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Sample records for range-finding developmental toxicity

  1. Emerging exposures of developmental toxicants.

    Science.gov (United States)

    Wolff, Mary S; Buckley, Jessie P; Engel, Stephanie M; McConnell, Rob S; Barr, Dana B

    2017-04-01

    The purpose of this review is to identify emerging developmental toxicants that are understudied in children's health. Exposures may arise from new products designed to improve utility, to reduce toxicity, or to replace undesirable chemicals. Exposures to less-toxic chemicals may also be significant if they are very commonly used, thereby generating widespread exposure. Sources of exposure include the workplace, personal, home, and office products; food, water, and air. We describe eight exposure categories that contain numerous potential developmental toxicants. References are discussed if reported in PubMed during the past decade at least 10 times more frequently than in 1990-2000. Examples included phthalates, phenols, sunscreens, pesticides, halogenated flame retardants, perfluoroalkyl coatings, nanoparticles, e-cigarettes, and dietary polyphenols. Replacements are often close structural homologs of their precursors. We suggest biomonitoring as preferred means of exposure assessment to emerging chemicals. Some existing analytic methods would require minimal modification to measure these exposures, but others require toxicokinetic and analytic investigation. A deliberate strategy for biomonitoring of emerging replacement chemicals is warranted, especially in view of concerns regarding developmental toxicity. To prevent adverse health effects, it is important to characterize such exposures before they become widely disseminated.

  2. CAESAR models for developmental toxicity

    Directory of Open Access Journals (Sweden)

    Piclin Nadège

    2010-07-01

    Full Text Available Abstract Background The new REACH legislation requires assessment of a large number of chemicals in the European market for several endpoints. Developmental toxicity is one of the most difficult endpoints to assess, on account of the complexity, length and costs of experiments. Following the encouragement of QSAR (in silico methods provided in the REACH itself, the CAESAR project has developed several models. Results Two QSAR models for developmental toxicity have been developed, using different statistical/mathematical methods. Both models performed well. The first makes a classification based on a random forest algorithm, while the second is based on an adaptive fuzzy partition algorithm. The first model has been implemented and inserted into the CAESAR on-line application, which is java-based software that allows everyone to freely use the models. Conclusions The CAESAR QSAR models have been developed with the aim to minimize false negatives in order to make them more usable for REACH. The CAESAR on-line application ensures that both industry and regulators can easily access and use the developmental toxicity model (as well as the models for the other four endpoints.

  3. Male-mediated developmental toxicity

    Directory of Open Access Journals (Sweden)

    Diana Anderson

    2014-02-01

    Full Text Available Male-mediated developmental toxicity has been of concern for many years. The public became aware of male-mediated developmental toxicity in the early 1990s when it was reported that men working at Sellafield might be causing leukemia in their children. Human and animal studies have contributed to our current understanding of male-mediated effects. Animal studies in the 1980s and 1990s suggested that genetic damage after radiation and chemical exposure might be transmitted to offspring. With the increasing understanding that there is histone retention and modification, protamine incorporation into the chromatin and DNA methylation in mature sperm and that spermatozoal RNA transcripts can play important roles in the epigenetic state of sperm, heritable studies began to be viewed differently. Recent reports using molecular approaches have demonstrated that DNA damage can be transmitted to babies from smoking fathers, and expanded simple tandem repeats minisatellite mutations were found in the germline of fathers who were exposed to radiation from the Chernobyl nuclear power plant disaster. In epidemiological studies, it is possible to clarify whether damage is transmitted to the sons after exposure of the fathers. Paternally transmitted damage to the offspring is now recognized as a complex issue with genetic as well as epigenetic components.

  4. Neurobehavioural effects of developmental toxicity

    DEFF Research Database (Denmark)

    Grandjean, Philippe; Landrigan, Philip J

    2014-01-01

    the known causes for this rise in prevalence. In 2006, we did a systematic review and identified five industrial chemicals as developmental neurotoxicants: lead, methylmercury, polychlorinated biphenyls, arsenic, and toluene. Since 2006, epidemiological studies have documented six additional developmental...... neurotoxicants-manganese, fluoride, chlorpyrifos, dichlorodiphenyltrichloroethane, tetrachloroethylene, and the polybrominated diphenyl ethers. We postulate that even more neurotoxicants remain undiscovered. To control the pandemic of developmental neurotoxicity, we propose a global prevention strategy. Untested...... chemicals should not be presumed to be safe to brain development, and chemicals in existing use and all new chemicals must therefore be tested for developmental neurotoxicity. To coordinate these efforts and to accelerate translation of science into prevention, we propose the urgent formation of a new...

  5. Developmental Exposure to Environmental Toxicants.

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    Falck, Alison J; Mooney, Sandra; Kapoor, Shiv S; White, Kimberly M R; Bearer, Cynthia; El Metwally, Dina

    2015-10-01

    Children interact with the physical environment differently than adults, and are uniquely susceptible to environmental toxicants. Routes of absorption, distribution, metabolism, and target organ toxicities vary as children grow and develop. This article summarizes the sources of exposure and known adverse effects of toxicants that are ubiquitous in our environment, including tobacco smoke, ethanol, solvents, heavy metals, volatile organic compounds, persistent organic pollutants, and pesticides. Preventive strategies that may be used in counseling children and their families are highlighted. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. 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 potentiall...... that production and application of nanomaterials are expected to increase, a testing strategy for NP should be established....

  7. Neurobehavioural effects of developmental toxicity

    OpenAIRE

    Grandjean, Philippe; Landrigan, Philip J.

    2014-01-01

    Neurodevelopmental disabilities, including autism, attention-deficit hyperactivity disorder, dyslexia, and other cognitive impairments, affect millions of children worldwide, and some diagnoses seem to be increasing in frequency. Industrial chemicals that injure the developing brain are among the known causes for this rise in prevalence. In 2006, we did a systematic review and identified five industrial chemicals as developmental neurotoxicants: lead, methylmercury, polychlorinated biphenyls,...

  8. Developmental toxicity of Citrus aurantium in rats.

    Science.gov (United States)

    Hansen, Deborah K; Juliar, Beth E; White, Gene E; Pellicore, Linda S

    2011-06-01

    Ephedra was commonly used in herbal products marketed for weight loss until safety concerns forced its removal from products. Even before the ban, manufacturers had begun to replace ephedra with other compounds, including Citrus aurantium, or bitter orange. The major component in the bitter orange extract is synephrine which is chemically similar to ephedrine. The purpose of this study was to determine if relatively pure synephrine or synephrine present as a constituent of a bitter orange extract produced developmental toxicity in rats. Sprague-Dawley rats were dosed daily by gavage with one of several different doses of synephrine from one of two different extracts. Caffeine was added to some doses. Animals were sacrificed on GD 21, and fetuses were examined for the presence of various developmental toxic endpoints. At doses up to 100 mg synephrine/kg body weight, there were no adverse effects on embryolethality, fetal weight, or incidences of gross, visceral, or skeletal abnormalities. There was a decrease in maternal weight at 50 mg synephrine/kg body weight when given as the 6% synephrine extract with 25 mg caffeine/kg body weight; there was also a decrease in maternal weight in the caffeine only group. This decrease in body weight may have been due to decreased food consumption which was also observed in these two groups. Overall, doses of up to 100 mg synephrine/kg body weight did not produce developmental toxicity in Sprague-Dawley rats. © 2011 Wiley-Liss, Inc.

  9. Perspectives on reproductive and developmental toxicity.

    Science.gov (United States)

    Johnson, E M

    1986-12-01

    Human reproduction and development is a cycle of interdependent events. Virtually all of its phases have been shown to be the primary target of one or more non-mutagenic exogenous agents. Such agents interfere with certain of the countless epigenetic or ontogenic events essential for normal completion of the cycle. Mutagens disrupt this cycle at some points, but the overwhelming majority of reproductive and developmental toxins are not mutagenic. As in all aspects of toxicology, the reproductive and developmental effects of chemicals are determined by the intrinsic nature of the chemical, the quantity of the chemical exposure, the duration of exposure and the stage of the cycle at which it occurs. Signs of reproductive toxicity range from reduced fertility to spontaneous abortion. Adverse effects on the conceptus are categorized as functional deficits, developmental retardation, structural abnormality and death. One or more of these is anticipated to occur as a result of excess exposure to most chemicals. Although the degree of hazard and risk potential can be calculated in each instance, chemicals differ markedly in their ability to interfere with reproduction (Amann, 1982) and/or development (Johnson, 1984). Standardized methods for reproductive and developmental toxicity safety evaluation are available for detecting adverse effects upon any aspect of reproduction and development. Data currently available establish that these state-of-the-art tests conducted in laboratory animals are often highly predictive of the type of adverse effect a particular chemical will have in humans, as well as the exposure level at which it will occur. By adding a modest safety factor to the no-observed-effect-level of well-executed animal studies, safe human exposure levels can be established. Responsibility for determining the intrinsic hazard potential and the risk estimate of exposure rests with manufacturers and major users of occupational and other environmental chemicals. As

  10. USING THE MEDAKA EMBRYO ASSAY TO INVESTIGATE DEVELOPMENTAL ETHANOL TOXICITY.

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    Ethanol (EtOH) is a well-known developmental toxicant that produces a range of abnormal phenotypes. While the toxic potential of developmental EtOH exposure is well characterized, the effect of the timing of exposure on the extent of toxicity remains unknown. Fish models such as ...

  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. Alternative testing strategies for predicting developmental toxicity of antifungal compound

    NARCIS (Netherlands)

    Li, H.

    2016-01-01

    Determination of safe human exposure levels of chemicals in toxicological risk assessments largely relies on animal toxicity data. In these toxicity studies, the highest number of animals are used for reproductive and developmental toxicity testing. Because of economic and ethical reasons, there is

  13. Oxidative Stress, Unfolded Protein Response, and Apoptosis in Developmental Toxicity

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    Kupsco, Allison; Schlenk, Daniel

    2016-01-01

    Physiological development requires precise spatiotemporal regulation of cellular and molecular processes. Disruption of these key events can generate developmental toxicity in the form of teratogenesis or mortality. The mechanism behind many developmental toxicants remains unknown. While recent work has focused on the unfolded protein response (UPR), oxidative stress, and apoptosis in the pathogenesis of disease, few studies have addressed their relationship in developmental toxicity. Redox regulation, UPR, and apoptosis are essential for physiological development and can be disturbed by a variety of endogenous and exogenous toxicants to generate lethality and diverse malformations. This review examines the current knowledge of the role of oxidative stress, UPR, and apoptosis in physiological development as well as in developmental toxicity, focusing on studies and advances in vertebrates model systems. PMID:26008783

  14. Relative parameter sensitivity in prenatal toxicity studies with substances classified as developmental toxicants

    NARCIS (Netherlands)

    Rorije, E.; van Hienen, F.J.W.; Dang, Z.C.; Hakkert, B.H.; Vermeire, T.; Piersma, A.H.|info:eu-repo/dai/nl/071276947

    2012-01-01

    Developmental toxicity testing according to the globally standardized OECD 414 protocol is an important basis for decisions on classification and labeling of developmental toxicants in the European Union (EU). This test requires relatively large animal numbers, given that parental and offspring

  15. Computer Simulation of Developmental Processes and Toxicities (SOT)

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    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 ...

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

    African Journals Online (AJOL)

    1College of Pharmacy, 2Department of Biopharmaceutical Research and Development Centre, Jinan University, Guangzhou. 510632, Guangdong ... developmental toxicity, using the embryonic stem cell test (EST), as well as ascertain how EGF influences ..... no pregnant animals need be sacrificed to obtain embryonic ...

  17. Current and future needs for developmental toxicity testing.

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    Makris, Susan L; Kim, James H; Ellis, Amy; Faber, Willem; Harrouk, Wafa; Lewis, Joseph M; Paule, Merle G; Seed, Jennifer; Tassinari, Melissa; Tyl, Rochelle

    2011-10-01

    A review is presented of the use of developmental toxicity testing in the United States and international regulatory assessment of human health risks associated with exposures to pharmaceuticals (human and veterinary), chemicals (agricultural, industrial, and environmental), food additives, cosmetics, and consumer products. Developmental toxicology data are used for prioritization and screening of pharmaceuticals and chemicals, for evaluating and labeling of pharmaceuticals, and for characterizing hazards and risk of exposures to industrial and environmental chemicals. The in vivo study designs utilized in hazard characterization and dose-response assessment for developmental outcomes have not changed substantially over the past 30 years and have served the process well. Now there are opportunities to incorporate new technologies and approaches to testing into the existing assessment paradigm, or to apply innovative approaches to various aspects of risk assessment. Developmental toxicology testing can be enhanced by the refinement or replacement of traditional in vivo protocols, including through the use of in vitro assays, studies conducted in alternative nonmammalian species, the application of new technologies, and the use of in silico models. Potential benefits to the current regulatory process include the ability to screen large numbers of chemicals quickly, with the commitment of fewer resources than traditional toxicology studies, and to refine the risk assessment process through an enhanced understanding of the mechanisms of developmental toxicity and their relevance to potential human risk. As the testing paradigm evolves, the ability to use developmental toxicology data to meet diverse critical regulatory needs must be retained. © 2011 Wiley Periodicals, Inc.

  18. Maternal and developmental toxicity of ayahuasca in Wistar rats.

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    Oliveira, Carolina Dizioli Rodrigues; Moreira, Camila Queiroz; de Sá, Lilian Rose Marques; Spinosa, Helenice de Souza; Yonamine, Mauricio

    2010-06-01

    Ayahuasca is a psychotropic plant beverage initially used by shamans throughout the Amazon region during traditional religious cult. In recent years, ayahuasca has also been used in ceremonies of a number of modern syncretic religious groups, including pregnant women. However, no documented study has been performed to evaluate the risk of developmental toxicity of ayahuasca. In the present work, maternal and developmental toxicity was evaluated in Wistar rats. Ayahuasca was administered to pregnant rats in three different doses [the equivalent typical dose (TD) administered to humans, five-fold TD and 10-fold TD] during the gestational period (6-20 days). Dams treated with the highest ayahuasca dose showed maternal toxicity with decrease of weight gain and food intake. Visceral fetal findings were observed in all treatment groups. Skeletal findings were observed in the intermediate- and high-dose groups. The fetuses deriving from the highest dose group also presented a decrease in body weight. From these results, it is possible to conclude that there is a risk of maternal and developmental toxicity following ayahuasca exposure and that the level of toxicity appears to be dose-dependent.

  19. 20161116 - Virtual Embryo: Cell-Agent Based Modeling of Developmental Processes and Toxicities (CSS BOSC)

    Science.gov (United States)

    Spatial regulation of cellular dynamics is fundamental to morphological development. As such, chemical disruption of spatial dynamics is a determinant of developmental toxicity. Incorporating spatial dynamics into AOPs for developmental toxicity is desired but constrained by the ...

  20. Characterization of a developmental toxicity dose-response model

    Energy Technology Data Exchange (ETDEWEB)

    Faustman, E.M.; Wellington, D.G.; Smith, W.P.; Kimmel, C.A.

    1989-02-01

    The Rai and Van Ryzin dose-response model proposed for teratology experiments has been characterized for its appropriateness and applicability in modeling the dichotomous response data from developmental toxicity studies. Modifications were made in the initial probability statements to reflect more accurately biological events underlying developmental toxicity. Data sets used for the evaluation were obtained from the National Toxicology Program and U.S. EPA laboratories. The studies included developmental evaluations of ethylene glycol, diethylhexyl phthalate, di- and triethylene glycol dimethyl ethers, and nitrofen in rats, mice, or rabbits. Graphic examination and statistical evaluation demonstrate that this model is sensitive to the data when compared to directly measured experimental outcomes. The model was used to interpolate to low-risk dose levels, and comparisons were made between the values obtained and the no-observed-adverse-effect levels (NOAELs) divided by an uncertainty factor. Our investigation suggests that the Rai and Van Ryzin model is sensitive to the developmental toxicity end points, prenatal deaths, and malformations, and appears to model closely their relationship to dose.

  1. 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

  2. Comparing rat and rabbit embryo-fetal developmental toxicity ...

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    A database of embryo-fetal developmental toxicity (EFDT) studies of 379 pharmaceutical compounds in rat and rabbit was analyzed for species differences based on toxicokinetic parameters of area under the curve (AUC) and maximum concentration (Cmax) at the developmental adverse effect level (dLOAEL). For the vast majority of cases (83% based on AUC of n=283), dLOAELs in rats and rabbits were within the same order of magnitude (less than 10-fold different) when compared based on available data on AUC and Cmax exposures. For 13.5% of the compounds the rabbit was more sensitive and for 3.5% of compounds the rat was more sensitive when compared based on AUC exposures. For 12% of the compounds the rabbit was more sensitive and for 1.3% of compounds the rat was more sensitive based on Cmax exposures. When evaluated based on human equivalent dose (HED) conversion using standard factors, the rat and rabbit were equally sensitive. The relative extent of embryo-fetal toxicity in the presence of maternal toxicity was not different between species. Overall effect severity incidences were distributed similarly in rat and rabbit studies. Individual rat and rabbit strains did not show a different general distribution of systemic exposure LOAELs as compared to all strains combined for each species. There were no apparent species differences in the occurrence of embryo-fetal variations. Based on power of detection and given differences in the nature of developmental effects betwe

  3. Assay for the developmental toxicity of safflower (Carthamus tinctorius L. to zebrafish embryos/larvae

    Directory of Open Access Journals (Sweden)

    Qing Xia

    2017-01-01

    Conclusion: Safflower exhibits developmental toxicity for zebrafish embryos/larvae. The developing heart was speculated as the target organ of toxicity. Oxidative stress and increased apoptosis have roles in the developmental toxicity of safflower. This article provides a novel method to research the teratogenicity and possible mechanisms of toxicity of traditional Chinese medicines that are prohibited or contraindicated in pregnant women.

  4. Reproductive and Developmental Toxicity of Formaldehyde: A Systematic Review

    Science.gov (United States)

    Duong, Anh; Steinmaus, Craig; McHale, Cliona M.; Vaughan, Charles P.; Zhang, Luoping

    2011-01-01

    Formaldehyde, the recently classified carcinogen and ubiquitous environmental contaminant, has long been suspected of causing adverse reproductive and developmental effects, but previous reviews were inconclusive, due in part, to limitations in the design of many of the human population studies. In the current review, we systematically evaluated evidence of an association between formaldehyde exposure and adverse reproductive and developmental effects, in human populations and in vivo animal studies, in the peer-reviewed literature. The mostly retrospective human studies provided evidence of an association of maternal exposure with adverse reproductive and developmental effects. Further assessment of this association by meta-analysis revealed an increased risk of spontaneous abortion (1.76, 95% CI 1.20–2.59, p=0.002) and of all adverse pregnancy outcomes combined (1.54, 95% CI 1.27–1.88, pformaldehyde-exposed women, although differential recall, selection bias, or confounding cannot be ruled out. Evaluation of the animal studies including all routes of exposure, doses and dosing regimens studied, suggested positive associations between formaldehyde exposure and reproductive toxicity, mostly in males. Potential mechanisms underlying formaldehyde-induced reproductive and developmental toxicities, including chromosome and DNA damage (genotoxicity), oxidative stress, altered level and/or function of enzymes, hormones and proteins, apoptosis, toxicogenomic and epigenomic effects (such as DNA methylation), were identified. To clarify these associations, well-designed molecular epidemiologic studies, that include quantitative exposure assessment and diminish confounding factors, should examine both reproductive and developmental outcomes associated with exposure in males and females. Together with mechanistic and animal studies, this will allow us to better understand the systemic effect of formaldehyde exposure. PMID:21787879

  5. Evaluation of the developmental toxicity of annatto in the rat.

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    Paumgartten, F J R; De-Carvalho, R R; Araujo, I B; Pinto, F M; Borges, O O; Souza, C A M; Kuriyama, S N

    2002-11-01

    Annatto, a dye extracted from Bixa orellana seeds, is used as a color additive in butter, cheese and in a variety of other foods as well as in drugs and cosmetics. Toxicological data on annatto and on its main carotenoid pigment bixin are still scarce. In this study we evaluated the developmental toxicity of annatto (28% of bixin). Annatto (0, 31.2, 62.5, 125, 250 and 500 mg/kg body weight/day) was given by gavage to Wistar rats on days 6-15 of pregnancy. Ceasarean sections were performed on day 21. Implantations, living and dead fetuses and resorptions were recorded. Fetuses were weighed and examined for externally-visible anomalies. One-third of fetuses from each litter was examined for visceral anomalies by a microsectioning technique. The remaining fetuses were cleared and stained with Alizarin Red S for skeleton evaluation. No adverse effect of annatto on the mothers was noted. No increase in embryolethality and no reduction of fetal body weight were observed among annatto-exposed rats. Annatto did not induce any increase in the incidence of externally-visible, visceral or skeletal anomalies in the exposed offspring. These findings suggest that annatto was neither maternally toxic nor embryotoxic in the rat. Therefore, the no-observed-adverse-effect level (NOAEL) for annatto-induced maternal and developmental toxicity was 500 mg/kg body weight/day or greater (or > or = 140 mg bixin/kg body weight/day) by the oral route.

  6. Molecular Mechanisms of Crude Oil Developmental Toxicity in Fish.

    Science.gov (United States)

    Incardona, John P

    2017-07-01

    With major oil spills in Korea, the United States, and China in the past decade, there has been a dramatic increase in the number of studies characterizing the developmental toxicity of crude oil and its associated polycyclic aromatic compounds (PACs). The use of model fish species with associated tools for genetic manipulation, combined with high throughput genomics techniques in nonmodel fish species, has led to significant advances in understanding the cellular and molecular bases of functional and morphological defects arising from embryonic exposure to crude oil. Following from the identification of the developing heart as the primary target of crude oil developmental toxicity, studies on individual PACs have revealed a diversity of cardiotoxic mechanisms. For some PACs that are strong agonists of the aryl hydrocarbon receptor (AHR), defects in heart development arise in an AHR-dependent manner, which has been shown for potent organochlorine agonists, such as dioxins. However, crude oil contains a much larger fraction of compounds that have been found to interfere directly with cardiomyocyte physiology in an AHR-independent manner. By comparing the cellular and molecular responses to AHR-independent and AHR-dependent toxicity, this review focuses on new insights into heart-specific pathways underlying both acute and secondary adverse outcomes to crude oil exposure during fish development.

  7. Developmental toxicity of intravenously injected zinc oxide nanoparticles in rats.

    Science.gov (United States)

    Lee, Jinsoo; Yu, Wook-Joon; Song, Jeongah; Sung, Changhyun; Jeong, Eun Ju; Han, Ji-Seok; Kim, Pilje; Jo, Eunhye; Eom, Ikchun; Kim, Hyun-Mi; Kwon, Jung-Taek; Choi, Kyunghee; Choi, Jonghye; Kim, Heyjin; Lee, Handule; Park, Juyoung; Jin, Seon Mi; Park, Kwangsik

    2016-12-01

    Recent toxicity studies of zinc oxide nanoparticles by oral administration showed relatively low toxicity, which may be resulted from low bioavailability. So, the intrinsic toxicity of zinc oxide nanoparticles needs to be evaluated in the target organs by intravenous injection for full systemic concentration of the administered dosage. Although the exposure chance of injection route is low compared to oral and/or inhalation route, it is important to see the toxicity with different exposure routes to get better risk management tool. In this study, the effects of zinc oxide nanoparticles on dams and fetuses were investigated in rats after intravenous injection (5, 10, and 20 mg/kg) from gestation day 6 to 20. Two of 20 dams in the 20 mg/kg treatment group died during the treatment period. Hematological examination and serum biochemistry showed dose-dependent toxicity in treated dams. Histopathological analysis of treated dams revealed multifocal mixed cell infiltration and thrombosis in lung, tubular dilation in kidneys, and extramedullary hemopoiesis in liver. Total dead fetuses (post-implantation loss) were increased and the body weight of fetus was decreased in the 20 mg/kg treatment group. Statistical differences in corpora lutea, resorption, placental weight, morphological alterations including external, visceral and skeletal malformations were not observed in treated groups. Based on the data, lowest observed adverse effect level of injection route was suggested to be 5 mg/kg in dams and no observed adverse effect level was suggested to be 10 mg/kg in fetal developmental toxicity.

  8. A Categorical Structure-Activity Relationship Analysis of the Developmental Toxicity of Antithyroid Drugs

    Directory of Open Access Journals (Sweden)

    Albert R. Cunningham

    2009-01-01

    Full Text Available The choice of therapeutic strategies for hyperthyroidism during pregnancy is limited. Surgery and radioiodine are typically avoided, leaving propylthiouracil and methimazole in the US. Carbimazole, a metabolic precursor of methimazole, is available in some countries outside of the US. In the US propylthiouracil is recommended because of concern about developmental toxicity from methimazole and carbimazole. Despite this recommendation, the data on developmental toxicity of all three agents are extremely limited and insufficient to support a policy given the broad use of methimazole and carbimazole around the world. In the absence of new human or animal data we describe the development of a new structure-activity relationship (SAR model for developmental toxicity using the cat-SAR expert system. The SAR model was developed from data for 323 compounds evaluated for human developmental toxicity with 130 categorized as developmental toxicants and 193 as nontoxicants. Model cross-validation yielded a concordance between observed and predicted results between 79% to 81%. Based on this model, propylthiouracil, methimazole, and carbimazole were observed to share some structural features relating to human developmental toxicity. Thus given the need to treat women with Graves's disease during pregnancy, new molecules with minimized risk for developmental toxicity are needed. To help meet this challenge, the cat-SAR method would be a useful in screening new drug candidates for developmental toxicity as well as for investigating their mechanism of action.

  9. A Categorical Structure-Activity Relationship Analysis of the Developmental Toxicity of Antithyroid Drugs

    Directory of Open Access Journals (Sweden)

    Cunningham AlbertR

    2009-11-01

    Full Text Available The choice of therapeutic strategies for hyperthyroidism during pregnancy is limited. Surgery and radioiodine are typically avoided, leaving propylthiouracil and methimazole in the US. Carbimazole, a metabolic precursor of methimazole, is available in some countries outside of the US. In the US propylthiouracil is recommended because of concern about developmental toxicity from methimazole and carbimazole. Despite this recommendation, the data on developmental toxicity of all three agents are extremely limited and insufficient to support a policy given the broad use of methimazole and carbimazole around the world. In the absence of new human or animal data we describe the development of a new structure-activity relationship (SAR model for developmental toxicity using the cat-SAR expert system. The SAR model was developed from data for 323 compounds evaluated for human developmental toxicity with 130 categorized as developmental toxicants and 193 as nontoxicants. Model cross-validation yielded a concordance between observed and predicted results between 79% to 81%. Based on this model, propylthiouracil, methimazole, and carbimazole were observed to share some structural features relating to human developmental toxicity. Thus given the need to treat women with Graves's disease during pregnancy, new molecules with minimized risk for developmental toxicity are needed. To help meet this challenge, the cat-SAR method would be a useful in screening new drug candidates for developmental toxicity as well as for investigating their mechanism of action.

  10. Toward in vitro biomarkers for developmental toxicity and their extrapolation to the in vivo situation

    NARCIS (Netherlands)

    Louisse, J.; Verwei, M.; Woutersen, R.A.; Blaauboer, B.J.; Rietjens, I.M.C.M.

    2012-01-01

    Introduction: Reliable in vitro and in silico assays as alternatives for in vivo developmental toxicity studies are urgently needed, for the replacement, reduction and refinement (3Rs) of animal use in toxicological research. Therefore, relevant biomarkers for in vivo developmental toxicity in in

  11. Inhalation developmental toxicology studies: Developmental toxicity of chloroprene vapors in New Zealand white rabbits. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Mast, T.J.; Evanoff, J.J.; Westerberg, R.B.; Rommereim, R.L.; Weigel, R.J.

    1994-04-01

    Chloroprene, 2-chloro-1,3-butadiene, is a colorless liquid with a pungent ethereal odor that is primarily used as an intermediate in the manufacture of neoprene rubber, and has been used as such since about 1930. This study addressed the potential for chloroprene to cause developmental toxicity in New Zealand white rabbits following gestational exposure to 0, 10, 40, or 175 ppm chloroprene vapors, 6h/dy, 7dy/wk. Each treatment group consisted of 15 artificially inseminated females exposed on 6 through 28 days of gestation (dg). Body weights were obtained throughout the study period, and uterine and fetal body weights were obtained at sacrifice on 29 dg. Implants were enumerated and their status recorded and live fetuses were examined for gross, visceral, skeletal, and soft-tissue craniofacial defects. There were no overt signs of maternal toxicity and the change in maternal body weight over the course of the study was not affected. Exposure of pregnant rabbits to chloroprene vapors on 6-28 dg had no effect on the number of implantation, the mean percent of live pups per litter, or on the incidence of resorptions per litter. The incidence of fetal malformations was not increased by exposure to chloroprene. Results of this study indicate that gestational exposure of New Zealand white rabbits to 10, 40, or 175 ppm chloroprene did not result in observable toxicity to either the dam or the offspring.

  12. Toward in vitro biomarkers for developmental toxicity and their extrapolation to the in vivo situation.

    Science.gov (United States)

    Louisse, Jochem; Verwei, Miriam; Woutersen, Ruud A; Blaauboer, Bas J; Rietjens, Ivonne M C M

    2012-01-01

    Reliable in vitro and in silico assays as alternatives for in vivo developmental toxicity studies are urgently needed, for the replacement, reduction and refinement (3Rs) of animal use in toxicological research. Therefore, relevant biomarkers for in vivo developmental toxicity in in vitro assays are needed. The present review gives an overview of alternative assays, as described in literature, for in vivo developmental toxicity, including the effects (readouts) assessed in these assays. The authors discuss how these data may be used to obtain relevant biomarkers for in vivo developmental toxicity, and how in vitro effect data can be translated to the in vivo situation using physiologically based kinetic (PBK) modeling. Relevance of readouts in in vitro developmental toxicity assays as predictive biomarkers for in vivo developmental toxicity should be evaluated by comparing the obtained in vitro effect concentrations with in vivo internal concentrations at dose levels causing developmental toxicity. Extrapolation of the in vitro effect concentrations to in vivo dose levels using PBK modeling (i.e., reverse dosimetry) is promising in its use to derive points of departure for risk assessment, enabling the use of in vitro toxicity data in the safety assessment of compounds.

  13. Developmental toxicity of L-selenomethionine in Macaca fascicularis.

    Science.gov (United States)

    Tarantal, A F; Willhite, C C; Lasley, B L; Murphy, C J; Miller, C J; Cukierski, M J; Book, S A; Hendrickx, A G

    1991-01-01

    Forty pregnant long-tailed macaques were dosed via nasogastric intubation with 0, 25, 150, or 300 micrograms/kg of L-selenomethionine (Se) daily during organogenesis [Gestational Day (GD) 20-50]. Clinical examination of the dams, maternal body weights, sonographic evaluations, clinical chemistry screens, and measures of serum progesterone and urinary estrone conjugates were used as indicators of maternal and fetal status in all animals. The pregnancies of two to three dams from each dose group were followed until term (approximately GD 165); the remainder (N = 7/dose group) were scheduled for hysterotomy on GD 100 +/- 2. A standard teratologic evaluation was performed including visceral and skeletal examinations. Fetal liver, kidney, skin, and smooth, cardiac, and skeletal muscles were examined by light microscopy; heart muscle was also evaluated by transmission electron microscopy. Neonates delivered at term remained with the dams and were removed periodically for morphometric, neurologic, behavioral, and ophthalmologic assessments on Days 1, 8, 15, 22, and 30 of age. Dose-dependent maternal toxicity as evidenced by anorexia, vomiting, and a significant reduction in body weight increased with increasing duration of Se exposure. One growth-retarded fetus was recovered on GD 131 from a compromised dam exposed to 25 micrograms/kg-day; one early embryonic death (GD 35) and two fetal deaths [GD 68 (followed by maternal death) and GD 123] occurred among animals dosed with 300 micrograms/kg-day. Pregnancy loss among treated animals was not significantly different from concurrent or historical controls. No statistically significant treatment-related effects were observed at necropsy on GD 100 +/- 2. One infant exposed to 150 micrograms/kg-day prenatally exhibited a unilateral cortical cataract, which may have been a spontaneous occurrence. The limited developmental effects observed and reported teratogenesis in nonmammalian species suggest that comparative pharmacokinetic

  14. Computational Modeling and Simulation of Developmental Toxicity (EuroTox 2016)

    Science.gov (United States)

    Standard practice for assessing developmental toxicity is the observation of apical endpoints (intrauterine death, fetal growth retardation, structural malformations) in pregnant rats/rabbits following exposure during organogenesis. EPA’s computational toxicology research program...

  15. Health Risk Assessment of Women in Submarines: Reproductive and Developmental Toxicity Evaluation of Major Submarine Atmosphere Components (CO, CO2, and O2) in Rats (Rattus norvegicus) - Phase 1 (Range Finding Study)

    Science.gov (United States)

    2011-06-27

    policy or position of the Department of the Navy, Department of Defense, or the U.S. Government. This article is approved for public release...16 n=16 n=16 Heart Chronic Infiltrates 1 0 0 0 (1+) Cardiomyopathy 0 1 0 0 (1+) Pancreas Chronic Infiltrates 0 0 3 4 (3

  16. In vitro developmental toxicity test detects inhibition of stem cell differentiation by silica nanoparticles.

    NARCIS (Netherlands)

    Park, M.V.; Annema, W.; Salvati, A.; Lesniak, A.; Elsaesser, A.; Barnes, C.; McKerr, G.; Howard, C.; Lynch, I.; Dawson, K.; Piersma, A.H.; de Jong, W.H.

    2009-01-01

    While research into the potential toxic properties of nanomaterials is now increasing, the area of developmental toxicity has remained relatively uninvestigated. The embryonic stem cell test is an in vitro screening assay used to investigate the embryotoxic potential of chemicals by determining

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

    Science.gov (United States)

    1997-08-01

    place the 35 number on the dorsal surface. Five groups of 5 males were assigned to treatment groups, randomized by block design using body weights as...extracts frogs or embryos. Methods of ^^"^^t the soil for 60 to 90 days. Methods (SCFE) via earthworms or other food and^recrexposur contaminated and of...Spills 4 2. The Need for Reproductive Toxicity Testing 3. Reproductive Toxicity Assay Design 4. The Need for Developmental Toxicity Testing 5

  18. Evaluation of developmental toxicant identification using gene expression profiling in embryonic stem cell differentiation cultures.

    Science.gov (United States)

    van Dartel, Dorien A M; Pennings, Jeroen L A; de la Fonteyne, Liset J J; Brauers, Karen J J; Claessen, Sandra; van Delft, Joost H; Kleinjans, Jos C S; Piersma, Aldert H

    2011-01-01

    The murine embryonic stem cell test (EST) is an alternative testing method designed to assess potential developmental toxicity of compounds. The implementation of transcriptomics in the EST has been shown to reduce the culture duration and improve endpoint evaluation and is expected to result in an enhanced predictability and definition of the applicability domain. We evaluated the identification of developmental toxicity in the EST using two gene sets ("Van_Dartel_heartdiff_24h" and "EST biomarker genes") defined in our earlier studies. Nonexposed embryonic stem cells (ESC) differentiation cultures were sampled 0, 24, and 48 h after initiation of differentiation. Additionally, cultures exposed to 12 diverse well-characterized positive and negative developmental toxicants were isolated 24 h after the onset of exposure. Inhibition of ESC differentiation was evaluated in parallel by morphological scoring on culture day 10. Transcriptomics analysis was conducted using the Affymetrix Gene Chips platform. We applied principal component analysis on the basis of the two predefined gene sets to define the "differentiation track" that represents ESC differentiation. The significance of derivations in the gene expression-based differentiation track because of compound exposures were evaluated to determine developmental toxicity of tested compounds. We successfully predicted developmental toxicity using transcriptomics for 83% (10/12) and 67% (8/12) of the compounds, respectively, using the two predefined gene sets ("Van_Dartel_heartdiff_24h" and "EST biomarker genes"). Our study suggests that the application of transcriptomics may improve the applicability of the EST for the prediction of the developmental toxicity of chemicals.

  19. Vulnerable windows for developmental ethanol toxicity in the Japanese medaka fish (Oryzias latipes).

    Science.gov (United States)

    Oxendine, Sharon L; Cowden, John; Hinton, David E; Padilla, Stephanie

    2006-12-30

    Ethanol (EtOH) is a well-known developmental toxicant that produces a range of abnormal phenotypes in mammalian systems including craniofacial abnormalities, cognitive deficits and growth retardation. While the toxic potential of developmental EtOH exposure is well characterized clinically, the effect of timing on the extent of toxicity remains unknown. Fish models such as the Japanese medaka, Oryzias latipes, provide a convenient system for investigating the effects of developmental EtOH exposure in vivo. In this study, medaka embryo toxicity tests were used to assess temporal variations in developmental EtOH toxicity. Fertilized eggs were collected and incubated during early, middle or late egg development (e.g., 0-3, 3-6 or 6-9 days post-fertilization) with various sub-lethal concentrations of EtOH [0.1% (17.2 mM), 0.5% (86.0 mM) or 1% (172 mM)]. Uptake of EtOH by the embryo was 60-68% of the solution concentration across all windows. Time to hatch, head width, total body length and whole embryo caspase activity were used to assess toxicity. Hatching delays were noted only at the highest concentration of EtOH. Head width was affected at all ethanol levels, regardless of the window of exposure. EtOH-induced decreases in body length, however, appeared to be most pronounced when exposure occurred either during the first or last window. The effect on caspase-3/7 activity also depended on the window of exposure, with increases in caspase noted in embryos treated on days 1 or 2 (first window) and decreases seen in embryos treated on day 6 (second window) or day 8 (third window). In general, these data suggest that critical periods for heightened sensitivity to developmental EtOH exposure may vary according to the specific endpoint used to assess toxicity.

  20. Alternative Models of Developmental and Reproductive Toxicity in Pharmaceutical Risk Assessment and the 3Rs.

    Science.gov (United States)

    Brannen, Kimberly C; Chapin, Robert E; Jacobs, Abigail C; Green, Maia L

    2016-12-01

    In the pharmaceutical industry, preclinical developmental and reproductive toxicity studies are conducted in laboratory animals in order to predict and prevent adverse effects of drugs on human reproductive health and development. However, these studies require a relatively large number of animals and are usually conducted late in the drug development process. Early, simple, and inexpensive screening assays could facilitate smarter decisions, reductions in animal use, and development of safe drugs. The current state and future needs for alternative models of developmental and reproductive toxicity are reviewed here. The most popular predictive developmental toxicity assays are embryonic stem cells, rodent whole embryo culture, and zebrafish, each of which involves fairly well-developed techniques with demonstrated utility in drug discovery and development. In vitro or ex vivo methods for male and female reproductive toxicity are less established, but there are promising assays available or being developed that may be useful in drug development, especially for elucidating mechanisms or screening backup compounds. While a number of challenges remain, much progress has been made in alternative developmental and reproductive toxicity models to date, and there is a strong collective enthusiasm in the industry to continue moving them forward. Therefore, it appears that these approaches may be widely used in the near future. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  1. Developmental toxicity from exposure to various forms of mercury compounds in medaka fish (Oryzias latipes embryos

    Directory of Open Access Journals (Sweden)

    Wu Dong

    2016-08-01

    Full Text Available This study examined developmental toxicity of different mercury compounds, including some used in traditional medicines. Medaka (Oryzias latipes embryos were exposed to 0.001–10 µM concentrations of MeHg, HgCl2, α-HgS (Zhu Sha, and β-HgS (Zuotai from stage 10 (6–7 hpf to 10 days post fertilization (dpf. Of the forms of mercury in this study, the organic form (MeHg proved the most toxic followed by inorganic mercury (HgCl2, both producing embryo developmental toxicity. Altered phenotypes included pericardial edema with elongated or tube heart, reduction of eye pigmentation, and failure of swim bladder inflation. Both α-HgS and β-HgS were less toxic than MeHg and HgCl2. Total RNA was extracted from survivors three days after exposure to MeHg (0.1 µM, HgCl2 (1 µM, α-HgS (10 µM, or β-HgS (10 µM to examine toxicity-related gene expression. MeHg and HgCl2 markedly induced metallothionein (MT and heme oxygenase-1 (Ho-1, while α-HgS and β-HgS failed to induce either gene. Chemical forms of mercury compounds proved to be a major determinant in their developmental toxicity.

  2. [Ethylene glycol and propylene glycol ethers - Reproductive and developmental toxicity].

    Science.gov (United States)

    Starek-Świechowicz, Beata; Starek, Andrzej

    2015-01-01

    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. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

  3. Reproductive and developmental toxicity of toluene: A review

    Energy Technology Data Exchange (ETDEWEB)

    Donald, J.M.; Hooper, K.; Hopenhayn-Rich, C. (California Dept. of Health Services, Sacramento (United States))

    1991-08-01

    Toulene is a widely used industrial solvent, and humans may also have high exposures to toulene from the deliberate inhalation (sniffing) of paint reducer, paint thinner, or paint for their narcotic effects. A number of case reports describe neonatal effects that have been attributed to toulene abuse during pregnancy. These effects may include intrauterine growth retardation, premature delivery, congenital malformations, and postnatal developmental retardation. The possibility of exposures to other fetotoxic agents, either as impurities or admixtures in toulene-containing products, or by deliberate or accidental exposures to other chemicals or drugs, cannot be excluded in these cases. The fetotoxic effects of toulene have been demonstrated in controlled studies in animals and are comparable to those observed in humans who have abused toulene-containing products before or during pregnancy. Intrauterine developmental retardation is the most clearly established effect in animals, as evidenced by decreased late fetal weight and retarded skeletal development. There is also limited evidence in rodents for skeletal and kidney abnormalities, as well as some evidence for effects on postnatal physical and possibly neurobehavioral development. Estimated daily exposures from experimental studies in animals are compared to estimated human daily intakes at the occupational permissible exposure level and at the level reported to produce euphoria in humans. Acceptable human intakes under California's Proposition 65 and under US Environmental Protection Agency procedures are discussed.

  4. DEVELOPMENTAL TOXICITY OF 2-CHLORO-2'-DEOXYADENOSINE IN THE RAT: INDUCTION OF LUMBAR HERNIA

    Science.gov (United States)

    DEVELOPMENTAL TOXICITY OF 2-CHLORO-2'DEOXYADENOSINE IN THE RAT: INDUCTION OF LUMBAR HERNIA. C. Lau1, M.G. Narotsky1, D. Lui1, D. Best1, R.W. Setzer2, T.B. Knudsen3. 1Reprod. Tox. Div., 2Exp. Tox. Div., NHEERL, US EPA, Research Triangle Park, NC, USA, 3Dept. Path. Anat. Cell Bio...

  5. Developmental toxicity study of vegetable oil-derived stanol fatty acid esters

    NARCIS (Netherlands)

    Slesinski, R.S.; Turnbull, D.; Frankos, V.H.; Wolterbeek, A.P.M.; Waalkens-Berendsen, D.H.

    1999-01-01

    In a standard developmental toxicity study, a mixture of vegetable oil- derived stanol fatty acid esters was administered in the diet to groups of 28 mated female HsdCpb:WU Wistar rats at concentrations that provided 0, 1, 2.5, and 5% total stanols (equivalent to 0, 1.75, 4.38, and 8.76% plant

  6. Prenatal developmental toxicity study with 7-hydroxymatairesinol potassium acetate (HMRlignan) in rats

    NARCIS (Netherlands)

    Wolterbeek, A.P.M.; Roberts, A.; Korte, H.; Unkila, M.; Waalkens-Berendsen, D.H.

    2004-01-01

    Plant lignan 7-hydromatairesinol, a novel precursor of the mammalian lignan enterolactone was evaluated in a prenatal developmental toxicity study conducted in the Wistar rat. Mated female rats were fed diets containing 0, 0.25, 1, and 4% (w/w) of 7-hydroxymatairesinol in the form of potassium

  7. Implementation of transcriptomics for developmental toxicity assessment in the zebrafish embryo model

    NARCIS (Netherlands)

    Hermsen, S.A.B.

    2014-01-01

    The zebrafish embryo is considered a promising alternative model for in vivo rodent predictive developmental toxicity testing. The objective of the research described in this thesis was to enhance the detection of embryotoxic compounds and the knowledge about their mechanisms of action by the

  8. DNA Damage Response Is Involved in the Developmental Toxicity of Mebendazole in Zebrafish Retina

    Directory of Open Access Journals (Sweden)

    Yuhei eNishimura

    2016-03-01

    Full Text Available Intestinal helminths cause iron-deficiency anemia in pregnant women, associated with premature delivery, low birth weight, maternal ill health, and maternal death. Although benzimidazole compounds such as mebendazole (MBZ are highly efficacious against helminths, there are limited data on its use during pregnancy. In this study, we performed in vivo imaging of the retinas of zebrafish larvae exposed to MBZ, and found that exposure to MBZ during 2 and 3 days post-fertilization caused malformation of the retinal layers. To identify the molecular mechanism underlying the developmental toxicity of MBZ, we performed transcriptome analysis of zebrafish eyes. The analysis revealed that the DNA damage response was involved in the developmental toxicity of MBZ. We were also able to demonstrate that inhibition of ATM significantly attenuated the apoptosis induced by MBZ in the zebrafish retina. These results suggest that MBZ causes developmental toxicity in the zebrafish retina at least partly by activating the DNA damage response, including ATM signaling, providing a potential adverse outcome pathway in the developmental toxicity of MBZ in mammals.

  9. Modeling Zebrafish Developmental Toxicity using a Concurrent In vitro Assay Battery (SOT)

    Science.gov (United States)

    We describe the development of computational models that predict activity in a repeat-dose zebrafish embryo developmental toxicity assay using a combination of physico-chemical parameters and in vitro (human) assay measurements. The data set covered 986 chemicals including pestic...

  10. Enhancement of developmental toxicity effects of chemicals by gestational stress. A review

    DEFF Research Database (Denmark)

    Hougaard, Karin S; Hansen, Åse Marie

    2007-01-01

    exposures with other factors, such as maternal stress, itself a modifier of fetal development. Gestational stress has been hypothesized to enhance the developmental toxicity of chemicals. This review identified 36 animal studies investigating if maternal stress may enhance the effects of prenatal chemical...

  11. Predictive value of cell assays for developmental toxicity and embryotoxicity of conazole fungicides

    DEFF Research Database (Denmark)

    Sørensen, Karin Dreisig; Taxvig, Camilla; Kjærstad, Mia Birkhøj

    2013-01-01

    This paper evaluates in vivo predictability of a battery of in vitro tests covering developmental toxicity and embryotoxicity of five widely used conazole fungicides. The conazoles were investigated in the embryonic stem cell test, and data were compared to in vivo embryotoxicity data. The same...

  12. Oral dietary developmental toxicity study with polyvinyl acetate phthalate (PVAP) in the rat.

    Science.gov (United States)

    DeMerlis, C C; Schoneker, D R; Borzelleca, J F

    2014-10-01

    Polyvinyl acetate phthalate (PVAP) was evaluated in a developmental toxicity study with Crl:CD(SD) rats. Female rats were provided continual access to the formulated diets on days 6 through 20 of presumed gestation (DGs 6 through 20) at concentrations of 0%, 0.75%, 1.5% and 3%. All surviving rats were sacrificed and Caesarean-sectioned on DG 21. The following parameters were evaluated: viability, clinical observations, body weights, feed consumption, necropsy observations, Caesarean-sectioning and litter observations, including gravid uterine weights, fetal body weights and sex, and fetal gross external, soft tissue and skeletal alterations. There were no treatment-related adverse effects reported in the developmental toxicity study. The maternal and developmental no-observable-adverse-effect level (NOAEL) of PVAP was the highest concentration administered, i.e., 3.0% (equivalent to 2324mgPVAP/kg/day). Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Fipronil-induced enantioselective developmental toxicity to zebrafish embryo-larvae involves changes in DNA methylation.

    Science.gov (United States)

    Qian, Yi; Wang, Cui; Wang, Jinghua; Zhang, Xiaofeng; Zhou, Zhiqiang; Zhao, Meirong; Lu, Chensheng

    2017-05-23

    Enantioselectivity in the aquatic toxicity of chiral pesticides has been widely investigated, while the molecular mechanisms remain unclear. Thus far, few studies has focused on genomic expression related to selective toxicity in chiral pesticide, nor on epigenetic changes, such as DNA methylation. Here, we used fipronil, a broad-spectrum insecticide, as a model chemical to probe its enantioselective toxicity in embryo development. Our results showed that S-(+)-fipronil caused severer developmental toxicity in embryos. The MeDIP-Seq analysis demonstrated that S-(+)-fipronil dysregulated a higher level of genomic DNA methylation than R-(-)-fipronil. Gene Ontology analysis revealed that S-(+)-fipronil caused more differentially methylated genes that are involved in developmental processes. Compared with R-(-)-fipronil, S-(+)-fipronil significantly disrupted 7 signaling pathways (i.e., mitogen-activated protein kinases, tight junctions, focal adhesion, transforming growth factor-β, vascular smooth muscle contraction, and the hedgehog and Wnt signaling pathways) by hyper-methylation of developmentally related genes, which further induced the downregulation of those genes. Together, these data suggest that differences in DNA methylation may partly explain the enantioselectivity of fipronil to zebrafish embryos. The application of epigenetics to investigate the enantioselective toxicity mechanism of chiral chemicals would provide a further understanding of their stereoselectivity biological effects.

  14. Comparing rat and rabbit embryo-fetal developmental toxicity studies for 379 pharmaceuticals: On systemic dose and developmental effects (Critical Reviews in Toxicology)

    Science.gov (United States)

    A database of embryo-fetal developmental toxicity (EFDT) studies of 379 pharmaceutical compounds in rat and rabbit was analyzed for species differences based on toxicokinetic parameters of area under the curve (AUC) and maximum concentration (Cmax) at the developmental adverse ef...

  15. Triphenyl phosphate-induced developmental toxicity in zebrafish: potential role of the retinoic acid receptor.

    Science.gov (United States)

    Isales, Gregory M; Hipszer, Rachel A; Raftery, Tara D; Chen, Albert; Stapleton, Heather M; Volz, David C

    2015-04-01

    Using zebrafish as a model, we previously reported that developmental exposure to triphenyl phosphate (TPP) - a high-production volume organophosphate-based flame retardant - results in dioxin-like cardiac looping impairments that are independent of the aryl hydrocarbon receptor. Using a pharmacologic approach, the objective of this study was to investigate the potential role of retinoic acid receptor (RAR) - a nuclear receptor that regulates vertebrate heart morphogenesis - in mediating TPP-induced developmental toxicity in zebrafish. We first revealed that static exposure of zebrafish from 5-72h post-fertilization (hpf) to TPP in the presence of non-toxic concentrations of an RAR antagonist (BMS493) significantly enhanced TPP-induced toxicity (relative to TPP alone), even though identical non-toxic BMS493 concentrations mitigated retinoic acid (RA)-induced toxicity. BMS493-mediated enhancement of TPP toxicity was not a result of differential TPP uptake or metabolism, as internal embryonic doses of TPP and diphenyl phosphate (DPP) - a primary TPP metabolite - were not different in the presence or absence of BMS493. Using real-time PCR, we then quantified the relative change in expression of cytochrome P450 26a1 (cyp26a1) - a major target gene for RA-induced RAR activation in zebrafish - and found that RA and TPP exposure resulted in a ∼5-fold increase and decrease in cyp26a1 expression, respectively, relative to vehicle-exposed embryos. To address whether TPP may interact with human RARs, we then exposed Chinese hamster ovary cells stably transfected with chimeric human RARα-, RARβ-, or RARγ to TPP in the presence of RA, and found that TPP significantly inhibited RA-induced luciferase activity in a concentration-dependent manner. Overall, our findings suggest that zebrafish RARs may be involved in mediating TPP-induced developmental toxicity, a mechanism of action that may have relevance to humans. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Folic acid improve developmental toxicity induced by aluminum sulphates.

    Science.gov (United States)

    Yassa, Heba A; George, Safaa M; Mohamed, Heba K

    2017-03-01

    Aluminum sulphate has a significant toxic effects for humans. Aluminum is one of the most abundant metal on the Earth crust. The purpose of this study is to evaluate the effects of short term exposure to aluminum sulphate on the bone development of the fetuses in rats, and if folic acid has a protective role upon that effects or not. Forty female rats were used, ten per group, GI served as negative control (receive nothing except normal feeding and water), GII served as positive control (receive water by gastric gavage), GIII treated with aluminum sulphate orally by gastric gavage and GIV treated with aluminum sulphate with folic acid. Mating occurred and known by presence of vaginal plug in the female rats. Rats were killed on day 18 of gestation. The female rats weight were significantly reduced in the treated group if compared with the control group (p>0.001), all parameters of the fetuses, fetal weight, malformation and the crown rump length reduced significantly p value were Folic acid gave a protective role for all the hazardous effects of aluminum sulphate and prove the diameters measured and also the histopathological effects. Aluminum sulphate can produce hazardous effects on bone of the fetuses, which may affect the life style of these fetuses later on. Folic acid might give a protective role and so should be given to females who tried to conceive. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Reproductive and developmental toxicity of carbon-based nanomaterials: A literature review.

    Science.gov (United States)

    Ema, Makoto; Hougaard, Karin Sørig; Kishimoto, Atsuo; Honda, Kazumasa

    2016-01-01

    We summarized the findings of reproductive and developmental toxicity studies on carbon-based nanomaterials (CNMs). Placental transfer of fullerenes in rats and single-walled (SW) and multi-walled (MW) CNTs in mice was shown after intravenous injection. SWCNTs appeared to be embryolethal and teratogenic in mice when given by intravenous injection and induced death and growth retardation in chicken embryos. In mice-administered MWCNTs, fetal malformations after intravenous and intraperitoneal injections and intratracheal instillation, fetal loss after intravenous injection, behavioral changes in offspring after intraperitoneal injection, and a delay in the delivery of the first litter after intratracheal instillation were reported. Oral gavage of MWCNTs had no developmental toxicity in mice and rats. MWCNTs produced morphological defects, developmental arrest, and death in zebrafish embryos. Intratracheal instillation of carbon black (CB) induced testicular toxicity in adult mice. Maternal airway exposure to CB in gestation had testicular toxicity and altered postnatal behavior, renal development, immune and genotoxic responses, and brain morphology in mouse offspring. Nanodiamonds and graphite nanoparticles inhibited vasculogenesis and/or angiogenesis in chicken embryos. Graphene oxide (GO) induced malformations in zebrafish embryos. Intravenous injection of reduced GO during late gestation caused maternal death and abortion in mice. Oral administration of GO during lactation caused growth retardation of offspring. Overall, the available data provide initial information on the potential reproductive and developmental toxicity of CNMs. However, confirmatory studies using well-characterized CNMs, state-of-the-art study protocol and appropriate route of exposure, are required to clarify the findings and provide information suitable for risk assessment.

  18. Enantioselective developmental toxicity and immunotoxicity of pyraclofos toward zebrafish (Danio rerio)

    Energy Technology Data Exchange (ETDEWEB)

    Zhuang, Shulin, E-mail: shulin@zju.edu.cn [Institute of Environmental Science, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058 (China); Zhejiang Provincial Key Laboratory of Organic Pollution Process and Control, Hangzhou 310058 (China); Zhang, Zhisheng [Institute of Environmental Science, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058 (China); Zhang, Wenjing; Bao, Lingling [Institute of Environmental Science, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058 (China); Zhejiang Provincial Key Laboratory of Organic Pollution Process and Control, Hangzhou 310058 (China); Xu, Chao, E-mail: chaoxu@zjut.edu.cn [Research Center of Environmental Science, College of Biological and Environmental Engineering, Zhejiang University of Technology, Hangzhou 310032 (China); Zhang, Hu [Institute of Quality and Standard for Agro-products, Zhejiang Academy of Agricultural Sciences, Hangzhou 210021 (China)

    2015-02-15

    Highlights: • Pyraclofos has significant enantioselective aquatic toxicities to zebrafish. • Pyraclofos induces time- and concentration-dependent developmental toxicity and immunotoxicity. • The mRNA level of IL-1β gene was significantly up-regulated by pyraclofos. • Pyraclofos binds potently to IL-1β, potentially affecting IL-1β-dependent proinflammatory signal transduction. • Our in vitro and in silico studies help to understand the molecular basis for aquatic toxicity of pyraclofos. - Abstract: Pyraclofos, a relatively new organophosphorus pesticide, has shown potential ecotoxicities, however, its aquatic toxicity, especially enantioselective aquatic toxicity, remains largely unknown. Using zebrafish (Danio rerio) as a preeminent vertebrate aquatic model, the enantioselective differences in the developmental toxicity and immunotoxicity of pyraclofos were evaluated. Following 96-h exposure, pyraclofos enantiomers exhibited acute toxicity and showed lethal concentration 50 of 2.23 and 3.99 mg/L for (R)-Pyraclofos and (S)-Pyraclofos, respectively. Exposure to pyraclofos caused time- and concentration-dependent malformations such as pericardial edema, yolk sac edema, crooked bodies and hatching during the embryonic development, with markedly higher percentages of malformation at higher concentrations. The concentration-dependent immunotoxicity to zebrafish embryo exposed to low level pyraclofos was induced with significant up-regulation of mRNA levels of immune-related interleukin-1β (IL-1β) gene. (R)-Pyraclofos was consistently more toxic than (S)-Pyraclofos for the acute toxicity, developmental toxicity and immunotoxicity to zebrafish. Molecular dynamics simulations revealed that at the atomic level, (R)-Pyraclofos binds more potently to IL-1β protein than (S)-Pyraclofos. This enantioselective binding is mainly contributed by the distinct binding mode of pyraclofos enantiomers and their electrostatic interactions with IL-1β, which potentially

  19. Subchronic and developmental toxicity studies in rats with Ac-Di-Sol croscarmellose sodium.

    Science.gov (United States)

    Freeman, Christine; Weiner, Myra L; Kotkoskie, Lois A; Borzelleca, Joseph; Butt, Mark

    2003-01-01

    Studies were conducted to evaluate the subchronic and developmental toxicity of Ac-Di-Sol (croscarmellose sodium). In the subchronic study, groups of Sprague-Dawley rats (20/sex/group) received 0 (control), 10000, or 50000 ppm Ac-Di-Sol in the diet for 90 consecutive days (equivalent to 757 and 893 mg/kg/day for males and females fed 10000 ppm, respectively, and to 3922 and 4721 mg/kg/day for males and females fed 50000 ppm, respectively). No mortality, clinical signs of toxicity, or adverse toxicological effects on hematology or serum chemistry parameters, feed consumption, or ophthalmologic examinations were noted in any treatment group. Body weight gain was depressed in high-dose males during the final 3 weeks. The only treatment-related histological lesion noted was moderate renal mineralization at the corticomedullary junction in one high-dose female. This lesion was not considered a specific effect of Ac-Di-Sol, but rather a secondary effect resulting from a potential increase in urinary pH and renal excretion of sodium due to the high intake of sodium associated with Ac-Di-Sol. In the developmental toxicity study, groups of pregnant Sprague-Dawley rats (25/group) received 0 (control), 10000, or 50000 ppm Ac-Di-Sol in the diet on gestational days 6 to 15. No evidence of maternal, fetal, or embryo toxicity was noted. The no-observed-adverse-effect level (NOAEL) for Ac-Di-Sol in both studies exceeds 50000 ppm in the diet, which represents doses of 3922 and 4712 mg/kg/day, for males and females, respectively. The results of these studies demonstrate the low subchronic oral toxicity and developmental toxicity of Ac-Di-Sol, and support the safe use of Ac-Di-Sol in oral applications such as pharmaceuticals, dietary supplements, and sweetener tablets.

