understand the persistence of cooperation by mutual benefits, it is important to document both the potential benefits of cooperation and the risks of cheating. We experimentally examined evidence of cooperation in the ocellated wrasse (Symphodus ocellatus), a fish species with males that exercise three reproductive strategies: satellite and sneaker males attempt to parasitically spawn in the nests of nesting males. Nesting males have been hypothesized to tolerate satellites as a result of satellite aid in defense against sneaker males and help in courting females. Here, we provide evidence that cooperation between reproductive competitors may arise in response to sperm competition from other males. After we experimentally removed satellites, nesting males had more sneakers at their nest and experienced a higher rate of sneaking when they spawned (increased sperm competition risk). When we experimentally distracted nesting males to prevent their acting aggressively toward satellites, satellites spawned with females and ate eggs in the nest. Our results suggest that nesting males and satellites gain fitness benefits of reduced direct reproductive and sperm competition through cooperation. However, nesting males risk losing paternity, while satellites experience increased aggression and must invest in aggression themselves (i.e., they act aggressively toward sneakers).

  8. Risk of poor neonatal outcome at term after medically assisted reproduction: a propensity score-matched study

    NARCIS (Netherlands)

    Ensing, Sabine; Abu-Hanna, Ameen; Roseboom, Tessa J.; Repping, Sjoerd; van der Veen, Fulco; Mol, Ben Willem J.; Ravelli, Anita C. J.

    2015-01-01

    To study risk of birth asphyxia and related morbidity among term singletons born after medically assisted reproduction (MAR). Population cohort study. Not applicable. A total of 1,953,932 term singleton pregnancies selected from a national registry for 1999-2011. None. Primary outcome Apgar score

  9. Towards an internationally harmonized test method for reproductive and developmental effects of endocrine disrupters in marine copepods

    DEFF Research Database (Denmark)

    Kusk, Kresten Ole; Wollenberger, Leah

    2007-01-01

    with marine copepods (Acartia tonsa, Nitocra spinipes, Tisbe battagliai, and Amphiascus tenuiremis). The present paper gives an overview on the endocrine system of crustaceans with special emphasis on development and reproduction, which are targets for endocrine disruption, and reviews available methods......New and updated methods to detect and characterize endocrine disrupting chemicals (EDCs) are urgently needed for the purpose of environmental risk assessment since these substances are often not detected using existing chronic toxicity tests. Numerous reports on the effects of EDCs on crustacean...... development and reproduction have been published and the development of life-cycle tests with crustaceans has been prioritized within the OECD work program for endocrine disrupter testing and assessment. As a result, Sweden, and Denmark initiated a proposal for development of a full life-cycle test...

  10. Age at menopause, reproductive history, and venous thromboembolism risk among postmenopausal women: the Women's Health Initiative Hormone Therapy clinical trials.

    Science.gov (United States)

    Canonico, Marianne; Plu-Bureau, Geneviève; O'Sullivan, Mary Jo; Stefanick, Marcia L; Cochrane, Barbara; Scarabin, Pierre-Yves; Manson, Joann E

    2014-03-01

    This study aims to investigate venous thromboembolism (VTE) risk in relation to age at menopause, age at menarche, parity, bilateral oophorectomy, and time since menopause, as well as any interaction with randomized hormone therapy (HT) assignment, among postmenopausal women. Using pooled data from the Women's Health Initiative HT clinical trials including 27,035 postmenopausal women aged 50 to 79 years who had no history of VTE, we assessed the risk of VTE in relation to age at menopause, age at menarche, parity, bilateral oophorectomy, and time since menopause by Cox proportional hazards models. Linear trends, quadratic relationships, and interactions of reproductive life characteristics with HT on VTE risk were systematically tested. During follow-up, 426 women reported a first VTE, including 294 non-procedure-related events. No apparent interaction of reproductive life characteristics with HT assignment on VTE risk was detected, and there was not a significant association between VTE and age at menarche, age at menopause, parity, oophorectomy, or time since menopause. However, analyses restricted to non-procedure-related VTE showed a U-shaped relationship between age at menopause and thrombotic risk that persisted after multivariable analysis (P menopause, those who had early menopause (age menopause (age >55 y) had a significantly increased VTE risk (hazard ratio [95% CI]: 1.8 [1.2-2.7] and 1.5 [1.0-2.4], respectively). Reproductive life characteristics have little association with VTE and do not seem to influence the effect of HT on thrombotic risk among postmenopausal women. Nevertheless, early and late onset of menopause might be newly identified risk factors for non-procedure-related VTE.

  11. Risk of Cancer in Children Conceived by Assisted Reproductive Technology.

    Science.gov (United States)

    Reigstad, Marte Myhre; Larsen, Inger Kristin; Myklebust, Tor Åge; Robsahm, Trude Eid; Oldereid, Nan Birgitte; Brinton, Louise A; Storeng, Ritsa

    2016-03-01

    An increasing number of children are born after assisted reproductive technology (ART), and monitoring their long-term health effects is of interest. This study compares cancer risk in children conceived by ART to that in children conceived without. The Medical Birth Registry of Norway contains individual information on all children born in Norway (including information of ART conceptions). All children born between 1984 and 2011 constituted the study cohort, and cancer data were obtained from the Cancer Registry of Norway. Follow-up started at date of birth and ended on the date of the first cancer diagnosis, death, emigration, or December 31, 2011. A Cox proportional hazards model was used to calculate hazard ratios (HR) and 95% confidence intervals (CI) of overall cancer risk between children conceived by ART and those not. Cancer risk was also assessed separately for all childhood cancer types. The study cohort comprised 1 628 658 children, of which 25 782 were conceived by ART. Of the total 4554 cancers, 51 occurred in ART-conceived children. Risk of overall cancer was not significantly elevated (HR 1.21; 95% CI 0.90-1.63). However, increased risk of leukemia was observed for children conceived by ART compared with those who were not (HR 1.67; 95% CI 1.02-2.73). Elevated risk of Hodgkin's lymphoma was also found for ART-conceived children (HR 3.63; 95% CI 1.12-11.72), although this was based on small numbers. This population-based cohort study found elevated risks of leukemia and Hodgkin's lymphoma in children conceived by ART. Copyright © 2016 by the American Academy of Pediatrics.

  12. Reproductive biology and its impact on body size: comparative analysis of mammalian, avian and dinosaurian reproduction.

    Science.gov (United States)

    Werner, Jan; Griebeler, Eva Maria

    2011-01-01

    Janis and Carrano (1992) suggested that large dinosaurs might have faced a lower risk of extinction under ecological changes than similar-sized mammals because large dinosaurs had a higher potential reproductive output than similar-sized mammals (JC hypothesis). First, we tested the assumption underlying the JC hypothesis. We therefore analysed the potential reproductive output (reflected in clutch/litter size and annual offspring number) of extant terrestrial mammals and birds (as "dinosaur analogs") and of extinct dinosaurs. With the exception of rodents, the differences in the reproductive output of similar-sized birds and mammals proposed by Janis and Carrano (1992) existed even at the level of single orders. Fossil dinosaur clutches were larger than litters of similar-sized mammals, and dinosaur clutch sizes were comparable to those of similar-sized birds. Because the extinction risk of extant species often correlates with a low reproductive output, the latter difference suggests a lower risk of population extinction in dinosaurs than in mammals. Second, we present a very simple, mathematical model that demonstrates the advantage of a high reproductive output underlying the JC hypothesis. It predicts that a species with a high reproductive output that usually faces very high juvenile mortalities will benefit more strongly in terms of population size from reduced juvenile mortalities (e.g., resulting from a stochastic reduction in population size) than a species with a low reproductive output that usually comprises low juvenile mortalities. Based on our results, we suggest that reproductive strategy could have contributed to the evolution of the exceptional gigantism seen in dinosaurs that does not exist in extant terrestrial mammals. Large dinosaurs, e.g., the sauropods, may have easily sustained populations of very large-bodied species over evolutionary time.

  13. Reproductive Biology and Its Impact on Body Size: Comparative Analysis of Mammalian, Avian and Dinosaurian Reproduction

    Science.gov (United States)

    Werner, Jan; Griebeler, Eva Maria

    2011-01-01

    Janis and Carrano (1992) suggested that large dinosaurs might have faced a lower risk of extinction under ecological changes than similar-sized mammals because large dinosaurs had a higher potential reproductive output than similar-sized mammals (JC hypothesis). First, we tested the assumption underlying the JC hypothesis. We therefore analysed the potential reproductive output (reflected in clutch/litter size and annual offspring number) of extant terrestrial mammals and birds (as “dinosaur analogs”) and of extinct dinosaurs. With the exception of rodents, the differences in the reproductive output of similar-sized birds and mammals proposed by Janis and Carrano (1992) existed even at the level of single orders. Fossil dinosaur clutches were larger than litters of similar-sized mammals, and dinosaur clutch sizes were comparable to those of similar-sized birds. Because the extinction risk of extant species often correlates with a low reproductive output, the latter difference suggests a lower risk of population extinction in dinosaurs than in mammals. Second, we present a very simple, mathematical model that demonstrates the advantage of a high reproductive output underlying the JC hypothesis. It predicts that a species with a high reproductive output that usually faces very high juvenile mortalities will benefit more strongly in terms of population size from reduced juvenile mortalities (e.g., resulting from a stochastic reduction in population size) than a species with a low reproductive output that usually comprises low juvenile mortalities. Based on our results, we suggest that reproductive strategy could have contributed to the evolution of the exceptional gigantism seen in dinosaurs that does not exist in extant terrestrial mammals. Large dinosaurs, e.g., the sauropods, may have easily sustained populations of very large-bodied species over evolutionary time. PMID:22194835

  14. Reproductive biology and its impact on body size: comparative analysis of mammalian, avian and dinosaurian reproduction.

    Directory of Open Access Journals (Sweden)

    Jan Werner

    Full Text Available Janis and Carrano (1992 suggested that large dinosaurs might have faced a lower risk of extinction under ecological changes than similar-sized mammals because large dinosaurs had a higher potential reproductive output than similar-sized mammals (JC hypothesis. First, we tested the assumption underlying the JC hypothesis. We therefore analysed the potential reproductive output (reflected in clutch/litter size and annual offspring number of extant terrestrial mammals and birds (as "dinosaur analogs" and of extinct dinosaurs. With the exception of rodents, the differences in the reproductive output of similar-sized birds and mammals proposed by Janis and Carrano (1992 existed even at the level of single orders. Fossil dinosaur clutches were larger than litters of similar-sized mammals, and dinosaur clutch sizes were comparable to those of similar-sized birds. Because the extinction risk of extant species often correlates with a low reproductive output, the latter difference suggests a lower risk of population extinction in dinosaurs than in mammals. Second, we present a very simple, mathematical model that demonstrates the advantage of a high reproductive output underlying the JC hypothesis. It predicts that a species with a high reproductive output that usually faces very high juvenile mortalities will benefit more strongly in terms of population size from reduced juvenile mortalities (e.g., resulting from a stochastic reduction in population size than a species with a low reproductive output that usually comprises low juvenile mortalities. Based on our results, we suggest that reproductive strategy could have contributed to the evolution of the exceptional gigantism seen in dinosaurs that does not exist in extant terrestrial mammals. Large dinosaurs, e.g., the sauropods, may have easily sustained populations of very large-bodied species over evolutionary time.

  15. Benefits and risks of ovarian function and reproduction for cancer development and prevention.

    Science.gov (United States)

    Schindler, Adolf E

    2011-12-01

    Ovarian function and menstrual cycle disturbances, pregnancy, and reproductive medicine procedures can either increase gynecological cancer risk or prevent cancer development. For ovarian cancer development, there are two hypotheses, which are connected with ovulation and gonadotropin secretion. Most of the ovarian cancers seem to be derived from displaced ovarian surfice epithelial cells. One year of ovulatory cycles increases the ovarian cancer risk by 6%. Ovulation between 22 and 29 years of age causes the highest risk increase per year. In contrast, progesterone or progestins appear to create protection. Lifestyle can affect or modify ovarian cancer risk. Breast cancer risk is very much related to age of menarche and menopause, pregnancy, and breast feeding. All of which are related to ovarian function and progestogenic impact that translates either into breast cancer risk increase or decrease. This is modified by body mass index, physical activity, and lifestyle in general. The risk of endometrial cancer is most closely related to endogenous progesterone during the menstrual cycle and pregnancy or by exogenous progestogens as in oral contraceptives. These effects are progestogen dose and time dependent. Endometrial cancer risk can also be increased by estrogen-producing tumors or long-term estrogen treatment.

  16. Developmental toxicity of engineered nanomaterials in rodents

    Energy Technology Data Exchange (ETDEWEB)

    Ema, Makoto, E-mail: ema-makoto@aist.go.jp; Gamo, Masashi; Honda, Kazumasa

    2016-05-15

    We summarized significant effects reported in the literature on the developmental toxicity of engineered nanomaterials (ENMs) in rodents. The developmental toxicity of ENMs included not only structural abnormalities, but also death, growth retardation, and behavioral and functional abnormalities. Most studies were performed on mice using an injection route of exposure. Teratogenic effects were indicated when multi-walled carbon nanotubes (MWCNTs), single-walled carbon nanotubes (SWCNTs), and TiO{sub 2}-nanoparticles were administered to mice during early gestation. Reactive oxygen species levels were increased in placentas and malformed fetuses and their placentas after prenatal exposure to MWCNTs and SWCNTs, respectively. The pre- and postnatal mortalities and growth retardation in offspring increased after prenatal exposure to ENMs. Histopathological and functional abnormalities were also induced in placentas after prenatal exposure to ENMs. Maternal exposure to ENMs induced behavioral alterations, histopathological and biochemical changes in the central nervous system, increased susceptibility to allergy, transplacental genotoxicity, and vascular, immunological, and reproductive effects in offspring. The size- and developmental stage-dependent placental transfer of ENMs was noted after maternal exposure. Silver accumulated in the visceral yolk sac after being injected with Ag-NPs during early gestation. Although currently available data has provided initial information on the potential developmental toxicity of ENMs, that on the developmental toxicity of ENMs is still very limited. Further studies using well-characterized ENMs, state-of the-art study protocols, and appropriate routes of exposure are required in order to clarify these developmental effects and provide information suitable for risk assessments of ENMs. - Highlights: • We review the developmental toxicity studies of engineered nanomaterials (ENMs). • Various developmental endpoints have been

  17. Acute and subacute toxicity of {sup 18}F-FDG; Toxicidade aguda e subaguda do radiofarmaco {sup 18}F-FDG

    Energy Technology Data Exchange (ETDEWEB)

    Dantas, Danielle Maia

    2013-07-01

    Before starting clinical trials of a new drug, it is necessary to perform a battery of safety tests for assessing human risk. Radiopharmaceuticals like any new drug must be tested taking into account its specificity, duration of treatment and especially the toxicity of both parties, the unlabeled molecule and its radionuclide, apart from impurities emanating from radiolysis. Regulatory agencies like the Food and Drug Administration - USA (FDA) and the European Medicine Agency (EMEA), establish guidelines for the regulation of production and research of radiopharmaceuticals. In Brazil the production of radiopharmaceuticals was not regulated until the end of 2009, when were established by the National Agency for Sanitary Surveillance (ANVISA) resolutions No. 63, which refers to the Good Manufacturing Practices of Radiopharmaceuticals and No. 64 which seeks the registration of record radiopharmaceuticals. To obtain registration of radiopharmaceuticals are necessary to prove the quality, safety, efficacy and specificity of the drug . For the safety of radiopharmaceuticals must be presented studies of acute toxicity, subacute and chronic toxicity as well as reproductive, mutagenic and carcinogenic. Nowadays IPEN-CNEN/SP produces one of the most important radiopharmaceutical of nuclear medicine, the {sup 18}F-FDG, which is used in many clinical applications, particularly in the diagnosis and staging of tumors. The objective of this study was to evaluate the systemic toxicity (acute/ subacute) radiopharmaceutical {sup 18}F-FDG in an in vivo test system, as recommended by the RDC No. 64, which will serve as a model for protocols toxicity of radiopharmaceuticals produced at IPEN. The following tests were performed: tests of acute and subacute toxicity, biodistribution studies of {sup 18}F-FDG, comet assay and reproductive toxicity. In acute toxicity, healthy rats were injected . (author)

  18. Limitations of the toxic equivalency factor (TEF) approach for risk assessment of halogenated aromatic hydrocarbons

    Energy Technology Data Exchange (ETDEWEB)

    Safe, S. [Texas A and M Univ., College Station, TX (United States). Dept. of Veterinary Physiology and Pharmacology

    1995-12-31

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and related halogenated aromatic hydrocarbons (HAHs) are present as complex mixtures of polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs) and biphenyls (PCBs) in most environmental matrices. Risk management of these mixtures utilize the toxic equivalency factor (TEF) approach in which the TCDD (dioxin) or toxic equivalents of a mixture is a summation of the congener concentration (Ci) times TEF{sub i} (potency relative to TCDD) where. TEQ{sub mixture} = {Sigma}[Cil] {times} TEF{sub i}. TEQs are determined only for those HAHs which are aryl hydrocarbon (Ah) receptor agonists and this approach assumes that the toxic or biochemical effects of individual compounds in a mixture are additive. Several in vivo and in vitro laboratory and field studies with different HAH mixtures have been utilized to validate the TEF approach. For some responses, the calculated toxicities of PCDD/PCDF and PCB mixtures predict the observed toxic potencies. However, for fetal cleft palate and immunotoxicity in mice, nonadditive (antagonistic) responses are observed using complex PCB mixtures or binary mixtures containing an Ah receptor agonist with 2,2{prime},4,4{prime},5,5{prime}-hexachlorobiphenyl (PCB153). The potential interactive effects of PCBs and other dietary Ah receptor antagonist suggest that the TEF approach for risk management of HAHs requires further refinement and should be used selectively.

  19. An empirical study of the toxic capsule crisis in China: risk perceptions and behavioral responses.

    Science.gov (United States)

    Feng, Tianjun; Keller, L Robin; Wu, Ping; Xu, Yifan

    2014-04-01

    The outbreak of the toxic capsule crisis during April 2012 aroused widespread public concern about the risk of chromium-contaminated capsules and drug safety in China. In this article, we develop a conceptual model to investigate risk perceptions of the pharmaceutical drug capsules and behavioral responses to the toxic capsule crisis and the relationship between associated factors and these two variables. An online survey was conducted to test the model, including questions on the measures of perceived efficacy of the countermeasures, trust in the State FDA (Food and Drug Administration), trust in the pharmaceutical companies, trust in the pharmaceutical capsule producers, risk perception, concern, need for information, information seeking, and risk avoidance. In general, participants reported higher levels of risk perception, concern, and risk avoidance, and lower levels of trust in the three different stakeholders. The results from the structural equation modeling procedure suggest that perceived efficacy of the countermeasures is a predictor of each of the three trust variables; however, only trust in the State FDA has a dampening impact on risk perception. Both risk perception and information seeking are significant determinants of risk avoidance. Risk perception is also positively related to concern. Information seeking is positively related to both concern and need for information. The theoretical and policy implications are also discussed. © 2013 Society for Risk Analysis.

  20. Toxic-metabolic Risk Factors in Pediatric Pancreatitis: Recommendations for Diagnosis, Management, and Future Research.

    Science.gov (United States)

    Husain, Sohail Z; Morinville, Veronique; Pohl, John; Abu-El-Haija, Maisam; Bellin, Melena D; Freedman, Steve; Hegyi, Peter; Heyman, Melvin B; Himes, Ryan; Ooi, Chee Y; Schwarzenberg, Sarah J; Usatin, Danielle; Uc, Aliye

    2016-04-01

    Pancreatitis in children can result from metabolic and toxic risk factors, but the evidence linking these factors is sparse. We review the evidence for association or causality of these risk factors in pancreatitis, discuss management strategies, and their rationale. We conducted a review of the pediatric pancreatitis literature with respect to the following risk factors: hyperlipidemia, hypercalcemia, chronic renal failure, smoking exposure, alcohol, and medications. Areas of additional research were identified. Hypertriglyceridemia of 1000 mg/dL or greater poses an absolute risk for pancreatitis; persistent elevations of calcium are predisposing. Further research is necessary to determine whether end-stage renal disease leads to increased pancreatitis in children similar to adults. It is unknown whether cigarette smoking exposure, which clearly increases risk in adults, also increases risk in children. The role of alcohol in pediatric pancreatitis, whether direct or modifying, needs to be elucidated. The evidence supporting most cases of medication-induced pancreatitis is poor. Drug structure, improper handling of drug by host, and bystander status may be implicated. Other pancreatitis risk factors must be sought in all cases. The quality of evidence supporting causative role of various toxic and metabolic factors in pediatric pancreatitis is variable. Careful phenotyping is essential, including search for other etiologic risk factors. Directed therapy includes correction/removal of any agent identified, and general supportive measures. Further research is necessary to improve our understanding of these pancreatitis risk factors in children.

  1. Tubal Factor Infertility and Perinatal Risk After Assisted Reproductive Technology

    Science.gov (United States)

    Kawwass, Jennifer F.; Crawford, Sara; Kissin, Dmitry M.; Session, Donna R.; Boulet, Sheree; Jamieson, Denise J.

    2014-01-01

    OBJECTIVE To assess trends of tubal factor infertility and to evaluate risk of miscarriage and delivery of preterm or low birth weight (LBW) neonates among women with tubal factor infertility using assisted reproductive technology (ART). METHODS We assessed trends of tubal factor infertility among all fresh and frozen, donor, and nondonor ART cycles performed annually in the United States between 2000 and 2010 (N=1,418,774) using the National ART Surveillance System. The data set was then limited to fresh, nondonor in vitro fertilization cycles resulting in pregnancy to compare perinatal outcomes for cycles associated with tubal compared with male factor infertility. We performed bivariate and multivariable analyses controlling for maternal characteristics and calculated adjusted risk ratios (RRs) and 95% confidence intervals (CI). RESULTS The percentage of ART cycles associated with tubal factor infertility diagnoses decreased from 2000 to 2010 (26.02–14.81%). Compared with male factor infertility, tubal factor portended an increased risk of miscarriage (14.0% compared with 12.7%, adjusted RR 1.08, 95% CI 1.04–1.12); risk was increased for both early and late miscarriage. Singleton neonates born to women with tubal factor infertility had an increased risk of pre-term birth (15.8% compared with 11.6%, adjusted RR 1.27, 95% CI 1.20–1.34) and LBW (10.9% compared with 8.5%, adjusted RR 1.28, 95% CI 1.20–1.36). Significant increases in risk persisted for early and late preterm delivery and very low and moderately LBW delivery. A significantly elevated risk was also detected for twin, but not triplet, pregnancies. CONCLUSION Tubal factor infertility, which is decreasing in prevalence in the United States, is associated with an increased risk of miscarriage, preterm birth, and LBW delivery as compared with couples with male factor infertility using ART. PMID:23812461

  2. Endocrine control of epigenetic mechanisms in male reproduction.

    Science.gov (United States)

    Ankolkar, Mandar; Balasinor, N H

    2016-01-01

    Endocrine control of reproduction is very well known and has been echoed by many research groups. However, recent developments point to the ability of toxic endocrine disrupting chemicals (EDC) to alter epigenetic information of the gametes which gets transferred to the developing embryo and affects the immediate reproductive outcome or even persists transgenerationally. These epigenetic aberrations contribute to the ensuing pathophysiology of reproductive disorders. Investigations of the female in cases of poor reproductive outcome have been the main strategy towards diagnosis. However, despite the male partner contributing half of his genome to the progeny, thorough investigations in the male have been ignored. Environmental pollutants are all pervading and are encountered in our day-to-day life. Many of these pollutants have potential to disrupt the endocrine system. Here, we discuss how the male gametes (spermatozoa) are susceptible to a myriad of epigenetic insults inflicted by exposure to endocrine disruptors and how important is the contribution of the epigenetic marks of the spermatozoa in healthy reproduction. We advocate that sperm epigenetics should be considered as a significant contributor to reproductive health and should be researched further and be subsequently included in routine diagnostic workup in cases of poor reproductive outcome.

  3. Ecotoxicogenomic assessment of diclofenac toxicity in soil

    International Nuclear Information System (INIS)

    Chen, Guangquan; Braver, Michiel W. den; Gestel, Cornelis A.M. van; Straalen, Nico M. van; Roelofs, Dick

    2015-01-01

    Diclofenac is widely used as nonsteroidal anti-inflammatory drug leaving residues in the environment. To investigate effects on terrestrial ecosystems, we measured dissipation rate in soil and investigated ecotoxicological and transcriptome-wide responses in Folsomia candida. Exposure for 4 weeks to diclofenac reduced both survival and reproduction of F. candida in a dose-dependent manner. At concentrations ≥200 mg/kg soil diclofenac remained stable in the soil during a 21-day incubation period. Microarrays examined transcriptional changes at low and high diclofenac exposure concentrations. The results indicated that development and growth were severely hampered and immunity-related genes, mainly directed against bacteria and fungi, were significantly up-regulated. Furthermore, neural metabolic processes were significantly affected only at the high concentration. We conclude that diclofenac is toxic to non-target soil invertebrates, although its mode of action is different from the mammalian toxicity. The genetic markers proposed in this study may be promising early markers for diclofenac ecotoxicity. - Highlights: • Diclofenac is toxic to the non-target soil invertebrate Folsomia candida. • Diclofenac mainly caused mortality and thus only indirectly affected reproduction. • Diclofenac mode of action in F. candida was checked with gene expression profiling. • Diclofenac significantly affected development, growth and immune related processes. • Diclofenac nervous system activity in F. candida was different from that in mammals. - Diclofenac is toxic to non-target soil invertebrates with a mode of action clearly different from mammalian toxicity

  4. The risk of contamination of food with toxic substances present in animal feed

    NARCIS (Netherlands)

    Kan, C.A.; Meijer, G.A.L.

    2007-01-01

    Toxic substances such as dioxins, mycotoxins, heavy metals, pesticides, veterinary drugs and polycyclic aromatic hydrocarbons are almost ubiquitous in the environment. Thus, they are also present in ingredients for animal feed. Adequate risk management depends on knowledge of absorption, metabolism,

  5. Reproductive studies with the anti-inflammatory agent, piroxicam: modification of classical protocols.

    Science.gov (United States)

    Perraud, J; Stadler, J; Kessedjian, M J; Monro, A M

    1984-02-14

    Reproductive toxicology studies were conducted in rabbits and rats given piroxicam, a non-steroidal anti-inflammatory agent (NSAI), orally at 2, 5 and 10 mg/kg/day. In teratology studies there was neither drug-related embryotoxicity nor teratogenicity. As piroxicam, like other NSAI, affects parturition in rats and leads to a progressive toxicity in lactating females, standard protocols were modified: dams of the female fertility study were treated from 2 weeks prior to mating until day 6 of gestation and females of the post-natal toxicity study were treated from parturition until day 12 of lactation. No other adverse effects on reproduction, fertility and postnatal development were observed.

  6. Nanoparticle interactions with co-existing contaminants: joint toxicity, bioaccumulation and risk.

    Science.gov (United States)

    Deng, Rui; Lin, Daohui; Zhu, Lizhong; Majumdar, Sanghamitra; White, Jason C; Gardea-Torresdey, Jorge L; Xing, Baoshan

    2017-06-01

    With their growing production and application, engineered nanoparticles (NPs) are increasingly discharged into the environment. The released NPs can potentially interact with pre-existing contaminants, leading to biological effects (bioaccumulation and/or toxicity) that are poorly understood. Most studies on NPs focus on single analyte exposure; the existing literature on joint toxicity of NPs and co-existing contaminants is rather limited but beginning to develop rapidly. This is the first review paper evaluating the current state of knowledge regarding the joint effects of NPs and co-contaminants. Here, we review: (1) methods for investigating and evaluating joint effects of NPs and co-contaminants; (2) simultaneous toxicities from NPs co-exposed with organic contaminants, metal/metalloid ions, dissolved organic matter (DOM), inorganic ligands and additional NPs; and (3) the influence of NPs co-exposure on the bioaccumulation of organic contaminants and heavy metal ions, as well as the influence of contaminants on NPs bioaccumulation. In addition, future research needs are discussed so as to better understand risk associated with NPs-contaminant co-exposure.

  7. Maternal and neonatal health outcomes following assisted reproduction.

    Science.gov (United States)

    Farhi, A; Reichman, B; Boyko, V; Hourvitz, A; Ron-El, R; Lerner-Geva, L

    2013-05-01

    This study assessed the risk for maternal complications in women and neonatal outcomes in children conceived following assisted reproductive treatment as compared with spontaneously conception and also separately evaluated conventional IVF and intracytoplasmic sperm injection (ICSI). The prospective cohort included 1161 women with singleton pregnancies: 561 who conceived following assisted reproduction (223 following IVF and 338 following ICSI) and 600 who conceived spontaneously. No differences were observed in pregnancy complications (including spontaneous abortion, pregnancy-induced hypertension, gestational diabetes and Caesarean delivery) except for significantly increased risk for excess vaginal bleeding in assisted reproduction pregnancies (21.4% versus 12.9%; OR 1.67, 95% CI 1.18-2.37), which was prominent in women who reported polycystic ovary syndrome. Neonates born following assisted reproduction had increased risk for prematurity (10.6% versus 5.3%; OR 1.72, 95% CI 1.04-2.87), and IVF, but not ICSI, was associated with significantly increased risk for prematurity (OR 2.36, 95% CI 1.28-4.37) and low birthweight (OR 1.89, 95% CI 1.03-3.46). In conclusion, this study observed only an increased risk for excess vaginal bleeding as a pregnancy-associated complication in singleton pregnancies following assisted compared with spontaneous conception. However, singleton neonates born following IVF, but not ICSI, were at increased risk for prematurity. Copyright © 2013 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  8. A family planning clinic partner violence intervention to reduce risk associated with reproductive coercion

    Science.gov (United States)

    Miller, Elizabeth; Decker, Michele R.; McCauley, Heather L.; Tancredi, Daniel J.; Levenson, Rebecca R.; Waldman, Jeffrey; Schoenwald, Phyllis; Silverman, Jay G.

    2010-01-01

    Background This study examined the efficacy of a family planning clinic-based intervention to address intimate partner violence (IPV) and reproductive coercion. Study Design Four free-standing urban family planning clinics in Northern California were randomized to intervention (trained family planning counselors) or standard-of-care. English-and Spanish-speaking females ages 16-29 years (N=906) completed audio computer-assisted surveys prior to a clinic visit and 12 to 24 weeks later (75% retention rate). Analyses included assessment of intervention effects on recent IPV, awareness of IPV services, and reproductive coercion. Results Among women reporting past 3-month IPV at baseline, there was a 71% reduction in the odds of pregnancy coercion among participants in intervention clinics compared to participants from the control clinics that provided standard of care. Women in the intervention arm were more likely to report ending a relationship because the relationship was unhealthy or unsafe regardless of IPV status (AOR 1.63, 95% CI 1.01 – 2.63). Conclusions Results of this pilot study suggest that this intervention may reduce risk for reproductive coercion from abusive male partners among family planning clients and support such women to leave unsafe relationships. PMID:21310291

  9. The ethics of human reproductive cloning.

    Science.gov (United States)

    Strong, Carson

    2005-03-01

    This article addresses the question of whether human reproductive cloning could be ethically justifiable in at least some cases involving infertile couples who would choose cloning as a way to have a genetically related child. At present, the risk of congenital anomalies constitutes a compelling argument against human reproductive cloning. The article explores whether reproductive cloning could be ethically justifiable if, at some future time, cloning becomes possible without an elevated risk of anomalies. It is argued that freedom to use cloning is a form of procreative freedom and, as such, deserves respect. All of the objections that have been raised against human reproductive cloning fall under three main categories: those that appeal to the interests of the child, those based on consequences for society, and those arising from teleological views. Objections that appeal to the child's interests are, in turn, of two main kinds: consequentialist and deontological. All of these types of objections are examined, and it is found that each involves serious problems that prevent it from being a reasonable objection in the context of the infertility cases considered. It is concluded that human reproductive cloning would be ethically justifiable in at least some cases involving infertile couples, provided that it could be performed without an elevated risk of anomalies.

  10. Are repeated assisted reproductive technology treatments and an unsuccessful outcome risk factors for unipolar depression in infertile women?

    DEFF Research Database (Denmark)

    Sejbaek, Camilla S; Pinborg, Anja; Hageman, Ida

    2015-01-01

    of unipolar depression compared with women with a live birth after ART treatment. MATERIAL AND METHODS: The Danish National ART-Couple (DANAC) Cohort is a national register-based cohort study that consists of women who received ART treatment from 1 January 1994 to 30 September 2009, in Denmark (n = 41 050......INTRODUCTION: Previous studies have shown conflicting results whether unsuccessful medically assisted reproduction is a risk factor for depression among women. This study therefore investigated if women with no live birth after assisted reproductive technology (ART) treatment had a higher risk......). Information on unipolar depression was obtained from the Danish Psychiatric Central Research Register. The analyses were conducted in Cox regression analysis. RESULTS: During the 308 494 person-years of follow up, 552 women were diagnosed with unipolar depression. A Cox proportional hazards model showed...

  11. Polycystic Ovary Syndrome: Important Underrecognised Cardiometabolic Risk Factor in Reproductive-Age Women

    Science.gov (United States)

    Baldani, Dinka Pavicic; Skrgatic, Lana; Ougouag, Roya

    2015-01-01

    Polycystic ovary syndrome (PCOS) is the most common endocrine disorder amongst women of reproductive age. Although PCOS is diagnosed exclusively based on reproductive criteria, it is also a metabolic disorder. Insulin resistance, impaired glucose tolerance, type 2 diabetes mellitus, obesity, and dyslipidemia are more common in women with PCOS than in age-comparable women without PCOS. Many of the metabolic abnormalities that manifest in PCOS are worsened by the concurrent incidence of obesity. However, some of these metabolic perturbations occur even in lean women with PCOS and therefore are rightfully recognized as intrinsic to PCOS. The intrinsic factors that produce these metabolic disturbances are reviewed in this paper. The consequences of obesity and the other metabolic aberrations are also discussed. The metabolic perturbations in PCOS patients lead to chronic low-grade inflammation and to cardiovascular impairments that heighten the risk of having cardiovascular disease. Even though many studies have shown an elevation in surrogate biomarkers of cardiovascular disease in PCOS women, it is still not clear to what extent and magnitude the elevation precipitates more frequent and earlier events. PMID:26124830

  12. Polycystic Ovary Syndrome: Important Underrecognised Cardiometabolic Risk Factor in Reproductive-Age Women

    Directory of Open Access Journals (Sweden)

    Dinka Pavicic Baldani

    2015-01-01

    Full Text Available Polycystic ovary syndrome (PCOS is the most common endocrine disorder amongst women of reproductive age. Although PCOS is diagnosed exclusively based on reproductive criteria, it is also a metabolic disorder. Insulin resistance, impaired glucose tolerance, type 2 diabetes mellitus, obesity, and dyslipidemia are more common in women with PCOS than in age-comparable women without PCOS. Many of the metabolic abnormalities that manifest in PCOS are worsened by the concurrent incidence of obesity. However, some of these metabolic perturbations occur even in lean women with PCOS and therefore are rightfully recognized as intrinsic to PCOS. The intrinsic factors that produce these metabolic disturbances are reviewed in this paper. The consequences of obesity and the other metabolic aberrations are also discussed. The metabolic perturbations in PCOS patients lead to chronic low-grade inflammation and to cardiovascular impairments that heighten the risk of having cardiovascular disease. Even though many studies have shown an elevation in surrogate biomarkers of cardiovascular disease in PCOS women, it is still not clear to what extent and magnitude the elevation precipitates more frequent and earlier events.

  13. Polycystic Ovary Syndrome: Important Underrecognised Cardiometabolic Risk Factor in Reproductive-Age Women.

    Science.gov (United States)

    Baldani, Dinka Pavicic; Skrgatic, Lana; Ougouag, Roya

    2015-01-01

    Polycystic ovary syndrome (PCOS) is the most common endocrine disorder amongst women of reproductive age. Although PCOS is diagnosed exclusively based on reproductive criteria, it is also a metabolic disorder. Insulin resistance, impaired glucose tolerance, type 2 diabetes mellitus, obesity, and dyslipidemia are more common in women with PCOS than in age-comparable women without PCOS. Many of the metabolic abnormalities that manifest in PCOS are worsened by the concurrent incidence of obesity. However, some of these metabolic perturbations occur even in lean women with PCOS and therefore are rightfully recognized as intrinsic to PCOS. The intrinsic factors that produce these metabolic disturbances are reviewed in this paper. The consequences of obesity and the other metabolic aberrations are also discussed. The metabolic perturbations in PCOS patients lead to chronic low-grade inflammation and to cardiovascular impairments that heighten the risk of having cardiovascular disease. Even though many studies have shown an elevation in surrogate biomarkers of cardiovascular disease in PCOS women, it is still not clear to what extent and magnitude the elevation precipitates more frequent and earlier events.

  14. Use of hydra for chronic toxicity assessment of waters intended for human consumption

    International Nuclear Information System (INIS)

    Arkhipchuk, Victor V.; Blaise, Christian; Malinovskaya, Maria V.

    2006-01-01

    Methods developed with the cnidarian, Hydra attenuata (Pallas), have proven effective for screening acute toxicity in aqueous samples, whereas their use in revealing (sub)chronic toxic effects have had mitigated success. We therefore sought to explore manifestations of hydra mortality and abnormal morphological changes, as well as the reproductive capacity of hydras to further enhance the bioassay sensitivity and to assess (sub)chronic toxicity. These parameters were recorded following the onset of experiments after 8, 12 and 19-21 days of hydra exposure. Results obtained with potable waters (30 brands of bottled waters and artesian waters from 9 wells) showed chronic sublethal and lethal effects or reproduction rate inhibition for most samples. The effectiveness of the hydra toxicity test was demonstrated in comparison with other widely used bioassays. Our previous and present investigations suggest that hydra is a reliable and relevant test organism for the assessment of acute and chronic water toxicity. - Hydra is a reliable and relevant test organism for the assessment of acute and chronic toxicity of waters intended for human consumption

  15. The Role of Biomarkers in Decreasing Risk of Cardiac Toxicity after Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Christine Henri

    2016-01-01

    Full Text Available With the improvement of cancer therapy, survival related to malignancy has improved, but the prevalence of long-term cardiotoxicity has also increased. Cancer therapies with known cardiac toxicity include anthracyclines, biologic agents (trastuzumab, and multikinase inhibitors (sunitinib. The most frequent presentation of cardiac toxicity is dilated cardiomyopathy associated with poorest prognosis. Monitoring of cardiac toxicity is commonly performed by assessment of left ventricular (LV ejection fraction, which requires a significant amount of myocardial damage to allow detection of cardiac toxicity. Accordingly, this creates the impetus to search for more sensitive and reproducible biomarkers of cardiac toxicity after cancer therapy. Different biomarkers have been proposed to that end, the most studied ones included troponin release resulting from cardiomyocyte damage and natriuretic peptides reflecting elevation in LV filling pressure and wall stress. Increase in the levels of troponin and natriuretic peptides have been correlated with cumulative dose of anthracycline and the degree of LV dysfunction. Troponin is recognized as a highly efficient predictor of early and chronic cardiac toxicity, but there remains some debate regarding the clinical usefulness of the measurement of natriuretic peptides because of divergent results. Preliminary data are available for other biomarkers targeting inflammation, endothelial dysfunction, myocardial ischemia, and neuregulin-1. The purpose of this article is to review the available data to determine the role of biomarkers in decreasing the risk of cardiac toxicity after cancer therapy.

  16. Reproductive/developmental toxicity and immunotoxicity assessment in the nonhuman primate model

    International Nuclear Information System (INIS)

    Buse, Eberhard; Habermann, Gunnar; Osterburg, Ingrid; Korte, Rainhart; Weinbauer, Gerhard F.

    2003-01-01

    Nonhuman primates are being used increasingly as a non-rodent animal model during preclinical toxicology and safety assessment on the basis of proven similarity and comparability between nonhuman primates and humans. The validity of the nonhuman primate models applies to many aspects of toxicological testing and holds particularly true for the evaluation of reproductive toxicology and developmental toxicology. More recently, the advent of humanized antibodies and vaccines imposed further demand on nonhuman primate models since many immunotherapeutics do not interact with rodent receptors but frequently only cross-react with primate tissue. In this paper we discuss the suitability of primate models for reproductive, developmental and immunotoxicology testing, and present our initial data on the development of lymphatic organs and immune system in a nonhuman primate model

  17. Integrative rodent models for assessing male reproductive toxicity of environmental endocrine active substances

    Directory of Open Access Journals (Sweden)

    Jacques Auger

    2014-02-01

    Full Text Available In the present review, we first summarize the main benefits, limitations and pitfalls of conventional in vivo approaches to assessing male reproductive structures and functions in rodents in cases of endocrine active substance (EAS exposure from the postulate that they may provide data that can be extrapolated to humans. Then, we briefly present some integrated approaches in rodents we have recently developed at the organism level. We particularly focus on the possible effects and modes of action (MOA of these substances at low doses and in mixtures, real-life conditions and at the organ level, deciphering the precise effects and MOA on the fetal testis. It can be considered that the in vivo experimental EAS exposure of rodents remains the first choice for studies and is a necessary tool (together with the epidemiological approach for understanding the reproductive effects and MOA of EASs, provided the pitfalls and limitations of the rodent models are known and considered. We also provide some evidence that classical rodent models may be refined for studying the multiple consequences of EAS exposure, not only on the reproductive axis but also on various hormonally regulated organs and tissues, among which several are implicated in the complex process of mammalian reproduction. Such models constitute an interesting way of approaching human exposure conditions. Finally, we show that organotypic culture models are powerful complementary tools, especially when focusing on the MOA. All these approaches have contributed in a combinatorial manner to a better understanding of the impact of EAS exposure on human reproduction.

  18. Application of rotifer Brachionus plicatilis in detecting the toxicity of harmful algae

    Science.gov (United States)

    Yan, Tian; Wang, Yunfeng; Wang, Liping; Chen, Yang; Han, Gang; Zhou, Mingjiang

    2009-05-01

    The toxicity of seven major HAB (harmful algal bloom) species/strains, Prorocentrum donghaiense, Phaeocystis globosa, Prorocentrum micans, Alexandrium tamarense (AT-6, non-PSP producer), Alexandrium lusitanicum, Alexandrum tamarense (ATHK) and Heterosigma akashiwo were studied against rotifer Brachionus plicatilis under laboratory conditions. The results show that P. donghaiense, P. globosa, P. micans, A. tamarense (AT-6), or A. lusitanicum could maintain the individual survival and reproduction, as well as the population increase of the rotifer, but the individual reproduction would decrease when exposed to these five algae at higher densities for nine days; H. akashiwo could decrease the individual survival and reproduction, as well as population increase of the rotifer, which is similar to that of the starvation group, indicating that starvation might be its one lethal factor except for the algal toxins; A. tamarense (ATHK) has strong lethal effect on the rotifer with 48h LC50 at 800 cells/mL. The experiment on ingestion ability indicated by gut pigment change shows that P. donghaiense, P. globosa, P. micans, A. tamarense (AT-6) and A. lusitanicum can be taken by the rotifers as food, but A. tamarense (ATHK) or H. akashiwo can be ingested by the rotifers. The results indicate that all the indexes of individual survival and reproduction, population increase, gut pigment change of the rotifers are good and convenient to be used to reflect the toxicities of HAB species. Therefore, rotifer is suggested as one of the toxicity testing organisms in detecting the toxicity of harmful algae.

  19. Scenario-targeted toxicity assessment through multiple endpoint bioassays in a soil posing unacceptable environmental risk according to regulatory screening values.

    Science.gov (United States)

    Rodriguez-Ruiz, A; Etxebarria, J; Boatti, L; Marigómez, I

    2015-09-01

    Lanestosa is a chronically polluted site (derelict mine) where the soil (Lanestosa (LA) soil) exceeds screening values (SVs) of regulatory policies in force (Basque Country; Europe) for Zn, Pb and Cd. A scenario-targeted toxicity assessment was carried out on the basis of a multi-endpoint bioassay approach. Acute and chronic toxicity bioassays were conducted with selected test species (Vibrio fischeri, Dictyostelium discoideum, Lactuca sativa, Raphanus sativus and Eisenia fetida) in combination with chemical analysis of soils and elutriates and with bioaccumulation studies in earthworms. Besides, the toxicity profile was compared with that of the mine runoff (RO) soil and of a fresh artificially polluted soil (LAAPS) resembling LA soil pollutant profile. Extractability studies in LA soil revealed that Pb, Zn and Cd were highly available for exchange and/or release into the environment. Indeed, Pb and Zn were accumulated in earthworms and LA soil resulted to be toxic. Soil respiration, V. fischeri, vegetative and developmental cycles of D. discoideum and survival and juvenile production of E. fetida were severely affected. These results confirmed that LA soil had unacceptable environmental risk and demanded intervention. In contrast, although Pb and Zn concentrations in RO soil revealed also unacceptable risk, both metal extractability and toxicity were much lower than in LA soil. Thus, within the polluted site, the need for intervention varied between areas that posed dissimilar risk. Besides, since LAAPS, with a high exchangeable metal fraction, was the most toxic, ageing under in situ natural conditions seemingly contributed to attenuate LA soil risk. As a whole, combining multi-endpoint bioassays with scenario-targeted analysis (including leaching and ageing) provides reliable risk assessment in soils posing unacceptable environmental risk according to SVs, which is useful to optimise the required intervention measures.

  20. Maternal reproductive history and the risk of isolated congenital malformations.

    Science.gov (United States)

    Materna-Kiryluk, A; Więckowska, B; Wiśniewska, K; Borszewska-Kornacka, M K; Godula-Stuglik, U; Limon, J; Rusin, J; Sawulicka-Oleszczuk, H; Szwałkiewicz-Warowicka, E; Walczak, M

    2011-03-01

    We examined the relationship between maternal reproductive history and the newborn's risk of isolated congenital malformations in a large case-control cohort from the Polish Registry of Congenital Malformations. Congenital malformations were classified into four categories: isolated congenital heart defects (n=1673), isolated cleft palate (n=255), cleft lip with or without cleft palate (n=448) and renal agenesis (n=103). The case groups were compared with a shared group of 2068 controls recruited in the same time period and geographic area. Multivariable logistic regression was used to assess the risk associated with maternal gravidity and of previous miscarriages after accounting for maternal age and other potential risk factors. In unadjusted analyses, maternal gravidity was significantly associated with increased risk of all four classes of congenital malformations. After adjustment, a significant association persisted for congenital heart defects [odds ratio (OR)=1.22, [95% confidence interval (CI) 1.09, 1.36], P=0.0007] and cleft lip with or without cleft palate (OR=1.21, [95% CI 1.09, 1.36], P=0.0005). A similar trend existed for isolated cleft palate (OR=1.18, [95% CI 1.02, 1.37], P=0.03). There was no appreciable increase in the risk of congenital malformations associated with a maternal history of miscarriages, but a trend for a protective effect on the occurrence of cleft lip with or without cleft palate was observed (OR=0.72, [95% CI 0.52, 0.99], P=0.045). Based on our data, maternal gravidity represents a significant risk factor for congenital heart defects and cleft lip with or without cleft palate in the newborn infant. Our data do not support an increase in risk because of past history of miscarriages. © 2011 Blackwell Publishing Ltd.

  1. Evaluation of toxic effects of metformin hydrochloride and ...

    African Journals Online (AJOL)

    olayemitoyin

    Drug Metabolism and Toxicology Research Laboratories, Department of ... This study was designed to investigate the toxic effect of MET and GB in the Liver, kidney and testis of rats. Twenty one ..... glibenclamide on male reproductive system,.

  2. Environmental & lifestyle factors in deterioration of male reproductive health

    Directory of Open Access Journals (Sweden)

    Sunil Kumar

    2014-01-01

    Full Text Available Background & objectives: Male reproductive function in the general population has been receiving attention in recent years due to reports of various reproductive and developmental defects, which might be associated with various lifestyle and environmental factors. This study was carried out to determine the role of various lifestyle and environmental factors in male reproduction and their possible association with declining semen quality, increased oxidative stress as well as sperm DNA damage. Methods: Semen samples were obtained from 240 male partners of the couples consulting for infertility problem. Semen analysis was carried out using WHO criteria and subjects were categorized on the basis of self reported history of lifestyle as well as environmental exposure. The oxidative and antioxidant markers; lipid peroxidation (LPO, superoxide dismutase (SOD and catalase (CAT as well as DNA damage by acridine orange test (AO were determined. Results: The presence of abnormal semen parameters was significantly higher among the lifestyle and/or environmental exposed subjects as compared to the non-exposed population. Further, the levels of antioxidants were reduced and sperm DNA damage was more among the lifestyle and/or environmental exposed subjects, though the changes were not significant. Interpretation & conclusions: These findings indicated that various lifestyle factors such as tobacco smoking, chewing and alcohol use as well as exposure to toxic agents might be attributed to the risk of declining semen quality and increase in oxidative stress and sperm DNA damage.

  3. Reproductive factors and risk of hormone receptor positive and negative breast cancer: a cohort study

    International Nuclear Information System (INIS)

    Ritte, Rebecca; Grote, Verena; Boeing, Heiner; Aleksandrova, Krasimira; Trichopoulou, Antonia; Lagiou, Pagona; Trichopoulos, Dimitrios; Palli, Domenico; Berrino, Franco; Mattiello, Amalia; Tumino, Rosario; Tikk, Kaja; Sacerdote, Carlotta; Quirós, José Ramón; Buckland, Genevieve; Molina-Montes, Esther; Chirlaque, María-Dolores; Ardanaz, Eva; Amiano, Pilar; Bueno-de-Mesquita, H Bas; Gils, Carla H van; Peeters, Petra HM; Lukanova, Annekatrin; Wareham, Nick; Khaw, Kay-Tee; Key, Timothy J; Travis, Ruth C; Weiderpass, Elisabete; Dumeaux, Vanessa; Lund, Eliv; Sund, Malin; Andersson, Anne; Romieu, Isabelle; Tjønneland, Anne; Rinaldi, Sabina; Vineis, Paulo; Merritt, Melissa A; Riboli, Elio; Kaaks, Rudolf; Olsen, Anja; Overvad, Kim; Dossus, Laure; Fournier, Agnès; Clavel-Chapelon, Françoise

    2013-01-01

    The association of reproductive factors with hormone receptor (HR)-negative breast tumors remains uncertain. Within the EPIC cohort, Cox proportional hazards models were used to describe the relationships of reproductive factors (menarcheal age, time between menarche and first pregnancy, parity, number of children, age at first and last pregnancies, time since last full-term childbirth, breastfeeding, age at menopause, ever having an abortion and use of oral contraceptives [OC]) with risk of ER-PR- (n = 998) and ER+PR+ (n = 3,567) breast tumors. A later first full-term childbirth was associated with increased risk of ER+PR+ tumors but not with risk of ER-PR- tumors (≥35 vs. ≤19 years HR: 1.47 [95% CI 1.15-1.88] p trend < 0.001 for ER+PR+ tumors; ≥35 vs. ≤19 years HR: 0.93 [95% CI 0.53-1.65] p trend = 0.96 for ER-PR- tumors; P het = 0.03). The risk associations of menarcheal age, and time period between menarche and first full-term childbirth with ER-PR-tumors were in the similar direction with risk of ER+PR+ tumors (p het = 0.50), although weaker in magnitude and statistically only borderline significant. Other parity related factors such as ever a full-term birth, number of births, age- and time since last birth were associated only with ER+PR+ malignancies, however no statistical heterogeneity between breast cancer subtypes was observed. Breastfeeding and OC use were generally not associated with breast cancer subtype risk. Our study provides possible evidence that age at menarche, and time between menarche and first full-term childbirth may be associated with the etiology of both HR-negative and HR-positive malignancies, although the associations with HR-negative breast cancer were only borderline significant

  4. Reproductive health and the environment: Counseling patients about risks.

    Science.gov (United States)

    Haruty, Bella; Friedman, Julie; Hopp, Stephanie; Daniels, Ryane; Pregler, Janet

    2016-05-01

    Endocrine-disrupting chemicals (EDCs) are associated with reproductive complications such as infertility, pregnancy complications, poor birth outcomes, and child developmental abnormalities, although not all chemicals of concern are EDCs. Pregnant patients and women of childbearing age need reasonable advice about environmental contaminants and reproductive health. Copyright © 2016 Cleveland Clinic.

  5. Toxic-Metabolic Risk Factors in Pediatric Pancreatitis: Recommendations for Diagnosis, Management and Future Research

    Science.gov (United States)

    Husain, Sohail Z.; Morinville, Veronique; Pohl, John; Abu-El-Haija, Maisam; Bellin, Melena D.; Freedman, Steve; Hegyi, Peter; Heyman, Melvin B; Himes, Ryan; Ooi, Chee Y.; Schwarzenberg, Sarah Jane; Usatin, Danielle; Uc, Aliye

    2016-01-01

    Objectives Pancreatitis in children can result from metabolic and toxic risk factors, but the evidence linking these factors is sparse. We review the evidence for association or causality of these risk factors in pancreatitis, discuss management strategies and their rationale. Methods We conducted a review of the pediatric pancreatitis literature with respect to the following risk factors: (a) hyperlipidemia, (b) hypercalcemia, (c) chronic renal failure, (d) smoking exposure, (e) alcohol, and (f) medications. Areas of additional research were identified. Results Hypertriglyceridemia of 1000 mg/dl or greater poses an absolute risk for pancreatitis; persistent elevations of calcium are predisposing. Further research is necessary to determine whether end stage renal disease leads to increased pancreatitis in children similar to adults. It is unknown whether cigarette smoking exposure, which clearly increases risk in adults, also increases risk in children. The role of alcohol in pediatric pancreatitis, whether direct or modifying, needs to be elucidated. The evidence supporting most cases of medication-induced pancreatitis is poor. Drug structure, improper handling of drug by host, and by-stander status may be implicated. Other pancreatitis risk factors must be sought in all cases. Conclusions The quality of evidence supporting causative role of various toxic and metabolic factors in pediatric pancreatitis is variable. Careful phenotyping is essential, including search for other etiologic risk factors. Directed therapy includes correction/ removal of any agent identified, and general supportive measures. Further research is necessary to improve our understanding of these pancreatitis risk factors in children. PMID:26594832

  6. Authors' reply to comment on "Are repeated assisted reproductive technology treatments and an unsuccessful outcome risk factors for unipolar depression in infertile women?"

    DEFF Research Database (Denmark)

    Sejbaek, Camilla S.; Pinborg, Anja; Hageman, Ida

    2016-01-01

    The aim of our national register-based study (1) was to investigate the risk of a new episode of unipolar depression among women treated with assisted reproductive technology (ART) in regards to whether they had achieved a live birth (as a result of treatment or spontaneous conception) or not. He...... compared to women having conceived spontaneously. This article is protected by copyright. All rights reserved.......The aim of our national register-based study (1) was to investigate the risk of a new episode of unipolar depression among women treated with assisted reproductive technology (ART) in regards to whether they had achieved a live birth (as a result of treatment or spontaneous conception) or not....... Hence, we did not aim to compare unipolar depression in women who received ART treatment with women who did not. However, a systematic review and meta-analysis (2) was published recently which shows no increased risk of post-partum depressive symptoms in women after medically assisted reproduction...

  7. Reproductive health of men of industrial territories: risk factors, pre-nosologic diagnostics, prophylaxis

    Directory of Open Access Journals (Sweden)

    Serdyuk A.M.

    2016-03-01

    Full Text Available Deterioration of the environment in the XX-XXI century under the influence of chemical, physical, radiological and other factors is not only and not just an ecological catastrophe of modern times, but a direct threat to the health and life of human society as a whole. Among the most important factors influencing people's health occupy chemical the leading place, because since 1957 more than 50 million chemical substances were synthesized, but only 15% of them have a toxicological evaluation, and 30% of the diseases in Europe are associated with chemical factor (ECHA-EXA. Chemical "pressing" determines a significant reduction in the reproduction of the population of Europe, and for Ukraine it means a large-scale depopulation, among possible reasons of which a significant role belongs to the deterioration of the reproductive capacity of population, men in particular, and this work is devoted to this problem. On the basis of profound analysis of literature data, complex ecologic-hygienic researches we identified markers of exposure, prognosticaly significant markers of impact for the early diagnostics of disorders of male generative system in conditions of low-dose impact of xenobiotics. We achieved convincing evidence of ecologically determined character of unogenital diseases and fertility decrease, we developed scientifically-justified principles of management of risk of development of ecologically-determined reproductive pathology in men.

  8. Mechanisms of toxicity of di(2-ethylhexyl) phthalate on the reproductive health of male zebrafish

    Energy Technology Data Exchange (ETDEWEB)

    Uren-Webster, Tamsyn M.; Lewis, Ceri; Filby, Amy L.; Paull, Gregory C. [Hatherly Laboratories, School of Biosciences, University of Exeter, Prince of Wales Road, Exeter, Devon EX4 4PS (United Kingdom); Santos, Eduarda M., E-mail: e.santos@exeter.ac.uk [Hatherly Laboratories, School of Biosciences, University of Exeter, Prince of Wales Road, Exeter, Devon EX4 4PS (United Kingdom)

    2010-09-01

    Phthalates are ubiquitous in the aquatic environment and are known to adversely affect male reproductive health in mammals through interactions with multiple receptor systems. However, little is known about the risks they pose to fish. This project investigated the effects of di(2-ethylhexyl) phthalate (DEHP), the most commonly used phthalate, on the reproductive health of male zebrafish (Danio rerio). Males were treated with 0.5, 50 and 5000 mg DEHP kg{sup -1} (body weight) for a period of 10 days via intraperitoneal injection. The effects of the exposure were assessed by analysing fertilisation success, testis histology, sperm DNA integrity and transcript profiles of the liver and testis. A significant increase in the hepatosomatic index and levels of hepatic vitellogenin transcript were observed following exposure to 5000 mg DEHP kg{sup -1}. Exposure to 5000 mg DEHP kg{sup -1} also resulted in a reduction in fertilisation success of oocytes spawned by untreated females. However, survival and development of the resulting embryos were unaffected by all treatments, and no evidence of DEHP-induced sperm DNA damage was observed. Exposure to 50 and 5000 mg DEHP kg{sup -1} caused alterations in the proportion of germ cells at specific stages of spermatogenesis in the testis, including a reduction in the proportion of spermatozoa and an increase in the proportion of spermatocytes, suggesting that DEHP may inhibit the progression of meiosis. In parallel, exposure to 5000 mg DEHP kg{sup -1} increased the levels of two peroxisome proliferator-activated receptor (PPAR) responsive genes (acyl-coenzyme A oxidase 1 (acox1) and enoyl-coenzyme A, hydratase/3-hydroxyacyl coenzyme A dehydrogenase (ehhadh). These data demonstrated that exposure to high concentrations of DEHP disrupts spermatogenesis in adult zebrafish with a consequent decrease in their ability to fertilise oocytes spawned by untreated females. Furthermore, our data suggest that the adverse effects caused by

  9. Risk of Late Toxicity in Men Receiving Dose-Escalated Hypofractionated Intensity Modulated Prostate Radiation Therapy: Results From a Randomized Trial

    Energy Technology Data Exchange (ETDEWEB)

    Hoffman, Karen E., E-mail: khoffman1@mdanderson.org; Voong, K. Ranh; Pugh, Thomas J.; Skinner, Heath; Levy, Lawrence B.; Takiar, Vinita; Choi, Seungtaek; Du, Weiliang; Frank, Steven J.; Johnson, Jennifer; Kanke, James; Kudchadker, Rajat J.; Lee, Andrew K.; Mahmood, Usama; McGuire, Sean E.; Kuban, Deborah A.

    2014-04-01

    Objective: To report late toxicity outcomes from a randomized trial comparing conventional and hypofractionated prostate radiation therapy and to identify dosimetric and clinical parameters associated with late toxicity after hypofractionated treatment. Methods and Materials: Men with localized prostate cancer were enrolled in a trial that randomized men to either conventionally fractionated intensity modulated radiation therapy (CIMRT, 75.6 Gy in 1.8-Gy fractions) or to dose-escalated hypofractionated IMRT (HIMRT, 72 Gy in 2.4-Gy fractions). Late (≥90 days after completion of radiation therapy) genitourinary (GU) and gastrointestinal (GI) toxicity were prospectively evaluated and scored according to modified Radiation Therapy Oncology Group criteria. Results: 101 men received CIMRT and 102 men received HIMRT. The median age was 68, and the median follow-up time was 6.0 years. Twenty-eight percent had low-risk, 71% had intermediate-risk, and 1% had high-risk disease. There was no difference in late GU toxicity in men treated with CIMRT and HIMRT. The actuarial 5-year grade ≥2 GU toxicity was 16.5% after CIMRT and 15.8% after HIMRT (P=.97). There was a nonsignificant numeric increase in late GI toxicity in men treated with HIMRT compared with men treated with CIMRT. The actuarial 5-year grade ≥2 GI toxicity was 5.1% after CIMRT and 10.0% after HIMRT (P=.11). In men receiving HIMRT, the proportion of rectum receiving 36.9 Gy, 46.2 Gy, 64.6 Gy, and 73.9 Gy was associated with the development of late GI toxicity (P<.05). The 5-year actuarial grade ≥2 GI toxicity was 27.3% in men with R64.6Gy ≥ 20% but only 6.0% in men with R64.6Gy < 20% (P=.016). Conclusions: Dose-escalated IMRT using a moderate hypofractionation regimen (72 Gy in 2.4-Gy fractions) can be delivered safely with limited grade 2 or 3 late toxicity. Minimizing the proportion of rectum that receives moderate and high dose decreases the risk of late rectal toxicity after this

  10. Risk of Late Toxicity in Men Receiving Dose-Escalated Hypofractionated Intensity Modulated Prostate Radiation Therapy: Results From a Randomized Trial

    International Nuclear Information System (INIS)

    Hoffman, Karen E.; Voong, K. Ranh; Pugh, Thomas J.; Skinner, Heath; Levy, Lawrence B.; Takiar, Vinita; Choi, Seungtaek; Du, Weiliang; Frank, Steven J.; Johnson, Jennifer; Kanke, James; Kudchadker, Rajat J.; Lee, Andrew K.; Mahmood, Usama; McGuire, Sean E.; Kuban, Deborah A.

    2014-01-01

    Objective: To report late toxicity outcomes from a randomized trial comparing conventional and hypofractionated prostate radiation therapy and to identify dosimetric and clinical parameters associated with late toxicity after hypofractionated treatment. Methods and Materials: Men with localized prostate cancer were enrolled in a trial that randomized men to either conventionally fractionated intensity modulated radiation therapy (CIMRT, 75.6 Gy in 1.8-Gy fractions) or to dose-escalated hypofractionated IMRT (HIMRT, 72 Gy in 2.4-Gy fractions). Late (≥90 days after completion of radiation therapy) genitourinary (GU) and gastrointestinal (GI) toxicity were prospectively evaluated and scored according to modified Radiation Therapy Oncology Group criteria. Results: 101 men received CIMRT and 102 men received HIMRT. The median age was 68, and the median follow-up time was 6.0 years. Twenty-eight percent had low-risk, 71% had intermediate-risk, and 1% had high-risk disease. There was no difference in late GU toxicity in men treated with CIMRT and HIMRT. The actuarial 5-year grade ≥2 GU toxicity was 16.5% after CIMRT and 15.8% after HIMRT (P=.97). There was a nonsignificant numeric increase in late GI toxicity in men treated with HIMRT compared with men treated with CIMRT. The actuarial 5-year grade ≥2 GI toxicity was 5.1% after CIMRT and 10.0% after HIMRT (P=.11). In men receiving HIMRT, the proportion of rectum receiving 36.9 Gy, 46.2 Gy, 64.6 Gy, and 73.9 Gy was associated with the development of late GI toxicity (P<.05). The 5-year actuarial grade ≥2 GI toxicity was 27.3% in men with R64.6Gy ≥ 20% but only 6.0% in men with R64.6Gy < 20% (P=.016). Conclusions: Dose-escalated IMRT using a moderate hypofractionation regimen (72 Gy in 2.4-Gy fractions) can be delivered safely with limited grade 2 or 3 late toxicity. Minimizing the proportion of rectum that receives moderate and high dose decreases the risk of late rectal toxicity after this

  11. Exposure to sennoside-digoxin interaction and risk of digoxin toxicity: a population-based nested case-control study.

    Science.gov (United States)

    Wang, Meng-Ting; Li, I-Hsun; Lee, Wan-Ju; Huang, Tien-Yu; Leu, Hsin-Bang; Chan, Agnes L F

    2011-11-01

    Digoxin is an important medication for heart failure (HF) patients and sennosides are widely used to treat constipation. Recently, safety concerns have been raised about a possible interaction between sennosides and digoxin, an issue that has not been studied empirically. This study therefore aimed to evaluate whether exposure to sennoside-digoxin interaction is associated with an increased risk of digoxin toxicity. This was a population-based nested case-control study that analysed data obtained from the Taiwan National Health Insurance Research Database between 1 January 2001 and 31 December 2004. All HF patients treated with digoxin for the first time were included as the study cohort. Of these, cases were identified as subjects hospitalized for digoxin toxicity (International Classification of Diseases, Ninth Revision, Clinical Modification, ICD-9-CM 972.1), and matched to randomly selected controls. Use of sennosides was compared between the two groups. Odds ratios (ORs) were employed to quantify the risk associated with exposure to sennoside-digoxin interaction by conditional logistic regression. The study cohort comprised 222,527 HF patients, of whom 524 were identified as cases and 2,502 as matched controls. Use of sennosides during the 14 days preceding the index date was found to be associated with a 1.61-fold increased risk of digoxin toxicity [95% confidence interval (CI) = 1.15, 2.25]. Additionally, a greater risk was observed for sennosides prescribed at an average daily dose ≥ 24 mg (adjusted OR = 1.93; 95% CI = 1.27, 2.94). The combined use of sennosides and digoxin was found to be associated with a modest increased risk of digoxin toxicity in HF patients.

  12. Evaluating the toxic effects of three priority hazardous and noxious substances (HNS) to rotifer Brachionus plicatilis.

    Science.gov (United States)

    Zheng, Lei; Pan, Luqing; Lin, Pengfei; Miao, Jingjing; Wang, Xiufen; Lin, Yufei; Wu, Jiangyue

    2017-12-01

    Hazardous and noxious substances (HNS) spill in the marine environment is an issue of growing concern, and it will mostly continue to do so in the future owing to the increase of high chemical traffic. Nevertheless, the effects of HNS spill on marine environment, especially on aquatic organisms are unclear. Consequently, it is emergent to provide valuable information for the toxicities to marine biota caused by HNS spill. Accordingly, the acute toxicity of three preferential HNS and sub-lethal effects of acrylonitrile on Brachionus plicatilis were evaluated. The median lethal concentration (LC 50 ) at 24 h were 47.2 mg acrylonitrile L -1 , 276.9 mg styrene L -1 , and 488.3 mg p-xylene L -1 , respectively. Sub-lethal toxicity effects of acrylonitrile on feeding behavior, development, and reproduction parameters of B. plicatilis were also evaluated. Results demonstrated that rates of filtration and ingestion were significantly reduced at 2.0, 4.0, and 8.0 mg L -1 of acrylonitrile. Additionally, reproductive period, fecundity, and life span were significantly decreased at high acrylonitrile concentrations. Conversely, juvenile period was significantly increased at the highest two doses and no effects were observed on embryonic development and post-reproductive period. Meanwhile, we found that ingestion rate decline could be a good predictor of reproduction toxicity in B. plicatilis and ecologically relevant endpoint for toxicity assessment. These data will be useful to assess and deal with marine HNS spillages.

  13. Chemical concentrations, exposures, health risks by census tract from National Scale Air Toxics Assessment (NATA)

    Data.gov (United States)

    U.S. Environmental Protection Agency — Chemical concentrations, exposures, health risks by census tract for the United States from National Scale Air Toxics Assessment (NATA). This dataset is associated...