  20. Light catalytically cracked naphtha: subchronic toxicity of vapors in rats and mice and developmental toxicity screen in rats.

    Science.gov (United States)

    Dalbey, W E; Feuston, M H; Yang, J J; Kommineni, C V; Roy, T A

    1996-01-01

    Both a subchronic inhalation study and a developmental toxicity screen were performed with vapors of light catalytically cracked naphtha (LCCN). In the subchronic study, four groups of mice and rats (10 animals per sex per species) were exposed for approximately 13 wk (6 h/d, 5 d/wk) to concentrations of LCCN vapors of 0, 530, 2060, or 7690 mg/m3. An untreated control group was also included. Animals were observed daily and body weights were taken weekly. No significant treatment-related changes were found in clinical signs, body weight, serum chemistry, hematology, histopathology of 24 tissues, or weights of 12 organs. A marginal decrease was noted in the number of sperm per gram of epididymis. In the developmental toxicity screen, presumed-pregnant Sprague-Dawley rats were exposed to 0, 2150, or 7660 mg/m3 of LCCN vapors, 6 h/d on d 0-19 of gestation. Females were sacrificed on d 20; dams and fetuses were examined grossly and fetuses were later evaluated for skeletal and visceral effects. The number of resorptions was increased by approximately 140% in the group receiving 7660 mg/m3; no other definite treatment-related changes were observed. Overall, the effects of exposure to partially vaporized LCCN were minimal.

  1. Relative developmental toxicity potencies of retinoids in the embryonic stem cell test compared with their relative potencies in in vivo and two other in vitro assays for developmental toxicity

    NARCIS (Netherlands)

    Louisse, J.; Gönen, S.; Rietjens, I.M.C.M.; Verwei, M.

    2011-01-01

    The present study determines the relative developmental toxicity potencies of retinoids in the embryonic stem (ES)-D3 cell differentiation assay of the embryonic stem cell test, and compares the outcomes with their relative potencies in in vivo and two other in vitro assays for developmental

  2. New animal-free concepts and test methods for developmental toxicity and peripheral neurotoxicity.

    Science.gov (United States)

    Leist, Marcel

    2017-11-01

    The complex toxicological fields of repeat dose organ toxicity (RDT) and developmental and reproductive toxicity (DART) still require new concepts and approaches to achieve a fully animal-free safety assessment of chemicals. One novel approach is the generation of relevant human cell types from pluripotent stem cells, and the use of such cells for the establishment of phenotypic test methods. Due to their broad endpoints, such tests capture multiple types of toxicants, i.e. they are a readout for the activation of many adverse outcome pathways (AOPs). The 2016 Lush Science Prize was awarded for the development of one such assay, the PeriTox test, which uses human peripheral neurons generated from stem cells. The assay endpoints measure various cell functions, and these give information on the potential neurotoxicity and developmental neurotoxicity hazard of test compounds. The PeriTox test method has a high predictivity and sensitivity for peripheral neurotoxicants, and thus addresses the inherent challenges in pesticide testing and drug development. Data from the test can be obtained quickly and at a relatively high-throughput, and thus, the assay has the potential to replace animal-based safety assessment during early product development or for screening potential environmental toxicants. 2017 FRAME.

  3. FUNCTIONAL-ASPECTS OF DEVELOPMENTAL TOXICITY OF POLYHALOGENATED AROMATIC-HYDROCARBONS IN EXPERIMENTAL-ANIMALS AND HUMAN INFANTS

    NARCIS (Netherlands)

    BROUWER, A; AHLBORG, UG; VANDENBERG, M; BIRNBAUM, LS; BOERSMA, ER; BOSVELD, B; DENISON, MS; GRAY, LE; HAGMAR, L; HOLENE, E; HUISMAN, M; JACOBSON, SW; JACOBSON, JL; KOOPMANESSEBOOM, C; KOPPE, JG; KULIG, BM; MORSE, DC; MUCKLE, G; PETERSON, RE; SAUER, PJJ; SEEGAL, RF; SMITSVANPROOIJE, AE; TOUWEN, BCL; WEISGLASKUPERUS, N; WINNEKE, G

    1995-01-01

    A scientific evaluation was made of functional aspects of developmental toxicity of polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) in experimental animals and in human infants. Persistent neurobehavioral, reproductive and

  4. ToxCast Profiling in a Human Stem Cell Assay for Developmental Toxicity (CompTox CoP)

    Science.gov (United States)

    Standard practice for assessing disruptions in embryogenesis involves testing pregnant animals of two species, typically rats and rabbits, exposed during major organogenesis and evaluated just prior to term. Under this design the major manifestations of developmental toxicity are...

  5. 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 ...

  6. Triphenyl phosphate-induced developmental toxicity in zebrafish: Potential role of the retinoic acid receptor

    Energy Technology Data Exchange (ETDEWEB)

    Isales, Gregory M.; Hipszer, Rachel A.; Raftery, Tara D. [Department of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, SC (United States); Chen, Albert; Stapleton, Heather M. [Division of Environmental Sciences and Policy, Nicholas School of the Environment, Duke University, Durham, NC (United States); Volz, David C., E-mail: volz@mailbox.sc.edu [Department of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, SC (United States)

    2015-04-15

    Highlights: • Triphenyl phosphate-induced toxicity in zebrafish embryos is enhanced in the presence of a retinoic acid receptor antagonist. • Triphenyl phosphate uptake or metabolism within zebrafish embryos is not altered in the presence of a retinoic acid receptor antagonist. • Triphenyl phosphate decreases expression of cytochrome P450 26a1 in zebrafish embryos. • Triphenyl phosphate inhibits retinoic acid-induced activation of human retinoic acid receptors. - Abstract: Using zebrafish as a model, we previously reported that developmental exposure to triphenyl phosphate (TPP) – a high-production volume organophosphate-based flame retardant – results in dioxin-like cardiac looping impairments that are independent of the aryl hydrocarbon receptor. Using a pharmacologic approach, the objective of this study was to investigate the potential role of retinoic acid receptor (RAR) – a nuclear receptor that regulates vertebrate heart morphogenesis – in mediating TPP-induced developmental toxicity in zebrafish. We first revealed that static exposure of zebrafish from 5–72 h post-fertilization (hpf) to TPP in the presence of non-toxic concentrations of an RAR antagonist (BMS493) significantly enhanced TPP-induced toxicity (relative to TPP alone), even though identical non-toxic BMS493 concentrations mitigated retinoic acid (RA)-induced toxicity. BMS493-mediated enhancement of TPP toxicity was not a result of differential TPP uptake or metabolism, as internal embryonic doses of TPP and diphenyl phosphate (DPP) – a primary TPP metabolite – were not different in the presence or absence of BMS493. Using real-time PCR, we then quantified the relative change in expression of cytochrome P450 26a1 (cyp26a1) – a major target gene for RA-induced RAR activation in zebrafish – and found that RA and TPP exposure resulted in a ∼5-fold increase and decrease in cyp26a1 expression, respectively, relative to vehicle-exposed embryos. To address whether TPP may

  7. Developmental Toxicity of Carbon Quantum Dots to the Embryos/Larvae of Rare Minnow (Gobiocypris rarus

    Directory of Open Access Journals (Sweden)

    Yuan-Yuan Xiao

    2016-01-01

    Full Text Available The toxic effects of CDs on rare minnow (Gobiocypris rarus embryos at different developmental stages were investigated. The results showed that rare minnow embryos had decreased spontaneous movements, body length, increased heart rate, pericardial edema, yolk sac edema, tail/spinal curvature, various morphological malformations, and decreased hatching rate. Biochemical analysis showed the CDs exposure significantly inhibited the activity of Na+/K+-ATPase and Ca2+-ATPase and increased the MDA contents and the activity of SOD, CAT, and GPX. Further examination suggested that the CDs exposure induced serious embryonic cellular DNA damage. Moreover, the CDs exposure induced upregulation of development related genes (Wnt8a and Mstn along with the downregulation of Vezf1. Overall, the present study revealed that the CDs exposure has significant development toxicity on rare minnow embryos/larvae. Mechanistically, this toxicity might result from the pressure of induced oxidative stress coordinate with the dysregulated development related gene expression mediated by the CDs exposure.

  8. Developmental Toxic Effects of Exposure to Chemical Warfare Nerve Agents in Rats: Effects on Brain and Behavior

    Science.gov (United States)

    2015-03-01

    Yourick D (2009) Analyzing large data sets acquired through telemetry from rats exposed to organophosphorus compounds: an EEG study. J Neurosci Methods...AWARD NUMBER: W81XWH-13-2-0082 TITLE: Developmental Toxic Effects of Exposure to Chemical Warfare Nerve Agents in Rats : Effects on Brain and...2014 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Developmental Toxic Effects of Exposure to Chemical Warfare Nerve Agents in Rats : Effects on Brain

  9. What we know and what we need to know about developmental aluminum toxicity.

    Science.gov (United States)

    Golub, M S; Domingo, J L

    1996-08-30

    Information concerning developmental aluminum (Al) toxicity is available from clinical studies and from animal testing. An Al toxicity syndrome including encephalopathy, osteomalacia, and anemia has been reported in uremic children receiving dialysis. In addition, some components of the syndrome, particularly osteomalacia, have been reported in non-dialyzed uremic children receiving Al-based phosphate binders, nonuremic infants receiving parenteral nutrition with Al-containing fluids, and nonuremic infants given high doses of Al antacids. The number of children in clinical populations that are at risk of Al toxicity is not known and needs to be determined. Work in animal models (rats, mice, and rabbits) demonstrates that Al is distributed transplacentally and is present in milk. Oral Al administration during pregnancy produces a syndrome including growth retardation, delayed ossification, and malformations at doses that also lead to reduced maternal weight gain. The severity of the effects is highly dependent on the form of Al administered. In the postnatal period, reduced pup weight gain and effects on neuromotor development have been described as a result of developmental exposures. The significance of these findings for human health requires better understanding of the amount and bioavailability of Al in food, drinking water, and medications and from sources unique to infants and children such as breast milk, soil ingestion, and medications used specifically by pregnant women and children. We also need a better understanding of the unique biological actions of Al that may occur during developmental periods, and unique aspects of the developing organism that make it more or less susceptible to Al toxicity.

  10. Embryo-Fetal Developmental Toxicity Studies with Pregabalin in Mice and Rabbits.

    Science.gov (United States)

    Morse, Dennis C

    2016-04-01

    Pregabalin was evaluated for potential developmental toxicity in mice and rabbits. Pregabalin was administered once daily by oral gavage to female albino mice (500, 1250, or 2500 mg/kg) and New Zealand White rabbits (250, 500, or 1250 mg/kg) during organogenesis (gestation day 6 through 15 [mice] or 6 through 20 [rabbits]). Fetuses were evaluated for viability, growth, and morphological development. Pregabalin administration to mice did not induce maternal or developmental toxicity at doses up to 2500 mg/kg, which was associated with a maternal plasma exposure (AUC0-24 ) of 3790 μg•hr/ml, ≥30 times the expected human exposure at the maximum recommended daily dose (MRD; 600 mg/day). In rabbits, treatment-related clinical signs occurred at all doses (AUC0-24 of 1397, 2023, and 4803 μg•hr/ml at 250, 500, and 1250 mg/kg, respectively). Maternal toxicity was evident at all doses and included ataxia, hypoactivity, and cool to touch. In addition, abortion and females euthanized moribund with total resorption occurred at 1250 mg/kg. There were no treatment-related malformations at any dose. At 1250 mg/kg, compared with study and historical controls, the percentage of fetuses with retarded ossification was significantly increased and the mean number of ossification sites was decreased, which correlated with decreased fetal and placental weights, consistent with in utero growth retardation. Therefore, the no-effect dose for developmental toxicity in rabbits was 500 mg/kg, which produced systemic exposure approximately 16-times human exposure at the MRD. These findings indicate that pregabalin, at the highest dose tested, was not teratogenic in mice or rabbits. © 2016 Wiley Periodicals, Inc.

  11. Developmental toxicity of Louisiana crude oil-spiked sediment to zebrafish.

    Science.gov (United States)

    Raimondo, Sandy; Jackson, Crystal R; Krzykwa, Julie; Hemmer, Becky L; Awkerman, Jill A; Barron, Mace G

    2014-10-01

    Embryonic exposures to the components of petroleum, including polycyclic aromatic hydrocarbons (PAHs), cause a characteristic suite of developmental defects and cardiotoxicity in a variety of fish species. We exposed zebrafish embryos to reference sediment mixed with laboratory weathered South Louisiana crude oil and to sediment collected from an oiled site in Barataria Bay, Louisiana in December 2010. Laboratory oiled sediment exposures caused a reproducible set of developmental malformations in zebrafish embryos including yolk sac and pericardial edema, craniofacial and spinal defects, and tissue degeneration. Dose-response studies with spiked sediment showed that total polycyclic aromatic hydrocarbons (tPAH) concentrations of 27mg tPAH/kg (dry weight normalized to 1 percent organic carbon [1 percent OC]) caused a significant increase in defects, and concentrations above 78mg tPAH/kg 1 percent OC caused nearly complete embryo mortality. No toxicity was observed in Barataria sediment with 2mg tPAH/kg 1 percent OC. Laboratory aging of spiked sediment at 4°C resulted in a nearly 10-fold decrease in sensitivity over a 40-day period. This study demonstrates oiled sediment as an exposure pathway to fish with dose-dependent effects on embryogenesis that are consistent with PAH mechanisms of developmental toxicity. The results have implications for effects on estuarine fish from oiled coastal areas during the Deepwater Horizon spill. Published by Elsevier Inc.

  12. Final report on the developmental toxicity of naphthalene (CAS No. 91-20-3) in New Zealand White (trade name) rabbits. Rept. for 26 Mar-1 Aug 91

    Energy Technology Data Exchange (ETDEWEB)

    Navarro, H.A.; Price, C.J.; Marr, M.C.; Myers, C.B.; Heindel, J.J.

    1992-07-13

    Naphthalene (NAP) is a polyaromatic hydrocarbon produced from petroleum and coal tar. NAP is widely used in the manufacture of dyes, synthetic tanning agents, and lubricants; it is also a common constituent of mothballs. Exposure to NAP can occur in the home and workplace, and ingestion or inhalation can cause severe toxicity in humans, especially in infants and individuals with a deficiency in the enzyme glucose-6-phosphate dehydrogenase. Because of the large population at risk, and since NAP readily crosses the placenta, it was evaluated as a developmental toxicant. Accordingly, NAP (0, 20, 80, or 120 mg/kg/day) was administered in corn oil by gavage to pregnant rabbits during the major period of organogenesis (gd 6-19). Maternal clinical signs, weight, and food consumption were monitored from gd 0 to 30. On gd 30, fetuses were removed from the does and examined for effects of NAP on growth, viability, and morphological development. The results from the study provide no definitive evidence for NAP being toxic to the fetus or doe at doses as high as 120 mg/kg/day. Higher doses were not examined in the study due to the reported incidence of 40% maternal mortality following administration of 150 mg/kg/day NAP to pregnant rabbits in a range-finding study.

  13. 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.

  14. Comparative developmental toxicity of a comprehensive suite of polycyclic aromatic hydrocarbons.

    Science.gov (United States)

    Geier, Mitra C; Chlebowski, Anna C; Truong, Lisa; Massey Simonich, Staci L; Anderson, Kim A; Tanguay, Robert L

    2017-11-01

    Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental contaminants that occur in complex mixtures. Several PAHs are known or suspected mutagens and/or carcinogens, but developmental toxicity data is lacking for PAHs, particularly their oxygenated and nitrated derivatives. Such data are necessary to understand and predict the toxicity of environmental mixtures. 123 PAHs were assessed for morphological and neurobehavioral effects for a range of concentrations between 0.1 and 50 µM, using a high throughput early-life stage zebrafish assay, including 33 parent, 22 nitrated, 17 oxygenated, 19 hydroxylated, 14 methylated, 16 heterocyclic, and 2 aminated PAHs. Additionally, each PAH was evaluated for AHR activation, by assessing CYP1A protein expression using whole animal immunohistochemistry (IHC). Responses to PAHs varied in a structurally dependent manner. High-molecular weight PAHs were significantly more developmentally toxic than the low-molecular weight PAHs, and CYP1A expression was detected in five distinct tissues, including vasculature, liver, skin, neuromasts and yolk.

  15. Developmental toxicity of copaiba tree (Copaifera reticulata Ducke, Fabaceae) oleoresin in rat.

    Science.gov (United States)

    Sachetti, Camile G; de Carvalho, Rosângela R; Paumgartten, Francisco J R; Lameira, Osmar A; Caldas, Eloisa D

    2011-05-01

    The oleoresin of the copaiba tree (Copaifera sp., Fabaceae) is traditionally used in Brazilian herbal medicine to treat a variety of illnesses and symptoms. This study, conducted according to the OECD Guideline 414, provides data on the developmental toxicity of oleoresin from C. reticulata (COPA-R) in rats. Pregnant Wistar rats (25 per dose group) were treated by gavage with COPA-R (0, 500, 1000 and 1250 mg/kg bw/day) on gestation days (GD) 6-19 and Caesarean sections performed on GD20. Implantations, living and dead fetuses and resorptions were recorded. Half of the fetuses from each litter were examined for visceral abnormalities and the remaining were cleared and stained for skeleton evaluation. COPA-R was maternally toxic (reduced food intake and weight gain) and embryotoxic (lower fetal body weight and increased occurrence of fetal skeleton variations) at the two highest doses, but did not cause embryo deaths or fetal malformations at any dose level. The study derived an oral no-observed-adverse-effect-level (NOAEL) for maternal and developmental toxicity induced by COPA-R of 500 mg/kg bw/day. The results suggest that copaiba oleoresin does not pose a health risk to pregnant women when used according to the recommended doses (up to five drops, three times a day). Copyright © 2011. Published by Elsevier Ltd.

  16. Growing knowledge of using embryonic stem cells as a novel tool in developmental risk assessment of environmental toxicants.

    Science.gov (United States)

    Rezvanfar, Mohammad Amin; Hodjat, Mahshid; Abdollahi, Mohammad

    2016-08-01

    Developmental toxicology is an important area of novel toxicology. In recent years, there have been big concerns toward the increasing exposure to pharmaceutical agents, food additives, pesticides, occupational toxicants, and environmental pollutants, as well as their possible association with all aspects of male or female-mediated transient or permanent defects in progeny. Therefore, it is of great importance to look for new predictive models to evaluate environmental toxicants before they can harm the human health and embryo development. In this regard, new cell-based in vitro screening models have been developed and validated in predictive toxicology to minimize assay costs and animal usage. Stem cell-based models have been increasingly applied for predicting the toxicity of chemicals. One of the most promising existing in vitro developmental toxicity tests is the validated embryonic stem cell test (EST) which employs marine or human embryonic stem cells to assess the potential of chemicals embryotoxicity. These cells are very suitable for embryotoxicity assessment as they have been demonstrated to specify cellular developmental processes during early embryogenesis and gene expression patterns of differentiation to functionally competent specialized cell types. The present paper aimed at criticizing the human and experimental evidence for developmental toxic effects of environmental toxicants based on ESCs models. Accordingly, pesticides, heavy metals, plasticizers, nanomaterials and some solvents have been considered as the main evaluated environmental toxicants inducing developmental toxicity. At the end, current challenges, pros and cons of using ESCs as an alternative validated in vitro model for specific developmental toxicity screening are discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. A systematic evaluation of chemicals in hydraulic-fracturing fluids and wastewater for reproductive and developmental toxicity.

    Science.gov (United States)

    Elliott, Elise G; Ettinger, Adrienne S; Leaderer, Brian P; Bracken, Michael B; Deziel, Nicole C

    2017-01-01

    Hydraulic-fracturing fluids and wastewater from unconventional oil and natural gas development contain hundreds of substances with the potential to contaminate drinking water. Challenges to conducting well-designed human exposure and health studies include limited information about likely etiologic agents. We systematically evaluated 1021 chemicals identified in hydraulic-fracturing fluids (n=925), wastewater (n=132), or both (n=36) for potential reproductive and developmental toxicity to triage those with potential for human health impact. We searched the REPROTOX database using Chemical Abstract Service registry numbers for chemicals with available data and evaluated the evidence for adverse reproductive and developmental effects. Next, we determined which chemicals linked to reproductive or developmental toxicity had water quality standards or guidelines. Toxicity information was lacking for 781 (76%) chemicals. Of the remaining 240 substances, evidence suggested reproductive toxicity for 103 (43%), developmental toxicity for 95 (40%), and both for 41 (17%). Of these 157 chemicals, 67 had or were proposed for a federal water quality standard or guideline. Our systematic screening approach identified a list of 67 hydraulic fracturing-related candidate analytes based on known or suspected toxicity. Incorporation of data on potency, physicochemical properties, and environmental concentrations could further prioritize these substances for future drinking water exposure assessments or reproductive and developmental health studies.

  18. Developmental Toxicity of Zinc Oxide Nanoparticles to Zebrafish (Danio rerio): A Transcriptomic Analysis.

    Science.gov (United States)

    Choi, Jin Soo; Kim, Ryeo-Ok; Yoon, Seokjoo; Kim, Woo-Keun

    2016-01-01

    Zinc oxide nanoparticles (ZnO NPs) are being utilized in an increasing number of fields and commercial applications. While their general toxicity and associated oxidative stress have been extensively studied, the toxicological pathways that they induce in developmental stages are still largely unknown. In this study, the developmental toxicity of ZnO NPs to embryonic/larval zebrafish was investigated. The transcriptional expression profiles induced by ZnO NPs were also investigated to ascertain novel genomic responses related to their specific toxicity pathway. Zebrafish embryos were exposed to 0.01, 0.1, 1, and 10 mg/L ZnO NPs for 96 h post-fertilization. The toxicity of ZnO NPs, based on their Zn concentration, was quite similar to that in embryonic/larval zebrafish exposed to corresponding ZnSO4 concentrations. Pericardial edema and yolk-sac edema were the principal malformations induced by ZnO NPs. Gene-expression profiling using microarrays demonstrated 689 genes that were differentially regulated (fold change >1.5) following exposure to ZnO NPs (498 upregulated, 191 downregulated). Several genes that were differentially regulated following ZnO NP exposure shared similar biological pathways with those observed with ZnSO4 exposure, but six genes (aicda, cyb5d1, edar, intl2, ogfrl2 and tnfsf13b) associated with inflammation and the immune system responded specifically to ZnO NPs (either in the opposite direction or were unchanged in ZnSO4 exposure). Real-time reverse-transcription quantitative polymerase chain reaction confirmed that the responses of these genes to ZnO NPs were significantly different from their response to ZnSO4 exposure. ZnO NPs may affect genes related to inflammation and the immune system, resulting in yolk-sac edema and pericardia edema in embryonic/larval developmental stages. These results will assist in elucidating the mechanisms of toxicity of ZnO NPs during development of zebrafish.

  19. Developmental Toxicity of Zinc Oxide Nanoparticles to Zebrafish (Danio rerio: A Transcriptomic Analysis.

    Directory of Open Access Journals (Sweden)

    Jin Soo Choi

    Full Text Available Zinc oxide nanoparticles (ZnO NPs are being utilized in an increasing number of fields and commercial applications. While their general toxicity and associated oxidative stress have been extensively studied, the toxicological pathways that they induce in developmental stages are still largely unknown. In this study, the developmental toxicity of ZnO NPs to embryonic/larval zebrafish was investigated. The transcriptional expression profiles induced by ZnO NPs were also investigated to ascertain novel genomic responses related to their specific toxicity pathway. Zebrafish embryos were exposed to 0.01, 0.1, 1, and 10 mg/L ZnO NPs for 96 h post-fertilization. The toxicity of ZnO NPs, based on their Zn concentration, was quite similar to that in embryonic/larval zebrafish exposed to corresponding ZnSO4 concentrations. Pericardial edema and yolk-sac edema were the principal malformations induced by ZnO NPs. Gene-expression profiling using microarrays demonstrated 689 genes that were differentially regulated (fold change >1.5 following exposure to ZnO NPs (498 upregulated, 191 downregulated. Several genes that were differentially regulated following ZnO NP exposure shared similar biological pathways with those observed with ZnSO4 exposure, but six genes (aicda, cyb5d1, edar, intl2, ogfrl2 and tnfsf13b associated with inflammation and the immune system responded specifically to ZnO NPs (either in the opposite direction or were unchanged in ZnSO4 exposure. Real-time reverse-transcription quantitative polymerase chain reaction confirmed that the responses of these genes to ZnO NPs were significantly different from their response to ZnSO4 exposure. ZnO NPs may affect genes related to inflammation and the immune system, resulting in yolk-sac edema and pericardia edema in embryonic/larval developmental stages. These results will assist in elucidating the mechanisms of toxicity of ZnO NPs during development of zebrafish.

  20. Comparison of rat and rabbit embryo-fetal developmental toxicity data for 379 pharmaceuticals: on the nature and severity of developmental effects (Critical Reviews in Toxicology)

    Science.gov (United States)

    Regulatory non-clinical safety testing of human pharmaceutical compounds typically requires embryo fetal developmental toxicity (EFDT) testing in two species, (one rodent and one non-rodent, usually the rat and the rabbit). The question has been raised whether under some conditio...

  1. The Developmental Toxicity of Complex Silica-Embedded Nickel Nanoparticles Is Determined by Their Physicochemical Properties.

    Science.gov (United States)

    Mahoney, Sharlee; Najera, Michelle; Bai, Qing; Burton, Edward A; Veser, Götz

    2016-01-01

    Complex engineered nanomaterials (CENs) are a rapidly developing class of structurally and compositionally complex materials that are expected to dominate the next generation of functional nanomaterials. The development of methods enabling rapid assessment of the toxicity risk associated with this type of nanomaterial is therefore critically important. We evaluated the toxicity of three differently structured nickel-silica nanomaterials as prototypical CENs: simple, surface-deposited Ni-SiO2 and hollow and non-hollow core-shell Ni@SiO2 materials (i.e., ~1-2 nm Ni nanoparticles embedded into porous silica shells with and without a central cavity, respectively). Zebrafish embryos were exposed to these CENs, and morphological (survival and malformations) and physiological (larval motility) endpoints were coupled with thorough characterization of physiochemical characteristics (including agglomeration, settling and nickel ion dissolution) to determine how toxicity differed between these CENs and equivalent quantities of Ni2+ salt (based on total Ni). Exposure to Ni2+ ions strongly compromised zebrafish larva viability, and surviving larvae showed severe malformations. In contrast, exposure to the equivalent amount of Ni CEN did not result in these abnormalities. Interestingly, exposure to Ni-SiO2 and hollow Ni@SiO2 provoked abnormalities of zebrafish larval motor function, indicating developmental toxicity, while non-hollow Ni@SiO2 showed no toxicity. Correlating these observations with physicochemical characterization of the CENs suggests that the toxicity of the Ni-SiO2 and hollow Ni@SiO2 material may result partly from an increased effective exposure at the bottom of the well due to rapid settling. Overall, our data suggest that embedding nickel NPs in a porous silica matrix may be a straightforward way to mitigate their toxicity without compromising their functional properties. At the same time, our results also indicate that it is critical to consider modification

  2. The Developmental Toxicity of Complex Silica-Embedded Nickel Nanoparticles Is Determined by Their Physicochemical Properties.

    Directory of Open Access Journals (Sweden)

    Sharlee Mahoney

    Full Text Available Complex engineered nanomaterials (CENs are a rapidly developing class of structurally and compositionally complex materials that are expected to dominate the next generation of functional nanomaterials. The development of methods enabling rapid assessment of the toxicity risk associated with this type of nanomaterial is therefore critically important. We evaluated the toxicity of three differently structured nickel-silica nanomaterials as prototypical CENs: simple, surface-deposited Ni-SiO2 and hollow and non-hollow core-shell Ni@SiO2 materials (i.e., ~1-2 nm Ni nanoparticles embedded into porous silica shells with and without a central cavity, respectively. Zebrafish embryos were exposed to these CENs, and morphological (survival and malformations and physiological (larval motility endpoints were coupled with thorough characterization of physiochemical characteristics (including agglomeration, settling and nickel ion dissolution to determine how toxicity differed between these CENs and equivalent quantities of Ni2+ salt (based on total Ni. Exposure to Ni2+ ions strongly compromised zebrafish larva viability, and surviving larvae showed severe malformations. In contrast, exposure to the equivalent amount of Ni CEN did not result in these abnormalities. Interestingly, exposure to Ni-SiO2 and hollow Ni@SiO2 provoked abnormalities of zebrafish larval motor function, indicating developmental toxicity, while non-hollow Ni@SiO2 showed no toxicity. Correlating these observations with physicochemical characterization of the CENs suggests that the toxicity of the Ni-SiO2 and hollow Ni@SiO2 material may result partly from an increased effective exposure at the bottom of the well due to rapid settling. Overall, our data suggest that embedding nickel NPs in a porous silica matrix may be a straightforward way to mitigate their toxicity without compromising their functional properties. At the same time, our results also indicate that it is critical to

  3. The Developmental Toxicity of Complex Silica-Embedded Nickel Nanoparticles Is Determined by Their Physicochemical Properties

    Science.gov (United States)

    Mahoney, Sharlee; Najera, Michelle; Bai, Qing; Burton, Edward A.; Veser, Götz

    2016-01-01

    Complex engineered nanomaterials (CENs) are a rapidly developing class of structurally and compositionally complex materials that are expected to dominate the next generation of functional nanomaterials. The development of methods enabling rapid assessment of the toxicity risk associated with this type of nanomaterial is therefore critically important. We evaluated the toxicity of three differently structured nickel-silica nanomaterials as prototypical CENs: simple, surface-deposited Ni-SiO2 and hollow and non-hollow core-shell Ni@SiO2 materials (i.e., ~1–2 nm Ni nanoparticles embedded into porous silica shells with and without a central cavity, respectively). Zebrafish embryos were exposed to these CENs, and morphological (survival and malformations) and physiological (larval motility) endpoints were coupled with thorough characterization of physiochemical characteristics (including agglomeration, settling and nickel ion dissolution) to determine how toxicity differed between these CENs and equivalent quantities of Ni2+ salt (based on total Ni). Exposure to Ni2+ ions strongly compromised zebrafish larva viability, and surviving larvae showed severe malformations. In contrast, exposure to the equivalent amount of Ni CEN did not result in these abnormalities. Interestingly, exposure to Ni-SiO2 and hollow Ni@SiO2 provoked abnormalities of zebrafish larval motor function, indicating developmental toxicity, while non-hollow Ni@SiO2 showed no toxicity. Correlating these observations with physicochemical characterization of the CENs suggests that the toxicity of the Ni-SiO2 and hollow Ni@SiO2 material may result partly from an increased effective exposure at the bottom of the well due to rapid settling. Overall, our data suggest that embedding nickel NPs in a porous silica matrix may be a straightforward way to mitigate their toxicity without compromising their functional properties. At the same time, our results also indicate that it is critical to consider

  4. Aerobic Bioremediation of PAH Contaminated Soil Results in Increased Genotoxicity and Developmental Toxicity.

    Science.gov (United States)

    Chibwe, Leah; Geier, Mitra C; Nakamura, Jun; Tanguay, Robert L; Aitken, Michael D; Simonich, Staci L Massey

    2015-12-01

    The formation of more polar and toxic polycyclic aromatic hydrocarbon (PAH) transformation products is one of the concerns associated with the bioremediation of PAH-contaminated soils. Soil contaminated with coal tar (prebioremediation) from a former manufactured gas plant (MGP) site was treated in a laboratory scale bioreactor (postbioremediation) and extracted using pressurized liquid extraction. The soil extracts were fractionated, based on polarity, and analyzed for 88 PAHs (unsubstituted, oxygenated, nitrated, and heterocyclic PAHs). The PAH concentrations in the soil tested, postbioremediation, were lower than their regulatory maximum allowable concentrations (MACs), with the exception of the higher molecular weight PAHs (BaA, BkF, BbF, BaP, and IcdP), most of which did not undergo significant biodegradation. The soil extract fractions were tested for genotoxicity using the DT40 chicken lymphocyte bioassay and developmental toxicity using the embryonic zebrafish (Danio rerio) bioassay. A statistically significant increase in genotoxicity was measured in the unfractionated soil extract, as well as in four polar soil extract fractions, postbioremediation (p soil extract fraction, postbioremediation (p soil extract fractions in embryonic zebrafish, both pre- and postbioremediation. The increased toxicity measured postbioremediation is not likely due to the 88 PAHs measured in this study (including quinones), because most were not present in the toxic polar fractions and/or because their concentrations did not increase postbioremediation. However, the increased toxicity measured postbioremediation is likely due to hydroxylated and carboxylated transformation products of the 3- and 4-ring PAHs (PHE, 1MPHE, 2MPHE, PRY, BaA, and FLA) that were most degraded.

  5. Developmental toxicity and oxidative stress induced by gamma irradiation in zebrafish embryos

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Miao; Hu, Nan; Ding, Dexin; Zhao, Weichao; Feng, Yongfu; Zhang, Hui; Li, Guangyue; Wang, Yongdong [University of South China, Key Discipline Laboratory for National Defense for Biotechnology in Uranium Mining and Hydrometallurgy, Hengyang, Hunan Province (China)

    2016-11-15

    This study aimed to evaluate the biological effects of gamma irradiation on zebrafish embryos. Different doses of gamma rays (0.01, 0.05, 0.1, 0.5 and 1 Gy) were used to irradiate zebrafish embryos at three developmental stages (stage 1, 6 h post-fertilization (hpf); stage 2, 12 hpf; stage three, 24 hpf), respectively. The survival, malformation and hatching rates of the zebrafish embryos were measured at the morphological endpoint of 96 hpf. The activities of superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx) and glutathione S-transferase (GST) were assayed. Morphology analysis showed that gamma irradiation inhibited hatching and induced developmental toxicity in a dose-dependent manner. Interestingly, after irradiation the malformation rate changed not only in a dose-dependent manner but also in a developmental stage-dependent manner, indicating that the zebrafish embryos at stage 1 were more sensitive to gamma rays than those at other stages. Biochemical analysis showed that gamma irradiation modulated the activities of antioxidant enzymes in a dose-dependent manner. A linear relationship was found between GPx activity and irradiation dose in 0.1-1 Gy group, and GPx was a suitable biomarker for gamma irradiation in the dose range from 0.1 to 1 Gy. Furthermore, the activities of SOD, CAT, GR and GPx of the zebrafish embryos at stage 3 were found to be much higher than those at other stages, indicating that the zebrafish embryos at stage 3 had a greater ability to protect against gamma rays than those at other stages, and thus the activities of antioxidant enzymes changed in a developmental stage-dependent manner. (orig.)

  6. Effect of allyl isothiocyanate on developmental toxicity in exposed Xenopus laevis embryos

    Directory of Open Access Journals (Sweden)

    John Russell Williams

    2015-01-01

    Full Text Available The pungent natural compound allyl isothiocyanate isolated from the seeds of Cruciferous (Brassica plants such as mustard is reported to exhibit numerous beneficial health-promoting antimicrobial, antifungal, anticarcinogenic, cardioprotective, and neuroprotective properties. Because it is also reported to damage DNA and is toxic to aquatic organisms, the objective of the present study was to determine whether it possesses teratogenic properties. The frog embryo teratogenesis assay-Xenopus (FETAX was used to determine the following measures of developmental toxicity of the allyl isothiocyanate: (a 96-h LC50, defined as the median concentration causing 50% embryo lethality; (b 96-h EC50, defined as the median concentration causing 50% malformations of the surviving embryos; and (c teratogenic malformation index (TI, equal to 96-h LC50/96-h EC50. The quantitative results and the photographs of embryos before and after exposure suggest that allyl isothiocyanate seems to exhibit moderate teratogenic properties. The results also indicate differences in the toxicity of allyl isothiocyanate toward exposed embryos observed in the present study compared to reported adverse effects of allyl isothiocyanate in fish, rodents, and humans. The significance of the results for food safety and possible approaches to protect against adverse effects of allyl isothiocyanate are discussed.

  7. Toxicological characteristics of endocrine-disrupting chemicals: developmental toxicity, carcinogenicity, and mutagenicity.

    Science.gov (United States)

    Choi, Seul Min; Yoo, Sun Dong; Lee, Byung Mu

    2004-01-01

    It is generally accepted that endocrine-disrupting chemicals (EDCs) play a role in a variety of adverse health effects in an intact organism or its progeny as a consequence of changes in the endocrine system. Primary toxic effects of EDCs were reported to be related to infertility, reduction in sperm count, and teratogenicity, but other important toxic effects of EDCs such as carcinogenicity and mutagenicity have also been demonstrated. The aim of the present study was to systematically analyze the toxicological characteristics of EDCs in pesticides, industrial chemicals, and metals. A comprehensive literature survey on the 48 EDCs classified by the Centers for Disease Control and Prevention (CDC) was conducted using a number of databases which included Medline, Toxline, and Toxnet. The survey results revealed that toxicological characteristics of EDCs were shown to produce developmental toxicity (81%), carcinogenicity (79%, when positive in at least one animal species; 48%, when classified based on IARC evaluation), mutagenicity (79%), immunotoxicity (52%), and neurotoxicity (50%). Regarding the hormone-modulating effects of the 48 EDCs, estrogenic effects were the most predominant in pesticides, while effects on thyroid hormone were found for heavy metals. EDCs showing estrogen-modulating effects were closely related to carcinogenicity or mutagenicity with a high degree of sensitivity. Systematic information on the toxicological characteristics of the EDCs will be useful for future research directions on EDCs, the development of new screening methods, legal regulation, and for investigations of their mechanism of action.

  8. Developmental toxicity and DNA damaging properties of silver nanoparticles in the catfish (Clarias gariepinus).

    Science.gov (United States)

    Sayed, Alaa El-Din H; Soliman, Hamdy A M

    2017-10-01

    Although, silver nanoparticles (AgNPs) are used in many different products, little information is known about their toxicity in tropical fish embryos. Therefore, this study evaluated the developmental toxicity of waterborne silver nanoparticles in embryos of Clarias gariepinus. Embryos were treated with (0, 25, 50, 75ng/L silver nanoparticles) in water up to 144h postfertilization stage (PFS). Results revealed various morphological malformations including notochord curvature and edema. The mortality rate, malformations, and DNA fragmentation in embryos exposed to silver nanoparticles increased in a dose- and embryonic stage-dependent manner. The total antioxidant capacity and the activity of catalase in embryos exposed to 25ng/L silver nanoparticles were decreased significantly while the total antioxidant capacity and the activity of catalase were insignificantly increased with increasing concentrations in the embryos from 24 to 144 h-PFS exposed to 50 and 75ng/L silver nanoparticles. Lipid peroxidation values showed fluctuations with doses of silver nanoparticles. Histopathological lesions including severely distorted and wrinkled notochord were observed. The current data propose that the toxicity of silver nanoparticles in C. gariepinus embryos is caused by oxidative stress and genotoxicity. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Oral 28-day and developmental toxicity studies of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate

    Science.gov (United States)

    Clarke, Kieran; Tchabanenko, Kirill; Pawlosky, Robert; Carter, Emma; Knight, Nicholas S.; Murray, Andrew J.; Cochlin, Lowri E.; King, M. Todd; Wong, Andrea W.; Roberts, Ashley; Robertson, Jeremy; Veech, Richard L.

    2013-01-01

    (R)-3-Hydroxybutyl (R)-3-hydroxybutyrate (ketone monoester) has been developed as an oral source of ketones, which may be utilized for energy. In a 28-day toxicity study, Crl:WI (Wistar) rats received diets containing, as 30% of the calories, ketone monoester (12 and 15 g/kg body weight/day for male and female rats, respectively). Control groups received either carbohydrate- or fat-based diets. Rats in the test group consumed less feed and gained less weight than control animals; similar findings have been documented in studies of ketogenic diets. Between-group differences were noted in selected hematology, coagulation, and serum chemistry parameters; however, values were within normal physiological ranges and/or were not accompanied by other changes indicative of toxicity. Upon gross and microscopic evaluation, there were no findings associated with the ketone monoester. In a developmental toxicity study, pregnant Crl:WI (Han) rats were administered 2 g/kg body weight/day ketone monoester or water (control) via gavage on days 6 through 20 of gestation. No Caesarean-sectioning or litter parameters were affected by the test article. The overall incidence of fetal alterations was higher in the test group; however, there were no specific alterations attributable to the test substance. The results of these studies support the safety of ketone monoester. PMID:22504461

  10. A comparison of potency differences among thyroid peroxidase (TPO) inhibitors to induce developmental toxicity and other thyroid gland-linked toxicities in humans and rats.

    Science.gov (United States)

    Motonaga, Kozo; Ota, Mika; Odawara, Kyoko; Saito, Shoji; Welsch, Frank

    2016-10-01

    The potencies of resorcinol, 6-propylthiouracil (PTU) and methimazole (MMI) for inducing developmental toxicity and neurotoxicity were compared in pregnant rats, regarded as valid model for human thyroid toxicity. Profound differences on maternal thyroid hormone levels (THs), maternal toxicity as well as developmental and neurotoxicity sequelae occurred. Resorcinol affected none of those end points. PTU and MMI caused significant effects. Therapy with either PTU or MMI during the first trimester of human pregnancy can cause reductions of maternal THs, accompanied by disruptions of prenatal development. Clinical MMI studies show sporadic evidence of teratogenic effects, with equivocal relation to thyroid peroxidase (TPO) inhibition. In recent decades no MMI associated prenatal toxicity has been reported, an outcome possibly related to carefully managed therapy. Orally administered resorcinol was rapidly absorbed, metabolized and excreted and was undetectable in the thyroid. In contrast, PTU or MMI accumulated. Resorcinol's potency to inhibit TPO was profoundly lower than that of PTU or MMI. Quantum chemical calculations may explain low resorcinol reactivity with TPO. Thus, distinctions in the target organ and the TPO inhibitory potency between these chemicals are likely contributing to different reductions of maternal THs levels and affecting the potency to cause developmental toxicity and neurotoxicity. Copyright © 2016. Published by Elsevier Inc.

  11. Health assessment of gasoline and fuel oxygenate vapors: developmental toxicity in rats.

    Science.gov (United States)

    Roberts, Linda G; Gray, Thomas M; Trimmer, Gary W; Parker, Robert M; Murray, F Jay; Schreiner, Ceinwen A; Clark, Charles R

    2014-11-01

    Gasoline-vapor condensate (BGVC) or condensed vapors from gasoline blended with methyl t-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 developmental toxicity in Sprague-Dawley rats exposed via inhalation on gestation days (GD) 5-20 for 6h/day at levels of 0 (control filtered air), 2000, 10,000, and 20,000mg/m(3). These exposure durations and levels substantially exceed typical consumer exposure during refueling (gasoline and gasoline blended with the ether or alcohol oxygenates. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Developmental toxic effects in suckling pups of rats from dams treated with betamethasone

    Directory of Open Access Journals (Sweden)

    M. K. Shindala

    2009-01-01

    Full Text Available Suckling pups of rats from dams treated with betamethasone 0.3, 0.6, 1.2 mg/kg, i.p. given once daily for 10 consecutive days (first nursing period demonstrated in a dose – dependent manner significant decreased (P<0.05 the percentage of survival of the pups to weaning, body weight, index of development, whereas brain, heart, kindey, lung,liver / body weight ratio significantly increased (P<0.05 as well as delays in physical maturation (ear opening, fur development, tooth eruption, eye opening in the pups. Swimming scores on postnatal day 9, 13, 15, 17, 20 was significantly decreased (P<0.05 in offspring from mothers treated with betamethasone 1.2 mg/kg, i.p. In conclusion, the results suggest that betamethasone induced developmental toxic effects in suckling pups exposed to its through the milk.

  13. Health assessment of gasoline and fuel oxygenate vapors: developmental toxicity in mice.

    Science.gov (United States)

    Roberts, L G; Gray, T M; Marr, M C; Tyl, R W; Trimmer, G W; Hoffman, G M; Murray, F J; Clark, C R; Schreiner, C A

    2014-11-01

    CD-1 mice were exposed to baseline gasoline vapor condensate (BGVC) alone or to vapors of gasoline blended with methyl tertiary butyl ether (G/MTBE). Inhalation exposures were 6h/d on GD 5-17 at levels of 0, 2000, 10,000, and 20,000mg/m(3). Dams were evaluated for evidence of maternal toxicity, and fetuses were weighed, sexed, and evaluated for external, visceral, and skeletal anomalies. Exposure to 20,000mg/m(3) of BGVC produced slight reductions in maternal body weight/gain and decreased fetal body weight. G/MTBE exposure did not produce statistically significant maternal or developmental effects; however, two uncommon ventral wall closure defects occurred: gastroschisis (1 fetus at 10,000mg/m(3)) and ectopia cordis (1 fetus at 2000mg/m(3); 2 fetuses/1 litter at 10,000mg/m(3)). A second study (G/MTBE-2) evaluated similar exposure levels on GD 5-16 and an additional group exposed to 30,000mg/m(3) from GD 5-10. An increased incidence of cleft palate was observed at 30,000mg/m(3) G/MTBE. No ectopia cordis occurred in the replicate study, but a single observation of gastroschisis was observed at 30,000mg/m(3). The no observed adverse effect levels for maternal/developmental toxicity in the BGVC study were 10,000/2000mg/m(3), 20,000/20,000 for the G/MTBE study, and 10,000/20,000 for the G/MTBE-2 study. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  14. Developmental toxicity of PAH mixtures in fish early life stages. Part II: adverse effects in Japanese medaka.

    Science.gov (United States)

    Le Bihanic, Florane; Clérandeau, Christelle; Le Menach, Karyn; Morin, Bénédicte; Budzinski, Hélène; Cousin, Xavier; Cachot, Jérôme

    2014-12-01

    In aquatic environments, polycyclic aromatic hydrocarbons (PAHs) mostly occur as complex mixtures, for which risk assessment remains problematic. To better understand the effects of PAH mixture toxicity on fish early life stages, this study compared the developmental toxicity of three PAH complex mixtures. These mixtures were extracted from a PAH-contaminated sediment (Seine estuary, France) and two oils (Arabian Light and Erika). For each fraction, artificial sediment was spiked at three different environmental concentrations roughly equivalent to 0.5, 4, and 10 μg total PAH g(-1) dw. Japanese medaka embryos were incubated on these PAH-spiked sediments throughout their development, right up until hatching. Several endpoints were recorded at different developmental stages, including acute endpoints, morphological abnormalities, larvae locomotion, and genotoxicity (comet and micronucleus assays). The three PAH fractions delayed hatching, induced developmental abnormalities, disrupted larvae swimming activity, and damaged DNA at environmental concentrations. Differences in toxicity levels, likely related to differences in PAH proportions, were highlighted between fractions. The Arabian Light and Erika petrogenic fractions, containing a high proportion of alkylated PAHs and low molecular weight PAHs, were more toxic to Japanese medaka early life stages than the pyrolytic fraction. This was not supported by the toxic equivalency approach, which appeared unsuitable for assessing the toxicity of the three PAH fractions to fish early life stages. This study highlights the potential risks posed by environmental mixtures of alkylated and low molecular weight PAHs to early stages of fish development.

  15. Morphology-based mammalian stem cell tests reveal potential developmental toxicity of donepezil.

    Science.gov (United States)

    Lau, Caroline G Y; Marikawa, Yusuke

    2014-11-01

    Various compounds, including therapeutic drugs, can adversely impact the survival and development of embryos in the uterus. Identification of such development-interfering agents is a challenging task, although multi-angle approaches--including the use of in vitro toxicology studies involving embryonic stem cells--should alleviate some of the current difficulties. In the present study, we utilized the in vitro elongation of embryoid bodies (EBs) derived from mouse embryonal carcinoma stem cell line P19C5 as a model of early embryological events, specifically that of gastrulation and axial patterning. From our study, we identified donepezil, a medication indicated for the management of Alzheimer's disease, as a potential developmental toxicant. The extent of P19C5 EB axial elongation was diminished by donepezil in a dose-dependent manner. Although donepezil is a known inhibitor of acetylcholinesterase, interference of elongation was not mediated through this enzyme. Quantitative reverse-transcriptase PCR revealed that donepezil altered the expression pattern of a specific set of developmental regulator genes involved in patterning along the anterior-posterior body axis. When tested in mouse whole embryo culture, donepezil caused morphological abnormalities including impaired somitogenesis. Donepezil also diminished elongation morphogenesis of EBs generated from human embryonic stem cells. These results suggest that donepezil interferes with axial elongation morphogenesis of early embryos by altering the expression pattern of regulators of axial development. © 2014 Wiley Periodicals, Inc.

  16. Developmental toxicity of arecoline, the major alkaloid in betel nuts, in zebrafish embryos.

    Science.gov (United States)

    Chang, Bei-En; Liao, Mei-Hui; Kuo, M Yen-Ping; Chen, Chi-Hsiang

    2004-01-01

    The major alkaloid in the betel nut, arecoline, has been reported to be potent in inducing developmentally toxic effects by generally lowering the embryo weight and retarding development of the embryo. This study examined the adverse effects of arecoline and tried to unravel the mechanism through the tools of molecular biology. Arecoline was administered to zebrafish embryos by incubation at concentrations ranging from 0.01-0.04% (wt/vol) and lethality and morphological changes were recorded. The expression of genes was analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and whole-mount in situ hybridization. In addition, the protective effects of several antioxidants were tested. The survival rate of treated embryos during a three-day incubation significantly declined as the arecoline concentration increased. Treated embryos showed general growth retardation and lower rate of heartbeat. When examined at the 24-hr stage, the relative amounts of transcripts of p53, p21, and cyclin D1, and the spatial expression patterns of these genes in treated groups, were comparable to those of the untreated early stages of embryos. Finally, the addition of glutathione (GSH) or its precursor, N-acetyl-L-cysteine (NAC), ameliorated the developmental retardation of embryos by arecoline. Arecoline-treated embryos exhibited general developmental retardation in a dose-dependent manner. Our results from RT-PCR, in situ hybridization, and antioxidant-protection experiments indicate that the mechanism underlying growth retardation by arecoline in embryos is predominantly due to a general cytotoxic effect induced by depletion of intracellular thiols. Copyright 2003 Wiley-Liss, Inc.

  17. Developmental toxicity of CdTe QDs in zebrafish embryos and larvae

    Energy Technology Data Exchange (ETDEWEB)

    Duan, Junchao; Yu, Yongbo [School of Public Health, Capital Medical University (China); Li, Yang [School of Public Health, Jilin University (China); Yu, Yang; Li, Yanbo; Huang, Peili; Zhou, Xianqing [School of Public Health, Capital Medical University (China); Peng, Shuangqing, E-mail: pengsq@hotmail.com [Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Evaluation and Research Centre for Toxicology (China); Sun, Zhiwei, E-mail: zwsun@ccmu.edu.cn [School of Public Health, Capital Medical University (China)

    2013-07-15

    Quantum dots (QDs) have widely been used in biomedical and biotechnological applications. However, few studies focus on the assessing toxicity of QDs exposure in vivo. In this study, zebrafish embryos were treated with CdTe QDs (4 nm) during 4-96 h post-fertilization (hpf). Mortality, hatching rate, malformation, heart rate, and QDs uptake were detected. We also measured the larval behavior to analyze whether QDs had persistent effects on larvae locomotor activity at 144 hpf. The results showed that as the exposure dosages increased, the hatching rate and heart rate of zebrafish embryos were decreased, while the mortality increased. Exposure to QDs caused embryonic malformations, including head malformation, pericardial edema, yolk sac edema, bent spine, and yolk not depleted. QDs fluorescence was mainly localized in the intestines region. The larval behavior testing showed that the total swimming distance was decreased in a dose-dependent manner. The lowest dose (2.5 nM QDs) produced substantial hyperactivity while the higher doses groups (5, 10, and 20 nM QDs) elicited remarkably hypoactivity in dark periods. In summary, the data of this article indicated that QDs caused embryonic developmental toxicity, resulted in persistent effects on larval behavior.

  18. Computational Approach using Mouse Embryonic Stem Cells to Define a Mechanistic Applicability Domain for Prenatal Developmental Toxicity

    Science.gov (United States)

    Identification of mechanisms responsible for adverse developmental effects is the first step in creating predictive toxicity models. Identification of putative mechanisms was performed by co-analyzing three datasets for the effects of ToxCast phase Ia and II chemicals: 1.In vitro...

  19. Developing predictions of in vivo developmental toxicity of ToxCast chemicals using mouse embryonic stem cells.

    Science.gov (United States)

    Developing predictions of in vivo developmental toxicity of ToxCast chemicals using mouse embryonic stem cells S. Hunter, M. Rosen, M. Hoopes, H. Nichols, S. Jeffay, K. Chandler1, Integrated Systems Toxicology Division, National Health and Environmental Effects Research Labor...

  20. Computational Modeling and Simulation of Developmental Toxicity. What can we learn from a virtual embryo? (FDA-CFSAN workshop)

    Science.gov (United States)

    SYNOPSIS: The question of how tissues and organs are shaped during development is crucial for understanding human birth defects. Data from high-throughput screening assays on human stem cells may be utilized predict developmental toxicity with reasonable accuracy. Other types of ...

  1. Use of physiologically based kinetic modeling-facilitated reverse dosimetry of in vitro toxicity data for prediction of in vivo developmental toxicity of tebuconazole in rats.

    Science.gov (United States)

    Li, Hequn; Zhang, Mengying; Vervoort, Jacques; Rietjens, Ivonne M C M; van Ravenzwaay, Bennard; Louisse, Jochem

    2017-01-15

    Toxicological hazard and risk assessment largely rely on animal testing. For economic and ethical reasons, the development and validation of reliable alternative methods for these animal studies, such as in vitro assays, are urgently needed. In vitro concentration-response curves, however, need to be translated into in vivo dose-response curves for risk assessment purposes. In the present study, we translated in vitro concentration-response data of the antifungal compound tebuconazole, obtained in the ES-D3 cell differentiation assay, into predicted in vivo dose-response data for developmental toxicity using physiologically based kinetic (PBK) modeling-facilitated reverse dosimetry. Using the predicted in vivo dose-response data BMD(L)10 values for developmental toxicity in rat were calculated and compared with NOAEL values for developmental toxicity data in rats as reported in the literature. The results show that the BMDL10 value from predicted dose-response data are a reasonable approximation of the NOAEL values (ca. 3-fold difference). It is concluded that PBK modeling-facilitated reverse dosimetry of in vitro toxicity data is a promising tool to predict in vivo dose-response curves and may have the potential to define a point of departure for deriving safe exposure limits in risk assessment. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  2. The role of apoptosis in MCLR-induced developmental toxicity in zebrafish embryos

    Energy Technology Data Exchange (ETDEWEB)

    Zeng, Cheng [College of Fisheries, Huazhong Agricultural University, Wuhan 430070 (China); Sun, Hong [Hubei Maternal and Child Health Hospital, Wuhan 430070 (China); Xie, Ping [Donghu Experimental Station of Lake Ecosystems, State Key Laboratory for Freshwater Ecology and Biotechnology of China, Institute of Hydrobiology, The Chinese Academy of Sciences, Wuhan 430072 (China); Wang, Jianghua; Zhang, Guirong; Chen, Nan [College of Fisheries, Huazhong Agricultural University, Wuhan 430070 (China); Yan, Wei, E-mail: Yanwei75126@163.com [Institute of Agricultural Quality Standards and Testing Technology, Hubei Academy of Agricultural Sciences, Wuhan 430064 (China); Li, Guangyu, E-mail: ligy2001@163.com [College of Fisheries, Huazhong Agricultural University, Wuhan 430070 (China); Freshwater Aquaculture Collaborative Innovation Center of Hubei Province, Wuhan 430070 (China)

    2014-04-01

    Highlights: • MCLR-induced apoptosis in the heart of developing embryos leads to the growth delay in zebrafish. • MCLR-triggered apoptosis might be induced by ROS. • P53–Bax–Bcl-2 and caspase-dependent apoptotic pathway contribute greatly to MCLR-induced apoptosis. Abstract: We previously demonstrated that cyanobacteria-derived microcystin–leucine–arginine (MCLR) is able to induce developing toxicity, such as malformation, growth delay and also decreased heart rates in zebrafish embryos. However, the molecular mechanisms by which MCLR induces its toxicity during the development of zebrafish remain largely unknown. Here, we evaluate the role of apoptosis in MCLR-induced developmental toxicity. Zebrafish embryos were exposed to various concentrations of MCLR (0, 0.2, 0.5, 2, and 5.0 mg L⁻¹ for 96 h, at which time reactive oxygen species (ROS) was significantly induced in the 2 and 5.0 mg L⁻¹ MCLR exposure groups. Acridine orange (AO) staining and terminal deoxynucleotide transferase-mediated deoxy-UTP nick end labelling (TUNEL) assay showed that MCLR exposure resulted in cell apoptosis. To test the apoptotic pathway, the expression pattern of several apoptotic-related genes was examined for the level of enzyme activity, gene and protein expression, respectively. The overall results demonstrate that MCLR induced ROS which consequently triggered apoptosis in the heart of developing zebrafish embryos. Our results also indicate that the p53–Bax–Bcl-2 pathway and the caspase-dependent apoptotic pathway play major roles in MCLR-induced apoptosis in the developing embryos.