  14. Evaluation of nano-specific toxicity of zinc oxide, copper oxide, and silver nanoparticles through toxic ratio

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Weicheng; Liu, Xiawei; Bao, Shaopan; Xiao, Bangding; Fang, Tao, E-mail: fangt@ihb.ac.cn [Chinese Academy of Sciences, Institute of Hydrobiology (China)

    2016-12-15

    For safety and environmental risk assessments of nanomaterials (NMs) and to provide essential toxicity data, nano-specific toxicities, or excess toxicities, of ZnO, CuO, and Ag nanoparticles (NPs) (20, 20, and 30 nm, respectively) to Escherichia coli and Saccharomyces cerevisiae in short-term (6 h) and long-term (48 h) bioassays were quantified based on a toxic ratio. ZnO NPs exhibited no nano-specific toxicities, reflecting similar toxicities as ZnO bulk particles (BPs) (as well as zinc salt). However, CuO and Ag NPs yielded distinctly nano-specific toxicities when compared with their BPs. According to their nano-specific toxicities, the capability of these NPs in eliciting hazardous effects on humans and the environment was as follows: CuO > Ag > ZnO NPs. Moreover, long-term bioassays were more sensitive to nano-specific toxicity than short-term bioassays. Overall, nano-specific toxicity is a meaningful measurement to evaluate the environmental risk of NPs. The log T{sub e}{sup particle} value is a useful parameter for quantifying NP nano-specific toxicity and enabling comparisons of international toxicological data. Furthermore, this value could be used to determine the environmental risk of NPs.

  15. A computational model linking oocyte growth and spawning to the hypothalamic-pituitary-gonadal axis in fathead minnow (Pimephales promelas)

    Science.gov (United States)

    Reproduction is vital to the survival of all living organisms, and reproductive toxicity is an important outcome in determining the ecological risks of chemicals in the environment. To evaluate reproductive toxicity, fathead minnow fecundity, as measured by the average number of...

  16. Point of view concerning new trends in the assessment and management of risks

    International Nuclear Information System (INIS)

    Masse, R.

    1993-01-01

    Because they result in the most severe constraints for exposure limitation, carcinogenicity mutagenicity and toxicity for human reproduction (CMT) make up the greatest concern for toxicants in general and this remains true for heavy metals. New guidelines have recently been proposed by EEC for including compounds in CMT categories. Categorization of substances toxic to reproduction has been the most widely reassessed including all the aspects from troubles of the libido to neonatal behaviour. Although epidemiology allows to evidence some carcinogenic potency of combined exposure to different metals, lifestyle confounding factors are multiple and do not permit in general to derive risk coefficient for exposure limitation. Thus the role of animal experiments remains crucial for that purpose. Identifying a carcinogenic hazard in animals is usually easy, however risk evaluation and extrapolation of risk coefficients to man is highly debatable owing to different toxicokinetics, to the use of non relevant ways or to the use of near MTD concentrations. This is especially true when lung carcinogens have to be dealt with. Overloading the lung can result from very little amount deposited in the exchange airways resulting in irritation which may turn to cell proliferation and tumor. Cadmium and beryllium are extremely potent carcinogens after low doses deposited in the airways of the rat. There is no evidence that this phenomenon relate to human situation since most occupationally exposed workers did not develop significant excess of tumors although they developed berylliosis and kidney disease. It is therefore suggested that the limitation system be based on specific human pathology and not on carcinogenic risks since elements cannot be banned from the environment. (author). 10 refs., 1 tab

  17. E-cigarette use among women of reproductive age: Impulsivity, cigarette smoking status, and other risk factors.

    Science.gov (United States)

    Chivers, Laura L; Hand, Dennis J; Priest, Jeff S; Higgins, Stephen T

    2016-11-01

    The study aim was to examine impulsivity and other risk factors for e-cigarette use among women of reproductive age comparing current daily cigarette smokers to never cigarette smokers. Women of reproductive age are of special interest because of the additional risk that tobacco and nicotine use represents should they become pregnant. Survey data were collected anonymously online using Amazon Mechanical Turk in 2014. Participants were 800 women ages 24-44years from the US. Half (n=400) reported current, daily smoking and half (n=400) reported smoking e-cigarette use were examined using logistic regression. Daily cigarette smoking was associated with greater impulsivity, lower education, past illegal drug use, and White race/ethnicity. E-cigarette use in the overall sample was associated with being a cigarette smoker and greater education. E-cigarette use among current smokers was associated with increased nicotine dependence and quitting smoking; among never smokers it was associated with greater impulsivity and illegal drug use. E-cigarette use was associated with hookah use, and for never smokers only with use of cigars and other nicotine products. E-cigarette use among women of reproductive age varies by smoking status, with use among current smokers reflecting attempts to quit smoking whereas among non-smokers use may be a marker of a more impulsive repertoire that includes greater use of alternative tobacco products and illegal drugs. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Reference manual for toxicity and exposure assessment and risk characterization. CERCLA Baseline Risk Assessment

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-03-01

    The Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA, 1980) (CERCLA or Superfund) was enacted to provide a program for identifying and responding to releases of hazardous substances into the environment. The Superfund Amendments and Reauthorization Act (SARA, 1986) was enacted to strengthen CERCLA by requiring that site clean-ups be permanent, and that they use treatments that significantly reduce the volume, toxicity, or mobility of hazardous pollutants. The National Oil and Hazardous Substances Pollution Contingency Plan (NCP) (USEPA, 1985; USEPA, 1990) implements the CERCLA statute, presenting a process for (1) identifying and prioritizing sites requiring remediation and (2) assessing the extent of remedial action required at each site. The process includes performing two studies: a Remedial Investigation (RI) to evaluate the nature, extent, and expected consequences of site contamination, and a Feasibility Study (FS) to select an appropriate remedial alternative adequate to reduce such risks to acceptable levels. An integral part of the RI is the evaluation of human health risks posed by hazardous substance releases. This risk evaluation serves a number of purposes within the overall context of the RI/FS process, the most essential of which is to provide an understanding of ``baseline`` risks posed by a given site. Baseline risks are those risks that would exist if no remediation or institutional controls are applied at a site. This document was written to (1) guide risk assessors through the process of interpreting EPA BRA policy and (2) help risk assessors to discuss EPA policy with regulators, decision makers, and stakeholders as it relates to conditions at a particular DOE site.

  19. Reference manual for toxicity and exposure assessment and risk characterization. CERCLA Baseline Risk Assessment

    International Nuclear Information System (INIS)

    1995-03-01

    The Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA, 1980) (CERCLA or Superfund) was enacted to provide a program for identifying and responding to releases of hazardous substances into the environment. The Superfund Amendments and Reauthorization Act (SARA, 1986) was enacted to strengthen CERCLA by requiring that site clean-ups be permanent, and that they use treatments that significantly reduce the volume, toxicity, or mobility of hazardous pollutants. The National Oil and Hazardous Substances Pollution Contingency Plan (NCP) (USEPA, 1985; USEPA, 1990) implements the CERCLA statute, presenting a process for (1) identifying and prioritizing sites requiring remediation and (2) assessing the extent of remedial action required at each site. The process includes performing two studies: a Remedial Investigation (RI) to evaluate the nature, extent, and expected consequences of site contamination, and a Feasibility Study (FS) to select an appropriate remedial alternative adequate to reduce such risks to acceptable levels. An integral part of the RI is the evaluation of human health risks posed by hazardous substance releases. This risk evaluation serves a number of purposes within the overall context of the RI/FS process, the most essential of which is to provide an understanding of ''baseline'' risks posed by a given site. Baseline risks are those risks that would exist if no remediation or institutional controls are applied at a site. This document was written to (1) guide risk assessors through the process of interpreting EPA BRA policy and (2) help risk assessors to discuss EPA policy with regulators, decision makers, and stakeholders as it relates to conditions at a particular DOE site

  20. The effects of food availability on growth and reproduction of Daphnia magna exposed to silver nanoparticles

    DEFF Research Database (Denmark)

    Mackevica, Aiga; Skjolding, Lars Michael; Gergs, A.

    ) were performed using 30 nm citric acid stabilized AgNP. The aim of the study was, besides providing data for the chronic toxicity of AgNP, to study the influence of the food availability on the reproductive toxicity of AgNP in Daphnia magna. The exposure concentrations applied ranged from 2 to 50 μg...... to controls, whereas concentrations above 10 μgAg/L resulted in inhibition of growth and reproduction as well as an increased mortality. The addition of higher amounts of food showed a beneficial effect on animal survival, growth and reproduction. Similar as in normal food availability treatment, animals......The number of available studies on the acute effects of silver nanoparticles (AgNP) on aquatic organisms has increased dramatically in recent years, but there is still very limited information available on chronic effects. In this study, a series of Daphnia magna 21-days reproduction test (OECD 211...

  1. A qualitative study of Ottawa university students' awareness, knowledge and perceptions of infertility, infertility risk factors and assisted reproductive technologies (ART).

    Science.gov (United States)

    Sabarre, Kelley-Anne; Khan, Zainab; Whitten, Amanda N; Remes, Olivia; Phillips, Karen P

    2013-08-20

    Awareness of infertility risk factors is an essential first step to safeguard future fertility. Whereas several studies have examined university students' awareness of female fertility and related risk factors, the topic of male infertility has not been well examined. The objective of this study was to assess young men and women's awareness, knowledge and perceptions of infertility, male and female infertility risk factors and assisted reproductive technologies (ART). Semi-structured interviews were conducted in 2008 with a multi-ethnic sample of sixteen male and twenty-three female Ottawa university students, followed by qualitative data analysis to identify major themes. Interview topics included awareness of male and female infertility risk factors, infertility diagnosis/treatments and personal options in the event of future infertility. Participants were generally familiar with infertility as a biomedical health problem, could identify sex-specific risk factors but overestimated fertility of women in their thirties and ART success rates. Reproductive health knowledge gaps and confusion of the physiological life-stage of menopause with infertility were apparent. Most participants would pursue in vitro fertilization or international adoption in the event of personal infertility. Some participants wished to use a 'natural' approach and were concerned with potential side effects of ART-related medications. The general awareness of infertility in young adults is promising and supports the potential uptake for health promotion of fertility preservation. This study underscores the continued need for comprehensive sexual and reproductive health education and promotion for adolescents and young adults.

  2. Effects of Ascorbic Acid on Reproductive Functions of Male Wistar ...

    African Journals Online (AJOL)

    In conclusion, ascorbic acid supplement may suppress nicotine toxic effects on reproductive functions in male rats. ... et al., 2007). Nicotine is rapidly absorbed by the brain .... difference (LSD) test. p<0.05 was considered significant. Statistical ...

  3. Individualized toxicity-titrated 6-mercaptopurine increments during high-dose methotrexate consolidation treatment of lower risk childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Frandsen, Thomas Leth; Abrahamsson, Jonas; Lausen, Birgitte Frederiksen

    2011-01-01

    This study explored the feasibility and toxicity of individualized toxicity-titrated 6-mercaptopurine (6MP) dose increments during post-remission treatment with High-dose methotrexate (HDM) (5000 mg/m2, ×3) in 38 patients with Childhood (ALL). Patients were increased in steps of 25 mg 6MP/m2 per...... the remaining patients (P = 0·03). This study shows individualized toxicity-titrated 6MP dosing during consolidation is feasible without increased risk of toxicity....

  4. Toxic chemicals: risk prevention through use reduction

    National Research Council Canada - National Science Library

    Higgins, Thomas E; Sachdev, Jayanti A; Engleman, Stephen A

    2011-01-01

    ... on the actual toxicity of chemicals currently in use, discusses variables that contribute to the relative toxicity of a substance, compares alternate emphases in existing programs for reducing environmental...

  5. Developmental toxicity of organotin compounds in animals

    Directory of Open Access Journals (Sweden)

    Lijiao eWu

    2014-09-01

    Full Text Available Organotin compounds (OTs have been used as biocides in antifouling paints and agriculture. The IMO introduced a global ban on the use of OTs in antifouling systems in 2001 due to their high toxicity. However, OTs have still been detected in the environment and pose a threat to the ecosystem. Several research groups have summarized the analytical methods, environmental fate, biochemistry, reproductive toxicity and mechanisms of actions of OTs. Here, we reviewed the developmental toxicity of OTs in various organisms such as sea urchin, ascidian, mussel and fish. The differences in sensitivity to OT exposure exist not only in different species but also at different stages in the same species. Though some hypotheses have been proposed to explain the developmental toxicity of OTs, the solid evidences are greatly in need.

  6. Knowledge, attitudes, and practices regarding antiretroviral management, reproductive health, sexually transmitted infections, and sexual risk behavior among perinatally HIV-infected youth in Thailand.

    Science.gov (United States)

    Lolekha, Rangsima; Boon-Yasidhi, Vitharon; Leowsrisook, Pimsiri; Naiwatanakul, Thananda; Durier, Yuitiang; Nuchanard, Wipada; Tarugsa, Jariya; Punpanich, Warunee; Pattanasin, Sarika; Chokephaibulkit, Kulkanya

    2015-01-01

    More than 30% of perinatally HIV-infected children in Thailand are 12 years and older. As these youth become sexually active, there is a risk that they will transmit HIV to their partners. Data on the knowledge, attitudes, and practices (KAP) of HIV-infected youth in Thailand are limited. Therefore, we assessed the KAP of perinatally HIV-infected youth and youth reporting sexual risk behaviors receiving care at two tertiary care hospitals in Bangkok, Thailand and living in an orphanage in Lopburi, Thailand. From October 2010 to July 2011, 197 HIV-infected youth completed an audio computer-assisted self-interview to assess their KAP regarding antiretroviral (ARV) management, reproductive health, sexual risk behaviors, and sexually transmitted infections (STIs). A majority of youth in this study correctly answered questions about HIV transmission and prevention and the importance of taking ARVs regularly. More than half of the youth in this study demonstrated a lack of family planning, reproductive health, and STI knowledge. Girls had more appropriate attitudes toward safe sex and risk behaviors than boys. Although only 5% of the youth reported that they had engaged in sexual intercourse, about a third reported sexual risk behaviors (e.g., having or kissing boy/girlfriend or consuming an alcoholic beverage). We found low condom use and other family planning practices, increasing the risk of HIV and/or STI transmission to sexual partners. Additional resources are needed to improve reproductive health knowledge and reduce risk behavior among HIV-infected youth in Thailand.

  7. Reproductive Issues in Women with Turner Syndrome.

    Science.gov (United States)

    Folsom, Lisal J; Fuqua, John S

    2015-12-01

    Turner syndrome is one of the most common chromosomal abnormalities affecting female infants. The severity of clinical manifestations varies and it affects multiple organ systems. Women with Turner syndrome have a 3-fold increase in mortality, which becomes even more pronounced in pregnancy. Reproductive options include adoption or surrogacy, assisted reproductive techniques, and in rare cases spontaneous pregnancy. Risks for women with Turner syndrome during pregnancy include aortic disorders, hepatic disease, thyroid disease, type 2 diabetes, and cesarean section delivery. Providers must be familiar with the risks and recommendations in caring for women with Turner syndrome of reproductive age. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Potential risks of metal toxicity in contaminated sediments of Deule river in Northern France

    International Nuclear Information System (INIS)

    Lourino-Cabana, Beatriz; Lesven, Ludovic; Charriau, Adeline; Billon, Gabriel; Ouddane, Baghdad; Boughriet, Abdel

    2011-01-01

    Research highlights: → A historical environmental pollution is evidenced with reference to background levels. → Sedimentary trace metals partitioning is examined under undisturbed conditions. → Anoxia and diagenetic processes induce geochemical and mineralogical variabilities. → Do metals present in particles and pore waters exhibit a potential toxicity risk? → Behaviour of binding fractions contributes to trace metals scavenging. - Abstract: The aim of this paper was to evaluate the potential sediment cumulative damage and toxicity due to metal contamination in a polluted zone of Deule river (in northern France) from nearby two smelters. Metal-enrichment factors and geoaccumulation indices measured with sediment depth revealed that - compared to background levels either in local reference soils or in world rivers sediments/suspended particulate matter - Cd contributed to the highest pollution levels, followed by Zn, Pb and to a much lesser extent Cu and Ni. A comparison of the vertical distribution of AVS (acid volatile sulfides), SEM (simultaneously extracted metals), TMC (total metal concentrations), TOC (total organic carbon) and interstitial water-metal concentrations in the sediment allowed us to highlight the extent of toxicity caused by Cd, Pb, Zn, Ni and Cu and to raise the possibility of their association with certain geochemical phases. To assess the actual environmental impacts of these metals in Deule river, numerical sediment quality guidelines were further used in the present work. Sedimentary Pb, Zn, and Cd contents largely exceeded PEC (probable effect concentration) values reported as consensus-based sediment quality guidelines for freshwater ecosystems. As for risks of toxicity from pore waters, metal concentrations reached their maxima at the surficial layers of the sediment (1-3 cm) and IWCTU (Interstitial Water Criteria Toxicity Unit) observed for Pb and to a lesser extent Cd, violated the corresponding water quality data recommended

  9. Photo-induced toxicity in early life stage fiddler crab (Uca longisignalis) following exposure to Deepwater Horizon oil.

    Science.gov (United States)

    Damare, Leigh M; Bridges, Kristin N; Alloy, Matthew M; Curran, Thomas E; Soulen, Brianne K; Forth, Heather P; Lay, Claire R; Morris, Jeffrey M; Stoeckel, James A; Roberts, Aaron P

    2018-05-01

    The 2010 explosion of the Deepwater Horizon (DWH) oil rig led to the release of millions of barrels of oil in the Gulf of Mexico. Oil in aquatic ecosystems exerts toxicity through multiple mechanisms, including photo-induced toxicity following co-exposure with UV radiation. The timing and location of the spill coincided with both fiddler crab reproduction and peak yearly UV intensities, putting early life stage fiddler crabs at risk of injury due to photo-induced toxicity. The present study assessed sensitivity of fiddler crab larvae to photo-induced toxicity during co-exposure to a range of environmentally relevant dilutions of high-energy water accommodated fractions of DWH oil, and either dark recovery period (duration: 17-h) in between. Survival was significantly decreased in treatments the presence of >10% UV and relatively low concentrations of oil. Results of the present study indicate fiddler crab larvae are sensitive to photo-induced toxicity in the presence of DWH oil. These results are of concern, as fiddler crabs play an important role as ecosystem engineers, modulating sediment biogeochemical processes via burrowing action. Furthermore, they occupy an important place in the food web in the Gulf of Mexico.

  10. Development of a standardized reproduction toxicity test with the earthworm species Eisenia fetida andrei using copper, pentachlorophenol and 2,4-dichloroaniline

    Energy Technology Data Exchange (ETDEWEB)

    van Gestel, C.A.; van Dis, W.A.; van Breemen, E.M.; Sparenburg, P.M. (National Institute of Public Health and Environmental Protection, BA Bilthoven (Netherland))

    1989-12-01

    This article describes a standardized test method for determining the effect of chemical substances on the reproduction of the earthworm Eisenia fetida andrei. It is based on the existing guidelines for acute toxicity testing with earthworms, and for reasons of standardization the same artificial soil substrate and earthworm species were chosen as prescribed by these guidelines. After being preconditioned for one week in untreated soil, earthworms are exposed to the chemical substances for 3 weeks. The number of cocoons produced is determined, and cocoons are incubated in untreated artificial soil for 5 weeks to assess hatchability. Results are presented from toxicity experiments with pentachlorophenol, copper, and 2,4-dichloroaniline. For these compounds no-effect levels (NEL) for cocoon production were 32, 60-120, and 56 mg.kg-1 dry soil, respectively. Hatching of cocoons was influenced by pentachlorophenol (NEL, 10 mg.kg-1), but not by copper and dichloroaniline. Following exposure, earthworms were incubated in clean soil again to study the possibility of recovery of cocoon production. For copper and dichloroaniline earthworms did recover cocoon production to a level as high as the control level or even higher; in case of pentachlorophenol, cocoon production was still reduced after 3 weeks in clean soil.

  11. Computer Simulation of Developmental Processes and Toxicities (SOT)

    Science.gov (United States)

    Rationale: Recent progress in systems toxicology and synthetic biology have paved the way to new thinking about in vitro/in silico modeling of developmental processes and toxicities, both for embryological and reproductive impacts. Novel in vitro platforms such as 3D organotypic ...

  12. Toxicity risk of insecticides to the insect egg parasitoid Trichogramma evanescens Westwood (Hymenoptera: Trichogrammatidae).

    Science.gov (United States)

    Wang, Yanhua; Wu, Changxing; Cang, Tao; Yang, Lizhi; Yu, Weihua; Zhao, Xueping; Wang, Qiang; Cai, Leiming

    2014-03-01

    Natural populations of Trichogramma evanescens contribute to the control of lepidopterous pests. The toxic effects of insecticides have been extensively reported on trichogrammatids, but are largely unknown on T. evanescens. In this study, the toxicities of seven classes of chemicals against the parasitoid were investigated. Among these classes, organophosphates and carbamates exhibited the highest levels of intrinsic toxicity, with LC50 values ranging from 0.025 (0.023-0.028) to 2.20 (1.71-3.09) and from 0.040 (0.032-0.053) to 1.84 (1.53-2.30) mg AI L(-1) respectively. Among the phenylpyrazoles, only ethiprole can be considered to be less toxic in the group. Avermectins, pyrethroids and neonicotinoids were less toxic, with LC50 values ranging from 1.29 to 2.57, from 2.26 to 14.03 and from 1.12 to 239.1 mg AI L(-1) respectively. In contrast, insect growth regulators (IGRs) showed the lowest toxicity to the parasitoid, with LC50 values ranging from 3383 (2406-5499) to 5650 (4228-8579) mg AI L(-1) . The results of risk quotient analysis indicated that neonicotinoids, avermectins, pyrethroids and IGRs were less hazardous, but phenylpyrazoles (except for ethiprole), organophosphates and carbamates were slightly to moderately or dangerously toxic to T. evanescens. The present results provide informative data for implementing biological and chemical control strategies in integrated pest management of lepidopterans. © 2013 Society of Chemical Industry.

  13. Collaborative work to evaluate toxicity on male reproductive organs by repeated dose studies in rats 22). Effects of 2- and 4-week administration of theobromine on the testis.

    Science.gov (United States)

    Funabashi, H; Fujioka, M; Kohchi, M; Tateishi, Y; Matsuoka, N

    2000-10-01

    The effects of theobromine, a xanthine derivative, on the testis were compared between rats dosed for 2 and 4 weeks to determine whether a 2-week dosing period is long enough to detect toxicity. Theobromine was administered orally to male Sprague-Dawley rats at dose levels of 250 and 500 mg/kg for 2 weeks starting at the age of 6 or 8 weeks, and for 4 weeks from the age of 6 weeks. Histopathological examination of reproductive organs revealed toxic findings in the testis at 500 mg/kg after 2 weeks of dosing at both ages, and at 250 and 500 mg/kg after 4 weeks of dosing. The primary findings were degeneration/necrosis and desquamation of spermatids and spermatocytes, vacuolization of seminiferous tubules, and multinucleated giant cell formation. These findings were present mainly in stages I-VI and XII-XIV. From these results, it is concluded that the toxic effects of theobromine on the testis can be detected by repeated dosing for 2 weeks as well as for 4 weeks.

  14. Do assisted-reproduction twin pregnancies require additional antenatal care?

    Science.gov (United States)

    Jauniaux, E; Ben-Ami, I; Maymon, R

    2013-02-01

    Iatrogenic twinning has become the main side-effect assisted reproduction treatment. We have evaluated the evidence for additional care that assisted-reproduction twins may require compared with spontaneous twins. Misacarriages are increased in women with tubal problems and after specific treatments. Assisted-reproduction twin pregnancies complicated by a vanishing twin after 8 weeks have an increased risk of preterm delivery and of low and very low birthweight compared with singleton assisted-reproduction pregnancies. Monozygotic twin pregnancies occur at a higher rate after assisted reproduction treatment and are associated with a higher risk of perinatal complications. The incidence of placenta praevia and vasa praevia is increased in assisted-reproduction twin pregnancies. Large cohort studies do not indicate a higher rate of fetal congenital malformations in assisted-reproduction twins. Overall, assisted-reproduction twins in healthy women assisted-reproduction twins is only increased in women with a pre-existing medical condition such as hypertensive disorders and diabetes and most of these risks can be avoided with single-embryo transfer. Following the birth of the first IVF baby, rumours started to spread in both the medical literature and the media about the long-term health effects for children born following assisted reproduction treatment. However, after more than 30 years, the most common complications associated with IVF treatment remain indirect and technical such as the failure of treatment and ovarian hyperstimulation. Iatrogenic twinning has become the main side-effect of assisted reproduction treatment and the increasing number of twin pregnancies, in particular in older women, has generated numerous debates on the need for additional healthcare provision. In this review, we have evaluated the evidence for additional care that assisted-conception twin pregnancies may require compared with spontaneous twin pregnancies. Twin pregnancies are

  15. Early menarche and teenager pregnancy as risk factors for morbid obesity among reproductive-age women: A case-control study.

    Science.gov (United States)

    Neves, Amanda Gonçalves; Kasawara, Karina Tamy; Godoy-Miranda, Ana Carolina; Oshika, Flávio Hideki; Chaim, Elinton Adami; Surita, Fernanda Garanhani

    2017-10-01

    The aim of this study was to evaluate potential risk factors, including non-communicable diseases, for morbid obesity in women between 20 and 49 years of age. We performed a case-control study with 110 morbidly obese women and 110 women with adequate weight who were matched by age and with a 1:1 case to control ratio. All women were between 20 to 49 years old and non-menopausal. Possible risk factors were evaluated through a self-report questionnaire assessing socio-demographic, obstetric and gynecological characteristics, presence of non-communicable diseases and habits. Multiple logistic regression was used to estimate the odds ratio with respective confidence intervals. Menarche under 12 years old, teenage pregnancy and lower educational level were shown to be risk factors for morbid obesity among women of reproductive age. Incidences of non-communicable diseases (diabetes, hypertension, dyslipidemia, liver disease, lung disease, thyroid dysfunction, and joint pain) were increased in women with morbid obesity. Early menarche, teenage pregnancy and low education level are risk factors for the occurrence of morbid obesity in women of reproductive age. Some non-communicable diseases were already more prevalent in women with morbid obesity even before 50 years of age.

  16. Evaluation of metals, metalloids, and ash mixture toxicity using sediment toxicity testing.

    Science.gov (United States)

    Stojak, Amber; Bonnevie, Nancy L; Jones, Daniel S

    2015-01-01

    In December 2008, a release of 4.1 million m(3) of coal ash from the Tennessee Valley Authority Kingston Fossil Plant occurred. Ash washed into the Emory River and migrated downstream into the Clinch and Tennessee Rivers. A Baseline Ecological Risk Assessment evaluated risks to ecological receptors from ash in the river system post-dredging. This article describes the approach used and results from sediment toxicity tests, discussing any causal relationships between ash, metals, and toxicity. Literature is limited in the realm of aquatic coal combustion residue (CCR) exposures and the potential magnitude of effects on benthic invertebrates. Sediment samples along a spectrum of ash content were used in a tiered toxicity testing approach and included a combination of 10 day sediment toxicity acute tests and longer-term, partial life cycle "definitive" tests with 2 species (Hyalella azteca and Chironomus dilutus). Arsenic, and to a lesser extent Se, in the ash was the most likely toxicant causing observed effects in the laboratory toxicity tests. Sites in the Emory River with the greatest statistical and biologically significant effects had As concentrations in sediments twice the probable effects concentration of 33 mg/kg. These sites contained greater than 50% ash. Sites with less than approximately 50% ash in sediments exhibited fewer significant toxic responses relative to the reference sediment in the laboratory. The results discussed here present useful evidence of only limited effects occurring from a worst-case exposure pathway. These results provided a valuable line of evidence for the overall assessment of risks to benthic invertebrates and to other ecological receptors, and were crucial to risk management and development of project remediation goals. © 2014 SETAC.

  17. Predicting molybdenum toxicity to higher plants: Estimation of toxicity threshold values

    Energy Technology Data Exchange (ETDEWEB)

    McGrath, S.P., E-mail: steve.mcgrath@bbsrc.ac.u [Soil Science Department, Centre for Soils and Ecosystems Function, Rothamsted Research, Harpenden, Hertfordshire AL5 2JQ (United Kingdom); Mico, C.; Zhao, F.J.; Stroud, J.L. [Soil Science Department, Centre for Soils and Ecosystems Function, Rothamsted Research, Harpenden, Hertfordshire AL5 2JQ (United Kingdom); Zhang, H.; Fozard, S. [Division of Environmental Science, Lancaster University, Lancaster LA1 4YQ (United Kingdom)

    2010-10-15

    Four plant species (oilseed rape, Brassica napus L.; red clover, Trifolium pratense L.; ryegrass, Lolium perenne L.; and tomato, Lycopersicon esculentum L.) were tested on ten soils varying widely in soil properties to assess molybdenum (Mo) toxicity. A larger range (66-fold-609-fold) of added Mo concentrations resulting in 50% inhibition of yield (ED{sub 50}) was found among soils than among plant species (2-fold-38-fold), which illustrated that the soils differed widely in the expression of Mo toxicity. Toxicity thresholds based on soil solution Mo narrowed the variation among soils compared to thresholds based on added Mo concentrations. We conclude that plant bioavailability of Mo in soil depends on Mo solubility, but this alone did not decrease the variability in observed toxicity enough to be used in risk assessment and that other soil properties influencing Mo toxicity to plants need to be considered. - Mo toxicity thresholds varied widely in different soils and therefore soil properties need to be taken into account in order to assess the risk of Mo exposure.

  18. Age at menopause, reproductive life span, and type 2 diabetes risk results from the EPIC-interAct Study

    NARCIS (Netherlands)

    Brand, J.S.; Schouw, van der Y.T.; Onland-Moret, N.; Sharp, S.J.; Feskens, E.J.M.

    2013-01-01

    OBJECTIVEAge at menopause is an important determinant of future health outcomes, but little is known about its relationship with type 2 diabetes. We examined the associations of menopausal age and reproductive life span (menopausal age minus menarcheal age) with diabetes risk.RESEARCH DESIGN AND

  19. Risk of reproductive complications following chlamydia testing

    DEFF Research Database (Denmark)

    Davies, Bethan; Turner, Katy M E; Frølund, Maria

    2016-01-01

    of pelvic inflammatory disease. Therefore, control programmes must prevent first and repeat infections to improve women's reproductive health. FUNDING: Unrestricted partial funding from Frederiksberg Kommune, Frederiksberg, Denmark. BD held an Medical Research Council Population Health Scientist Fellowship...

  20. Incorporating pharmacokinetic differences between children and adults in assessing children's risks to environmental toxicants

    International Nuclear Information System (INIS)

    Ginsberg, Gary; Hattis, Dale; Sonawane, Babasaheb

    2004-01-01

    Children's risks from environmental toxicant exposure can be affected by pharmacokinetic factors that affect the internal dose of parent chemical or active metabolite. There are numerous physiologic differences between neonates and adults that affect pharmacokinetics including size of lipid, and tissue compartments, organ blood flows, protein binding capacity, and immature function of renal and hepatic systems. These factors combine to decrease the clearance of many therapeutic drugs, which can also be expected to occur with environmental toxicants in neonates. The net effect may be greater or lesser internal dose of active toxicant depending upon how the agent is distributed, metabolized, and eliminated. Child/adult pharmacokinetic differences decrease with increasing postnatal age, but these factors should still be considered in any children's age group, birth through adolescence, for which there is toxicant exposure. Physiologically based pharmacokinetic (PBPK) models can simulate the absorption, distribution, metabolism, and excretion of xenobiotics in both children and adults, allowing for a direct comparison of internal dose and risk across age groups. This review provides special focus on the development of hepatic cytochrome P-450 enzymes (CYPs) in early life and how this information, along with many factors unique to children, can be applied to PBPK models for this receptor population. This review describes a case study involving the development of neonatal PBPK models for the CYP1A2 substrates caffeine and theophylline. These models were calibrated with pharmacokinetic data in neonates and used to help understand key metabolic differences between neonates and adults across these two drugs

  1. Indicators of Ceriodaphnia dubia chronic toxicity test performance and sensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Rosebrock, M.M.; Bedwell, N.J.; Ausley, L.W. [North Carolina Division of Environmental Management, Raleigh, NC (United States)

    1994-12-31

    The North Carolina Division of Environmental Management has begun evaluation of the sensitivity of test results used for measuring chronic whole effluent toxicity in North Carolina wastewater discharges. Approximately 67% of 565 facilities required to monitor toxicity by an NPDES permit perform a Ceriodaphnia dubia chronic, single effluent concentration (pass/fail) analysis. Data from valid Ceriodaphnia dubia chronic pass/fail tests performed by approximately 20 certified biological laboratories and submitted by North Carolina NPDES permittees were recorded beginning January 1992. Control and treatment reproduction data from over 2,500 tests submitted since 1992 were analyzed to determine the minimum significant difference (MSD) at a 99% confidence level for each test and the percent reduction from the control mean that the MSD represents (%MSD) for each certified laboratory. Initial results for the 20 laboratories indicate that the average intralaboratory percent MSD ranges 12.72% (n = 367) to 34.91% (n = 7) with an average of 23.08%. Additionally, over 3,800 tests were analyzed to determine the coefficient of variation (CV) for control reproduction for each test and the average for each certified biological laboratory. Preliminary review indicates that average interlaboratory control reproduction CV values range from 10.59% (n = 367) to 31.08% (n = 572) with a mean of 20.35%. The statistics investigated are indicators of intra/interlaboratory performance and sensitivity of Ceriodaphnia chronic toxicity analyses.

  2. Past, present and emerging toxicity issues for jet fuel.

    Science.gov (United States)

    Mattie, David R; Sterner, Teresa R

    2011-07-15

    The US Air Force wrote the specification for the first official hydrocarbon-based jet fuel, JP-4, in 1951. This paper will briefly review the toxicity of the current fuel, JP-8, as compared to JP-4. JP-8 has been found to have low acute toxicity with the adverse effects being slight dermal irritation and weak dermal sensitization in animals. JP-4 also has low acute toxicity with slight dermal irritation as the adverse effect. Respiratory tract sensory irritation was greater in JP-8 than in JP-4. Recent data suggest exposure to jet fuel may contribute to hearing loss. Subchronic studies for 90 days with JP-8 and JP-4 showed little toxicity with the primary effect being male rat specific hydrocarbon nephropathy. A 1-year study was conducted for JP-4. The only tumors seen were associated with the male rat specific hydrocarbon nephropathy. A number of immunosuppressive effects have been seen after exposure to JP-8. Limited neurobehavioral effects have been associated with JP-8. JP-8 is not a developmental toxicant and has little reproductive toxicity. JP-4 has not been tested for immune, neurobehavioral or reproductive endpoints. JP-8 and JP-4 were negative in mutagenicity tests but JP-4 showed an increase in unscheduled DNA synthesis. Currently, JP-8 is being used as the standard for comparison of future fuels, including alternative fuels. Emerging issues of concern with jet fuels include naphthalene content, immunotoxicity and inhalation exposure characterization and modeling of complex mixtures such as jet fuels. Copyright © 2011 Elsevier Inc. All rights reserved.

  3. Past, present and emerging toxicity issues for jet fuel

    International Nuclear Information System (INIS)

    Mattie, David R.; Sterner, Teresa R.

    2011-01-01

    The US Air Force wrote the specification for the first official hydrocarbon-based jet fuel, JP-4, in 1951. This paper will briefly review the toxicity of the current fuel, JP-8, as compared to JP-4. JP-8 has been found to have low acute toxicity with the adverse effects being slight dermal irritation and weak dermal sensitization in animals. JP-4 also has low acute toxicity with slight dermal irritation as the adverse effect. Respiratory tract sensory irritation was greater in JP-8 than in JP-4. Recent data suggest exposure to jet fuel may contribute to hearing loss. Subchronic studies for 90 days with JP-8 and JP-4 showed little toxicity with the primary effect being male rat specific hydrocarbon nephropathy. A 1-year study was conducted for JP-4. The only tumors seen were associated with the male rat specific hydrocarbon nephropathy. A number of immunosuppressive effects have been seen after exposure to JP-8. Limited neurobehavioral effects have been associated with JP-8. JP-8 is not a developmental toxicant and has little reproductive toxicity. JP-4 has not been tested for immune, neurobehavioral or reproductive endpoints. JP-8 and JP-4 were negative in mutagenicity tests but JP-4 showed an increase in unscheduled DNA synthesis. Currently, JP-8 is being used as the standard for comparison of future fuels, including alternative fuels. Emerging issues of concern with jet fuels include naphthalene content, immunotoxicity and inhalation exposure characterization and modeling of complex mixtures such as jet fuels.

  4. A qualitative study of Ottawa university students’ awareness, knowledge and perceptions of infertility, infertility risk factors and assisted reproductive technologies (ART)

    Science.gov (United States)

    2013-01-01

    Background Awareness of infertility risk factors is an essential first step to safeguard future fertility. Whereas several studies have examined university students’ awareness of female fertility and related risk factors, the topic of male infertility has not been well examined. The objective of this study was to assess young men and women’s awareness, knowledge and perceptions of infertility, male and female infertility risk factors and assisted reproductive technologies (ART). Methods Semi-structured interviews were conducted in 2008 with a multi-ethnic sample of sixteen male and twenty-three female Ottawa university students, followed by qualitative data analysis to identify major themes. Interview topics included awareness of male and female infertility risk factors, infertility diagnosis/treatments and personal options in the event of future infertility. Results Participants were generally familiar with infertility as a biomedical health problem, could identify sex-specific risk factors but overestimated fertility of women in their thirties and ART success rates. Reproductive health knowledge gaps and confusion of the physiological life-stage of menopause with infertility were apparent. Most participants would pursue in vitro fertilization or international adoption in the event of personal infertility. Some participants wished to use a ‘natural’ approach and were concerned with potential side effects of ART-related medications. Conclusions The general awareness of infertility in young adults is promising and supports the potential uptake for health promotion of fertility preservation. This study underscores the continued need for comprehensive sexual and reproductive health education and promotion for adolescents and young adults. PMID:23962162

  5. Exposure monitoring and risk assessment of biphenyl in the workplace.

    Science.gov (United States)

    Kim, Hyeon-Yeong; Shin, Sae-Mi; Ham, Miran; Lim, Cheol-Hong; Byeon, Sang-Hoon

    2015-05-13

    This study was performed to assess exposure to and the risk caused by biphenyl in the workplace. Biphenyl is widely used as a heat transfer medium and as an emulsifier and polish in industry. Vapor or high levels of dust inhalation and dermal exposure to biphenyl can cause eye inflammation, irritation of respiratory organs, and permanent lesions in the liver and nervous system. In this study, the workplace environment concentrations were assessed as central tendency exposure and reasonable maximum exposure and were shown to be 0.03 and 0.12 mg/m³, respectively. In addition, the carcinogenic risk of biphenyl as determined by risk assessment was 0.14 × 10⁻⁴ (central tendency exposure) and 0.56 × 10⁻⁴ (reasonable maximum exposure), which is below the acceptable risk value of 1.0 × 10⁻⁴. Furthermore, the central tendency exposure and reasonable maximum exposure hazard quotients were 0.01 and 0.06 for oral toxicity, 0.05 and 0.23 for inhalation toxicity, and 0.08 and 0.39 for reproduction toxicity, respectively, which are all lower than the acceptable hazard quotient of 1.0. Therefore, exposure to biphenyl was found to be safe in current workplace environments. Because occupational exposure limits are based on socioeconomic assessment, they are generally higher than true values seen in toxicity experiments. Based on the results of exposure monitoring of biphenyl, the current occupational exposure limits in Korea could be reviewed.

  6. Exposure Monitoring and Risk Assessment of Biphenyl in the Workplace

    Directory of Open Access Journals (Sweden)

    Hyeon-Yeong Kim

    2015-05-01

    Full Text Available This study was performed to assess exposure to and the risk caused by biphenyl in the workplace. Biphenyl is widely used as a heat transfer medium and as an emulsifier and polish in industry. Vapor or high levels of dust inhalation and dermal exposure to biphenyl can cause eye inflammation, irritation of respiratory organs, and permanent lesions in the liver and nervous system. In this study, the workplace environment concentrations were assessed as central tendency exposure and reasonable maximum exposure and were shown to be 0.03 and 0.12 mg/m3, respectively. In addition, the carcinogenic risk of biphenyl as determined by risk assessment was 0.14 × 10−4 (central tendency exposure and 0.56 × 10−4 (reasonable maximum exposure, which is below the acceptable risk value of 1.0 × 10−4. Furthermore, the central tendency exposure and reasonable maximum exposure hazard quotients were 0.01 and 0.06 for oral toxicity, 0.05 and 0.23 for inhalation toxicity, and 0.08 and 0.39 for reproduction toxicity, respectively, which are all lower than the acceptable hazard quotient of 1.0. Therefore, exposure to biphenyl was found to be safe in current workplace environments. Because occupational exposure limits are based on socioeconomic assessment, they are generally higher than true values seen in toxicity experiments. Based on the results of exposure monitoring of biphenyl, the current occupational exposure limits in Korea could be reviewed.

  7. Pregnancy outcomes after assisted human reproduction.

    Science.gov (United States)

    Okun, Nanette; Sierra, Sony

    2014-01-01

    independent risk factor for obstetrical complications and adverse perinatal outcomes, even without the addition of assisted human reproduction. (II-2) 2. The relative risk for an imprinting phenotype such as Silver-Russell syndrome, Beckwith-Wiedemann syndrome, or Angelman syndrome is increased in the assisted reproduction population, but the actual risk for one of these phenotypes to occur in an assisted pregnancy is estimated to be low, at less than 1 in 5000. The exact biological etiology for this increased imprinting risk is likely heterogeneous and requires more research. (II-2) Recommendations 1. All men with severe oligozoospermia or azoospermia (sperm count assisted human reproductive treatments. (II-2A) 4. The benefits and cumulative pregnancy rates of elective single embryo transfer support a policy of using this protocol in couples with good prognosis for success, and elective single embryo transfer should be strongly encouraged in this population. (II-2A) 5. To reduce the incidence of multiple pregnancy, health care policies that support public funding for assisted human reproduction, with regulations promoting best practice regarding elective single embryo transfer, should be strongly encouraged. (II-2A) 6. Among singleton pregnancies, assisted reproductive technology is associated with increased risks of preterm birth and low birth weight infants, and ovulation induction is associated with an increased risk of low birth weight infants. Until sufficient research has clarified the independent roles of infertility and treatment for infertility, couples should be counselled about the risks associated with treatment. (II-2B) There is a role for closer obstetric surveillance of women who conceive with assisted human reproduction. (III-L) 7. There is growing evidence that pregnancy outcomes are better for cryopreserved embryos fertilized in vitro than for fresh embryo transfers. This finding supports a policy of elective single embryo transfer for women with a good

  8. Mercury in fish and adverse reproductive outcomes: results from South Carolina

    Science.gov (United States)

    2014-01-01

    Background Mercury is a metal with widespread distribution in aquatic ecosystems and significant neurodevelopmental toxicity in humans. Fish biomonitoring for total mercury has been conducted in South Carolina (SC) since 1976, and consumption advisories have been posted for many SC waterways. However, there is limited information on the potential reproductive impacts of mercury due to recreational or subsistence fish consumption. Methods To address this issue, geocoded residential locations for live births from the Vital Statistics Registry (1995–2005, N = 362,625) were linked with spatially interpolated total mercury concentrations in fish to estimate potential mercury exposure from consumption of locally caught fish. Generalized estimating equations were used to test the hypothesis that risk of low birth weight (LBW, mercury in fish, after adjustment for confounding. Separate analyses estimated term LBW and PTB risks using residential proximity to rivers with fish consumption advisories to characterize exposure. Results Term LBW was more likely among women residing in areas in the upper quartile of predicted total mercury in fish (odds ratio [OR] = 1.04; 95% confidence interval [CI]: 1.00-1.09) or within 8 kilometers of a river with a ‘do not eat’ fish advisory (1.05; 1.00-1.11) compared to the lowest quartile, or rivers without fish consumption restrictions, respectively. When stratified by race, risks for term LBW or PTB were 10-18% more likely among African-American (AA) mothers living in areas with the highest total fish mercury concentrations. Conclusions To our knowledge, this is the first study to examine the relationship between fish total mercury concentrations and adverse reproductive outcomes in a large population-based sample that included AA women. The ecologic nature of exposure assessment in this study precludes causal inference. However, the results suggest a need for more detailed investigations to characterize patterns of local

  9. Prostate cancer and toxicity from critical use exemptions of methyl bromide: Environmental protection helps protect against human health risks

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    Budnik Lygia T

    2012-01-01

    Full Text Available Abstract Background Although ozone-depleting methyl bromide was destined for phase-out by 2005, it is still widely applied as a consequence of various critical-use-exemptions and mandatory international regulations aiming to restrict the spread of pests and alien species (e.g. in globalized transport and storage. The withdrawal of methyl bromide because of its environmental risk could fortuitously help in the containment of its human toxicity. Methods We performed a systematic review of the literature, including in vitro toxicological and epidemiological studies of occupational and community exposure to the halogenated hydrocarbon pesticide methyl bromide. We focused on toxic (especially chronic or carcinogenic effects from the use of methyl bromide, on biomonitoring data and reference values. Eligible epidemiological studies were subjected to meta-analysis. Results Out of the 542 peer reviewed publications between 1990-2011, we found only 91 referring to toxicity of methyl bromide and 29 using the term "carcinogenic", "neoplastic" or "mutagenic". Several studies provide new additional data pertaining to the mechanistic aspects of methyl bromide toxicity. Few studies have performed a detailed exposure assessment including biomonitoring. Three evaluated epidemiological studies assessed a possible association between cancer and methyl bromide. Overall, exposure to methyl bromide is associated with an increased risk of prostate cancer OR, 1.21; 95% CI (0,98-1.49, P = 0.076. Two epidemiological studies have analyzed environmental, non-occupational exposure to methyl bromide providing evidence for its health risk to the general public. None of the epidemiological studies addressed its use as a fumigant in freight containers, although recent field and case reports do refer to its toxic effects associated with its use in shipping and storage. Conclusions Both the epidemiological evidence and toxicological data suggest a possible link between methyl

  10. Potentially Toxic Elements and Health Risk Assessment in Farmland Systems around High-Concentrated Arsenic Coal Mining in Xingren, China

    Directory of Open Access Journals (Sweden)

    Ying-ju Li

    2018-01-01

    Full Text Available The health risk of potentially toxic elements (PTEs via contamination of the food chain has attracted widespread concern. The aim of this study is to evaluate the effects of PTEs in environment and human body (fingernail, hair, and blood of people living in agricultural soil near arsenic coal mining areas in Xingren County (Guizhou, southwest China. 89 crop samples which included vegetables, rice, maize, and coix seed and their corresponding soils and 17 local surface water and biological tissue samples (41 × 3 in near arsenic coal mining areas were collected, and the concentrations of potentially toxic elements (As, Cd, Cu, Cr, and Pb in all the samples were determined. The health risk assessment methods developed by the United States Environmental Protection Agency were employed to explore the potential health hazards of PTEs in soils growing crops. Results showed that 4 toxic elements, Cd, Cu, As, and Cr, were found to have different degrees of contamination in soils in the studied area. The total concentration of toxic elements (As, Cr, Cu, and Pb in fingernail, hair, and blood samples were 90.50, 69.31, and 6.90 mg·kg−1, respectively. Fingernail samples from females were more likely to show exposure to trace metals compared to males. As the age of the subject increased, the concentration of As also increased in all three biological samples. The risk assessment for the mean hazard index value from the consumption of local food crops was 14.81, indicating that consumers may experience adverse, noncarcinogenic health effects. The estimated mean total cancer risk value of was 5.3 × 10−3, which was approximately 10 to 1000 times higher than the acceptable range of 10−6–10−4, indicating serious carcinogenic risks for local people consuming crops from the area. This study provides evidence that local residents in this study area may be at a high risk of disease caused from toxic element exposure.

  11. Reproductive effects of two neonicotinoid insecticides on mouse sperm function and early embryonic development in vitro.

    Directory of Open Access Journals (Sweden)

    Yi-Hua Gu

    Full Text Available Acetamiprid (ACE and imidacloprid (IMI are two major members in the family of neonicotinoid pesticides, which are synthesized with a higher selectivity to insects. The present study determined and compared in vitro effects of ACE, IMI and nicotine on mammalian reproduction by using an integrated testing strategy for reproductive toxicology, which covered sperm quality, sperm penetration into oocytes and preimplantation embryonic development. Direct chemical exposure (500 µM or 5 mM on spermatozoa during capacitation was performed, and in vitro fertilization (IVF process, zygotes and 2-cell embryos were respectively incubated with chemical-supplemented medium until blastocyst formation to evaluate the reproductive toxicity of these chemicals and monitor the stages mainly affected. Generally, treatment of 500 µM or 5 mM chemicals for 30 min did not change sperm motility and DNA integrity significantly but the fertilization ability in in vitro fertilization (IVF process, indicating that IVF process could detect and distinguish subtle effect of spermatozoa exposed to different chemicals. Culture experiment in the presence of chemicals in medium showed that fertilization process and zygotes are adversely affected by direct exposure of chemicals (PIMI>ACE, whereas developmental progression of 2-cell stage embryos was similar to controls (P>0.05. These findings unveiled the hazardous effects of neonicotinoid pesticides exposure on mammalian sperm fertilization ability as well as embryonic development, raising the concerns that neonicotinoid pesticides may pose reproductive risks on human reproductive health, especially in professional populations.

  12. Preliminary Assessment of Health Risks of Potentially Toxic Elements in Settled Dust over Beijing Urban Area

    Directory of Open Access Journals (Sweden)

    Dejun Wan

    2016-05-01

    Full Text Available To examine levels, health risks, sources, and spatial distributions of potentially toxic elements in settled dust over Beijing urban area, 62 samples were collected mostly from residential building outdoor surfaces, and their <63 μm fractions were measured for 12 potentially toxic elements. The results show that V, Cr, Mn, Co, Ni, and Ba in dust are from predominantly natural sources, whereas Cu, Zn, As, Cd, Sb, and Pb mostly originate from anthropogenic sources. Exposure to these elements in dust has significant non-cancer risks to children but insignificant to adults. Cancer risks of Cr, Co, Ni, As, and Cd via inhalation and dermal contact are below the threshold of 10−6–10−4 but As via dust ingestion shows a tolerable risk. The non-cancer risks to children are contributed mainly (75% by As, Pb, and Sb, and dominantly (92% via dust ingestion, with relatively higher risks mainly occurring in the eastern and northeastern Beijing urban areas. Although Cd, Zn, and Cu in dust are heavily affected by anthropogenic sources, their health risks are insignificant. Source appointments suggest that coal burning emissions, the dominant source of As, are likely the largest contributors to the health risk, and traffic-related and industrial emissions are also important because they contribute most of the Pb and Sb in dust.

  13. Clinical endometritis in an Argentinean herd of dairy cows: risk factors and reproductive efficiency.

    Science.gov (United States)

    Giuliodori, M J; Magnasco, R P; Becu-Villalobos, D; Lacau-Mengido, I M; Risco, C A; de la Sota, R L

    2013-01-01

    The objectives of this study were to assess the clinical and metabolic risk factors for clinical endometritis, the likelihood for having a normal vaginal discharge during postpartum, and the effects of endometritis on milk yield, reproductive efficiency, and metabolic status in Holstein cows. The study was conducted in a commercial dairy herd (Cordoba, Argentina) where 303 Holstein cows were enrolled. Cows were body condition scored (1 to 5) and tail bled on -14, 7, 21, 31, 41, and 50 d relative to parturition. Cows having a vaginal discharge with presence of pus between 21 and 41 d postpartum (dpp) were diagnosed as having clinical endometritis. Plasma blood samples were analyzed for nonesterified fatty acids (NEFA), β-hydroxybutyrate (BHBA), and blood urea nitrogen using commercial kits and insulin-like growth factor 1, insulin, and leptin by RIA. Data were analyzed with PROC MIXED, PROC GENMOD, and PROC PHREG of SAS (SAS Institute Inc., Cary, NC). Abnormal calving and puerperal metritis increased the risk for endometritis [adjusted odds ratio (AOR)=2.21 for both]. High prepartum NEFA and high postpartum BHBA increased the risk for endometritis (AOR=1.003 and 1.001, respectively), whereas high prepartum blood urea nitrogen reduced it (AOR=0.853). Cut-offs of 456.6 μM NEFA and 402.5 μM BHBA had sensitivities of 0.69 and 0.58, and specificities of 0.88 and 0.86, respectively. The likelihood for having normal vaginal discharge increased with time (∼1% × dpp) and with normal calving. Cows with endometritis had higher milk yield than normal herdmates (27.8±0.9 vs. 25.7±0.4 kg/d), lower risk for pregnancy by 100 dpp (AOR=0.10), higher nonpregnancy risk by 200 dpp (AOR=2.87), and higher risk for culling than normal cows (AOR=2.28). Cows with endometritis had a lower hazard rate (0.44) for pregnancy and had approximately 70 d longer calving-to-conception intervals. Finally, endometritis had no effect on metabolic hormones. In conclusion, the risk for clinical

  14. Adverse effects of tributyltin on reproduction of Japanese medaka, Oryzias latipes

    OpenAIRE

    NAKAYAMA, Kei; OSHIMA, Yuji

    2008-01-01

    Tributyltin (TBT) is a typical endocrine disruptor that can induce imposex in mollusks and interfere with the reproduction in bivalves and fish. Our group has been studied the toxic effects of TBT using Japanese medaka (Oryzias latipes) as a model organism, and evaluated the effects on reproduction and behavior of medaka exposed to TBT. A series of our studies has demonstrated that TBT suppresses mating behavior in male and depresses fertility. We also observed that TBT exposure causes abnorm...

  15. Evaluating the toxicity of selected types of nanochemicals.

    Science.gov (United States)

    Kumar, Vineet; Kumari, Avnesh; Guleria, Praveen; Yadav, Sudesh Kumar

    2012-01-01

    . NPs have produced an array of different toxic effects in many different types of in vivo and in vitro studies. The types of effects that NPs have produced are those on the pulmonary, cardiac, reproductive, renal and cutaneous systems, as well as on various cell lines. After exposures, significant accumulations of NPs have been found in the lungs, brain, liver, spleen, and bones of test species. It has been well established that the degree of toxicity produced by NPs is linked to their surface properties. Soluble NPs are rendered toxic because of their constituents; however, the situation is entirely different for insoluble NPs. Stable metal oxides do not show any toxicity, whereas metallic NPs that have redox potential may be cytotoxic and genotoxic. The available data on NP toxicity is unfortunately limited, and hence, does not allow scientists to yet make a significant quantitative risk assessment of the safety of synthesized NPs. In this review, we have endeavored to illustrate the importance of having and using results from existing nanotoxicological studies and for developing new and more useful future risk assessment systems. Increased efforts of both an individual and collective nature are required to explore the future pros and cons of nanotechnology.

  16. Health risks in international container and bulk cargo transport due to volatile toxic compounds.

    Science.gov (United States)

    Baur, Xaver; Budnik, Lygia Therese; Zhao, Zhiwei; Bratveit, Magne; Djurhuus, Rune; Verschoor, Louis; Rubino, Federico Maria; Colosio, Claudio; Jepsen, Jorgen R

    2015-01-01

    To ensure the preservation and quality of the goods, physical (i.e. radiation) or chemical pest control is needed. The dark side of such consents may bear health risks in international transport and production sharing. In fact, between 10% and 20% of all containers arriving European harbors were shown to contain volatile toxic substances above the exposure limit values. Possible exposure to these toxic chemicals may occur not only for the applicators but also the receiver by off gassing from products, packing materials or transport units like containers. A number of intoxications, some with lethal outcome, occur not only during the fumigation, but also during freight transport (on bulk carriers and other transport vessels), as well as in the logistic lines during loading and unloading. Risk occupations include dock-workers, seafarers, inspectors, as well as the usually uninformed workers of importing enterprises that unload the products. Bystanders as well as vulnerable consumers may also be at risk. Ongoing studies focus on the release of these toxic volatile substances from various goods. It was shown that the half-lives of the off-gassing process range between minutes and months, depending on the toxic substance, its chemical reactivity, concentration, the temperature, the contaminated matrix (goods and packing materials), and the packing density in the transport units. Regulations on declaration and handling dangerous goods are mostly not followed. It is obvious that this hazardous situation in freight transport urgently requires preventive steps. In order to improve awareness and relevant knowledge there is a need for more comprehensive information on chemical hazards and a broader implementation of the already existing regulations and guidelines, such as those from ILO, IMO, and national authorities. It is also necessary to have regular controls by the authorities on a worldwide scale, which should be followed by sanctions in case of disregarding regulations

  17. Triclosan: environmental exposure, toxicity and mechanisms of action.

    Science.gov (United States)

    Dann, Andrea B; Hontela, Alice

    2011-05-01

    Triclosan [5-chloro-2-(2,4-dichlorophenoxy)phenol; TCS] is a broad spectrum antibacterial agent used in personal care, veterinary, industrial and household products. TCS is commonly detected in aquatic ecosystems, as it is only partially removed during the wastewater treatment process. Sorption, biodegradation and photolytic degradation mitigate the availability of TCS to aquatic biota; however the by-products such as methyltriclosan and other chlorinated phenols may be more resistant to degradation and have higher toxicity than the parent compound. The continuous exposure of aquatic organisms to TCS, coupled with its bioaccumulation potential, have led to detectable levels of the antimicrobial in a number of aquatic species. TCS has been also detected in breast milk, urine and plasma, with levels of TCS in the blood correlating with consumer use patterns of the antimicrobial. Mammalian systemic toxicity studies indicate that TCS is neither acutely toxic, mutagenic, carcinogenic, nor a developmental toxicant. Recently, however, concern has been raised over TCS's potential for endocrine disruption, as the antimicrobial has been shown to disrupt thyroid hormone homeostasis and possibly the reproductive axis. Moreover, there is strong evidence that aquatic species such as algae, invertebrates and certain types of fish are much more sensitive to TCS than mammals. TCS is highly toxic to algae and exerts reproductive and developmental effects in some fish. The potential for endocrine disruption and antibiotic cross-resistance highlights the importance of the judicious use of TCS, whereby the use of TCS should be limited to applications where it has been shown to be effective. Copyright © 2011 John Wiley & Sons, Ltd.

  18. Altered Reproductive Function and Amphibian Declines

    OpenAIRE

    Gallipeau, Sherrie

    2014-01-01

    Agrochemical exposure is one of the factors that contributes to worldwide amphibian declines. Most studies that examine agrochemicals and amphibian declines focus on toxicity. However, declines are more likely caused by the sub-lethal effects of agrochemical exposure. Past emphases on the lethal effects of agrochemical exposure have overshadowed the contribution of decreased recruitment in amphibian declines. Additionally, studies that examine agrochemicals and reproductive function tend to f...

  19. Patients Undergoing Radiation Therapy Are at Risk of Financial Toxicity: A Patient-based Prospective Survey Study.

    Science.gov (United States)

    Palmer, Joshua D; Patel, Tejash T; Eldredge-Hindy, Harriet; Keith, Scott W; Patel, Tapas; Malatesta, Theresa; DiNome, Jessie; Lowther, Anne; Ferguson, Linda; Wagenborg, Sally; Smyles, John; Babaria, Usha; Stabile, Richard; Gressen, Eric; Rudoler, Shari; Fisher, Scot A

    2018-06-01

    Little is known about the financial burden experienced by patients receiving radiation therapy. Furthermore, currently, no financial toxicity screening tools have been validated for use in radiation oncology. Physician surveys were used to gauge provider understanding of treatment costs and their willingness to adopt the use of financial toxicity screening tools. Post-treatment patient surveys were used to investigate the covariates of treatment-induced financial risk. Of the 210 radiation oncologists who completed our survey, 53% reported being "very concerned" with treatment-related costs negatively affecting their patients, and 80% believed that a financial toxicity screening tool would be useful in practice. An analysis of patient surveys using logistic regression found age and cancer site to be the most important variables associated with financial toxicity. Thirty-four patients (22%) experienced financial toxicity related to treatment. The financial toxicities experienced were loss of job (28%), loss of income (24%), difficulty paying their rent or mortgage (20%), difficulty paying for transportation (15%), and difficulty paying for meals (13%). Financial toxicity is an important measure for patients and providers and is experienced by approximately one quarter of patients. Further studies to improve models to predict financial toxicity and how financial toxicity is related to patient outcomes and quality of life are warranted. Copyright © 2018 Elsevier Inc. All rights reserved.

  20. Effects of dietary uranium on reproductive endpoints--fecundity, survival, reproductive success--of the fish Danio rerio.

    Science.gov (United States)

    Simon, Olivier; Mottin, Elmina; Geffroy, Benjamin; Hinton, Thomas

    2011-01-01

    Exposure to metal-contaminated water has been shown to result in a number of reproductive abnormalities in adult and larvae fish, such as failure of oocyte maturation and teratogenic effects. Recently, dietary uptake of metals by fish has been recognized as a critical route of exposure, however, the mechanisms of metal uptake and toxicity are poorly understood and in need of further investigation. The objectives of the present study are to quantify uranium (U dietary transfers from spiked artificial diets) in Danio rerio tissues and embryos, as well as establish its effect on reproduction and embryonic development. Uranium's environmental prominence is currently increasing because of new mining and milling activities. Uranium concentrations range from 0.02 µg/L in natural waters to 2 mg/L. The focus of this study was to examine the trophic transfer and effects of U following exposure modalities (dose, exposure duration 1 to 20 d). Two different isotopes were used to distinguish between chemical and radioactivity toxicity of U. Results showed that U trophic transfer was low (0.52%). Uranium tissue distributions showed that accumulation occurred in digestive organs (liver, digestive tract) following dietary exposure. High levels of U were measured in the gonads (female in particular, >20% of relative burden). High U accumulation levels in eggs indicated maternal transfer of the contaminant. Moreover, U trophic exposure led to a reduction in reproduction success as a function of U accumulated levels. High U exposure conditions strongly reduced the total number of eggs (50%) and their viability at 10 d (reduction of the clutch number, low quality of eggs). © 2010 SETAC.

  1. Influence of heavy metals and 4-nonylphenol on reproductive function in fish.

    Science.gov (United States)

    Popek, Włodzimierz; Dietrich, Grzegorz; Glogowski, Jan; Demska-Zakeś, Krystyna; Drag-Kozak, Ewa; Sionkowski, Jan; Łuszczek-Trojan, Ewa; Epler, Piotr; Demianowicz, Wiesław; Sarosiek, Beata; Kowalski, Radosław; Jankun, Małgorzata; Zakeś, Zdzisław; Król, Jarosław; Czerniak, Stanisław; Szczepkowski, Mirosław

    2006-01-01

    Many industrial and agricultural chemicals (including heavy metals and alkylphenols) present in the environment have adverse effects on the reproductive function in fish. Three studies were conducted to assess toxicity of these chemicals towards reproduction of freshwater fish. It was shown that heavy metals added to the diets accumulate in brain tissue of carp, and this accumulation results in inhibition of the secretion of noradrenaline and stimulation of the secretion of dopamine in the hypothalamus. These processes results in a disturbance of hormonal equilibrium of the hypothalamo-pituitary system, which can unfavorably influence the efficiency of artificial spawning in fish. Quality of salmonid and sturgeon sperm was impaired after in vitro exposure to heavy metals. The degree of this toxic effect was species-specific. It was demonstrated that sperm motility parameters appeared to be good indicators of adverse effects of heavy metals fish sperm. The protection role of seminal plasma against toxic effects of heavy metals was suggested for salmonid fish. Oral application of 4-nonylphenol (NP) disrupted reproduction in pikeperch. In juvenile fish a decrease in the percentage of males and an increase of intersex fish was observed in relation to dose of NP and time of exposure to this alkylphenol. Exposure of adult males to the NP led to the reduction in fecundity, milt quality and fertility.

  2. Risk factors and the economic impact of ovarian cysts on reproductive performance of dairy cows in Korea.

    Science.gov (United States)

    Kim, Ki-Doek; Ki, Kwang-Sook; Kang, Hyun-Gu; Kim, Ill-Hwa

    2005-08-01

    The objectives of this study were to determine the risk factors for development of postpartum ovarian cysts by evaluating several reproductive factors in individual cows, and to determine the economic impact of ovarian cysts on subsequent reproductive performance in dairy herds in Korea. The data, including cow parity, abnormal puerperium, endometritis, body condition score (BCS), and breeding status were collected from 634 cows in 9 dairy herds. We used logistic regression to evaluate the effects of these factors on ovarian cysts. A stepwise procedure, used to obtain the appropriate model with alpha=0.05, revealed that cow parity was the most important risk factor for ovarian cyst development within 8 weeks postpartum, while development of endometritis and BCS loss>or=1 from the dry period to 8 weeks postpartum were the most important risk factors for ovarian cyst development beyond 8 weeks postpartum. The occurrence of ovarian cysts beyond 8 weeks postpartum prolonged (Pconception (77 days), and increased (Prate (7.8%), while ovarian cyst development within 8 weeks postpartum did not affect (P>0.05) the mean intervals from calving to first service and conception or the culling rate. The economic loss resulting from the occurrence of ovarian cysts was estimated at approximately 823,996 won ($687) due to effects on the cost of nutrition, average growth of calves, labor and medical costs, and culling. These results suggest that cow parity is correlated with the development of ovarian cysts within 8 weeks postpartum, and endometritis and BCS loss>or=1 from the dry period to 8 weeks postpartum are correlated with the development of ovarian cysts after 8 weeks postpartum, which decreases reproductive performance and results in economic loss in dairy herds in Korea.

  3. Sexual dysfunction among reproductive-aged Chinese married women in Hong Kong: prevalence, risk factors, and associated consequences.

    Science.gov (United States)

    Zhang, Huiping; Fan, Susan; Yip, Paul S F

    2015-03-01

    Although female sexual dysfunction (FSD) is a serious public health issue endangering women's well-being, systematic research on FSD among reproductive-aged Chinese women in Hong Kong is quite scarce. This study aims to estimate the prevalence, risk factors, and associated consequences of FSD among reproductive-aged Chinese married women in Hong Kong. This study was based on a community-based survey across Hong Kong conducted by the Family Planning Association of Hong Kong in 2012 with 1,518 married women aged 21-49 years. The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition classification was adopted to assess FSD. It was found that 25.6% of the married women surveyed reported at least one form of sexual dysfunction and that the prevalence of six domains of sexual dysfunction was as follows: 10.6% for lack of interest in sex, 10.5% for not finding sex pleasurable, 9.3% for lubrication difficulties, 8.8% for inability to achieve orgasm, 8.8% for orgasm delay, and 8.4% for physical pain during sex. Multivariate analyses showed that low education and income, average or poor health, lower frequency of sex, abortion history, traditional attitudes toward sex, and marital dissatisfaction are all significant risk factors for different components of FSD. It was also been found that four domains of FSD (the exceptions being orgasm delay and physical pain during sex) have severe consequences for married women's life satisfaction and sexual satisfaction. The prevalence of FSD is lower among reproductive-aged Chinese married women in Hong Kong than among women in the United States and some Asian countries. The risk factors associated with FSD include sociodemographic factors, physical health, sexual experience and attitudes, and relationship factors. FSD has significant consequences for married women's life quality. These findings have great implications for FSD prevention and relevant service delivery. © 2014 International Society for Sexual

  4. Adjuvant chemotherapy and risk of gastrointestinal, hematologic, and cardiac toxicities in elderly patients with stage III colon cancer.

    Science.gov (United States)

    Hu, Chung-Yuan; Chan, Wenyaw; Delclos, George P; Du, Xianglin L

    2012-06-01

    Randomized trials have established the effectiveness of 5-fluorouracil-based adjuvant chemotherapy for stage III resectable colon cancer but the toxicity has not been well established outside the trial setting. The objective of this study was to estimate the risk of various toxicity-related endpoints among the elderly patients. Patients diagnosed with stage III colon cancer in 1991 to 2005 were identified from the Surveillance, Epidemiology, and End Results-Medicare database. Chemotherapy use within 3 months after tumor resection was identified from submitted claims. We reported the 3-month cumulative incidence rate (CIR) for gastrointestinal and hematologic toxicities. The risk of ischemic heart disease in relation to chemotherapy use and length was assessed using Cox regression models, stratified by age and comorbidity subgroups. Of the 12,099 patients, 63.9% (n=7740) received adjuvant chemotherapy. Common gastrointestinal and hematologic toxicities among chemotherapy group include volume depletion disorder (CIR=9.1%), agranulocytosis (CIR=3.4%), diarrhea (CIR=2.4%), nausea and vomiting (CIR=2.3%). Chemotherapy use was significantly associated with the onset of these toxicities [hazard ratio (HR)=2.76; 95% confidence interval (95% CI)=2.42-3.15]. The risk of ischemic heart disease was slightly associated with chemotherapy use (HR=1.08, 95% CI=0.96-1.22), but significant only among patients aged colon cancer. On account of the effects of these side effects on treatment discontinuation, rehospitalization, and overall health status, some close monitoring and preventive measures may be emphasized to maximize the benefits of adjuvant chemotherapy.