  3. Identifying developmental toxicity pathways for a subset of ToxCast chemicals using human embryonic stem cells and metabolomics

    Energy Technology Data Exchange (ETDEWEB)

    Kleinstreuer, N.C., E-mail: kleinstreuer.nicole@epa.gov [NCCT, US EPA, RTP, NC 27711 (United States); Smith, A.M.; West, P.R.; Conard, K.R.; Fontaine, B.R. [Stemina Biomarker Discovery, Inc., Madison, WI 53719 (United States); Weir-Hauptman, A.M. [Covance, Inc., Madison, WI 53704 (United States); Palmer, J.A. [Stemina Biomarker Discovery, Inc., Madison, WI 53719 (United States); Knudsen, T.B.; Dix, D.J. [NCCT, US EPA, RTP, NC 27711 (United States); Donley, E.L.R. [Stemina Biomarker Discovery, Inc., Madison, WI 53719 (United States); Cezar, G.G. [Stemina Biomarker Discovery, Inc., Madison, WI 53719 (United States); University of Wisconsin-Madison, Madison, WI 53706 (United States)

    2011-11-15

    Metabolomics analysis was performed on the supernatant of human embryonic stem (hES) cell cultures exposed to a blinded subset of 11 chemicals selected from the chemical library of EPA's ToxCast Trade-Mark-Sign chemical screening and prioritization research project. Metabolites from hES cultures were evaluated for known and novel signatures that may be indicative of developmental toxicity. Significant fold changes in endogenous metabolites were detected for 83 putatively annotated mass features in response to the subset of ToxCast chemicals. The annotations were mapped to specific human metabolic pathways. This revealed strong effects on pathways for nicotinate and nicotinamide metabolism, pantothenate and CoA biosynthesis, glutathione metabolism, and arginine and proline metabolism pathways. Predictivity for adverse outcomes in mammalian prenatal developmental toxicity studies used ToxRefDB and other sources of information, including Stemina Biomarker Discovery's predictive DevTox Registered-Sign model trained on 23 pharmaceutical agents of known developmental toxicity and differing potency. The model initially predicted developmental toxicity from the blinded ToxCast compounds in concordance with animal data with 73% accuracy. Retraining the model with data from the unblinded test compounds at one concentration level increased the predictive accuracy for the remaining concentrations to 83%. These preliminary results on a 11-chemical subset of the ToxCast chemical library indicate that metabolomics analysis of the hES secretome provides information valuable for predictive modeling and mechanistic understanding of mammalian developmental toxicity. -- Highlights: Black-Right-Pointing-Pointer We tested 11 environmental compounds in a hESC metabolomics platform. Black-Right-Pointing-Pointer Significant changes in secreted small molecule metabolites were observed. Black-Right-Pointing-Pointer Perturbed mass features map to pathways critical for normal

  4. Relative developmental toxicity of short-chain chlorinated paraffins in Zebrafish (Danio rerio) embryos.

    Science.gov (United States)

    Liu, Lihua; Li, Yifan; Coelhan, Mehmet; Chan, Hing Man; Ma, Wanli; Liu, Liyan

    2016-12-01

    Short-chain chlorinated paraffins (SCCPs) are ubiquitous in the environment and might cause adverse environmental and human health effects. Little is known about the relative toxicity of different SCCP compounds especially during development. The objective of this study was to characterize and compare effects of seven SCCP groups at environmentally relevant levels, using a zebrafish (Danio rerio) model. Observations on malformation, survival rates at 96 h post fertilization (hpf), and hatching rates at 72 hpf indicated that the C 10- groups (C 10 H 18 Cl 4 , 1,2,5,6,9,10-C 10 H 16 Cl 6 and C 10 H 15 Cl 7 ) were more toxic than the C 12- groups (C 12 H 22 Cl 4 , C 12 H 19 Cl 7 and 1,1,1,3,10,12,12,12-C 12 H 18 Cl 8 ) and Cereclor 63L. The C 10- groups were also more potent than C 12- groups and Cereclor 63L in decreasing thyroid hormone levels. Among the three compounds within the C 10- group, the compounds with less chlorine content had stronger effects on sub-lethal malformations but less effects on triiodothyronine (T3) and tetraiodothyronine (T4). Only C 10 H 18 Cl 4 significantly decreased the mRNA expression of tyr, ttr, dio2 and dio3 at a dose-dependent manner suggesting that the specific mode of actions differ with different congeners. The mechanisms of disruption of thyroid status by different SCCPs could be different. C 10 H 18 Cl 4 might inhibit T3 production through the inhibition effect on dio2. These results indicate that SCCP exposure could alter gene expression in the hypothalamic-pituitary-thyroid (HPT) axis and thyroid hormone levels. The mechanisms of disruption of thyroid status by different SCCPs could be different. Our results on the relative developmental toxicities of SCCPs will be useful to reach a better understanding of SCCP toxicity supporting environmental risk evaluation and regulation and used as a guidance for environmental monitoring of SCCPs in the future. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Developmental Toxicant Exposure Is Associated with Transgenerational Adenomyosis in a Murine Model.

    Science.gov (United States)

    Bruner-Tran, Kaylon L; Duleba, Antoni J; Taylor, Hugh S; Osteen, Kevin G

    2016-10-01

    The common environmental toxicant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD or, commonly, dioxin) is a known endocrine disruptor that has been linked to the development of endometriosis in experimental models. Using a murine model, we previously demonstrated that in utero TCDD exposure promotes the transgenerational development of an "endometriosis-like" uterine phenotype consisting of reduced responsiveness to progesterone, subfertility and an increased risk of preterm birth. Since adenomyosis is frequently observed as a comorbidity in women with endometriosis, herein, we sought to determine the incidence of adenomyosis in non-pregnant mice with a history of direct or indirect TCDD exposure. Using histologic assessment and immunohistochemical staining, we analyzed murine uteri for adenomyosis, microvessel density and expression of estrogen receptors alpha and beta (ESR1 and ESR2). Our studies revealed that unexposed control mice did not exhibit adenomyosis while this disease was frequently observed in mice with a history of early life TCDD exposure. A transgenerational impact of developmental TCDD exposure was demonstrated since a subset of mice with only an indirect exposure (F3) also exhibited adenomyosis. Microvessel density within the uterus was significantly higher in all groups of TCDD exposed mice compared to control animals, with density correlated to the severity of disease. Both ESR1 and ESR2 protein exhibited alterations in expression in experimental mice compared to controls. Similar to women with endometriosis, we observed a significant reduction in the ratio of Esr1/Esr2 mRNA in all F1 mice compared to controls. Although this retrospective study was not designed to specifically address mechanisms associated with development of adenomyosis, our data suggest that developmental TCDD exposure permanently alters adult steroid responses which may contribute to the transgenerational development of adenomyosis. Copyright 2016 by The Society for the Study of

  6. 3D Visualization of Developmental Toxicity of 2,4,6-Trinitrotoluene in Zebrafish Embryogenesis Using Light-Sheet Microscopy

    Directory of Open Access Journals (Sweden)

    Juneyong Eum

    2016-11-01

    Full Text Available Environmental contamination by trinitrotoluene is of global concern due to its widespread use in military ordnance and commercial explosives. Despite known long-term persistence in groundwater and soil, the toxicological profile of trinitrotoluene and other explosive wastes have not been systematically measured using in vivo biological assays. Zebrafish embryos are ideal model vertebrates for high-throughput toxicity screening and live in vivo imaging due to their small size and transparency during embryogenesis. Here, we used Single Plane Illumination Microscopy (SPIM/light sheet microscopy to assess the developmental toxicity of explosive-contaminated water in zebrafish embryos and report 2,4,6-trinitrotoluene-associated developmental abnormalities, including defects in heart formation and circulation, in 3D. Levels of apoptotic cell death were higher in the actively developing tissues of trinitrotoluene-treated embryos than controls. Live 3D imaging of heart tube development at cellular resolution by light-sheet microscopy revealed trinitrotoluene-associated cardiac toxicity, including hypoplastic heart chamber formation and cardiac looping defects, while the real time PCR (polymerase chain reaction quantitatively measured the molecular changes in the heart and blood development supporting the developmental defects at the molecular level. Identification of cellular toxicity in zebrafish using the state-of-the-art 3D imaging system could form the basis of a sensitive biosensor for environmental contaminants and be further valued by combining it with molecular analysis.

  7. 3D Visualization of Developmental Toxicity of 2,4,6-Trinitrotoluene in Zebrafish Embryogenesis Using Light-Sheet Microscopy.

    Science.gov (United States)

    Eum, Juneyong; Kwak, Jina; Kim, Hee Joung; Ki, Seoyoung; Lee, Kooyeon; Raslan, Ahmed A; Park, Ok Kyu; Chowdhury, Md Ashraf Uddin; Her, Song; Kee, Yun; Kwon, Seung-Hae; Hwang, Byung Joon

    2016-11-17

    Environmental contamination by trinitrotoluene is of global concern due to its widespread use in military ordnance and commercial explosives. Despite known long-term persistence in groundwater and soil, the toxicological profile of trinitrotoluene and other explosive wastes have not been systematically measured using in vivo biological assays. Zebrafish embryos are ideal model vertebrates for high-throughput toxicity screening and live in vivo imaging due to their small size and transparency during embryogenesis. Here, we used Single Plane Illumination Microscopy (SPIM)/light sheet microscopy to assess the developmental toxicity of explosive-contaminated water in zebrafish embryos and report 2,4,6-trinitrotoluene-associated developmental abnormalities, including defects in heart formation and circulation, in 3D. Levels of apoptotic cell death were higher in the actively developing tissues of trinitrotoluene-treated embryos than controls. Live 3D imaging of heart tube development at cellular resolution by light-sheet microscopy revealed trinitrotoluene-associated cardiac toxicity, including hypoplastic heart chamber formation and cardiac looping defects, while the real time PCR (polymerase chain reaction) quantitatively measured the molecular changes in the heart and blood development supporting the developmental defects at the molecular level. Identification of cellular toxicity in zebrafish using the state-of-the-art 3D imaging system could form the basis of a sensitive biosensor for environmental contaminants and be further valued by combining it with molecular analysis.

  8. Current challenges in toxicological research: Evaluation of the developmental toxicity of manufactured nanomaterials

    Directory of Open Access Journals (Sweden)

    Isabella Fernandes Delgado

    2013-11-01

    Full Text Available Nanomaterials are particles or fibers with at least one of the three dimensions in the size range between 1 and 100 nm. Owing to unique physical and chemical properties, na-no-sized particles (NPs have a variety of industrial uses and are more and more preva-lent in everyday life. However, despite the growing number of nanotechnology products, health risk assessment of NPs is in its early infancy. The potential adverse effects of NPs on prenatal development are even less well investigated. This article summarizes the literature on the developmental toxicity of NPs. Generally, the studies are very recent and include ex vivo experiments using non-mammalian species, in vitro assays (mouse embryonic stem cell test and in vivo investigations using rodents. Very little has been published on the effects of NPs on the development and function of the human placenta or on the transference of NPs into the human embryo and fetus. Some limitations of using ex vivo and in vitro assays to predict adverse effects of NPs on human prenatal development are discussed in this overview. The structural and functional differences between the rodent and human placenta in early pregnancy and their possible relevance to the transplacental passage of NPs are also commented upon.

  9. Nanotoxicology using the sea anemone Nematostella vectensis: from developmental toxicity to genotoxicology.

    Science.gov (United States)

    Ambrosone, Alfredo; Marchesano, Valentina; Mazzarella, Veronica; Tortiglione, Claudia

    2014-08-01

    Concomitant with the fast-growing advances in the synthesis and engineering of colloidal nanocrystals, an urgent evaluation of their toxicity on human beings and environment is strongly encouraged by public health organisations. Despite the in vitro approaches employed for toxicological screening of hazardous compounds, the use of simple and cost-effective living organisms may enormously contribute to solve unanswered questions related to embryotoxic and teratogenic effects of nanomaterials. Here, the sea anemone Nematostella vectensis (Cnidaria, Anthozoa) is presented as a novel model organism to profile bio/non-bio interactions and to show a comprehensive toxicological analysis performed on embryos, larvae and adults treated with fluorescent cadmium-based nanocrystals. Spanning from in vivo biodistribution to molecular investigations, different behaviours and effects depending on the composition and surface coatings are showed. Rod-shaped cadmium selenide/cadmium sulfide (CdSe/CdS) nanocrystals resulted in excellent imaging probes to track N. vectensis development with negligible adverse effects, while spherical CdTe nanocrystals severely impaired embryogenesis, resulting in aberrant phenotypes and deregulation of developmental genes, which raise severe worries for a safe use of this type of nanoparticles for human purposes and environmental contamination.

  10. Fluoride-elicited developmental testicular toxicity in rats: Roles of endoplasmic reticulum stress and inflammatory response

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Shun [Department of Environmental Health and MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Hangkong Road 13, Wuhan 430030, Hubei (China); Jiang, Chunyang [Department of Environmental Health and MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Hangkong Road 13, Wuhan 430030, Hubei (China); Department of Thoracic Surgery, Tianjin Union Medicine Centre, 190 Jieyuan Road, Hongqiao District, Tianjin 300121, Tianjin (China); Liu, Hongliang [Tianjin Center for Disease Control and Prevention, Huayue Road 6, Hedong Region, Tianjin 300011, Tianjin (China); Guan, Zhizhong [Department of Pathology, Guiyang Medical College, Guiyang 550004, Guizhou (China); Zeng, Qiang [Tianjin Center for Disease Control and Prevention, Huayue Road 6, Hedong Region, Tianjin 300011, Tianjin (China); Zhang, Cheng; Lei, Rongrong; Xia, Tao; Gao, Hui; Yang, Lu; Chen, Yihu; Wu, Xue; Zhang, Xiaofei [Department of Environmental Health and MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Hangkong Road 13, Wuhan 430030, Hubei (China); Cui, Yushan; Yu, Linyu [Tianjin Center for Disease Control and Prevention, Huayue Road 6, Hedong Region, Tianjin 300011, Tianjin (China); Wang, Zhenglun [Department of Environmental Health and MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Hangkong Road 13, Wuhan 430030, Hubei (China); Wang, Aiguo, E-mail: wangaiguo@mails.tjmu.edu.cn [Department of Environmental Health and MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Hangkong Road 13, Wuhan 430030, Hubei (China)

    2013-09-01

    Long-term excessive fluoride intake is known to be toxic and can damage a variety of organs and tissues in the human body. However, the molecular mechanisms underlying fluoride-induced male reproductive toxicity are not well understood. In this study, we used a rat model to simulate the situations of human exposure and aimed to evaluate the roles of endoplasmic reticulum (ER) stress and inflammatory response in fluoride-induced testicular injury. Sprague–Dawley rats were administered with sodium fluoride (NaF) at 25, 50 and 100 mg/L via drinking water from pre-pregnancy to gestation, birth and finally to post-puberty. And then the testes of male offspring were studied at 8 weeks of age. Our results demonstrated that fluoride treatment increased MDA accumulation, decreased SOD activity, and enhanced germ cell apoptosis. In addition, fluoride elevated mRNA and protein levels of glucose-regulated protein 78 (GRP78), inositol requiring ER-to-nucleus signal kinase 1 (IRE1), and C/EBP homologous protein (CHOP), indicating activation of ER stress signaling. Furthermore, fluoride also induced testicular inflammation, as manifested by gene up-regulation of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), in a nuclear factor-κB (NF-κB)-dependent manner. These were associated with marked histopathological lesions including injury of spermatogonia, decrease of spermatocytes and absence of elongated spermatids, as well as severe ultrastructural abnormalities in testes. Taken together, our results provide compelling evidence that ER stress and inflammation would be novel and significant mechanisms responsible for fluoride-induced disturbance of spermatogenesis and germ cell loss in addition to oxidative stress. - Highlights: • We used a rat model to simulate the situations of human fluoride (F) exposure. • Developmental F exposure induces testicular damage related with oxidative stress.

  11. Target organ specific activity of drosophila MRP (ABCC1) moderates developmental toxicity of methylmercury.

    Science.gov (United States)

    Prince, Lisa; Korbas, Malgorzata; Davidson, Philip; Broberg, Karin; Rand, Matthew Dearborn

    2014-08-01

    Methylmercury (MeHg) is a ubiquitous and persistent neurotoxin that poses a risk to human health. Although the mechanisms of MeHg toxicity are not fully understood, factors that contribute to susceptibility are even less well known. Studies of human gene polymorphisms have identified a potential role for the multidrug resistance-like protein (MRP/ABCC) family, ATP-dependent transporters, in MeHg susceptibility. MRP transporters have been shown to be important for MeHg excretion in adult mouse models, but their role in moderating MeHg toxicity during development has not been explored. We therefore investigated effects of manipulating expression levels of MRP using a Drosophila development assay. Drosophila MRP (dMRP) is homologous to human MRP1-4 (ABCC1-4), sharing 50% identity and 67% similarity with MRP1. A greater susceptibility to MeHg is seen in dMRP mutant flies, demonstrated by reduced rates of eclosion on MeHg-containing food. Furthermore, targeted knockdown of dMRP expression using GAL4>UAS RNAi methods demonstrates a tissue-specific function for dMRP in gut, Malpighian tubules, and the nervous system in moderating developmental susceptibility to MeHg. Using X-ray synchrotron fluorescence imaging, these same tissues were also identified as the highest Hg-accumulating tissues in fly larvae. Moreover, higher levels of Hg are seen in dMRP mutant larvae compared with a control strain fed an equivalent dose of MeHg. In sum, these data demonstrate that dMRP expression, both globally and within Hg-targeted organs, has a profound effect on susceptibility to MeHg in developing flies. Our findings point to a potentially novel and specific role for dMRP in neurons in the protection against MeHg. Finally, this experimental system provides a tractable model to evaluate human polymorphic variants of MRP and other gene variants relevant to genetic studies of mercury-exposed populations. © The Author 2014. Published by Oxford University Press on behalf of the Society of

  12. Developmental Toxicity Assay for Food Additive Tartrazine Using Zebrafish ( Danio rerio) Embryo Cultures.

    Science.gov (United States)

    Joshi, Vani; Katti, Pancharatna

    Tartrazine (TTZ) is an azo dye used as a colorant in food products, drugs, and cosmetics. The present study evaluates the impacts of TTZ on embryonic development of zebrafish ( Danio rerio). Laboratory-raised D. rerio embryos (n = 20/concentration) were exposed to graded dilutions of TTZ (0, 0.1, 1, 2, 3, 4, 5, 10, 20, 30, 40, 50, 75, and 100 mM) from gastrulation stage (5.25 hours postfertilization [hpf]) until hatching and developmental trajectory was traced up to day 7. The no observed effect concentration (NOEC), median lethal concentration (LC50), median effective concentration (EC50), and teratogenic index (TI) were calculated. Exposure of embryos to < 10 mM TTZ had no effects; 20 to 30 mM TTZ caused tail bending, cardiac and yolk sac edema in 50% of larvae; in 30 to 50 mM TTZ-exposed embryos the heart rates declined along with the above mentioned deformities, causing mortality within 96 to 144 hpf; development ceased completely at 75 to 100 mM concentration. The NOEC and LC50 were recorded at 5 and 29.4 mM dose, respectively. The EC50 values for heart rate, cardiac edema, tail bending, and hatching success were at 59.60, 53.81, 98.28, and 58.97 mM with TI quotient 0.49, 0.54, 0.29, and 0.49, respectively. We conclude that TTZ is not embryo toxic/teratogenic for zebrafish embryos up to a dose level of 10 mM concentration.

  13. Initial evaluation of developmental malformation as an end point in mixture toxicity hazard assessment for aquatic vertebrates

    Energy Technology Data Exchange (ETDEWEB)

    Dawson, D.A.; Wilke, T.S. (Department of Animal Science, College of Veterinary Medicine, University of Tennessee, Knoxville (USA))

    1991-04-01

    The joint toxic action of three binary mixtures was determined for the embryo malformation endpoint of the aquatic FETAX (frog embryo teratogenesis assay: Xenopus) test system. Osteolathyrogenic compounds and short-chain carboxylic acids, representing separate, distinct modes of action for induction of malformation, were selected for testing in 96-hr, static-renewal tests. Three mixtures were tested for each combination, with each combination being tested on three separate occasions. Using toxic unit analysis, the combination of osteolathyrogens and the combination of carboxylic acids produced strictly additive (concentration addition) rates of malformation, while the combination of an osteolathyrogen and a carboxylic acid was less-than-additive (response addition) for induction of malformation. Therefore, developmental malformation may have value as an endpoint in mixture toxicity hazard assessment.

  14. Extended evaluation on the ES-D3 cell differentiation assay combined with the BeWo transport model, to predict relative developmental toxicity of triazole compounds.

    Science.gov (United States)

    Li, Hequn; Flick, Burkhard; Rietjens, Ivonne M C M; Louisse, Jochem; Schneider, Steffen; van Ravenzwaay, Bennard

    2016-05-01

    The mouse embryonic stem D3 (ES-D3) cell differentiation assay is based on the morphometric measurement of cardiomyocyte differentiation and is a promising tool to detect developmental toxicity of compounds. The BeWo transport model, consisting of BeWo b30 cells grown on transwell inserts and mimicking the placental barrier, is useful to determine relative placental transport velocities of compounds. We have previously demonstrated the usefulness of the ES-D3 cell differentiation assay in combination with the in vitro BeWo transport model to predict the relative in vivo developmental toxicity potencies of a set of reference azole compounds. To further evaluate this combined in vitro toxicokinetic and toxicodynamic approach, we combined ES-D3 cell differentiation data of six novel triazoles with relative transport rates obtained from the BeWo model and compared the obtained ranking to the developmental toxicity ranking as derived from in vivo data. The data show that the combined in vitro approach provided a correct prediction for in vivo developmental toxicity, whereas the ES-D3 cell differentiation assay as stand-alone did not. In conclusion, we have validated the combined in vitro approach for developmental toxicity, which we have previously developed with a set of reference azoles, for a set of six novel triazoles. We suggest that this combined model, which takes both toxicodynamic and toxicokinetic aspects into account, should be further validated for other chemical classes of developmental toxicants.

  15. Toxicity evaluation of petroleum blending streams: reproductive and developmental effects of light catalytic cracked naphtha distillate in rats.

    Science.gov (United States)

    Schreiner, C; Bui, Q; Breglia, R; Burnett, D; Koschier, F; Podhasky, P; Lapadula, E; White, R; Schroeder, R E

    1999-11-26

    A distillate of light catalytic cracked naphtha (CAS number 64741-55-5, LCCN-D), administered by inhalation, was tested for reproductive and developmental toxicity in Sprague-Dawley rats, following a modified OECD Guideline 421, Reproductive/Developmental Toxicity Screening Protocol. LCCN-D was administered as a vapor, 6 h/d, 7 d/wk at target concentrations of 0, 750, 2500 or 7500 ppm to female rats for approximately 7 wk from 2 wk prior to mating, during mating through gestational d 19, and to males beginning 2 wk prior to mating for 8 consecutive weeks. Dams and litters were sacrificed on postnatal d 4, and males were sacrificed within the following week. Parental systemic effects observed at the 7500 ppm exposure level were increased kidney weights and relative liver weights in males and increased spleen weights in high-dose females. Livers and spleens from rats in the high-dose group were normal in appearance at necropsy. IncreaSed kidney weights in high-dose males were indicative of male-rat-specific light hydrocarbon nephropathy. No test-related microscopic changes were observed in the reproductive organs or nasal turbinate tissues of either sex. Reproductive performance was unaffected by treatment with LCCN-D. Fertility index was > or =90% in all dose groups. There were no exposure-related differences in implantation sites and live pups per litter, and no gross abnormalities were observed. Pups born from treated dams showed comparable body weights and weight gains to controls. The viability index on postpartum d 4 was > or =97%; the high-dose group had more male than female pups at birth and at d 4 postpartum. Under the conditions of this study, the no-observable-adverse-effect level (NOAEL) for exposure to light catalytic cracked naphtha distillate for parental toxicity was 2500 ppm and the NOAEL for reproductive performance and developmental toxicity was 7500 ppm.

  16. Developmental toxicity study in rats and rabbits administered an emulsion containing medium chain triglycerides as an alternative caloric source.

    Science.gov (United States)

    Henwood, S; Wilson, D; White, R; Trimbo, S

    1997-12-01

    Triglyceride-containing lipid emulsions have been designed as caloric sources that can be administered intravenously to patients that cannot meet their nutritional needs by conventional parenteral therapies. In their study, we evaluate the developmental toxicity of a 20% lipid emulsion that contains a 3:1 ratio of medium chain triglyceride (MCT) to one long chain containing lipid emulsion (LCT). This emulsion was administered by intravenous infusion to rats and rabbits at dosages of 1 and 4.28 g lipid/kg body weight (g lipid/kg) at dose volumes of 5 and 21.4 mL/kg, respectively, once daily during organogenesis to assess the potential developmental toxicity of the test article. The control group received 0.9% saline at a dose volume of 21.4 mL/kg. Animals were observed for clinical signs of toxicity and adverse effects on body weights and feed consumption. On Day 20 (rats) or Day 29 (rabbits), females were necropsied and examined for maternal and embryo/fetal toxicity. Fetuses were removed, weighed, and examined for external, soft tissue, and skeletal abnormalities. Dosages of 4.28 g lipid/kg resulted in lower feed consumption for rats and rabbits, an expected finding based on the high-caloric nature of the test article. Potentially test article-related gross necropsy findings, including enlarged lymph nodes and spleen, small thymus, and enlarged renal pelvis, for rats given 4.28 g lipid/kg were present at a low incidence. There were no adverse effects on fetal parameters for rats even in the presence of some maternal toxicity. However, embryo and fetal toxicity (i.e., resorptions) and skeletal abnormalities were present for rabbits given 4.28 g lipid/kg. Under the conditions of this study, the no-observable-effect level for developmental toxicity was greater than or equal to 4.28 g lipid/kg for rats and greater than or equal to 1 g lipid/kg but less than 4.28 g lipid/kg for rabbits.

  17. Evaluation of the developmental toxicity of formamide in New Zealand white rabbits.

    Science.gov (United States)

    George, Julia D; Price, Catherine J; Marr, Melissa C; Myers, Christina B; Jahnke, Gloria D

    2002-09-01

    -live implants per litter in the 140-mg/kg/day group were higher than maximum historical values, suggesting an increase in late gestational deaths in the surviving high-dose animals. Formamide decreased the mean number of live fetuses per litter at the high dose to 66% of the control value. Mean fetal body weight per litter for males and the sexes combined was significantly decreased at the high dose; mean female fetal body weight was also decreased, although the difference did not reach statistical significance. There was no effect of treatment on the incidence of external, visceral, or skeletal malformations or variations in animals surviving to scheduled necropsy. In summary, the no-observed-adverse-effect level (NOAEL) for maternal toxicity was 70 mg/kg/day and the lowest-observed-adverse-effect level (LOAEL) was 140 mg/kg/day under the conditions of this study. Similarly, the NOAEL for developmental toxicity was 70 mg/kg/day and the LOAEL was 140 mg/kg/day.

  18. Synergistic interaction of glycoalkaloids alpha-chaconine and alpha-solanine on developmental toxicity in Xenopus embryos.

    Science.gov (United States)

    Rayburn, J R; Friedman, M; Bantle, J A

    1995-12-01

    The embryo toxicities of two major potato glycoalkaloids, alpha-chaconine and alpha-solanine, were examined individually and in mixtures using the frog embryo teratogenesis assay-Xenopus. Calculations of toxic units (TUs) were used to assess possible antagonism, synergism or response addition of several mixtures ranging from approximately 3:1 to 1:20 TUs of alpha-chaconine to alpha-solanine. Some combinations exhibited strong synergism in the following measures of developmental toxicity: (a) 96-hr LC50, defined as the median concentration causing 50% embryo lethality; (b) 96-hr EC50 (malformation), defined as the concentration causing 50% malformation of the surviving embryos; and (c) teratogenic index which is equal to LC50/EC50 (malformation). The results indicated that each of the mixtures caused synergistic mortality or malformation. Furthermore, these studies suggested that the synergism observed for a specific mixture cannot be used to predict possible synergism of other mixtures with different ratios of the two glycoalkaloids; toxicities observed for individual glycoalkaloids may not be able to predict toxicities of mixtures; and specific combinations found in different potato varieties need to be tested to assess the safety of a particular cultivar.

  19. Toxicogenomics in vitro as an alternative tool for safety evaluation of petroleum substances and PAHs with regard to prenatal developmental toxicity

    NARCIS (Netherlands)

    Tsitou, Polyxeni; Heneweer, Marjoke; Boogaard, P.J.

    2015-01-01

    The REACH legislation requires chemicals - including petroleum substances - that are put on the EU market in quantities greater than 1000 tonnes/year, to be tested for prenatal developmental toxicity. This will require large numbers of animals since prenatal development toxicity testing is

  20. Use of In Vitro Morphogenesis of Mouse Embryoid Bodies to Assess Developmental Toxicity of Therapeutic Drugs Contraindicated in Pregnancy.

    Science.gov (United States)

    Warkus, Erica L L; Yuen, Angela A Y Q; Lau, Caroline G Y; Marikawa, Yusuke

    2016-01-01

    In utero exposure to certain chemicals can impair embryo development, causing embryonic death, growth retardation, or severe birth defects. Establishment of effective in vitro tests is crucial for identifying developmental toxicants and for reducing the financial and ethical burden of animal-based tests. Previously, we created an in vitro morphogenesis model using pluripotent P19C5 mouse embryonal carcinoma stem cells that mimics the process of gastrulation and axial body elongation of embryos. Because many birth defects are caused by dysregulation of cellular behaviors during embryogenesis, the morphogenesis model may serve as a unique tool to investigate the impacts of developmental toxicants. The aim of this study is to evaluate the applicability and limitations of the model using 20 therapeutic drugs, 16 of which are contraindicated in pregnancy and 4 are considered safe. P19C5 embryoid bodies (EBs) were exposed to different concentrations of drugs during 4 days of 3-dimensional culture. The treatment effects on growth and morphogenesis were analyzed using morphometric measurements of EB size and shape, respectively. Viability assays of P19C5 cells and NIH/3T3 fibroblasts were used to determine the drug concentrations that caused general cytotoxicity and those that selectively diminished P19C5 proliferation relative to NIH/3T3 proliferation. Thirteen contraindicated drugs diminished P19C5 cell proliferation, reduced EB growth, or altered morphogenesis at concentrations below generally cytotoxic levels. Two safe drugs also exhibited these impacts at the highest concentration tested. Although additional validation studies are required, this study introduces morphogenesis-based stem cell models as potentially effective in vitro tools for developmental toxicity research. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  1. Toxicity evaluation of petroleum blending streams: reproductive and developmental effects of light catalytic reformed naphtha distillate in rats.

    Science.gov (United States)

    Schreiner, C; Bui, Q; Breglia, R; Burnett, D; Koschier, F; Podhasky, P; White, R; Hoffman, G; Schroeder, R

    2000-06-09

    A distillate of light catalytic reformed naphtha (CAS number 64741-63-5, LCRN-D) administered by inhalation was tested for reproductive and developmental toxicity in Sprague-Dawley rats, following a modified OECD Guideline 421, Reproductive/Developmental Toxicity Screening protocol. LCRN-D was administered as a vapor, 6 h/d, 7 d/wk at target concentrations of 0, 750, 2500 or 7500 ppm to female rats for approximately 6 wk from 2 wk prior to mating, during mating through gestational d 19, and to males beginning 2 wk prior to mating for approximately 7 consecutive weeks. Dams and litters were sacrificed on postnatal d 4 and males were sacrificed within the week after the last litter was necropsied. Parental systemic effects observed at the 7500 ppm exposure level included slightly lower body weights for males throughout the study. Increased kidney to body weight and increased liver to body weight ratio in male rats exposed to 7500 ppm LCRN-D may be related to slightly lower final mean body weights. Body and organ weight data for female rats in all exposure groups were comparable to controls. No test-material-related microscopic changes were observed in the reproductive organs or nasal turbinate tissue of either sex. Reproductive performance was unaffected by exposure to LCRN-D. The mating and fertility indices were 100% in all groups. There were no significant exposure-related differences in implantation sites or live pups per litter, and no gross abnormalities were observed in pups from treated dams. Pups born from LCRN-D-exposed dams showed comparable body weights and weight gain to control pups. The viability index on postpartum d 4 was > or =97%. Under conditions of this study, the no-observed-adverse-effect level (NOAEL) for exposure to light catalytic reformed naphtha distillate for parental effects was 2500 ppm and the NOAEL for reproductive and developmental toxicity was 7500 ppm.

  2. Evaluation of reproductive and developmental toxicities of Pu-erh black tea (Camellia sinensis var. assamica) extract in Sprague Dawley rats.

    Science.gov (United States)

    Wang, Di; Meng, Jie; Gao, Hui; Xu, Kunlong; Xiao, Rong; Zhong, Ying; Luo, Xiao; Yao, Ping; Yan, Hong; Liu, Liegang

    2013-06-21

    Pu-erh black tea, which is obtained by first parching crude green tea leaves and followed by secondary fermentation with microorganisms, has been believed to be beneficial beverages for health in PR China. But its potential toxicity when administered at a high dose as concentrated extract has not been completely investigated. The present study was aimed at evaluating potential reproductive and developmental toxicities of Pu-erh black tea extract (BTE) in Sprague Dawley rats. Growing rats were given BTE by gavage at levels of 0, 200, 700 and 2500mg/kg/day as the F0 generation in reproductive toxicity study. Additionally, BTE was administered to mate female rats from gestation day 0.5 through 19.5 at the doses of 0, 200, 700 and 2500mg/kg/day to evaluate the developmental toxicity. In the reproductive toxicity study, only 2500mg/kg/day BTE reduced the body weight gain and altered the relative organ weights including testes, prostata and ovary both for F0 parents and F1 offspring compared to the controls. High dose of BTE (2500mg/kg/day) administration caused developmental disturbances in embryo-to-foetus period including resorbed embryos, decreased embryo size and skeletal anomalies. In conclusion, the no-observed-adverse-effect level of BTE is 700mg/kg/day both for reproductive toxicity and developmental toxicities. Crown Copyright © 2013. Published by Elsevier Ireland Ltd. All rights reserved.

  3. Early childhood adversity, toxic stress, and the role of the pediatrician: translating developmental science into lifelong health.

    Science.gov (United States)

    Garner, Andrew S; Shonkoff, Jack P

    2012-01-01

    Advances in a wide range of biological, behavioral, and social sciences are expanding our understanding of how early environmental influences (the ecology) and genetic predispositions (the biologic program) affect learning capacities, adaptive behaviors, lifelong physical and mental health, and adult productivity. A supporting technical report from the American Academy of Pediatrics (AAP) presents an integrated ecobiodevelopmental framework to assist in translating these dramatic advances in developmental science into improved health across the life span. Pediatricians are now armed with new information about the adverse effects of toxic stress on brain development, as well as a deeper understanding of the early life origins of many adult diseases. As trusted authorities in child health and development, pediatric providers must now complement the early identification of developmental concerns with a greater focus on those interventions and community investments that reduce external threats to healthy brain growth. To this end, AAP endorses a developing leadership role for the entire pediatric community-one that mobilizes the scientific expertise of both basic and clinical researchers, the family-centered care of the pediatric medical home, and the public influence of AAP and its state chapters-to catalyze fundamental change in early childhood policy and services. AAP is committed to leveraging science to inform the development of innovative strategies to reduce the precipitants of toxic stress in young children and to mitigate their negative effects on the course of development and health across the life span.

  4. In vitro to in vivo extrapolation of effective dosimetry in developmental toxicity testing: Application of a generic PBK modelling approach.

    Science.gov (United States)

    Fragki, Styliani; Piersma, Aldert H; Rorije, Emiel; Zeilmaker, Marco J

    2017-10-01

    Incorporation of kinetics to quantitative in vitro to in vivo extrapolations (QIVIVE) is a key step for the realization of a non-animal testing paradigm, in the sphere of regulatory toxicology. The use of Physiologically-Based Kinetic (PBK) modelling for determining systemic doses of chemicals at the target site is accepted to be an indispensable element for such purposes. Nonetheless, PBK models are usually designed for a single or a group of compounds and are considered demanding, with respect to experimental data needed for model parameterization. Alternatively, we evaluate here the use of a more generic approach, i.e. the so-called IndusChemFate model, which is based on incorporated QSAR model parametrization. The model was used to simulate the in vivo kinetics of three diverse classes of developmental toxicants: triazoles, glycol ethers' alkoxyacetic acid metabolites and phthalate primary metabolites. The model required specific input per each class of compounds. These compounds were previously tested in three alternative assays: the whole-embryo culture (WEC), the zebrafish embryo test (ZET), and the mouse embryonic stem cell test (EST). Thereafter, the PBK-simulated blood levels at toxic in vivo doses were compared to the respective in vitro effective concentrations. Comparisons pertaining to relative potency and potency ranking with integration of kinetics were similar to previously obtained comparisons. Additionally, all three in vitro systems produced quite comparable results, and hence, a combination of alternative tests is still preferable for predicting the endpoint of developmental toxicity in vivo. This approach is put forward as biologically more plausible since plasma concentrations, rather than external administered doses, constitute the most direct in vivo dose metric. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Acute and developmental toxicity assessment of erincine A-enriched Hericium erinaceus mycelia in Sprague-Dawley rats.

    Science.gov (United States)

    Li, I-Chen; Chen, Wan-Ping; Chen, Yen-Po; Lee, Li-Ya; Tsai, Yueh-Ting; Chen, Chin-Chu

    2018-01-23

    This study aimed to establish an in vitro model to confirm the efficacy of erinacine A-enriched Hericium erinaceus (EAHE) mycelia and investigate its potential adverse effects in a preclinical experimental setting, including an assessment on the oral administration of EAHE mycelia in acute and prenatal developmental toxicity tests. At a single dose of 5000 mg/kg body weight, EAHE mycelia elicited no death or treatment-related signs of toxicity in ten Sprague-Dawley rats of both sexes during the 14 days of the experimental period. After considering the recommended dose range of EAHE mycelia from the acute toxicity test as well as the therapeutic doses, EAHE mycelia was administered to 66 pregnant rats in the low, medium, and high-dose groups by gavage at 875, 1750, and 2625 mg/kg body weight, respectively. All dams were subjected to a Caesarean section on the 20th day of pregnancy, and the fetuses were examined for any morphological abnormalities. Results indicated that weight of uterus, fetal body weight, number of corpora lutea, implantation sites, pre-implantation loss, and post-implantation loss of the treatment groups and the control group exhibited no statistical difference. In addition, no significant differences were observed in the fetal external, organ, and skeletal examinations. Taken together, it can be concluded that EAHE mycelia is considered safe and practically nontoxic for consumption within the appropriate doses and investigation period in this study.

  6. Human Pluripotent Stem Cell Based Developmental Toxicity Assays for Chemical Safety Screening and Systems Biology Data Generation.

    Science.gov (United States)

    Shinde, Vaibhav; Klima, Stefanie; Sureshkumar, Perumal Srinivasan; Meganathan, Kesavan; Jagtap, Smita; Rempel, Eugen; Rahnenführer, Jörg; Hengstler, Jan Georg; Waldmann, Tanja; Hescheler, Jürgen; Leist, Marcel; Sachinidis, Agapios

    2015-06-17

    Efficient protocols to differentiate human pluripotent stem cells to various tissues in combination with -omics technologies opened up new horizons for in vitro toxicity testing of potential drugs. To provide a solid scientific basis for such assays, it will be important to gain quantitative information on the time course of development and on the underlying regulatory mechanisms by systems biology approaches. Two assays have therefore been tuned here for these requirements. In the UKK test system, human embryonic stem cells (hESC) (or other pluripotent cells) are left to spontaneously differentiate for 14 days in embryoid bodies, to allow generation of cells of all three germ layers. This system recapitulates key steps of early human embryonic development, and it can predict human-specific early embryonic toxicity/teratogenicity, if cells are exposed to chemicals during differentiation. The UKN1 test system is based on hESC differentiating to a population of neuroectodermal progenitor (NEP) cells for 6 days. This system recapitulates early neural development and predicts early developmental neurotoxicity and epigenetic changes triggered by chemicals. Both systems, in combination with transcriptome microarray studies, are suitable for identifying toxicity biomarkers. Moreover, they may be used in combination to generate input data for systems biology analysis. These test systems have advantages over the traditional toxicological studies requiring large amounts of animals. The test systems may contribute to a reduction of the costs for drug development and chemical safety evaluation. Their combination sheds light especially on compounds that may influence neurodevelopment specifically.

  7. Developmental toxicity of orally administered sildenafil citrate (Viagra) in SWR/J mice.

    Science.gov (United States)

    Abou-Tarboush, Faisal Mohamed; Abdel-Samad, Mohamed Fathy; Al-Meteri, Mokhlid Hamed

    2011-04-01

    Normal adult inbred SWR/J mice were used to investigate the teratogenic and other possible toxic effects of various dose levels of sildenafil citrate (Viagra) on fetuses. Multiple dose levels of 6.5, 13.0, 19.5, 26.0, 32.5 or 40.0 mg of sildenafil citrate/kg body weight (which correspond to the multiples of 1, 2, 3, 4, 5 or 6 of human 50 mg Viagra, respectively) were orally administered into pregnant mice on days 7-9, 10-12 or 13-15 of gestation. On day 17 of pregnancy, all fetuses were removed and examined for toxic phenomena (embryo-fetal toxicity) and for external, internal and skeletal malformations. A total of 285 pregnant mice were used in the present study. None of the dams treated with sildenafil citrate at any of the oral dose levels used in the present study died during the experimental period and all dams treated with the drug failed to reveal overt signs of maternal toxicity. Moreover, the results of the present study clearly demonstrate that none of the multiple oral dose levels of the drug at any time interval used has induced any external, internal or skeletal malformations in the fetuses obtained from treated females. However, the dose level of 40 mg/kg body weight of sildenafil citrate has a growth suppressing effect on alive fetuses when it was administered at all the time intervals used in the present study. Furthermore, the dose levels 26.0, 32.5 and 40 mg/kg of the drug have embryo-fetal toxicity when the drug is applied on days 13-15 of gestation. The possible mechanisms involved in the embryo-fetal toxicity and fetal growth suppressing effects of sildenafil citrate were discussed. The results of this study have important implications for the widespread use of this drug.

  8. Safety assessment for ethanol-based topical antiseptic use by health care workers: Evaluation of developmental toxicity potential.

    Science.gov (United States)

    Maier, Andrew; Ovesen, Jerald L; Allen, Casey L; York, Raymond G; Gadagbui, Bernard K; Kirman, Christopher R; Poet, Torka; Quiñones-Rivera, Antonio

    2015-10-01

    Ethanol-based topical antiseptic hand rubs, commonly referred to as alcohol-based hand sanitizers (ABHS), are routinely used as the standard of care to reduce the presence of viable bacteria on the skin and are an important element of infection control procedures in the healthcare industry. There are no reported indications of safety concerns associated with the use of these products in the workplace. However, the prevalence of such alcohol-based products in healthcare facilities and safety questions raised by the U.S. FDA led us to assess the potential for developmental toxicity under relevant product-use scenarios. Estimates from a physiologically based pharmacokinetic modeling approach suggest that occupational use of alcohol-based topical antiseptics in the healthcare industry can generate low, detectable concentrations of ethanol in blood. This unintended systemic dose probably reflects contributions from both dermal absorption and inhalation of volatilized product. The resulting internal dose is low, even under hypothetical, worst case intensive use assumptions. A significant margin of exposure (MOE) exists compared to demonstrated effect levels for developmental toxicity under worst case use scenarios, and the MOE is even more significant for typical anticipated occupational use patterns. The estimated internal doses of ethanol from topical application of alcohol-based hand sanitizers are also in the range of those associated with consumption of non-alcoholic beverages (i.e., non-alcoholic beer, flavored water, and orange juice), which are considered safe for consumers. Additionally, the estimated internal doses associated with expected exposure scenarios are below or in the range of the expected internal doses associated with the current occupational exposure limit for ethanol set by the Occupational Safety and Health Administration. These results support the conclusion that there is no significant risk of developmental or reproductive toxicity from

  9. QSAR pre-screen of 70,983 substances for genotoxic carcinogenicity, mutagenicity and developmental toxicity in the EU FP7 project ChemScreen

    DEFF Research Database (Denmark)

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

    2014-01-01

    be performed in REACH on known genotoxic carcinogens or germ cell mutagens with appropriate risk management measures implemented, a QSAR pre-screen for genotoxic carcinogenicity, germ cell mutagenicity and (limited) developmental toxicity was included in the project. Predictions for estrogenic and anti...... algorithms were applied to combine the predictions from the individual models to reach overall predictions for genotoxic carcinogenicity, germ cell mutagenicity and developmental toxicity. Furthermore, the full list of REACH pre-registered substances (143,835) was searched for substances containing certain...

  10. Interpreting in vitro developmental toxicity test battery results: The consideration of toxicokinetics

    NARCIS (Netherlands)

    Bosgra, S.; Westerhout, J.

    2015-01-01

    In the EU collaborative project ChemScreen an alternative, in vitro assay-based test strategy was developed to screen compounds for reproductive toxicity. A toxicokinetic modeling approach was used to allow quantitative comparison between effective concentrations in the in vitro test battery and

  11. Screening for angiogenic inhibitors in zebrafish to evaluate a predictive model for developmental vascular toxicity

    Science.gov (United States)

    Chemically-induced vascular toxicity during embryonic development may cause a wide range of adverse effects. To identify putative vascular disrupting chemicals (pVDCs), a predictive signature was constructed from U.S. EPA ToxCast high-throughput screening (HTS) assays that map to...

  12. 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.

  13. Fertility, developmental toxicity and teratogenicity in albino rats treated with methanol sub-fraction of Carica papaya seeds.

    Science.gov (United States)

    Shrivastava, S; Ansari, A S; Lohiya, N K

    2011-07-01

    To evaluate the status of fertility, developmental stages during gestation and teratological changes, if any, following oral administration of methanol sub-fraction (MSF) of the benzene chromatographic fraction of the chloroform extract of the seeds of Carica papaya in rats. The MSF was administered at the doses of 50 mg contraceptive dose (CD), 100 mg (2× CD), 250 mg (5× CD) and 500 mg (10× CD)/kg body wt/day along with vehicle-treated control using 10 male and 20 female Wistar rats in each group. Necropsies were performed one day before the expected parturition. Status of gravid/non-gravid uterus, the number of corpora lutea in the ovary, implantation status, fetal wellbeing, fetal resorption, fetal body weight, external, visceral and skeletal malformations were recorded. Pregnancies were recorded in vehicle-treated control animals and in the animals treated with 50 mg/kg body wt/day. The animals treated with 2× CD, 5× CD and 10× CD did not get pregnant. The fetuses and the status of the ovary, uterus and implantation, fetal body weight, soft tissues and skeletal structures were recorded normal. Data were comparable to those of control. The results suggest that the test substance had no developmental toxicity and teratogenicity which could affect pregnancy, implantation and gestation.

  14. 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

  15. "Simulated gastric hydrolysis and developmental toxicity of dioctyltin bis(2-Ethylhexylthioglycolate) [DOTE] in rabbits and mice".

    Science.gov (United States)

    Costlow, Richard D; Nasshan, Hans; Frenkel, Peter

    2017-07-01

    Based on previous studies, dioctyltin dichloride [DOTC] was a putative toxophore for dioctyltin thioesters. Our results, generated with the use of 119Sn-NMR spectroscopy demonstrated that dioctyltin bis(2-ethylhexyl thioglycolate) [DOTE] hydrolyzed to form dioctyltin chloro-(2-ethylhexyl thioglycolate) [DOTCE] under simulated gastric conditions, but no DOTC was formed. DOTE was administered orally at 4, 20, and 80 mg/kg/day [GD6-GD28; rabbits] or at 15, 30, and 60 mg/kg/day [GD5-GD17; mice]. There were no maternal deaths, treatment-related statistically significant reductions in maternal body weight or weight gain, or adverse gestational outcomes in either species. Maternal thymus weight was significantly reduced in mice at 30 and 60 mg/kg. There were no effects on fetal growth, no dose-dependent pattern of external, visceral or skeletal malformations and no increase in anatomical variations in either species. We conclude that DOTE likely forms DOTCE, not DOTC, in the stomach and DOTE was not teratogenic or fetotoxic in rabbits or mice. The rabbit maternal NOAEL was 80 mg/kg/day. The rabbit developmental NOAEL was 80 mg/kg/day. The mouse maternal LOAEL was 30 mg/kg/day based on reduced thymus weight and a dose-dependent effect on maternal weight at 60 mg/kg. The mouse developmental NOAEL was 60 mg/kg bw/day, the high dose. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Developmental toxicity of two common corn pesticides to the endangered southern bell frog (Litoria raniformis)

    Energy Technology Data Exchange (ETDEWEB)

    Choung, Catherine B., E-mail: Catherine.Choung@mq.edu.au [Department of Biological Sciences, Macquarie University, Sydney, NSW 2109 (Australia); Hyne, Ross V. [Ecotoxicology and Environmental Contaminants Section, Office of Environment and Heritage, PO Box 29, Lidcombe, NSW 1825 (Australia); Mann, Reinier M. [Centre for Environmental Sustainability, University of Technology - Sydney, PO Box 123, Broadway, NSW 2007 (Australia); Stevens, Mark M. [EH Graham Centre for Agricultural Innovation (Industry and Investment NSW and Charles Sturt University), Yanco Agricultural Institute, Private Mail Bag, Yanco, NSW 2703 (Australia); Hose, Grant C. [Department of Biological Sciences, Macquarie University, Sydney, NSW 2109 (Australia)

    2011-10-15

    To examine the link between corn agriculture and the observed decline of the endangered southern bell frog (SBF), the effects of two corn crop pesticides on larval growth and development were investigated. Tadpoles were exposed to terbufos sulfone (10 {mu}g/L), a major breakdown product of the insecticide terbufos, and the herbicide atrazine (25 {mu}g/L) individually and as a mixture until the completion of metamorphosis. Atrazine did not interact synergistically with terbufos sulfone or result in significant effects on growth and development alone, although there was some indication of accelerated metamorphosis in the pilot study. Terbufos sulfone alone and as a mixture (terbufos/atrazine) significantly slowed larval development and ultimately delayed metamorphosis. The observed developmental effects from an environmentally relevant concentration of terbufos sulfone indicates a risk posed by this persistent degradation product to the endangered SBF, which breeds and develops in the rice bays adjacent to corn fields treated with pesticides. - Highlights: > The effect of terbufos sulfone and atrazine on larval growth and development was investigated. > Terbufos sulfone alone significantly slowed development and delayed metamorphosis of tadpoles. > Atrazine had no observable effects alone nor did it interact synergistically with terbufos sulfone. > The developmental effects indicates a risk to endangered southern bell frogs in the irrigation area. > The results highlight the toxicological importance of some pesticide breakdown products. - A breakdown product of the insecticide terbufos retards development and delays metamorphosis of southern bell frog tadpoles.

  17. Determination of developmental toxicity of zebrafish exposed to propyl gallate dosed lower than ADI (acceptable daily intake).

    Science.gov (United States)

    Baran, Alper; Köktürk, Mine; Atamanalp, Muhammed; Ceyhun, Saltuk Buğrahan

    2018-01-03

    Propyl gallate (PG) is an antioxidant substance widely used in cosmetics, pharmaceutical and food industries. The aim of this study was to evaluate the potential toxic effect of PG injected to zebrafish embryos. To this end, zebrafish embryos were exposed to PG with 0, 1, 10 and 50 ppm concentrations which are lower than ADI and were monitored at 24, 48, 72 and 96 hpf. Survival rate, hatching rate and malformations were evaluated during this period. Moreover, it has been detected the accumulation of fluorescence signal of ROS and apoptotic cell in whole body at the end of 96 hpf. According to results, survival rate slightly decreased in highest concentration, and PG accelerated hatching in 1 and 10 ppm concentrations whereas delayed in 50 ppm concentration. In addition, it has been detected accumulation of fluorescence signal of ROS and apoptotic cells in a dose dependent-manner. Consequently, it has been considered that increased embryonic or larval malformation in this study may have been caused by ROS-induced apoptosis. The obtained data suggested that the developmental toxicity caused by PG and/or multiple hydroxyl groups arose when PG hydrolyze to gallic acid is probably triggered by the induction of ROS formation and consequent apoptosis. Copyright © 2017. Published by Elsevier Inc.

  18. Developmental toxicity testing in the 21st century: the sword of Damocles shattered by embryonic stem cell assays?

    Science.gov (United States)

    Seiler, Andrea; Oelgeschläger, Michael; Liebsch, Manfred; Pirow, Ralph; Riebeling, Christian; Tralau, Tewes; Luch, Andreas

    2011-11-01

    Modern society faces an inherent dilemma. In our globalized society, we are spoilt for choice by an ever-increasing number of products, many of which are made of new materials and compound mixtures. At the same time, as consumers we got accustomed to the idea of a life minimized for risk, including our own exposure to chemicals from the environment or to compounds present in and released from everyday products. Chemical safety testing bridges these obviously diverging interests, and the corresponding legislation has hence been tremendously extended (e.g., introduction of the European legislation REACH in 2007). However, the underlying regulatory toxicology still relies mainly on animal testing, which is relatively slow, expensive, and ethically arguable. Meanwhile, recent years have seen a surge in efforts to develop alternative testing systems and strategies. Expectations are particularly high for the applicability of stem cells as test systems especially for developmental toxicity testing in vitro. For the first time in history, test systems can be based on differentiating cells and tissue progenitors in culture, thus bringing the 'vision of toxicity testing in the 21st century' a step closer.

  19. Drosophila embryos as model to assess cellular and developmental toxicity of multi-walled carbon nanotubes (MWCNT in living organisms.

    Directory of Open Access Journals (Sweden)

    Boyin Liu

    Full Text Available Different toxicity tests for carbon nanotubes (CNT have been developed to assess their impact on human health and on aquatic and terrestrial animal and plant life. We present a new model, the fruit fly Drosophila embryo offering the opportunity for rapid, inexpensive and detailed analysis of CNTs toxicity during embryonic development. We show that injected DiI labelled multi-walled carbon nanotubes (MWCNTs become incorporated into cells in early Drosophila embryos, allowing the study of the consequences of cellular uptake of CNTs on cell communication, tissue and organ formation in living embryos. Fluorescently labelled subcellular structures showed that MWCNTs remained cytoplasmic and were excluded from the nucleus. Analysis of developing ectodermal and neural stem cells in MWCNTs injected embryos revealed normal division patterns and differentiation capacity. However, an increase in cell death of ectodermal but not of neural stem cells was observed, indicating stem cell-specific vulnerability to MWCNT exposure. The ease of CNT embryo injections, the possibility of detailed morphological and genomic analysis and the low costs make Drosophila embryos a system of choice to assess potential developmental and cellular effects of CNTs and test their use in future CNT based new therapies including drug delivery.

  20. Introducing Environmental Toxicology in Instructional Labs: The Use of a Modified Amphibian Developmental Toxicity Assay to Support Inquiry-Based Student Projects

    Science.gov (United States)

    Sauterer, Roger; Rayburn, James R.

    2012-01-01

    Introducing students to the process of scientific inquiry is a major goal of high school and college labs. Environmental toxins are of great concern and public interest. Modifications of a vertebrate developmental toxicity assay using the frog Xenopus laevis can support student-initiated toxicology experiments that are relevant to humans. Teams of…

  1. Use of the ES-D3 cell differentiation assay, combined with the BeWo transport model, to predict relative in vivo developmental toxicity of antifungal compounds.

    Science.gov (United States)

    Li, Hequn; Rietjens, Ivonne M C M; Louisse, Jochem; Blok, Martine; Wang, Xinyi; Snijders, Linda; van Ravenzwaay, Bennard

    2015-03-01

    We investigated the applicability of the ES-D3 cell differentiation assay combined with the in vitro BeWo transport model to predict the relative in vivo developmental toxicity potencies. To this purpose, the in vitro developmental toxicity of five antifungal compounds was investigated by characterizing their inhibitory effect on the differentiation of ES-D3 cells into cardiomyocytes. The BeWo transport model, consisting of BeWo b30 cells grown on transwell inserts and mimicking the placental barrier, was used to determine the relative placental transport velocity. The ES-D3 cell differentiation data were first compared to benchmark doses (BMDs) for in vivo developmental toxicity as derived from data reported in the literature. Correlation between the benchmark concentration for 50% effect (BMCd50) values, obtained in the ES-D3 cell differentiation assay, with in vivo BMD10 values showed a reasonable correlation (R(2)=0.57). When the ES-D3 cell differentiation data were combined with the relative transport rates obtained from the BeWo model, the correlation with the in vivo data increased (R(2)=0.95). In conclusion, we show that the ES-D3 cell differentiation assay is able to better predict the in vivo developmental toxicity ranking of antifungal compounds when combined with the BeWo transport model, than as a stand-alone assay. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. The use of in vitro toxicity data and physiologically based kinetic modeling to predict dose-response curves for in vivo developmental toxicity of glycol ethers in rat and man.

    Science.gov (United States)

    Louisse, Jochem; de Jong, Esther; van de Sandt, Johannes J M; Blaauboer, Bas J; Woutersen, Ruud A; Piersma, Aldert H; Rietjens, Ivonne M C M; Verwei, Miriam

    2010-12-01

    At present, regulatory assessment of systemic toxicity is almost solely carried out using animal models. The European Commission's REACH legislation stimulates the use of animal-free approaches to obtain information on the toxicity of chemicals. In vitro toxicity tests provide in vitro concentration-response curves for specific target cells, whereas in vivo dose-response curves are regularly used for human risk assessment. The present study shows an approach to predict in vivo dose-response curves for developmental toxicity by combining in vitro toxicity data and in silico kinetic modeling. A physiologically based kinetic (PBK) model was developed, describing the kinetics of four glycol ethers and their embryotoxic alkoxyacetic acid metabolites in rat and man. In vitro toxicity data of these metabolites derived in the embryonic stem cell test were used as input in the PBK model to extrapolate in vitro concentration-response curves to predicted in vivo dose-response curves for developmental toxicity of the parent glycol ethers in rat and man. The predicted dose-response curves for rat were found to be in concordance with the embryotoxic dose levels measured in reported in vivo rat studies. Therefore, predicted dose-response curves for rat could be used to set a point of departure for deriving safe exposure limits in human risk assessment. Combining the in vitro toxicity data with a human PBK model allows the prediction of dose-response curves for human developmental toxicity. This approach could therefore provide a means to reduce the need for animal testing in human risk assessment practices.