  5. Toxic Effects of Bisphenol A, Propyl Paraben, and Triclosan on Caenorhabditis elegans

    Directory of Open Access Journals (Sweden)

    María Cecilia García-Espiñeira

    2018-04-01

    Full Text Available Bisphenol A (BPA is a ubiquitous plasticizer which is absorbed by ingestion and dermal contact; propyl paraben (PPB inhibits the microbiome and extends the shelf life of many personal care products, whereas triclosan (TCS is commonly found in antiseptics, disinfectants, or additives. In this work, Caenorhabditis elegans was used as a biological model to assess the toxic effects of BPA, PPB, and TCS. The wild type strain, Bristol N2, was used in bioassays with the endpoints of lethality, growth, and reproduction; green fluorescent protein (GFP transgenic strains with the hsp-3, hsp-4, hsp-16.2, hsp-70, sod-1, sod-4, cyp-35A4, cyp-29A2, and skn-1 genes were evaluated for their mRNA expression through fluorescence measurement; and quick Oil Red O (q ORO was utilized to stain lipid deposits. Lethality was concentration-dependent, while TCS and PPB showed more toxicity than BPA. BPA augmented worm length, while PPB reduced it. All toxicants moderately increased the width and the width–length ratio. BPA and PPB promoted reproduction, in contrast to TCS, which diminished it. All toxicants affected the mRNA expression of genes related to cellular stress, control of reactive oxygen species, and nuclear receptor activation. Lipid accumulation occurred in exposed worms. In conclusion, BPA, PPB, and TCS alter the physiology of growth, lipid accumulation, and reproduction in C. elegans, most likely through oxidative stress mechanisms.

  6. Mercury and selenium contamination in waterbird eggs and risk to avian reproduction at Great Salt Lake, Utah

    Science.gov (United States)

    Ackerman, Joshua T.; Herzog, Mark P.; Hartman, Christopher A.; Isanhart, John P.; Herring, Garth; Vaughn, Sharon; Cavitt, John F.; Eagles-Smith, Collin A.; Browers, Howard; Cline, Chris; Vest, Josh

    2015-01-01

    The wetlands of the Great Salt Lake ecosystem are recognized regionally, nationally, and hemispherically for their importance as breeding, wintering, and migratory habitat for diverse groups of waterbirds. Bear River Migratory Bird Refuge is the largest freshwater component of the Great Salt Lake ecosystem and provides critical breeding habitat for more than 60 bird species. However, the Great Salt Lake ecosystem also has a history of both mercury and selenium contamination, and this pollution could reduce the health and reproductive success of waterbirds. The overall objective of this study was to evaluate the risk of mercury and selenium contamination to birds breeding within Great Salt Lake, especially at Bear River Migratory Bird Refuge, and to identify the waterbird species and areas at greatest risk to contamination. We sampled eggs from 33 species of birds breeding within wetlands of Great Salt Lake during 2010 ̶ 2012 and focused on American avocets (Recurvirostra americana), black-necked stilts (Himantopus mexicanus), Forster’s terns (Sterna forsteri), white-faced ibis (Plegadis chihi), and marsh wrens (Cistothorus palustris) for additional studies of the effects of contaminants on reproduction.

  7. Gene-environment interaction and male reproductive function

    Science.gov (United States)

    Axelsson, Jonatan; Bonde, Jens Peter; Giwercman, Yvonne L.; Rylander, Lars; Giwercman, Aleksander

    2010-01-01

    As genetic factors can hardly explain the changes taking place during short time spans, environmental and lifestyle-related factors have been suggested as the causes of time-related deterioration of male reproductive function. However, considering the strong heterogeneity of male fecundity between and within populations, genetic variants might be important determinants of the individual susceptibility to the adverse effects of environment or lifestyle. Although the possible mechanisms of such interplay in relation to the reproductive system are largely unknown, some recent studies have indicated that specific genotypes may confer a larger risk of male reproductive disorders following certain exposures. This paper presents a critical review of animal and human evidence on how genes may modify environmental effects on male reproductive function. Some examples have been found that support this mechanism, but the number of studies is still limited. This type of interaction studies may improve our understanding of normal physiology and help us to identify the risk factors to male reproductive malfunction. We also shortly discuss other aspects of gene-environment interaction specifically associated with the issue of reproduction, namely environmental and lifestyle factors as the cause of sperm DNA damage. It remains to be investigated to what extent such genetic changes, by natural conception or through the use of assisted reproductive techniques, are transmitted to the next generation, thereby causing increased morbidity in the offspring. PMID:20348940

  8. The combined fixed-dose antituberculous drugs alter some reproductive functions with oxidative stress involvement in wistar rats

    Directory of Open Access Journals (Sweden)

    O. Awodele, B.Pharm M.Sc MPH PhD D.Sc FPCPharm FASI

    Full Text Available The reproductive toxicity of combined fixed-dose first-line antituberculosis (CFDAT regimen was assessed in rats. Thirty-two (32 Wistar rats weighing 168.1 ± 8.0 g were divided into four groups of eight rats per group. Two groups of male and female rats were administered oral distilled water (1.6 ml and CFDAT drugs containing rifampicin, isoniazid, pyrazinamide and ethambutol (RIPE, 92.5 mg/m2 per body surface area respectively for forty-five days. Serum follicle stimulating hormone, luteinizing and testosterone were reduced significantly (p  0.05 levels in the treated females. In addition, RIPE reduced (p < 0.05 total proteins levels and increased (p < 0.05, 53% catalase levels in male but not female animals. Superoxide dismutase, glutathione-S-transferase, glutathione peroxidase, reduced glutathione levels as well as lipid peroxidation were unaltered in all rats respectively. Histopathological studies revealed congested peritesticular vessels and no changes in the ovary when compared with control. Overall, our results demonstrate reproductive toxicity potentials of RIPE in the rat, thus, suggesting that these reproductive parameters be monitored during antituberculous chemotherapy. Keywords: Fixed dose combined antituberculous drugs, Sub-chronic study, Reproductive toxicity, Rats

  9. Reproductive health and access to healthcare facilities: risk factors for depression and anxiety in women with an earthquake experience.

    Science.gov (United States)

    Anwar, Jasim; Mpofu, Elias; Matthews, Lynda R; Shadoul, Ahmed Farah; Brock, Kaye E

    2011-06-30

    The reproductive and mental health of women contributes significantly to their overall well-being. Three of the eight Millennium Development Goals are directly related to reproductive and sexual health while mental disorders make up three of the ten leading causes of disease burden in low and middle-income countries. Among mental disorders, depression and anxiety are two of the most prevalent. In the context of slower progress in achieving Millennium Development Goals in developing countries and the ever-increasing man-made and natural disasters in these areas, it is important to understand the association between reproductive health and mental health among women with post-disaster experiences. This was a cross-sectional study with a sample of 387 women of reproductive age (15-49 years) randomly selected from the October 2005 earthquake affected areas of Pakistan. Data on reproductive health was collected using the Centers for Disease Control reproductive health assessment toolkit. Depression and anxiety were measured using the Hopkins Symptom Checklist-25, while earthquake experiences were captured using the Harvard Trauma Questionnaire. The association of either depression or anxiety with socio-demographic variables, earthquake experiences, reproductive health and access to health facilities was estimated using multivariate logistic regression. Post-earthquake reproductive health events together with economic deprivation, lower family support and poorer access to health care facilities explained a significant proportion of differences in the experiencing of clinical levels of depression and anxiety. For instance, women losing resources for subsistence, separation from family and experiencing reproductive health events such as having a stillbirth, having had an abortion, having had abnormal vaginal discharge or having had genital ulcers, were at significant risk of depression and anxiety. The relationship between women's post-earthquake mental health and

  10. Green Tea Protects Testes against Atrazine-induced Toxicity in Rat

    Directory of Open Access Journals (Sweden)

    Reza Kheirandish

    2017-06-01

    Full Text Available Background: Atrazine (ATZ is a common herbicide in agriculture for control of grass and broad-leaved weeds. It persists in the environment and causes reproductive problems in both human and animals. The present study was aimed at protective effect of green tea against ATZ toxicity in the reproductive system of male rats. Methods: The present study was performed in Veterinary School, Shahid Bahonar University of Kerman in 2016. ATZ and treatment groups received ATZ daily 200 mg/kg BW orally for 14 d. In addition, 0.2% methanolic green tea extract was administrated in the treatment group. Results: In histopathologic investigation, number of germinal layers reduced in the most seminiferous tubules in the ATZ group and spermatids were absence. Necrotic spermatocytes, spermatids, and spermatozoa were evident in the testicular tubules. In the morphometric measurements, tubular diameter, germinal epithelium height, and meiosis index decreased significantly. Conclusion: Green tea extract had reduced testicular toxicity of atrazine significantly. ATZ induces toxicity through oxidative damage and green tea extract can protect the testes due to antioxidant activity of its polyphenols especially flavonoids.

  11. Computational Modeling and Simulation of Developmental Toxicity: what can we learn from a virtual embryo? (RIVM, Brussels)

    Science.gov (United States)

    Developmental and Reproductive Toxicity (DART) testing is important for assessing the potential consequences of drug and chemical exposure on human health and well-being. Complexity of pregnancy and the reproductive cycle makes DART testing challenging and costly for traditional ...

  12. Toxicity risk of non-target organs at risk receiving low-dose radiation: case report

    International Nuclear Information System (INIS)

    Shueng, Pei-Wei; Lin, Shih-Chiang; Chang, Hou-Tai; Chong, Ngot-Swan; Chen, Yu-Jen; Wang, Li-Ying; Hsieh, Yen-Ping; Hsieh, Chen-Hsi

    2009-01-01

    The spine is the most common site for bone metastases. Radiation therapy is a common treatment for palliation of pain and for prevention or treatment of spinal cord compression. Helical tomotherapy (HT), a new image-guided intensity modulated radiotherapy (IMRT), delivers highly conformal dose distributions and provides an impressive ability to spare adjacent organs at risk, thus increasing the local control of spinal column metastases and decreasing the potential risk of critical organs under treatment. However, there are a lot of non-target organs at risk (OARs) occupied by low dose with underestimate in this modern rotational IMRT treatment. Herein, we report a case of a pathologic compression fracture of the T9 vertebra in a 55-year-old patient with cholangiocarcinoma. The patient underwent HT at a dose of 30 Gy/10 fractions delivered to T8-T10 for symptom relief. Two weeks after the radiotherapy had been completed, the first course of chemotherapy comprising gemcitabine, fluorouracil, and leucovorin was administered. After two weeks of chemotherapy, however, the patient developed progressive dyspnea. A computed tomography scan of the chest revealed an interstitial pattern with traction bronchiectasis, diffuse ground-glass opacities, and cystic change with fibrosis. Acute radiation pneumonitis was diagnosed. Oncologists should be alert to the potential risk of radiation toxicities caused by low dose off-targets and abscopal effects even with highly conformal radiotherapy

  13. Reproductive toxicity of chromium in adult bonnet monkeys (Macaca radiata Geoffrey). Reversible oxidative stress in the semen

    International Nuclear Information System (INIS)

    Subramanian, Senthivinayagam; Rajendiran, Gopalakrishnan; Sekhar, Pasupathi; Gowri, Chandrahasan; Govindarajulu, Pera; Aruldhas, Mariajoseph Michael

    2006-01-01

    The present study was designed to test the hypothesis that oxidative stress mediates chromium-induced reproductive toxicity. Monthly semen samples were collected from adult monkeys (Macaca radiata), which were exposed to varying doses (50, 100, 200 and 400 ppm) of chromium (as potassium dichromate) for 6 months through drinking water. Chromium treatment decreased sperm count, sperm forward motility and the specific activities of antioxidant enzymes, superoxide dismutase and catalase, and the concentration of reduced glutathione in both seminal plasma and sperm in a dose- and duration-dependent manner. On the other hand, the quantum of hydrogen peroxide in the seminal plasma/sperm from monkeys exposed to chromium increased with increasing dose and duration of chromium exposure. All these changes were reversed after 6 months of chromium-free exposure period. Simultaneous supplementation of vitamin C (0.5 g/L; 1.0 g/L; 2.0 g/L) prevented the development of chromium-induced oxidative stress. Data support the hypothesis and show that chronic chromium exposure induces a reversible oxidative stress in the seminal plasma and sperm by creating an imbalance between reactive oxygen species and antioxidant system, leading to sperm death and reduced motility of live sperm

  14. Toxic metals in tissues of fishes from the Black Sea and associated human health risk exposure.

    Science.gov (United States)

    Plavan, Gabriel; Jitar, Oana; Teodosiu, Carmen; Nicoara, Mircea; Micu, Dragos; Strungaru, Stefan-Adrian

    2017-03-01

    The anthropogenic activities in the Black Sea area are responsible for toxic metal contamination of sea food products. In this study, several toxic metals: cadmium, lead, nickel, chromium, and copper were quantified in different tissues (digestive tract, muscle, skeleton, skin) of nine fish species (Neogobius melanostomus, Belone belone, Solea solea, Trachurus mediterraneus ponticus, Sardina pilchardus, Engraulis encrasicolus, Pomatomus saltatrix, Sprattus sprattus, Scorpaena porcus) by using atomic absorption spectrometer with a high-resolution continuum source and graphite furnace technique (HR-CS GF-AAS), and the risk of fish meat consumption by the young human population was evaluated. These metals are used in high amounts in industries located near the coastline such as shipyard construction and industrial plants. Toxic metal accumulation depends on fish feeding behavior, abiotic conditions, metal chemistry, and animal physiology. For instance, cadmium was measured in the muscle of the investigated species and average values of 0.0008-0.0338 mg kg -1 were obtained. The lowest average value of this metal was measured at benthic species N. melanostomus and the highest at the pelagic predator T. mediterraneus ponticus. Generally, the highest metal concentration was measured in the digestive tract that has the role of biofilter for these contaminants. The risk of contamination is significantly reduced by avoiding the consumption of certain fish tissues (digestive tract and skin for copper and skeleton for nickel). An estimation of the dietary metal intake to young consumers was realized for each of the studied species of fish from Romanian, Bulgarian, and Turkish waters, during the period 2001-2014 in order to evaluate the risks of chronic exposure in time due to metal toxicity. This estimation is important for the prevention of chronic exposure due to metal toxicity. Food exposure to studied metals showed a negative trend for Romania, Turkey, and Bulgaria based

  15. Emerging contaminants in Belgian marine waters: single toxicant and mixture risks of pharmaceuticals.

    Science.gov (United States)

    Claessens, Michiel; Vanhaecke, Lynn; Wille, Klaas; Janssen, Colin R

    2013-06-15

    Knowledge on the effects of pharmaceuticals on aquatic marine ecosystems is limited. The aim of this study was therefore to establish the effect thresholds of pharmaceutical compounds occurring in the Belgian marine environment for the marine diatom Phaeodactylum tricornutum, and subsequently perform an environmental risk assessment for these substances. Additionally, a screening-level risk assessment was performed for the pharmaceutical mixtures. No immediate risk for acute toxic effects of these compounds on P. tricornutum were apparent at the concentrations observed in the Belgian marine environment. In two Belgian coastal harbours however, a potential chronic risk was observed for the β-blocker propranolol. No additional risks arising from the exposure to mixtures of pharmaceuticals present in the sampling area could be detected. However, as risk characterization ratios for mixtures of up to 0.5 were observed, mixture effects could emerge should more compounds be taken into account. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Effects of two polybrominated diphenyl ethers (BDE-47, BDE-209) on the swimming behavior, population growth and reproduction of the rotifer Brachionus plicatilis.

    Science.gov (United States)

    Sha, Jingjing; Wang, You; Lv, Jianxia; Wang, Hong; Chen, Hongmei; Qi, Leilei; Tang, Xuexi

    2015-02-01

    Polybrominated diphenyl ethers (PBDEs) are new kinds of persistent organic pollutants (POPs) and their potential threats to the equilibrium and sustainability of marine ecosystems have raised worldwide concerns. Here, two kinds of PBDEs, tetra-BDE (BDE-47) and deca-BDE (BDE-209) were applied, and their toxic effects on the swimming behavior, population growth and reproduction of Brachionus plicatilis were investigated. The results showed that: (1) The actual concentrations of BDE-47 and -209 in the seawater phase measured by GC-MS (Gas Chromatography-Mass Spectrometer) were much lower than their nominal concentrations. (2) In accordance with the 24-hr acute tests, BDE-209 did not show any obvious swimming inhibition to rotifers, but a good correlation did exist between the swimming inhibition rate and BDE-47 concentration suggesting that BDE-47 is more toxic than BDE-209. (3) Both BDE-47 and -209 had a significant influence on the population growth and reproduction parameters of B. plicatilis including the population growth rate, the ratio of ovigerous females/non-ovigerous females (OF/NOF), the ratio of mictic females/amictic females (MF/AF), resting egg production and the mictic rate, which indicate that these parameters in B. plicatilis population were suitable for monitoring and assessing PBDEs. Our results suggest that BDE-47 and -209 are not acute lethal toxicants and may pose a low risk to marine rotifers at environmental concentrations for short-term exposure. They also accumulate differently into rotifers. Further research data are needed to understand the mechanisms responsible for the effects caused by PBDEs and to assess their risks accurately. Copyright © 2014. Published by Elsevier B.V.

  17. Progressive effects of silver nanoparticles on hormonal regulation of reproduction in male rats

    International Nuclear Information System (INIS)

    Dziendzikowska, K.; Krawczyńska, A.; Oczkowski, M.; Królikowski, T.; Brzóska, K.; Lankoff, A.; Dziendzikowski, M.; Stępkowski, T.; Kruszewski, M.

    2016-01-01

    The growing use of silver nanoparticles (AgNPs) in various applications, including consumer, agriculture and medicine products, has raised many concerns about the potential risks of nanoparticles (NPs) to human health and the environment. An increasing body of evidence suggests that AgNPs may have adverse effects of humans, thus the aim of this study was to investigate the effects of AgNPs on the male reproductive system. Silver particles (20 nm AgNPs (groups Ag I and Ag II) and 200 nm Ag sub-micron particles (SPs) (group Ag III)) were administered intravenously to male Wistar rats at a dose of 5 (groups Ag I and Ag III) or 10 (group Ag II) mg/kg of body weight. The biological material was sampled 24 h, 7 days and 28 days after injection. The obtained results revealed that the AgNPs had altered the luteinising hormone concentration in the plasma and the sex hormone concentration in the plasma and testes. Plasma and intratesticular levels of testosterone and dihydrotestosterone were significantly decreased both 7 and 28 days after treatment. No change in the prolactin and sex hormone-binding globulin concentration was observed. Exposure of the animals to AgNPs resulted in a considerable decrease in 5α-reductase type 1 and the aromatase protein level in the testis. Additionally, expression analysis of genes involved in steroidogenesis and the steroids metabolism revealed significant down-regulation of Star, Cyp11a1, Hsd3b1, Hsd17b3 and Srd5a1 mRNAs in AgNPs/AgSPs-exposed animals. The present study demonstrates the potential adverse effect on the hormonal regulation of the male reproductive function following AgNP/AgSP administration, in particular alterations of the sex steroid balance and expression of genes involved in steroidogenesis and the steroids metabolism. - Highlights: • Assessment of the toxic effects of AgNPs/AgSPs on the regulation of male reproductive function • AgNP −/AgSP-induced alterations of sex steroid status in male Wistar rats.

  18. Progressive effects of silver nanoparticles on hormonal regulation of reproduction in male rats

    Energy Technology Data Exchange (ETDEWEB)

    Dziendzikowska, K., E-mail: k.dziendzikowska@gmail.com [Division of Nutrition Physiology, Department of Dietetics, Faculty of Human Nutrition and Consumer Science, Warsaw University of Life Sciences – SGGW, Nowoursynowska 159C, 02-776 Warsaw (Poland); Krawczyńska, A. [Laboratory of Molecular Biology, The Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences, Instytucka 3, 05-110 Jabłonna (Poland); Oczkowski, M.; Królikowski, T. [Division of Nutrition Physiology, Department of Dietetics, Faculty of Human Nutrition and Consumer Science, Warsaw University of Life Sciences – SGGW, Nowoursynowska 159C, 02-776 Warsaw (Poland); Brzóska, K. [Centre for Radiobiology and Biological Dosimetry, Institute of Nuclear Chemistry and Technology, Dorodna 16, 03-195 Warsaw (Poland); Lankoff, A. [Centre for Radiobiology and Biological Dosimetry, Institute of Nuclear Chemistry and Technology, Dorodna 16, 03-195 Warsaw (Poland); Department of Radiobiology and Immunology, Institute of Biology, Jan Kochanowski University, Świetokrzyska 15, 25-406 Kielce (Poland); Dziendzikowski, M. [Airworthiness Division, Air Force Institute of Technology, Ks. Boleslawa 6, 01-494 Warsaw (Poland); Stępkowski, T. [Centre for Radiobiology and Biological Dosimetry, Institute of Nuclear Chemistry and Technology, Dorodna 16, 03-195 Warsaw (Poland); Kruszewski, M. [Department of Medical Biology and Translational Research, Faculty of Medicine, University of Information Technology and Management, Sucharskiego 2, 35-225 Rzeszów (Poland); Department of Molecular Biology and Translational Research, Institute of Rural Health, Jaczewskiego 2, 20-090 Lublin (Poland); and others

    2016-12-15

    The growing use of silver nanoparticles (AgNPs) in various applications, including consumer, agriculture and medicine products, has raised many concerns about the potential risks of nanoparticles (NPs) to human health and the environment. An increasing body of evidence suggests that AgNPs may have adverse effects of humans, thus the aim of this study was to investigate the effects of AgNPs on the male reproductive system. Silver particles (20 nm AgNPs (groups Ag I and Ag II) and 200 nm Ag sub-micron particles (SPs) (group Ag III)) were administered intravenously to male Wistar rats at a dose of 5 (groups Ag I and Ag III) or 10 (group Ag II) mg/kg of body weight. The biological material was sampled 24 h, 7 days and 28 days after injection. The obtained results revealed that the AgNPs had altered the luteinising hormone concentration in the plasma and the sex hormone concentration in the plasma and testes. Plasma and intratesticular levels of testosterone and dihydrotestosterone were significantly decreased both 7 and 28 days after treatment. No change in the prolactin and sex hormone-binding globulin concentration was observed. Exposure of the animals to AgNPs resulted in a considerable decrease in 5α-reductase type 1 and the aromatase protein level in the testis. Additionally, expression analysis of genes involved in steroidogenesis and the steroids metabolism revealed significant down-regulation of Star, Cyp11a1, Hsd3b1, Hsd17b3 and Srd5a1 mRNAs in AgNPs/AgSPs-exposed animals. The present study demonstrates the potential adverse effect on the hormonal regulation of the male reproductive function following AgNP/AgSP administration, in particular alterations of the sex steroid balance and expression of genes involved in steroidogenesis and the steroids metabolism. - Highlights: • Assessment of the toxic effects of AgNPs/AgSPs on the regulation of male reproductive function • AgNP −/AgSP-induced alterations of sex steroid status in male Wistar rats.

  19. Chronic disease risk factors among American Indian/Alaska Native women of reproductive age.

    Science.gov (United States)

    Amparo, Pamela; Farr, Sherry L; Dietz, Patricia M

    2011-11-01

    The magnitude of chronic conditions and risk factors among American Indian/Alaska Native women of reproductive age is unknown. The objective of our study was to estimate this magnitude. We analyzed data for 2,821 American Indian/Alaska Native women and 105,664 non-Hispanic white women aged 18 to 44 years from the 2005 and 2007 Behavioral Risk Factor Surveillance System. We examined prevalence of high cholesterol, high blood pressure, diabetes, body mass index (kg/m(2)) ≥25.0, physical inactivity, smoking, excessive alcohol consumption, and frequent mental distress, and the cumulative number of these chronic conditions and risk factors (≥3, 2, 1, or 0). In a multivariable, multinomial logistic regression model, we examined whether American Indian/Alaska Native race was associated with the cumulative number of chronic conditions and risk factors. American Indian/Alaska Native women, compared with white women, had significantly higher rates of high blood pressure, diabetes, obesity, smoking, and frequent mental distress. Of American Indian/Alaska Native women, 41% had 3 or more chronic conditions or risk factors compared with 27% of white women (χ(2), P Indian/Alaska Native race was not associated with having either 1, 2, or 3 or more chronic conditions or risk factors. Three out of every 5 American Indian/Alaska Native women aged 18 to 44 years have 3 or more chronic conditions or risk factors. Improving economic status and education for AI/AN women could help eliminate disparities in health status.

  20. Modelling the impact of toxic and disturbance stress on white-tailed eagle (Haliaeetus albicilla) populations.

    Science.gov (United States)

    Korsman, John C; Schipper, Aafke M; Lenders, H J Rob; Foppen, Ruud P B; Hendriks, A Jan

    2012-01-01

    Several studies have related breeding success and survival of sea eagles to toxic or non-toxic stress separately. In the present investigation, we analysed single and combined impacts of both toxic and disturbance stress on populations of white-tailed eagle (Haliaeetus albicilla), using an analytical single-species model. Chemical and eco(toxico)logical data reported from laboratory and field studies were used to parameterise and validate the model. The model was applied to assess the impact of ∑PCB, DDE and disturbance stress on the white-tailed eagle population in The Netherlands. Disturbance stress was incorporated through a 1.6% reduction in survival and a 10-50% reduction in reproduction. ∑PCB contamination from 1950 up to 1987 was found to be too high to allow the return of white-tailed eagle as a breeding species in that period. ∑PCB and population trends simulated for 2006-2050 suggest that future population growth is still reduced. Disturbance stress resulted in a reduced population development. The combination of both toxic and disturbance stress varied from a slower population development to a catastrophical reduction in population size, where the main cause was attributed to the reduction in reproduction of 50%. Application of the model was restricted by the current lack of quantitative dose-response relationships between non-toxic stress and survival and reproduction. Nevertheless, the model provides a first step towards integrating and quantifying the impacts of multiple stressors on white-tailed eagle populations.

  1. Choline supplementation alleviates fluoride-induced testicular toxicity by restoring the NGF and MEK expression in mice.

    Science.gov (United States)

    Zhang, Jianhai; Zhang, Yufang; Liang, Chen; Wang, Nasui; Zheng, Heping; Wang, Jundong

    2016-11-01

    Fluoride is known to cause male reproductive toxicity, and the elucidation of its underlying mechanisms is an ongoing research focus in reproductive toxicology and epidemiology. Choline, an essential nutrient, has been extensively studied for its benefits in nervous system yet was rarely discussed for its prospective effect in male reproductive system. This study aims to explore the potential protective role of choline against NaF-induced male reproductive toxicity via MAPK pathway. The male mice were administrated by 150mg/L NaF in drinking water, 5.75g/kg choline in diet, and their combination respectively from maternal gestation to postnatal 15weeks. The results showed that fluoride exposure reduced body weight growth, lowered sperm count and survival percentages, altered testicular histology, down-regulated the mRNA expressions of NGF, Ras, Raf, and MEK genes in testes, as well as significantly decreased the expressions of both NGF and phosphor-MEK proteins in testes. Examination of data from choline-treated mice revealed that choline supplementation ameliorated these fluoride-induced changes. Taken together, our findings suggest that choline supplementation alleviates fluoride-induced testicular toxicity by restoring the NGF and phosphor-MEK expression. The suitable dosage and supplementation periods of choline await further exploration. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Natural fertility, infertility and the role of medically assisted reproduction: The knowledge amongst women of reproductive age in North Queensland.

    Science.gov (United States)

    Cheung, Nicole K; Coffey, Anne; Woods, Cindy; de Costa, Caroline

    2018-04-16

    The demand for medically assisted reproduction continues to increase, with more women encountering challenges with fertility. Due to misconceptions and gaps in knowledge, women are often unaware of the risks related to delayed childbearing. Lack of understanding of natural fertility, infertility and the role of medically assisted reproduction can lead to emotional suffering and changes in family plans. To assess the understanding and knowledge that women of reproductive age in North Queensland have regarding natural fertility, infertility and the role of medically assisted reproduction. Data were collected from 120 women (30 nurses, 30 teachers, 30 university students and 30 Technical and Further Education students) via the distribution of a structured questionnaire. Participants were surveyed in person about their personal plans and opinions, knowledge about natural fertility, infertility and medically assisted reproduction, and their preferred source of information. Participants demonstrated suboptimal knowledge levels throughout all sections of the questionnaire, in particular when asked about medically assisted reproduction. When asked to identify their main source of information, 'friends and family' was the most popular choice. Results from this North Queensland study add to the existing international literature, highlighting the widespread nature of the problem. Without adequate understanding of natural fertility, the risks of infertility, and the role and limitations of medically assisted reproduction, women make uninformed decisions. Development of local reproductive health education programs need to be instigated in response. © 2018 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

  3. Low-protein diet does not alter reproductive, biochemical, and hematological parameters in pregnant Wistar rats

    Directory of Open Access Journals (Sweden)

    M.A.V. Barros

    2018-05-01

    Full Text Available The aim of this study was to investigate the reproductive, biochemical, and hematological outcomes of pregnant rats exposed to protein restriction. Wistar rat dams were fed a control normal-protein (NP, 17% protein, n=8 or a low-protein (LP, 8% protein, n=14 diet from the 1st to the 20th day of pregnancy. On the 20th day, the clinical signs of toxicity were evaluated. The pregnant rats were then anesthetized and blood samples were collected for biochemical-hematological analyses, and laparotomy was performed to evaluate reproductive parameters. No sign of toxicity, or differences (P>0.05 in body weight gain and biochemical parameters (urea, creatinine, albumin, globulin, and total protein between NP and LP pregnant dams were observed. Similarly, hematological data, including red blood cell count, white blood cell count, hemoglobin, hematocrit, red blood cell distribution width (coefficient of variation, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, % lymphocytes, absolute lymphocyte count, platelet count, and mean platelet volume were similar (P>0.05 at the end of pregnancy. Reproductive parameters (the dam-offspring relationship, ovary mass, placenta mass, number of corpora lutea, implantation index, resorption index, and the pre- and post-implantation loss rates were also not different (P>0.05 between NP and LP pregnant dams. The present data showed that a protein-restricted diet during pregnancy did not alter reproductive, biochemical, and hematological parameters and seems not to have any toxic effect on pregnant Wistar rats.

  4. Overview of toxicity data and risk assessment methods for evaluating the chemical effects of depleted uranium compounds

    International Nuclear Information System (INIS)

    Hartmann, H.M.; Monette, F.A.; Avci, H.I.

    2000-01-01

    In the United States, depleted uranium is handled or used in several chemical forms by both governmental agencies and private industry (primarily companies producing and machining depleted uranium metal for military applications). Human exposure can occur as a result of handling these compounds, routine low-level effluent releases to the environment from processing facilities, or materials being accidentally released from storage locations or during processing or transportation. Exposure to uranium can result in both chemical and radiological toxicity, but in most instances chemical toxicity is of greater concern. This article discusses the chemical toxic effects from human exposure to depleted uranium compounds that are likely to be handled during the long-term management and use of depleted uranium hexafluoride (UF 6 ) inventories in the United States. It also reviews representative publications in the toxicological literature to establish appropriate reference values for risk assessments. Methods are described for evaluating chemical toxicity caused by chronic low-level exposure and acute exposure. Example risk evaluations are provided for illustration. Preliminary results indicate that chemical effects of chronic exposure to uranium compounds under normal operating conditions would be negligibly small. Results also show that acute exposures under certain accident conditions could cause adverse chemical effects among the populations exposed.

  5. Suitability of a Saccharomyces cerevisiae-based assay to assess the toxicity of pyrimethanil sprayed soils via surface runoff: comparison with standard aquatic and soil toxicity assays.

    Science.gov (United States)

    Gil, Fátima N; Moreira-Santos, Matilde; Chelinho, Sónia; Pereira, Carla; Feliciano, Joana R; Leitão, Jorge H; Sousa, José P; Ribeiro, Rui; Viegas, Cristina A

    2015-02-01

    The present study is aimed at evaluating whether a gene expression assay with the microbial eukaryotic model Saccharomyces cerevisiae could be used as a suitable warning tool for the rapid preliminary screening of potential toxic effects on organisms due to scenarios of soil and water contamination with pyrimethanil. The assay consisted of measuring changes in the expression of the selected pyrimethanil-responsive genes ARG3 and ARG5,6 in a standardized yeast population. Evaluation was held by assessing the toxicity of surface runoff, a major route of pesticide exposure in aquatic systems due to non-point-source pollution, which was simulated with a pyrimethanil formulation at a semifield scale mimicking worst-case scenarios of soil contamination (e.g. accident or improper disposal). Yeast cells 2-h exposure to the runoff samples led to a significant 2-fold increase in the expression of both indicator genes. These results were compared with those from assays with organisms relevant for the aquatic and soil compartments, namely the nematode Caenorhabditis elegans (reproduction), the freshwater cladoceran Daphnia magna (survival and reproduction), the benthic midge Chironomus riparius (growth), and the soil invertebrates Folsomia candida and Enchytraeus crypticus (survival and reproduction). Under the experimental conditions used to simulate accidental discharges into soil, runoff waters were highly toxic to the standard test organisms, except for C. elegans. Overall, results point out the usefulness of the yeast assay to provide a rapid preview of the toxicity level in preliminary screenings of environmental samples in situations of inadvertent high pesticide contamination. Advantages and limitations of this novel method are discussed. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Variability of sediment-contact tests in freshwater sediments with low-level anthropogenic contamination - Determination of toxicity thresholds

    International Nuclear Information System (INIS)

    Hoess, S.; Ahlf, W.; Fahnenstich, C.; Gilberg, D.; Hollert, H.; Melbye, K.; Meller, M.; Hammers-Wirtz, M.; Heininger, P.; Neumann-Hensel, H.; Ottermanns, R.; Ratte, H.-T.