  3. Comparison of the developmental toxicity of aspirin in rabbits when administered throughout organogenesis or during sensitive windows of development.

    Science.gov (United States)

    Cappon, G D; Gupta, U; Cook, J C; Tassinari, M S; Hurtt, M E

    2003-02-01

    A review of the nonsteroidal anti-inflammatory drug (NSAID) literature suggested occurrences of low-level incidences of cardiovascular and midline defects in rabbit fetuses exposed in utero. Aspirin (acetylsalicylic acid, ASA) is a widely used NSAID that irreversibly inhibits cyclooxygenases (COXs) 1 and 2. ASA has been studied extensively in rats and has consistently increased low-incidence cardiovascular malformations and defects in midline closure. The objectives of the current study were to comprehensively define the developmental toxicology profile of ASA in rabbits by using a dosing paradigm encompassing the period of organogenesis and to test the hypothesis that maternal gastrointestinal toxicity after repeated dose administrations hampers the detection of low-incidence malformations with ASA in rabbits by limiting ASA administration to sensitive windows for cardiovascular development and midline closure. ASA was administered to pregnant New Zealand White rabbits from gestation days (GDs) 7 to 19 at dose levels of 125, 250, and 350 mg/kg per day and as single doses of 500, 750, or 1000 mg/kg on GD 9, 10, or 11. Cesarean sections were performed on GD 29, and the fetuses were examined for external, visceral and skeletal development. In the repeated dose study, maternal toxicity was exhibited in the 250- and 350-mg/kg per day groups by mortality and decreased food consumption and body weight gain. In the single dose studies, maternal toxicity was exhibited at all doses by reductions in body weight gain and food consumption for 3 days after treatment. Fetal body weight was significantly reduced in the repeated dose study at 350 mg/kg per day. Fetal weights were not affected by single doses of ASA on GD 9, 10, or 11. There were no treatment-related external, visceral or skeletal malformations associated with ASA administration throughout organogenesis or with single doses administered during critical developmental windows. These findings supported previous work

  4. Developmental and reproductive toxicity of PVP/PEI-coated silver nanoparticles to zebrafish.

    Science.gov (United States)

    Orbea, Amaia; González-Soto, Nagore; Lacave, José María; Barrio, Irantzu; Cajaraville, Miren P

    2017-09-01

    Cellular and molecular mechanisms of toxicity of silver nanoparticles (NPs) and their toxicity to fish embryos after waterborne exposure have been widely investigated, but much less information is available regarding the effect of Ag NPs on physiological functions such as growth or reproduction. In this work, the effects of waterborne exposure of adult zebrafish (Danio rerio) to PVP/PEI coated Ag NPs (~5nm) on reproduction (fecundity) were investigated. Moreover, the development of the embryos after parental exposure was compared with the development of embryos after direct waterborne exposure to the NPs. For this, two experiments were run: 1) embryos from unexposed parents were treated for 5days with Ag NPs (10μgAgL -1 -10mgAgL -1 ) and development was monitored, and 2) selected breeding zebrafish were exposed for 3weeks to 100ngAgL -1 (environmentally relevant concentration) or to 10μgAgL -1 of Ag NPs, fecundity was scored and development of resulting embryos was monitored up to 5days. Waterborne exposure of embryos to Ag NPs resulted in being highly toxic (LC50 at 120h=50μgAgL -1 ), causing 100% mortality during the first 24h of exposure at 0.1mgAgL -1 . Exposure of adults, even at the environmentally relevant silver concentration, caused a significant reduction of fecundity by the second week of treatment and resulting embryos showed a higher prevalence of malformations than control embryos. Exposed adult females presented higher prevalence of vacuolization in the liver. These results show that Ag NPs at an environmentally relevant concentration are able to affect population level parameters in zebrafish. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Developmental toxicity studies of lumefantrine and artemether in rats and rabbits.

    Science.gov (United States)

    Clark, Robert L; Youreneff, Maureen; DeLise, Anthony M

    2016-12-01

    The combination of artemether plus lumefantrine is a type of artemisinin-based combination therapy (ACT) recommended by the World Health Organization for uncomplicated falciparum malaria except in the first trimester of pregnancy. The first trimester restriction was based on the marked embryotoxicity in animals (including embryo death and cardiac and skeletal malformations) of artemisinins such as artesunate, dihydroartemisinin, and artemether. Before recommending ACTs for use in the first trimester, the World Health Organization has requested that all information relevant to the assessment of risk of ACTs to the embryo be made available to the public. This report describes the results of embryo-fetal development studies of artemether alone, lumefantrine alone, and the combination in rats and rabbits as well as toxicokinetic studies of lumefantrine in pregnant rabbits. The developmental no-effect levels for lumefantrine were 300 mg/kg/day in rats (based on a 25% decrease in litter size at 1000 mg/kg/day) and 1000 mg/kg/day in rabbits. The calculated safety margins based on human equivalent dose and plasma Cmax and AUC values were in the range of 2.5- to 17-fold. The developmental no-effect levels for artemether were 3 mg/kg/day in rats and 25 mg/kg/day in rabbits. Lumefantrine caused no teratogenicity and was not a potent embryotoxin in rats and rabbits. Expected artemisinin-like findings were seen with artemether alone and with artemether/lumefantrine combined except that no malformations were observed. There were no findings in pregnant rats and rabbits that would cause increased concern for the use of artemether-lumefantrine in the first trimester compared to other ACTs. © 2016 Wiley Periodicals, Inc.

  6. Ovipositional response, developmental effects and toxicity of hexavalent chromium to Megaselia scalaris, a terrestrial detritivore.

    Science.gov (United States)

    Trumble, John T; Jensen, Peter D

    2004-04-01

    The effects of hexavalent chromium (Cr VI) on ovipositional response, development, and survival of a common terrestrial detritivore, Megaselia scalaris (Diptera: Phoridae), were assessed in the laboratory. Ovipositing females did not discriminate between substrates containing 0, 50, 500, or 1000 microg/g, indicating a lack of avoidance behavior. Eggs placed on artificial diets containing up to 1000 microg/g either did not absorb Cr VI or were unaffected as measured by eclosion rates. However, development and survival of larvae were significantly reduced at the higher concentrations tested. Concentrations of 500 microg/g in their food increased larval development times by nearly 65%. At 1000 microg/g, larval developmental times doubled. The time required from onset to completion of pupariation was not significantly different regardless of Cr VI concentration. Although males eclosed before females, there was no significant difference between the sexes in the time required for adult eclosion. In addition, there were no significant differences in the percentage of males and females emerging from any of the treatments. At concentrations of 500 or 1000 microg/g, Cr VI decreased larval survival. Survival was reduced by 44.3% at 500 microg/g as compared with the controls. There was no additional mortality from the onset of the puparial stage to adult eclosion for larvae fed diets containing 500 microg/g Cr VI. At 1000 microg/g Cr VI, larval survival decreased by 86.6%. An additional 7.4% mortality was recorded in the puparial stage, for a decrease in total survival (larval plus puparial stages) of 94%. Thus, nearly all of the observed mortality occurred during the larval stage rather than the puparial stage. The population level implications of lack of avoidance of contaminated food and the effects of increased developmental times and reduced survivorship are discussed.

  7. Developmental toxicity of N-methylaniline following prenatal oral administration in rats

    Directory of Open Access Journals (Sweden)

    Krystyna Sitarek

    2016-06-01

    Full Text Available Objectives: The objective of the study was to assess prenatal toxicity of N-methylaniline (NMA administered by gavage to pregnant female rats. Material and Methods: Pregnant female rats were administered N-methylaniline in corn oil by gavage at daily doses of 0.8 mg/kg of body weight (b.w., 4 mg/kg b.w., 20 mg/kg b.w. and 100 mg/kg b.w. from implantation (the 5th day post mating to the day prior to the scheduled caesarean section (the 20th day of pregnancy. General behavior, body weight, food and water consumption, hematological, biochemical analyses and pathomorphological changes of the dams were recorded. Results: All the females survived until the end of the study. The test substance was toxic to pregnant females, even at the lowest of the used doses, i.e., 0.8 mg/kg b.w./day. Lower weight gain during pregnancy and significantly higher NMA-dose-dependent absolute weight of the organs were noted in the exposed females. The females from the groups exposed at doses of 20 mg/kg b.w./day and 100 mg/kg b.w./day developed anemia and showed higher concentrations of free thyroxine (FT3 and free triiodothyronine (FT4 thyroid hormones. Total protein concentration exhibited an increase in all the exposed groups of females. In the prenatal toxicity study, administration of N-methylaniline throughout the embryonic and fetal periods produced embryotoxic effects at doses ranging 4–100 mg/kg b.w./day. Conclusions: Considering the data obtained in this study, it is reasonable to assume that N-methylaniline administered orally to pregnant rats is toxic for mothers even at a low dose of 0.8 mg/kg b.w./day. However, this dose was not associated with any significant effects to their offspring. This prenatal exposure level may be considered as no-observed-adverse-effect level (NOAEL for the progeny and a dose of 4 mg/kg b.w./day as the lowest-observed-adverse-effect level (LOAEL for the progeny.

  8. Developmental toxicity of endocrine disruptors in early life stages of zebrafish, a genetic and embryogenesis study.

    Science.gov (United States)

    Santos, Dércia; Matos, Manuela; Coimbra, Ana M

    2014-01-01

    Endocrine disrupting compounds (EDCs) are capable of interfering with the endocrine system and are increasingly widespread in the aquatic environments. In the present study, zebrafish (Danio rerio) embryos and larvae were used to assess how EDCs may interfere with embryogenesis. Therefore, zebrafish embryos were exposed to 17α-ethinylestradiol (EE2: 0.4, 2, 4 and 20 ng/L), genistein (Gen: 2, 20, 200 and 2000 ng/L) and fadrozole (Fad: 2, 10, 50 and 250 μg/L), between 2 and 144 h post-fertilization (hpf). Somite development, heartbeat, malformations, mortality and hatching rates were evaluated. In parallel, the expression patterns of hormone receptors (esr1, esr2a, esr2b and ar) and apoptotic pathways related genes (p53 and c-jun) were determined using quantitative real-time PCR. Results showed that EE2, Gen and Fad caused a higher mortality and also malformations in larvae compared with control. A significant toxic effect was observed in the heartbeat rate, at 144 hpf, in larvae exposed to EE2 and Fad. QPCR revealed alterations in the expression levels of all the evaluated genes, at different time points. esr1 and c-jun genes were upregulated by EE2 and Gen exposure while the expression of esr2a, esr2b and ar genes was downregulated. Fad exposure decreased esr1, p53 and c-jun expression levels. This study shows a toxic effect of EE2, Gen and Fad to vertebrate embryogenesis and a relation between hormones action and apoptosis pathways. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Developmental toxicity of lead-contaminated sediment in Canada geese (Branta canadensis)

    Science.gov (United States)

    Hoffman, David J.; Heinz, Gary H.; Sileo, Louis; Audet, Daniel J.; Campbell, Juile K.; Obrecht, Holly H.

    2000-01-01

    Sediment ingestion has recently been identified as an important exposure route for toxicants in waterfowl. The effects of lead-contaminated sediment from the Coeur d'Alene River Basin (CDARB) in Idaho on posthatching development of Canada geese (Branta canadensis) were examined for 6 wk. Day-old goslings received either untreated control diet, clean sediment (48%) supplemented control diet, or CDARB sediment (3449 mug/g lead) supplemented diets at 12%, 24%, or 48%. The 12% CDARB diet resulted in a geometric mean blood lead concentration of 0.68 ppm (ww), with over 90% depression of red blood cell ALAD activity and over fourfold elevation of free erythrocyte protoporphyrin concentration. The 24% CDARB diet resulted in blood lead of 1.61 ppm with decreased hematocrit, hemoglobin, and plasma protein in addition to the effects just described. The 48% CDARB diet resulted in blood lead of 2.52 ppm with 22% mortality, decreased growth, and elevated plasma lactate dehydrogenase-L (LDH-L) activity. In this group the liver lead concentration was 6.57 ppm (ww), with twofold increases in hepatic lipid peroxidation (thiobarbituric acid-reactive substances, TBARS) and in reduced glutathione concentration; associated effects included elevated glutathione reductase activity but lower protein-bound thiols concentration and glucose-6-phosphate dehydrogenase (G-6-PDH) activity. The kidney lead concentration in this group was 14.93 ppm with subacute renal tubular nephrosis in one of the surviving goslings. Three other geese in this treatment group exhibited calcified areas of marrow, and one of these displayed severe chronic fibrosing pancreatitis. Lead from CDARB sediment accumulated less readily in gosling blood and tissues than reported in ducklings but at given concentrations was generally more toxic to goslings. Many of these effects were similar to those reported in wild geese and mallards within the Coeur d'Alene River Basin.

  10. Developmental toxicity of nicotine: A transdisciplinary synthesis and implications for emerging tobacco products.

    Science.gov (United States)

    England, Lucinda J; Aagaard, Kjersti; Bloch, Michele; Conway, Kevin; Cosgrove, Kelly; Grana, Rachel; Gould, Thomas J; Hatsukami, Dorothy; Jensen, Frances; Kandel, Denise; Lanphear, Bruce; Leslie, Frances; Pauly, James R; Neiderhiser, Jenae; Rubinstein, Mark; Slotkin, Theodore A; Spindel, Eliot; Stroud, Laura; Wakschlag, Lauren

    2017-01-01

    While the health risks associated with adult cigarette smoking have been well described, effects of nicotine exposure during periods of developmental vulnerability are often overlooked. Using MEDLINE and PubMed literature searches, books, reports and expert opinion, a transdisciplinary group of scientists reviewed human and animal research on the health effects of exposure to nicotine during pregnancy and adolescence. A synthesis of this research supports that nicotine contributes critically to adverse effects of gestational tobacco exposure, including reduced pulmonary function, auditory processing defects, impaired infant cardiorespiratory function, and may contribute to cognitive and behavioral deficits in later life. Nicotine exposure during adolescence is associated with deficits in working memory, attention, and auditory processing, as well as increased impulsivity and anxiety. Finally, recent animal studies suggest that nicotine has a priming effect that increases addiction liability for other drugs. The evidence that nicotine adversely affects fetal and adolescent development is sufficient to warrant public health measures to protect pregnant women, children, and adolescents from nicotine exposure. Published by Elsevier Ltd.

  11. Reproductive and developmental toxicity of the Ginkgo biloba special extract EGb 761® in mice.

    Science.gov (United States)

    Koch, Egon; Nöldner, Michael; Leuschner, Jost

    2013-12-15

    Extracts from leaves of Ginkgo biloba are among the most widely used and best investigated phytopharmaceuticals worldwide. Almost all clinical trials and the majority of preclinical studies have been performed with a specifically defined extract (EGb 761(®)) standardized to contain confined concentrations of active ingredients and limited quantities of potentially harmful substances. Besides pharmaceutical grade extracts poorly characterized Ginkgo preparations are now increasingly appearing on the market as nutraceuticals. While the safety of EGb 761(®) has been evaluated in an extensive set of toxicology studies, adverse effects of Ginkgo extracts of non-pharmaceutical quality on reproductive functions in mice have been reported in several publications in recent years. As this species has not previously been used in reproductive toxicity studies with EGb 761(®), the present investigation was conducted to examine the influence of EGb 761(®) (100, 350 and 1225mg/kg/day) on embryo-fetal development in mice during the critical period of organogenesis. During external and internal inspection of the fetuses as well as examination of skeletal and soft tissues no embryotoxic properties were noted. In particular, the incidence of malformations, variations or retardations was not increased and the general condition of dams was not influenced. Thus, the no-observed-effect level (NOEL) was above 1225mg/kg/day for the dams and the fetuses. Copyright © 2013 Elsevier GmbH. All rights reserved.

  12. Comparative Developmental Toxicity of Desalination Brine and Sulfate-Dominated Saltwater in a Euryhaline Fish.

    Science.gov (United States)

    Kupsco, Allison; Sikder, Rafid; Schlenk, Daniel

    2017-02-01

    Desalination is a promising sustainable solution to meet growing water needs of cities across the United States. However, the environmental impacts of the resulting filtrate (brine) discharged to surface water need to be evaluated before large-scale desalination can be successful in the United States. Developing fish are especially sensitive to changes in salinity and varying ionic composition. Limited research is available on the impacts of hypersalinity on chronic vertebrate embryonic development, particularly on sublethal effects. To investigate this, Japanese medaka (Oryzias latipes) embryos were treated with: (1) graphite filtered freshwater; (2) artificial seawater [17, 35, 42, 56, and 70 parts per thousand (ppt)]; (3) effluent from a desalination facility at Monterey Bay Aquarium, CA, diluted to 75, 50, and 25% with 35 ppt artificial seawater to simulate mixing (39, 42, 46, and 50 ppt); (4) artificial San Joaquin River water (CA, USA) (9, 13, and 17 ppt); and (5) artificial San Joaquin River water diluted to 75, 50, and 25% with artificial seawater to simulate estuarine mixing in the San Francisco Bay (13, 19, 24, and 30 ppt). Percent hatch, survival post hatch, deformities, swim bladder inflation, and median day to hatch were recorded to calculate EC50 (50% effect concentration) and NOEC (no observable effect concentration) values. No significant difference was observed between artificial seawater and Monterey Bay aquarium effluent (EC50 = 45-55 ppt). However, San Joaquin River water decreased survival post hatch and increased deformities in comparison to artificial seawater and San Joaquin River water mixed with seawater, suggesting that unique ion compositions may play a role in embryo and larval toxicity.

  13. Gestational Zearalenone Exposure Causes Reproductive and Developmental Toxicity in Pregnant Rats and Female Offspring

    Directory of Open Access Journals (Sweden)

    Xin Gao

    2017-01-01

    Full Text Available Zearalenone (ZEN is an oestrogenic mycotoxin commonly found in food and feed products and can affect reproduction and development in both humans and animals. This study aimed to determine the toxic effects of ZEN on maternal SD rats and the F1 female offspring. Sixty-four pregnant rats were divided into 4 groups and exposed to feed contaminated with ZEN (0, 5, 10, and 20 mg/kg feed on gestational days (GDs 0–21. Compared with the controls, the groups exposed to 10 and 20 mg/kg ZEN showed significantly decreased feed intake and body weight of pregnant rats and/or female offspring. Meanwhile, 20 mg/kg ZEN significantly decreased the birth weight and viability of F1 newborn rats. Moreover, 10 and 20 mg/kg ZEN diets increased follicle-stimulating hormone concentrations but decreased oestradiol in both maternal and F1 adult rats. In the F1 generation, ZEN caused no pathological changes in ovaries and uterus in weaned rats, but significant follicular atresia and a thinning uterine layer were found in F1 female adult rats in the 20 mg/kg ZEN group. These impairments concurred with the inhibited mRNA and protein levels of oestrogen receptor-alpha (Esr1 and 3β-hydroxysteroid dehydrogenase (HSD in the adult uterus and/or ovaries. Furthermore, 10 and/or 20 mg/kg ZEN exposure significantly reduced Esr1, gonadotropin-releasing hormone receptor (GnRHr, and ATP binding cassette transporters b1 and c1 (ABCb1 and ABCc1 in the placenta and foetal and weaned F1 brains, and also produced a dose-dependent increase in 3β-HSD in the placenta. Additionally, 20 mg/kg ZEN significantly upregulated ABCc5 expression in the placenta and ovaries of weaned rats. These results suggested that prenatal ZEN exposure in rats affected maternal and foetal development and may lead to long-term reproductive impairment in F1 adult females.

  14. Development of a Combined In Vitro Physiologically Based Kinetic (PBK) and Monte Carlo Modelling Approach to Predict Interindividual Human Variation in Phenol-Induced Developmental Toxicity.

    Science.gov (United States)

    Strikwold, Marije; Spenkelink, Bert; Woutersen, Ruud A; Rietjens, Ivonne M C M; Punt, Ans

    2017-06-01

    With our recently developed in vitro physiologically based kinetic (PBK) modelling approach, we could extrapolate in vitro toxicity data to human toxicity values applying PBK-based reverse dosimetry. Ideally information on kinetic differences among human individuals within a population should be considered. In the present study, we demonstrated a modelling approach that integrated in vitro toxicity data, PBK modelling and Monte Carlo simulations to obtain insight in interindividual human kinetic variation and derive chemical specific adjustment factors (CSAFs) for phenol-induced developmental toxicity. The present study revealed that UGT1A6 is the primary enzyme responsible for the glucuronidation of phenol in humans followed by UGT1A9. Monte Carlo simulations were performed taking into account interindividual variation in glucuronidation by these specific UGTs and in the oral absorption coefficient. Linking Monte Carlo simulations with PBK modelling, population variability in the maximum plasma concentration of phenol for the human population could be predicted. This approach provided a CSAF for interindividual variation of 2.0 which covers the 99th percentile of the population, which is lower than the default safety factor of 3.16 for interindividual human kinetic differences. Dividing the dose-response curve data obtained with in vitro PBK-based reverse dosimetry, with the CSAF provided a dose-response curve that reflects the consequences of the interindividual variability in phenol kinetics for the developmental toxicity of phenol. The strength of the presented approach is that it provides insight in the effect of interindividual variation in kinetics for phenol-induced developmental toxicity, based on only in vitro and in silico testing. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  15. 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

    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...... QSAR predictions may be used to identify potential genotoxic carcinogens, mutagens and developmental toxicants by high-throughput virtual screening....

  16. Assessing water quality in a tropical lake using biomarkers in zebrafish embryos: developmental toxicity and stress protein responses.

    Science.gov (United States)

    Hallare, A V; Pagulayan, R; Lacdan, N; Köhler, H R; Triebskorn, R

    2005-05-01

    In order to achieve a more substantial appraisal of lake water quality, the assessment must not be based only on chemical measurements and analyses of the water itself, but even more so on the impact of existing conditions on aquatic biota. This is possible with the use of biotests or biomarkers, e.g. investigations of the developmental parameters (96-h embryotoxicity evaluate) or of the induction of heat shock proteins (proteotoxicity evaluate). To evaluate the suitability of these tests for environmental screening, fertilized zebrafish eggs were exposed to water samples collected from five sites of varying levels of stress from Laguna Lake, Philippines. Reconstituted water was used as laboratory control while water samples from a highly polluted freshwater source was used as positive control. Developmental parameters were noted and described within 48 and 96 h of exposure. Dilution experiments of the positive control were also done to further assess and compare toxicity potentials of Laguna Lake waters with those originating from a polluted freshwater. After the 96-h exposure, the levels of stress proteins (hsp 70) were determined in embryos from all exposure groups. Results showed 100% mortality in embryos exposed to undiluted positive control (PC) within only 12 h. Increasing dilution levels, however, resulted in lower mortality and lower abnormality rates. No detectable developmental differences were noted among embryos exposed to either the laboratory control or Laguna Lake waters at the end of 96 h, regardless of the source. Very high survival rates and high hatching success rates were observed in embryos exposed to lake waters as well as laboratory control, and the data did not differ significantly among the groups. Likewise, no significant malformations were noted among all developing embryos throughout the exposure period. However, the levels of heat shock proteins in the two sites located closest to Manila, the Philippine capital (Northern West Bay and

  17. Monoisoamyl dimercaptosuccinic acid abrogates arsenic-induced developmental toxicity in human embryonic stem cell-derived embryoid bodies: comparison with in vivo studies.

    Science.gov (United States)

    Flora, S J S; Mehta, Ashish

    2009-11-15

    The ability of human embryonic stem (ES) cells to differentiate into the three germ layers has proposed its application in studying human developmental toxicity in vitro. In the current study we investigated if the prompted application could be utilized to evaluate the efficacy of a newly developed arsenic antidote, monoisoamyl dimercaptosuccinic acid (MiADMSA) against arsenic (III) and if the results obtained in vitro were in concordance with the animal model for studying developmental toxicity. On the basis of real time PCR (qRT-PCR) and cytotoxicity analysis of human embryoid bodies (EBs), we observed that arsenic (III) caused a significant down regulation of gene expression in all the three germ layers, which could be correlated with high mortality, visceral and skeletal defects in pups. Reversal of arsenic-induced dysfunctioning could be observed with concomitant treatment of MiADMSA in vitro and in vivo, indicating ES-EB model could provide toxicity information similar to in vivo model. IR spectroscopy further suggested that MiADMSA bind to arsenic to form adduct, which prevents arsenic from exerting its toxic effect in both models. To our knowledge this study provides first experimental evidence suggesting human ES cells could be utilized in studying the efficacy of drugs in a comparable manner with animal models. We conclude that the ES-EB model seems to be an effective, faster, cost effective method for predicting efficacy of a drug.

  18. Computer Simulation of Embryonic Systems: What can a virtual embryo teach us about developmental toxicity? Microcephaly: Computational and organotypic modeling of a complex human birth defect (seminar and lecture - Thomas Jefferson University, Philadelphia, PA)

    Science.gov (United States)

    (1) Standard practice for assessing developmental toxicity is the observation of apical endpoints (intrauterine death, fetal growth retardation, structural malformations) in pregnant rats/rabbits following exposure during organogenesis. EPA’s computational toxicology research pro...

  19. Comparison of Birth-and Conception-Based Definitions of Postnatal Age in Developmental and Reproductive Rodent Toxicity Studies: Influence of Gestation Length and Timing of Neonatal Examinations on Litter Data in Controls

    Science.gov (United States)

    Laboratories conducting developmental and reproductive toxicity studies with rodents use varied protocols for determining the timing of neonatal litter examinations and subsequent measurements. Most laboratories determine timing based on the day of birth (DOB); l.e., gestation le...

  20. Fertility and developmental toxicity assessment in rats and rabbits with LY500307, a selective estrogen receptor beta (ERβ) agonist.

    Science.gov (United States)

    Hilbish, Kim G; Breslin, William J; Johnson, Jason T; Sloter, Eddie D

    2013-10-01

    less than proportionally in rabbits. In conclusion, the no-observed adverse effect levels following LY500307 administration were 1 mg/kg/day for male rat fertility, 0.3 mg/kg/day for female rat fertility and EFD, and 25 mg/kg/day for rabbit EFD. Adverse reproductive and developmental effects only occurred at or above parentally toxic dosage levels and were considered predominantly due to off-target ERα effects. © 2013 Wiley Periodicals, Inc.

  1. Persistent developmental toxicity in rat offspring after low dose exposure to a mixture of endocrine disrupting pesticides

    DEFF Research Database (Denmark)

    Jacobsen, Pernille Rosenskjold; Petersen, Marta Axelstad; Boberg, Julie

    2012-01-01

    There is growing concern of permanent damage to the endocrine and nervous systems after developmental exposure to endocrine disrupting chemicals. In this study the permanent reproductive and neurobehavioral effects of combined exposure to five endocrine disrupting pesticides, epoxiconazole...

  2. 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.

  3. Developmental toxicity studies with 6 forms of titanium dioxide test materials (3 pigment-different grade & 3 nanoscale) demonstrate an absence of effects in orally-exposed rats.

    Science.gov (United States)

    Warheit, D B; Boatman, R; Brown, S C

    2015-12-01

    Six different commercial forms and sizes of titanium dioxide particles were tested in separate developmental toxicity assays. The three pigment-grade (pg) or 3 ultrafine (uf)/nanoscale (anatase and/or rutile) titanium dioxide (TiO2) particle-types were evaluated for potential maternal and developmental toxicity in pregnant rats by two different laboratories. All studies were conducted according to OECD Guideline 414 (Prenatal Developmental Toxicity Study). In addition, all test materials were robustly characterized. The BET surface areas of the pg and uf samples ranged from 7 to 17 m(2)/g and 50-82 m(2)/g respectively (see Table 1). The test substances were formulated in sterile water. In all of the studies, the formulations were administered by oral gavage to time-mated rats daily beginning around the time of implantation and continuing until the day prior to expected parturition. In 3 of the studies (uf-1, uf-3, & pg-1), the formulations were administered to Crl:CD(SD) rats beginning on gestation day (GD) 6 through GD 20. In 3 additional studies (uf-2, and pg-2, pg-3 TiO2 particles), the formulations were administered to Wistar rats beginning on GD 5 through 19. The dose levels used in all studies were 0, 100, 300, or 1000 mg/kg/day; control group animals were administered the vehicle. During the in-life portions of the studies, body weights, food consumption, and clinical observations before and after dosing were collected on a daily basis. All dams were euthanized just prior to expected parturition (GD 21 for Crl:CD(SD) rats and GD 20 for Wistar rats). The gross necropsies included an examination and description of uterine contents including counts of corpora lutea, implantation sites, resorptions, and live and dead fetuses. All live fetuses were sexed, weighed, and examined externally and euthanized. Following euthanasia, fresh visceral and head examinations were performed on selected fetuses. The fetal carcasses were then processed and examined for skeletal

  4. Multiple bio-analytical methods to reveal possible molecular mechanisms of developmental toxicity in zebrafish embryos/larvae exposed to tris(2-butoxyethyl) phosphate

    Energy Technology Data Exchange (ETDEWEB)

    Han, Zhihua [State Key Laboratory of Pollution Control and Resource Reuse and School of the Environment, Nanjing University, Nanjing 210023 (China); Wang, Qiangwei [State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072 (China); Fu, Jie [State Key Laboratory of Pollution Control and Resource Reuse and School of the Environment, Nanjing University, Nanjing 210023 (China); Chen, Hongshan [State Environmental Protection Key Laboratory of Wetland Ecology and Vegetation Restoration, School of the Environment, Northeast Normal University, Changchun 130024 (China); Department of Biological Sciences, National University of Singapore (Singapore); Zhao, Ye [Department of Biological Sciences, National University of Singapore (Singapore); Zhou, Bingsheng [State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072 (China); Gong, Zhiyuan [Department of Biological Sciences, National University of Singapore (Singapore); Wei, Si; Li, Jun; Liu, Hongling; Zhang, Xiaowei [State Key Laboratory of Pollution Control and Resource Reuse and School of the Environment, Nanjing University, Nanjing 210023 (China); Liu, Chunsheng, E-mail: liuchunshengidid@126.com [State Key Laboratory of Pollution Control and Resource Reuse and School of the Environment, Nanjing University, Nanjing 210023 (China); Department of Biological Sciences, National University of Singapore (Singapore); College of Fisheries, Huazhong Agricultural University, Wuhan 430070 (China); Yu, Hongxia, E-mail: yuhx@nju.edu.cn [State Key Laboratory of Pollution Control and Resource Reuse and School of the Environment, Nanjing University, Nanjing 210023 (China)

    2014-05-01

    Highlights: • TBEP exposure decreased the survival of zebrafish embryos/larvae. • TBEP exposure led to its bioconcentration in zebrafish lavare. • TBEP caused developmental toxicity by inhibiting the degradation and utilization of nutrients. • TBEP exposure caused developmental toxicity by inducing apoptosis. - Abstract: The flame retardant tris(2-butoxyethyl) phosphate (TBEP) is a frequently detected contaminant in the environment, wildlife and human milk. The potentially toxic effects of TBEP and their underlying molecular mechanisms have not been elucidated. Here, zebrafish embryos were exposed to different concentrations of TBEP from 4 hours of post-fertilization (hpf) to 120 hpf, and effects on embryonic development and global protein expression patterns examined. Our results demonstrate that treatment with TBEP (0.8–100 mg/L) causes a concentration- and time-dependent decrease in embryonic survival and the hatching percentage. The median lethal concentration was 10.7 mg/L at 120 hpf. Furthermore, exposure to 150 or 800 μg/L TBEP inhibited the degradation and utilization of vitellogenins and down-regulated the expression of proteins related to cation binding, and lipid transport, uptake and metabolism, accompanied by a decrease in heart rate and body length. Exposure to TBEP (150 or 800 μg/L) also decreased the expression of proteins involved in cell proliferation and DNA repair, and led to an increased number of apoptotic cells in the tail region. Collectively, our results suggest that exposure to TBEP causes toxicity in the developing zebrafish by inhibiting the degradation and utilization of nutrients from the mother and inducing apoptosis.

  5. Nanosecond pulsed electric field incorporation technique to predict molecular mechanisms of teratogenicity and developmental toxicity of estradiol-17β on medaka embryos.

    Science.gov (United States)

    Yamaguchi, Akemi; Ishibashi, Hiroshi; Kono, Susumu; Iida, Midori; Uchida, Masaya; Arizono, Koji; Tominaga, Nobuaki

    2017-12-27

    Herein, we propose using a nanosecond pulsed electric field (nsPEF) technique to assess teratogenicity and embryonic developmental toxicity of estradiol-17β (E 2 ) and predict the molecular mechanisms of teratogenicity and embryonic developmental defects caused by E 2 on medaka (Oryzias latipes). The 5 hour post-fertilization embryos were exposed to co-treatment with 10 μm E 2 and nsPEF for 2 hours and then continuously cultured under non-E 2 and nsPEF conditions until hatching. Results documented that the time to hatching of embryos was significantly delayed in comparison to the control group and that typical abnormal embryo development, such as the delay of blood vessel formation, was observed. For DNA microarray analysis, 6 day post-fertilization embryos that had been continuously cultured under the non-E 2 and nsPEF condition after 2 hour co-treatments were used. DNA microarray analysis identified 542 upregulated genes and one downregulated gene in the 6 day post-fertilization embryos. Furthermore, bioinformatic analyses using differentially expressed genes revealed that E 2 exposure affected various gene ontology terms, such as response to hormone stimulus. The network analysis also documented that the estrogen receptor α in the mitogen-activated protein kinase signaling pathway may be involved in regulating several transcription factors, such as FOX, AKT1 and epidermal growth factor receptor. These results suggest that our nsPEF technique is a powerful tool for assessing teratogenicity and embryonic developmental toxicity of E 2 and predict their molecular mechanisms in medaka embryos. Copyright © 2017 John Wiley & Sons, Ltd.

  6. Zebrafish on a chip: a novel platform for real-time monitoring of drug-induced developmental toxicity.

    Directory of Open Access Journals (Sweden)

    Yinbao Li

    Full Text Available Pharmaceutical safety testing requires a cheap, fast and highly efficient platform for real-time evaluation of drug toxicity and secondary effects. In this study, we have developed a microfluidic system for phenotype-based evaluation of toxic and teratogenic effects of drugs using zebrafish (Danio rerio embryos and larvae as the model organism. The microfluidic chip is composed of two independent functional units, enabling the assessment of zebrafish embryos and larvae. Each unit consists of a fluidic concentration gradient generator and a row of seven culture chambers to accommodate zebrafish. To test the accuracy of this new chip platform, we examined the toxicity and teratogenicity of an anti-asthmatic agent-aminophylline (Apl on 210 embryos and 210 larvae (10 individuals per chamber. The effect of Apl on zebrafish embryonic development was quantitatively assessed by recording a series of physiological indicators such as heart rate, survival rate, body length and hatch rate. Most importantly, a new index called clonic convulsion rate, combined with mortality was used to evaluate the toxicities of Apl on zebrafish larvae. We found that Apl can induce deformity and cardiovascular toxicity in both zebrafish embryos and larvae. This microdevice is a multiplexed testing apparatus that allows for the examination of indexes beyond toxicity and teratogenicity at the sub-organ and cellular levels and provides a potentially cost-effective and rapid pharmaceutical safety assessment tool.

  7. Environmentally relevant levels of λ-cyhalothrin, fenvalerate, and permethrin cause developmental toxicity and disrupt endocrine system in zebrafish (Danio rerio) embryo.

    Science.gov (United States)

    Zhang, Quan; Zhang, Yi; Du, Jie; Zhao, Meirong

    2017-10-01

    Synthetic pyrethroids (SPs) are one of the most widely used pesticides and frequently detected in the aquatic environment. Previous studies have shown that SPs posed high aquatic toxicity, but information on the developmental toxicity and endocrine disruption on zebrafish (Danio rerio) at environmentally relevant concentrations is limited. In this study, zebrafish embryos were employed to examine the adverse effects of λ-cyhalothrin (LCT), fenvalerate (FEN), and permethrin (PM) at 2.5, 10, 25, 125, 500 nM for 96 h. The results showed these 3 SPs caused dose-dependent mortality, malformation rate, and hatching rate. Thyroid hormone triiodothyronine (T3) levels were significantly decreased after exposure to LCT and FEN. Quantitative real-time PCR analysis was then performed on a series of nuclear receptors (NRs) genes involved in the hypothalamic-pituitary-gonadal (HPG), hypothalamic-pituitary-thyroid (HPT), hypothalamic-pituitary-adrenocortical (HPA) axes, and oxidative-stress-related system. Our results showed that LCT, FEN, and PM downregulated AR expression while upregulated ER1 expression, and caused alteration to ER2a and ER2b expression. As for the expression of TRα and TRβ, they were both decreased following exposure to the 3 SPs. LCT and PM downregulated the MR expression and FEN induced MR expression. In addition, the expression of GR was increased after treating with LCT, while it was suppressed after exposure to FEN and PM. The 3 SPs also caused various alterations to the expression of genes including AhRs, PPARα, and PXR. These findings suggest that these 3 SPs may cause developmental toxicity to zebrafish larvae by disrupting endocrine signaling at environmentally relevant concentrations. Copyright © 2017. Published by Elsevier Ltd.

  8. Integrating in vitro data and physiologically based kinetic (PBK) modelling to assess the in vivo potential developmental toxicity of a series of phenols.

    Science.gov (United States)

    Strikwold, Marije; Spenkelink, Bert; de Haan, Laura H J; Woutersen, Ruud A; Punt, Ans; Rietjens, Ivonne M C M

    2017-05-01

    Toxicity outcomes derived in vitro do not always reflect in vivo toxicity values, which was previously observed for a series of phenols tested in the embryonic stem cell test (EST). Translation of in vitro data to the in vivo situation is therefore an important, but still limiting step for the use of in vitro toxicity outcomes in the safety assessment of chemicals. The aim of the present study was to translate in vitro embryotoxicity data for a series of phenols to in vivo developmental toxic potency values for the rat by physiologically based kinetic (PBK) modelling-based reverse dosimetry. To this purpose, PBK models were developed for each of the phenols. The models were parameterised with in vitro-derived values defining metabolism and transport of the compounds across the intestinal and placental barrier and with in silico predictions and data from the literature. Using PBK-based reverse dosimetry, in vitro concentration-response curves from the EST were translated into in vivo dose-response curves from which points of departure (PoDs) were derived. The predicted PoDs differed less than 3.6-fold from PoDs derived from in vivo toxicity data for the phenols available in the literature. Moreover, the in vitro PBK-based reverse dosimetry approach could overcome the large disparity that was observed previously between the in vitro and the in vivo relative potency of the series of phenols. In conclusion, this study shows another proof-of-principle that the in vitro PBK approach is a promising strategy for non-animal-based safety assessment of chemicals.

  9. PROLIFERATION AS A KEY EVENT IN DEVELOPMENTAL TOXICITY: "CHEMICAL SCREENING IN HUMAN NEURAL STEM CELLS USING HIGH CONTENT IMAGING

    Science.gov (United States)

    New toxicity testing approaches will rely on in vitro assays to assess chemical effects at the cellular and molecular level. Cell proliferation is imperative to normal development, and chemical disruption of this process can be detrimental to the organism. As part of an effort to...

  10. 20161106 - Human Pluripotent Stem Cell-Based Assay Predicts Developmental Toxicity Potential of ToxCast Chemicals (ACT meeting)

    Science.gov (United States)

    Worldwide initiatives to screen for toxicity potential among the thousands of chemicals currently in use require inexpensive and high-throughput in vitro models to meet their goals. The devTOX quickPredict platform is an in vitro human pluripotent stem cell-based assay used to as...

  11. Human Pluripotent Stem Cell-Based Assay Predicts Developmental Toxicity Potential of ToxCast Chemicals (ACT meeting)

    Science.gov (United States)

    Worldwide initiatives to screen for toxicity potential among the thousands of chemicals currently in use require inexpensive and high-throughput in vitro models to meet their goals. The devTOX quickPredict platform is an in vitro human pluripotent stem cell-based assay used to as...

  12. Signal management in pharmacovigilance and human risk assessment of CpG 7909, integrating embryo-fetal and post-natal developmental toxicity studies in rats and rabbits.

    Science.gov (United States)

    Delannois, Frédérique; Planty, Camille; Giordano, Giulia; Destexhe, Eric; Stanislaus, Dinesh; Da Silva, Fernanda Tavares; Stegmann, Jens-Ulrich; Thacker, Karen; Reynaud, Lucie; Garçon, Nathalie; Segal, Lawrence

    2018-01-01

    The potential reproductive and developmental toxicity of the synthetic oligodeoxynucleotide (ODN) CpG 7909, a component of GSK's AS15 immunostimulant, was examined in rat and rabbit studies following intermittent intramuscular injections. Previous studies using subcutaneous and intraperitoneal injections in mice, rats and rabbits revealed that CpG ODNs induced developmental effects. To analyze the safety signal, GSK conducted additional animal studies using the intended clinical route of administration. CpG 7909 injections were administered intramuscularly to rats or rabbits 28 and 14days before pairing, on 4 or 5 occasions during gestation, and on lactation day 7. The No Observed Adverse Effect Level for female fertility, embryo-fetal and pre- and post-natal development was 4.2mg/kg in both species, approximately 500-fold higher than the anticipated human dose. In conclusion, the anticipated risk to humans is considered low for sporadic intramuscular exposure to CpG 7909. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Arsenic (III, V), indium (III), and gallium (III) toxicity to zebrafish embryos using a high-throughput multi-endpoint in vivo developmental and behavioral assay.

    Science.gov (United States)

    Olivares, Christopher I; Field, Jim A; Simonich, Michael; Tanguay, Robert L; Sierra-Alvarez, Reyes

    2016-04-01

    Gallium arsenide (GaAs), indium gallium arsenide (InGaAs) and other III/V materials are finding increasing application in microelectronic components. The rising demand for III/V-based products is leading to increasing generation of effluents containing ionic species of gallium, indium, and arsenic. The ecotoxicological hazard potential of these streams is unknown. While the toxicology of arsenic is comprehensive, much less is known about the effects of In(III) and Ga(III). The embryonic zebrafish was evaluated for mortality, developmental abnormalities, and photomotor response (PMR) behavior changes associated with exposure to As(III), As(V), Ga(III), and In(III). The As(III) lowest observable effect level (LOEL) for mortality was 500 μM at 24 and 120 h post fertilization (hpf). As(V) exposure was associated with significant mortality at 63 μM. The Ga(III)-citrate LOEL was 113 μM at 24 and 120 hpf. There was no association of significant mortality over the tested range of In(III)-citrate (56-900 μM) or sodium citrate (213-3400 μM) exposures. Only As(V) resulted in significant developmental abnormalities with LOEL of 500 μM. Removal of the chorion prior to As(III) and As(V) exposure was associated with increased incidence of mortality and developmental abnormality suggesting that the chorion may normally attenuate mass uptake of these metals by the embryo. Finally, As(III), As(V), and In(III) caused PMR hypoactivity (49-69% of control PMR) at 900-1000 μM. Overall, our results represent the first characterization of multidimensional toxicity effects of III/V ions in zebrafish embryos helping to fill a significant knowledge gap, particularly in Ga(III) and In(III) toxicology. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. 3D Visualization of Developmental Toxicity of 2,4,6-Trinitrotoluene in Zebrafish Embryogenesis Using Light-Sheet Microscopy

    OpenAIRE

    Juneyong Eum; Jina Kwak; Hee Joung Kim; Seoyoung Ki; Kooyeon Lee; Ahmed A. Raslan; Ok Kyu Park; Md Ashraf Uddin Chowdhury; Song Her; Yun Kee; Seung-Hae Kwon; Byung Joon Hwang

    2016-01-01

    Environmental contamination by trinitrotoluene is of global concern due to its widespread use in military ordnance and commercial explosives. Despite known long-term persistence in groundwater and soil, the toxicological profile of trinitrotoluene and other explosive wastes have not been systematically measured using in vivo biological assays. Zebrafish embryos are ideal model vertebrates for high-throughput toxicity screening and live in vivo imaging due to their small size and transparency ...

  15. Design of a high-throughput human neural crest cell migration assay to indicate potential developmental toxicants.

    Science.gov (United States)

    Nyffeler, Johanna; Karreman, Christiaan; Leisner, Heidrun; Kim, Yong Jun; Lee, Gabsang; Waldmann, Tanja; Leist, Marcel

    2017-01-01

    Migration of neural crest cells (NCCs) is one of the pivotal processes of human fetal development. Malformations arise if NCC migration and differentiation are impaired genetically or by toxicants. In the currently available test systems for migration inhibition of NCC (MINC), the manual generation of a cell-free space results in extreme operator dependencies, and limits throughput. Here a new test format was established. The assay avoids scratching by plating cells around a commercially available circular stopper. Removal of the stopper barrier after cell attachment initiates migration. This microwell-based circular migration zone NCC function assay (cMINC) was further optimized for toxicological testing of human pluripotent stem cell (hPSC)-derived NCCs. The challenge of obtaining data on viability and migration by automated image processing was addressed by developing a freeware. Data on cell proliferation were obtained by labelling replicating cells, and by careful assessment of cell viability for each experimental sample. The role of cell proliferation as an experimental confounder was tested experimentally by performing the cMINC in the presence of the proliferation-inhibiting drug cytosine arabinoside (AraC), and by a careful evaluation of mitotic events over time. Data from these studies led to an adaptation of the test protocol, so that toxicant exposure was limited to 24 h. Under these conditions, a prediction model was developed that allows classification of toxicants as either inactive, leading to unspecific cytotoxicity, or specifically inhibiting NC migration at non-cytotoxic concentrations.

  16. 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.

  17. 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...

  18. Developmental Toxicity and Fertility Assessment in Rabbits with Tabalumab: A Human IgG4 Monoclonal Antibody.

    Science.gov (United States)

    Breslin, William J; Hilbish, Kim G; Martin, Jennifer A; Halstead, Carolyn A; Edwards, Tammy L

    2015-06-01

    Tabalumab is a human immunoglobulin G subclass 4 monoclonal antibody that has been under development for autoimmune disorders. Tabalumab has full neutralizing activity against both soluble and membrane B-cell activating factor, a B-cell survival factor. The objectives of these studies were to assess the effects of tabalumab on embryo-fetal development and on male (M) and female (F) fertility in rabbits, a pharmacologically relevant species. Doses were administered at 0 (vehicle control), 0.3 (embryo-fetal study only), 1.0, and 30 mg/kg. In the embryo-fetal study, pregnant rabbits does were given a single dose by intravenous injection on gestation day (GD) 7. In the fertility studies, tabalumab was administered by intravenous injection every 7 days starting 2 (F) or 4 (M) weeks before mating, during cohabitation, and until necropsy (M) or through GD 18 (F). Treated animals were mated with untreated partners. Parental clinical signs, body weight, food consumption, blood lymphocyte phenotyping, organ weights, morphologic pathology, ovarian and uterine observations, sperm parameters, and fertility indices were evaluated along with conceptus viability, weight, and morphology. Exposure assessments were made in all main study animals and satellite animals. No adverse parental, reproductive, or developmental effects were observed in any study at any dose. A pharmacodynamic response consisting of dose-dependent decreases in the percent and number of total B lymphocytes and increases in the percent and/or number of total T lymphocytes was observed in parental rabbits at 1.0 and 30 mg/kg. In conclusion, no adverse reproductive or developmental effects were observed in rabbits following exposure to tabalumab at doses as high as 30 mg/kg and exposures at least 14-fold greater than human exposure levels. © 2015 Wiley Periodicals, Inc.

  19. Implications of exposure to dextran-coated and uncoated iron oxide nanoparticles to developmental toxicity in zebrafish

    Science.gov (United States)

    de Oliveira, Giovanna Medeiros Tavares; de Oliveira, Elisa Magno Nunes; Pereira, Talita Carneiro Brandão; Papaléo, Ricardo Meurer; Bogo, Maurício Reis

    2017-12-01

    Iron oxide nanoparticles (IONPS) have been widely investigated as a platform for a new class of multifunctional theranostic agents. They are considered biocompatible, and some formulations are already available in the market for clinical use. However, contradictory results regarding toxicity of IONPs raise a concern about the potential harm of these nanoparticles. Changes in the nanoparticle (NP) physicochemical properties or exposure media can significantly alter their behavior and, as a consequence, their toxic effects. Here, behavior and two-step RT-qPCR were employed to access the potential toxicological effects of dextran-coated IONPs (CLIO-NH2) and uncoated IONPs (UCIO) in zebrafish larvae. Animals were exposed for 7 days to NP solutions ranging from 0.1-100 μg/mL directly mixed to the system water. UCIO showed high decantation and instability in solution, altering zebrafish mortality but showing no alterations in behavior and molecular expression analysis. CLIO-NH2 exposure did not cause significant mortality or changes in hatching rate of zebrafish larvae; however, behavior and expression profiles of the group exposed to lower concentration (1 μg/mL) presented a tendency to decrease the locomotor activity and apoptotic pathway activation.

  20. Developmental toxicity of Fe3O4 nanoparticles on cysts and three larval stages of Artemia salina.

    Science.gov (United States)

    Zhu, Song; Xue, Ming-Yang; Luo, Fei; Chen, Wei-Chao; Zhu, Bin; Wang, Gao-Xue

    2017-11-01

    Using Artemia salina cysts (capsulated and decapsulated) and larvae (instar I, II and III) as experimental models, the potential effects of Fe3O4 nanoparticles (Fe3O4-NPs) on marine ecosystems were investigated. Hatchability, mortality and a number of ethological, morphological and biochemical parameters were selected as end-points to define the toxic responses. Data showed that the hatching rates of capsulated and decapsulated cysts were significantly decreased (p < 0.01) following exposure to 600 mg/L for 24 and 36 h. The LC50 values for instar II and III were 482 and 561 mg/L (could not be measured for instar I), and the EC50 values for swimming inhibition of instar I, II and III were 474, 365 and 421 mg/L, respectively. Effects on hatchability, mortality and swimming were accounted for Fe3O4-NPs rather than iron ion released from the NPs. Instar II larvae showed the greatest sensitivity to Fe3O4-NPs, and followed by instar III, instar I, decapsulated cysts and capsulated cysts. Body lengths of instar I, II and III larvae were decreased in dose-dependent manners. Fe3O4-NPs attached onto the gills and body surface, resulting in irreversible damages. Reactive oxygen species, malondialdehyde content, total antioxidant capacity and antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase) activities were substantially increased following exposure, indicating that toxic effects were related to oxidative stress. Mitochondrial malformation, cristae rupturing and membranous structure disruption were clearly observed after Fe3O4-NPs exposure. Fe3O4-NPs were ingested and well distributed in the gut, yolk and primary body cavity. Uptake kinetics data showed that the maximum Fe3O4-NPs content (16.4 mg/g) was reached at 30 h. The combined results so far indicate that Fe3O4-NPs have the potential to affect aquatic organisms when released into the marine ecosystems. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Mammary Gland Evaluation in Juvenile Toxicity Studies: Temporal Developmental Patterns in the Male and Female Harlan Sprague Dawley Rat

    Science.gov (United States)

    Filgo, Adam J.; Foley, Julie F.; Puvanesarajah, Samantha; Borde, Aditi R.; Midkiff, Bentley R.; Reed, Casey E.; Chappell, Vesna A.; Alexander, Lydia B.; Borde, Pretish R.; Troester, Melissa A.; Hayes Bouknight, Schantel A.; Fenton, Suzanne E.

    2016-01-01

    There are currently no reports describing mammary gland development in the Harlan Sprague Dawley (HSD) rat, the current strain of choice for National Toxicology Program (NTP) testing. Our goals were to empower the NTP, contract labs and other researchers in understanding and interpretation of chemical effects in this rat strain. To delineate similarities/differences between the female and male mammary gland, data were compiled starting on embryonic day 15.5 through postnatal day 70. Mammary gland whole mounts, histology sections, and immunohistochemically-stained tissues for estrogen, progesterone and androgen receptors were evaluated in both sexes; qualitative and quantitative differences are highlighted using a comprehensive visual timeline. Research on endocrine disrupting chemicals in animal models has highlighted chemically-induced mammary gland anomalies which may potentially impact human health. In order to investigate these effects within the HSD strain, 2,3,7,8-tetrachlorodibenzo p-dioxin, diethylstilbestrol or vehicle control was gavage dosed on gestation day 15 and 18 to demonstrate delayed, accelerated and control mammary gland growth in offspring, respectively. We provide illustrations of normal and chemically altered mammary gland development in HSD male and female rats to help inform researchers unfamiliar with the tissue and may facilitate enhanced evaluation of both male and female mammary glands in juvenile toxicity studies. PMID:27613106

  2. Developmental toxicity and DNA damage from exposure to parking lot runoff retention pond samples in the Japanese medaka (Oryzias latipes).

    Science.gov (United States)

    Colton, Meryl D; Kwok, Kevin W H; Brandon, Jennifer A; Warren, Isaac H; Ryde, Ian T; Cooper, Ellen M; Hinton, David E; Rittschof, Daniel; Meyer, Joel N

    2014-08-01

    Parking lot runoff retention ponds (PLRRP) receive significant chemical input, but the biological effects of parking lot runoff are not well understood. We used the Japanese medaka (Oryzias latipes) as a model to study the toxicity of water and sediment samples from a PLRRP in Morehead City, NC. Medaka exposed in ovo to a dilution series of PLRRP water had increased odds of death before hatching, but not teratogenesis or delayed hatching. Next, we adapted a long-amplicon quantitative PCR (LA-QPCR) assay for DNA damage for use with the Japanese medaka. We employed LA-QPCR to test the hypotheses that PLRRP water and sediments would cause nuclear and mitochondrial DNA damage with and without full-spectrum, natural solar radiation. Fluoranthene with and without natural sunlight was a positive control for phototoxic polycyclic aromatic hydrocarbon-induced DNA damage. Fluoranthene exposure did not result in detectable DNA damage by itself, but in combination with sunlight caused significant DNA damage to both genomes. PLRRP samples caused DNA damage to both genomes, and this was not increased by sunlight exposure, suggesting the DNA damage was unlikely the result of PAH phototoxicity. We report for the first time that PLRRP-associated pollutants cause both nuclear and mitochondrial DNA damage, and that fluoranthene-mediated phototoxicity results in similar levels of damage to the nuclear and mitochondrial genomes. These effects may be especially significant in sensitive marine ecosystems. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Combining in vitro embryotoxicity data with physiologically based kinetic (PBK) modelling to define in vivo dose-response curves for developmental toxicity of phenol in rat and human.

    Science.gov (United States)

    Strikwold, Marije; Spenkelink, Bert; Woutersen, Ruud A; Rietjens, Ivonne M C M; Punt, Ans

    2013-09-01

    In vitro assays are often used for the hazard characterisation of compounds, but their application for quantitative risk assessment purposes is limited. This is because in vitro assays cannot provide a complete in vivo dose-response curve from which a point of departure (PoD) for risk assessment can be derived, like the no observed adverse effect level (NOAEL) or the 95 % lower confidence limit of the benchmark dose (BMDL). To overcome this constraint, the present study combined in vitro data with a physiologically based kinetic (PBK) model applying reverse dosimetry. To this end, embryotoxicity of phenol was evaluated in vitro using the embryonic stem cell test (EST), revealing a concentration-dependent inhibition of differentiation into beating cardiomyocytes. In addition, a PBK model was developed on the basis of in vitro and in silico data and data available from the literature only. After evaluating the PBK model performance, effective concentrations (ECx) obtained with the EST served as an input for in vivo plasma concentrations in the PBK model. Applying PBK-based reverse dosimetry provided in vivo external effective dose levels (EDx) from which an in vivo dose-response curve and a PoD for risk assessment were derived. The predicted PoD lies within the variation of the NOAELs obtained from in vivo developmental toxicity data from the literature. In conclusion, the present study showed that it was possible to accurately predict a PoD for the risk assessment of phenol using in vitro toxicity data combined with reverse PBK modelling.

  4. Dose- and time-related changes in aerobic metabolism, chorionic disruption, and oxidative stress in embryonic medaka (Oryzias latipes): Underlying mechanisms for silver nanoparticle developmental toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Wu Yuan, E-mail: uyuan@mail.ustc.edu.cn [Department of Public Health, Anhui Medical University, Hefei (China); State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, P.O. Box 2871, Beijing (China); Zhou Qunfang [State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, P.O. Box 2871, Beijing (China)

    2012-11-15

    Silver nanoparticles (AgNPs) are widely employed in commercial products, and are thus inevitably released into the aquatic environment. Many studies have indicated that AgNPs could induce toxicological effects on embryonic fish. To understand the mechanism of AgNP developmental toxicity, we determined the effects of AgNPs on the egg membrane, aerobic metabolism, antioxidant system, lipid peroxidation, as well as reactive oxygen species (ROS) and singlet oxygen ({sup 1}O{sub 2}) generation in early-life medaka fish (Oryzias latipes). AgNP treatment at 62.5-1000 {mu}g/L caused significant increase in retarded development and abnormalities. Destruction of the surface ornamentation and egg envelope was observed at a higher AgNP concentration ({>=}125 {mu}g/L) using light microscopy and scanning electron microscopy. A dose-dependent increase in lactate dehydrogenase activity, an indicator of anaerobic metabolism, and superoxide dismutase activity was observed in the treated embryos. In contrast, the total reduced glutathione level decreased. A high thiobarbituric acid reactive substance concentration was generated upon AgNP exposure from day 1 to day 7 postfertilisation. The biochemical parameters suggested that oxidative stress was induced by the AgNPs. Unexpectedly, a dose-dependent reduction in ROS and {sup 1}O{sub 2} generation upon high AgNP exposure ({>=}250 {mu}g/L) was observed. Although the morphological damages induced by the AgNPs were irreversible, restorable antioxidant defenses were noted in the well-developed embryos. This finding supported the idea that the stage of morphogenesis and organogenesis is a critical window to chemical exposure or environmental stress. Overall, the results suggested that hypoxia, disturbed egg chorion, and oxidative stress are mechanistically associated with AgNP toxicity in embryonic fish.

  5. Oral (Gavage) Combined Developmental and Perinatal/Postnatal Reproduction Toxicity Study of Ammonium Salt of Perfluorinated Hexanoic Acid in Mice.

    Science.gov (United States)

    Iwai, Hiroyuki; Hoberman, Alan M

    2014-05-01

    The reproductive toxicity potential of Ammonium Salt of Perfluorinated Hexanoic Acid (PFHxA Ammonium Salt) in pregnant Crl: CD1(ICR) mice was investigated. Twenty females/group were administered the test substance or vehicle once daily from gestation day 6 through 18. Phase 1 doses: 0, 100, 350, and 500 mg/kg/d; phase 2: 0, 7, 35, and 175 mg/kg/d. Parameters evaluated include mortality, viability, body weights, clinical signs, abortions, premature deliveries, pregnancy and fertility, litter observations, maternal behavior, and sexual maturity in the F1 generation. The level of PFHxA Ammonium Salt was measured in the liver of F0 and F1 mice. At doses of 350 and 500 mg/kg/d maternal mortalities, excess salivation and changes in body weight gains occurred. Pup body weights were reduced on postpartum day (PPD) 0 in all the dosage groups, but persisted only in the 350 and 500 mg/kg/d groups. Additional effects at 300 and 500 mg/kg/d included stillbirths, reductions in viability indices, and delays in physical development. Levels of PFHxA Ammonium Salt in the livers of the 100 mg/kg/d dams were all below the lower limit of quantization (0.02 µg/mL); in the 350 mg/kg/d group, 3 of the 8 samples had quantifiable analytical results. In phase 2 no PFHxA Ammonium Salt was found in the liver. Adverse effects occurred only in the 175 mg/kg/d group and consisted of increased stillborn pups, pups dying on PPD 1, and reduced pup weights on PPD 1. Based on these data, the maternal and reproductive no observable adverse effect level of PFHxA Ammonium Salt is 100 mg/kg/d. © The Author(s) 2014.

  6. Toxicity evaluation of petroleum blending streams: reproductive and developmental effects of a distillate from light alkylate naphtha.

    Science.gov (United States)

    Bui, Q Q; Burnett, D M; Breglia, R J; Koschier, F J; Lapadula, E S; Podhasky, P I; Schreiner, C A; White, R D; Dalbey, W E; Feuston, M H

    1998-01-23

    A distillate of light alkylate naphtha (CAS number 64741-66-8; LAN distillate) was administered via inhalation, 6 h/d, 7 d/wk to 4 groups of Sprague-Dawley rats (10/sex/dose) at target concentrations of 0 (filtered air control), 5, 12.5, or 25 g/m3 with the highest dose exceeding 60% of the lower explosive limit of LAND. Exposure began 2 wk prior to mating and continued throughout gestation until postnatal d 4 for females or for 8 consecutive weeks for males. No apparent clinical signs indicative of systemic toxicity were observed in the F0 and F1 animals of either sex. Inhalation exposure to LAND up to and including the 25 g/m3 dose level had no effect on parental food consumption, body weights, absolute and relative organ weights, and reproductive indices. All groups had comparable delivery data and a fertility index > or 80%. Pups in all groups showed comparable birth weights, weight gain, a viability index (postnatal d 4) for all groups of > or = 97%, and no histopathological changes. In the dams, there were no significant differences in the mean numbers of corpora lutea, implantation sites, and resorptions recorded at necropsy. In the males, the only remarkable findings at necropsy were a small right epididymis and testis seen in one mid-dose male and an abscess on the right epididymis of a high-dose male. In both cases, the dams that had been bred to these males produced normal litters. There were no test material-related microscopic changes observed in the testes and epididymis of the F0 male rats or ovaries of the F0 female rats exposed to LAND. Under the conditions of this experiment, the no-observed-adverse-effect level (NOAEL) for LAND via inhalation in rats is established at greater than 24.7 g/m3 (analytical concentration).

  7. Final report on the developmental toxicity of ethylenediamine (CAS No. 107-15-3) in New Zealand white rabbits. Report for November-February 1992

    Energy Technology Data Exchange (ETDEWEB)

    1993-03-01

    Ethylenediamine (EDA) is a major industrial chemical with an estimated U.S. production of 64 million pounds in 1985. EDA is used as a chemical intermediate or solvent in manufacturing, as a paint thinner, and as a constituent of certain cosmetic, pharmaceutical and veterinary products. Based upon its widespread applications and the potential for exposure in pregnant women, EDA was evaluated for maternal and developmental toxicity using a laboratory animal model. Artificially-inseminated New Zealand White rabbits (26/group) were administered ethylenediamine (0, 10, 40 or 80 mg/kg/day) by gavage on gestational days (gd) 6 through 19. The doses administered were equivalent to 0, 22, 89 or 178 of EDA.2HC1. Maternal clinical signs, body weight, and food consumption were monitored at regular intervals throughout gestation. At termination (gd 30), the uterus was removed and examined to determine pregnancy status and to evaluate the number of resorptions, and dead or live fetuses. Dead or live fetuses were weighed, and live fetuses examined for external, visceral and skeletal defects.

  8. SU-F-J-206: Systematic Evaluation of the Minimum Detectable Shift Using a Range- Finding Camera

    Energy Technology Data Exchange (ETDEWEB)

    Platt, M; Platt, M [College of Medicine University of Cincinnati, Cincinnati, OH (United States); Lamba, M [University of Cincinnati, Cincinnati, OH (United States); Mascia, A [University of Cincinnati Medical Center, Cincinnati, OH (United States); Huang, K [UC Health Barret Cancer Center, Cincinnati, OH (United States)

    2016-06-15

    Purpose: The robotic table used for patient alignment in proton therapy is calibrated only at commissioning under well-defined conditions and table shifts may vary over time and with differing conditions. The purpose of this study is to systematically investigate minimum detectable shifts using a time-of-flight (TOF) range-finding camera for table position feedback. Methods: A TOF camera was used to acquire one hundred 424 × 512 range images from a flat surface before and after known shifts. Range was assigned by averaging central regions of the image across multiple images. Depth resolution was determined by evaluating the difference between the actual shift of the surface and the measured shift. Depth resolution was evaluated for number of images averaged, area of sensor over which depth was averaged, distance from camera to surface, central versus peripheral image regions, and angle of surface relative to camera. Results: For one to one thousand images with a shift of one millimeter the range in error was 0.852 ± 0.27 mm to 0.004 ± 0.01 mm (95% C.I.). For varying regions of the camera sensor the range in error was 0.02 ± 0.05 mm to 0.47 ± 0.04 mm. The following results are for 10 image averages. For areas ranging from one pixel to 9 × 9 pixels the range in error was 0.15 ± 0.09 to 0.29 ± 0.15 mm (1σ). For distances ranging from two to four meters the range in error was 0.15 ± 0.09 to 0.28 ± 0.15 mm. For an angle of incidence between thirty degrees and ninety degrees the average range in error was 0.11 ± 0.08 to 0.17 ± 0.09 mm. Conclusion: It is feasible to use a TOF camera for measuring shifts in flat surfaces under clinically relevant conditions with submillimeter precision.

  9. A human induced pluripotent stem cell-based in vitro assay predicts developmental toxicity through a retinoic acid receptor-mediated pathway for a series of related retinoid analogues.

    Science.gov (United States)

    Palmer, Jessica A; Smith, Alan M; Egnash, Laura A; Colwell, Michael R; Donley, Elizabeth L R; Kirchner, Fred R; Burrier, Robert E

    2017-07-23

    The relative developmental toxicity potency of a series of retinoid analogues was evaluated using a human induced pluripotent stem (iPS) cell assay that measures changes in the biomarkers ornithine and cystine. Analogue potency was predicted, based on the assay endpoint of the ornithine/cystine (o/c) ratio, to be all-trans-retinoic acid>TTNPB>13-cis-retinoic acid≈9-cis-retinoic acid>acitretin>etretinate>retinol. These rankings correlate with in vivo data and demonstrate successful application of the assay to rank a series of related toxic and non-toxic compounds. The retinoic acid receptor α (RARα)-selective antagonist Ro 41-5253 inhibited the cystine perturbation caused by all-trans-retinoic acid, TTNPB, 13-cis-retinoic acid, 9-cis-retinoic acid, and acitretin. Ornithine was altered independent of RARα in all retinoids except acitretin. These results suggest a role for an RARα-mediated mechanism in retinoid-induced developmental toxicity through altered cystine metabolism. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Methylmercury toxicity and functional programming

    DEFF Research Database (Denmark)

    Grandjean, Philippe

    2007-01-01

    PURPOSE: Adverse health effects of developmental toxicants may induce abnormal functional programming that leads to lasting functional deficits. This notion is considered from epidemiological evidence using developmental methylmercury neurotoxicity as an example. MOST IMPORTANT FINDINGS: Accumula...

  11. Development of a combined in Vitro Physiologically Based Kinetic (PBK) and Monte Carlo modelling approach to predict interindividual human variation in phenol-induced developmental toxicity

    NARCIS (Netherlands)

    Strikwold, Marije; Spenkelink, Bert; Woutersen, Ruud A.; Rietjens, Ivonne M.C.M.; Punt, Ans

    2017-01-01

    With our recently developed in vitro physiologically based kinetic (PBK) modelling approach, we could extrapolate in vitro toxicity data to human toxicity values applying PBK-based reverse dosimetry. Ideally information on kinetic differences among human individuals within a population should be

  12. The application of mouse and human embryonic stem cells with transcriptomics in alternative developmental toxicity tests : A bridge from model species to man

    NARCIS (Netherlands)

    Schulpen, S.H.W.

    2015-01-01

    During life humans are exposed to diverse hazardous compounds, which can have toxicological effects. Reproductive and developmental toxicology are research areas dedicated to the study of the potential of a compound to affect male and female fertility, and development of the embryo and fetus during

  13. Relative developmental toxicity of glycol ether alkoxy acid metabolites in the embryonic stem cell test as compared with the in vivo potency of their parent compounds

    NARCIS (Netherlands)

    Jong, E. de; Louisse, J.; Verwei, M.; Blaauboer, B.J.; Sandt, J.J.M. van de; Woutersen, R.A.; Rietjens, I.M.C.M.; Piersma, A.H.

    2009-01-01

    The embryonic stem cell test (EST) has been proposed as an in vitro assay that might reduce animal experimentation in regulatory developmental toxicology. So far, evaluation of the EST was not performed using compounds within distinct chemical classes. Evaluation within a distinct class of

  14. Developmental Screening

    Science.gov (United States)

    ... bye,” and pointing to something interesting are all developmental milestones, or things most children can do by a ... screening are ways to look for your child’s developmental milestones. Developmental Monitoring Developmental Screening WHO: You — parents, grandparents, ...

  15. Contaminant mixtures and repoductive health: Developmental toxicity effects in rats after mixed exposure to environmentally relevant endocrine disrupting chemicals, with focus on effects in females

    DEFF Research Database (Denmark)

    Jacobsen, Pernille Rosenskjold; Christiansen, Sofie; Hass, Ulla

    disorders or later onset adult diseases. However, experimental evidence on the effects of developmental exposure to environmentally relevant endocrine disrupting chemicals in females has been missing attention. Since chemical exposure can affect female reproductive development it is important to investigate...... offspring including anogenital distance (AGD), number of nipples, onset of puberty, measurements of Anti-Müllerian hormone (AMH) and estrous cyclicity at several time point during the animals life span. Results and discussion: Prolonged gestational length was observed in the Pestimix studies at mixture...

  16. RNA seq- and DEG-based comparison of developmental toxicity in fish embryos of two species exposed to Iranian heavy crude oil.

    Science.gov (United States)

    Jung, Jee-Hyun; Ko, Junsu; Lee, Eun-Hee; Choi, Kwang-Min; Kim, Moonkoo; Yim, Un Hyuk; Lee, Jae-Seong; Shim, Won Joon

    2017-06-01

    To determine and compare the toxic effects of Iranian heavy crude oil (IHCO) on the embryonic development of two fish species, we examined transcriptome profiles using RNA-seq. The assembled contigs were 66,070 unigenes in olive flounder embryos and 76,498 unigenes in spotted seabass embryos. In the differential gene expression (DEG) profiles, olive flounder embryos showed different up- and down-regulated patterns than spotted seabass embryos in response to fresh IHCO (FIHCO) and weathered IHCO (WIHCO). In this work, we categorized DEG profiles into six pathways: ribosome, oxidative phosphorylation, Parkinson's disease, Alzheimer's disease, Huntington's disease, and cardiac muscle contraction, validating the expression patterns of 13 DEGs using real-time quantitative RT-PCR. The expression of the CYP1A, CYP1B1, and CYP1C1 genes in spotted seabass embryos was higher than in olive flounder embryos, whereas genes related to cell processing, development, and the immune system showed the opposite trend. Orthologous gene cluster analysis showed that olive flounder embryos were sensitive (fold change of genes with cutoff Poil spills. Overall, our study provides new insight on the different embryonic susceptibilities of two marine fish species to FIHCO and WIHCO and a better understanding of the underlying molecular mechanisms via RNA-seq and DEGs. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. The influence of study design and sex-differences on results from developmental neurotoxicity studies of bisphenol A: implications for toxicity testing.

    Science.gov (United States)

    Beronius, Anna; Johansson, Niklas; Rudén, Christina; Hanberg, Annika

    2013-09-06

    Developmental neurotoxicity (DNT) of bisphenol A (BPA) has been investigated in a large number of studies. However, there are discrepancies in the results reported between the studies. The aim of this study was to identify and analyze factors that may contribute to these differences and to assess whether there are sex-differences in the sensitivity of certain endpoints or tests used in DNT-studies. Forty-four DNT studies of BPA were identified from the open literature. Details about study design and results from each study, as well as the criteria for DNT testing according to the standardized OECD test guideline (TG) 426, were collected in a database. This enabled systematic and detailed comparisons between studies as well as to the criteria and recommendations stated in TG 426. Multivariate analyses were also used to investigate how different factors of the study design contributed to differences in study results. The analyses showed behavioral effects were often observed for endpoints that are not required according to OECD TG 426, such as anxiety-related, social and sexual behaviors, especially at very low doses and in female offspring. On the other hand relatively few studies observed any effects on motor activity, which is commonly used in screening for neurotoxic effects in regulatory testing. However, varied and to some extent seemingly contradictory results have been reported in these studies, especially for endpoints related to motor activity and anxiety and exploration. Many studies were also poorly reported, limiting these analyses. No strong conclusions could be drawn from the multivariate analyses. A few factors of study design, such as the size of the dose and number of dose levels used and the use of litter or individual pup as statistical unit seemed to have some influence on study results. In conclusion, this analysis suggests that DNT-studies conducted according to the standardized OECD TG 426 may overlook sensitive effects of BPA, and possibly

  18. Developmental Milestones

    Science.gov (United States)

    ... Early Initiative Act Early Ambassadors Research and evaluation Developmental Milestones Language: English (US) Español (Spanish) Recommend on Facebook ... first time, and waving “bye bye” are called developmental milestones. Children reach milestones in how they play, learn, ...

  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. Developmental Dysphasia

    OpenAIRE

    J Gordon Millichap

    1989-01-01

    The neuropatho1ogica1 findings in a seven year old girl with developmental dysphasia who died of complications of infectious mononucleosis are reported from the Departments of Neurology and Pediatrics and the Department of Pathology, Medical College of Georgia, Augusta, GA.

  1. Developmental Research

    NARCIS (Netherlands)

    Klaassen, Kees; Kortland, Koos

    2015-01-01

    Developmental research is a particular way of addressing the basic questions of why and how to teach what to whom. It involves a cyclical process of small-scale in-depth development and evaluation, at a content-specific level, of exemplary teaching-learning sequences. It aims to produce an

  2. Developmental Work

    DEFF Research Database (Denmark)

    Møller, Niels; Hvid, Helge; Kristensen, Tage Søndergaard

    2003-01-01

    Human Deveoplment and Working Life - Work for Welfare explores whether the development of human resources at company level can improve individuals' quality of life, companies' possibilities of development, and welfare and democracy in society. Chapter two discuss the concept "developmental work......" from theoretical and empirical perspectives....

  3. Developmental dyscalculia.

    Science.gov (United States)

    Shalev, R S; Weirtman, R; Amir, N

    1988-12-01

    We conducted a neurobehavioral evaluation on eleven children with developmental dyscalculia in order to determine which aspects of arithmetic processes are affected in this disorder. Our results indicate that memorization of numerical facts in these children was poor or virtually non-existent and the ability to solve simple arithmetic exercises impaired. By contrast, comprehension and production of number functions were intact. Although all children had been referred for evaluation of selective deficits in arithmetic skills, they also displayed a mild degree of dyslexia, dysgraphia, anomia, and grapho-motor dysfunction. We conclude that cognitive mechanisms underlying arithmetic ability can be dissociated developmentally and suggest that remediation programs be designed only after detailed analyses of arithmetic and associated cognitive skills.

  4. Subchronic oral toxicity studies with α-cyclodextrin in rats

    NARCIS (Netherlands)

    Lina, B.A.R.; Bär, A.

    2004-01-01

    The toxicity of α-cyclodextrin (α-CD), a cyclic polymer of six α-1,4-linked glucopyranosyl units with potential applications as a food ingredient, more specifically a water-soluble dietary fiber, was examined in a 4-week range finding study and a 13-week oral toxicity study in rats. In the 4-week

  5. Vehicle Based Laser Range Finding in Crops

    OpenAIRE

    Hans-Juergen Horn; Rolf Adamek; Detlef Ehlert

    2009-01-01

    Laser rangefinders and laser scanners are widely used for industrial purposes and for remote sensing. In agriculture information about crop parameters like volume, height, and density can support the optimisation of production processes. In scientific papers the measurement of these parameters by low cost laser rangefinders with one echo has been presented for short ranges. Because the cross section area of the beam increases with the measuring range, it can be expected that laser rangefinder...

  6. Vehicle based laser range finding in crops.

    Science.gov (United States)

    Ehlert, Detlef; Adamek, Rolf; Horn, Hans-Juergen

    2009-01-01

    Laser rangefinders and laser scanners are widely used for industrial purposes and for remote sensing. In agriculture information about crop parameters like volume, height, and density can support the optimisation of production processes. In scientific papers the measurement of these parameters by low cost laser rangefinders with one echo has been presented for short ranges. Because the cross section area of the beam increases with the measuring range, it can be expected that laser rangefinders will have a reduced measuring accuracy in small sized crops and when measuring far distances. These problems are caused by target areas smaller than the beam and by the beam striking the edges of crop objects. Lab tests under defined conditions and a real field test were performed to assess the measuring properties under such difficult conditions of a chosen low cost sensor. Based on lab tests it was shown that the accuracy was reduced, but the successful use of the sensor under field conditions demonstrated the potential to meet the demands for agricultural applications, Insights resulting from investigations made in the paper contribute to facilitating the choice or the development of laser rangefinder sensors for vehicle based measurement of crop parameters for optimisation of production processes.

  7. Range Finding with a Plenoptic Camera

    Science.gov (United States)

    2014-03-27

    obtaining depth information. Two such methods include aerial photogrammetry and lidar. Photogrammetry is the process of extracting real-world position...information from images of objects. In the era of film photography, stereo-plotters enabled cartog- raphers to identify correspondences between... photogrammetry , in which 3D maps can be generated with comparable accuracy and greater efficiency than afforded by laser scanning techniques [33]. Due

  8. Developmental immunotoxicology of lead.

    Science.gov (United States)

    Dietert, Rodney R; Lee, Ji-Eun; Hussain, Irshad; Piepenbrink, Michael

    2004-07-15

    The heavy metal, lead, is a known developmental immunotoxicant that has been shown to produce immune alterations in humans as well as other species. Unlike many compounds that exert adverse immune effects, lead exposure at low to moderate levels does not produce widespread loss of immune cells. In contrast, changes resulting from lead exposure are subtle at the immune cell population level but, nevertheless, can be functionally dramatic. A hallmark of lead-induced immunotoxicity is a pronounced shift in the balance in T helper cell function toward T helper 2 responses at the expense of T helper 1 functions. This bias alters the nature and range of immune responses that can be produced thereby influencing host susceptibility to various diseases. Immunotoxic responses to lead appear to differ across life stages not only quantitatively with regard to dose response, but also qualitatively in terms of the spectrum of immune alterations. Experimental studies in several lab animal species suggest the latter stages of gestation are a period of considerable sensitivity for lead-induced immunotoxicity. This review describes the basic characteristics of lead-induced immunotoxicity emphasizing experimental animal results. It also provides a framework for the consideration of toxicant exposure effects across life stages. The existence of and probable basis for developmental windows of immune hyper-susceptibility are presented. Finally, the potential for lead to serve as a perinatal risk factor for childhood asthma as well as other diseases is considered.

  9. Developmental dyslexia.

    Science.gov (United States)

    Peterson, Robin L; Pennington, Bruce F

    2015-01-01

    This review uses a levels-of-analysis framework to summarize the current understanding of developmental dyslexia's etiology, brain bases, neuropsychology, and social context. Dyslexia is caused by multiple genetic and environmental risk factors as well as their interplay. Several candidate genes have been identified in the past decade. At the brain level, dyslexia is associated with aberrant structure and function, particularly in left hemisphere reading/language networks. The neurocognitive influences on dyslexia are also multifactorial and involve phonological processing deficits as well as weaknesses in other oral language skills and processing speed. We address contextual issues such as how dyslexia manifests across languages and social classes as well as what treatments are best supported. Throughout the review, we highlight exciting new research that cuts across levels of analysis. Such work promises eventually to provide a comprehensive explanation of the disorder as well as its prevention and remediation.

  10. Assessing the toxic effects of ethylene glycol ethers using Quantitative Structure Toxicity Relationship models.

    Science.gov (United States)

    Ruiz, Patricia; Mumtaz, Moiz; Gombar, Vijay

    2011-07-15

    Experimental determination of toxicity profiles consumes a great deal of time, money, and other resources. Consequently, businesses, societies, and regulators strive for reliable alternatives such as Quantitative Structure Toxicity Relationship (QSTR) models to fill gaps in toxicity profiles of compounds of concern to human health. The use of glycol ethers and their health effects have recently attracted the attention of international organizations such as the World Health Organization (WHO). The board members of Concise International Chemical Assessment Documents (CICAD) recently identified inadequate testing as well as gaps in toxicity profiles of ethylene glycol mono-n-alkyl ethers (EGEs). The CICAD board requested the ATSDR Computational Toxicology and Methods Development Laboratory to conduct QSTR assessments of certain specific toxicity endpoints for these chemicals. In order to evaluate the potential health effects of EGEs, CICAD proposed a critical QSTR analysis of the mutagenicity, carcinogenicity, and developmental effects of EGEs and other selected chemicals. We report here results of the application of QSTRs to assess rodent carcinogenicity, mutagenicity, and developmental toxicity of four EGEs: 2-methoxyethanol, 2-ethoxyethanol, 2-propoxyethanol, and 2-butoxyethanol and their metabolites. Neither mutagenicity nor carcinogenicity is indicated for the parent compounds, but these compounds are predicted to be developmental toxicants. The predicted toxicity effects were subjected to reverse QSTR (rQSTR) analysis to identify structural attributes that may be the main drivers of the developmental toxicity potential of these compounds. Copyright © 2010. Published by Elsevier Inc.

  11. Toxic Elements

    DEFF Research Database (Denmark)

    Hajeb, Parvaneh; Shakibazadeh, Shahram; Sloth, Jens Jørgen

    2016-01-01

    Food is considered the main source of toxic element (arsenic, cadmium, lead, and mercury) exposure to humans, and they can cause major public health effects. In this chapter, we discuss the most important sources for toxic element in food and the foodstuffs which are significant contributors...... to human exposure. The occurrence of each element in food classes from different regions is presented. Some of the current toxicological risk assessments on toxic elements, the human health effect of each toxic element, and their contents in the food legislations are presented. An overview of analytical...... techniques and challenges for determination of toxic elements in food is also given....

  12. Developmental dyscalculia.

    Science.gov (United States)

    Kucian, Karin; von Aster, Michael

    2015-01-01

    Numerical skills are essential in our everyday life, and impairments in the development of number processing and calculation have a negative impact on schooling and professional careers. Approximately 3 to 6 % of children are affected from specific disorders of numerical understanding (developmental dyscalculia (DD)). Impaired development of number processing skills in these children is characterized by problems in various aspects of numeracy as well as alterations of brain activation and brain structure. Moreover, DD is assumed to be a very heterogeneous disorder putting special challenges to define homogeneous diagnostic criteria. Finally, interdisciplinary perspectives from psychology, neuroscience and education can contribute to the design for interventions, and although results are still sparse, they are promising and have shown positive effects on behaviour as well as brain function. In the current review, we are going to give an overview about typical and atypical development of numerical abilities at the behavioural and neuronal level. Furthermore, current status and obstacles in the definition and diagnostics of DD are discussed, and finally, relevant points that should be considered to make an intervention as successful as possible are summarized.

  13. Research Models in Developmental Behavioral Toxicology.

    Science.gov (United States)

    Dietrich, Kim N.; Pearson, Douglas T.

    Developmental models currently used by child behavioral toxicologists and teratologists are inadequate to address current issues in these fields. Both child behavioral teratology and toxicology scientifically study the impact of exposure to toxic agents on behavior development: teratology focuses on prenatal exposure and postnatal behavior…

  14. Overview: developmental toxicology: new directions.

    Science.gov (United States)

    Shuey, Dana; Kim, James H

    2011-10-01

    Since regulatory agencies began implementing the use of standardized developmental toxicology protocols in the mid-1960s, our knowledge base of embryo-fetal development and technologies for experimentation has grown exponentially. These developmental toxicology protocols were a direct result of the thalidomide tragedy from earlier that decade, when large numbers of women were exposed to the drug and over 10,000 cases of phocomelia resulted. In preventing a recurrence of such tragedies, the testing protocols are immensely successful and the field of toxicology has been dedicated to using them to advance safety and risk assessment of chemicals and pharmaceuticals. Recently, our perspectives on toxicity testing have been challenged by a growing awareness that while we have excelled in hazard identification, we are in dire need of improved methodologies for human health risk assessment, particularly with respect to the large numbers of environmental chemicals for which we have little toxicology data and to the growing sentiment that better alternatives to whole animals tests are needed. To provide a forum for scientists, researchers, and regulators, the Developmental and Reproductive Toxicology Technical Committee of the Health and Environmental Sciences Institute organized a 2-day workshop titled "Developmental Toxicology-New Directions" to evaluate lessons learned over the past 30 years and discuss the future of toxicology testing. The following four articles describe different presentations and discussions that were held over the course of those 2 days. © 2011 Wiley Periodicals, Inc.

  15. Antimony toxicity

    National Research Council Canada - National Science Library

    Sundar, Shyam; Chakravarty, Jaya

    2010-01-01

    Antimony toxicity occurs either due to occupational exposure or during therapy. Occupational exposure may cause respiratory irritation, pneumoconiosis, antimony spots on the skin and gastrointestinal symptoms...

  16. Review of toxicity studies of carbon nanotubes.

    Science.gov (United States)

    Kobayashi, Norihiro; Izumi, Hiroto; Morimoto, Yasuo

    2017-09-28

    We reviewed studies on pulmonary, reproductive, and developmental toxicity caused by carbon nanotubes (CNTs). In paricular, we analyzed how CNT exposure affects the several processes of pulmonary toxicity, including inflammation, injury, fibrosis, and pulmonary tumors. In pulmonary toxicity, there are various processes, including inflammation, injury, fibrosis, respiratory tumor in the lungs, and biopersistence of CNTs and genotoxicity as tumor-related factors, to develop the respiratory tumor. We evaluated the evidence for the carcinogenicity of CNTs in each process. In the fields of reproductive and developmental toxicity, studies of CNTs have been conducted mainly with mice. We summarized the findings of reproductive and developmental toxicity studies of CNTs. In animal studies, exposure to CNTs induced sustained inflammation, fibrosis, lung cancer following long-term inhalation, and gene damage in the lung. CNTs also showed high biopersistence in animal studies. Fetal malformations after intravenous and intraperitoneal injections and intratracheal instillation, fetal loss after intravenous injection, behavioral changes in offsprings after intraperitoneal injection, and a delay in the delivery of the first litter after intratracheal instillation were reported in mice-administered multi-walled carbon nanotubes (MWCNTs). Single-walled carbon nanotubes (SWCNTs) appeared to be embryolethal and teratogenic in mice when given by intravenous injection; moreover, the tubes induced death and growth retardation in chicken embryos. CNTs are considered to have carcinogenicity and can cause lung tumors. However, the carcinogenicity of CNTs may attenuate if the fiber length is shorter. The available data provide initial information on the potential reproductive and developmental toxicity of CNTs.

  17. Evaluating the male and female reproductive toxicity of high-boiling petroleum substances.

    Science.gov (United States)

    Murray, F Jay; Gray, Thomas M; Roberts, Linda G; Roth, Randy N; Nicolich, Mark J; Simpson, Barry J

    2013-11-01

    To meet the EPA HPV Chemical Challenge Program requirement for reproductive toxicity data on sponsored high-boiling petroleum substances (HBPS), an analysis was conducted using the results of 39 repeat-dose and 59 developmental rat dermal toxicity studies on HBPS samples spanning the boiling range of the sponsored substances, and the results of three one-generation reproductive toxicity studies on two samples spanning the concentration range of polycyclic aromatic compounds of sponsored substances. The analysis found little evidence of male or female reproductive tract toxicity based on histopathology, reproductive organ weight, and sperm parameters, and no evidence of effects on fertility, while significant developmental toxicity and/or systemic repeat-dose toxicity were frequently observed. Among 14 samples of HBPS tested in both repeat-dose toxicity and developmental toxicity studies, there were no studies in which an adverse reproductive tract finding occurred at a dose lower than that producing developmental toxicity or other adverse effects in repeat-dose toxicity studies. The current analysis supports the hypothesis that effects in developmental and/or repeat-dose toxicity studies of HBPS occur at doses lower than those that might affect fertility in rat one-generation reproductive studies. When adequate developmental and repeat-dose toxicity studies are available, a reproductive toxicity study of HBPS appears unnecessary. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Using Developmental Trajectories to Understand Developmental Disorders

    Science.gov (United States)

    Thomas, Michael S. C.; Annaz, Dagmara; Ansari, Daniel; Scerif, Gaia; Jarrold, Chris; Karmiloff-Smith, Annette

    2009-01-01

    Purpose: In this article, the authors present a tutorial on the use of developmental trajectories for studying language and cognitive impairments in developmental disorders and compare this method with the use of matching. Method: The authors assess the strengths, limitations, and practical implications of each method. The contrast between the…

  19. Assessment of the toxicity of radiographic developer effluent on ...

    African Journals Online (AJOL)

    Toxicity of radiographic developer effluent on catfish juveniles (H. longfilis) from the Institute of Oceanography fish farm, University of Calabar was assessed. Seventy five (75) juveniles of H. longifilis were acclimated in about 5 litres of habitat water for 48 hours with minimum feeding. Range finding test was conducted at ...

  20. 40 CFR 799.9110 - TSCA acute oral toxicity.

    Science.gov (United States)

    2010-07-01

    ... mg/kg.) If compound-related mortality is produced in the limit test, further study may need to be... sufficient to produce a dose-response curve and permit an acceptable estimation of the LD50. Range finding... death after dosing. (iv) Dose-response curves for mortality and other toxic effects (when permitted by...

  1. assessment of the toxicity of radiographic developer effluent on ...

    African Journals Online (AJOL)

    Stephen

    Toxicity of radiographic developer effluent on catfish juveniles (H. longfilis) from the Institute of Oceanography fish farm, University of Calabar was assessed. Seventy five (75) juveniles of H. longifilis were acclimated in about 5 litres of habitat water for 48 hours with minimum feeding. Range finding test was conducted at ...

  2. Bridging environmental mixtures and toxic effects.

    Science.gov (United States)

    Allan, Sarah E; Smith, Brian W; Tanguay, Robert L; Anderson, Kim A

    2012-12-01

    Biological Response Indicator Devices Gauging Environmental Stressors (BRIDGES) is a bioanalytical tool that combines passive sampling with the embryonic zebrafish developmental toxicity bioassay to provide a quantitative measure of the toxicity of bioavailable complex mixtures. Passive sampling devices (PSDs), which sequester and concentrate bioavailable organic contaminants from the environment, were deployed in the Willamette and Columbia Rivers within and outside of the Portland Harbor Superfund site in Portland, OR, USA. Six sampling events were conducted in the summer and fall of 2009 and 2010. Passive sampling device extracts were analyzed for polycyclic aromatic hydrocarbon (PAH) compounds and screened for 1,201 chemicals of concern using deconvolution-reporting software. The developmental toxicity of the extracts was analyzed using the embryonic zebrafish bioassay. The BRIDGES tool provided site-specific, temporally resolved information about environmental contaminant mixtures and their toxicity. Multivariate modeling approaches were applied to paired chemical and toxic effects data sets to help unravel chemistry-toxicity associations. Modeling elucidated spatial and temporal trends in PAH concentrations and the toxicity of the samples and identified a subset of PAH analytes that were the most highly correlated with observed toxicity. Although the present study highlights the complexity of discerning specific bioactive compounds in complex mixtures, it demonstrates methods for associating toxic effects with chemical characteristics of environmental samples. Copyright © 2012 SETAC.

  3. Antimony Toxicity

    Science.gov (United States)

    Sundar, Shyam; Chakravarty, Jaya

    2010-01-01

    Antimony toxicity occurs either due to occupational exposure or during therapy. Occupational exposure may cause respiratory irritation, pneumoconiosis, antimony spots on the skin and gastrointestinal symptoms. In addition antimony trioxide is possibly carcinogenic to humans. Improvements in working conditions have remarkably decreased the incidence of antimony toxicity in the workplace. As a therapeutic, antimony has been mostly used for the treatment of leishmaniasis and schistosomiasis. The major toxic side-effects of antimonials as a result of therapy are cardiotoxicity (~9% of patients) and pancreatitis, which is seen commonly in HIV and visceral leishmaniasis co-infections. Quality control of each batch of drugs produced and regular monitoring for toxicity is required when antimonials are used therapeutically. PMID:21318007

  4. Developmental milestones record

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/002002.htm Developmental milestones record To use the sharing features on this page, please enable JavaScript. Developmental milestones are behaviors or physical skills seen in infants ...

  5. Comparison of the leading-edge timing walk in pulsed TOF laser range finding with avalanche bipolar junction transistor (BJT) and metal-oxide-semiconductor (MOS) switch based laser diode drivers.

    Science.gov (United States)

    Hintikka, Mikko; Hallman, Lauri; Kostamovaara, Juha

    2017-12-01

    Timing walk error in pulsed time-of-flight based laser range finding was studied using two different types of laser diode drivers. The study compares avalanche bipolar junction transistor (BJT) and metal-oxide-semiconductor field-effect transistor switch based laser pulse drivers, both producing 1.35 ns current pulse length (full width at half maximum), and investigates how the slowly rising part of the current pulse of the avalanche BJT based driver affects the leading edge timing walk. The walk error was measured to be very similar with both drivers within an input signal dynamic range of 1:10 000 (receiver bandwidth of 700 MHz) but increased rapidly with the avalanche BJT based driver at higher values of dynamic range. The slowly rising part does not exist in the current pulse produced by the metal-oxide-semiconductor (MOS) based laser driver, and thus the MOS based driver can be utilized in a wider dynamic range.

  6. [Toxic megacolon].

    Science.gov (United States)

    Leppkes, M; Ganslmayer, M; Strauß, R; Neurath, M F

    2015-10-01

    Toxic megacolon constitutes a feared, life-threatening complication of severe intestinal inflammation and is a challenge for interdisciplinary medical care. Specific aspects of conservative treatment based on current scientific evidence derived from guidelines, qualified reviews, and scientific studies are presented, which provide a rational approach and maximize therapeutic success. This work is based on a selective literature review and the authors' experience of many years in gastroenterology and intensive care. Toxic megacolon requires a rapid interdisciplinary assessment. Depending on the underlying etiology, an individual treatment concept needs to be developed. If an infectious or inflammatory cause is probable, a conservative approach can reduce perioperative morbidity and mortality. A step-wise approach with controlled reevaluations of the response to therapy after 72 h and 7 days avoids uncontrolled delay of surgical options further ensuring patient safety. Despite a decreasing incidence of toxic megacolon, it remains an interdisciplinary therapeutic challenge.

  7. In vitro and field studies on the contact and fumigant toxicity of a neem-product (Mite-Stop) against the developmental stages of the poultry red mite Dermanyssus gallinae.

    Science.gov (United States)

    Locher, Nina; Al-Rasheid, Khaled A S; Abdel-Ghaffar, Fathy; Mehlhorn, Heinz

    2010-07-01

    The acaricidal activity of the neem product MiteStop was investigated for its potential use as a botanical acaricide for the control of the poultry red mite Dermanyssus gallinae. This neem product is a special formulation of an extract of the seeds of the neem tree Azadirachta indica A. Juss. The efficacy was tested under laboratory conditions as well as in poultry houses. Four different methods of application were used in a filter paper bioassay to evaluate contact and vapour phase toxicity tests. The neem product proved to be already active in very small doses. In order to investigate the efficacy under field conditions, a poultry house was sprayed twice within a 7-day period using 1:33 and 1:50 diluted MiteStop. Cardboard traps were used to assess the mite population before, during and after the treatment. The mite population could be reduced by 89%. In a second poultry house, the spraying of defined areas with a 1:30, 1:33 or 1:50 dilution of the acaricide proved to be highly efficacious against all mite stages. Three other field trials proved that MiteStop is highly active against the red poultry mite. The most efficient dilution is 1:33 with tap water and spraying two or three times at intervals of 7 days.

  8. Computer Simulation of Developmental Processes and ...

    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 culture models, engineered microscale tissues and complex microphysiological systems (MPS), together with computational models and computer simulation of tissue dynamics, lend themselves to a integrated testing strategies for predictive toxicology. As these emergent methodologies continue to evolve, they must be integrally tied to maternal/fetal physiology and toxicity of the developing individual across early lifestage transitions, from fertilization to birth, through puberty and beyond. Scope: This symposium will focus on how the novel technology platforms can help now and in the future, with in vitro/in silico modeling of complex biological systems for developmental and reproductive toxicity issues, and translating systems models into integrative testing strategies. The symposium is based on three main organizing principles: (1) that novel in vitro platforms with human cells configured in nascent tissue architectures with a native microphysiological environments yield mechanistic understanding of developmental and reproductive impacts of drug/chemical exposures; (2) that novel in silico platforms with high-throughput screening (HTS) data, biologically-inspired computational models of

  9. Computational Modeling and Simulation of Developmental ...

    Science.gov (United States)

    Standard practice for assessing developmental toxicity is the observation of apical endpoints (intrauterine death, fetal growth retardation, structural malformations) in pregnant rats/rabbits following exposure during organogenesis. EPA’s computational toxicology research program (ToxCast) generated vast in vitro cellular and molecular effects data on >1858 chemicals in >600 high-throughput screening (HTS) assays. The diversity of assays has been increased for developmental toxicity with several HTS platforms, including the devTOX-quickPredict assay from Stemina Biomarker Discovery utilizing the human embryonic stem cell line (H9). Translating these HTS data into higher order-predictions of developmental toxicity is a significant challenge. Here, we address the application of computational systems models that recapitulate the kinematics of dynamical cell signaling networks (e.g., SHH, FGF, BMP, retinoids) in a CompuCell3D.org modeling environment. Examples include angiogenesis (angiodysplasia) and dysmorphogenesis. Being numerically responsive to perturbation, these models are amenable to data integration for systems Toxicology and Adverse Outcome Pathways (AOPs). The AOP simulation outputs predict potential phenotypes based on the in vitro HTS data ToxCast. A heuristic computational intelligence framework that recapitulates the kinematics of dynamical cell signaling networks in the embryo, together with the in vitro profiling data, produce quantitative predic

  10. Developmental Prosopagnosia: A Review

    OpenAIRE

    Thomas Kress; Irene Daum

    2003-01-01

    This article reviews the published literature on developmental prosopagnosia, a condition in which the ability to recognize other persons by facial information alone has never been acquired. Due to the very low incidence of this syndrome, case reports are sparse. We review the available data and suggest assessment strategies for patients suffering from developmental prosopagnosia. It is suggested that developmental prosopagnosia is not a unitary condition but rather consists of different subf...

  11. Developmental Prosopagnosia: A Review

    Science.gov (United States)

    Kress, Thomas; Daum, Irene

    2003-01-01

    This article reviews the published literature on developmental prosopagnosia, a condition in which the ability to recognize other persons by facial information alone has never been acquired. Due to the very low incidence of this syndrome, case reports are sparse. We review the available data and suggest assessment strategies for patients suffering from developmental prosopagnosia. It is suggested that developmental prosopagnosia is not a unitary condition but rather consists of different subforms that can be dissociated on the grounds of functional impairments. On the basis of the available evidence, hypotheses about the aetiology of developmental prosopagnosia as well as about the selectivity of deficits related to face recognition are discussed. PMID:14757987

  12. Developmental Prosopagnosia: A Review

    Directory of Open Access Journals (Sweden)

    Thomas Kress

    2003-01-01

    Full Text Available This article reviews the published literature on developmental prosopagnosia, a condition in which the ability to recognize other persons by facial information alone has never been acquired. Due to the very low incidence of this syndrome, case reports are sparse. We review the available data and suggest assessment strategies for patients suffering from developmental prosopagnosia. It is suggested that developmental prosopagnosia is not a unitary condition but rather consists of different subforms that can be dissociated on the grounds of functional impairments. On the basis of the available evidence, hypotheses about the aetiology of developmental prosopagnosia as well as about the selectivity of deficits related to face recognition are discussed.

  13. Reproductive and developmental toxicology

    National Research Council Canada - National Science Library

    Gupta, Ramesh C

    2011-01-01

    .... Reproductive and Developmental Toxicology is a comprehensive and authoritative resource providing the latest literature enriched with relevant references describing every aspect of this area of science...

  14. Evolutionary developmental psychology

    National Research Council Canada - National Science Library

    King, Ashley C; Bjorklund, David F

    2010-01-01

    The field of evolutionary developmental psychology can potentially broaden the horizons of mainstream evolutionary psychology by combining the principles of Darwinian evolution by natural selection...

  15. Human Toxicity

    DEFF Research Database (Denmark)

    Jolliet, Olivier; Fantke, Peter

    2015-01-01

    This chapter reviews the human toxicological impacts of chemicals and how to assess these impacts in life cycle impact assessment (LCIA), in order to identify key processes and pollutants. The complete cause-effect pathway – from emissions of toxic substances up to damages on human health...... on characterisation factors means that results should by default be reported and interpreted in log scales when comparing scenarios or substance contribution! We conclude by outlining future trends in human toxicity modelling for LCIA, with promising developments for (a) better estimates of degradation halflives, (b......) the inclusion of ionization of chemicals in human exposure including bioaccumulation, (c) metal speciation, (d) spatialised models to differentiate the variability associated with spatialisation from the uncertainty, and (e) the assessment of chemical exposure via consumer products and occupational settings...

  16. Alternative models in developmental toxicology.

    Science.gov (United States)

    Lee, Hyung-yul; Inselman, Amy L; Kanungo, Jyotshnabala; Hansen, Deborah K

    2012-02-01

    In light of various pressures, toxicologists have been searching for alternative methods for safety testing of chemicals. According to a recent policy in the European Union (Regulation, Evaluation Authorisation and Restriction of Chemicals, REACH), it has been estimated that over the next twelve to fifteen years, approximately 30,000 chemicals may need to be tested for safety, and under current guidelines such testing would require the use of approximately 7.2 million laboratory animals [ Hofer et al. 2004 ]. It has also been estimated that over 80% of all animals used for safety testing under REACH legislation would be used for examining reproductive and developmental toxicity [Hofer et al., 2004]. In addition to REACH initiatives, it has been estimated that out of 5,000 to 10,000 new drug entities that a pharmaceutical company may start with, only one is finally approved by the Food and Drug Administration at a cost of over one billion dollars [ Garg et al. 2011 ]. A large portion of this cost is due to animal testing. Therefore, both the pharmaceutical and chemical industries are interested in using alternative models and in vitro tests for safety testing. This review will examine the current state of three alternative models - whole embryo culture (WEC), the mouse embryonic stem cell test (mEST), and zebrafish. Each of these alternatives will be reviewed, and advantages and disadvantages of each model will be discussed. These models were chosen because they are the models most commonly used and would appear to have the greatest potential for future applications in developmental toxicity screening and testing.

  17. Studying toxicity

    Science.gov (United States)

    Elkus, A.; LeBlanc, L.; Kim, C.; Van Beneden, R.; Mayer, G.

    2006-01-01

    With funding from the George Mitchell Center for the Environment at the University of Maine, a team of scientists used a simple laboratory-based sediment resuspension design, and two well-established aquatic toxicology models, fathead minnows (Pimephales promelas) and zebrafish (Danio rerio), to evaluate if resuspension of Penobscot river sediment significantly elevates the toxicity of river water and to provide preliminary information on the types of chemicals likely to desorb during resuspension. The group collected sediments from two sites with known chemical contamination downstream of the Great Works and Veazie dams. The sediments were examined to determine the dynamics of PAH desorption and degradation under different resuspension frequencies. The scientists used clarified water from resuspension experiments for toxicity tests with the water-flea Ceriodaphnia dubia, and other aquatic test organisms to infer toxicity from sediments from northern California rivers. Data from the study will help ascertain whether metals and/or xenoestrogens are present in the desorption water and give insight into possible avenues of sediment remediation.

  18. Genetics and Developmental Psychology

    Science.gov (United States)

    Plomin, Robert

    2004-01-01

    One of the major changes in developmental psychology during the past 50 years has been the acceptance of the important role of nature (genetics) as well as nurture (environment). Past research consisting of twin and adoption studies has shown that genetic influence is substantial for most domains of developmental psychology. Present research…

  19. 'developmental' local government to

    African Journals Online (AJOL)

    1. DEVELOPMENTAL CHALLENGES. FACING SOUTH AFRICAN. URBAN REGIONS AND. GOVERNMENTS. As an introduction to this article it would be appropriate to begin the discussion with some developmental acumen from the office of the Presidency. The new Green Paper: National Strategic. Planning, published by ...

  20. Developmental Hypothyroidism Alters Brain-Derived Neurotrophic Factor (BDNF) Expression in Adulthood.

    Science.gov (United States)

    Severe developmental thyroid hormone (TH) insufficiency results in alterations in brain structure/function and lasting behavioral impairments. Environmental toxicants reduce circulating levels of TH, but the disruption is modest and the doseresponse relationships of TH and neuro...

  1. Toxic shock syndrome

    Science.gov (United States)

    Staphylococcal toxic shock syndrome; Toxic shock-like syndrome; TSLS ... Toxic shock syndrome is caused by a toxin produced by some types of staphylococcus bacteria. A similar problem, called toxic shock- ...

  2. Toxicity of Copper (11) Tetraoxo Sulphate to African Catfish (Clarias Gariepinus) Fingerlings

    OpenAIRE

    F.O. Agbebi; Owoeye, O.

    2012-01-01

    This study was carried out to determine the toxicity of copper sulphate to African Catfish (Clarias gariepinus). The range – finding test was conducted twice in order to get reliable values that could be used for the definitive test. The toxicant (copper sulphate) was introduced at varying concentrations of 10g/l, 20g/l, 30g/l and 40g/l in the first range- finding test, while it was introduced at concentrations of 2g/l, 4g/l, 6g/l and 8g/l in the second range- finding test. However, in the de...

  3. Life Span Developmental Approach

    Directory of Open Access Journals (Sweden)

    Ali Eryilmaz

    2011-03-01

    Full Text Available The Life Span Developmental Approach examines development of individuals which occurs from birth to death. Life span developmental approach is a multi-disciplinary approach related with disciplines like psychology, psychiatry, sociology, anthropology and geriatrics that indicates the fact that development is not completed in adulthood, it continues during the life course. Development is a complex process that consists of dying and death. This approach carefully investigates the development of individuals with respect to developmental stages. This developmental approach suggests that scientific disciplines should not explain developmental facts only with age changes. Along with aging, cognitive, biological, and socioemotional development throughout life should also be considered to provide a reasonable and acceptable context, guideposts, and reasonable expectations for the person. There are three important subjects whom life span developmental approach deals with. These are nature vs nurture, continuity vs discontinuity, and change vs stability. Researchers using life span developmental approach gather and produce knowledge on these three most important domains of individual development with their unique scientific methodology.

  4. Developmental immunotoxicity of Diazepam in prenatally exposed weanling Wistar rats

    NARCIS (Netherlands)

    Loveren H van; Piersma AH; Jong WH de; Waal EJ de; LPI; LEO; LGM

    A prenatal developmental toxicity study was conducted in rats receiving the pharmaceutical Diazepam from gestation days 14 to 20. Reports from the literature claim that Diazepam has impaired the immune function in the offspring of rats receiving treatment during the third trimester of gestation.

  5. An Experimental Protocol for Maternal Pulmonary Exposure in Developmental Toxicology

    DEFF Research Database (Denmark)

    Jackson, Petra; Lund, Søren P.; Kristiansen, Gitte

    2011-01-01

    To establish a protocol for studying effects of pulmonary exposure in developmental toxicity studies, the effects of intratracheal sham instillation under short-term isoflurane anaesthesia were evaluated with a protocol including multiple instillations during gestation. Twelve time-mated mice (C5...

  6. 40 CFR 795.250 - Developmental neurotoxicity screen.

    Science.gov (United States)

    2010-07-01

    .... “The effects of inter-trial interval on avoidance learning in the rat.” Journal of Comparative... 40 Protection of Environment 31 2010-07-01 2010-07-01 true Developmental neurotoxicity screen. 795.250 Section 795.250 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC...

  7. [Toxic methemoglobinemia].

    Science.gov (United States)

    Bender, P; Neuhaus, H

    2011-04-01

    A 19 year-old female patient suffered from severe hypoxemia after an ambulant surgery for splayfeet. Local anesthesia had been performed with prilocain and bupivacain. Methemoglobinemia was suspected and treated with ascorbine acid and methylene blue. The patient was then admitted to hospital. The patient was well orientated and awake. She complained of a mild headache and general illness. There was marked central cyanosis. A blood sample was dark-red to brownish. The periphere oxygen saturation was 85%. A cardiac ultrasound and a chest X ray were without pathological findings. Initial arterial blood gas analysis showed a concentration of methemoglobin of 24%. On intensive care clinical and laboratory findings quickly resolved and methemoglobin concentration normalized after one day. The patient had no symptoms anymore and was discharged the next day. In treatment-resistent hypoxemia after local anesthesia toxic methemoglobinaemia should be suspected. Therapy of choice is immediate administration of methylene blue. © Georg Thieme Verlag KG Stuttgart · New York.

  8. Intellectual and Developmental Disabilities

    Science.gov (United States)

    ... Videos Get to Know NICHD Podcasts and Audio Social Media Join NICHD Listservs About NICHD Organization Office of ... IDDs; and the effect of individual factors on social interactions, behavior, and emotions. Common Name Intellectual and developmental disabilities (IDDs) Medical ...

  9. Facts about Developmental Disabilities

    Science.gov (United States)

    ... an autism spectrum disorder. Low birthweight , premature birth, multiple birth, and infections during pregnancy are associated with an increased risk for many developmental disabilities. Untreated newborn jaundice (high levels of bilirubin in ...

  10. Computational Modeling and Simulation of Developmental ...

    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 (animal-based) methods. A compendium of in vitro data from ToxCast/Tox21 high-throughput screening (HTS) programs is available for predictive toxicology. ‘Predictive DART’ will require an integrative strategy that mobilizes HTS data into in silico models that capture the relevant embryology. This lecture addresses progress on EPA's 'virtual embryo'. The question of how tissues and organs are shaped during development is crucial for understanding (and predicting) human birth defects. While ToxCast HTS data may predict developmental toxicity with reasonable accuracy, mechanistic models are still necessary to capture the relevant biology. Subtle microscopic changes induced chemically may amplify to an adverse outcome but coarse changes may override lesion propagation in any complex adaptive system. Modeling system dynamics in a developing tissue is a multiscale problem that challenges our ability to predict toxicity from in vitro profiling data (ToxCast/Tox21). (DISCLAIMER: The views expressed in this presentation are those of the presenter and do not necessarily reflect the views or policies of the US EPA). This was an invited seminar presentation to the National Institute for Public H

  11. Developmental Idealism in China.

    Science.gov (United States)

    Thornton, Arland; Xie, Yu

    2016-10-01

    This paper examines the intersection of developmental idealism with China. It discusses how developmental idealism has been widely disseminated within China and has had enormous effects on public policy and programs, on social institutions, and on the lives of individuals and their families. This dissemination of developmental idealism to China began in the 19th century, when China met with several military defeats that led many in the country to question the place of China in the world. By the beginning of the 20th century, substantial numbers of Chinese had reacted to the country's defeats by exploring developmental idealism as a route to independence, international respect, and prosperity. Then, with important but brief aberrations, the country began to implement many of the elements of developmental idealism, a movement that became especially important following the assumption of power by the Communist Party of China in 1949. This movement has played a substantial role in politics, in the economy, and in family life. The beliefs and values of developmental idealism have also been directly disseminated to the grassroots in China, where substantial majorities of Chinese citizens have assimilated them. These ideas are both known and endorsed by very large numbers in China today.

  12. Toxicity of Nitro-Heterocyclic and Nitroaromatic Energetic Materials to Terrestrial Plants in a Natural Sandy Loam Soil

    Science.gov (United States)

    2005-04-01

    bacteria and pre-incubated at room temperature , and Buttercrunch lettuce seeds were used for the range-finding tests to determine the three most sensitive...range-finding tests and based on seeding emergence and shoot growth measurement endpoints (Table 40), no toxic effects were observed for RDX and HMX at...kg-1 RDX (Cataldo et al., 1989), and bush bean ( Phaseolus vulgaris ) was also hydroponically exposed to 10 mg L-1 RDX for 1 or 7 days (Harvey et al

  13. Developmental and acquired dyslexias.

    Science.gov (United States)

    Temple, Christine M

    2006-08-01

    Marshall (1984) highlighted potential parallels between children with developmental disorders of reading and adults who had acquired reading disorders. He advocated the use of a cognitive neuropsychological framework in the investigation of children with developmental abnormalities of cognition, including those with developmental dyslexias. Developmental phonological dyslexia has been extensively described and is a pervasive disorder. The relationship between reading difficulty and phonological difficulties evident in explicit oral phonological tasks continues to be a focus for debate. Clear cases of developmental deep dyslexia have now been described and the syndrome has also been described as characterising early reading development in Williams syndrome (WS), where there are also semantic errors in other domains, including naming and receptive vocabulary and there may be a generalised difficulty with the activation of fine grain semantic specifications. In the domain of number, highly selective reading disorders characterised by high rates of semantic errors have been documented, indicating that semantic reading errors can be domain-specific. They can occur to number words despite intact ability to read Arabic numbers and they can occur to Arabic numbers and number words despite intact ability to read words in other domains. Current models of reading written words do not allow for such material-specific dissociation. Developmental surface dyslexia has also been described in a range of countries, languages and orthographies. Descriptions of cases for whom there is no phonological impairment in reading have generated contrary evidence for theories suggesting that phonological impairment underlies all developmental dyslexia. As reading develops in Williams Syndrome, phonological reading skills may improve with over-reliance on these leading to surface dyslexia. Surface dyslexia has also been reported in cases of developmental amnesia in which there are semantic

  14. Developmental origins of adult diseases and neurotoxicity: Epidemiological and experimental studies

    DEFF Research Database (Denmark)

    Fox, Donald A; Grandjean, Philippe; de Groot, Didima

    2012-01-01

    and the development of metabolic-related diseases and neurotoxicity later in life. The four speakers at this symposium presented their research results on different neurotoxic chemicals relating to the developmental origins of health and adult disease (DOHaD). Philippe Grandjean presented epidemiological data......To date, only a small number of commercial chemicals have been tested and documented as developmental neurotoxicants. Moreover, an increasing number of epidemiological, clinical and experimental studies suggest an association between toxicant or drug exposure during the perinatal period...... and neurotoxic risk assessment. The results indicate that developmental neurotoxicity results in permanent changes, thus emphasizing the need to prevent such toxicity....

  15. 40 CFR 798.4350 - Inhalation developmental toxicity study.

    Science.gov (United States)

    2010-07-01

    ... of the test substance. It is used to compare particles of different sizes, shapes, and densities and... the generating system, particle size analysis shall be performed to establish the stability of aerosol concentrations with respect to particle size. During exposure, analysis shall be conducted as often as necessary...

  16. 40 CFR 798.4900 - Developmental toxicity study.

    Science.gov (United States)

    2010-07-01

    ... unless the chemical or physical characteristics of the test substance or pattern of human exposure... as respiratory, autonomic and central nervous systems, somatomotor activity and behavioral pattern... be prepared and examined for skeletal anomalies, and the remaining part of each litter shall be...

  17. A perspective on the developmental toxicity of inhaled nanoparticles

    DEFF Research Database (Denmark)

    Hougaard, Karin Sørig; Campagnolo, Luisa; Chavatte-Palmer, Pascale

    2015-01-01

    This paper aimed to clarify whether maternal inhalation of engineered nanoparticles (NP) may constitute a hazard to pregnancy and fetal development, primarily based on experimental animal studies of NP and air pollution particles. Overall, it is plausible that NP may translocate from the respirat......This paper aimed to clarify whether maternal inhalation of engineered nanoparticles (NP) may constitute a hazard to pregnancy and fetal development, primarily based on experimental animal studies of NP and air pollution particles. Overall, it is plausible that NP may translocate from...

  18. Developmental toxicity in rat fetuses exposed to the benzimidazole netobimin.

    Science.gov (United States)

    Navarro, M; Canut, L; Carretero, A; Cristofol, C; Pérez-Aparicio, F J; Arboix, M; Ruberte, J

    1999-01-01

    Netobimin (NTB) is a prodrug of albendazole (ABZ) and is used as a broad-spectrum anthelmintic both in human and veterinary medicine. Pregnant Sprague-Dawley rats were treated po with 50, 59.5 and 70.7 mg/kg of NTB on Gestational Day (GD) 10. The results, observed on GD 20, demonstrated that NTB induced a significant increase of resorptions. Moreover, decreased fetal body weight and an increase in skeletal malformations were observed in treated groups. We report the first study in which vascular malformations are described in rats after the administration of a benzimidazole compound. An interesting relationship between intercostal vessel and rib malformations was found.

  19. Examining the interaction between developmental toxicity and microbiota colonization

    Science.gov (United States)

    There is growing evidence that microbiota can modify the toxicokinetics and/or toxicodynamics of environmental chemicals. Commonly used mammalian systems have limited ability to link phenotypic effects in exposed animals to colonization status. Here, we used gnotobiotic zebrafish...

  20. 40 CFR 799.9370 - TSCA prenatal developmental toxicity.