    2010-01-01

    Freshwater sediments with low levels of anthropogenic contamination and a broad range of geochemical properties were investigated using various sediment-contact tests in order to study the natural variability and to define toxicity thresholds for the various toxicity endpoints. Tests were performed with bacteria (Arthrobacter globiformis), yeast (Saccharomyces cerevisiae), nematodes (Caenorhabditis elegans), oligochaetes (Lumbriculus variegatus), higher plants (Myriophyllum aquaticum), and the eggs of zebrafish (Danio rerio). The variability in the response of some of the contact tests could be explained by particle size distribution and organic content. Only for two native sediments could a pollution effect not be excluded. Based on the minimal detectable difference (MDD) and the maximal tolerable inhibition (MTI), toxicity thresholds (% inhibition compared to the control) were derived for each toxicity parameter: >20% for plant growth and fish-egg survival, >25% for nematode growth and oligochaete reproduction, >50% for nematode reproduction and >60% for bacterial enzyme activity. - Sediment-contact tests require toxicity thresholds based on their variability in native sediments with low-level contamination.

  7. Variability of sediment-contact tests in freshwater sediments with low-level anthropogenic contamination - Determination of toxicity thresholds

    Energy Technology Data Exchange (ETDEWEB)

    Hoess, S., E-mail: hoess@ecossa.d [Ecossa, Giselastr. 6, 82319 Starnberg (Germany); Institute of Biodiversity - Network (IBN), Dreikronengasse 2, 93047 Regensburg (Germany); Ahlf, W., E-mail: ahlf@tu-harburg.d [Institute of Environmental Technology and Energy Economics, Technical University Hamburg-Harburg, Eissendorfer Str. 40, 21071 Hamburg (Germany); Fahnenstich, C. [Institute of Environmental Technology and Energy Economics, Technical University Hamburg-Harburg, Eissendorfer Str. 40, 21071 Hamburg (Germany); Gilberg, D., E-mail: d-gilberg@ect.d [ECT Oekotoxikologie, Boettgerstr. 2-14, 65439 Floersheim (Germany); Hollert, H., E-mail: henner.hollert@bio5.rwth-aachen.d [Department of Ecosystem Analysis, Institute for Environmental Research (Biology 5), RWTH Aachen University, Worringerweg 1, 52074 Aachen (Germany); Melbye, K. [Dr. Fintelmann and Dr. Meyer, Mendelssohnstr. 15D, 22761 Hamburg (Germany); Meller, M., E-mail: m-meller@ecotox-consult.d [ECT Oekotoxikologie, Boettgerstr. 2-14, 65439 Floersheim (Germany); Hammers-Wirtz, M., E-mail: hammers-wirtz@gaiac.rwth-aachen.d [Research Institute for Ecosystem Analysis and Assessment (gaiac), RWTH Aachen University, Worringerweg 1, 52056 Aachen (Germany); Heininger, P., E-mail: heininger@bafg.d [Federal Institute of Hydrology (BfG), Am Mainzer Tor 1, 56070 Koblenz (Germany); Neumann-Hensel, H., E-mail: hensel@fintelmann-meyer.d [Dr. Fintelmann and Dr. Meyer, Mendelssohnstr. 15D, 22761 Hamburg (Germany); Ottermanns, R., E-mail: ottermanns@bio5.rwth-aachen.d [Chair for Environmental Biology and Chemodynamics, Institute for Environmental Research (Biology 5), RWTH Aachen University, Worringerweg 1, 52074 Aachen (Germany); Ratte, H.-T., E-mail: toni.ratte@bio5.rwth-aachen.d [Chair for Environmental Biology and Chemodynamics, Institute for Environmental Research (Biology 5), RWTH Aachen University, Worringerweg 1, 52074 Aachen (Germany)

    2010-09-15

    Freshwater sediments with low levels of anthropogenic contamination and a broad range of geochemical properties were investigated using various sediment-contact tests in order to study the natural variability and to define toxicity thresholds for the various toxicity endpoints. Tests were performed with bacteria (Arthrobacter globiformis), yeast (Saccharomyces cerevisiae), nematodes (Caenorhabditis elegans), oligochaetes (Lumbriculus variegatus), higher plants (Myriophyllum aquaticum), and the eggs of zebrafish (Danio rerio). The variability in the response of some of the contact tests could be explained by particle size distribution and organic content. Only for two native sediments could a pollution effect not be excluded. Based on the minimal detectable difference (MDD) and the maximal tolerable inhibition (MTI), toxicity thresholds (% inhibition compared to the control) were derived for each toxicity parameter: >20% for plant growth and fish-egg survival, >25% for nematode growth and oligochaete reproduction, >50% for nematode reproduction and >60% for bacterial enzyme activity. - Sediment-contact tests require toxicity thresholds based on their variability in native sediments with low-level contamination.

  8. Size- and composition-dependent toxicity of synthetic and soil-derived Fe oxide colloids for the nematode Caenorhabditis elegans.

    Science.gov (United States)

    Höss, Sebastian; Fritzsche, Andreas; Meyer, Carolin; Bosch, Julian; Meckenstock, Rainer U; Totsche, Kai Uwe

    2015-01-06

    Colloidal iron oxides (FeOx) are increasingly released to the environment due to their use in environmental remediation and biomedical applications, potentially harming living organisms. Size and composition could affect the bioavailability and toxicity of such colloids. Therefore, we investigated the toxicity of selected FeOx with variable aggregate size and variably composed FeOx-associated organic matter (OM) toward the nematode Caenorhabditis elegans. Ferrihydrite colloids containing citrate were taken up by C. elegans with the food and accumulated inside their body. The toxicity of ferrihydrite, goethite, and akaganeite was dependent on aggregate size and specific surface area, with EC50 values for reproduction ranging from 4 to 29 mg Fe L(-1). Experiments with mutant strains lacking mitochondrial superoxide dismutase (sod-2) showed oxidative stress for two FeOx and Fe(3+)-ions, however, revealed that it was not the predominant mechanism of toxicity. The OM composition determined the toxicity of mixed OM-FeOx phases on C. elegans. FeOx associated with humic acids or citrate were less toxic than OM-free FeOx. In contrast, soil-derived ferrihydrite, containing proteins and polysaccharides from mobile OM, was even more toxic than OM-free Fh of similar aggregate size. Consequently, the careful choice of the type of FeOx and the type of associated OM may help in reducing the ecological risks if actively applied to the subsurface.

  9. Chemotherapy Toxicity Risk Score for Treatment Decisions in Older Adults with Advanced Solid Tumors.

    Science.gov (United States)

    Nishijima, Tomohiro F; Deal, Allison M; Williams, Grant R; Sanoff, Hanna K; Nyrop, Kirsten A; Muss, Hyman B

    2018-05-01

    The decision whether to treat older adults with advanced cancer with standard therapy (ST) or reduced therapy (RT) is complicated by heterogeneity in aging. We assessed the potential utility of the chemotherapy toxicity risk score (CTRS) [J Clin Oncol 2011;29:3457-3465] for treatment decisions in older adults. This was a prospective observational study of patients aged ≥65 years receiving first-line chemotherapy for advanced cancer for which combination chemotherapy is the standard of care. Patients were categorized as high risk (CTRS ≥10), for whom RT (dose-reduced combination or single-agent chemotherapy) is deemed appropriate, or nonhigh risk (CTRS statistic. Fifty-eight patients (median age, 71 years) were enrolled. Thirty-eight patients received ST (21 had CTRS advanced solid tumors receiving first-line chemotherapy was assessed. Little agreement was found between chemotherapy treatment decisions based on the clinical impression versus what was recommended based on the CTRS. Among patients treated with standard-dose combination chemotherapy, patients with CTRS ≥10 had a very high incidence of grade 3-4 toxicities and hospitalization, which was significantly greater than that of patients with a low CTRS (<10). These findings suggest that the addition of CTRS to the clinical impression has a potential to improve treatment decisions. © AlphaMed Press 2018.

  10. Menstrual and reproductive factors and type 2 diabetes risk: the Japan Public Health Center-based Prospective Study.

    Science.gov (United States)

    Nanri, Akiko; Mizoue, Tetsuya; Noda, Mitsuhiko; Goto, Atsushi; Sawada, Norie; Tsugane, Shoichiro

    2018-04-18

    Menstrual and reproductive factors, including age at menarche, parity, and breastfeeding, have been linked to type 2 diabetes risk. We prospectively investigated the association between these factors and type 2 diabetes risk in a large Japanese cohort. Participants were 37,511 women aged 45-75 years who participated in the baseline (1990-1993), second (1995-1998), and third surveys (2000-2003) of the Japan Public Health Center-based Prospective Study and who had no history of diabetes at the second survey. Menstrual and reproductive history was ascertained using questionnaires at the baseline and second surveys. Odds ratios of self-reported, physician-diagnosed type 2 diabetes over the 5-year period from the second survey were estimated using logistic regression. At the third survey, 513 new cases of type 2 diabetes were self-reported. The odds ratios of type 2 diabetes tended to increase with the number of parity, after adjustment for covariates other than body mass index (P for trend = 0.029). The multivariable-adjusted odds ratios (95% confidence interval) of type 2 diabetes for women with ≥3 births was 1.56 (0.96-2.53) compared to those who were nulliparous. The association between parity and type 2 diabetes risk was attenuated after additional adjustment for body mass index (P for trend = 0.12). No factors other than parity were significantly associated with type 2 diabetes risk. Higher parity may be associated with increased risk of type 2 diabetes among Japanese women, partly through increasing body weight. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  11. Increased reproductive success of women after prenatal undernutrition

    NARCIS (Netherlands)

    Painter, Rebecca C.; Westendorp, Rudi G. J.; de Rooij, Susanne R.; Osmond, Clive; Barker, David J. P.; Roseboom, Tessa J.

    2008-01-01

    BACKGROUND: Prenatal exposure to the Dutch famine is associated with an increased risk of chronic degenerative disease. We now investigate whether prenatal famine exposure affected reproductive success. METHODS: We assessed reproductive success (number of children, number of twins, age at delivery,

  12. A qualitative study of Ottawa university students? awareness, knowledge and perceptions of infertility, infertility risk factors and assisted reproductive technologies (ART)

    OpenAIRE

    Sabarre, Kelley-Anne; Khan, Zainab; Whitten, Amanda N; Remes, Olivia; Phillips, Karen P

    2013-01-01

    Background Awareness of infertility risk factors is an essential first step to safeguard future fertility. Whereas several studies have examined university students? awareness of female fertility and related risk factors, the topic of male infertility has not been well examined. The objective of this study was to assess young men and women?s awareness, knowledge and perceptions of infertility, male and female infertility risk factors and assisted reproductive technologies (ART). Methods Semi-...

  13. Toxicant emissions from hazardous wastes in landfills - implications for disposal risk management decisions

    International Nuclear Information System (INIS)

    Assmuth, T.W.

    1991-01-01

    The environmental impacts and risks of hazardous wastes disposed in Finnish landfills were assessed in a 5-yr field study. By systematic analysis of the acquired information, the toxicological impacts and risks of landfills seem as a whole small when compared with those caused by other kinds of environmental toxicants. Locally more significant risks arise, and may be difficult to manage. Scientific information on risk factors and their development is as yet insufficient, and additional research and monitoring are needed. Since uncertainties will remain, the prevention and control of risks, e.g. by improved hazardous waste management and disposal, are advocated by safety principles, but are made difficult by many technical and societal factors. Control strategies and remedial actions should thus be based on more comprehensive, comparative risk assessments and improved decision methods. Ethical, political and methodological issues in the management of hazardous waste disposal are discussed, with special reference to the interaction of science with regulatory decision-making related to the risks of old chemical waste sites. (44 refs.) (au)

  14. Reproductive prognosis in daughters of women with and without endometriosis

    DEFF Research Database (Denmark)

    Dalsgaard, T; Hansen, Maj Vadskjær Hjordt; Hartwell, D

    2013-01-01

    Do daughters of women with endometriosis exhibit an increased risk of endometriosis and impaired long-term reproductive prognosis when compared with daughters of women without endometriosis?......Do daughters of women with endometriosis exhibit an increased risk of endometriosis and impaired long-term reproductive prognosis when compared with daughters of women without endometriosis?...

  15. The developmental toxicity of perfluoroalkyl acids and their derivatives

    International Nuclear Information System (INIS)

    Lau, Christopher; Butenhoff, John L.; Rogers, John M.

    2004-01-01

    Perfluoroalkyl acids such as perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) have applications in numerous industrial and consumer products. Although the toxicology of some of these compounds has been investigated in the past, the widespread prevalence of PFOS and PFOA in humans, as demonstrated in recent bio-monitoring studies, has drawn considerable interest from the public and regulatory agencies as well as renewed efforts to better understand the hazards that may be inherent in these compounds. This review provides a brief overview of the perfluoroalkyl chemicals and a summary of the available information on the developmental toxicity of the eight-carbon compounds, PFOS and PFOA. Although the teratological potentials of some of these chemicals had been studied in the past and the findings were generally unremarkable, results from recent postnatal studies on developmental and reproductive indices have prompted consideration of their relevance to human health risk. Based on current understanding of the developmental effects of PFOS and PFOA in rodents, several avenues of research are suggested that would further support the risk assessment of these perfluorinated organic chemicals

  16. Treatment of primary liver tumors with Yttrium-90 microspheres (TheraSphere) in high risk patients: analysis of survival and toxicities.

    Science.gov (United States)

    Reardon, Kelli A; McIntosh, Alyson F; Shilling, A Tanner; Hagspiel, Klaus D; Al-Osaimi, Abdullah; Berg, Carl; Caldwell, Stephen H; Northup, Patrick G; Angle, Fritz; Mulder, Robert; Rich, Tyvin A

    2009-02-01

    This retrospective study was undertaken to obtain information regarding the survival and toxicities after Yttrium-90 microspheres treatment in patients with primary liver malignancies. Baseline, treatment, and follow-up data were collected and analyzed for 21 patients treated with Yttrium-90 microspheres. Survival analysis was then performed. The results of this study showed that median survival for all the patients was 120 days. Twenty of 21 patients were categorized as high-risk with a median survival of 114 days. It was also found that one high-risk patient has survived 858 days with no recurrence of disease. Acute grade 3-5 toxicities were recorded for nine patients and consisted of elevations in AST and bilirubin, thrombocytopenia, abdominal pain, ascites, nausea, fatigue, and death. This study concluded that Yttrium-90 is a low-toxicity, outpatient alternative for individuals with liver cancer and without many options. The maximal value, however, may lie in the treatment of low-risk patients.

  17. An integrative risk assessment approach for persistent chemicals: a case study on dioxins, furans and dioxin-like PCBs in France.

    Science.gov (United States)

    Béchaux, Camille; Zeilmaker, Marco; Merlo, Mathilde; Bokkers, Bas; Crépet, Amélie

    2014-10-01

    For persistent chemicals slowly eliminated from the body, the accumulated concentration (body burden), rather than the daily exposure, is considered the proper starting point for the risk assessment. This work introduces an integrative approach for persistent chemical risk assessment by means of a dynamic body burden approach. To reach this goal a Kinetic Dietary Exposure Model (KDEM) was extended with the long term time trend in the exposure (historic exposure) and the comparison of bioaccumulation with body burden references for toxicity. The usefulness of the model was illustrated on the dietary exposure to PolyChlorinatedDibenzo-p-Dioxins (PCDDs), PolyChlorinatedDibenzoFurans (PCDFs) and PolyChlorinated Biphenyls (PCBs) in France. Firstly the dietary exposure to these compounds was determined in 2009 and combined with its long term time trend. In order to take differences between the kinetics of PCDD/F and dl-PCBs into account, three groups of congeners were considered i.e. PCDD/Fs, PCB 126 and remaining dl-PCBs. The body burden was compared with reference body burdens corresponding to reproductive, hepatic and thyroid toxicity. In the case of thyroid toxicity this comparison indicated that in 2009 the probability of the body burden to exceed its reference ranged from 2.8% (95% CI: 1.5-4.9%) up to 3.9% (95% CI: 2.7-7.1%) (18-29 vs. 60-79year olds). Notwithstanding the decreasing long-term time trend of the dietary dioxin exposure in France, this probability still is expected to be 1.5% (95% CI: 0.3-2.5%) in 2030 in 60-79 olds. In the case of reproductive toxicity the probability of the 2009 body burden to exceed its reference ranged from 3.1% (95% CI: 1.4-5.0%) (18-29year olds) to 3.5% (95% CI: 2.2-5.2%) (30-44year olds). In 2030 this probability is negligible in 18-29year olds, however small though significant in 30-44year olds (0.7%, 95% CI: 0-1.6%). In the case of hepatic toxicity the probability in 2009 even in 60-79year olds already was negligible. In

  18. Dose-Escalated Hypofractionated Intensity-Modulated Radiotherapy in High-Risk Carcinoma of the Prostate: Outcome and Late Toxicity

    Directory of Open Access Journals (Sweden)

    David Thomson

    2012-01-01

    Results. Median followup was 84 months. Five-year overall survival (OS was 83% and biochemical progression-free survival (bPFS was 50% for 57 Gy. Five-year OS was 75% and bPFS 58% for 60 Gy. At 7 years, toxicity by RTOG criteria was acceptable with no grade 3 or above toxicity. Compared with baseline, there was no significant change in urinary symptoms at 2 or 7 years. Bowel symptoms were stable between 2 and 7 years. All patients continued to have significant sexual dysfunction. Conclusion. In high-risk prostate cancer, dose-escalated hypofractionated radiotherapy using IMRT results in encouraging outcomes and acceptable late toxicity.

  19. Reproductive Status at First Diagnosis Influences Risk of Radiation-Induced Second Primary Contralateral Breast Cancer in the WECARE Study

    Energy Technology Data Exchange (ETDEWEB)

    Brooks, Jennifer D., E-mail: brooksj@mskcc.org [Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Boice, John D. [International Epidemiology Institute, Rockville, MD and Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt School of Medicine, Nashville, TN (United States); Stovall, Marilyn [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Reiner, Anne S. [Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Bernstein, Leslie [Division of Cancer Etiology, Department of Population Sciences, Beckman Research Institute and City of Hope Comprehensive Cancer Center, Duarte, CA (United States); John, Esther M. [Cancer Prevention Institute of California, Fremont, CA, and Stanford University School of Medicine and Stanford Cancer Institute, Stanford, CA (United States); Lynch, Charles F. [Department of Epidemiology, University of Iowa, Iowa City, IA (United States); Mellemkjaer, Lene [Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen (Denmark); Knight, Julia A. [Dalla Lana School of Public Health, University of Toronto and Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario (Canada); Thomas, Duncan C.; Haile, Robert W. [Department of Preventive Medicine, University of Southern California, Los Angeles, CA (United States); Smith, Susan A. [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Capanu, Marinela; Bernstein, Jonine L. [Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Shore, Roy E. [Department of Environmental Medicine, New York University, New York, NY (United States); Radiation Effects Research Foundation, Hiroshima (Japan)

    2012-11-15

    Purpose: Our study examined whether reproductive and hormonal factors before, at the time of, or after radiation treatment for a first primary breast cancer modify the risk of radiation-induced second primary breast cancer. Methods and Materials: The Women's Environmental, Cancer and Radiation Epidemiology (WECARE) Study is a multicenter, population-based study of 708 women (cases) with asynchronous contralateral breast cancer (CBC) and 1399 women (controls) with unilateral breast cancer. Radiotherapy (RT) records, coupled with anthropomorphic phantom simulations, were used to estimate quadrant-specific radiation dose to the contralateral breast for each patient. Rate ratios (RR) and 95% confidence intervals (CI) were computed to assess the relationship between reproductive factors and risk of CBC. Results: Women who were nulliparous at diagnosis and exposed to {>=}1 Gy to the contralateral breast had a greater risk for CBC than did matched unexposed nulliparous women (RR = 2.2; 95% CI, 1.2-4.0). No increased risk was seen in RT-exposed parous women (RR = 1.1; 95% CI, 0.8-1.4). Women treated with RT who later became pregnant (8 cases and 9 controls) had a greater risk for CBC (RR = 6.0; 95% CI, 1.3-28.4) than unexposed women (4 cases and 7 controls) who also became pregnant. The association of radiation with risk of CBC did not vary by number of pregnancies, history of breastfeeding, or menopausal status at the time of first breast cancer diagnosis. Conclusion: Nulliparous women treated with RT were at an increased risk for CBC. Although based on small numbers, women who become pregnant after first diagnosis also seem to be at an increased risk for radiation-induced CBC.

  20. Distribution, relationship, and risk assessment of toxic heavy metals in walnuts and growth soil.

    Science.gov (United States)

    Han, Yongxiang; Ni, Zhanglin; Li, Shiliang; Qu, Minghua; Tang, Fubin; Mo, Runhong; Ye, Caifen; Liu, Yihua

    2018-04-14

    Walnut is one of the most popular nuts worldwide and contains various mineral nutrients. Little is known, however, about the relationship between toxic heavy metals in walnuts and growth soil. In this study, we investigated the distribution, relationship, and risk assessment of five toxic heavy metals-lead (Pb), arsenic (As), chromium (Cr), cadmium (Cd), and mercury (Hg)-in walnuts and growth soil in the main production areas of China. The results showed that the main heavy metal pollution in walnut and soil was Pb and Cd. Regionally, positive relationships existed between heavy metals and the pH and organic matter of soil. In addition, we observed a notable uptake effect between walnut and growth soil. In this study, we found a significant correlation (r = 0.786, P toxic heavy metal pollution in walnuts and growth soil could be helpful to screen suitable planting sites to prevent and control heavy metal pollution and improve the quality and safety of walnut.

  1. Joint Estimation of Cardiac Toxicity and Recurrence Risks After Comprehensive Nodal Photon Versus Proton Therapy for Breast Cancer

    DEFF Research Database (Denmark)

    Stick, Line B; Yu, Jen; Maraldo, Maja V

    2017-01-01

    PURPOSE: The study aims to perform joint estimation of the risk of recurrence caused by inadequate radiation dose coverage of lymph node targets and the risk of cardiac toxicity caused by radiation exposure to the heart. Delivered photon plans are compared with realistic proton plans, thereby pro...

  2. Risk and toxicity assessments of heavy metals in sediments and fishes from the Yangtze River and Taihu Lake, China.

    Science.gov (United States)

    Fu, Jie; Hu, Xin; Tao, Xiancong; Yu, Hongxia; Zhang, Xiaowei

    2013-11-01

    Heavy metal pollution is one of the most serous environmental issues globally. To evaluate the metal pollution in Jiangsu Province of China, the total concentrations of heavy metals in sediments and fishes from the Yangtze River and Taihu Lake were analyzed. Ecological risk of sediments and human health risk of fish consumption were assessed respectively. Furthermore, toxicity of samples on expression of the stress responsive genes was evaluated using microbial live cell-array method. The results showed that the heavy metals concentrations in sediments from the Yangtze River were much higher than those in sediments from the Taihu Lake. However, the fishes from the Taihu Lake had higher concentrations of heavy metals than fishes from the Yangtze River. Ecological risk evaluation showed that the heavy metal contaminants in sediments from the Yangtze River posed higher risk of adverse ecological effects, while sediments from the study areas of Taihu Lake were relatively safe. Health risk assessment suggested that the heavy metals in fishes of both Yangtze River and Taihu Lake might have risk of adverse health effects to human. The toxicity assessment indicated that the heavy metals in these sediments and fishes showed transcriptional effects on the selected 21 stress responsive genes, which were involved in the pathways of DNA damage response, chemical stress, and perturbations of electron transport. Together, this field investigation combined with chemical analysis, risk assessment and toxicity bioassay would provide useful information on the heavy metal pollution in Jiangsu Province. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Rs895819 in MIR27A improves the predictive value of DPYD variants to identify patients at risk of severe fluoropyrimidine-associated toxicity.

    Science.gov (United States)

    Meulendijks, Didier; Henricks, Linda M; Amstutz, Ursula; Froehlich, Tanja K; Largiadèr, Carlo R; Beijnen, Jos H; de Boer, Anthonius; Deenen, Maarten J; Cats, Annemieke; Schellens, Jan H M

    2016-06-01

    The objective of this study was to determine whether genotyping of MIR27A polymorphisms rs895819A>G and rs11671784C>T can be used to improve the predictive value of DPYD variants to identify patients at risk of severe fluoropyrimidine-associated toxicity (FP-toxicity). Patients treated previously in a prospective study with fluoropyrimidine-based chemotherapy were genotyped for rs895819 and rs11671784, and DPYD c.2846A>T, c.1679T>G, c.1129-5923C>G and c.1601G>A. The predictive value of MIR27A variants for early-onset grade ≥3 FP-toxicity, alone or in combination with DPYD variants, was tested in multivariable logistic regression models. Random-effects meta-analysis was performed, including previously published data. A total of 1,592 patients were included. Allele frequencies of rs895819 and rs11671784 were 0.331 and 0.020, respectively. In DPYD wild-type patients, MIR27A variants did not affect risk of FP-toxicity (OR 1.3 for ≥1 variant MIR27A allele vs. none, 95% CI: 0.87-1.82, p = 0.228). In contrast, in patients carrying DPYD variants, the presence of ≥1 rs895819 variant allele was associated with increased risk of FP-toxicity (OR 4.9, 95% CI: 1.24-19.7, p = 0.023). Rs11671784 was not associated with FP-toxicity (OR 2.9, 95% CI: 0.47-18.0, p = 0.253). Patients carrying a DPYD variant and rs895819 were at increased risk of FP-toxicity compared to patients wild type for rs895819 and DPYD (OR 2.4, 95% CI: 1.27-4.37, p = 0.007), while patients with a DPYD variant but without a MIR27A variant were not (OR 0.3 95% CI: 0.06-1.17, p = 0.081). In meta-analysis, rs895819 remained significantly associated with FP-toxicity in DPYD variant allele carriers, OR 5.4 (95% CI: 1.83-15.7, p = 0.002). This study demonstrates the clinical validity of combined MIR27A/DPYD screening to identify patients at risk of severe FP-toxicity. © 2016 UICC.

  4. Human health risk assessment based on toxicity characteristic leaching procedure and simple bioaccessibility extraction test of toxic metals in urban street dust of Tianjin, China.

    Directory of Open Access Journals (Sweden)

    Binbin Yu

    Full Text Available The potential ecological and human health risk related with urban street dust from urban areas of Tianjin, China was quantitatively analyzed using the method of toxicity characteristic leaching procedure (TCLP and simple bioaccessibility extraction test (SBET. In the study, Hakason index, Nemerow index (P, the hazard index (HI and the cancer risk index (RI were calculated to assess the potential risk. The sequence of potential ecological risk based on Hakason index was arsenic (As > cadmium (Cd > lead (Pb > copper (Cu > chromium (Cr, in particular, As and Cd were regarded as high polluted metals. While the results of extraction of TCLP were assessed using P, the sequence was As > Pb > Cd > Cr > Cu, which mean that As and Pb should be low polluted, and Cd, Cr and Cu would barely not polluted. For human health, total carcinogenic risk for children and adults was 2.01 × 10(-3 and 1.05 × 10(-3, respectively. This could be considered to be intolerable in urban street dust exposure. The sequence in the hazard quotient (HQ of each element was As > Cr > Pb > Cu > Cd. The HI value of these toxic metals in urban street dust for children and adults was 5.88 × 10(-1 and 2.80 × 10(-1, respectively. According to the characters of chemistry, mobility, and bioavailability of metals in urban street dust, we estimated the hazards on the environment and human health, which will help us to get more reasonable information for risk management of metals in urban environment.

  5. Toxicity of copper to the collembolan Folsomia fimetaria in relation to the age of soil contamination.

    NARCIS (Netherlands)

    Bruus Pedersen, M.; van Gestel, C.A.M.

    2001-01-01

    The toxicity of copper to the collembolan Folsomia fimetaria L. was studied in soil incubated with copper sulfate for different periods before the introduction of collembolans, to assess the effect of aging of contamination on the toxicity of copper. Adult survival, reproduction, and juvenile size

  6. Neurodevelopmental toxicity risks due to occupational exposure to industrial chemicals during pregnancy

    DEFF Research Database (Denmark)

    Julvez, Jordi; Grandjean, Philippe

    2009-01-01

    Exposure to neurotoxic chemicals is of particular concern when it occurs during early development. The immature brain is highly vulnerable prenatally and is therefore at risk due to occupational exposures incurred by pregnant women. A systematic search of the literature has been performed...... by occupational health researchers and practitioners from the need to protect pregnant workers. Due to the vulnerability of the brain during early development, a precautionary approach to neurodevelopmental toxicity needs to be applied in occupational health....

  7. Reproduction, women, and the workplace: legal issues.

    Science.gov (United States)

    Bertin, J E

    1986-01-01

    Legal conflict has marked the effort to protect workers against reproductive injury, and legal activity in the management of occupational risks reflects a much broader range of important social issues, such as sexual discrimination in the workplace. This article describes the evolving law related to reproductive hazards that concern men, women and children.

  8. Choline supplementation alleviates fluoride-induced testicular toxicity by restoring the NGF and MEK expression in mice

    International Nuclear Information System (INIS)

    Zhang, Jianhai; Zhang, Yufang; Liang, Chen; Wang, Nasui; Zheng, Heping; Wang, Jundong

    2016-01-01

    Fluoride is known to cause male reproductive toxicity, and the elucidation of its underlying mechanisms is an ongoing research focus in reproductive toxicology and epidemiology. Choline, an essential nutrient, has been extensively studied for its benefits in nervous system yet was rarely discussed for its prospective effect in male reproductive system. This study aims to explore the potential protective role of choline against NaF-induced male reproductive toxicity via MAPK pathway. The male mice were administrated by 150 mg/L NaF in drinking water, 5.75 g/kg choline in diet, and their combination respectively from maternal gestation to postnatal 15 weeks. The results showed that fluoride exposure reduced body weight growth, lowered sperm count and survival percentages, altered testicular histology, down-regulated the mRNA expressions of NGF, Ras, Raf, and MEK genes in testes, as well as significantly decreased the expressions of both NGF and phosphor-MEK proteins in testes. Examination of data from choline-treated mice revealed that choline supplementation ameliorated these fluoride-induced changes. Taken together, our findings suggest that choline supplementation alleviates fluoride-induced testicular toxicity by restoring the NGF and phosphor-MEK expression. The suitable dosage and supplementation periods of choline await further exploration. - Highlights: • Fluoride exposure altered the growth and development, sperm count and sperm survival percentages, testicular histology • Fluoride exposure decreased NGF, Ras, and Mek mRNA and NGF and p-MEK protein expressions in testis of mice. • Choline supplementation diminishes fluoride-induced testicular toxicity.

  9. Choline supplementation alleviates fluoride-induced testicular toxicity by restoring the NGF and MEK expression in mice

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Jianhai [Shanxi Key Laboratory of Ecological Animal Science and Environmental Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi 030801 (China); Zhang, Yufang [Shanxi Key Laboratory of Ecological Animal Science and Environmental Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi 030801 (China); Veterinary Station in Chen Villages of Lin Country, Linxian, Shanxi 033200 (China); Liang, Chen [Shanxi Key Laboratory of Ecological Animal Science and Environmental Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi 030801 (China); Wang, Nasui [Division of Endocrinology and Metabolism, Department of Medicine, University of Virginia, Charlottesville, VA 22908 (United States); Division of Endocrinology and Metabolism, Department of Medicine, The First Affiliated Hospital of Shantou University Medical College, Shantou (China); Zheng, Heping [Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, VA 22908 (United States); Wang, Jundong, E-mail: wangjd53@outlook.com [Shanxi Key Laboratory of Ecological Animal Science and Environmental Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi 030801 (China)

    2016-11-01

    Fluoride is known to cause male reproductive toxicity, and the elucidation of its underlying mechanisms is an ongoing research focus in reproductive toxicology and epidemiology. Choline, an essential nutrient, has been extensively studied for its benefits in nervous system yet was rarely discussed for its prospective effect in male reproductive system. This study aims to explore the potential protective role of choline against NaF-induced male reproductive toxicity via MAPK pathway. The male mice were administrated by 150 mg/L NaF in drinking water, 5.75 g/kg choline in diet, and their combination respectively from maternal gestation to postnatal 15 weeks. The results showed that fluoride exposure reduced body weight growth, lowered sperm count and survival percentages, altered testicular histology, down-regulated the mRNA expressions of NGF, Ras, Raf, and MEK genes in testes, as well as significantly decreased the expressions of both NGF and phosphor-MEK proteins in testes. Examination of data from choline-treated mice revealed that choline supplementation ameliorated these fluoride-induced changes. Taken together, our findings suggest that choline supplementation alleviates fluoride-induced testicular toxicity by restoring the NGF and phosphor-MEK expression. The suitable dosage and supplementation periods of choline await further exploration. - Highlights: • Fluoride exposure altered the growth and development, sperm count and sperm survival percentages, testicular histology • Fluoride exposure decreased NGF, Ras, and Mek mRNA and NGF and p-MEK protein expressions in testis of mice. • Choline supplementation diminishes fluoride-induced testicular toxicity.

  10. Reproductive desires and intentions of HIV‑positive women of ...

    African Journals Online (AJOL)

    Key words: HIV‑positive women of reproductive age; Jos; reproductive intention; serodiscordant or ... with plasma viral RNA suppression with HAART, can reduce the risk of ..... Evalution of sperm washing as a potential method of reducing.

  11. The Protective Effect of Hydroalcoholic Extract of Zingiber officinale Roscoe (Ginger) on Ethanol-Induced Reproductive Toxicity in Male Rats.

    Science.gov (United States)

    Akbari, Abolfazl; Nasiri, Khadijeh; Heydari, Mojtaba; Mosavat, Seyed Hamdollah; Iraji, Aida

    2017-10-01

    This study was conducted to evaluate the prophylactic effect of ginger extract on ethanol-induced reproductive toxicity in male rats. Twenty-eight adult male Sprague-Dawley rats were randomly divided into 4 groups and treated daily for 28 days as follows: control, control-ginger (1 g/kg of body weight [BW]/day by gavage), ethanol group (ethanol 4 g/kg of BW/day by gavage), and ginger-ethanol group. At the end of the experiment, all the rats were sacrificed and their testes were removed and used for measurement of the total homocysteine (tHcy), trace elements, antioxidant enzymes activity, and malondialdehyde (MDA). The results in the ethanol group indicate that ethanol decreased antioxidant enzymes activity and increased MDA and tHcy compared with the control groups ( P < .05). In ginger-ethanol group, ginger improved antioxidant enzymes activity and reduced tHcy and MDA compared to ethanol group ( P < .05). It can be concluded that ginger protects the ethanol-induced testicular damage and improves the hormonal levels, trace elements, antioxidant enzymes activity, and decreases tHcy and MDA.