    Science.gov (United States)

    2010-07-01

    ..., except legal holidays. (1) Aliverti, V.L. et al. The extent of fetal ossification as an index of delayed.... Prenatal ossification in rabbits as indicative of fetal maturity. Teratology. 11:313-320 (1974). (6) Fritz, H. and Hess, R. Ossification of the rat and mouse skeleton in the perinatal period. Teratology. 3...

  1. Revolutionizing Toxicity Testing For Predicting Developmental Outcomes (DNT4)

    Science.gov (United States)

    Characterizing risk from environmental chemical exposure currently requires extensive animal testing; however, alternative approaches are being researched to increase throughput of chemicals screened, decrease reliance on animal testing, and improve accuracy in predicting adverse...

  2. DEVELOPMENTAL TOXICITY EVALUATION OF WATER FROM ALTERNATIVE DISINFECTION SCENARIOS

    Science.gov (United States)

    NAROTSKY1, M.G., D.S. BEST1, E.H. ROGERS1, A. McDONALD1, Y.M. SEY1, E.S. HUNTER III 1, L.K. TEUSCHLER2, R.J. MILTNER3, T.F. SPETH3, G. RICE2, K.M. SCHENCK3, S.D. RICHARDSON4, M.C. MARR5, and J.E. SIMMONS1. 1US Environmental Protection Agency (EPA), National Health and Environment...

  3. Transgenerational developmental programming.

    Science.gov (United States)

    Aiken, Catherine E; Ozanne, Susan E

    2014-01-01

    The concept of developmental programming suggests that the early life environment influences offspring characteristics in later life, including the propensity to develop diseases such as the metabolic syndrome. There is now growing evidence that the effects of developmental programming may also manifest in further generations without further suboptimal exposure. This review considers the evidence, primarily from rodent models, for effects persisting to subsequent generations, and evaluates the mechanisms by which developmental programming may be transmitted to further generations. In particular, we focus on the potential role of the intrauterine environment in contributing to a developmentally programmed phenotype in subsequent generations. The literature was systematically searched at http://pubmed.org and http://scholar.google.com to identify published findings regarding transgenerational (F2 and beyond) developmental programming effects in human populations and animal models. Transmission of programming effects is often viewed as a form of epigenetic inheritance, either via the maternal or paternal line. Evidence exists for both germline and somatic inheritance of epigenetic modifications which may be responsible for phenotypic changes in further generations. However, there is increasing evidence for the role of both extra-genomic components of the zygote and the interaction of the developing conceptus with the intrauterine environment in propagating programming effects. The contribution of a suboptimal reproductive tract environment or maternal adaptations to pregnancy may be critical to inheritance of programming effects via the maternal line. As the effects of age exacerbate the programmed metabolic phenotype, advancing maternal age may increase the likelihood of developmental programming effects being transmitted to further generations. We suggest that developmental programming effects could be propagated through the maternal line de novo in generations

  4. 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.

  5. Toxicity of cyanogen to insects of stored grain.

    Science.gov (United States)

    Hooper, Jacqueline L; Desmarchelier, James M; Ren, Yonglin; Allen, Sylvia E

    2003-03-01

    Range-finding studies on the toxicity of cyanogen to all stages of five species of stored product Coleoptera are reported. The species were Rhyzopertha dominica (F), Sitophilus granarius (L), Sitophilus Oryzae (L), Tribolium castaneum (Herbst), Tribolium confusum Jacquelin du Val and Ephestia cautella (Walker). Exposures for 24 h to cyanogen at 1.3 mg litre(-1) controlled all external stages. Control of internal stages of Sitophilus species was achieved by a 5-day exposure to initial concentrations between 13.7 and 27.4 mg litre(-1), whereas R. dominica was controlled at 13.7 mg litre(-1). Cyanogen showed similar toxicity to all tested external stages and, in this respect, was more similar to methyl bromide than to phosphine. Its toxicity to insects increased with both relative humidity and concentration of carbon dioxide. Cyanogen was toxic to insects whether applied as a gas or in an aqueous solution.

  6. Distributed Structure Searchable Toxicity

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Distributed Structure Searchable Toxicity (DSSTox) online resource provides high quality chemical structures and annotations in association with toxicity data....

  7. Zebrafish as potential model for developmental neurotoxicity testing: a mini review.

    Science.gov (United States)

    de Esch, Celine; Slieker, Roderick; Wolterbeek, André; Woutersen, Ruud; de Groot, Didima

    2012-01-01

    The zebrafish is a powerful toxicity model; biochemical assays can be combined with observations at a structural and functional level within one individual. This mini review summarises the potency of zebrafish as a model for developmental neurotoxicity screening, and its possibilities to investigate working mechanisms of toxicants. The use of zebrafish in toxicity research can ultimately lead to the refinement or reduction of animal use. Copyright © 2012 Elsevier Inc. All rights reserved.

  8. Developmental Reinforcement and Education.

    Science.gov (United States)

    Garris, Raymond P.

    Using a developmental model, the author explains a hierarchy which describes how a young child learns to respond to various types of environmental stimuli and discusses some educational consequences of a reinforcement stimuli deficit. Development is seen to take place in succession beginning with the primary level, proceeding to the social,…

  9. Developmental paediatric anaesthetic pharmacology

    DEFF Research Database (Denmark)

    Hansen, Tom Giedsing

    2015-01-01

    Safe and effective drug therapy in neonates, infants and children require detailed knowledge about the ontogeny of drug disposition and action as well how these interact with genetics and co-morbidity of children. Recent advances in developmental pharmacology in children follow the increased...

  10. [Developmental Disorders and Dementia].

    Science.gov (United States)

    Midorikawa, Akira

    2015-09-01

    This article reviews the relationship between developmental disorders and dementia with ageing. Persons with autistic spectrum disorder (ASD) are vulnerable to life events, even in their old age. In certain cases, senile persons with undiagnosed ASD, who developed maladaptive behaviors after negative life events, were considered as having a behavioral variant of frontotemporal dementia (bvFTD). However, to our knowledge, there are no reports on the relationships between ASD and bvFTD. Alternatively, there are only a limited number of reports, which address the relationships between developmental disorders and dementia. One such relationship is that in patients with dementia with Lewy bodies (DLB) and those with Parkinson's disease (PD), who also show a tendency for having attention-deficit/hyperactivity disorder (ADHD) at a younger age. Another such relationship is seen in patients with primary progressive aphasia (PPA) who show a high occurrence of learning disability (LD) among their first-degree relatives. These results imply that the neurotransmitter pathway or language network in the brain is vulnerable in some subjects. These retrospective studies have demonstrated a possible relationship between developmental disorders and dementia; however, no study has shown a causality of developmental disorders and dementia.

  11. Alcoholism: A Developmental Disorder.

    Science.gov (United States)

    Tarter, Ralph E.; Vanyukov, Michael

    1994-01-01

    Alcoholism etiology is discussed from developmental behavior genetic perspective. Temperament features that appear to be associated with heightened risk for alcoholism are examined. Their interactions with the environment during course of development are considered within epigenetic framework and, as discussed, have ramifications for improving…

  12. Evolutionary Developmental Psychology.

    Science.gov (United States)

    Geary, David C.; Bjorklund, David F.

    2000-01-01

    Describes evolutionary developmental psychology as the study of the genetic and ecological mechanisms that govern the development of social and cognitive competencies common to all human beings and the epigenetic (gene-environment interactions) processes that adapt these competencies to local conditions. Outlines basic assumptions and domains of…

  13. Developmental Behavioral Genetics.

    Science.gov (United States)

    Plomin, Robert

    1983-01-01

    Provides an introduction to a special section on developmental behavioral genetics (the study of genetic and environmental influences on individual differences in behavioral development), discussing the potentialities of the interdiscipline and presenting an overview of the following articles. (Author/RH)

  14. The Developmental Work

    DEFF Research Database (Denmark)

    Møller, Niels; Hvid, Helge

    2001-01-01

    AbstractIn the nineties, the concept of the developmental work (DW) has become a significant point of orientation for the actors on Danish labour market. The DW has moved the focus of the labour market from wages and working time towards work and production. For employees, the DW promises develop...

  15. Child Developmental Theorist Paper

    OpenAIRE

    Margaret L. Johnson

    2017-01-01

    Many different child developmental theories have contributed to the better understanding and development of the child. This paper researches the theories of Margaret Mahler. It first aims to develop an understanding of her background and the different elements of her theory. Then, it compares Mahler with Daniel Stern, and finally it will understand the relevance of the theory in today’s world.

  16. The relevance of developmental-psychobiological metatheory to developmental neuropsychology.

    Science.gov (United States)

    Gottlieb, G

    2001-01-01

    This article reviews 4 aspects of developmental-psychobiological metatheory that are of particular relevance to developmental conceptions of neuropsychology: probabilistic epigenesis, the various roles of experience in affecting the development of the nervous system, and the developmental principles of equifinality and equipotentiality, the latter being especially pertinent to the understanding of compensatory phenomena observed in studies of early brain damage.

  17. A risk assessment of topical tretinoin as a potential human developmental toxin based on animal and comparative human data.

    Science.gov (United States)

    Johnson, E M

    1997-03-01

    Although topically applied all-trans-retinoic acid (tretinoin) undergoes minimal absorption and adds negligibly to normal endogenous levels, its safety in humans is occasionally questioned because oral ingestion of retinoids at therapeutic levels is known to entail teratogenic risks. To assess the actual potential for developmental toxicity from treatment with topical tretinoin. Risk assessments were conducted on four known human developmental toxicants (valproic acid, methotrexate, thalidomide, and isotretinoin) and a potential developmental toxicant (acetylsalicylic acid). The margin of safety for each chemical was calculated from the ratio of animal no-observed adverse effect levels to human lowest-observed adverse effect levels or estimated exposure doses. The derived safety margin of more than 100 for topical tretinoin (with 2% absorption) contrasted sharply with the near unity values for valproic acid, methotrexate, thalidomide, and isotretinoin and was larger than that for acetylsalicylic acid. These data support other epidemiologic and animal data that topical tretinoin is not a potential human developmental toxicant.

  18. Behavior Analysis and Developmental Psychology.

    Science.gov (United States)

    Morris, Edward K.; And Others

    1982-01-01

    Examines relationships between the fields of behavior analysis and developmental psychology, surveying the influence of behavior-analytic research within developmental psychology and investigating the integration of the two approaches with respect to metatheory and methodology. (Author/MP)

  19. Qualitative methodology in developmental psychology

    DEFF Research Database (Denmark)

    Demuth, Carolin; Mey, Günter

    2015-01-01

    Qualitative methodology presently is gaining increasing recognition in developmental psychology. Although the founders of developmental psychology to a large extent already used qualitative procedures, the field was long dominated by a (post) positivistic quantitative paradigm. The increasing...

  20. Developmental milestones record - 18 months

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/002011.htm Developmental milestones record - 18 months To use the sharing features ... physical and mental skills. These skills are called developmental milestones. Information All children develop a little differently. If ...

  1. Developmental milestones record - 12 months

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/002005.htm Developmental milestones record - 12 months To use the sharing features ... physical and mental skills. These skills are called developmental milestones. Information All children develop a little differently. If ...

  2. Developmental milestones record - 6 months

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/002008.htm Developmental milestones record - 6 months To use the sharing features ... months References Centers for Disease Control and Prevention. Developmental milestones. www.cdc.gov/ncbddd/actearly/milestones/. Updated May ...

  3. Developmental milestones record - 4 years

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/002015.htm Developmental milestones record - 4 years To use the sharing features ... physical and mental skills. These skills are called developmental milestones. Information All children develop a little differently. If ...

  4. Developmental milestones record - 2 months

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/002006.htm Developmental milestones record - 2 months To use the sharing features ... months; Growth milestones for children - 2 months Images Developmental milestones References Centers for Disease Control and Prevention. Infants ( ...

  5. Developmental Milestones of Early Literacy

    Science.gov (United States)

    ... Size Email Print Share Developmental Milestones of Early Literacy Page Content ​In the spirit of making both ... at the well-defined developmental milestones of early literacy. Younger Than 6 Months: Never Too Young Unlike ...

  6. Developmental Purposes of Commercial Games.

    Science.gov (United States)

    Practical Pointers, 1977

    1977-01-01

    Listed are 45 table, target, manipulative, active, and creative games with such developmental purposes as associative learning, tactile discrimination, and visual motor integration. Information includes the name of the item, distributor, price, description, and developmental purpose. (JYC)

  7. NIDCAP and developmental care

    Directory of Open Access Journals (Sweden)

    Dominique Haumont

    2014-06-01

    Full Text Available Perinatal mortality in very low birth weight infants has dramatically decreased during the last decades. However, 15-25% of these infants will show neurodevelopmental impairment later on. The aim of implementing early developmental care (EDC, emerged as a new field in neonatology, is to create an intervention program designed to provide support for optimal neurobehavioral development during this highly vulnerable period of brain growth. The theoretical framework, which underlies the approach, is supported by research in different scientific fields, including neuroscience, psychology, medicine and nursing. EDC utilizes a range of medical and nursing interventions that aim to decrease the stress of preterm neonates in neonatal intensive care units (NICUs. The Neonatal Individualized Developmental Care Assessment Program (NIDCAP is an integrated and holistic form of family-centered developmental care. Changing the traditional NICU towards an EDC-NICU includes training nursing and medical staff, investing in their quality and most importantly keeping parents in proximity to the infants. The new challenge of modern neonatology is to restore the mother-infant dyad applying “couplet care” starting at birth until discharge. Most of the European NICUs apply some elements of EDC, but it is more consistent in northern Europe. The development of NIDCAP training centers in Europe demonstrates the evolution of care. It is likely that future research and intervention programs will optimize our practices. Developmental care could prove to be an important recent step in improving outcome in extremely preterm neonates. Proceedings of the 10th International Workshop on Neonatology · Cagliari (Italy · October 22nd-25th, 2014 · The last ten years, the next ten years in Neonatology Guest Editors: Vassilios Fanos, Michele Mussap, Gavino Faa, Apostolos Papageorgiou

  8. Evolutionary developmental psychology.

    Science.gov (United States)

    King, Ashley C; Bjorklund, David F

    2010-02-01

    The field of evolutionary developmental psychology can potentially broaden the horizons of mainstream evolutionary psychology by combining the principles of Darwinian evolution by natural selection with the study of human development, focusing on the epigenetic effects that occur between humans and their environment in a way that attempts to explain how evolved psychological mechanisms become expressed in the phenotypes of adults. An evolutionary developmental perspective includes an appreciation of comparative research and we, among others, argue that contrasting the cognition of humans with that of nonhuman primates can provide a framework with which to understand how human cognitive abilities and intelligence evolved. Furthermore, we argue that several aspects of childhood (e.g., play and immature cognition) serve both as deferred adaptations as well as imparting immediate benefits. Intense selection pressure was surely exerted on childhood over human evolutionary history and, as a result, neglecting to consider the early developmental period of children when studying their later adulthood produces an incomplete picture of the evolved adaptations expressed through human behavior and cognition.

  9. The memory of hunger: developmental plasticity of dietary selectivity in the European starling, Sturnus vulgaris.

    Science.gov (United States)

    Bloxham, Louise; Bateson, Melissa; Bedford, Thomas; Brilot, Ben; Nettle, Daniel

    2014-05-01

    The decision to consume toxic prey is a trade-off between the benefits of obtaining nutrients and the costs of ingesting toxins. This trade-off is affected by current state: animals will consume more toxic prey if they are food deprived. However, whether the trade-off is affected by developmental history is currently unknown. We studied the decision to eat quinine-injected mealworms in adult starling siblings that had been exposed to either high or low levels of food competition as chicks, via a brood size manipulation. At the time of our experiments, the two groups of birds did not differ in size, body weight or current environment. Each bird was presented with the toxic prey while living on a high-quality diet and a low-quality diet. We found an effect of diet, with birds consuming more toxic prey while on the low-quality diet, and also of developmental history, with birds from the high-competition brood size treatment eating more toxic prey than their low-competition siblings. The effects of brood size treatment were not completely mediated by early growth, although we did find evidence that early growth affected toxic prey consumption independently of brood size treatment. We discuss our results in relation to adaptive developmental plasticity and the developmental origins of behavioural variation.

  10. Developmental neurotoxicity after toluene inhalation exposure in rats

    DEFF Research Database (Denmark)

    Hass, Ulla; Lund, Søren Peter; Hougaard, Karin Sørig

    1999-01-01

    TG for Developmental Neurotoxicity Study, i.e., physical development, reflex ontogeny, motor function, motor activity, sensory function, and learning and memory. The exposure did not cause maternal toxicity or decreased viability of the offspring. Lower birth weight, delayed ontogeny of reflexes......Rats were exposed to 1200 ppm or 0 ppm toluene (CAS 108-88-3) for 6 h per day from day 7 of pregnancy until day 18 postnatally. Developmental and neurobehavioral effects in the offspring were investigated using a test battery including assessment of functions similar to those in the proposed OECD...... was not related to poorer swimming capabilities, because swim speeds were similar to control values. The results show that exposure to 1200 ppm toluene during brain development caused long-lasting developmental neurotoxicity in rats. (C) 1999 Elsevier Science Inc. All rights reserved....

  11. Toxic hemolytic anemias.

    OpenAIRE

    ZEMANOVÁ, Vendula

    2014-01-01

    This thesis deals with toxic hemolytic anemias which are often unheeded. There are described laboratory signs of hemolytic anemias, their dividing into the various groups and it focuses mainly to toxic and drug-related hemolytic anemias and their causations.

  12. Topographic processing in developmental prosopagnosia

    DEFF Research Database (Denmark)

    Klargaard, Solja K.; Starrfelt, Randi; Petersen, Anders

    2016-01-01

    deficit in visual processing or visual short-term memory. Interestingly, a classical dissociation could be demonstrated between impaired face memory and preserved topographic memory in two developmental prosopagnosics. We conclude that impairments in topographic memory tend to co-occur with developmental......Anecdotal evidence suggests a relation between impaired spatial (navigational) processing and developmental prosopagnosia. To address this formally, we tested two aspects of topographic processing ? that is, perception and memory of mountain landscapes shown from different viewpoints. Participants...

  13. Connectionism and developmental psychology.

    Science.gov (United States)

    Plunkett, K; Karmiloff-Smith, A; Bates, E; Elman, J L; Johnson, M H

    1997-01-01

    What features of brain processing and neural development support linguistic and cognitive development in young children? To what extent are the profile and timing of development in young children determined by a preordained genetic programme? Does the environment play a crucial role in determining the patterns of change observed in children growing up? These questions have been of central concern to developmental psychologists for well over a century. Yet none of them have received answers that are generally accepted by the profession. This article reviews some recent computational modelling of developmental change in children that promises to contribute to a deeper understanding of the issues behind these questions. The modelling work exploits artificial neural networks that mimic some of the basic properties of neural processing in the brain. These networks involve densely connected webs of simple processing units that propagate and transform complex patterns of activity. When exposed to a training environment, they undergo a process of self-organisation, yielding information processing systems that support new forms of behaviour. The study of the dynamics of these systems and their learning capabilities promises to provide us with important clues as to the nature of the mechanisms underlying development in infants and young children.

  14. Constructivist developmental theory is needed in developmental neuroscience

    Science.gov (United States)

    Arsalidou, Marie; Pascual-Leone, Juan

    2016-12-01

    Neuroscience techniques provide an open window previously unavailable to the origin of thoughts and actions in children. Developmental cognitive neuroscience is booming, and knowledge from human brain mapping is finding its way into education and pediatric practice. Promises of application in developmental cognitive neuroscience rests however on better theory-guided data interpretation. Massive amounts of neuroimaging data from children are being processed, yet published studies often do not frame their work within developmental models—in detriment, we believe, to progress in this field. Here we describe some core challenges in interpreting the data from developmental cognitive neuroscience, and advocate the use of constructivist developmental theories of human cognition with a neuroscience interpretation.

  15. Neurobehavioral effects of developmental methylmercury exposure

    Energy Technology Data Exchange (ETDEWEB)

    Gilbert, S.G.; Grant-Webster, K.S. [Univ. of Washington, Seattle, WA (United States)

    1995-09-01

    Methylmercury (MeHg) is a global environmental problem and is listed by the International Program of Chemical Safety as one of the six most dangerous chemicals in the world`s environment. Human exposure to MeHg primarily occurs through the consumption of contaminated food such as fish, although catastrophic exposures due to industrial pollution have occurred. The fetus is particularly sensitive to MeHg exposure and adverse effects on infant development have been associated with levels of exposure that result in few, if any, signs of maternal clinical illness or toxicity. High levels of prenatal exposure in humans result in neurobehavioral effects such as cerebral palsy and severe mental retardation. Prenatal exposure to MeHg in communities with chronic low-level exposure is related to decreased birthweight and early sensorimotor dysfunction such as delayed onset of walking. Neurobehavioral alterations have also been documented in studies with non human primates and rodents. Available information on the developmental neurotoxic effects of MeHg, particularly the neurobehavioral effects, indicates that the fetus and infant are more sensitive to adverse effects of MEHg. It is therefore recommended that pregnant women and women of childbearing age be strongly advised to limit their exposure to potential sources of MeHg. Based on results from human and animal studies on the developmental neurotoxic effects of methylmercury, the accepted reference dose should be lowered to 0.025 to 0.06 MeHg {mu}g/kg/day. Continued research on the neurotoxic effects associated with low level developmental exposure is needed. 107 refs., 3 tabs.

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

    Science.gov (United States)

    Yang, Zhendong; Xue, Kathy S; Sun, Xiulan; Tang, Lili; Wang, Jia-Sheng

    2015-12-02

    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.

  17. Potential protective effect of L-cysteine against the toxicity of acrylamide and furan in exposed Xenopus laevis embryos: an interaction study

    Science.gov (United States)

    The embryo toxicities of two food-processing-induced toxic compounds, acrylamide and furan, with and without added L-cysteine were examined individually and in mixtures using the frog embryo teratogenesis assay-Xenopus (FETAX). The following measures of developmental toxicity were used (a) 96-h LC5...

  18. [Developmental venous anomaly (DVA)].

    Science.gov (United States)

    Zimmer, A; Hagen, T; Ahlhelm, F; Viera, J; Reith, W; Schulte-Altedorneburg, G

    2007-10-01

    As congenital anatomic variants of venous drainage, developmental venous anomalies (DVA) represent up to 60% of all cerebral vascular malformations. The prior term "venous angioma" is a misnomer implicating an abnormal vascular structure with an increased bleeding risk. They are often found incidentally and are hardly ever symptomatic. Their morphologic characteristics are dilated vessels in the white matter, which converge on a greater collector vein, forming the typical caput medusae. They drain into the superficial or deep venous system. The frequent association with other, potentially bleeding-prone vascular malformations is clinically relevant, in particular cavernous angioma, which might require therapeutic action. Therefore, coincident vascular lesions need to be actively sought by appropriate additional imaging techniques.

  19. Developmental programming of happiness.

    Science.gov (United States)

    Schmidt, Louis A; Fortier, Paz; Lahat, Ayelet; Tang, Alva; Mathewson, Karen J; Saigal, Saroj; Boyle, Michael H; Van Lieshout, Ryan J

    2017-09-01

    Being born at an extremely low birth weight (ELBW; programming hypotheses. Interfacing prenatal programming and differential susceptibility hypotheses, we tested whether individuals with ELBW in different childhood rearing environments showed different attention biases to positive and negative facial emotions in adulthood. Using the oldest known, prospectively followed cohort of ELBW survivors, we found that relative to normal birth weight controls (NBW; >2,500 grams), ELBW survivors displayed the highest and lowest attention bias to happy faces at age 30-35, depending on whether their total family income at age 8 was relatively low (environmental match) or high (environmental mismatch), respectively. This bias to happy faces was associated with a reduced likelihood of emotional problems. Findings suggest that differential susceptibility to positive emotions may be prenatally programmed, with effects lasting into adulthood. We discuss implications for integrating prenatal programming and differential susceptibility hypotheses, and the developmental origins of postnatal plasticity and resilience. © 2017 Wiley Periodicals, Inc.

  20. Developmental colour agnosia.

    Science.gov (United States)

    van Zandvoort, Martine J E; Nijboer, Tanja C W; de Haan, Edward

    2007-08-01

    Colour agnosia concerns the inability to recognise colours despite intact colour perception, semantic memory for colour information, and colour naming. Patients with selective colour agnosia have been described and the deficit is associated with left hemisphere damage. Here we report a case study of a 43-year-old man who was referred to us with a stroke in his right cerebellar hemisphere. During the standard assessment it transpired that he was unable to name coloured patches. Detailed assessment of his colour processing showed that he suffers from a selective colour agnosia. As he claimed to have had this problem all his life, and the fact that the infratentorial infarct that he had incurred was in an area far away from the brain structures that are known to be involved in colour processing, we suggest that he is the first reported case of developmental colour agnosia.

  1. Developmental Trigger Thumb.

    Science.gov (United States)

    Twu, Jonathan; Angeles, Jovito

    2016-04-01

    Developmental trigger thumb, although uncommon, can be easily identifiable in the pediatric outpatient visit. Patients often present with their thumb locked in flexion and a firm nodule at the base of the thumb. The thumb is usually passively correctable and nonpainful. It is important to examine the opposite thumb as bilateral trigger thumbs occur at a rate of 25% to 30%. Nonsurgical options have been proposed in the past including watchful waiting, extension exercises, splinting, and steroid injections with mixed results. Surgical intervention is indicated when there is painful triggering or the thumb is not passively correctable. Surgical treatment is an outpatient procedure that involves releasing the thumb flexor tendon from a small fibrous sheath called the A1 pulley. The overall recurrence rate after surgery is 1.4%. Our recommendation is for early referral to a pediatric orthopedic surgeon to evaluate for the need for surgical intervention. Copyright 2016, SLACK Incorporated.

  2. Intoeing: a developmental norm.

    Science.gov (United States)

    Ryan, D J

    2001-01-01

    Intoeing, often referred to as pigeon-toes, is a frequent reason for referral to the pediatric orthopaedic surgeon's practice. Parents and grandparents are concerned about the appearance of the legs and a history of frequent tripping and falling. Many of the "abnormalities" that these children present with are variations of normal development of the lower extremities and include flat footedness, and torsional or angular "deformity." The approach of the specialist team is to identify the source of the intoeing, to rule out neuromuscular dysfunction or other serious conditions, and to counsel the family on anticipatory guidance of the natural history of intoeing. The focus of this article is intoeing, associated examination techniques, and nursing considerations of education and treatment. An understanding of musculoskeletal developmental norms, the clinical examination for intoeing, and the current recommendations for treatment will enable the provider to educate and accurately inform families.

  3. Developmental prosopagnosia in childhood.

    Science.gov (United States)

    Dalrymple, Kirsten A; Corrow, Sherryse; Yonas, Albert; Duchaine, Brad

    2012-01-01

    Developmental prosopagnosia (DP) is defined by severe face recognition problems resulting from a failure to develop the necessary visual mechanisms for processing faces. While there is a growing literature on DP in adults, little has been done to study this disorder in children. The profound impact of abnormal face perception on social functioning and the general lack of awareness of childhood DP can result in severe social and psychological consequences for children. This review discusses possible aetiologies of DP and summarizes the few cases of childhood DP that have been reported. It also outlines key objectives for the growth of this emerging research area and special considerations for studying DP in children. With clear goals and concerted efforts, the study of DP in childhood will be an exciting avenue for enhancing our understanding of normal and abnormal face perception for all age groups.

  4. Developmental milestones record - 2 years

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/002012.htm Developmental milestones record - 2 years To use the sharing features ... two years. www.cdc.gov/ncbddd/actearly/milestones/milestones-2yr.html . ... T. Global developmental delay and regression. In: Daroff RB, Jankovich J, ...

  5. Promoting Multiculturalism in Developmental Education.

    Science.gov (United States)

    Higbee, Jeanne L.

    2001-01-01

    Asserts that the teaching profession needs to recognize the natural connections between multicultural and developmental education. Presents eight steps developmental educators can take to promote pluralism, including (1) establishing a clear link between cultural pluralism and institutional and programmatic mission and goals; (2) striving for…

  6. [Developmental Placement.] Collected Research References.

    Science.gov (United States)

    Bjorklund, Gail

    Drawing on information and references in the ERIC system, this literature review describes research related to a child's developmental placement. The issues examined include school entrance age; predictive validity, reliability, and features of Gesell School Readiness Assessment; retention; and the effectiveness of developmental placement. A…

  7. Developmentally Appropriate Peace Education Curricula

    Science.gov (United States)

    Lewsader, Joellen; Myers-Walls, Judith A.

    2017-01-01

    Peace education has been offered to children for decades, but those curricula have been only minimally guided by children's developmental stages and needs. In this article, the authors apply their research on children's developmental understanding of peace along with peace education principles and Vygotsky's sociocultural theory to present…

  8. Prenatal Programming and Toxicity (PPTOX) Introduction.

    Science.gov (United States)

    Birnbaum, Linda S; Miller, Mark F

    2015-10-01

    The developmental origin of health and disease hypothesis posits that early-life exposures, including prenatal, can influence disease outcomes throughout the entire lifespan of an organism. Over the past 30 years, scientific researchers have compiled robust epidemiological and mechanistic data showing the effects of early-life nutrition, chemical exposures, and stress on prenatal programing and toxicity. Using novel techniques in genomics and epigenetics, science is now establishing strong links between low-level early-life environmental exposures and the later development of noncommunicable diseases, such as cardiovascular disease, obesity, diabetes, neurodevelopmental and neurodegenerative disease, reproductive effects, immune system function and cancer. Now scientists must engage with communities, industry, policy makers, and clinicians to leverage our newfound understanding of prenatal programing and toxicity into better health outcomes across the lifespan.

  9. Embryogenomics: developmental biology meets genomics.

    Science.gov (United States)

    Ko, M S

    2001-12-01

    Fundamental questions in developmental biology are: what genes are expressed, where and when they are expressed, what is the level of expression and how are these programs changed by the functional and structural alteration of genes? These questions have been addressed by studying one gene at a time, but a new research field that handles many genes in parallel is emerging. The methodology is at the interface of large-scale genomics approaches and developmental biology. Genomics needs developmental biology because one of the goals of genomics--collection and analysis of all genes in an organism--cannot be completed without working on embryonic tissues in which many genes are uniquely expressed. However, developmental biology needs genomics--the high-throughput approaches of genomics generate information about genes and pathways that can give an integrated view of complex processes. This article discusses these new approaches and their applications to mammalian developmental biology.

  10. Phenotypic Dichotomy Following Developmental Exposure to Perfluorooctanic Acid (PFOA) Exposure in CD-1 Mice: Low Doses Induce Elevated Serum, Leptin, Insulin, and Overweight in Mid-Life.

    Science.gov (United States)

    The synthetic surfactant, perfluorooctanoic acid (PFOA) is a proven developmental toxicant in mice, causing prenatal pregnancy loss, increased neonatal mortality, delayed eye opening, and abnormal mammary gland growth in animals exposed during fetal life. PFOA is found in the ser...

  11. Females and Toxic Leadership

    Science.gov (United States)

    2012-12-14

    than uplifting followers. Toxic leadership plummets productivity and applies brakes to organizational growth , causing progress to screech to a halt...uplifting followers. Toxic leadership plummets productivity and applies brakes to organizational growth , causing progress to screech to a halt.”5...FEMALES AND TOXIC LEADERSHIP A thesis presented to the Faculty of the U.S. Army Command and General Staff College in

  12. CHEMICAL TOXICITY OF URANIUM

    Directory of Open Access Journals (Sweden)

    Sermin Cam

    2007-06-01

    Full Text Available Uranium, occurs naturally in the earth’s crust, is an alpha emitter radioactive element from the actinide group. For this reason, U-235 and U-238, are uranium isotopes with long half lives, have got radiological toxicity. But, for natural-isotopic-composition uranium (NatU, there is greater risk from chemical toxicity than radiological toxicity. When uranium is get into the body with anyway, also its chemical toxicity must be thought. [TAF Prev Med Bull 2007; 6(3.000: 215-220

  13. Attentional networks in developmental dyscalculia

    Directory of Open Access Journals (Sweden)

    Henik Avishai

    2010-01-01

    Full Text Available Abstract Background Very little is known about attention deficits in developmental dyscalculia, hence, this study was designed to provide the missing information. We examined attention abilities of participants suffering from developmental dyscalculia using the attention networks test - interactions. This test was designed to examine three different attention networks--executive function, orienting and alerting--and the interactions between them. Methods Fourteen university students that were diagnosed as suffering from developmental dyscalculia--intelligence and reading abilities in the normal range and no indication of attention-deficit hyperactivity disorder--and 14 matched controls were tested using the attention networks test - interactions. All participants were given preliminary tests to measure mathematical abilities, reading, attention and intelligence. Results The results revealed deficits in the alerting network--a larger alerting effect--and in the executive function networks--a larger congruity effect in developmental dyscalculia participants. The interaction between the alerting and executive function networks was also modulated by group. In addition, developmental dyscalculia participants were slower to respond in the non-cued conditions. Conclusions These results imply specific attentional deficits in pure developmental dyscalculia. Namely, those with developmental dyscalculia seem to be deficient in the executive function and alertness networks. They suffer from difficulty in recruiting attention, in addition to the deficits in numerical processing.

  14. Attentional networks in developmental dyscalculia.

    Science.gov (United States)

    Askenazi, Sarit; Henik, Avishai

    2010-01-07

    Very little is known about attention deficits in developmental dyscalculia, hence, this study was designed to provide the missing information. We examined attention abilities of participants suffering from developmental dyscalculia using the attention networks test - interactions. This test was designed to examine three different attention networks--executive function, orienting and alerting--and the interactions between them. Fourteen university students that were diagnosed as suffering from developmental dyscalculia--intelligence and reading abilities in the normal range and no indication of attention-deficit hyperactivity disorder--and 14 matched controls were tested using the attention networks test-interactions. All participants were given preliminary tests to measure mathematical abilities, reading, attention and intelligence. The results revealed deficits in the alerting network--a larger alerting effect--and in the executive function networks--a larger congruity effect in developmental dyscalculia participants. The interaction between the alerting and executive function networks was also modulated by group. In addition, developmental dyscalculia participants were slower to respond in the non-cued conditions. These results imply specific attentional deficits in pure developmental dyscalculia. Namely, those with developmental dyscalculia seem to be deficient in the executive function and alertness networks. They suffer from difficulty in recruiting attention, in addition to the deficits in numerical processing.

  15. Developmental breast asymmetry.

    Science.gov (United States)

    Chan, WoanYi; Mathur, Bhagwat; Slade-Sharman, Diana; Ramakrishnan, Venkat

    2011-01-01

    Developmental breast asymmetry (DBA) can affect psychosocial well-being in the young female. Correction of breast asymmetry may present a reconstructive challenge, especially in tuberous breasts. Fifty-two cases of DBA treated between January 2002 and January 2006 were reviewed. Preoperative clinical assessment of the specific anatomical deformity, subsequent surgical treatment modalities, esthetic outcome, and patient's satisfaction were evaluated. Surgical modalities used in our series include augmentation mammaplasty with or without tissue expansion, parenchymal scoring, nipple areola complex reduction, glanduloplasty techniques, mastopexy and reduction mammaplasty. The mean age of DBA presentation was 21 years; 69% (36/52) patients had tuberous breasts, of which 67% (24/36) were unilateral and 33% (12/36) were bilateral deformities. Patients with tuberous breast deformity presented consistently under the age of 25 years. Esthetic outcome was rated "good" in 75% (39/52), and symmetry rated as "good" in 58% (30/52) by professional evaluation. Surgical treatment is tailored to the affected esthetic units of the individual breast. In our experience, symmetry is the hardest parameter to achieve, particularly in tuberous breasts. Operative treatment is of great value to the psychosocial well-being of the patient. A conceptual approach in the assessment and treatment of DBA is emphasized by this series. © 2011 Wiley Periodicals, Inc.

  16. Developmental dyslexia and vision

    Directory of Open Access Journals (Sweden)

    Quercia P

    2013-05-01

    Full Text Available Patrick Quercia,1 Léonard Feiss,2 Carine Michel31Department of Ophthalmology, University Hospital, Dijon, France; 2Office of Ophthalmology, Beaune, France; 3University of Burgundy, Dijon, INSERM U1093, Cognition, Action et Plasticité Sensorimotrice, Dijon, FranceAbstract: Developmental dyslexia affects almost 10% of school-aged children and represents a significant public health problem. Its etiology is unknown. The consistent presence of phonological difficulties combined with an inability to manipulate language sounds and the grapheme–phoneme conversion is widely acknowledged. Numerous scientific studies have also documented the presence of eye movement anomalies and deficits of perception of low contrast, low spatial frequency, and high frequency temporal visual information in dyslexics. Anomalies of visual attention with short visual attention spans have also been demonstrated in a large number of cases. Spatial orientation is also affected in dyslexics who manifest a preference for spatial attention to the right. This asymmetry may be so pronounced that it leads to a veritable neglect of space on the left side. The evaluation of treatments proposed to dyslexics whether speech or oriented towards the visual anomalies remains fragmentary. The advent of new explanatory theories, notably cerebellar, magnocellular, or proprioceptive, is an incentive for ophthalmologists to enter the world of multimodal cognition given the importance of the eye's visual input.Keywords: reading, ocular motility, dyslexia, neglect, spatial representation

  17. Developmental programming and epigenetics.

    Science.gov (United States)

    Gabory, Anne; Attig, Linda; Junien, Claudine

    2011-12-01

    The ways in which epigenetic modifications fix the effects of early environmental events, ensuring sustained responses to transient stimuli that result in modified gene expression patterns and phenotypes later in life, are a topic of considerable interest. This article focuses on recently discovered mechanisms and calls into question prevailing views about the dynamics, positions, and functions of epigenetic marks. Most epigenetic studies have addressed the long-term effects of environmental stressors on a small number of epigenetic marks, at the global or individual gene level, in humans and in animal models. In parallel, increasing numbers of studies based on high-throughput technologies are revealing additional complexity in epigenetic processes by highlighting the importance of crosstalk between different epigenetic marks in humans and mice. A number of studies focusing on metabolic programming and the developmental origin of health and disease have identified links between early nutrition, epigenetic processes, and long-term illness. The existence of a self-propagating epigenetic cycle has been shown. Moreover, recent studies have shown an obvious sexual dimorphism both for programming trajectories and in response to the same environmental insult. Despite recent progress, however, we are still far from understanding how, when, and where environmental stressors disturb key epigenetic mechanisms. Thus, the need to identify original key marks and monitor the changes they undergo throughout development, during an individual's lifetime, or over several generations remains a challenging issue.

  18. Toxic proteins in plants.

    Science.gov (United States)

    Dang, Liuyi; Van Damme, Els J M

    2015-09-01

    Plants have evolved to synthesize a variety of noxious compounds to cope with unfavorable circumstances, among which a large group of toxic proteins that play a critical role in plant defense against predators and microbes. Up to now, a wide range of harmful proteins have been discovered in different plants, including lectins, ribosome-inactivating proteins, protease inhibitors, ureases, arcelins, antimicrobial peptides and pore-forming toxins. To fulfill their role in plant defense, these proteins exhibit various degrees of toxicity towards animals, insects, bacteria or fungi. Numerous studies have been carried out to investigate the toxic effects and mode of action of these plant proteins in order to explore their possible applications. Indeed, because of their biological activities, toxic plant proteins are also considered as potentially useful tools in crop protection and in biomedical applications, such as cancer treatment. Genes encoding toxic plant proteins have been introduced into crop genomes using genetic engineering technology in order to increase the plant's resistance against pathogens and diseases. Despite the availability of ample information on toxic plant proteins, very few publications have attempted to summarize the research progress made during the last decades. This review focuses on the diversity of toxic plant proteins in view of their toxicity as well as their mode of action. Furthermore, an outlook towards the biological role(s) of these proteins and their potential applications is discussed. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Glyphosate induces cardiovascular toxicity in Danio rerio.

    Science.gov (United States)

    Roy, Nicole M; Ochs, Jeremy; Zambrzycka, Ewelina; Anderson, Ariann

    2016-09-01

    Glyphosate is a broad spectrum herbicide used aggressively in agricultural practices as well as home garden care. Although labeled "safe" by the chemical industry, doses tested by industry do not mimic chronic exposures to sublethal doses that organisms in the environment are exposed to over long periods of time. Given the widespread uses of and exposure to glyphosate, studies on developmental toxicity are needed. Here we utilize the zebrafish vertebrate model system to study early effects of glyphosate on the developing heart. Treatment by embryo soaking with 50μg/ml glyphosate starting at gastrulation results in structural abnormalities in the atrium and ventricle, irregular heart looping, situs inversus as well as decreased heartbeats by 48h as determined by live imaging and immunohistochemistry. Vasculature in the body was also affected as determined using fli-1 transgenic embryos. To determine if the effects noted at 48h post fertilization are due to early stage alterations in myocardial precursors, we also investigate cardiomyocyte development with a Mef2 antibody and by mef2ca in situ hybridization and find alterations in the Mef2/mef2ca staining patterns during early cardiac patterning stages. We conclude that glyphosate is developmentally toxic to the zebrafish heart. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Mechanisms of Phosphine Toxicity

    Directory of Open Access Journals (Sweden)

    Nisa S. Nath

    2011-01-01

    Full Text Available Fumigation with phosphine gas is by far the most widely used treatment for the protection of stored grain against insect pests. The development of high-level resistance in insects now threatens its continued use. As there is no suitable chemical to replace phosphine, it is essential to understand the mechanisms of phosphine toxicity to increase the effectiveness of resistance management. Because phosphine is such a simple molecule (PH3, the chemistry of phosphorus is central to its toxicity. The elements above and below phosphorus in the periodic table are nitrogen (N and arsenic (As, which also produce toxic hydrides, namely, NH3 and AsH3. The three hydrides cause related symptoms and similar changes to cellular and organismal physiology, including disruption of the sympathetic nervous system, suppressed energy metabolism and toxic changes to the redox state of the cell. We propose that these three effects are interdependent contributors to phosphine toxicity.

  1. Developmental origins of adult diseases and neurotoxicity: Epidemiological and experimental studies

    NARCIS (Netherlands)

    Fox, D.A.; Grandjean, P.; Groot, D. de; Paule, M.G.

    2012-01-01

    To date, only a small number of commercial chemicals have been tested and documented as developmental neurotoxicants. Moreover, an increasing number of epidemiological, clinical and experimental studies suggest an association between toxicant or drug exposure during the perinatal period and the

  2. Parental tobacco smoke exposure: Epigenetics and the developmental origins of health and disease

    Science.gov (United States)

    Epigenetic programming is an important mechanism underlying the Developmental Origins of Health and Disease (DOHaD). Much of the research in this area has focused on maternal nutrition. Parental smoking has emerged as a prime example of how exposure to environmental toxicants dur...

  3. PREVALENCE AND EFFECT OF DEVELOPMENTAL ...

    African Journals Online (AJOL)

    uvp

    School Beginners questionnaire. INTRODUCTION. Children with Developmental Coordination Disorder (DCD) experience considerable difficulties in motor learning and in the performance of functional motor tasks that are critical for success in the school environment (APA, 2013). These children demonstrate poor motor.

  4. Pervasive Developmental Disorder and ADHD

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2006-05-01

    Full Text Available The relationship between patients with attention deficit hyperactivity disorder (ADHD and those with pervasive developmental disorders (PDD was studied at Okayama University Graduate School of Medicine, Japan.

  5. Pesticides: an update of human exposure and toxicity.

    Science.gov (United States)

    Mostafalou, Sara; Abdollahi, Mohammad

    2017-02-01

    Pesticides are a family of compounds which have brought many benefits to mankind in the agricultural, industrial, and health areas, but their toxicities in both humans and animals have always been a concern. Regardless of acute poisonings which are common for some classes of pesticides like organophosphoruses, the association of chronic and sub-lethal exposure to pesticides with a prevalence of some persistent diseases is going to be a phenomenon to which global attention has been attracted. In this review, incidence of various malignant, neurodegenerative, respiratory, reproductive, developmental, and metabolic diseases in relation to different routes of human exposure to pesticides such as occupational, environmental, residential, parental, maternal, and paternal has been systematically criticized in different categories of pesticide toxicities like carcinogenicity, neurotoxicity, pulmonotoxicity, reproductive toxicity, developmental toxicity, and metabolic toxicity. A huge body of evidence exists on the possible role of pesticide exposures in the elevated incidence of human diseases such as cancers, Alzheimer, Parkinson, amyotrophic lateral sclerosis, asthma, bronchitis, infertility, birth defects, attention deficit hyperactivity disorder, autism, diabetes, and obesity. Most of the disorders are induced by insecticides and herbicides most notably organophosphorus, organochlorines, phenoxyacetic acids, and triazine compounds.

  6. Developmental constraint of insect audition

    OpenAIRE

    Strauß Johannes; Lakes-Harlan Reinhard

    2006-01-01

    Abstract Background Insect ears contain very different numbers of sensory cells, from only one sensory cell in some moths to thousands of sensory cells, e.g. in cicadas. These differences still await functional explanation and especially the large numbers in cicadas remain puzzling. Insects of the different orders have distinct developmental sequences for the generation of auditory organs. These sensory cells might have different functions depending on the developmental stages. Here we propos...

  7. Developmental stability and human violence.

    OpenAIRE

    Furlow, B; Gangestad, S W; Armijo-Prewitt, T

    1998-01-01

    Developmental stability (the precision with which genotypes are translated into phenotypes under physically stressful developmental conditions), is a major source of phenotypic and behavioural variation, yet researchers have largely ignored its potential role in the ontogeny of individual propensities toward human aggression and violence. In this study, we measured fluctuating asymmetry of the body and administered aggression and fighting history questionnaires to 229 college students (139 fe...

  8. The contemporary psychodynamic developmental perspective.

    Science.gov (United States)

    Malberg, Norka T; Mayes, Linda C

    2013-01-01

    Authors address the transformations taking place in the last 25 years in the theory and practice of developmental psychoanalysis. They emphasize the role of attachment theory in this process and its clinical applications to the work with children and families and the social systems supporting them. The article also describes and explores a move toward an integrative and systemic developmental psychodynamic approach and its relevance to today's practitioner. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. 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.

  10. Developmental Science: Past, Present, and Future

    Science.gov (United States)

    Lerner, Richard M.

    2012-01-01

    The goal of developmental science is to describe, explain, and optimize intraindividual changes in adaptive developmental regulations and, as well, interindividual differences in such relations, across life. The history of developmental science is reviewed and its current foci, which are framed by relational developmental systems models that…

  11. Pediatric Toxic Shock Syndrome

    Directory of Open Access Journals (Sweden)

    Jennifer Yee

    2017-09-01

    Full Text Available Audience: This scenario was developed to educate emergency medicine residents on the diagnosis and management of a pediatric patient with toxic shock syndrome. The case is also appropriate for teaching of medical students and advanced practice providers, as well as a review of the principles of crisis resource management, teamwork, and communication. Introduction: Toxic shock syndrome is a low-frequency, high-acuity scenario requiring timely identification and aggressive management. If patients suffering from this condition are managed incorrectly, they may progress into multi-organ dysfunction and potentially death. Toxic shock syndrome has been associated with Streptococcus and Staphylococcus aureus (Staph. Approximately half of Staph cases are associated with menstruation, which was first described in the 1970s-1980s and was associated with the use of absorbent tampons.1 Group A Streptococcus may cause complications such as necrotizing fasciitis and gangrenous myositis.2 Pediatric patients may present critically ill from toxic shock syndrome. Providers need to perform a thorough history and physical exam to discern the source of infection. Management requires aggressive care with antibiotics and IV fluids. Objectives: By the end of this simulation session, the learner will be able to: 1 Recognize toxic shock syndrome. 2 Review the importance of a thorough physical exam. 3 Discuss management of toxic shock syndrome, including supportive care and the difference in antibiotic choices for streptococcal and staphylococcal toxic shock syndrome. 4 Appropriately disposition a patient suffering from toxic shock syndrome. 5 Communicate effectively with team members and nursing staff during a resuscitation of a critically ill patient. Method: This session was conducted using high-fidelity simulation, followed by a debriefing session and lecture on toxic shock syndrome.

  12. Electronic Cigarette Toxicity.

    Science.gov (United States)

    Payne, J Drew; Michaels, David; Orellana-Barrios, Menfil; Nugent, Kenneth

    2017-04-01

    Electronic cigarettes (e-cigarettes) are often advertised as a healthier product when compared with traditional cigarettes. Currently, there are limited data to support this and only a threat of federal regulation from the US Food and Drug Administration. Calls to poison control centers about e-cigarette toxicity, especially in children, and case reports of toxic exposures have increased over the past 3 years. This research letter reports the frequency of hazardous exposures to e-cigarettes and characterizes the reported adverse health effects associated with e-cigarette toxicity.

  13. Assessing Nanoparticle Toxicity

    Science.gov (United States)

    Love, Sara A.; Maurer-Jones, Melissa A.; Thompson, John W.; Lin, Yu-Shen; Haynes, Christy L.

    2012-07-01

    Nanoparticle toxicology, an emergent field, works toward establishing the hazard of nanoparticles, and therefore their potential risk, in light of the increased use and likelihood of exposure. Analytical chemists can provide an essential tool kit for the advancement of this field by exploiting expertise in sample complexity and preparation as well as method and technology development. Herein, we discuss experimental considerations for performing in vitro nanoparticle toxicity studies, with a focus on nanoparticle characterization, relevant model cell systems, and toxicity assay choices. Additionally, we present three case studies (of silver, titanium dioxide, and carbon nanotube toxicity) to highlight the important toxicological considerations of these commonly used nanoparticles.

  14. Liquid Nicotine Toxicity.

    Science.gov (United States)

    Kim, Ji Won; Baum, Carl R

    2015-07-01

    E-cigarettes, also known as electronic nicotine delivery systems and electronic cigarettes, are advertised as a healthier alternative product to tobacco cigarettes despite limited data on the consequences of e-cigarette use. Currently, there are no US Food and Drug Administration or other federal regulations of e-cigarettes, and calls to poison control centers regarding liquid nicotine toxicity, especially in children, are on the rise. This article presents the background and mechanism of action of e-cigarettes as well as up-to-date details of the toxicity of liquid nicotine. We also present management strategies in the setting of liquid nicotine toxicity.

  15. Acute, subchronic, and developmental toxicological properties of lubricating oil base stocks.

    Science.gov (United States)

    Dalbey, Walden E; McKee, Richard H; Goyak, Katy Olsavsky; Biles, Robert W; Murray, Jay; White, Russell

    2014-01-01

    Lubricating oil base stocks (LOBs) are substances used in the manufacture of finished lubricants and greases. They are produced from residue remaining after atmospheric distillation of crude oil that is subsequently fractionated by vacuum distillation and additional refining steps. Initial LOB streams that have been produced by vacuum distillation but not further refined may contain polycyclic aromatic compounds (PACs) and may present carcinogenic hazards. In modern refineries, LOBs are further refined by multistep processes including solvent extraction and/or hydrogen treatment to reduce the levels of PACs and other undesirable constituents. Thus, mildly (insufficiently) refined LOBs are potentially more hazardous than more severely (sufficiently) refined LOBs. This article discusses the evaluation of LOBs using statistical models based on content of PACs; these models indicate that insufficiently refined LOBs (potentially carcinogenic LOBs) can also produce systemic and developmental effects with repeated dermal exposure. Experimental data were also obtained in ten 13-week dermal studies in rats, eight 4-week dermal studies in rabbits, and seven dermal developmental toxicity studies with sufficiently refined LOBs (noncarcinogenic and commonly marketed) in which no observed adverse effect levels for systemic toxicity and developmental toxicity were 1000 to 2000 mg/kg/d with dermal exposures, typically the highest dose tested. Results in both oral and inhalation developmental toxicity studies were similar. This absence of toxicologically relevant findings was consistent with lower PAC content of sufficiently refined LOBs. Based on data on reproductive organs with repeated dosing and parameters in developmental toxicity studies, sufficiently refined LOBs are likely to have little, if any, effect on reproductive parameters.

  16. Protocol Development and Preliminary Toxicity Study of CBRN Nanomaterials

    Science.gov (United States)

    2013-12-05

    developmental problems in offspring. One study found titanium dioxide ( TiO2 ) nanoparticles were present in the placenta, fetal liver and fetal brain. This...lungs, but can also cross into the blood stream and disseminate deeper inside the body to threaten the brain, liver, kidney , and other tissues/organs...is quite different than for micro-sized TiO2 particles, which are considered inert and relatively non-toxic to experimental animals and humans

  17. Developmental Neurotoxicants in E-Waste: An Emerging Health Concern

    Science.gov (United States)

    Chen, Aimin; Dietrich, Kim N.; Huo, Xia; Ho, Shuk-mei

    2011-01-01

    Objective Electronic waste (e-waste) has been an emerging environmental health issue in both developed and developing countries, but its current management practice may result in unintended developmental neurotoxicity in vulnerable populations. To provide updated information about the scope of the issue, presence of known and suspected neurotoxicants, toxicologic mechanisms, and current data gaps, we conducted this literature review. Data sources We reviewed original articles and review papers in PubMed and Web of Science regarding e-waste toxicants and their potential developmental neurotoxicity. We also searched published reports of intergovernmental and governmental agencies and nongovernmental organizations on e-waste production and management practice. Data extraction We focused on the potential exposure to e-waste toxicants in vulnerable populations—that is, pregnant women and developing children—and neurodevelopmental outcomes. In addition, we summarize experimental evidence of developmental neurotoxicity and mechanisms. Data synthesis In developing countries where most informal and primitive e-waste recycling occurs, environmental exposure to lead, cadmium, chromium, polybrominated diphenyl ethers, polychlorinated biphenyls, and polycyclic aromatic hydrocarbons is prevalent at high concentrations in pregnant women and young children. Developmental neurotoxicity is a serious concern in these regions, but human studies of adverse effects and potential mechanisms are scarce. The unprecedented mixture of exposure to heavy metals and persistent organic pollutants warrants further studies and necessitates effective pollution control measures. Conclusions Pregnant women and young children living close to informal e-waste recycling sites are at risk of possible perturbations of fetus and child neurodevelopment. PMID:21081302

  18. Alternative acute inhalation toxicity testing by determination of the concentration-time-mortality relationship : experimental comparison with standard LC50 testing

    NARCIS (Netherlands)

    Zwart, A.; Arts, J.H.E.; Berge, W.F. ten; Appelman, L.M.

    1992-01-01

    A new design for acute inhalation toxicity testing was evaluated and compared with results obtained according to OECD guideline 403. The new design consists of a range-finding test, which is compatible with a conventional limit test, and can be followed by determination of a

  19. Complex Mixture-Associated Hormesis and Toxicity: The Case of Leather Tanning Industry

    Science.gov (United States)

    Pagano, Giovanni; Castello, Giuseppe; Gallo, Marialuisa; Borriello, Ilaria; Guida, Marco

    2008-01-01

    A series of studies investigated the toxicities of tannery-derived complex mixtures, i.e. vegetable tannin (VT) from Acacia sp. or phenol-based synthetic tannin (ST), and waste-water from tannin-based vs. chromium-based tanneries. Toxicity was evaluated by multiple bioassays including developmental defects and loss of fertilization rate in sea urchin embryos and sperm (Paracentrotus lividus and Sphaerechinus granularis), and algal growth inhibition (Dunaliella tertiolecta and Selenastrum capricornutum). Both VT and ST water extracts resulted in hormetic effects at concentrations ranging 0.1 to 0.3%, and toxicity at levels ≥1%, both in sea urchin embryo and sperm, and in algal growth bioassays. When comparing tannin-based tannery wastewater (TTW) vs. chromium-based tannery effluent (CTE), a hormesis to toxicity trend was observed for TTW both in terms of developmental and fertilization toxicity in sea urchins, and in algal growth inhibition, with hormetic effects at 0.1 to 0.2% TTW, and toxicity at TTW levels ≥1%. Unlike TTW, CTE showed a monotonic toxicity increase from the lowest tested level (0.1%) and CTE toxicity at higher levels was significantly more severe than TTW-induced toxicity. The results support the view that leather production utilizing tannins might be regarded as a more environmentally friendly procedure than chromium-based tanning process. PMID:19088903

  20. Toxics Release Inventory (TRI)

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Toxics Release Inventory (TRI) is a dataset compiled by the U.S. Environmental Protection Agency (EPA). It contains information on the release and waste...

  1. Toxicity Reference Database

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Toxicity Reference Database (ToxRefDB) contains approximately 30 years and $2 billion worth of animal studies. ToxRefDB allows scientists and the interested...

  2. Local anaesthetic toxicity

    African Journals Online (AJOL)

    treatment strategies. Introduction ... depression and central nervous system and cardiovascular toxicity increased .... requiring analgesic therapy beyond that of surgery. ..... Progress in Biophysics and Molecular Biology 2006;91:1 –82. 32.

  3. [Toxicity of hydroxyquinoline derivatives].

    Science.gov (United States)

    Pashov, D; Simeonov, S P; Drumev, D; Peĭnikova, Ts; Dzhurov, A

    1980-01-01

    We studied a 90 day toxicity in dogs of the compound broxyquinoline + broxaldine--5:1 (enteroquin), applied orally and daily in doses of 0.1 and 0.2/kg t/24 h. We established the toxic manifestations during the period after the 15th day of the treatment: leukopenia, neutropenia and lymphocytosis (by 0.2 kg t/24 h). After the second and fifth day we observed a decrease of appetite, depression of the CNS, paralyses, arrhythmia, progressing loss in weight, proteinorrhea (more pronounced with those receiving 0.2/kg t (24 h); lethal consequence with some part of the animals 25% (ba 0.1/kg t) and 50% (by 0.2 kg t). We found out pathohistologically necrobiotic changes in the medulla oblongata and the kidneys, toxic distrophy of the liver, blood-vessel injuries. The toxic changes observed can be interpreted in connection with the presence of a species specific reaction.

  4. Recurrent amiodarone pulmonary toxicity.

    Science.gov (United States)

    Chendrasekhar, A; Barke, R A; Druck, P

    1996-01-01

    Amiodarone, a widely used antiarrhythmic drug, is associated with pulmonary toxicity, with an estimated mortality of 1% to 33%. Standard treatment for amiodarone pulmonary toxicity (APT) has been discontinuance of the drug and steroid therapy. We report a case of APT that recurred after withdrawal of steroids and failed to respond to reinstatement of steroid therapy. Recurrent APT is a rare clinical entity that has been reported only twice in recent literature.

  5. [Toxic alcohol poisonings].

    Science.gov (United States)

    Kulicki, Paweł; Głogowski, Tomasz

    Accidental or intentional poisonings with ethylene glycol or methanol constitute a serious toxicological problem in many countries. Both alcohols are quickly metabolized by alcohol dehydrogenase to toxic metabolites responsible for high anion gap severe metabolic acidosis and profound neurological, cardiopulmonary, renal disturbances and death. In the early period, the competing inhibition the alcohol dehydrogenase with ethanol or fomepizol may successfully prevent the formation of the toxic metabolites. Once severe acidosis develops an emergency hemodialysis is required.

  6. Developmental evolution facilitates rapid adaptation.

    Science.gov (United States)

    Lin, Hui; Kazlauskas, Romas J; Travisano, Michael

    2017-11-21

    Developmental evolution has frequently been identified as a mode for rapid adaptation, but direct observations of the selective benefits and associated mechanisms of developmental evolution are necessarily challenging to obtain. Here we show rapid evolution of greatly increased rates of dispersal by developmental changes when populations experience stringent selection. Replicate populations of the filamentous fungus Trichoderma citrinoviride underwent 85 serial transfers, under conditions initially favoring growth but not dispersal. T. citrinoviride populations shifted away from multicellular growth toward increased dispersal by producing one thousand times more single-celled asexual conidial spores, three times sooner than the ancestral genotype. Conidia of selected lines also germinated fifty percent faster. Gene expression changed substantially between the ancestral and selected fungi, especially for spore production and growth, demonstrating rapid evolution of tight regulatory control for down-regulation of growth and up-regulation of conidia production between 18 and 24 hours of growth. These changes involved both developmentally fixed and plastic changes in gene expression, showing that complex developmental changes can serve as a mechanism for rapid adaptation.

  7. The renaissance of developmental biology.

    Science.gov (United States)

    St Johnston, Daniel

    2015-05-01

    Since its heyday in the 1980s and 90s, the field of developmental biology has gone into decline; in part because it has been eclipsed by the rise of genomics and stem cell biology, and in part because it has seemed less pertinent in an era with so much focus on translational impact. In this essay, I argue that recent progress in genome-wide analyses and stem cell research, coupled with technological advances in imaging and genome editing, have created the conditions for the renaissance of a new wave of developmental biology with greater translational relevance.

  8. Developmental and Reproductive Effects of SE5-OH: An Equol-Rich Soy-Based Ingredient

    Directory of Open Access Journals (Sweden)

    Ray A. Matulka

    2009-01-01

    Full Text Available Consumption of the isoflavones daidzein, genistein, glycitein, and their structural analogues is generally considered beneficial to human health. Equol is not found in soy, but is converted from daidzein by human gut bacterial flora. Research indicates that between 30–50% of the population is capable of converting daidzein to equol; therefore, there has been recent development of a new equol-rich functional food that relies on bacterial conversion of daidzein to equol under strictly controlled conditions. Therefore, a new equol-rich soy product (SE5-OH has been developed, based on the bacterial conversion of daidzein; and its reproductive and developmental toxicity has been evaluated in a two-generation study and a developmental toxicity study with Sprague-Dawley rats at dose levels of 200, 1000, and 2000 mg/kg/day by gavage. SE5-OH contains approximately 0.65% equol, 0.024% daidzein, 0.022% genistein, and 0.30% glycitein. From the reproductive study, the no-observed-adverse-effect-level (NOAEL for SE5-OH determined for both male and female rats is 1000 mg/kg/day (6.5 mg equol/kg/day. In the developmental toxicity phase of the study, no effects by SE5-OH were found in the embryo-fetus at any of the doses tested. The NOAEL for developmental effects of SE5-OH is 2000 mg/kg/day (13 mg equol/kg/day.

  9. [Toxicity of puffer fish fins].

    Science.gov (United States)

    Honda, Shunichi; Ichimaru, Shunichi; Arakawa, Osamu; Takatani, Tomohiro; Noguchi, Tamao; Ishizaki, Shoichiro; Nagashima, Yuji

    2007-10-01

    Puffer fish is prized as a Japanese traditional food and its fin is also used in the cuisine. However, whether the fin is edible or not is determined for convenience from the toxicity of skin, since little information is available about the toxicity of puffer fish fins. In the present study, we examined the toxicity of fins and skin of three toxic species, Takifugu vermicularis, T. snyderi, and T. porphyreus. The toxicity of T. vermicularis fins (puffer fish with toxic skin also have toxic fins.

  10. Developmental neurotoxicity test guidelines: problems and perspectives.

    Science.gov (United States)

    Tohyama, Chiharu

    2016-01-01

    Epidemiologic evidence has demonstrated associations between early life exposure to industrial chemicals and the occurrence of disease states, including cognitive and behavioral abnormalities, in children. The developing brain in the fetal and infantile periods is extremely vulnerable to chemicals because the blood-brain barrier is not completely formed during these periods. The Organisation for Economic Co-operation and Development (OECD) developmental neurotoxicity (DNT) test guideline, TG426, updated in 2007, comprises in vivo behavioral observational tests and other tests intended to assess DNT induced by exposure to industrial chemicals. These chemicals may enter the market without having been subjected to DNT testing, as DNT test data is not mandated by law at the time of chemical registration. In addition, proprietary rights have led to problems concerning the non-disclosure of industrial chemical toxicity test data, including DNT test data. To overcome the disadvantages of high-cost and low time efficiency of in vivo DNT tests, in vitro or in silico tests are the proposed alternatives, but it is unlikely that the results of such tests would reflect changes in higher brain functions. Accordingly, the current DNT test guidelines need to be revised to avoid overlooking or neglecting the occurrence of DNT induced by exposure to low doses of chemicals. This review also proposes the introduction of novel in vivo DNT testing methods in light of a cost-performance analysis.

  11. Toxicity Data to Determine Refrigerant Concentration Limits

    Energy Technology Data Exchange (ETDEWEB)

    Calm, James M.

    2000-09-30

    This report reviews toxicity data, identifies sources for them, and presents resulting exposure limits for refrigerants for consideration by qualified parties in developing safety guides, standards, codes, and regulations. It outlines a method to calculate an acute toxicity exposure limit (ATEL) and from it a recommended refrigerant concentration limit (RCL) for emergency exposures. The report focuses on acute toxicity with particular attention to lethality, cardiac sensitization, anesthetic and central nervous system effects, and other escape-impairing effects. It addresses R-11, R-12, R-22, R-23, R-113, R-114, R-116, R-123, R-124, R-125, R-134, R-134a, R-E134, R-141b, R-142b, R-143a, R-152a, R-218, R-227ea, R-236fa, R-245ca, R-245fa, R-290, R-500, R-502, R-600a, R-717, and R-744. It summarizes additional data for R-14, R-115, R-170 (ethane), R-C318, R-600 (n-butane), and R-1270 (propylene) to enable calculation of limits for blends incorporating them. The report summarizes the data a nd related safety information, including classifications and flammability data. It also presents a series of tables with proposed ATEL and RCL concentrations-in dimensionless form and the latter also in both metric (SI) and inch-pound (IP) units of measure-for both the cited refrigerants and 66 zerotropic and azeotropic blends. They include common refrigerants, such as R-404A, R-407C, R-410A, and R-507A, as well as others in commercial or developmental status. Appendices provide profiles for the cited single-compound refrigerants and for R-500 and R-502 as well as narrative toxicity summaries for common refrigerants. The report includes an extensive set of references.

  12. A Developmental Approach to Woodworking for Young Children.

    Science.gov (United States)

    Adams, Polly; Taylor, Michaell K.

    1990-01-01

    Presents a developmental approach to young children's woodworking. Discusses seven developmental stages of children's woodworking and woodworking activities appropriate to each developmental stage. (BB)

  13. Acute Toxicity of Vildagliptin.

    Science.gov (United States)

    Hoffmann, Peter; Martin, Lori; Keselica, Michael; Gunson, Diane; Skuba, Elizabeth; Lapadula, Dan; Hayes, Michael; Bentley, Phil; Busch, Steve

    2017-01-01

    This article describes acute toxicity data in cynomolgus monkeys following oral treatment with vildagliptin, a dipeptidyl peptidase-4 inhibitor. Acute toxicity symptoms in cynomolgus monkeys include edema formation of the extremities, tails, and face associated with skeletal muscle necrosis, and elevations of lactate dehydrogenase, creatine kinase, alanine transaminase, and aspartate aminotransferase activities in the serum; hypothermia; hypotension; tachycardia; moribundity; and death in a few isolated instances. In surviving animals, symptoms were reversible even if treatment was continued. Cynomolgus monkeys from Mauritius appear more sensitive than monkeys of Asian origin. The underlying mechanism(s) of these symptoms in cynomolgus monkeys is currently not well understood, although a vascular mechanism including initial vasoconstriction and subsequent vascular leakage in distal extremities may play a role. The monkey data are reviewed and discussed in the context of other preclinical and clinical data, and it is concluded that acute toxicity following vildagliptin treatment is a monkey-specific phenomenon without relevance for humans.

  14. Argumentative Text Writing: Developmental Trends.

    Science.gov (United States)

    Golder, Caroline; Coirier, Pierre

    1994-01-01

    Describes the essential factors of developmental changes in argumentative writing behavior of children between the ages of 10 and 16, in particular on 4 tasks: an argumentative writing task, a textuality task, an argumentative script inference task, and an argumentativity judgment task. (SR)

  15. Developmental transitions: So what's new?

    NARCIS (Netherlands)

    van der Maas, H.L.J.; Hopkins, B.

    1998-01-01

    Structural approaches to development, such as Piaget's stage theory, have proved to be problematic in dealing with developmental transitions. More promising in this respect are models of qualitative change that address macroscopical phase shifts in non-linear dynamicalsystems that arise from

  16. Dissociation: a developmental psychoneurobiological perspective

    African Journals Online (AJOL)

    Adele

    stress disorders of adults.2 A central tenet of a developmental psychoneurobiological ... pathologies, from reactive attachment disorder of infants to dissociative identity disorders, psychotic experiences, borderline personality disorders and .... ambiguus that is necessary for social communication.2 The vagal brake must be ...

  17. The diversification of developmental biology.

    Science.gov (United States)

    Crowe, Nathan; Dietrich, Michael R; Alomepe, Beverly S; Antrim, Amelia F; ByrneSim, Bay Lauris; He, Yi

    2015-10-01

    In the 1960s, "developmental biology" became the dominant term to describe some of the research that had previously been included under the rubrics of embryology, growth, morphology, and physiology. As scientific societies formed under this new label, a new discipline took shape. Historians, however, have a number of different perspectives on what changes led to this new field of developmental biology and how the field itself was constituted during this period. Using the General Embryological Information Service, a global index of post-World War II development-related research, we have documented and visualized significant changes in the kinds of research that occurred as this new field formed. In particular, our analysis supports the claim that the transition toward developmental biology was marked by a growth in new topics and forms of research. Although many historians privilege the role of molecular biology and/or the molecularization of biology in general during this formative period, we have found that the influence of molecular biology is not sufficient to account for the wide range of new research that constituted developmental biology at the time. Overall, our work creates a robust characterization of the changes that occurred with regard to research on growth and development in the decades following World War II and provides a context for future work on the specific drivers of those changes. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Program for Developmentally Disabled Children

    Science.gov (United States)

    Panzer, Barry M.; And Others

    1978-01-01

    Children who are developmentally disabled are more often handicapped by a lack of social skills than by intellectual limitations. The pilot program described here improved the psychosocial functioning of such children by involving them in one-to-one relationships with caring adults. (Author)

  19. Ecdysone Control of Developmental Transitions

    DEFF Research Database (Denmark)

    Rewitz, Kim; Yamanaka, Naoki; O'Connor, Michael B.

    2013-01-01

    The steroid hormone ecdysone is the central regulator of insect developmental transitions. Recent new advances in our understanding of ecdysone action have relied heavily on the application of Drosophila melanogaster molecular genetic tools to study insect metamorphosis. In this review, we focus...

  20. Developmental Principles: Fact or Fiction

    Directory of Open Access Journals (Sweden)

    A. J. Durston

    2012-01-01

    Full Text Available While still at school, most of us are deeply impressed by the underlying principles that so beautifully explain why the chemical elements are ordered as they are in the periodic table, and may wonder, with the theoretician Brian Goodwin, “whether there might be equally powerful principles that account for the awe-inspiring diversity of body forms in the living realm”. We have considered the arguments for developmental principles, conclude that they do exist and have specifically identified features that may generate principles associated with Hox patterning of the main body axis in bilaterian metazoa in general and in the vertebrates in particular. We wonder whether this exercise serves any purpose. The features we discuss were already known to us as parts of developmental mechanisms and defining developmental principles (how, and at which level? adds no insight. We also see little profit in the proposal by Goodwin that there are principles outside the emerging genetic mechanisms that need to be taken into account. The emerging developmental genetic hierarchies already reveal a wealth of interesting phenomena, whatever we choose to call them.

  1. Successful Aging: A Developmental Approach.

    Science.gov (United States)

    Ryff, Carol D.

    1982-01-01

    Examines earlier conceptualizations of successful aging and calls for a reformulation that is more responsive to developmental processes and theoretical guidance. Discusses issues of operational definitions, selective sampling, and stage theory. The perspective is illustrated with empirical research in the personality realm. (Author)

  2. Remarriage: A Family Developmental Process.

    Science.gov (United States)

    Whiteside, Mary F.

    1982-01-01

    Outlines a developmental perspective for understanding the dynamics of remarried families. Uses case examples to illustrate the importance of adding to the current family situation both a view of critical points in a family's history, and expectation for its future paths. (RC)

  3. Transforming Developmental Education in Texas

    Science.gov (United States)

    Journal of Developmental Education, 2014

    2014-01-01

    In recent years, with support from the Texas Legislature, the Texas Higher Education Coordinating Board has funded various developmental education initiatives, including research and evaluation efforts, to help Texas public institutions of higher education provide more effective programs and services to underprepared students. Based on evaluation…

  4. Developmental Entrepreneurship Program : Massachusetts Institute ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    The Developmental Entrepreneurship Program at the Massachusetts Institute of Technology (MIT) helps researchers, students and practitioner from developing countries to investigate private-sector-driven solutions to health, energy and environmental problems. As a premier institution for technological innovation with an ...

  5. Measuring Developmental Students' Mathematics Anxiety

    Science.gov (United States)

    Ding, Yanqing

    2016-01-01

    This study conducted an item-level analysis of mathematics anxiety and examined the dimensionality of mathematics anxiety in a sample of developmental mathematics students (N = 162) by Multi-dimensional Random Coefficients Multinominal Logit Model (MRCMLM). The results indicate a moderately correlated factor structure of mathematics anxiety (r =…

  6. Causal Inference and Developmental Psychology

    Science.gov (United States)

    Foster, E. Michael

    2010-01-01

    Causal inference is of central importance to developmental psychology. Many key questions in the field revolve around improving the lives of children and their families. These include identifying risk factors that if manipulated in some way would foster child development. Such a task inherently involves causal inference: One wants to know whether…

  7. Vygotsky's Developmental and Educational Psychology

    Science.gov (United States)

    Langford, Peter E.

    2005-01-01

    Vygotsky is widely considered one of the most significant and influential psychologists of the twentieth century. Nevertheless, true appreciation of his theories has been hindered by a lack of understanding of the background to his thought. "Vygotsky's Developmental and Educational Psychology" aims to demonstrate how we can come to a new and…

  8. Developmental trends in adaptive memory.

    Science.gov (United States)

    Otgaar, Henry; Howe, Mark L; Smeets, Tom; Garner, Sarah R

    2014-01-01

    Recent studies have revealed that memory is enhanced when information is processed for fitness-related purposes. The main objective of the current experiments was to test developmental trends in the evolutionary foundation of memory using different types of stimuli and paradigms. In Experiment 1, 11-year-olds and adults were presented with neutral, negative, and survival-related DRM word lists. We found a memory benefit for the survival-related words and showed that false memories were more likely to be elicited for the survival-related word lists than for the other lists. Experiment 2 examined developmental trends in the survival processing paradigm using neutral, negative, and survival-related pictures. A survival processing advantage was found for survival-related pictures in adults, for negative pictures in 11/12-year-olds, and for neutral pictures in 7/8-year-olds. In Experiment 3, 11/12-year-olds and adults had to imagine the standard survival scenario or an adapted survival condition (or pleasantness condition) that was designed to reduce the possibilities for elaborative processing. We found superior memory retention for both survival scenarios in children and adults. Collectively, our results evidently show that the survival processing advantage is developmentally invariant and that certain proximate mechanisms (elaboration and distinctiveness) underlie these developmental trends.

  9. Developmental dyscalculia: a dysconnection syndrome?

    Science.gov (United States)

    Kucian, Karin; Ashkenazi, Simone Schwizer; Hänggi, Jürgen; Rotzer, Stephanie; Jäncke, Lutz; Martin, Ernst; von Aster, Michael

    2014-09-01

    Numerical understanding is important for everyday life. For children with developmental dyscalculia (DD), numbers and magnitudes present profound problems which are thought to be based upon neuronal impairments of key regions for numerical understanding. The aim of the present study was to investigate possible differences in white matter fibre integrity between children with DD and controls using diffusion tensor imaging. White matter integrity and behavioural measures were evaluated in 15 children with developmental dyscalculia aged around 10 years and 15 matched controls. The main finding, obtained by a whole brain group comparison, revealed reduced fractional anisotropy in the superior longitudinal fasciculus in children with developmental dyscalculia. In addition, a region of interest analysis exhibited prominent deficits in fibres of the superior longitudinal fasciculus adjacent to the intraparietal sulcus, which is thought to be the core region for number processing. To conclude, our results outline deficient fibre projection between parietal, temporal and frontal regions in children with developmental dyscalculia, and therefore raise the question of whether dyscalculia can be seen as a dysconnection syndrome. Since the superior longitudinal fasciculus is involved in the integration and control of distributed brain processes, the present results highlight the importance of considering broader domain-general mechanisms in the diagnosis and therapy of dyscalculia.

  10. Developmental Dyscalculia and Medical Assessment.

    Science.gov (United States)

    Shalev, Ruth S.; Gross-Tsur, Varda

    1993-01-01

    Medical evaluation of seven third-grade children with developmental dyscalculia in a mainstream setting identified neurological conditions (including petit mal seizures, Gerstmann syndrome, and attention deficit disorder without hyperactivity) in all the children. Findings suggest that children who are not improving academically should undergo…

  11. Neuropsychological Aspects of Developmental Dyscalculia.

    Science.gov (United States)

    Shalev, R. S.; Manor, O.; Gross-Tsur, V.

    1997-01-01

    Classification of arithmetic disorders is predicated on neuropsychological features and associated learning disabilities. Assesses the compatibility of these classifications on a nonreferred, population-based cohort of children (N=139) with developmental dyscalculia. Concludes that children with dyscalculia and disabilities in reading and/or…

  12. Inhalation developmental toxicology studies: Teratology study of n-hexane in mice: Final report

    Energy Technology Data Exchange (ETDEWEB)

    Mast, T.J.; Decker, J.R.; Stoney, K.H.; Westerberg, R.B.; Evanoff, J.J.; Rommereim, R.L.; Weigel, R.J.

    1988-05-01

    Gestational exposure to n-hexane resulted in an increase in the number of resorbed fetuses for exposure groups relative to the control group; however, the increases were not directly correlated to exposure concentration. The differences were statistically significant for the 200-ppM with respect to total intrauterine death (early plus late resorptions), and with respect to late resorptions for the 5000-ppM group. A small, but statistically significant, reduction in female (but not male) fetal body weight relative to the control group was observed at the 5000-ppM exposure level. There were no exposure-related increases in any individual fetal malformation or variation, nor was there any increase in the incidence of combined malformations or variations. Gestational exposure of CD-1 mice to n-hexane vapors appeared to cause a degree of concentration-related developmental toxicity in the absence of overt maternal toxicity, but the test material was not found to be teratogenic. This developmental toxicity was manifested as an increase in the number of resorptions per litter for all exposure levels, and as a decrease in the uterine: extra-gestational weight gain ratio at the 5000-ppM exposure level. Because of the significant increase in the number of resorptions at the 200-ppM exposure level, a no observable effect level (NOEL) for developmental toxicity was not established for exposure of mice to 200, 1000 or 5000-ppM n-hexane vapors. 21 refs., 3 figs., 9 tabs.

  13. The toxicity of refrigerants

    Energy Technology Data Exchange (ETDEWEB)

    Calm, J.M.

    1996-07-01

    This paper presents toxicity data and exposure limits for refrigerants. The data address both acute (short-term, single exposure) and chronic (long-term, repeated exposure) effects, with emphasis on the former. The refrigerants covered include those in common use for the last decade, those used as components in alternatives, and selected candidates for future replacements. The paper also reviews the toxicity indicators used in both safety standards and building, mechanical, and fire codes. It then outlines current classification methods for refrigerant safety and relates them to standard and code usage.

  14. Ecophysiological perspectives on engineered nanomaterial toxicity in fish and crustaceans.

    Science.gov (United States)

    Callaghan, Neal Ingraham; MacCormack, Tyson James

    2017-03-01

    Engineered nanomaterials (ENMs) are incorporated into numerous industrial, clinical, food, and consumer products and a significant body of evidence is now available on their toxicity to aquatic organisms. Environmental ENM concentrations are difficult to quantify, but production and release estimates suggest wastewater treatment plant effluent levels ranging from 10 -4 to >10 1 μgL -1 for the most common formulations by production volume. Bioavailability and ENM toxicity are heavily influenced by water quality parameters and the physicochemical properties and resulting colloidal behaviour of the particular ENM formulation. ENMs generally induce only mild acute toxicity to most adult fish and crustaceans under environmentally relevant exposure scenarios; however, sensitivity may be considerably higher for certain species and life stages. In adult animals, aquatic ENM exposure often irritates respiratory and digestive epithelia and causes oxidative stress, which can be associated with cardiovascular dysfunction and the activation of immune responses. Direct interactions between ENMs (or their dissolution products) and proteins can also lead to ionoregulatory stress and/or developmental toxicity. Chronic and developmental toxicity have been noted for several common ENMs (e.g. TiO 2 , Ag), however more data is necessary to accurately characterize long term ecological risks. The bioavailability of ENMs should be limited in saline waters but toxicity has been observed in marine animals, highlighting a need for more study on possible impacts in estuarine and coastal systems. Nano-enabled advancements in industrial processes like water treatment and remediation could provide significant net benefits to the environment and will likely temper the relatively modest impacts of incidental ENM release and exposure. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. A Review of Recent Developmental THeories

    OpenAIRE

    OMORI, Mika

    2001-01-01

    Theorists of developmental psychology have been long caught in the traditional nativist-empiricist controversy. With the aim of exploring new directions in theory construction in the field of developmental psychology, ...

  16. Development of a new integrative toxicity index based on an improvement of the sea urchin embryo toxicity test.

    Science.gov (United States)

    Morroni, L; Pinsino, A; Pellegrini, D; Regoli, F; Matranga, V

    2016-01-01

    The sea urchin embryo toxicity test is classically used to assess the noxious effects of contaminated marine waters and sediments. In Italian guidelines on quality of dredged sediments, the standard toxicity criteria used for this assay are based on a single endpoint at 48 hours of development, corresponding to the pluteus stage. Different typologies of abnormalities, including those which occur at earlier stages, are not categorized, thus preventing the evaluation of the actual teratogenic hazards. A new integrative toxicity index has been developed in this study based on the analysis of two developmental stages, at 24 and 48h post-fertilization, and the differentiation between development delays and germ layers impairments: the new toxicity index is calculated by integrating the frequency of abnormal embryos with the severity of such abnormalities. When tested on dredged sediments, the evaluation of increasing levels of toxicity affecting embryonic outcomes enhanced the capability to discriminate different samples, appearing particularly relevant to validate the sea urchin embryo toxicity assay, and supporting its utility in practical applications such as the sediments classification in harbor areas. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Developmental and reproductive toxicological evaluation of arachidonic acid (ARA)-Rich oil and docosahexaenoic acid (DHA)-Rich oil.

    Science.gov (United States)

    Falk, Michael C; Zheng, Xiaohui; Chen, Dieling; Jiang, Yue; Liu, Zeshen; Lewis, Kara D

    2017-05-01

    The purpose of this study was to investigate the reproductive and developmental toxicity of dietary exposure to DHA-rich oil from Schizochytrium sp. and ARA-rich oil from Mortierella alpina. In a developmental toxicity study, pregnant Wistar rats were untreated (control) or administered corn oil (vehicle control), 1000, 2500, or 5000 mg/kg bw/day of DHA-rich oil or ARA-rich oil via gavage from gestation days 6 through 20. In the reproductive toxicity study, male and female Wistar rats were administered vehicle control (corn oil), or 1000, 2500, or 5000 mg/kg bw/day of DHA- or ARA-rich oil via gavage throughout the mating period, pregnancy, and the nursing and lactation period. Differences in the number of fetuses, fetal skeletal malformations, and external and visceral anomalies in the developmental study and mortality, clinical signs, fertility indices, physical observations, gross necropsy findings, and gestation period length in the reproductive toxicity study were not dose-related or significantly different from control groups, and were not considered to be treatment related. The no observed adverse effect level (NOAEL) for maternal toxicity and embryo/fetal development and for paternal or maternal treatment-related reproductive toxicity for the DHA-rich oil and ARA-rich oil administered by gavage, was 5000 mg/kg bw/day. Copyright © 2017. Published by Elsevier Ltd.

  18. Nanomaterials and Retinal Toxicity

    Science.gov (United States)

    The neuroretina should be considered as a potential site of nanomaterial toxicity. Engineered nanomaterials may reach the retina through three potential routes of exposure including; intra­ vitreal injection of therapeutics; blood-borne delivery in the retinal vasculature an...

  19. Respiratory Toxicity Biomarkers

    Science.gov (United States)

    The advancement in high throughput genomic, proteomic and metabolomic techniques have accelerated pace of lung biomarker discovery. A recent growth in the discovery of new lung toxicity/disease biomarkers have led to significant advances in our understanding of pathological proce...

  20. ANTIRETROVIRAl TOXICITY IN CHILDREN

    African Journals Online (AJOL)

    vertical transmission prophylaxis (VrP), and the other is treatment for symptomatic HIV infection. Fig. 7. Disease profile ofHN-positivechildren in the Italian. Collaborative Multicentric Study. Antiretroviral (ARV) toxicity is an important issue that must be fully appreciated by prescribing doctors. While the benefits of therapy are ...

  1. Monosodium Glutamate Toxicity

    African Journals Online (AJOL)

    Dr Olaleye

    on the brain, it is used as a major taste enhancer in most eateries and cafeteria in Nigeria. However, information is scanty on the potential of Sida acuta leaf ethanolic extract. (SALEE) to mitigate MSG-induced effect on the brain. This study aimed to investigate the possible toxic effect of MSG, a natural constituent of many ...

  2. Safety and side effects of ayahuasca in humans--an overview focusing on developmental toxicology.

    Science.gov (United States)

    dos Santos, Rafael Guimarães

    2013-01-01

    Despite being relatively well studied from a botanical, chemical, and (acute) pharmacological perspective, little is known about the possible toxic effects of ayahuasca (an hallucinogenic brew used for magico-ritual purposes) in pregnant women and in their children, and the potential toxicity of long-term ayahuasca consumption. It is the main objective of the present text to do an overview of the risks and possible toxic effects of ayahuasca in humans, reviewing studies on the acute ayahuasca administration to humans, on the possible risks associated with long-term consumption by adults and adolescents, and on the possible toxic effects on pregnant animals and in their offspring. Acute ayahuasca administration, as well as long-term consumption of this beverage, does not seem to be seriously toxic to humans. Although some nonhuman developmental studies suggested possible toxic effects of ayahuasca or of some of its alkaloids, the limited human literature on adolescents exposed to ayahuasca as early as in the uterus reports no serious toxic effects of the ritual consumption of the brew. Researchers must take caution when extrapolating nonhuman data to humans and more data are needed in basic and human research before a definite opinion can be made regarding the possible toxic effects of ayahuasca in pregnant women and in their children.

  3. Developmental Milestones in Toddlers with Atypical Development

    Science.gov (United States)

    Horovitz, Max; Matson, Johnny L.

    2011-01-01

    The attainment of developmental milestones was examined and compared in 162 infants and toddlers with developmental disabilities, including Down Syndrome (n = 26), Cerebral Palsy (n = 19), Global Developmental Delay (n = 22), Premature birth (n = 66), and Seizure Disorder (n = 29). Toddlers in the Seizures Disorder group began crawling at a…

  4. Developmental Dyslexia: An Evaluation of a Theory.

    Science.gov (United States)

    Satz, Paul; Van Nostrand, Gary K.

    The paper reviews a theory advanced by Satz and Sparrow (1970) which purports to explain the nature and cause of specific developmental dyslexia, and evaluates several developmental hypotheses which are generated bythe theory. The theory postulates that developmental dyslexia is not a unitary syndrome but rather reflects a lag in the maturation of…

  5. β-Cyclodextrin Attenuates Perfluorooctanoic Acid Toxicity in the Zebrafish Embryo Model

    Directory of Open Access Journals (Sweden)

    Mary Jo Weiss-Errico

    2017-11-01

    Full Text Available Perfluorooctanoic acid (PFOA has been linked to negative health outcomes including cancer, thyroid disease, infertility, and developmental delays. β-Cyclodextrin (β-CD, a cyclic sugar, has been previously shown to form strong host–guest complexes with PFOA, and is proposed as a means of environmental remediation with respect to this widespread contaminant. In the present study, β-CD was directly examined with regards to possible attenuation of the toxicity of PFOA specifically employing the zebrafish (Danio rerio embryo model. Zebrafish embryos were exposed to various concentrations of PFOA without β-CD, and with equimolar (1:1 and excess (2:1 molar ratios of β-CD to PFOA, and assessed for lethality and developmental toxicity through seven days post-fertilization (dpf. Rapid onset of lethality with limited morphological abnormalities was observed at relatively low concentrations of PFOA (LC50 ≈ 50 ppm, along with effects on morphometric and neurobehavioral parameters in surviving embryos. A highly significant difference (p < 0.0001 was observed between the 2:1 treatment, and both 1:1 and PFOA only treatments, with respect to lethal concentration and apparent neurobehavioral effects, suggesting an effectively reduced toxicity of the fully complexed PFOA. In contrast, however, neither β-CD treatment reduced developmental toxicity with respect to the morphometric endpoint (i.e., interocular distance. Whereas LC50 of PFOA alone did not change over 7 dpf, the 1:1 and 2:1 values decreased slightly over time, suggesting either delayed or alternative toxic effects on later developmental stages at presumptively lowered levels. This study, therefore, indicates β-CD may be an effective agent to reduce toxicity of and mitigate environmental health concerns associated with PFOA, but that further study is required to elucidate the mechanism of complexation as it relates to the attenuation of toxicity.

  6. [Toxicity study of realgar].

    Science.gov (United States)

    Liang, Aihua; Li, Chunying; Wang, Jinhua; Xue, Baoyun; Li, Hua; Yang, Bing; Wang, Jingyu; Xie, Qing; Nilsen, Odd Georg

    2011-07-01

    To investigate the toxicity of realgar and provide the scientific basis for safety use of realgar in clinic. Acute toxicity was tested by single oral administration. Chronic toxicity of realgar was tested at different dose levels (5, 10, 20, 80, 160 mg x kg(-1) x d(-1)) which correspond to 1/2, 1, 2, 8, 16 times of human dose levels. The rats were treated with the test substances through oral administration once daily for successively 90 days. Urinary qualitative test, blood routine examination, serum chemistry measurement, and histomorphologic observation were conducted at day 30, 60 and 90. Toxic changes related to the treatment of realgar and no-observed adverse effect level (NOAEL) was evaluated. With the content of 90% total arsenic and 1.696 mg x g(-1) soluble asenic, LD50 of Realgar with oral administration was 20.5 g x kg(-1) (corresponding to 34.8 mg x kg(-1) soluble arsenic), equivalent to 12 812 times of clinical daily dose for an adult. Realgar can cause kidney toxicity or/and liver toxicity after administration for over 30, 60 or 90 days respectively. The kidney was more sensitive to realgar than liver. Based on repeated dose toxicity study, NOAELs were 160 mg x kg(-1) x d(-1) for 30 day's administration, 20 mg x kg(-1) x d(-1) for 60 day's administration, 10 mg x kg(-1) x d(-1) mg x kg(-1) x d(-1) for 90 day's administration respectively. Thus, for safety use of realgar, it is recommended that the daily doses of realgar (with soluble arsenic realgar can cause kidney and liver pathological change, so the doses and administration duration should be limited. The suggestion is as follows: realgar which contains soluble arsenic < or = 1.7 mg x g(-1) should be used less than 2 weeks at daily dose 160 mg, less than 4 weeks at the dose of 20 mg and less than 6 weeks at the dose of 10 mg.

  7. 16 CFR 1500.135 - Summary of guidelines for determining chronic toxicity.

    Science.gov (United States)

    2010-01-01

    ... “sufficient evidence” criteria of developmental or reproductive toxicity in animals. The Food and Drug... exposure is above the “acceptable daily intake” (“ADI”). The ADI is based on the risks posed by the... risks and the ADI to children and adults, and assessment of risk. (1) Assessment of Exposure. An...

  8. Harmonization of description and classification of fetal observations: Achievements and problems still unresolved. Report of the 7th Workshop on the Terminology in Developmental Toxicology Berlin, 4-6 May 2011

    NARCIS (Netherlands)

    Solecki, R.; Barbellion, S.; Bergmann, B.; Bürgin, H.; Buschmann, J.; Clark, R.; Comotto, L.; Fuchs, A.; Faqi, A.S.; Gerspach, R.; Grote, K.; Hakansson, H.; Heinrich, V.; Heinrich-Hirsch, B.; Hofmann, T.; Hübel, U.; Inazaki, T.H.; Khalil, S.; Knudsen, T.B.; Kudicke, S.; Lingk, W.; Makris, S.; Müller, S.; Paumgartten, F.; Pfeil, R.; Rama, E.M.; Schneider, S.; Shiota, K.; Tamborini, E.; Tegelenbosch, M.; Ulbrich, B.; Duijnhoven, E.A.J. van; Wise, D.; Chahoud, I.

    2013-01-01

    This article summarizes the 7th Workshop on the Terminology in Developmental Toxicology held in Berlin, May 4-6, 2011. The series of Berlin Workshops has been mainly concerned with the harmonization of terminology and classification of fetal anomalies in developmental toxicity studies. The main

  9. Auditory learning: a developmental method.

    Science.gov (United States)

    Zhang, Yilu; Weng, Juyang; Hwang, Wey-Shiuan

    2005-05-01

    Motivated by the human autonomous development process from infancy to adulthood, we have built a robot that develops its cognitive and behavioral skills through real-time interactions with the environment. We call such a robot a developmental robot. In this paper, we present the theory and the architecture to implement a developmental robot and discuss the related techniques that address an array of challenging technical issues. As an application, experimental results on a real robot, self-organizing, autonomous, incremental learner (SAIL), are presented with emphasis on its audition perception and audition-related action generation. In particular, the SAIL robot conducts the auditory learning from unsegmented and unlabeled speech streams without any prior knowledge about the auditory signals, such as the designated language or the phoneme models. Neither available before learning starts are the actions that the robot is expected to perform. SAIL learns the auditory commands and the desired actions from physical contacts with the environment including the trainers.

  10. Multilocular developmental salivary gland defect

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jin Soo [Dept. of Oral and Maxillofacial Radiology and Oral Biology Research Institute, School of Dentistry, Chosun University, Gwangju (Korea, Republic of)

    2012-09-15

    Developmental salivary gland defect is a bone depression on the lingual surface of the mandible containing salivary gland or fatty soft tissue. The most common location is within the submandibular gland fossa and often close to the inferior border of the mandible. This defect is asymptomatic and generally discovered only incidentally during radiographic examination of the area. This defect also appears as a well-defined, corticated, unilocular radiolucency below the mandibular canal. Although it is not uncommon for this defect to appear as a round or ovoid radiolucency, multilocular radiolucency of these defects is relatively rare. This report presents a case of a developmental salivary gland defect with multilocular radiolucency in a male patient.

  11. Developmental Dynamics of Rett Syndrome.

    Science.gov (United States)

    Feldman, Danielle; Banerjee, Abhishek; Sur, Mriganka

    2016-01-01

    Rett Syndrome was long considered to be simply a disorder of postnatal development, with phenotypes that manifest only late in development and into adulthood. A variety of recent evidence demonstrates that the phenotypes of Rett Syndrome are present at the earliest stages of brain development, including developmental stages that define neurogenesis, migration, and patterning in addition to stages of synaptic and circuit development and plasticity. These phenotypes arise from the pleotropic effects of MeCP2, which is expressed very early in neuronal progenitors and continues to be expressed into adulthood. The effects of MeCP2 are mediated by diverse signaling, transcriptional, and epigenetic mechanisms. Attempts to reverse the effects of Rett Syndrome need to take into account the developmental dynamics and temporal impact of MeCP2 loss.

  12. Developmental insights into mature cognition.

    Science.gov (United States)

    Keil, Frank C

    2015-02-01

    Three cases are described that illustrate new ways in which developmental research is informing the study of cognition in adults: statistical learning, neural substrates of cognition, and extended concepts. Developmental research has made clear the ubiquity of statistical learning while also revealing is limitations as a stand-alone way to acquire knowledge. With respect to neural substrates, development has uncovered links between executive processing and fronto-striatal circuits while also pointing to many aspects of high-level cognition that may not be neatly reducible to coherent neural descriptions. For extended concepts, children have made especially clear the weaknesses of intuitive theories in both children and adults while also illustrating other cognitive capacities that are used at all ages to navigate the socially distributed aspects of knowledge. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Advances in developmental prosopagnosia research.

    Science.gov (United States)

    Susilo, Tirta; Duchaine, Bradley

    2013-06-01

    Developmental prosopagnosia (DP) refers to face recognition deficits in the absence of brain damage. DP affects ∼2% of the population, and it often runs in families. DP studies have made considerable progress in identifying the cognitive and neural characteristics of the disorder. A key challenge is to develop a valid taxonomy of DP that will facilitate many aspects of research. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Psychology is a Developmental Science

    OpenAIRE

    Greenberg, Gary; Partridge, Ty; Mosack, Victoria; Lambdin, Charles

    2006-01-01

    In this paper we argue that psychology should be understood as a developmental science, and we place the discipline squarely in the realm of the natural sciences. The case is made that scientific progress in psychology has been (and still is) impeded by prolonged misadventures down conceptual dead ends such as biological reductionism, the nature/nurture debate, evolutionary psychology, and the persistent insistence on emphasizing dependent variables that defy observation and measurement, such...

  15. Differences in cardiovascular toxicities associated with cigarette smoking and snuff use revealed using novel zebrafish models.

    Science.gov (United States)

    Folkesson, Maggie; Sadowska, Natalia; Vikingsson, Svante; Karlsson, Matts; Carlhäll, Carl-Johan; Länne, Toste; Wågsäter, Dick; Jensen, Lasse

    2016-07-15

    Tobacco use is strongly associated with cardiovascular disease and the only avoidable risk factor associated with development of aortic aneurysm. While smoking is the most common form of tobacco use, snuff and other oral tobacco products are gaining popularity, but research on potentially toxic effects of oral tobacco use has not kept pace with the increase in its use. Here, we demonstrate that cigarette smoke and snuff extracts are highly toxic to developing zebrafish embryos. Exposure to such extracts led to a palette of toxic effects including early embryonic mortality, developmental delay, cerebral hemorrhages, defects in lymphatics development and ventricular function, and aneurysm development. Both cigarette smoke and snuff were more toxic than pure nicotine, indicating that other compounds in these products are also associated with toxicity. While some toxicities were found following exposure to both types of tobacco product, other toxicities, including developmental delay and aneurysm development, were specifically observed in the snuff extract group, whereas cerebral hemorrhages were only found in the group exposed to cigarette smoke extract. These findings deepen our understanding of the pathogenic effects of cigarette smoking and snuff use on the cardiovascular system and illustrate the benefits of using zebrafish to study mechanisms involved in aneurysm development. © 2016. Published by The Company of Biologists Ltd.

  16. Developmental transcriptome of Aplysia californica'

    KAUST Repository

    Heyland, Andreas

    2010-12-06

    Genome-wide transcriptional changes in development provide important insight into mechanisms underlying growth, differentiation, and patterning. However, such large-scale developmental studies have been limited to a few representatives of Ecdysozoans and Chordates. Here, we characterize transcriptomes of embryonic, larval, and metamorphic development in the marine mollusc Aplysia californica and reveal novel molecular components associated with life history transitions. Specifically, we identify more than 20 signal peptides, putative hormones, and transcription factors in association with early development and metamorphic stages-many of which seem to be evolutionarily conserved elements of signal transduction pathways. We also characterize genes related to biomineralization-a critical process of molluscan development. In summary, our experiment provides the first large-scale survey of gene expression in mollusc development, and complements previous studies on the regulatory mechanisms underlying body plan patterning and the formation of larval and juvenile structures. This study serves as a resource for further functional annotation of transcripts and genes in Aplysia, specifically and molluscs in general. A comparison of the Aplysia developmental transcriptome with similar studies in the zebra fish Danio rerio, the fruit fly Drosophila melanogaster, the nematode Caenorhabditis elegans, and other studies on molluscs suggests an overall highly divergent pattern of gene regulatory mechanisms that are likely a consequence of the different developmental modes of these organisms. © 2010 Wiley-Liss, Inc., A Wiley Company.

  17. Animal Toxicity of Phytopathogenic Fungi

    Science.gov (United States)

    Main, C. E.; Hamilton, P. B.

    1972-01-01

    Twelve genera of phytopathogenic fungi comprising 27 species previously reported to produce phytotoxins were tested concurrently for animal and plant toxicity. There appeared to be no direct relationship between plant and animal toxicity. PMID:5059620

  18. Allegheny County Toxics Release Inventory

    Data.gov (United States)

    Allegheny County / City of Pittsburgh / Western PA Regional Data Center — The Toxics Release Inventory (TRI) data provides information about toxic substances released into the environment or managed through recycling, energy recovery, and...

  19. The memory of hunger: developmental plasticity of dietary selectivity in the European starling, Sturnus vulgaris

    OpenAIRE

    Bloxham, Louise; Bateson, Melissa; Bedford, Thomas; Brilot, Ben; Nettle, Daniel

    2014-01-01

    The decision to consume toxic prey is a trade-off between the benefits of obtaining nutrients and the costs of ingesting toxins. This trade-off is affected by current state: animals will consume more toxic prey if they are food deprived. However, whether the trade-off is affected by developmental history is currently unknown. We studied the decision to eat quinine-injected mealworms in adult starling siblings that had been exposed to either high or low levels of food competition as chicks, vi...

  20. Developmental Biology: We Are All Walking Mutants.

    Science.gov (United States)

    Trainor, Paul A

    2016-01-01

    What is Developmental Biology? Developmental Biology is a discipline that evolved from the collective fields of embryology, morphology, and anatomy, which firmly established that structure underpins function. In its simplest terms, Developmental Biology has come to describe how a single cell becomes a completely formed organism. However, this definition of Developmental Biology is too narrow. Developmental Biology describes the properties of individual cells; their organization into tissues, organs, and organisms; their homeostasis, regeneration, aging, and ultimately death. Developmental Biology provides a context for cellular reprogramming, stem cell biology, regeneration, tissue engineering, evolutionary development and ecology, and involves the reiterated use of the same cellular mechanisms and signaling pathways throughout the lifespan of an organism. Using neural crest cells as an example, this review explores the contribution of Developmental Biology to our understanding of development, evolution, and disease. © 2016 Elsevier Inc. All rights reserved.

  1. Psychotherapy with people with developmental disabilities

    Directory of Open Access Journals (Sweden)

    Barbara Zafošnik

    2011-08-01

    Full Text Available People with developmental disabilities can experience any psychological abnormalitiy and psychiatric illness as do people without developmental disabilities. Due to different diagnostic criteria, assessment procedures and instruments, we lack definite prevalence rates for people with developmental disabilities, also suffering from mental health problems, eventhough most studies place the rate at 20 to 40%. One of the possible treatment alternatives for augmenting psychological well-being is psychotherapy, but is extremely rarely used for people with severe and profound disabilities, where speech cannot be the main therapeutic medium. So, those that are included in the psychotherapuetic process are predominantly clients with mild developmental disabilities, and they are mostly in cognitive-behavioral therapy. Recently, two models of (psychotherapy for persons with severe and profound developmental disabilities were developed: developmental-dynamic relationship therapy and attachment-based behaviour therapy for children. Conceptually, they both originate form developmental psychoanalytic theories.

  2. Toxicological assessment of heavy straight run naphtha in a repeated dose/reproductive toxicity screening test.

    Science.gov (United States)

    McKee, Richard H; Steup, David; Schreiner, Ceinwen; Podhasky, Paula; Malley, Linda A; Roberts, Linda

    2014-01-01

    Gasoline blending stocks (naphthas) are comprised of normal, iso- and cycloparaffins and aromatic hydrocarbons with carbon numbers ranging from C4 to C12. Heavy straight run naphtha (HSRN, CAS number 64741-41-9) was selected for toxicity screening because substances of this type contain relatively high levels (28%) of cycloparaffins by comparison to other naphtha streams and the data complement toxicity information on other gasoline blending streams. Rats were exposed by inhalation to wholly vaporized material at levels of approximately 100, 500, or 3000 parts per million (ppm) daily to screen the potential for systemic toxicity, neurotoxicity, reproductive toxicity, and developmental effects to postnatal day 4. All animals survived the treatment period. Principal effects of repeated exposure included increased liver weights in males and females, increased kidney weights in males, and histological changes in the thyroid, secondary to liver enzyme induction. These changes were not considered to be toxicologically meaningful and are not relevant to humans. There were no treatment-related effects in functional observation tests or motor activity; no significant reductions in fertility or changes in other reproductive parameters; and no evidence of developmental toxicity in offspring. The overall no observed adverse effect concentration was 3000 ppm (approximately 13, 600 mg/m(3)). In conclusion the HSRN effects on liver and kidney are consistent with the results of other studies of volatile fractions or other naphthas or formulated gasoline, and there were no HSRN effects on neurological developmental or reproductive parameters.

  3. Embryo-fetal exposure and developmental outcome of thalidomide following oral and intravaginal administration to pregnant rabbits.

    Science.gov (United States)

    Hui, Julia Y; Hoffmann, Matthew; Kumar, Gondi

    2014-09-01

    Studies in pregnant rabbits were conducted to evaluate if there are any differences in the uptake of thalidomide into the intrauterine compartment and developmental toxicity risk following oral and intravaginal administration. Thalidomide concentrations in maternal plasma, yolk sac cavity (YSC) fluid and embryo following intravaginal administration were 2- to 7-fold lower than their respective levels after oral administration. Ratios of thalidomide concentration in YSC fluid to maternal plasma were similar between these two routes, indicating no difference in uptake into the intrauterine compartment. A rabbit embryo-fetal development study using oral and intravaginal thalidomide administration at 2mg/kg/day (a dose >10,000-fold higher than the expected amount of thalidomide in human semen) did not result in any developmental abnormalities. These data demonstrated no preferential transfer mechanism of thalidomide from vagina to conceptus, and no additional embryo-fetal developmental toxicity risks with thalidomide exposure via the vaginal route. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Mixtures of endocrine-disrupting contaminants induce adverse developmental effects in preweaning rats

    DEFF Research Database (Denmark)

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

    2014-01-01

    Reproductive toxicity was investigated in rats after developmental exposure to a mixture of 13 endocrine-disrupting contaminants, including pesticides, plastic and cosmetic ingredients, and paracetamol. The mixture was composed on the basis of information about high-end human exposures, and the d......Reproductive toxicity was investigated in rats after developmental exposure to a mixture of 13 endocrine-disrupting contaminants, including pesticides, plastic and cosmetic ingredients, and paracetamol. The mixture was composed on the basis of information about high-end human exposures...... to the safety margin covered by the regulatory uncertainty factor of 100. This suggests that highly exposed human population groups may not be sufficiently protected against mixtures of endocrine-disrupting chemicals....

  5. Kombucha--toxicity alert.

    Science.gov (United States)

    The Kombucha mushroom, also known as Manchurian mushroom, is a mail-order product touted to lower blood pressure and raise T-cell counts. No controlled trials have been conducted to test these claims. Aspergillus, a mold that may grow on the Kombucha mushroom, attacks the brain and may be fatal to persons with weakened immune systems. Reported toxicity reactions have included stomach problems and yeast infections. Taking Kombucha in combination with other drugs may affect the drugs potency.

  6. Toxicity of Depleted Uranium

    Science.gov (United States)

    1997-02-01

    cancer in dogs and humans1 and mice and humans.2 The information for inert metal toxicity in humans is foreign-body carcinogenesis data related to...high dose of Thorotrast® (> 0.4 Bq/g) developed fibrosarcomas from perivascular leakage of some injections.19 Plutonium fragments have been injected...into the footpads of dogs to simulate the plutonium-contaminated wounds of plutonium machinists.2" The plutonium was translocated to the local lymph

  7. Toxic Substances Control Act

    Energy Technology Data Exchange (ETDEWEB)

    1992-05-15

    This Reference Book contains a current copy of the Toxic Substances Control Act and those regulations that implement the statute and appear to be most relevant to DOE activities. The document is provided to DOE and contractor staff for informational purposes only and should not be interpreted as legal guidance. Questions concerning this Reference Book may be directed to Mark Petts, EH-231 (202/586-2609).

  8. Toxicity of nanomaterials.

    Science.gov (United States)

    Sharifi, Shahriar; Behzadi, Shahed; Laurent, Sophie; Forrest, M Laird; Stroeve, Pieter; Mahmoudi, Morteza

    2012-03-21

    Nanoscience has matured significantly during the last decade as it has transitioned from bench top science to applied technology. Presently, nanomaterials are used in a wide variety of commercial products such as electronic components, sports equipment, sun creams and biomedical applications. There are few studies of the long-term consequences of nanoparticles on human health, but governmental agencies, including the United States National Institute for Occupational Safety and Health and Japan's Ministry of Health, have recently raised the question of whether seemingly innocuous materials such as carbon-based nanotubes should be treated with the same caution afforded known carcinogens such as asbestos. Since nanomaterials are increasing a part of everyday consumer products, manufacturing processes, and medical products, it is imperative that both workers and end-users be protected from inhalation of potentially toxic NPs. It also suggests that NPs may need to be sequestered into products so that the NPs are not released into the atmosphere during the product's life or during recycling. Further, non-inhalation routes of NP absorption, including dermal and medical injectables, must be studied in order to understand possible toxic effects. Fewer studies to date have addressed whether the body can eventually eliminate nanomaterials to prevent particle build-up in tissues or organs. This critical review discusses the biophysicochemical properties of various nanomaterials with emphasis on currently available toxicology data and methodologies for evaluating nanoparticle toxicity (286 references).

  9. Amiodarone Pulmonary Toxicity

    Directory of Open Access Journals (Sweden)

    Norman Wolkove

    2009-01-01

    Full Text Available Amiodarone is an antiarrhythmic agent commonly used to treat supraventricular and ventricular arrhythmias. This drug is an iodine-containing compound that tends to accumulate in several organs, including the lungs. It has been associated with a variety of adverse events. Of these events, the most serious is amiodarone pulmonary toxicity. Although the incidence of this complication has decreased with the use of lower doses of amiodarone, it can occur with any dose. Because amiodarone is widely used, all clinicians should be vigilant of this possibility. Pulmonary toxicity usually manifests as an acute or subacute pneumonitis, typically with diffuse infiltrates on chest x-ray and high-resolution computed tomography. Other, more localized, forms of pulmonary toxicity may occur, including pleural disease, migratory infiltrates, and single or multiple nodules. With early detection, the prognosis is good. Most patients diagnosed promptly respond well to the withdrawal of amiodarone and the administration of corticosteroids, which are usually given for four to 12 months. It is important that physicians be familiar with amiodarone treatment guidelines and follow published recommendations for the monitoring of pulmonary as well as extrapulmonary adverse effects.

  10. Amiodarone pulmonary toxicity

    Science.gov (United States)

    Wolkove, Norman; Baltzan, Marc

    2009-01-01

    Amiodarone is an antiarrhythmic agent commonly used to treat supraventricular and ventricular arrhythmias. This drug is an iodine-containing compound that tends to accumulate in several organs, including the lungs. It has been associated with a variety of adverse events. Of these events, the most serious is amiodarone pulmonary toxicity. Although the incidence of this complication has decreased with the use of lower doses of amiodarone, it can occur with any dose. Because amiodarone is widely used, all clinicians should be vigilant of this possibility. Pulmonary toxicity usually manifests as an acute or subacute pneumonitis, typically with diffuse infiltrates on chest x-ray and high-resolution computed tomography. Other, more localized, forms of pulmonary toxicity may occur, including pleural disease, migratory infiltrates, and single or multiple nodules. With early detection, the prognosis is good. Most patients diagnosed promptly respond well to the withdrawal of amiodarone and the administration of corticosteroids, which are usually given for four to 12 months. It is important that physicians be familiar with amiodarone treatment guidelines and follow published recommendations for the monitoring of pulmonary as well as extrapulmonary adverse effects. PMID:19399307

  11. Modern toxic antipersonnel projectiles.

    Science.gov (United States)

    Gaillard, Yvan; Regenstreif, Philippe; Fanton, Laurent

    2014-12-01

    In the spring of 1944, Kurt von Gottberg, the SS police chief in Minsk, was shot and injured by 2 Soviet agents. Although he was only slightly injured, he died 6 hours later. The bullets were hollow and contained a crystalline white powder. They were 4-g bullets, semi-jacketed in cupronickel, containing 28 mg of aconitine. They were later known as akonitinnitratgeschosse. The Sipo (the Nazi security police) then ordered a trial with a 9-mm Parabellum cartridge containing Ditran, an anticholinergic drug with hallucinogenic properties causing intense mental confusion. In later years, QNB was used and given the NATO code BZ (3-quinuclidinyl-benzylate). It was proven that Saddam Hussein had this weapon (agent 15) manufactured and used it against the Kurds. Serbian forces used the same type of weapon in the Bosnian conflict, particularly in Srebrenica.The authors go on to list the Cold War toxic weapons developed by the KGB and the Warsaw pact countries for the discreet elimination of dissidents and proindependence leaders who had taken refuge in the West. These weapons include PSZh-13 launchers, the Troika electronic sequential pistol, and the ingenious 4-S110T captive piston system designed by the engineer Stechkin. Disguised as a cigarette case, it could fire a silent charge of potassium cyanide. This rogues gallery also includes the umbrella rigged to inject a pellet of ricin (or another phytalbumin of similar toxicity, such as abrin or crotin) that was used to assassinate the Bulgarian writer and journalist Georgi Markov on September 7, 1978, in London.During the autopsy, the discovery of a bullet burst into 4 or 5 parts has to make at once suspecting the use of a toxic substance. Toxicological analysis has to look for first and foremost aconitine, cyanide, suxamethonium, Ditran, BZ, or one of the toxic phytalbumins. The use of such complex weapons has to make suspect a powerful organization: army, secret service, terrorism. The existence of the Russian UDAR spray

  12. Developmentalism

    African Journals Online (AJOL)

    Student Non-violent Coordinating Committee, and Vietnam War resisters. The. University of Dar es Salaam during the same period had become the centre for the guerrilla-intellectuals and activists of African liberation movements. As a champion of Academic Freedom, Nyerere was cautious enough not to impose.

  13. PM2.5-bound metal metabolic distribution and coupled lipid abnormality at different developmental windows.

    Science.gov (United States)

    Ku, Tingting; Zhang, Yingying; Ji, Xiaotong; Li, Guangke; Sang, Nan

    2017-09-01

    Atmospheric fine particulate matter (PM2.5) is a serious threat to human health. As a toxicant constituent, metal leads to significant health risks in a population, but exposure to PM2.5-bound metals and their biological impacts are not fully understood. In this study, we determined the metal contents of PM2.5 samples collected from a typical coal-burning city and then investigated the metabolic distributions of six metals (Zn, Pb, Mn, As, Cu, and Cd) following PM2.5 inhalation in mice in different developmental windows. The results indicate that fine particles were mainly deposited in the lung, but PM2.5-bound metals could reach and gather in secondary off-target tissues (the lung, liver, heart and brain) with a developmental window-dependent property. Furthermore, elevations in triglycerides and cholesterol levels in sensitive developmental windows (the young and elderly stages) occurred, and significant associations between metals (Pb, Mn, As and Cd) and cholesterol in the heart, brain, liver and lung were observed. These findings suggest that PM2.5 inhalation caused selective metal metabolic distribution in tissues with a developmental window-dependent property and that the effects were associated with lipid alterations. This provides a foundation for the underlying systemic toxicity following PM2.5 exposure based on metal components. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Toxicity profiles and solvent-toxicant interference in the planarian Schmidtea mediterranea after dimethylsulfoxide (DMSO) exposure.

    Science.gov (United States)

    Stevens, An-Sofie; Pirotte, Nicky; Plusquin, Michelle; Willems, Maxime; Neyens, Thomas; Artois, Tom; Smeets, Karen

    2015-03-01

    To investigate hydrophobic test compounds in toxicological studies, solvents like dimethylsulfoxide (DMSO) are inevitable. However, using these solvents, the interpretation of test compound-induced responses can be biased. DMSO concentration guidelines are available, but are mostly based on acute exposures involving one specific toxicity endpoint. Hence, to avoid solvent-toxicant interference, we use multiple chronic test endpoints for additional interpretation of DMSO concentrations and propose a statistical model to assess possible synergistic, antagonistic or additive effects of test compounds and their solvents. In this study, the effects of both short- (1 day) and long-term (2 weeks) exposures to low DMSO concentrations (up to 1000 µl l(-1) ) were studied in the planarian Schmidtea mediterranea. We measured different biological levels in both fully developed and developing animals. In a long-term exposure set-up, a concentration of 500 µl l(-1) DMSO interfered with processes on different biological levels, e.g. behaviour, stem cell proliferation and gene expression profiles. After short exposure times, 500 µl l(-1) DMSO only affected motility, whereas the most significant changes on different parameters were observed at a concentration of 1000 µl l(-1) DMSO. As small sensitivity differences exist between biological levels and developmental stages, we advise the use of this solvent in concentrations below 500 µl l(-1) in this organism. In the second part of our study, we propose a statistical approach to account for solvent-toxicant interactions and discuss full-scale solvent toxicity studies. In conclusion, we reassessed DMSO concentration limits for different experimental endpoints in the planarian S. mediterranea. Copyright © 2014 John Wiley & Sons, Ltd.