  12. Gossypol Toxicity from Cottonseed Products

    Directory of Open Access Journals (Sweden)

    Ivana Cristina N. Gadelha

    2014-01-01

    Full Text Available Gossypol is a phenolic compound produced by pigment glands in cotton stems, leaves, seeds, and flower buds (Gossypium spp.. Cottonseed meal is a by-product of cotton that is used for animal feeding because it is rich in oil and proteins. However, gossypol toxicity limits cottonseed use in animal feed. High concentrations of free gossypol may be responsible for acute clinical signs of gossypol poisoning which include respiratory distress, impaired body weight gain, anorexia, weakness, apathy, and death after several days. However, the most common toxic effects is the impairment of male and female reproduction. Another important toxic effect of gossypol is its interference with immune function, reducing an animal’s resistance to infections and impairing the efficiency of vaccines. Preventive procedures to limit gossypol toxicity involve treatment of the cottonseed product to reduce the concentration of free gossypol with the most common treatment being exposure to heat. However, free gossypol can be released from the bound form during digestion. Agronomic selection has produced cotton varieties devoid of glands producing gossypol, but these varieties are not normally grown because they are less productive and are more vulnerable to attacks by insects.

  13. Human exposure to endocrine disrupting compounds: Their role in reproductive systems, metabolic syndrome and breast cancer. A review.

    Science.gov (United States)

    Giulivo, Monica; Lopez de Alda, Miren; Capri, Ettore; Barceló, Damià

    2016-11-01

    Endocrine disrupting chemicals (EDCs) are released into the environment from different sources. They are mainly used in packaging industries, pesticides and food constituents. Clinical evidence, experimental models, and epidemiological studies suggest that EDCs have major risks for humans by targeting different organs and systems in the body (e.g. reproductive system, breast tissue, adipose tissue, pancreas, etc.). Due to the ubiquity of human exposure to these compounds the aim of this review is to describe the most recent data on the effects induced by phthalates, bisphenol A and parabens in a critical window of exposure: in utero, during pregnancy, infants, and children. The interactions and mechanisms of toxicity of EDCs in relation to human general health problems, especially those broadening the term of endocrine disruption to 'metabolic disruption', should be deeply investigated. These include endocrine disturbances, with particular reference to reproductive problems and breast, testicular and ovarian cancers, and metabolic diseases such as obesity or diabetes. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. A Risk Assessment Example for Soil Invertebrates Using Spatially Explicit Agent-Based Models

    DEFF Research Database (Denmark)

    Reed, Melissa; Alvarez, Tania; Chelinho, Sonia

    2016-01-01

    Current risk assessment methods for measuring the toxicity of plant protection products (PPPs) on soil invertebrates use standardized laboratory conditions to determine acute effects on mortality and sublethal effects on reproduction. If an unacceptable risk is identified at the lower tier...... population models for ubiquitous soil invertebrates (collembolans and earthworms) as refinement options in current risk assessment. Both are spatially explicit agent-based models (ABMs), incorporating individual and landscape variability. The models were used to provide refined risk assessments for different...... application scenarios of a hypothetical pesticide applied to potato crops (full-field spray onto the soil surface [termed “overall”], in-furrow, and soil-incorporated pesticide applications). In the refined risk assessment, the population models suggest that soil invertebrate populations would likely recover...

  15. A combined approach to investigate the toxicity of an industrial landfill's leachate: Chemical analyses, risk assessment and in vitro assays

    International Nuclear Information System (INIS)

    Baderna, D.; Maggioni, S.; Boriani, E.; Gemma, S.; Molteni, M.; Lombardo, A.; Colombo, A.; Bordonali, S.; Rotella, G.; Lodi, M.; Benfenati, E.

    2011-01-01

    Solid wastes constitute an important and emerging problem. Landfills are still one of the most common ways to manage waste disposal. The risk assessment of pollutants from landfills is becoming a major environmental issue in Europe, due to the large number of sites and to the importance of groundwater protection. Furthermore, there is lack of knowledge for the environmental, ecotoxicological and toxicological characteristics of most contaminants contained into landfill leacheates. Understanding leachate composition and creating an integrated strategy for risk assessment are currently needed to correctly face the landfill issues and to make projections on the long-term impacts of a landfill, with particular attention to the estimation of possible adverse effects on human health and ecosystem. In the present study, we propose an integrated strategy to evaluate the toxicity of the leachate using chemical analyses, risk assessment guidelines and in vitro assays using the hepatoma HepG2 cells as a model. The approach was applied on a real case study: an industrial waste landfill in northern Italy for which data on the presence of leachate contaminants are available from the last 11 years. Results from our ecological risk models suggest important toxic effects on freshwater fish and small rodents, mainly due to ammonia and inorganic constituents. Our results from in vitro data show an inhibition of cell proliferation by leachate at low doses and cytotoxic effect at high doses after 48 h of exposure. - Research highlights: → We study the toxicity of leachate from a non-hazardous industrial waste landfill. → We perform chemical analyses, risk assessments and in vitro assays on HepG2 cells. → Risk models suggest toxic effects due to ammonia and inorganic constituents. → In vitro assays show that leachate inhibits cell proliferation at low doses. → Leachate can induce cytotoxic effects on HepG2 cells at high doses.

  16. Cervical conization doubles the risk of preterm and very preterm birth in assisted reproductive technology twin pregnancies

    DEFF Research Database (Denmark)

    Pinborg, A; Ortoft, G; Loft, A

    2015-01-01

    for the height of the cervical cone or the severity of the cervical intraepithelial neoplasia (CIN) or the time window between diagnosis of CIN and ART treatment. The finding on an increased risk of VPTB in ART twin pregnancies after dysplasia without conization may be random as we found no other increased risk......STUDY QUESTION: Does cervical conization add an additional risk of preterm birth (PTB) in assisted reproduction technology (ART) singleton and twin pregnancies? SUMMARY ANSWER: Cervical conization doubles the risk of preterm and very PTB in ART twin pregnancies. WHAT IS KNOWN ALREADY: ART...... and cervical conization are both risk factors for PTB. STUDY DESIGN, SIZE, DURATION: In this national population-based controlled cohort study, we included all ART singletons and twin deliveries from 1995 to 2009 in Denmark by cross-linkage of maternal and child data from the National IVF register...

  17. Mechanisms of the Testis Toxicity Induced by Chronic Exposure to Mequindox

    Directory of Open Access Journals (Sweden)

    Qianying Liu

    2017-09-01

    Full Text Available Mequindox (MEQ is a synthetic antimicrobial agent widely used in China since the 1980s. Although the toxicity of MEQ is well recognized, its testis toxicity has not been adequately investigated. In the present study, we provide evidence that MEQ triggers oxidative stress, mitochondrion dysfunction and spermatogenesis deficiency in mice after exposure to MEQ (0, 25, 55, and 110 mg/kg in the diet for up to 18 months. The genotoxicity and adrenal toxicity may contribute to sperm abnormalities caused by MEQ. Moreover, using LC/MS-IT-TOF analysis, two metabolites, 3-methyl-2-(1-hydroxyethyl quinoxaline-N4-monoxide (M4 and 3-methyl-2-(1-hydroxyethyl quinoxaline-N1-monoxide (M8, were detected in the serum of mice, which directly confirms the relationship between the N→O group reduction metabolism of MEQ and oxidative stress. Interestingly, only M4 was detected in the testes, suggesting that the higher reproductive toxicity of M4 than M8 might be due to the increased stability of M4-radical (M4-R compared to M8-radical (M8-R. Furthermore, the expression of the blood-testis barrier (BTB-associated junctions such as tight junctions, gap junctions and basal ectoplasmic specializations were also examined. The present study demonstrated for the first time the role of the M4 in testis toxicity, and illustrated that the oxidative stress, mitochondrion dysfunction and interference in spermatogenesis, as well as the altered expression of BTB related junctions, were involved in the reproductive toxicity mediated by MEQ in vivo.

  18. Caffeine intake, toxicity and dependence and lifetime risk for psychiatric and substance use disorders: an epidemiologic and co-twin control analysis.

    Science.gov (United States)

    Kendler, Kenneth S; Myers, John; O Gardner, Charles

    2006-12-01

    Although caffeine is the most commonly used psychoactive substance and often produces symptoms of toxicity and dependence, little is known, especially in community samples, about the association between caffeine use, toxicity and dependence and risk for common psychiatric and substance use disorders. Assessments of lifetime maximal caffeine use and symptoms of caffeine toxicity and dependence were available on over 3600 adult twins ascertained from the population-based Virginia Twin Registry. Lifetime histories of major depression (MD), generalized anxiety disorder (GAD) and panic disorder, alcohol dependence, adult antisocial behavior and cannabis and cocaine abuse/dependence were obtained at personal interview. Logistic regression analyses in the entire sample and within monozygotic (MZ) twin pairs were conducted in SAS. In the entire sample, measures of maximal caffeine use, heavy caffeine use, and caffeine-related toxicity and dependence were significantly and positively associated with all seven psychiatric and substance use disorders. However, within MZ twin pairs, controlling for genetic and family environmental factors, these associations, while positive, were all non-significant. These results were similar when excluding twins who denied regular caffeine use. Maximal lifetime caffeine intake and caffeine-associated toxicity and dependence are moderately associated with risk for a wide range of psychiatric and substance use disorders. Analyses of these relationships within MZ twin pairs suggest that most of the observed associations are not causal. Rather, familial factors, which are probably in part genetic, predispose to both caffeine intake, toxicity and dependence and the risk for a broad array of internalizing and externalizing disorders.

  19. Model-based approach for quantitative estimates of skin, heart, and lung toxicity risk for left-side photon and proton irradiation after breast-conserving surgery.

    Science.gov (United States)

    Tommasino, Francesco; Durante, Marco; D'Avino, Vittoria; Liuzzi, Raffaele; Conson, Manuel; Farace, Paolo; Palma, Giuseppe; Schwarz, Marco; Cella, Laura; Pacelli, Roberto

    2017-05-01

    Proton beam therapy represents a promising modality for left-side breast cancer (BC) treatment, but concerns have been raised about skin toxicity and poor cosmesis. The aim of this study is to apply skin normal tissue complication probability (NTCP) model for intensity modulated proton therapy (IMPT) optimization in left-side BC. Ten left-side BC patients undergoing photon irradiation after breast-conserving surgery were randomly selected from our clinical database. Intensity modulated photon (IMRT) and IMPT plans were calculated with iso-tumor-coverage criteria and according to RTOG 1005 guidelines. Proton plans were computed with and without skin optimization. Published NTCP models were employed to estimate the risk of different toxicity endpoints for skin, lung, heart and its substructures. Acute skin NTCP evaluation suggests a lower toxicity level with IMPT compared to IMRT when the skin is included in proton optimization strategy (0.1% versus 1.7%, p < 0.001). Dosimetric results show that, with the same level of tumor coverage, IMPT attains significant heart and lung dose sparing compared with IMRT. By NTCP model-based analysis, an overall reduction in the cardiopulmonary toxicity risk prediction can be observed for all IMPT compared to IMRT plans: the relative risk reduction from protons varies between 0.1 and 0.7 depending on the considered toxicity endpoint. Our analysis suggests that IMPT might be safely applied without increasing the risk of severe acute radiation induced skin toxicity. The quantitative risk estimates also support the potential clinical benefits of IMPT for left-side BC irradiation due to lower risk of cardiac and pulmonary morbidity. The applied approach might be relevant on the long term for the setup of cost-effectiveness evaluation strategies based on NTCP predictions.

  20. Gene-environment interaction and male reproductive function

    DEFF Research Database (Denmark)

    Axelsson, Jonatan; Bonde, Jens Peter; Giwercman, Yvonne L

    2010-01-01

    As genetic factors can hardly explain the changes taking place during short time spans, environmental and lifestyle-related factors have been suggested as the causes of time-related deterioration of male reproductive function. However, considering the strong heterogeneity of male fecundity between...... that specific genotypes may confer a larger risk of male reproductive disorders following certain exposures. This paper presents a critical review of animal and human evidence on how genes may modify environmental effects on male reproductive function. Some examples have been found that support this mechanism...... of reproduction, namely environmental and lifestyle factors as the cause of sperm DNA damage. It remains to be investigated to what extent such genetic changes, by natural conception or through the use of assisted reproductive techniques, are transmitted to the next generation, thereby causing increased morbidity...

  1. EXPOSURE TO INTERMITTENT AIR POLLUTION AND CHANGES IN SEMEN QUALITY: EVIDENCE FOR AN ASSOCIATION AND IMPLICATIONS FOR REPRODUCTIVE RISK ASSESSMENT

    Science.gov (United States)

    Exposure to Intermittent Air Pollution and Changes in Semen Quality:Evidence for an Association and Implications for Reproductive Risk Assessment. S. D. Perreault1, S.G. Selevan2, J. Rubes3, D. Zudova3, and D.P. Evenson4 1US EPA, ORD/NHEERL, Research Triangle Pa...

  2. [Occupational toxic exposure in the pregnant woman. 1: principles fo individual risk assessment ].

    Science.gov (United States)

    Testud, F; Lambert-Chhum, R; Bellemin, B; Descotes, J

    2001-12-01

    Many women of childbearing age are occupationally exposed to chemicals and concerned with the ensuing risk when pregnant. To describe the principles of individual risk assessment to be applied in pregnant women or women wishing to become pregnant that are exposed to chemicals at the workplace. Each request for risk assessment is based on a comprehensive review of the hazards of the handled products together with a thorough evaluation of the actual exposure at the workplace. A toxicological advice is then written to the gynecologist or the general practitioner in charge of the patient. When the exposure is estimated to be hazardous for the pregnancy, either total withdrawal, avoidance of certain activities or improvements of individual protective devices are recommended. The outcome of the pregnancy is systematically followed-up. An objective assessment of toxic risks in pregnant women exposed to chemicals at the workplace can be done. Thus, patients who must be withdrawn or benefit from improvements of their workstation can be selected.

  3. Toxicovigilance: A new approach for the hazard identification and risk assessment of toxicants in human beings

    International Nuclear Information System (INIS)

    Descotes, Jacques; Testud, Francois

    2005-01-01

    The concept of toxicovigilance encompasses the active detection, validation and follow-up of clinical adverse events related to toxic exposures in human beings. Poison centers are key players in this function as poisoning statistics are essential to define the cause, incidence and severity of poisonings occurring in the general population. In addition, the systematic search for unexpected shifts in the recorded causes of poisonings, e.g., following the introduction of a new product, or change in the formulation or recommended use of an old product, allows for a rapid detection of potential adverse health consequences and the implementation of preventive or corrective measures. However, toxicovigilance is genuinely a medical and not only a statistical approach of human toxicity issues. In contrast to epidemiology, toxicovigilance is based on the in-depth medical assessment of acute or chronic intoxications on an individual basis, which requires detailed information that poison centers can rarely obtain via emergency telephone calls and that epidemiologists cannot collect or process. Validation of this medical information must primarily be based on toxicological expertise to help identify causal links between otherwise unexplained pathological conditions and documented toxic exposures. Thus, toxicovigilance can contribute to hazard identification and risk assessment by providing medically validated data which are often overlooked in the process of risk assessment. So far, very few structured toxicovigilance systems have been set up and hopefully national and international initiatives will bridge this gap in our knowledge of the toxicity of many chemicals and commercial products in human beings

  4. Toxicovigilance: a new approach for the hazard identification and risk assessment of toxicants in human beings.

    Science.gov (United States)

    Descotes, Jacques; Testud, François

    2005-09-01

    The concept of toxicovigilance encompasses the active detection, validation and follow-up of clinical adverse events related to toxic exposures in human beings. Poison centers are key players in this function as poisoning statistics are essential to define the cause, incidence and severity of poisonings occurring in the general population. In addition, the systematic search for unexpected shifts in the recorded causes of poisonings, e.g., following the introduction of a new product, or change in the formulation or recommended use of an old product, allows for a rapid detection of potential adverse health consequences and the implementation of preventive or corrective measures. However, toxicovigilance is genuinely a medical and not only a statistical approach of human toxicity issues. In contrast to epidemiology, toxicovigilance is based on the in-depth medical assessment of acute or chronic intoxications on an individual basis, which requires detailed information that poison centers can rarely obtain via emergency telephone calls and that epidemiologists cannot collect or process. Validation of this medical information must primarily be based on toxicological expertise to help identify causal links between otherwise unexplained pathological conditions and documented toxic exposures. Thus, toxicovigilance can contribute to hazard identification and risk assessment by providing medically validated data which are often overlooked in the process of risk assessment. So far, very few structured toxicovigilance systems have been set up and hopefully national and international initiatives will bridge this gap in our knowledge of the toxicity of many chemicals and commercial products in human beings.

  5. Effects of the essential oil from fruits of Schinus terebinthifolius Raddi (Anacardiaceae) on reproductive functions in male rats

    OpenAIRE

    Affonso, Cristiano R. G.; Fernandes, Rozeverter M.; Oliveira, Jamylla M. G. de; Martins, Maria do Carmo de Carvalho e; Lima, Sidney G. de; Sousa Júnior, Gustavo R. de; Fernandes, Maria Zenaide de Lima C. Moreno; Zanini, Surama F.

    2012-01-01

    The essential oil of Schinus terebinthifolius (Anacardiaceae) was analyzed by GC and GC-MS. α-Fenchene, limonene, β-pinene, α-phellandrene, and β-isosylvestrene represent about 80% of the oil composition. The reproductive toxicity of the essential oil in Wistar male rats was evaluated. No changes were observed in the mass of the reproductive organs, number and morphology of spermatozoa, reproductive rates, and the body mass of offspring of male rats after treatment with the essential oil of S...

  6. Reproductive success and failure: the role of winter body mass in reproductive allocation in Norwegian moose.

    Science.gov (United States)

    Milner, Jos M; van Beest, Floris M; Solberg, Erling J; Storaas, Torstein

    2013-08-01

    A life history strategy that favours somatic growth over reproduction is well known for long-lived iteroparous species, especially in unpredictable environments. Risk-sensitive female reproductive allocation can be achieved by a reduced reproductive effort at conception, or the subsequent adjustment of investment during gestation or lactation in response to unexpected environmental conditions or resource availability. We investigated the relative importance of reduced investment at conception compared with later in the reproductive cycle (i.e. prenatal, perinatal or neonatal mortality) in explaining reproductive failure in two high-density moose (Alces alces) populations in southern Norway. We followed 65 multiparous, global positioning system (GPS)-collared females throughout the reproductive cycle and focused on the role of maternal nutrition during gestation in determining reproductive success using a quasi-experimental approach to manipulate winter forage availability. Pregnancy rates in early winter were normal (≥0.8) in all years while spring calving rates ranged from 0.4 to 0.83, with prenatal mortality accounting for most of the difference. Further losses over summer reduced autumn recruitment rates to 0.23-0.69, despite negligible predation. Over-winter mass loss explained variation in both spring calving and autumn recruitment success better than absolute body mass in early or late winter. Although pregnancy was related to body mass in early winter, overall reproductive success was unrelated to pre-winter body condition. We therefore concluded that reproductive success was limited by winter nutritional conditions. However, we could not determine whether the observed reproductive allocation adjustment was a bet-hedging strategy to maximise reproduction without compromising survival or whether females were simply unable to invest more resources in their offspring.

  7. Understanding environmental health inequalities through comparative intracategorical analysis: racial/ethnic disparities in cancer risks from air toxics in El Paso County, Texas.

    Science.gov (United States)

    Collins, Timothy W; Grineski, Sara E; Chakraborty, Jayajit; McDonald, Yolanda J

    2011-01-01

    This paper contributes to the environmental justice literature by analyzing contextually relevant and racial/ethnic group-specific variables in relation to air toxics cancer risks in a US-Mexico border metropolis at the census block group-level. Results indicate that Hispanics' ethnic status interacts with class, gender and age status to amplify disproportionate risk. In contrast, results indicate that non-Hispanic whiteness attenuates cancer risk disparities associated with class, gender and age status. Findings suggest that a system of white-Anglo privilege shapes the way in which race/ethnicity articulates with other dimensions of inequality to create unequal cancer risks from air toxics. Copyright © 2010 Elsevier Ltd. All rights reserved.

  8. Effects of waterborne zinc on reproduction, survival and morphometrics of Gyrodactylus turnbulli (Monogenea) on guppies (Poecilia reticulata).

    Science.gov (United States)

    Gheorghiu, Cristina; Cable, Joanne; Marcogliese, David J; Scott, Marilyn E

    2007-03-01

    Recent reviews indicate that pollutants in the surrounding macroenvironment directly influence the population dynamics, distribution and dispersal of fish ectoparasites, often leading to increased parasitism. The aim of the current study was to explore the effects of sublethal concentrations of waterborne zinc (up to 240 microg Zn/L) on survival, reproduction and morphometrics of Gyrodactylus turnbulli, a viviparous monogenean infecting the skin and fins of the guppy, Poecilia reticulata. Parasite survival and reproduction on the fish were recorded daily for individual parasites maintained in isolated containers. Both survival and reproduction were reduced in 30 and 120 microg Zn/L, compared with 0, 15, and 60 microg Zn/L indicating direct toxic effects of Zn on the parasite. However, as generation time was unaffected by Zn, we attribute the reduced reproduction to the shorter lifespan. Parasite survival off the fish was monitored hourly. Average lifespan of the detached parasites decreased linearly from 19.5 h in 0 microg Zn/L to 17.3h in 240 microg Zn/L, further supporting the direct toxic effect of Zn to the parasite. In addition, temporal dynamics of parasite morphometrics were monitored from mini-epidemics sampled after 1, 5, 10, and 15 days exposure to various Zn concentrations. All morphological parameters decreased significantly in response both to concentration and duration of exposure to waterborne Zn. Together these data clearly indicate that concentrations as low as 120 microg Zn/L are directly toxic to G. turnbulli.

  9. Air toxics concentrations, source identification, and health risks: An air pollution hot spot in southwest Memphis, TN

    Science.gov (United States)

    Jia, Chunrong; Foran, Jeffery

    2013-12-01

    Southwest Memphis is a residential region surrounded by fossil fuel burning, steel, refining, and food processing industries, and considerable mobile sources whose emissions may pose adverse health risks to local residents. This study characterizes cancer and non-cancer risks resulting from exposure to ambient air toxics in southwest Memphis. Air toxics samples were collected at a central location every 6 days from June 5, 2008 to January 8, 2010. Volatile organic compounds (VOCs) were collected in evacuated stainless-steel canisters and aldehydes by DNPH cartridges, and samples were analyzed for 73 target compounds. A total of 60 compounds were detected and 39 were found in over 86% of the samples. Mean concentrations of many compounds were higher than those measured in many industrial communities throughout the U.S. The cumulative cancer risk associated with exposure to 13 carcinogens found in southwest Memphis air was 2.3 × 10-4, four times higher than the national average of 5.0 × 10-5. Three risk drivers were identified: benzene, formaldehyde, and acrylonitrile, which contributed 43%, 19%, and 14% to the cumulative risk, respectively. This is the first field study to confirm acrylonitrile as a potential risk driver. Mobile, secondary, industrial, and background sources contributed 57%, 24%, 14%, and 5% of the risk, respectively. The results of this study indicate that southwest Memphis, a region of significant income, racial, and social disparities, is also a region under significant environmental stress compared with surrounding areas and communities.

  10. Assisted reproductive technologies and the issue of risks to women and embryos: the tip of the iceberg

    Directory of Open Access Journals (Sweden)

    Kalline Carvalho Gonçalves Eler

    2016-10-01

    Full Text Available In assisted reproduction, not everything that is technically possible is ethically acceptable or socially desirable. The impact it has on women and embryos needs to be considered. The risk to women involves the ingestion of hormones, which can cause potentially serious complications. As regards embryos, there are risks of prematurity, low birth weight and other diseases. This article advocates a strong protective guardianship for women and the extracorporeal embryo. Faced with new bioethical dilemmas, the essence of the human being is in question. It is therefore the task of all spheres of knowledge to make a distinction between the personalizing and depersonalizing of human beings.

  11. Bioaccumulation and toxicity of selenium during a life-cycle exposure with desert pupfish (Cyprinodon macularius)

    Science.gov (United States)

    Besser, John M.; Brumbaugh, William G.; Papoulias, Diana M.; Ivey, Chris D.; Kunz, James L.; Annis, Mandy; Ingersoll, Christopher G.

    2012-01-01

    Populations of desert pupfish (Cyprinodon macularius; pupfish), a federally-listed endangered species, inhabit irrigation drains in the Imperial Valley agricultural area of southern California. These drains have varying degrees of selenium (Se) contamination of water, sediment, and aquatic biota. Published Se toxicity studies suggest that these levels of Se contamination may pose risk of chronic toxicity to Se-sensitive fish, but until recently there have been no studies of the chronic toxicity of Se to desert pupfish.A life-cycle Se exposure with pupfish was conducted to estimate dietary and tissue thresholds for toxic effects of Se on all life stages. The dietary exposure was based on live oligochaete worms (Lumbriculus variegatus) dosed with Se by a laboratory food chain based on selenized yeast. Oligochaetes readily accumulated Se from mixtures of selenized and control yeasts. The protocol for dosing oligochaetes for pupfish feeding studies included long-term (at least 28 days) feeding of a low-ration of yeast mixtures to large batches of oligochaetes. Oligochaetes were dosed at five Se levels in a 50-percent dilution series. Pupfish were simultaneously fed Se-dosed oligochaetes and exposed to a series of Se concentrations in water (consisting of 85 percent selenate and 15 percent selenite) to produce exposures that were consistent with Se concentrations and speciation in pupfish habitats. The nutritional characteristics of oligochaete diets were consistent across the range of oligochaete Se concentrations tested.The life-cycle exposure started with laboratory-cultured juvenile pupfish that were exposed to Se through sexual maturation and reproduction (150 days; F0 exposure). The Se exposure continued with eggs, larvae, and juveniles produced by Se-exposed parents (79 days; F1 exposure). Selenium exposure (water and diets), Se bioaccumulation (whole-body and eggs), and toxicity endpoints (juvenile and adult survival and growth; egg production and hatching

  12. National cohort study of reproductive risk factors for rheumatoid arthritis in Denmark: a role for hyperemesis, gestational hypertension and pre-eclampsia?

    DEFF Research Database (Denmark)

    Jørgensen, K T; Pedersen, B V; Jacobsen, S

    2010-01-01

    While reproductive factors might plausibly be involved in the aetiology of rheumatoid arthritis (RA), the female predominance remains unexplained. A study was undertaken to address the possible impact of live births, pregnancy losses and pregnancy complications on the subsequent risk of RA...

  13. Developmental toxicity of engineered nanomaterials

    DEFF Research Database (Denmark)

    Hougaard, Karin S.; Hansen, Jitka S.; Jackson, Petra

    2016-01-01

    Study of air pollution indicates that minute particles may adversely interfere with pregnancy and fetal development. As engineering of nanoparticles have emerged, so has concern that these might interfere with reproductive and developmental functions. This is because nanotechnology may potentially...... increase the overall particle burden in air and introduce particles with novel characteristics and surface reactivity. To evaluate safety for pregnant women, we have studied developmental toxicity of engineered nanoparticles (ENPs), following exposure of pregnant mice by inhalation (ENPs of titanium...

  14. NTP-CERHR monograph on the potential human reproductive and developmental effects of hydroxyurea.

    Science.gov (United States)

    2008-10-01

    The National Toxicology Program (NTP) Center for the Evaluation of Risks to Human Reproduction (CERHR) conducted an evaluation of the potential for hydroxyurea to cause adverse effects on reproduction and development in humans. Hydroxyurea is a drug used to treat cancer, sickle cell disease, and thalassemia. It is the only treatment for sickle cell disease in children, aside from blood transfusion and, in severe cases, hematopoietic stem cell transplantation. Hydroxyurea is FDA-approved for use in adults with sickle cell anemia to reduce the frequency of painful crises and the need for blood transfusions. Hydroxyurea may be given to children and adults with sickle cell disease for an extended period of time or for repeated cycles of therapy. Treatment with hydroxyurea is associated with known side effects such as cytotoxicity and myelosuppression, and hydroxyurea is genotoxic (can damage DNA). CERHR selected hydroxyurea for evaluation because of: its increasing use for treatment of sickle cell disease in children and adults, knowledge that it inhibits DNA synthesis and is cytotoxic, and published evidence of reproductive and developmental toxicity in rodents. The results of this evaluation are published in the NTP-CERHR Monograph on Hydroxyurea, which includes the NTP Brief and Expert Panel Report on the Reproductive and Developmental Toxicity of Hydroxyurea. Additional information related to the evaluation process, including public comments received on the draft NTP Brief and the final expert panel report, are available on the CERHR website (http:// cerhr.niehs.nih.gov/). See hydroxyurea under "CERHR Chemicals" on the homepage or go directly to http://cerhr.niehs.nih.gov/chemicals/hydroxyurea/hydroxyurea-eval.html). The NTP reached the following conclusions on the possible effects of exposure to hydroxyurea on human reproduction or development. The possible levels of concern, from lowest to highest, are negligible concern, minimal concern, some concern, concern

  15. Does Bleomycin Lung Toxicity Increase the Risk of Radiation Pneumonitis in Hodgkin Lymphoma?

    International Nuclear Information System (INIS)

    Abou Yehia, Zeinab; Mikhaeel, George N.; Smith, Grace; Pinnix, Chelsea C.; Milgrom, Sarah A.; Tang, Chad; Jiang, Wen; Fanale, Michelle A.; Oki, Yasuhiro; Shank, JoAnn H.; Horace, Trisha; Reddy, Jay; Akhtari, Mani; Gunther, Jillian R.; Suki, Tina; Allen, Pamela K.; Turner, Shryll; Mawlawi, Osama; Dabaja, Bouthaina S.

    2016-01-01

    Purpose: Bleomycin pulmonary toxicity (BPT) is a well-known complication of treatment in patients with Hodgkin lymphoma (HL). We undertook the present study to investigate the risk of radiation pneumonitis (RP) in the setting of BPT and to determine the need for delay or omission of radiation therapy (RT) in these patients. Methods and Materials: We identified 123 HL patients treated with ABVD (Adriamycin, bleomycin, vinblastine, dacarbazine) followed by RT to the chest from January 2009 to December 2014. The medical records were reviewed for clinical, pathologic, and treatment information and toxicities. Our primary outcome was RP of any grade. Univariate and multivariate analyses were used to assess the association of BPT, baseline patient characteristics, and treatment variables with the incidence of RP. Results: A total of 123 patients were included, of whom 99 (80%) received consolidation intensity modulated RT after ABVD treatment. We identified 31 patients (25.2%) with BPT after frontline ABVD. Seventeen patients (13.8%) developed RP a median of 8 weeks (range 1-39) after RT completion. BPT did not correlate with the risk of developing RP (P=.36). We evaluated the RP outcomes with respect to the bleomycin to RT interval (≤6 weeks vs >6 weeks), and we found that this interval did not predict for RP risk (P=.60). Dosimetric parameters such as the volume covered by 5 Gy and the mean lung dose were analyzed. A volume covered by 5 Gy of >55% and mean lung dose >13.5 Gy increased the risk of RP by 1.14-fold (P=.002) and 4.24-fold (P=.007), respectively. Conclusions: The results of our study suggest that BPT does not increase the risk of developing RP. Furthermore, RT initiation does not need to be delayed after chemotherapy, except to allow for the completion of steroid therapy or clinical recovery from BPT.

  16. Does Bleomycin Lung Toxicity Increase the Risk of Radiation Pneumonitis in Hodgkin Lymphoma?

    Energy Technology Data Exchange (ETDEWEB)

    Abou Yehia, Zeinab [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Mikhaeel, George N. [Department of Clinical Oncology, Guy' s & St Thomas' Hospital, London (United Kingdom); Smith, Grace; Pinnix, Chelsea C.; Milgrom, Sarah A.; Tang, Chad; Jiang, Wen [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Fanale, Michelle A.; Oki, Yasuhiro [Department of Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Shank, JoAnn H.; Horace, Trisha; Reddy, Jay [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Akhtari, Mani [Department of Radiation Oncology, The University of Texas Medical Branch Hospitals, Galveston, Texas (United States); Gunther, Jillian R. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Suki, Tina [The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Allen, Pamela K.; Turner, Shryll [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Mawlawi, Osama [Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Dabaja, Bouthaina S., E-mail: bdabaja@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2016-12-01

    Purpose: Bleomycin pulmonary toxicity (BPT) is a well-known complication of treatment in patients with Hodgkin lymphoma (HL). We undertook the present study to investigate the risk of radiation pneumonitis (RP) in the setting of BPT and to determine the need for delay or omission of radiation therapy (RT) in these patients. Methods and Materials: We identified 123 HL patients treated with ABVD (Adriamycin, bleomycin, vinblastine, dacarbazine) followed by RT to the chest from January 2009 to December 2014. The medical records were reviewed for clinical, pathologic, and treatment information and toxicities. Our primary outcome was RP of any grade. Univariate and multivariate analyses were used to assess the association of BPT, baseline patient characteristics, and treatment variables with the incidence of RP. Results: A total of 123 patients were included, of whom 99 (80%) received consolidation intensity modulated RT after ABVD treatment. We identified 31 patients (25.2%) with BPT after frontline ABVD. Seventeen patients (13.8%) developed RP a median of 8 weeks (range 1-39) after RT completion. BPT did not correlate with the risk of developing RP (P=.36). We evaluated the RP outcomes with respect to the bleomycin to RT interval (≤6 weeks vs >6 weeks), and we found that this interval did not predict for RP risk (P=.60). Dosimetric parameters such as the volume covered by 5 Gy and the mean lung dose were analyzed. A volume covered by 5 Gy of >55% and mean lung dose >13.5 Gy increased the risk of RP by 1.14-fold (P=.002) and 4.24-fold (P=.007), respectively. Conclusions: The results of our study suggest that BPT does not increase the risk of developing RP. Furthermore, RT initiation does not need to be delayed after chemotherapy, except to allow for the completion of steroid therapy or clinical recovery from BPT.

  17. Advanced reproductive age and fertility.

    Science.gov (United States)

    Liu, Kimberly; Case, Allison

    2011-11-01

    To improve awareness of the natural age-related decline in female and male fertility with respect to natural fertility and assisted reproductive technologies (ART) and provide recommendations for their management, and to review investigations in the assessment of ovarian aging. This guideline reviews options for the assessment of ovarian reserve and fertility treatments using ART with women of advanced reproductive age presenting with infertility. The outcomes measured are the predictive value of ovarian reserve testing and pregnancy rates with natural and assisted fertility. Published literature was retrieved through searches of PubMed or Medline, CINAHL, and The Cochrane Library in June 2010, using appropriate key words (ovarian aging, ovarian reserve, advanced maternal age, advanced paternal age, ART). Results were restricted to systematic reviews, randomized controlled trials/controlled clinical trials, and observational studies. There were no date or language restrictions. Searches were updated on a regular basis and incorporated into the guideline to December 2010. The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care. Recommendations for practice were ranked according to the method described in that report (Table). Primary and specialist health care providers and women will be better informed about ovarian aging and the age-related decline in natural fertility and about options for assisted reproductive technology. 1. Women in their 20s and 30s should be counselled about the age-related risk of infertility when other reproductive health issues, such as sexual health or contraception, are addressed as part of their primary well-woman care. Reproductive-age women should be aware that natural fertility and assisted reproductive technology success (except with egg donation) is significantly lower for women in their late 30s and 40s. (II-2A) 2. Because of the decline in fertility and the

  18. Reproductive factors, menopausal hormone therapies and primary liver cancer risk: a systematic review and dose-response meta-analysis of observational studies.

    Science.gov (United States)

    Zhong, Guo-Chao; Liu, Yan; Chen, Nan; Hao, Fa-Bao; Wang, Kang; Cheng, Jia-Hao; Gong, Jian-Ping; Ding, Xiong

    2016-12-01

    A striking gender disparity in the incidence and outcome of primary liver cancer (PLC) has been well recognized. Mounting evidence from basic research suggests that hormonal factors may be involved in the gender disparity of PLC. Whether hormonal exposures in human subjects are associated with PLC risk is largely unknown. Whether reproductive factors and use of menopausal hormone therapies (MHTs) in women are associated with PLC risk remains controversial. We conducted this study to clarify this issue. PubMed and EMBASE were searched to July, 2016 for studies published in English or Chinese. Observational studies (cohort, nested case-control and case-control) that provided risk estimates of reproductive factors, MHTs and PLC risk were eligible. The quality of included studies was determined based on the Newcastle-Ottawa quality assessment scale. Summary risk ratios (RRs) were calculated using a random-effects model. Dose-response analysis was conducted where possible. Fifteen peer-reviewed studies, involving 1795 PLC cases and 2 256 686 women, were included. Overall meta-analyses on parity and PLC risk did not find any significant associations; however, when restricting to studies with PLC cases ≥100, increasing parity was found to be significantly associated with a decreased risk of PLC [RR for the highest versus lowest parity 0.67, 95% CI 0.52, 0.88; RR for parous versus nulliparous 0.71, 95% CI 0.53, 0.94; RR per one live birth increase 0.93, 95% CI 0.88, 0.99]. A J-shaped relationship between parity and PLC risk was identified (P non-linearity  Parity is associated with PLC risk in a J-shaped dose-response pattern. Late age at menarche and ever use of MHT are associated with a reduced risk of PLC, whereas there is no association of ever use of ET and EPT, age at first birth, or spontaneous and induced abortion with PLC risk. Compared to women with no history of oophorectomy, those with a history of oophorectomy are at an increased risk of PLC. Our findings

  19. Differential reconstructed gene interaction networks for deriving toxicity threshold in chemical risk assessment.

    Science.gov (United States)

    Yang, Yi; Maxwell, Andrew; Zhang, Xiaowei; Wang, Nan; Perkins, Edward J; Zhang, Chaoyang; Gong, Ping

    2013-01-01

    Pathway alterations reflected as changes in gene expression regulation and gene interaction can result from cellular exposure to toxicants. Such information is often used to elucidate toxicological modes of action. From a risk assessment perspective, alterations in biological pathways are a rich resource for setting toxicant thresholds, which may be more sensitive and mechanism-informed than traditional toxicity endpoints. Here we developed a novel differential networks (DNs) approach to connect pathway perturbation with toxicity threshold setting. Our DNs approach consists of 6 steps: time-series gene expression data collection, identification of altered genes, gene interaction network reconstruction, differential edge inference, mapping of genes with differential edges to pathways, and establishment of causal relationships between chemical concentration and perturbed pathways. A one-sample Gaussian process model and a linear regression model were used to identify genes that exhibited significant profile changes across an entire time course and between treatments, respectively. Interaction networks of differentially expressed (DE) genes were reconstructed for different treatments using a state space model and then compared to infer differential edges/interactions. DE genes possessing differential edges were mapped to biological pathways in databases such as KEGG pathways. Using the DNs approach, we analyzed a time-series Escherichia coli live cell gene expression dataset consisting of 4 treatments (control, 10, 100, 1000 mg/L naphthenic acids, NAs) and 18 time points. Through comparison of reconstructed networks and construction of differential networks, 80 genes were identified as DE genes with a significant number of differential edges, and 22 KEGG pathways were altered in a concentration-dependent manner. Some of these pathways were perturbed to a degree as high as 70% even at the lowest exposure concentration, implying a high sensitivity of our DNs approach

  20. Sexual Maturity and Life Stage Influences Toxic Metal Accumulation in Croatian Brown Bears.

    Science.gov (United States)

    Lazarus, Maja; Sekovanić, Ankica; Orct, Tatjana; Reljić, Slaven; Jurasović, Jasna; Huber, Đuro

    2018-02-01

    The influence of reproductive and (early) life stages on toxic metal levels was investigated in the brown bear (Ursus arctos), the largest mammalian predator species in Croatia. The purpose was to examine critical clusters in a population that might be at a higher risk of adverse health effects caused by metals as environmental contaminants. Levels of cadmium, mercury and lead in muscle, liver and kidney cortex of 325 male and 139 female bears, quantified by inductively coupled plasma mass spectrometry, were analysed according to distinct bear life stages (young: cub, yearling, subadult; mature: adult). Metal levels did not differ among sexes in young animals (< 4 years), except for mercury in muscles (higher in females), and adult females had higher cadmium and mercury. A trend of renal cadmium accumulation with age in immature male animals disappeared once they reached maturity, whereas for females this trend has only slowly declined in mature compared to immature bears. In early life stage (< 1 year), bear cubs had lower cadmium, comparable mercury, and higher lead in the kidneys than the bears of the following age category (yearlings). Due to a higher proportion of renal lead transfer from the mother to the cub compared with cadmium, it may be that the high burden of cadmium found in kidneys of older females has lower toxicological concern for their cubs than the lead content. Sex, reproductive, and life stages of bears were confirmed as important in assessing toxic metal burden.

  1. QSAR development and bioavailability determination: the toxicity of chloroanilines to the soil dwelling springtail Folsomia candida.

    Science.gov (United States)

    Giesen, Daniel; van Gestel, Cornelis A M

    2013-03-01

    Quantitative structure-activity relationships (QSARs) are an established tool in environmental risk assessment and a valuable alternative to the exhaustive use of test animals under REACH. In this study a QSAR was developed for the toxicity of a series of six chloroanilines to the soil-dwelling collembolan Folsomia candida in standardized natural LUFA2.2 soil. Toxicity endpoints incorporated in the QSAR were the concentrations causing 10% (EC10) and 50% (EC50) reduction in reproduction of F. candida. Toxicity was based on concentrations in interstitial water estimated from nominal concentrations in the soil and published soil-water partition coefficients. Estimated effect concentrations were negatively correlated with the lipophilicity of the compounds. Interstitial water concentrations for both the EC10 and EC50 for four compounds were determined by using solid-phase microextraction (SPME). Measured and estimated concentrations were comparable only for tetra- and pentachloroaniline. With decreasing chlorination the disparity between modelled and actual concentrations increased. Optimisation of the QSAR therefore could not be accomplished, showing the necessity to move from total soil to (bio)available concentration measurements. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. Effects of Artemisia lanata Extract on Reproductive Parameters of Female Rats

    Directory of Open Access Journals (Sweden)

    Ainehchi Nava

    2014-04-01

    Full Text Available Objective: Until date, there is no report on safety of Artemisia lanata. This study aimed to determine the possible undesirable effects of A. lanata on reproduction of female rats. Materials and Methods: The pregnant rats were treated (i.p. with vehicle or 200 and 400mg/kg of A. lanata hydroalcoholic extract from the 2-8 day of pregnancy. Then, number and weight of neonates, duration of pregnancy, and percent of dead fetuses were determined. Furthermore, cytotoxicity of this plant was tested using fibroblast (L929 and Chinese hamster ovary (Cho cell lines. Results: The A. lanata had no significant effect on duration of pregnancy, average number of neonates, and weight of neonates. However, administration of 200 and 400 mg/kg of the extract led to 30 and 44% abortion in animals, respectively. The extract at concentrations ≥ 200 μg/ml significantly (P < 0.001 inhibited the proliferation of L929 fibroblast cells. Regarding the Cho cells, the extract induced toxicity only at concentration of 800 μg/ml (P < 0.010. Conclusion: Our results showed that continuous consumption of A. lanata in pregnancy may increase the risk of abortion and also may have toxic effect on some cells.

  3. Associations between noncommunicable disease risk factors, race, education, and health insurance status among women of reproductive age in Brazil - 2011.

    Science.gov (United States)

    Mpofu, Jonetta Johnson; de Moura, Lenildo; Farr, Sherry L; Malta, Deborah Carvalho; Iser, Betine Moehlecke; Ivata Bernal, Regina Tomie; Robbins, Cheryl L; Lobelo, Felipe

    2016-06-01

    Noncommunicable disease (NCD) risk factors increase the risk of adverse reproductive health outcomes and are becoming increasingly common in Brazil. We analyzed VIGITEL 2011 telephone survey data for 13,745 Brazilian women aged 18-44 years in a probabilistic sample from 26 Brazilian state capitals and the Federal District. We examined associations between NCD risk factors (fruit and vegetable intake, leisure time physical activity, alcohol consumption, smoking status, BMI and hypertension status) and race, education, and insurance using chi-square tests and multivariable logistic regression models, estimating the average marginal effects to produce adjusted relative risk ratios (aRRs). Analyses were conducted using SAS 9.3 survey procedures and weighted to reflect population estimates. Women with less than a college education were more likely to report physical inactivity (adjusted relative risk (aRR) and 95% confidence interval = 1.1 (1.1-1.2)), smoking (aRR = 1.7 (1.3-2.2)), and self-reported diagnoses of hypertension (aRR = 2.0 (1.6-2.5)) compared to women with a college education or greater. Similarly, women without health insurance were more likely to report physical inactivity (aRR = 1.1 (1.1-1.2)), smoking (aRR = 1.4 (1.1-1.8)), and self-reported diagnoses of hypertension aRR = 1.4 (1.1-1.7)) compared to women with health insurance. Less variation was found by race and NCD risk factors. Targeted public health strategies and policies are needed to increase healthcare access and decrease educational and racial disparities in NCD risk factors among women of reproductive age in Brazil.

  4. Tributyltin impaired reproductive success in female zebrafish through disrupting oogenesis, reproductive behaviors and serotonin synthesis.

    Science.gov (United States)

    Xiao, Wei-Yang; Li, Ying-Wen; Chen, Qi-Liang; Liu, Zhi-Hao

    2018-07-01

    study demonstrated that TBT may impair the reproductive success of zebrafish females probably through disrupting oogenesis, disturbing reproductive behaviors and altering serotonin synthesis. The present study greatly extends our understanding on the reproductive toxicity of TBT on fish. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. Toxicity of nanoparticulate and bulk ZnO, Al2O3 and TiO2 to the nematode Caenorhabditis elegans

    International Nuclear Information System (INIS)

    Wang Huanhua; Wick, Robert L.; Xing Baoshan

    2009-01-01

    Limited information is available on the environmental behavior and associated potential risk of manufactured oxide nanoparticles (NPs). In this research, toxicity of nanoparticulate and bulk ZnO, Al 2 O 3 and TiO 2 were examined to the nematode Caenorhabditis elegans with Escherichia coli as a food source. Parallel experiments with dissolved metal ions from NPs were also conducted. The 24-h median lethal concentration (LC 50 ) and sublethal endpoints were assessed. Both NPs and their bulk counterparts were toxic, inhibiting growth and especially the reproductive capability of the nematode. The 24-h LC 50 for ZnO NPs (2.3 mg L -1 ) and bulk ZnO was not significantly different, but significantly different between Al 2 O 3 NPs (82 mg L -1 ) and bulk Al 2 O 3 (153 mg L -1 ), and between TiO 2 NPs (80 mg L -1 ) and bulk TiO 2 (136 mg L -1 ). Oxide solubility influenced the toxicity of ZnO and Al 2 O 3 NPs, but nanoparticle-dependent toxicity was indeed observed for the investigated NPs. - ZnO, Al 2 O 3 and TiO 2 nanoparticles are more toxic than their bulk counterparts to the nematode, Caenorhabditis elegans

  6. Reproductive Investment and Health Costs in Roma Women

    Directory of Open Access Journals (Sweden)

    Jelena Čvorović

    2017-11-01

    Full Text Available In this paper, we examine whether variation in reproductive investment affects the health of Roma women using a dataset collected through original anthropological fieldwork among Roma women in Serbia. Data were collected in 2014–2016 in several Roma semi-urban settlements in central Serbia. The sample consisted of 468 Roma women, averaging 44 years of age. We collected demographic data (age, school levels, socioeconomic status, risk behaviors (smoking and alcohol consumption, marital status, and reproductive history variables (the timing of reproduction, the intensity of reproduction, reproductive effort and investment after birth, in addition to self-reported health, height, and weight. Data analyses showed that somatic, short-term costs of reproduction were revealed in this population, while evolutionary, long-term costs were unobservable—contrariwise, Roma women in poor health contributed more to the gene pool of the next generation than their healthy counterparts. Our findings appear to be consistent with simple trade-off models that suggest inverse relationships between reproductive effort and health. Thus, personal sacrifice—poor health as an outcome—seems crucial for greater reproductive success.

  7. Joint Estimation of Cardiac Toxicity and Recurrence Risks After Comprehensive Nodal Photon Versus Proton Therapy for Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Stick, Line B., E-mail: line.bjerregaard.stick@regionh.dk [Department of Clinical Oncology, Rigshospitalet, University of Copenhagen, Copenhagen (Denmark); Niels Bohr Institute, Faculty of Science, University of Copenhagen, Copenhagen (Denmark); Yu, Jen [Maryland Proton Treatment Center, University of Maryland School of Medicine, Baltimore, Maryland (United States); Maraldo, Maja V. [Department of Clinical Oncology, Rigshospitalet, University of Copenhagen, Copenhagen (Denmark); Aznar, Marianne C. [Department of Clinical Oncology, Rigshospitalet, University of Copenhagen, Copenhagen (Denmark); Nuffield Department of Population Health, University of Oxford, Oxford (United Kingdom); Pedersen, Anders N. [Department of Clinical Oncology, Rigshospitalet, University of Copenhagen, Copenhagen (Denmark); Bentzen, Søren M. [Department of Clinical Oncology, Rigshospitalet, University of Copenhagen, Copenhagen (Denmark); Maryland Proton Treatment Center, University of Maryland School of Medicine, Baltimore, Maryland (United States); Greenebaum Comprehensive Cancer Center and Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, Maryland (United States); Vogelius, Ivan R. [Department of Clinical Oncology, Rigshospitalet, University of Copenhagen, Copenhagen (Denmark)

    2017-03-15

    Purpose: The study aims to perform joint estimation of the risk of recurrence caused by inadequate radiation dose coverage of lymph node targets and the risk of cardiac toxicity caused by radiation exposure to the heart. Delivered photon plans are compared with realistic proton plans, thereby providing evidence-based estimates of the heterogeneity of treatment effects in consecutive cases for the 2 radiation treatment modalities. Methods and Materials: Forty-one patients referred for postlumpectomy comprehensive nodal photon irradiation for left-sided breast cancer were included. Comparative proton plans were optimized by a spot scanning technique with single-field optimization from 2 en face beams. Cardiotoxicity risk was estimated with the model of Darby et al, and risk of recurrence following a compromise of lymph node coverage was estimated by a linear dose-response model fitted to the recurrence data from the recently published EORTC (European Organisation for Research and Treatment of Cancer) 22922/10925 and NCIC-CTG (National Cancer Institute of Canada Clinical Trials Group) MA.20 randomized controlled trials. Results: Excess absolute risk of cardiac morbidity was small with photon therapy at an attained age of 80 years, with median values of 1.0% (range, 0.2%-2.9%) and 0.5% (range, 0.03%-1.0%) with and without cardiac risk factors, respectively, but even lower with proton therapy (0.13% [range, 0.02%-0.5%] and 0.06% [range, 0.004%-0.3%], respectively). The median estimated excess absolute risk of breast cancer recurrence after 10 years was 0.10% (range, 0.0%-0.9%) with photons and 0.02% (range, 0.0%-0.07%) with protons. The association between age of the patient and benefit from proton therapy was weak, almost non-existing (Spearman rank correlations of −0.15 and −0.30 with and without cardiac risk factors, respectively). Conclusions: Modern photon therapy yields limited risk of cardiac toxicity in most patients, but proton therapy can reduce the

  8. Short- and Long-Term Effects of Prenatal Exposure to Iron Oxide Nanoparticles: Influence of Surface Charge and Dose on Developmental and Reproductive Toxicity

    Directory of Open Access Journals (Sweden)

    Kristin R. Di Bona

    2015-12-01

    Full Text Available Iron oxide nanoparticles (NPs are commonly utilized for biomedical, industrial, and commercial applications due to their unique properties and potential biocompatibility. However, little is known about how exposure to iron oxide NPs may affect susceptible populations such as pregnant women and developing fetuses. To examine the influence of NP surface-charge and dose on the developmental toxicity of iron oxide NPs, Crl:CD1(ICR (CD-1 mice were exposed to a single, low (10 mg/kg or high (100 mg/kg dose of positively-charged polyethyleneimine-Fe2O3-NPs (PEI-NPs, or negatively-charged poly(acrylic acid-Fe2O3-NPs (PAA-NPs during critical windows of organogenesis (gestation day (GD 8, 9, or 10. A low dose of NPs, regardless of charge, did not induce toxicity. However, a high exposure led to charge-dependent fetal loss as well as morphological alterations of the uteri (both charges and testes (positive only of surviving offspring. Positively-charged PEI-NPs given later in organogenesis resulted in a combination of short-term fetal loss (42% and long-term alterations in reproduction, including increased fetal loss for second generation matings (mice exposed in utero. Alternatively, negatively-charged PAA-NPs induced fetal loss (22% earlier in organogenesis to a lesser degree than PEI-NPs with only mild alterations in offspring uterine histology observed in the long-term.

  9. [Assisted Reproduction and Preimplantation Genetic Diagnosis in Patients Susceptible to Breast Cancer].

    Science.gov (United States)

    Veselá, K; Kocur, T; Horák, J; Horňák, M; Oráčová, E; Hromadová, L; Veselý, J; Trávník, P

    2016-01-01

    Assisted reproduction, as well as pregnancy itself, in patients with breast cancer or other hereditary type of cancer, is a widely discussed topic. In the past, patients treated for breast cancer were rarely involved in the discussion about reproductive possibilities or infertility treatment. However, current knowledge suggests, that breast cancer is neither a contraindication to pregnancy, nor to assisted reproduction techniques. On the contrary, assisted reproduction and preimplantation genetic diagnosis methods might prevent the transmission of genetic risks to the fetus. In this review we summarize data concerning pregnancy risks in patients with increased risk of breast cancer. In addition, we introduce current possibilities and approaches to fertility preservation prior to assisted reproduction treatment as well as novel methods improving the safety of fertility treatment. In the second part of this review, we focus on karyomapping--an advanced molecular genetic tool for elimination of germinal mutations in patients with predisposition to cancer. Moreover, the rapid development of preimplantation genetic diagnosis methods contributes to detection of both chromosomal aneuploidy and causal mutations in a relatively short time-span.

  10. Glutathione transferase activity and oocyte development in copepods exposed to toxic phytoplankton

    DEFF Research Database (Denmark)

    Kozlowsky-Suzuki, Betina; Koski, Marja; Hallberg, Eric

    2009-01-01

    toxins generally observed in copepods. In addition, decreasing gross growth efficiency (GGE) of copepods with increasing concentration of toxic diets could be caused either by a high expenditure coping with toxins (e.g., increase in the activity of detoxification enzymes) or by a deterioration...... of reproductive tissues. To assess the effect of toxic phytoplankton on the activity of detoxification enzymes and on oocyte maturation of Acartia tonsa and Temora longicornis, feeding and egg production experiments were carried out with a variety of toxic diets and an adequate non-toxic food control (Rhodomonas...... spp.) all provided as single species diets. Toxic diets included the nodularin-producing cyanobacterium Nodularia spumigena, the dinoflagellates Alexandrium minutum, and A. tamarense, which contained Paralytic Shellfish Poisoning (PSP) toxins, the dinoflagellate Prorocentrum lima with Diarrhetic...

  11. Eco-toxicity and human estrogenic exposure risks from "·OH-initiated photochemical transformation of four phthalates in water: A computational study

    International Nuclear Information System (INIS)

    Gao, Yanpeng; An, Taicheng; Ji, Yuemeng; Li, Guiying; Zhao, Cunyuan

    2015-01-01

    Transformation products (TPs) of emerging organic contaminates (EOCs) in water are still rarely considered in environmental risk assessment, although some have been found to be concern. "·OH is believed as an important reactive species both in indirect phototransformation and advanced oxidation technology. Thus, eco-toxicity and human estrogenic exposure risks of four phthalates and TPs during the "·OH-initiated photochemical process were investigated using computational approach. Four phthalates can be degraded through "·OH-addition and H-transfer pathways. The "·OH-addition TPs were predominant for dimethyl phthalates, while H-transfer TPs were predominant for other three phthalates. Compared with phthalates, "·OH-addition TPs (o-OH-phthalates) were one level more toxic to aquatic organisms, and m-OH-phthalates exhibit higher estrogenic activity. Although H-transfer TPs were less harmful than "·OH-addition TPs, some of them still have aquatic toxicity and estrogenic activity. Therefore, more attentions should be paid to photochemical TPs and original EOCs, particularly those exhibiting high estrogenic activity to humans. - Highlights: • Phthalates can be degraded with "·OH-addition and H-transfer pathways. • "·OH-addition products are mainly formed during DMP transformation. • H-transfer products were predominant for the transformation of DEP, DPP and DBP. • o-"·OH-addition products have greater eco-toxicity than corresponding phthalates. • m-"·OH-addition products have higher estrogenic activity than corresponding phthalates. - Computational approach could provide valuable information on the mechanisms, kinetics, eco-toxicity as well as human estrogenic exposure risks of EOCs and their transformation products.

  12. Leachate From Expanded Polystyrene Cups Is Toxic to Aquatic Invertebrates (Ceriodaphnia dubia

    Directory of Open Access Journals (Sweden)

    Clara Thaysen

    2018-02-01

    Full Text Available Expanded polystyrene (EPS products and their associated chemicals (e.g., styrenes are widespread in the marine environment. As a consequence, bans on their use for single-use packaging materials are being proposed in several municipalities. To better understand how science can inform decision-making, we looked at the available scientific literature about contamination and effects and conducted experiments to measure chemical leachate from polystyrene products and toxicity from the leachate. We conducted leaching experiments with common food matrices (water, soup broth, gravy, black coffee and coffee with cream and sugar at relevant temperatures (70 and 95°C that are consumed in or with several polystyrene products (coffee cup lids, polystyrene stir sticks, polystyrene spoons, EPS cups, EPS bowls, and EPS takeout containers. We analyzed each sample for styrene, ethylbenzene, toluene, benzene, meta- and para- xylene, isopropylbenzene, and isopropyltoluene—chemicals associated with polystyrene products. To determine whether the leachates are toxic, we conducted chronic toxicity tests, measuring survival and reproductive output in Ceriodaphnia dubia. Toxicity tests included nine treatments: seven concentrations of ethylbenzene, EPS cup leachate and a negative control. Overall, we found that temperature has a significant effect on leaching. We only detected leachates in trials conducted at higher temperature −95°C. Ethylbenzene was the only target analyte with final concentrations above the method limit of detection, and was present in the greatest concentrations in EPS and with soup broth. Measurable concentrations of ethylbenzene in the leachate ranged from 1.3 to 3.4 μg/L. In toxicity tests, the calculated LC50 for ethylbenzene was 14 mg/L and the calculated LC20 was 210 μg/L. For the treatment exposed to the EPS cup leachate, mortality was 40%—four times greater than the negative control. Finally, there was no significant difference (p

  13. Early smoking initiation, sexual behavior and reproductive health - a large population-based study of Nordic women

    DEFF Research Database (Denmark)

    Hansen, Bo Terning; Kjaer, Susanne Krüger; Plum, Christian Edinger Munk

    2010-01-01

    To investigate associations between early smoking initiation, risk-taking behavior and reproductive health.......To investigate associations between early smoking initiation, risk-taking behavior and reproductive health....

  14. Identification of causes of oil sands coke leachate toxicity

    International Nuclear Information System (INIS)

    Puttaswamy, N.; Liber, K.

    2010-01-01

    The potential causes of oil sands coke leachate toxicity were investigated. Chronic 7-day toxicity tests were conducted to demonstrate that oil sands coke leachates (CL) are acutely toxic to Ceriodaphnia dubia (C. dubia). CLs were generated in a laboratory to perform toxicity identification evaluation (TIE) tests in order to investigate the causes of the CL toxicity. The coke was subjected to a 15-day batch leaching process at 5.5 and 9.5 pH values. The leachates were then filtered and used for chemical and toxicological characterization. The 7-day estimates for the C. dubia survival were 6.3 for a pH of 5.5 and 28.7 per cent for the 9.5 CLs. The addition of EDTA significantly improved survival and reproduction in a pH of 5.5 CL, but not in a pH of 9.5 CL. The toxicity of the pH 5.5 CL was removed with a cationic resin treatment. The toxicity of the 9.5 pH LC was removed using an anion resin treatment. Toxicity re-appeared when nickel (Ni) and vanadium (V) were added back to the resin-treated CLs. Results of the study suggested that Ni and V were acting as primary toxicants in the pH 5.5 CL, while V was the primary cause of toxicity in the pH 9.5 CL.

  15. Determination of toxic metals, trace and essentials, and macronutrients in Sarpa salpa and Chelon labrosus: risk assessment for the consumers.

    Science.gov (United States)

    Afonso, Aridani; Gutiérrez, Angel J; Lozano, Gonzalo; González-Weller, Dailos; Rubio, Carmen; Caballero, José M; Hardisson, Arturo; Revert, Consuelo

    2017-04-01

    Due to increased environmental pollution, monitoring of contaminants in the environment and marine organisms is a fundamental tool for assessing the existence of risk from their consumption to human health. The levels of toxic heavy metals (Cd, Pb, and Al), trace and essential metals (B, Ba, Co, Cu, Cr, Fe, Li, Mn, Mo, Ni, Sr, V, and Zn), and macronutrients (Ca, K, Mg, Na) in two species of fish for human consumption were quantified in the present study. Eighty samples of muscle tissue and 80 samples of liver tissue belonging to two species of Osteichthyes fish; Sarpa salpa and Chelon labrosus were analyzed. The studied specimens were caught on the northern coast of Gran Canaria (Canary Islands) with fishing rods. As they caught from the shore, they are suitable samples for assessing the toxic levels of representative species caught by local amateur fishermen. The results show that both species are fit for human consumption since they have toxic levels of heavy metals (Cd, Pb, and Al) which are below the maximum established levels; however, the toxic levels of the liver samples are several orders of magnitude higher than the muscle samples, so we discourage their regular consumption. The risk assessment indicated that the two species of fish are safe for the average consumer; however, if the livers of these species are consumed, there could be risks because they exceed the PTWI for Pb and the TWI for Cd.

  16. Reproductive toxicity and pharmacokinetics of 2,3,7,8-tetrachlorodibenzo-p-dioxin. Pt. 1

    International Nuclear Information System (INIS)

    Chahoud, I.; Krowke, R.; Schimmel, A.; Merker, H.J.; Neubert, D.

    1989-01-01

    A study on the reproductive toxicity of 14 C-TCDD in male rats was performed. Two dose regimes were applied subcutaneously: TCDD-25 (initial dose: 25 μg/kg body wt; maintenance dose: 5 μg/kg body wt) and TCDD-75 (initial dose: 75 μg/kg body wt; maintenance dose: 15 μg/kg body wt); the maintenance dose was administered once weekly. The rats were treated for 10 weeks before they were mated and throughout the entire mating period. The dose regime TCDD-75 led to a mortality rate of 93% within a period of 16 weeks. The first animals died during 4 weeks, and an LD 50 was reached after 8 weeks. The dose regime TCDD-25 did not cause any mortality over a period of 12 weeks; but an LD 10 was reached within 13-20 weeks. The body weight was significantly decreased in both groups treated with TCDD after 1 week of treatment. It stabilized in the TCDD-25-group 4 weeks after treatment and stayed at this level until the end of the treatment period. The most significant finding is the delayed fertilization by the treated males; 15% of the males were found to be sterile. The mating index (84%) and fertility index (14±11 days) of the TCDD-25-group were lower when compared with controls (95%, 8±5), but the pregnancy index was not reduced. Application of the chosen TCDD doses led to clear-cut morphological changes of the testes. The Sertoli cells were changed (increased occurrence of vacuoles, swelling of endoplasmatic cavities), and the contact between the Sertoli cells and spermatogonia was disturbed, which might indicate an inhibited maturation of spermatozoa percursors. (orig.)

  17. Obsessive-compulsive disorder and female reproductive cycle events: results from the OCD and reproduction collaborative study.

    Science.gov (United States)

    Guglielmi, Valeria; Vulink, Nienke C C; Denys, Damiaan; Wang, Ying; Samuels, Jack F; Nestadt, Gerald

    2014-12-01

    Women with obsessive-compulsive disorder (OCD) often report that symptoms first appear or exacerbate during reproductive cycle events; however, little is known about these relationships. The goals of this study were to examine, in a US and a European female OCD sample, onset and exacerbation of OCD in reproductive cycle events, and to investigate the likelihood of repeat exacerbation in subsequent pregnancies and postpartum periods. Five hundred forty-two women (United States, n = 352; Dutch, n = 190) who met DSM-IV criteria for OCD, completed self-report questionnaires designed to assess OCD onset and symptom exacerbation associated with reproductive events. OCD onset occurred within 12 months after menarche in 13.0%, during pregnancy in 5.1%, at postpartum in 4.7%, and at menopause in 3.7%. Worsening of pre-existing OCD was reported by 37.6% of women at premenstruum, 33.0% during pregnancy, 46.6% postpartum, and 32.7% at menopause. Exacerbation in first pregnancy was significantly associated with exacerbation in second pregnancy (OR = 10.82, 95% CI 4.48-26.16), as was exacerbation in first postpartum with exacerbation in second postpartum (OR = 6.86, 95% CI 3.27-14.36). Results were replicated in both samples. Reproductive cycle events are periods of increased risk for onset and exacerbation of OCD in women. The present study is the first to provide significant evidence that exacerbation in or after first pregnancy is a substantial risk factor for exacerbation in or after a subsequent pregnancy. Further research is needed to identify factors related to exacerbation, so that physicians may provide appropriate recommendations to women regarding clinical issues involving OCD and reproductive cycle events. © 2014 Wiley Periodicals, Inc.

  18. Mercury-Resistant Marine Bacteria and their Role in Bioremediation of Certain Toxicants

    Digital Repository Service at National Institute of Oceanography (India)

    De, J.

    of heavy metals (mercury, cadmium, lead to name a few). Without efficient retention technologies, toxic chemicals including Hg are let into the environment, endangering ecosystems and public health. The main focus in this section is on literature review... toxicity. For the most sensitive species, Daphnia magna, the NOTEL for reproductive impairment is 3 ppb for inorganic mercury and lesser than 0.04 ppb for methylmercury (Canstein, 2000). Hence it is of great importance for both environment and public health...

  19. Rethinking reproductive "tourism" as reproductive "exile".

    Science.gov (United States)

    Inhorn, Marcia C; Patrizio, Pasquale

    2009-09-01

    Whereas reproductive "tourism" implies leisure travel, reproductive "exile" bespeaks the numerous difficulties and constraints faced by infertile patients who are "forced" to travel globally for assisted reproduction. Given this reality, it is time to rethink the language of "reproductive tourism," replacing it with more accurate and patient-centered terms.

  20. Reproductive, cytological and biochemical toxicity of Yohimbe in male Swiss albino mice.

    Science.gov (United States)

    Al-Majed, Abdulhakeem A; Al-Yahya, Abdulaziz A; Al-Bekairi, A M; Al-Shabanah, Othman A; Qureshi, Shoeb

    2006-07-01

    To study the effect of Corynanthe Yohimbe (Yohimbe) on germ cells in Swiss albino mice. Adult male mice were orally (gavage) treated with different doses (188, 375 and 750 mg/[kg x day]) of aqueous suspension of Yohimbe for 90 days. The following parameters were evaluated: (i) reproductive organ weight, (ii) motility and count of sperm, (iii) study on rate of pregnancy and mean implants, (iv) spermatozoa morphology, (v) cytology of the testes chromosomes, and (vi) biochemical study on estimation of proteins, RNA, DNA, malondialdehyde, nonprotein sulfhydryl (NP-SH) and hormones. The treatment caused significant increase in the weight of seminal vesicles, motility and count of spermatozoa, pre- and post-implants. Male fertility was decreased. These results are confirmed by our data on spermatozoa abnormalities and chromosomal aberrations. The data on biochemical parameters showed increase of malondialdehyde and depletion of NP-SH, proteins, RNA and DNA in the testicular cells. Our results elucidated the role of free radical species in cytological and reproductive changes, possibly, under the influence of yohimbine (principal constituent of Yohimbe) on neurotransmitters, including norephinephrine. These data warrant careful use of Yohimbe.