  15. Developmental modes and developmental mechanisms can channel brain evolution

    Directory of Open Access Journals (Sweden)

    Christine J Charvet

    2011-02-01

    Full Text Available Anseriform birds (ducks and geese as well as parrots and songbirds have evolved a disproportionately enlarged telencephalon compared with many other birds. However, parrots and songbirds differ from anseriform birds in their mode of development. Whereas ducks and geese are precocial (e.g., hatchlings feed on their own, parrots and songbirds are altricial (e.g., hatchlings are fed by their parents. We here consider how developmental modes may limit and facilitate specific changes in the mechanisms of brain development. We suggest that altriciality facilitates the evolution of telencephalic expansion by delaying telencephalic neurogenesis. We further hypothesize that delays in telencephalic neurogenesis generate delays in telencephalic maturation, which in turn foster neural adaptations that facilitate learning. Specifically, we propose that delaying telencephalic neurogenesis was a prerequisite for the evolution of neural circuits that allow parrots and songbirds to produce learned vocalizations. Overall, we argue that developmental modes have influenced how some lineages of birds increased the size of their telencephalon and that this, in turn, has influenced subsequent changes in brain circuits and behavior.

  16. Developmental venous anomaly (DVA); Developmental Venous Anomaly (DVA)

    Energy Technology Data Exchange (ETDEWEB)

    Zimmer, A.; Ahlhelm, F.; Viera, J.; Reith, W.; Schulte-Altedorneburg, G. [Universitaetsklinikum des Saarlandes, Klinik fuer Diagnostische und Interventionelle Neuroradiologie, Homburg/Saar (Germany); Hagen, T. [Radiologische Praxis, Augsburg (Germany)

    2007-10-15

    As congenital anatomic variants of venous drainage, developmental venous anomalies (DVA) represent up to 60% of all cerebral vascular malformations. The prior term ''venous angioma'' is a misnomer implicating an abnormal vascular structure with an increased bleeding risk. They are often found incidentally and are hardly ever symptomatic. Their morphologic characteristics are dilated vessels in the white matter, which converge on a greater collector vein, forming the typical caput medusae. They drain into the superficial or deep venous system. The frequent association with other, potentially bleeding-prone vascular malformations is clinically relevant, in particular cavernous angioma, which might require therapeutic action. Therefore, coincident vascular lesions need to be actively sought by appropriate additional imaging techniques. (orig.) [German] Als eine embryologische Variante der venoesen Drainage macht die so genannte ''developmental venous anomaly'' (DVA) etwa 60% aller zerebralen vaskulaeren Malformationen aus. Der vormalige Terminus ''venoeses Angiom'' sollte nicht mehr benutzt werden, da er abnormale Gefaessstrukturen mit einem erhoehten Blutungsrisiko impliziert. Die DVA werden oft inzidentell entdeckt und sind nur selten symptomatisch. Das typische Erscheinungsbild ist durch dilatierte, medusenhauptartig angeordnete venoese Marklagergefaesse gekennzeichnet, die in eine groessere Sammelvene drainieren. Der Abfluss erfolgt ueber das oberflaechliche oder tiefe Venensystem. Klinisch wichtig ist die haeufige Assoziation mit anderen zerebralen Gefaessmalformationen, insbesondere kavernoesen Angiomen, nach denen im Rahmen der Diagnostik explizit gesucht werden muss, da diese eine potenzielle Blutungsquelle darstellen und ein therapeutisches Vorgehen erfordern koennen. (orig.)

  17. Developmental origins of adult diseases

    Directory of Open Access Journals (Sweden)

    Vivek Mathew

    2012-01-01

    Full Text Available There is considerable evidence for the fact that early life environment in human beings are associated with future development of various metabolic diseases. Fetal programming and perinatal events appear to exert effects on later life that are independent of environmental risk factors in adults. Our understanding of the underlying mechanisms are limited and remains unclear. However several animal models and epidemiological studies have shown this association, and it is assumed secondary to the penalties of developmental plasticity. In this review, we amalgamate facts from several disciplines to support this hypothesis.

  18. Music cognition: a developmental perspective.

    Science.gov (United States)

    Stalinski, Stephanie M; Schellenberg, E Glenn

    2012-10-01

    Although music is universal, there is a great deal of cultural variability in music structures. Nevertheless, some aspects of music processing generalize across cultures, whereas others rely heavily on the listening environment. Here, we discuss the development of musical knowledge, focusing on four themes: (a) capabilities that are present early in development; (b) culture-general and culture-specific aspects of pitch and rhythm processing; (c) age-related changes in pitch perception; and (d) developmental changes in how listeners perceive emotion in music. Copyright © 2012 Cognitive Science Society, Inc.

  19. Developmental robotics: manifesto and application.

    Science.gov (United States)

    Elliott, Terry; Shadbolt, Nigel R

    2003-10-15

    We argue that all embodied organisms, whether robots or animals, face the same challenge: of adapting to bodies, brains and environments that undergo constant and inevitable change. After highlighting the evidence for the universal role of a class of molecular factors called neurotrophic factors in the response of animals to this challenge, we suggest that implementing models of neurotrophic interactions on robots may confer on them the adaptability and robustness exhibited by animals. We briefly review a mathematical model of neurotrophic interactions and then discuss its application in a robotic context. Finally, we examine the potential, or otherwise, of our approach to developmental robotics.

  20. Is LSD toxic?

    Science.gov (United States)

    Nichols, David E; Grob, Charles S

    2018-02-01

    LSD (lysergic acid diethylamide) was discovered almost 75 years ago, and has been the object of episodic controversy since then. While initially explored as an adjunctive psychiatric treatment, its recreational use by the general public has persisted and on occasion has been associated with adverse outcomes, particularly when the drug is taken under suboptimal conditions. LSD's potential to cause psychological disturbance (bad trips) has been long understood, and has rarely been associated with accidental deaths and suicide. From a physiological perspective, however, LSD is known to be non-toxic and medically safe when taken at standard dosages (50-200μg). The scientific literature, along with recent media reports, have unfortunately implicated "LSD toxicity" in five cases of sudden death. On close examination, however, two of these fatalities were associated with ingestion of massive overdoses, two were evidently in individuals with psychological agitation after taking standard doses of LSD who were then placed in maximal physical restraint positions (hogtied) by police, following which they suffered fatal cardiovascular collapse, and one case of extreme hyperthermia leading to death that was likely caused by a drug substituted for LSD with strong effects on central nervous system temperature regulation (e.g. 25i-NBOMe). Given the renewed interest in the therapeutic potential of LSD and other psychedelic drugs, it is important that an accurate understanding be established of the true causes of such fatalities that had been erroneously attributed to LSD toxicity, including massive overdoses, excessive physical restraints, and psychoactive drugs other than LSD. Copyright © 2018 Elsevier B.V. All rights reserved.

  1. Toxic metals and autophagy.

    Science.gov (United States)

    Chatterjee, Sarmishtha; Sarkar, Shuvasree; Bhattacharya, Shelley

    2014-11-17

    The earth's resources are finite, and it can no longer be considered a source of inexhaustible bounty for the human population. However, this realization has not been able to contain the human desire for rapid industrialization. The collateral to overusing environmental resources is the high-level contamination of undesirable toxic metals, leading to bioaccumulation and cellular damage. Cytopathological features of biological systems represent a key variable in several diseases. A review of the literature revealed that autophagy (PCDII), a high-capacity process, may consist of selective elimination of vital organelles and/or proteins that intiate mechanisms of cytoprotection and homeostasis in different biological systems under normal physiological and stress conditions. However, the biological system does survive under various environmental stressors. Currently, there is no consensus that specifies a particular response as being a dependable biomarker of toxicology. Autophagy has been recorded as the initial response of a cell to a toxic metal in a concentration- and time-dependent manner. Various signaling pathways are triggered through cellular proteins and/or protein kinases that can lead to autophagy, apoptosis (or necroptosis), and necrosis. Although the role of autophagy in tumorigenesis is associated with promoting tumor cell survival and/or acting as a tumor suppressive mechanism, PCDII in metal-induced toxicity has not been extensively studied. The aim of this review is to analyze the comparative cytotoxicity of metals/metalloids and nanoparticles (As, Cd, Cr, Hg, Fe, and metal-NP) in cells enduring autophagy. It is noted that metals/metalloids and nanoparticles prefer ATG8/LC3 as a potent inducer of autophagy in several cell lines or animal cells. MAP kinases, death protein kinases, PI3K, AKT, mTOR, and AMP kinase have been found to be the major components of autophagy induction or inhibition in the context of cellular responses to metals/metalloids and

  2. Evolutionary developmental biology its roots and characteristics.

    Science.gov (United States)

    Morange, Michel

    2011-09-01

    The rise of evolutionary developmental biology was not the progressive isolation and characterization of developmental genes and gene networks. Many obstacles had to be overcome: the idea that all genes were more or less involved in development; the evidence that developmental processes in insects had nothing in common with those of vertebrates. Different lines of research converged toward the creation of evolutionary developmental biology, giving this field of research its present heterogeneity. This does not prevent all those working in the field from sharing the conviction that a precise characterization of evolutionary variations is required to fully understand the evolutionary process. Some evolutionary developmental biologists directly challenge the Modern Synthesis. I propose some ways to reconcile these apparently opposed visions of evolution. The turbulence seen in evolutionary developmental biology reflects the present entry of history into biology. Copyright © 2011 Elsevier Inc. All rights reserved.

  3. Nanoparticle toxicity and cancer

    Energy Technology Data Exchange (ETDEWEB)

    Prevenslik, T, E-mail: nanoqed@gmail.com [QED Radiations, Discovery Bay, Hong Kong (Hong Kong)

    2011-07-06

    Nanoparticles (NPs) have provided significant advancements in cancer treatment. But as in any technology, there is a darkside. Experiments have shown NPs in body fluids pose a health risk by causing DNA damage that in of itself may lead to cancer. To avoid the dilemma that NPs are toxic to both cancer cells and DNA alike, the mechanism of NP toxicity must be understood so that the safe use of NPs may go forward. Reactive oxidative species (ROS) of peroxide and hydroxyl radicals damage the DNA by chemical reaction, but require NPs provide energies of about 5 eV not possible by surface effects. Only electromagnetic (EM) radiations beyond ultraviolet (UV) levels may explain the toxicity of NPs. Indeed, experiments show DNA damage from <100 nm NPs mimic the same reaction pathways of conventional sources of ionizing radiation, Hence, it is reasonable to hypothesize that NPs produce their own source of UV radiation, albeit at low intensity. Ionizing radiation from NPs at UV levels is consistent with the theory of QED induced EM radiation. QED stands for quantum electrodynamics. By this theory, fine < 100 nm NPs absorb low frequency thermal energy in the far infrared (FIR) from collisions with the water molecules in body fluids. Since quantum mechanics (QM) precludes NPs from having specific heat, absorbed EM collision energy cannot be conserved by an increase in temperature. But total internal reflection (TIR) momentarily confines the absorbed EM energy within the NP. Conservation proceeds by the creation of QED photons by frequency up-conversion of the absorbed EM energy to the TIR confinement frequency, typically beyond the UV. Subsequently, the QED photons upon scattering from atoms within the NP avoid TIR confinement and leak UV to the surroundings, thereby explaining the remarkable toxicity of NPs. But QED radiation need not be limited to natural or man-made NPs. Extensions suggest UV radiation is produced from biological NPs within the body, e.g., enzyme induced

  4. Neurological oxygen toxicity.

    Science.gov (United States)

    Farmery, Scott; Sykes, Oliver

    2012-10-01

    SCUBA diving has several risks associated with it from breathing air under pressure--nitrogen narcosis, barotrauma and decompression sickness (the bends). Trimix SCUBA diving involves regulating mixtures of nitrogen, oxygen and helium in an attempt to overcome the risks of narcosis and decompression sickness during deep dives, but introduces other potential hazards such as hypoxia and oxygen toxicity convulsions. This study reports on a seizure during the ascent phase, its potential causes and management and discusses the hazards posed to the diver and his rescuer by an emergency ascent to the surface.

  5. 40 CFR 799.9365 - TSCA combined repeated dose toxicity study with the reproduction/developmental toxicity screening...

    Science.gov (United States)

    2010-07-01

    ... of the substance to affect fertility, pregnancy, maternal and suckling behaviour, and growth and... (pregnant) animals, disturbs lactation and nursing behaviour, and, particularly in feeding studies, may... and dead), sex ratio, postnatal growth (pup weights) and survival (litter size), gross abnormalities...

  6. Developmental Robotics: From Babies to Robots

    OpenAIRE

    Cangelosi, A.; Schlesinger, M.

    2015-01-01

    Developmental robotics is a collaborative and interdisciplinary approach to robotics that is directly inspired by the developmental principles and mechanisms observed in children’s cognitive development. It builds on the idea that the robot, using a set of intrinsic developmental principles regulating the real-time interaction of its body, brain, and environment, can autonomously acquire an increasingly complex set of sensorimotor and mental capabilities. This volume, drawing on insights from...

  7. Specific language impairment as systemic developmental disorders

    OpenAIRE

    Parisse, Christophe; Maillart, Christelle

    2009-01-01

    International audience; Specific Language Impairment (SLI) is a disorder characterised by slow, abnormal language development.Most children with this disorder do not present any other cognitive or neurological deficits. Thereare many different pathological developmental profiles and switches from one profile to another oftenoccur. An alternative would be to consider SLI as a generic name covering three developmental languagedisorders: developmental verbal dyspraxia, linguistic dysphasia, and ...

  8. Comorbidity and diagnosis of developmental disorders

    OpenAIRE

    Williams, David M.; Lind, Sophie E.

    2013-01-01

    This chapter explores two main themes in two separate sections. The first section explores some of the challenges involved in the diagnosis of complex developmental disorders such as specific language impairment (SLI), developmental dyslexia, attention deficit hyperactivity disorder (ADHD), and autism spectrum disorder (ASD). The second section of the chapter will consider the issue of co-morbidity between developmental disorders, and discuss the various models that have been proposed to expl...

  9. An introduction to evolutionary developmental psychology.

    Science.gov (United States)

    Machluf, Karin; Liddle, James R; Bjorklund, David F

    2014-04-29

    Evolutionary developmental psychology represents a synthesis of modern evolutionary theory and developmental psychology. Here we introduce the special issue on evolutionary developmental psychology by briefly discussing the history of this field and then summarizing the variety of topics that are covered. In this special issue, leading researchers provide a collection of theoretical and empirical articles that highlight recent findings and propose promising areas for future research.

  10. An Introduction to Evolutionary Developmental Psychology

    OpenAIRE

    Karin Machluf; James R. Liddle; David F. Bjorklund

    2014-01-01

    Evolutionary developmental psychology represents a synthesis of modern evolutionary theory and developmental psychology. Here we introduce the special issue on evolutionary developmental psychology by briefly discussing the history of this field and then summarizing the variety of topics that are covered. In this special issue, leading researchers provide a collection of theoretical and empirical articles that highlight recent findings and propose promising areas for future research.

  11. An Introduction to Evolutionary Developmental Psychology

    Directory of Open Access Journals (Sweden)

    Karin Machluf

    2014-04-01

    Full Text Available Evolutionary developmental psychology represents a synthesis of modern evolutionary theory and developmental psychology. Here we introduce the special issue on evolutionary developmental psychology by briefly discussing the history of this field and then summarizing the variety of topics that are covered. In this special issue, leading researchers provide a collection of theoretical and empirical articles that highlight recent findings and propose promising areas for future research.

  12. Preliminary acute toxicity study on imidacloprid in Swiss albino mice

    Directory of Open Access Journals (Sweden)

    Preeti Bagri

    2013-12-01

    Full Text Available Aim: To ascertain the maximum tolerated dose (MTD and to investigate the acute oral toxic effects of imidacloprid towards Swiss albino male mice.Materials and Methods: The MTD of imidacloprid was determined in pilot dose range finding study following the standard method. Animals were observed for toxic signs and symptoms after oral administration of MTD of imidacloprid in single dose. The body weights of animals were recorded on alternate day. Animals were sacrificed on 14th day and changes in hematological parameters (Hb, TEC, TLC and DLC and morphometric measurements (length, breadth, thickness and weight of various body organs (heart, liver, spleen, kidney, testis and epididymis were examined. The student's t-test was applied to statistically analyze the results.Results: The MTD of imidacloprid was determined to be 110 mg/kg body weight. The sign and symptoms of acute toxicity were ataxia, rigidity and fasciculation of muscles, protrusion of eye ball and tremors of head. Imidacloprid treatment resulted in decreased body weight gain as compared to the control group. The changes in hematological parameters were not significant between imidacloprid treated and control groups. Also the values of relative organ weights and morphometric measurements of various body organs did not differ significantly between the control and imidacloprid treated animals.Conclusions: MTD of imidacloprid in Swiss albino male mice through oral route was determined for the first time. Study revealed a non-toxic effect of imidacloprid on body weight, relative organs weight, hematological parameters and morphometric measurements of various body organs in mice.

  13. Interoception and psychopathology: A developmental neuroscience perspective

    National Research Council Canada - National Science Library

    Murphy, Jennifer; Brewer, Rebecca; Catmur, Caroline; Bird, Geoffrey

    2017-01-01

    .... This qualitative review and opinion paper provides a brief overview of interoception, discussing its relevance for developmental psychopathology, and highlighting measurement issues, before surveying...

  14. Becoming a schoolchild - a positive developmental crisis

    DEFF Research Database (Denmark)

    Winther-Lindqvist, Ditte Alexandra

    2017-01-01

    In this Chapter the transition from day care into primary school is investigated from the point of view of cultural-historical developmental psychology, mainly the works by L. Vygotsky, L. Bozhovich and M. Hedegaard. The central point is that starting school and the transition to becoming...... and organizing the transition into a step-by-step process is discussed critically from the point of view of cultural-historical developmental psychology....... a schoolchild should be viewed as a positive developmental crisis. It is argued that institutional transitions are both characterized by preparation (institutionally and personally) and of actualization. A general descriptive model of identity tasks and developmental demands is offered to account...

  15. Sexual dysfunction within an adult developmental perspective.

    Science.gov (United States)

    Fagan, P J; Meyer, J K; Schmidt, C W

    1986-01-01

    The focus of this paper is on the adult who has adequately mastered the oedipal stage of psychosexual development and who presents with a sexual dysfunction. Drawing on the developmental sequence of Erik Erikson, the authors suggest that failure to address adequately an adult psychosocial crisis may result in sexual dysfunction. There may be both adult developmental deficits and regression to adolescent and adult stages previously negotiated. Both may be symptomatically represented by sexual dysfunction. The authors urge that the sexual and marital problems be evaluated within an adult developmental framework and that the therapy address the psychosocial issues which are appropriate to the developmental stage of the patient.

  16. A developmental metatheory of psychopathology.

    Science.gov (United States)

    Karasu, T B

    1994-01-01

    The author proposes an integrative model of psychopathology in light of the contemporary need to bridge diverse ideological frameworks. This model has its major foundations in drive, ego, object relations, and self psychoanalytic perspectives as they impact upon interactional patterns of infancy. The chronology of these theoretical orientations is presented as parallel to a changing focus upon different successive stages in the course of individual development. The longstanding controversy between conflict and deficit theories, which undergirds the various schools of thought, is addressed: a developmental orientation is offered as the overriding conceptual connection between them. Conflict and deficit phenomena are regarded as intertwined and not incompatible: Unconscious drives, desires and wishes, ego defenses, and compromise formations as well as object relationship deficiencies and structural voids and defects in the self are combined to encompass a broad spectrum of psychopathology and its sources: the above intrapsychic and interpersonal factors are interfaced with significant reciprocal dyadic (mother/child) and triadic (father/mother/child) influences upon ongoing maturational processes. For heuristic purposes, a fourfold matrix--dyadic deficit, dyadic conflict, triadic deficit, and triadic conflict--is delineated. Clinical characteristics and developmental precursors of each of the four prototypes, especially with regard to early relational events, are examined.

  17. Developmental constraint of insect audition.

    Science.gov (United States)

    Lakes-Harlan, Reinhard; Strauss, Johannes

    2006-12-12

    Insect ears contain very different numbers of sensory cells, from only one sensory cell in some moths to thousands of sensory cells, e.g. in cicadas. These differences still await functional explanation and especially the large numbers in cicadas remain puzzling. Insects of the different orders have distinct developmental sequences for the generation of auditory organs. These sensory cells might have different functions depending on the developmental stages. Here we propose that constraints arising during development are also important for the design of insect ears and might influence cell numbers of the adults. We propose that the functional requirements of the subadult stages determine the adult complement of sensory units in the auditory system of cicadas. The hypothetical larval sensory organ should function as a vibration receiver, representing a functional caenogenesis. Experiments at different levels have to be designed to test the hypothesis. Firstly, the neuroanatomy of the larval sense organ should be analyzed to detail. Secondly, the function should be unraveled neurophysiologically and behaviorally. Thirdly, the persistence of the sensory cells and the rebuilding of the sensory organ to the adult should be investigated. Usually, the evolution of insect ears is viewed with respect to physiological and neuronal mechanisms of sound perception. This view should be extended to the development of sense organs. Functional requirements during postembryonic development may act as constraints for the evolution of adult organs, as exemplified with the auditory system of cicadas.

  18. Developmental constraint of insect audition

    Directory of Open Access Journals (Sweden)

    Strauß Johannes

    2006-12-01

    Full Text Available Abstract Background Insect ears contain very different numbers of sensory cells, from only one sensory cell in some moths to thousands of sensory cells, e.g. in cicadas. These differences still await functional explanation and especially the large numbers in cicadas remain puzzling. Insects of the different orders have distinct developmental sequences for the generation of auditory organs. These sensory cells might have different functions depending on the developmental stages. Here we propose that constraints arising during development are also important for the design of insect ears and might influence cell numbers of the adults. Presentation of the hypothesis We propose that the functional requirements of the subadult stages determine the adult complement of sensory units in the auditory system of cicadas. The hypothetical larval sensory organ should function as a vibration receiver, representing a functional caenogenesis. Testing the hypothesis Experiments at different levels have to be designed to test the hypothesis. Firstly, the neuroanatomy of the larval sense organ should be analyzed to detail. Secondly, the function should be unraveled neurophysiologically and behaviorally. Thirdly, the persistence of the sensory cells and the rebuilding of the sensory organ to the adult should be investigated. Implications of the hypothesis Usually, the evolution of insect ears is viewed with respect to physiological and neuronal mechanisms of sound perception. This view should be extended to the development of sense organs. Functional requirements during postembryonic development may act as constraints for the evolution of adult organs, as exemplified with the auditory system of cicadas.

  19. Developmental stability and human violence.

    Science.gov (United States)

    Furlow, B; Gangestad, S W; Armijo-Prewitt, T

    1998-01-07

    Developmental stability (the precision with which genotypes are translated into phenotypes under physically stressful developmental conditions), is a major source of phenotypic and behavioural variation, yet researchers have largely ignored its potential role in the ontogeny of individual propensities toward human aggression and violence. In this study, we measured fluctuating asymmetry of the body and administered aggression and fighting history questionnaires to 229 college students (139 female and 90 male undergraduates). Among males, but not females, fluctuating asymmetry correlated negatively and significantly with the participants' number of fights and propensity to escalate agonistic encounters to physical violence. Principal components analyses and scree tests suggested that two psychometric factors underlie observed correlations between self-report measures of aggressive tendencies. The first factor, 'aggressive negative affect', reflected verbal aggression and hostility toward others, while the second factor, 'self-assessed fighting ability', reflected physical violence and a tendency to win fights. The two factors correlated minimally. For both males and females, the second factor correlated with number of fights while the first factor did not. Fluctuating asymmetry did not significantly correlate with either factor for either sex, but for both sexes, psychometric intelligence (IQ) correlated positively with the first factor.

  20. Molecular toxicity of nanomaterials.

    Science.gov (United States)

    Chang, Xue-Ling; Yang, Sheng-Tao; Xing, Gengmei

    2014-10-01

    With the rapid developments in the fields of nanoscience and nanotechnlogy, more and more nanomaterials and their based consumer products have been used into our daily life. The safety concerns of nanomaterials have been well recognized by the scientific community and the public. Molecular mechanism of interactions between nanomaterials and biosystems is the most essential topic and final core of the biosafety. In the last two decades, nanotoxicology developed very fast and toxicity phenomena of nanomaterials have been reported. To achieve better understanding and detoxication of nanomaterials, thorough studies of nanotoxicity at molecular level are important. The interactions between nanomaterials and biomolecules have been widely investigated as the first step toward the molecular nanotoxicology. The consequences of such interactions have been discussed in the literature. Besides this, the chemical mechanism of nanotoxicology is gaining more attention, which would lead to a better design of nontoxic nanomaterials. In this review, we focus on the molecular nanotoxicology and explore the toxicity of nanomaterials at molecular level. The molecular level studies of nanotoxicology are summarized and the published nanotoxicological data are revisited.

  1. An Interpretation of Part of Gilbert Gottlieb's Legacy: Developmental Systems Theory Contra Developmental Behavior Genetics

    Science.gov (United States)

    Molenaar, Peter C. M.

    2015-01-01

    The main theme of this paper concerns the persistent critique of Gilbert Gottlieb on developmental behavior genetics and my reactions to this critique, the latter changing from rejection to complete acceptation. Concise characterizations of developmental behavior genetics, developmental systems theory (to which Gottlieb made essential…

  2. Biological control of toxic cyanobacteria

    CSIR Research Space (South Africa)

    Ndlela, L

    2016-04-01

    Full Text Available • If successful, the biocontrol agent may produce conformational changes to the cyanobacterial toxins or reduced eco-toxicity effects • The laboratory study may give insight into the factors inhibiting the natural balance of predatory bacteria... studies have been done on the eco-toxicity resulting from biocontrol as well as the changes to cyanotoxins, if any. Research Plan The study will be conducted at whole cell level and with specific metabolites and toxins, with eco-toxicity studied...

  3. Comparison of rat and rabbit embryo-fetal developmental ...

    Science.gov (United States)

    Regulatory non-clinical safety testing of human pharmaceutical compounds typically requires embryo fetal developmental toxicity (EFDT) testing in two species, (one rodent and one non-rodent, usually the rat and the rabbit). The question has been raised whether under some conditions EFDT testing could be limited to one species, or whether the need for testing in a second species could be decided on a case by case basis. As part of an RIVM/CBG-MEB/HESI/US EPA consortium initiative, we built and queried a database of 379 EFDT studies conducted for marketed and non-marketed pharmaceutical compounds. The animal models (rat and rabbit) were assessed for their potential for adverse developmental and maternal outcomes. The database was analyzed for the prevalence of EFDT incidence and the nature and severity of adverse findings in the two species. Some manifestation of EFDT in either one or both species (rat and rabbit) was demonstrated for 282 compounds (74%), and EFDT was detected in only one species (rat or rabbit) in almost a third (31%, 118 compounds), with approximately 58% rat and 42% rabbit studies identifying an EFDT signal among the 379 compounds tested. For 24 compounds (6%), fetal malformations were observed in one species (rat or rabbit) in the absence of any EFDT in the second species. In general, growth retardation, fetal variations, and malformations were more prominent in the rat, whereas embryo-fetal death was observed more often in the rabbit. Discor

  4. Tapentadol toxicity in children.

    Science.gov (United States)

    Borys, Douglas; Stanton, Matthew; Gummin, David; Drott, Tracy

    2015-02-01

    Tapentadol (Nucynta) is indicated for the treatment of moderate to severe pain in adults. Tapentadol's mechanism of action consists of acting as an agonist on the μ-opioid receptor and by inhibiting the reuptake of norepinephrine. There are no published reports on the toxicity of tapentadol in pediatric patients. The goals of this study are to describe the incidence, medical outcomes, clinical effects, and treatment secondary to tapentadol exposure. This retrospective observational study used data from the National Poison Data System. Inclusion criteria were exposure to tapentadol from November 1, 2008 to December 31, 2013; age 0 to 17 years; single ingestion; and followed to a known outcome. There were 104 patients who met the inclusion criteria. Eighty patients were aged ≤ 6, 2-year-olds the most common age group (60.6%). There were 52 male and 52 female patients. Of the 104 patients, 93 had unintentional exposures. No deaths were reported. Sixty-two of the patients had no effect, 34 had minor effects, 6 had moderate and 2 had major effects. Thirty patients reported drowsiness and lethargy. Other effects reported included nausea, vomiting, miosis, tachycardia, respiratory depression, dizziness/vertigo, coma, dyspnea, pallor, vomiting, edema, hives/welts, slurred speech, pruritus, and hallucinations/delusions. Fifty-three patients were reported to have no medical intervention. This is the first study examining the toxic effects of tapentadol in a pediatric population. Although a majority of the patients in this review developed no effect from their exposure, two had life-threatening events. The most common effects reported were opioidlike. Copyright © 2015 by the American Academy of Pediatrics.

  5. Lead toxicity: Current concerns

    Energy Technology Data Exchange (ETDEWEB)

    Goyer, R.A. (Univ. of Western Ontario, London (Canada))

    1993-04-01

    Over the 20-year period since the first issue of Environmental Health Perspectives was published, there has been considerable progress in the understanding of the potential toxicity of exposure to lead. Many of these advances have been reviewed in published symposia, conferences, and review papers in EHP. This brief review identifies major advances as well as a number of current concerns that present opportunities for prevention and intervention strategies. The major scientific advance has been the demonstration that blood lead (PbB) levels of 10-15 micrograms/dL in newborn and very young infants result in cognitive and behavioral deficits. Further support for this observation is being obtained by prospective or longitudinal studies presently in progress. The mechanism(s) for the central nervous system effects of lead is unclear but involve lead interactions within calcium-mediated intracellular messenger systems and neurotransmission. Effects of low-level lead exposure on blood pressure, particularly in adult men, may be related to the effect of lead on calcium-mediated control of vascular smooth muscle contraction and on the renin-angiotensin system. Reproductive effects of lead have long been suspected, but low-level effects have not been well studied. Whether lead is a carcinogen or its association with renal adenocarcinoma is a consequence of cystic nephropathy is uncertain. Major risk factors for lead toxicity in children in the United States include nutrition, particularly deficiencies of essential metals, calcium, iron, and zinc, and housing and socioeconomic status. A goal for the year 2000 is to reduce prevalence of blood lead levels exceeding 15 micrograms/dL. 97 refs.

  6. Developmental hip dysplasia in adolescence

    Directory of Open Access Journals (Sweden)

    Vukašinović Zoran

    2009-01-01

    Full Text Available The authors define adolescence and developmental dysplasia of the hip (DDH. Special attention is paid to pathological findings characteristic of DDH in adolescence (unrecognized and untreated DDH; treated DDH, but non-terminated treatment; DDH diagnosed with delay, inadequately treated, with complications. The authors emphasise that DDH treatment has to be successfully terminated well before the adolescence; possibilities are explained on management modes at the time of adolescence, and possible persons guilty for the persistence of later hip problems are indicated. Based on the authors' experience and having in mind all surgical possibilities for the treatment (pelvic osteotomies, femoral osteotomies, trochanteroplasties, leg length equalization procedures the authors propose treatment protocols. The intention is to provide better treatment results and to prevent secondary hip arthrosis. Furthermore, how to improve the struggle against DDH is suggested.

  7. Children's Ability to Recognise Toxic and Non-Toxic Fruits

    Science.gov (United States)

    Fancovicova, Jana; Prokop, Pavol

    2011-01-01

    Children's ability to identify common plants is a necessary prerequisite for learning botany. However, recent work has shown that children lack positive attitudes toward plants and are unable to identify them. We examined children's (aged 10-17) ability to discriminate between common toxic and non-toxic plants and their mature fruits presented in…

  8. Psychological Resources of Adults with Developmental Dyslexia

    Science.gov (United States)

    Lockiewicz, Marta; Bogdanowicz, Katarzyna M.; Bogdanowicz, Marta

    2014-01-01

    The aim of our study was to describe specific psychological resources of adults with developmental dyslexia and compare them with psychological resources of adults without developmental dyslexia. Potential differences were analyzed in visual-spatial, creative, and motivational abilities. No evidence was found for either creative, or visuospatial…

  9. A Taxometric Investigation of Developmental Dyslexia Subtypes

    Science.gov (United States)

    O'Brien, Beth A.; Wolf, Maryanne; Lovett, Maureen W.

    2012-01-01

    Long-standing issues with the conceptualization, identification and subtyping of developmental dyslexia persist. This study takes an alternative approach to examine the heterogeneity of developmental dyslexia using taxometric classification techniques. These methods were used with a large sample of 671 children ages 6-8 who were diagnosed with…

  10. Developmental Planning: An Introduction for Parents

    Science.gov (United States)

    Noland, Jim

    2009-01-01

    "Developmental Planning" is the thinking process of using developmental milestones as a general basis for planning and predicting needs for the child within the early years. It considers the time frames associated with normal development across all facets of the child's development. The areas include bone and joint development, movement, sensory…

  11. Developmental spinal canal stenosis and somatotype.

    OpenAIRE

    Nightingale, S.

    1989-01-01

    The hypothesis that somatotype and cervical spine developmental canal stenosis may be associated has been investigated by anthropometry and measurement of lateral projection cervical spine radiographs. A significant association of canal size with somatotype has been found such that those with developmentally narrow canals are more likely to have relatively shorter long-bones, particularly in the upper arm, and longer trunks.

  12. Pleiotropic consequences of misexpression of the developmentally ...

    Indian Academy of Sciences (India)

    The non-coding hsr gene of Drosophila melanogaster is expressed in nearly all cell types and developmental stages. However, in the absence of conventional mutant alleles of this gene, its developmental functions remain largely unknown. In the present study, we used a variety of GAL4 drivers to overexpress or ablate ...

  13. Working Memory in Children with Developmental Disorders

    Science.gov (United States)

    Alloway, Tracy Packiam; Rajendran, Gnanathusharan; Archibald, Lisa M. D.

    2009-01-01

    The aim of the present study was to directly compare working memory skills across students with different developmental disorders to investigate whether the uniqueness of their diagnosis would impact memory skills. The authors report findings confirming differential memory profiles on the basis of the following developmental disorders: Specific…

  14. Developmental Cognitive Neuroscience: Origins, Issues, and Prospects

    Science.gov (United States)

    Pennington, Bruce F.; Snyder, Kelly A.; Roberts, Ralph J., Jr.

    2007-01-01

    This commentary explains how the field of developmental cognitive neuroscience (DCN) holds the promise of a much wider interdisciplinary integration across sciences concerned with development: psychology, molecular genetics, neurobiology, and evolutionary developmental biology. First we present a brief history of DCN, including the key theoretical…

  15. The developmental stages of Pseudodiaptomus hessei (Copepoda ...

    African Journals Online (AJOL)

    The developmental stages of Pseudodiaptomus hessei (Copepoda: Calanoida). H.L. Jerling, T.H. Wooldridge. Abstract. Nauplii and copepodid developmental stages of the estuarine copepod, Pseudodiaptomus hessei, are described and illustrated. Five post-embryonic naupliar and five copepodid stages (excluding adults) ...

  16. Desiccation stress induces developmental heterochrony in

    Indian Academy of Sciences (India)

    Stressful environments are known to perturb developmental patterns in insects. In the purview of desiccation as astressor, relatively little is known about the developmental consequences linked with desiccation tolerance. In thisstudy, we have particularly focused on the exploration of the temporal profile of postembryonic ...

  17. Programs for Individuals with Developmental Disabilities. Revised.

    Science.gov (United States)

    Sizemore, C. J.

    This publication describes the programs and services offered through the Office of Developmental Disabilities of the Illinois Department of Human Services. Introductory information includes an overview of supports and service, a definition of "developmental disability," and a guide to the publication. This is followed by a description of…

  18. Combined Developmental Constructs and Job Performance of ...

    African Journals Online (AJOL)

    Combined Developmental Constructs and Job Performance of Librarians in University Libraries in South-South Geo-Political Zone of Nigeria. ... The results showed that librarians' on-the-job performance depends significantly on the combined effect of the six developmental constructs. Further analysis showed that only ...

  19. Piaget's Enduring Contribution to Developmental Psychology.

    Science.gov (United States)

    Beilin, Harry

    1992-01-01

    Describes Jean Piaget's transformation of society's conception of childhood thought. Emphasizes the enduring contribution to developmental psychology of Piaget's constructivism, his description of developmental mechanisms, his cognitivism, his explication of structural and functional analysis, and his addressing of epistemological issues and…

  20. Menstrual suppression for adolescents with developmental disabilities.

    Science.gov (United States)

    Savasi, I; Spitzer, R F; Allen, L M; Ornstein, M P

    2009-06-01

    The approach to menstrual suppression for adolescents with developmental disabilities has evolved considerably over the years due to changing philosophies and evolving treatment options. We review the medical management options available for menstrual suppression with a focus on the needs and treatment of adolescents with developmental disabilities.

  1. Static balance and developmental coordination disorder

    NARCIS (Netherlands)

    Geuze, RH

    2003-01-01

    The development of static balance is a basic characteristic of normal motor development. Most of the developmental motor tests include a measure of static balance. Children with a developmental coordination disorder (DCD) often fail this item. Twenty-four children at risk for DCD with balance

  2. Developmental Dislocation (Dysplasia) of the Hip (DDH)

    Science.gov (United States)

    ... bone. In babies and children with developmental dysplasia (dislocation) of the hip (DDH), the hip joint has not formed normally. ... the American Academy of Orthopaedic Surgeons. .org Developmental Dislocation (Dysplasia) of the Hip cont. • Family history of DDH (parents or siblings) • ...

  3. Innovative Developmental Education Programs: A Texas Model

    Science.gov (United States)

    Booth, Eric A.; Capraro, Mary Margaret; Capraro, Robert M.; Chaudhuri, Nandita; Dyer, James; Marchbanks, Miner P., III

    2014-01-01

    This article provides insights from a 2-year, cross-site evaluation of state funded developmental education sites and serves as a focus article for response by those sites. Receiving grants from the Texas Higher Education Coordinating Board (THECB), nine sites (5 community colleges and 4 universities) implemented innovative developmental education…

  4. Challenges to the Developmental Study of Coping

    Science.gov (United States)

    Skinner, Ellen A.; Zimmer-Gembeck, Melanie J.

    2009-01-01

    We summarize progress in the developmental study of coping, including specification of a multilevel framework, construction of definitions of coping that rely on regulation as a core concept, and identification of developmentally graded members of families of coping. We argue that these accomplishments are a prelude to the real tasks of a…

  5. Reflections on Multiculturalism in Developmental Education.

    Science.gov (United States)

    Bruch, Patrick L.; Higbee, Jeanne L.

    2002-01-01

    Reports on an effort to better understand the impasse and create conditions for constructive local discussions and reforms relating to multiculturalism. Reports how a group of developmental education professionals in a large, interdisciplinary developmental education unit understand multiculturalism. Explores the potentials and challenges involved…

  6. Sexism in Developmental Education: Tackling the Demon.

    Science.gov (United States)

    Green, Sharon

    1994-01-01

    Discusses the effects of sexism in education and the means by which educators can reduce it. Indicates that developmental educators are in a unique position to counteract sexism. Contains suggestions for overcoming sexism in five areas of developmental education (math, reading, writing, counseling, and administration) and in the classroom. (35…

  7. Essential Role of Culture in Developmental Psychology

    Science.gov (United States)

    Miller, Joan G.

    2005-01-01

    This chapter argues for the essential role of culture in forming the basic constructs and theories of developmental psychology. The case is made for the need to overcome the cultural insularity of core developmental concepts and methods in order to create a psychology that is more truly universal.

  8. Crowding, reading, and developmental dyslexia.

    Science.gov (United States)

    Martelli, Marialuisa; Di Filippo, Gloria; Spinelli, Donatella; Zoccolotti, Pierluigi

    2009-04-17

    We tested the hypothesis that crowding effects are responsible for the reading slowness characteristic of developmental dyslexia. A total of twenty-nine Italian dyslexics and thirty-three age-matched controls participated in various parts of the study. In Experiment 1, we measured contrast thresholds for identifying letters and words as a function of stimulus duration. Thresholds were higher in dyslexics than controls for words (at a limited time exposure) but not for single letters. Adding noise to the stimuli produced comparable effects in dyslexics and controls. At the long time exposure thresholds were comparable in the two groups. In Experiment 2, we measured the spacing between a target letter and two flankers at a fixed level of performance as a function of eccentricity and size. With eccentricity, the critical spacing (CS) scaled in the control group with 0.62 proportionality (a value of b close to Bouma's law, 0.50) and with a greater proportionality (0.95) in the dyslexic group. CS was independent of size in both groups. In Experiment 3, we examined the critical print size (CPS), that is, the increase in reading rate up to a critical character size (S. T. Chung, J. S. Mansfield, & G. E. Legge, 1998). CPS of dyslexic children was greater than that of controls. Individual maximal reading speed was predicted by individual bs (from Experiment 2). The maximal reading rate achieved by dyslexics at CPS (and also for larger print sizes) was below the values observed in controls. We conclude that word analysis in dyslexics is slowed because of greater crowding effects, which limit letter identification in multi-letter arrays across the visual field. We propose that the peripheral reading of normal readers might constitute a model for dyslexic reading. The periphery model accounts for 60% of dyslexics' slowness. After compensating for crowding, the dyslexics' reading rate remains slower than that of proficient readers. This failure is discussed in terms of a

  9. Early Intervention in Children with Developmental Disabilities

    Directory of Open Access Journals (Sweden)

    Beena Johnson

    2016-01-01

    Full Text Available Developmental disabilities consist of conditions that delay or impair the physical, cognitive, and/or psychological development of children. If not intervened at the earliest, these disabilities will cause significant negative impact on multiple domains of functioning such as learning, language, self-care and capacity for independent living. Common developmental disabilities include autism spectrum disorders, intellectual disabilities, developmental delay and cerebral palsy. About one fourth of young children in developing countries are at risk for or have developmental delay or disabilities. Inadequate stimulation has significant negative impact on physical, socioemotional and cognitive development of children. Hence early scientific intervention programs are necessary in the management of children at risk for developmental delay.

  10. Future Directions in Sleep and Developmental Psychopathology.

    Science.gov (United States)

    Meltzer, Lisa J

    2017-01-01

    It is critical for psychologists to gain a better understanding about the intersection between sleep and developmental psychopathology. However, while many strive to answer the question of whether sleep causes developmental psychopathology, or vice versa, ultimately the relationship between sleep and developmental psychopathology is complex and dynamic. This article considers future directions in the field of clinical child and adolescent psychology that go beyond this mechanistic question, highlighting areas important to address for clinicians and researchers who strive to better understand how best to serve children and adolescents with developmental psychopathology. Questions are presented about what is normal in terms of sleep across development, the role of individual variability in terms of sleep needs and vulnerability to sleep loss, and how sleep may serve as a risk or resilience factor for developmental psychopathology, concluding with considerations for interventions.

  11. Toxication or detoxication? In vivo toxicity assessment of ozonation as advanced wastewater treatment with the rainbow trout.

    Science.gov (United States)

    Stalter, Daniel; Magdeburg, Axel; Weil, Mirco; Knacker, Thomas; Oehlmann, Jörg

    2010-01-01

    Ozonation as advanced wastewater treatment method is an effective technique for micropollutant removal. However, the application of this method carries the inherent danger to produce toxic oxidation byproducts. For an ecotoxicological assessment conventionally treated wastewater, wastewater after ozonation and ozonated wastewater after sand filtration were evaluated in parallel at an operating treatment plant via the fish early life stage toxicity test (FELST) using rainbow trout (Oncorhynchus mykiss). The FELST revealed a considerable developmental retardation of test organisms exposed to ozonated WW. This was accompanied by a significant decrease in body weight and length compared to reference water, to the conventionally treated WW and to the ozonated water after sand filtration. Hence sand filtration obviously prevents from adverse ecotoxicological effects of ozonation. An additional test with yolk-sac larvae resulted in a significant reduction of vitellogenin levels in fish exposed to ozonated wastewater compared to fish reared in conventionally treated wastewater. This demonstrates the effective removal of estrogenic activity by ozonation. Adverse ozonation effects may have been a result of the conversion of chemicals into more toxic metabolites. However, sand filtration reduced toxication effects indicating that these oxidation byproducts are readily degradable or adsorbable. The results indicate that in any case ozonation should not be applied without subsequent post treatment appropriate for oxidation byproducts removal (e.g. sand filtration). (c) 2009 Elsevier Ltd. All rights reserved.

  12. A systematic review of Mancozeb as a reproductive and developmental hazard.

    Science.gov (United States)

    Runkle, Jennifer; Flocks, Joan; Economos, Jeannie; Dunlop, Anne L

    2017-02-01

    The potential adverse reproductive and developmental effects of Mancozeb, especially in sensitive subpopulations, have not been fully reviewed for this widely used fungicide. To review the experimental and epidemiologic evidence for the association between exposure to Mancozeb and reproductive and developmental health outcomes using an adaptation of the National Toxicology Program's Office of Health Assessment and Translation (OHAT) systematic review framework. Four databases (PubMed, TOXNET, Web of Science, Google Scholar) were searched for published studies on Mancozeb. Of 403 identified articles, 30 met our inclusion criteria for systematic review. Results from in vitro studies provide evidence that Mancozeb may indirectly disrupt or impair reproduction at the cellular level and should be regarded as a reproductive toxicant. Animal studies confirm reproductive and developmental toxicity in mammals and suggest that males chronically exposed to Mancozeb experience significant changes in physiological, biochemical, and pathological processes that may lead to infertility. Epidemiological studies were limited to indirect methods of exposure assessment and examined the effect of fungicides more broadly during pre-conception, pregnancy, and birth, yielding mixed results. High confidence ratings from in vitro and animal studies, in combination with moderate confidence ratings from epidemiologic studies employing indirect methods of exposure assessment, provide evidence that Mancozeb should be regarded as a suspected developmental hazard and a presumed reproductive hazard in humans. More population-based studies linking direct measures and/or biomarkers of exposure to adverse effects on male and female fertility, as well as in utero and early life development, are needed to improve the quality of the evidence base concerning the human reproductive and developmental consequences of Mancozeb exposure. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Identifying the cause of toxicity in an algal whole effluent toxicity study - an unanticipated toxicant.

    Science.gov (United States)

    Naddy, Rami B; Tapp, Kelly; Rehner, Anita B; Pillard, David A; Schrage, Laura

    2011-10-01

    Toxicity was observed in whole effluent toxicity (WET) studies with the freshwater alga, Pseudokirchneriella subcapitata, in three consecutive monthly studies, (NOEC=50-75%). Toxicity was not observed to Ceriodaphnia dubia or the fathead minnow, Pimephales promelas in concurrent studies. Selected toxicity identification evaluation (TIE) tests were conducted in a tiered approach to eliminate possible toxicants and progressively identify the causative agent. Filtration following alkaline adjustment (pH 10 or 11) was effective in eliminating significant growth effects and also reduced phosphate concentration. The TIE studies confirmed that the observed effluent toxicity was caused by excess ortho-phosphate in the effluent not by overstimulation or related to unfavorable N:P ratios; but due to direct toxicity. The 96-h 25% inhibition concentration (IC25) of ortho-phosphate to P. subcapitata was 3.4 mg L⁻¹ while the maximum acceptable toxicant concentration was 4.8 mg L⁻¹. This study illustrates the value of multi-species testing and also provides an example of an effective TIE using algae identifying an unanticipated toxicant. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. Acquisition of Developmental Milestones in Young Children: Educational.

    Science.gov (United States)

    Sapir, Selma G.

    Children's acquisition of developmental milestones is examined within the framework of a developmental-interactive system. Piaget's stages of cognitive development are reviewed and developmental aspects of language acquisition including inner language and expressive language are discussed. (JMB)

  15. Height and blood chemistry in adults with a history of developmental arsenic poisoning from contaminated milk powder

    DEFF Research Database (Denmark)

    Yorifuji, Takashi; Matsuoka, Kenichi; Grandjean, Philippe

    2017-01-01

    BACKGROUND: Arsenic poisoning interferes with bone metabolism in laboratory animal studies, and human studies suggest lowered bone mass density at elevated exposures. As the long-term consequences of developmental arsenic toxicity are poorly known, we carried out a clinical pilot study of survivors...... of the mass arsenic poisoning of bottle-fed infants in Japan in 1955. OBJECTIVES: The purpose was to evaluate the association between developmental arsenic exposure and physical stature and routine blood chemistry reflecting major organ functions more than 50 years later. METHODS: The study sample consisted...

  16. Species Differences in Renal Development and Associated Developmental Nephrotoxicity.

    Science.gov (United States)

    Frazier, Kendall S

    2017-10-02

    The developing kidney is sensitive to both morphological and functional disturbances during the gestational and postnatal phases of growth and differentiation. Exposure to drugs or chemicals during these critical windows of renal development can result in aplasia, dysplasia, polycystic kidney disease, hydronephrosis, or other features characteristic of nephrotoxicity, including tubule dilation, necrosis, or mineralization. Functional effects can occur without associated morphological abnormalities. Differences in the timing of nephrogenesis and morphologic renal development among species help to explain specific phenotypes of various gestational and postnatal teratogens and nephrotoxins. Functional maturation follows anatomical maturation, but important differences in maximally achieved glomerular filtration rate, concentrating ability and acid-base equilibrium between species makes comparison of these timings critical for accurate and consistent translation of laboratory animal toxicity data to the human clinical experience. Species and age dependent differences in the maturation of kidney transporters, renal xenobiotic metabolism and renal blood flow can have a profound effect on the toxicity profiles of agents and marked differences in the tolerability based on age. Advances in the understanding of the genetics of inherited renal diseases and the underlying cellular and molecular pathogenesis of renal developmental anomalies has helped provide mechanistic understanding of many teratogenic and perinatal nephrotoxic agents. Investigative studies have provided important translational and mechanistic information for assessing human pediatric nephrotoxic potential. Birth Defects Research 109:1243-1256, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  17. Externalization of the Toxic Introject

    Science.gov (United States)

    Beck, Michael

    1975-01-01

    The therapist encounters patients who have incorporated toxic introjects. Therapy helps them to provide room for incorporation of a healthy object by externalizing the toxic introject. This technique is illustrated with several cases and comparison is made between the use of this technique in the treatment of adults and children. (Author)

  18. Toxic Leadership in Educational Organizations

    Science.gov (United States)

    Green, James E.

    2014-01-01

    While research on the traits and skills of effective leaders is plentiful, only recently has the phenomenon of toxic leadership begun to be investigated. This research report focuses on toxic leadership in educational organizations--its prevalence, as well as the characteristics and early indicators. Using mixed methods, the study found four…

  19. One Health and Toxic Cyanobacteria

    Science.gov (United States)

    One Health and toxic cyanobacteria Blooms of toxic freshwater blue-green algae or cyanobacteria (HABs) have been in the news after HABs associated with human and animal health problems have been reported in Florida, California and Utah during 2016. HABs occur in warm, slow moving...

  20. The toxicity of X material

    Energy Technology Data Exchange (ETDEWEB)

    Ferry, J.L.

    1943-12-31

    This report addresses toxicity (largely chemical) of Manhattan Project materials from the point of worker protection. Known chemical toxicities of X material (uranium), nitrous fumes, fluorine, vanadium, magnesium, and lime are described followed by safe exposure levels, symptoms of exposure, and treatment recommendations. The report closes with an overview of general policy in a question and answer format.

  1. Mode of Action: Oxalate Crystal-Induced Renal Tubule Degeneration and Glycolic Acid-Induced Dysmorphogenesis—Renal and Developmental Effects of Ethylene Glycol

    Energy Technology Data Exchange (ETDEWEB)

    Corley, Rick A.; Meek, M E.; Carney, E W.

    2005-10-01

    Ethylene glycol can cause both renal and developmental toxicity, with metabolism playing a key role in the mode of action (MOA) for each form of toxicity. Renal toxicity is ascribed to the terminal metabolite oxalic acid, which precipitates in the kidney in the form of calcium oxalate crystals and is believed to cause physical damage to the renal tubules. The human relevance of the renal toxicity of ethylene glycol is indicated by the similarity between animals and humans of metabolic pathways, the observation of renal oxalate crystals in toxicity studies in experimental animals and human poisonings, and cases of human kidney and bladder stones related to dietary oxalates and oxalate precursors. High-dose gavage exposures to ethylene glycol also cause axial skeletal defects in rodents (but not rabbits), with the intermediary metabolite, glycolic acid, identified as the causative agent. However, the mechanism by which glycolic acid perturbs development has not been investigated sufficiently to develop a plausible hypothesis of mode of action, nor have any cases of ethylene glycol-induced developmental effects been reported in humans. Given this, and the variations in sensitivity between animal species in response, the relevance to humans of ethylene glycol-induced developmental toxicity in animals is unknown at this time.

  2. Polish Toxic Currency Options

    Directory of Open Access Journals (Sweden)

    Waldemar Gontarski

    2009-04-01

    Full Text Available Toxic currency options are defined on the basis of the opposition to the nature (essence of an option contract, which is justified in terms of norms founded on the general law clause of characteristics (nature of a relation (which represents an independent premise for imposing restrictions on the freedom of contracts. So-understood toxic currency options are unlawful. Indeed they contravene iuris cogentis regulations. These include for instance option contracts, which are concluded with a bank, if the bank has not informed about option risk before concluding the contract; or the barrier options, which focus only on the protection of banks interests. Therefore, such options may appear to be invalid. Therefore, performing contracts for toxic currency options may be qualified as a criminal mismanagement. For the sake of security, the manager should then take into consideration filing a claim for stating invalidity (which can be made in a court verdict. At the same time, if the supervisory board member in a commercial company, who can also be a subject to mismanagement offences, commits an omission involving lack of reaction (for example, if he/she fails to notify of the suspected offence committed by the management board members acting to the companys detriment when the management board makes the company conclude option contracts which are charged with absolute invalidity the supervisory board member so acting may be considered to act to the companys detriment. In the most recent Polish jurisprudence and judicature the standard of a good host is treated to be the last resort for determining whether the managers powers resulting from criminal regulations were performed. The manager of the exporter should not, as a rule, issue any options. Issuing options always means assuming an obligation. In the case of currency put options it is an absolute obligation to purchase a given amount in euro at exchange rate set in advance. On the other hand issuing

  3. 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.

  4. Hydrocarbon toxicity: A review.

    Science.gov (United States)

    Tormoehlen, L M; Tekulve, K J; Nañagas, K A

    2014-06-01

    Clinical effects of hydrocarbon exposure have been reported since 1897. These substances are ubiquitous, and their exposures are common. The specific hydrocarbon and route of exposure will determine the clinical effect, and an understanding of this is helpful in the care of the hydrocarbon-exposed patient. To complete a comprehensive review of the literature on hydrocarbon toxicity and summarize the findings. Relevant literature was identified through searches of Medline (PubMed/OVID) and Cochrane Library databases (inclusive of years 1975-2013), as well as from multiple toxicology textbooks. Bibliographies of the identified articles were also reviewed. Search terms included combinations of the following: hydrocarbons, inhalants, encephalopathy, coma, cognitive deficits, inhalant abuse, huffing, sudden sniffing death, toluene, renal tubular acidosis, metabolic acidosis, arrhythmia, dermatitis, and aspiration pneumonitis. All pertinent clinical trials, observational studies, and case reports relevant to hydrocarbon exposure and published in English were reviewed. Chronic, occupational hydrocarbon toxicity was not included. Exposure to hydrocarbons occurs through one of the following routes: inhalation, ingestion with or without aspiration, or dermal exposure. Inhalational abuse is associated with central nervous system depression, metabolic acidosis, and arrhythmia. The exact mechanism of the CNS depression is unknown, but experimental evidence suggests effects on NMDA, dopamine, and GABA receptors. Chronic toluene inhalation causes a non-anion gap metabolic acidosis associated with hypokalemia. Halogenated hydrocarbon abuse can cause a fatal malignant arrhythmia, termed "sudden sniffing death". Individuals who regularly abuse hydrocarbons are more likely to be polysubstance users, exhibit criminal or violent behavior, and develop memory and other cognitive deficits. Heavy, long-term use results in cerebellar dysfunction, encephalopathy, weakness, and dementia

  5. A Lymnaea stagnalis Embryo Test for Toxicity Bioindication of Acidification and Ammonia Pollution in Water

    Directory of Open Access Journals (Sweden)

    Robert Mazur

    2016-07-01

    Full Text Available The paper presents a study leading to a new acute toxicity test on embryonic and juvenile organisms of the great pond snail (Lymnaea stagnalis Linnaeus. Sulfuric acid, nitric acid, and ammonium hydroxide were used as waterborne toxicants in laboratory experiments. The exposure time was 24 h. Tests were conducted in 5–10 replications for each toxicant. The toxicity of the substances was classified according to different scales and the test’s sensitivity was compared to that of the commonly used bioindicator Daphnia magna Straus. The assessment of toxicity impact was supported by microscopic observations. The probit method was used as a parametric statistical procedure to estimate LC50 and the associated 95% confidence interval. Our study showed that the early developmental stages of Lymnaea stagnalis are very sensitive bioindicators, making it possible to detect even very low levels of the above-mentioned water toxicants. The highest toxicity is shown by ammonium hydroxide with LC50/24h values, respectively, 24.27 for embryos and 24.72 for juvenile forms, and the lowest is shown by nitric acid ions with LC50/24h values, respectively, 105.19 for embryos and 170.47 for juvenile forms. It is highly cost-effective due to simple and efficient breeding and the small size of the organisms in the bioassay population. Compared with Daphnia magna, relatively low concentrations of toxicants caused a lethal effect on embryonic and juvenile organisms of the great pond snail. Owing to their common occurrence and sensitivity, early developmental forms of Lymnaea stagnalis can be a valuable new tool in biomonitoring of the freshwater environment.

  6. Caring for a Person Who Has Intellectual or Developmental Disabilities

    Science.gov (United States)

    ... and Prevention, Developmental Disabilities U.S. National Library of Medicine, Developmental Disabilities Last Updated: October 2017 This article was contributed by: familydoctor.org editorial staff Categories: ...

  7. Developmental Disorders in Children – Importance of Parent Training Interventions

    National Research Council Canada - National Science Library

    Beena Johnson

    2018-01-01

    ... and specific learning disorder are the common developmental disorders seen in children. The key interventions for the management of developmental disorders in children are parent training interventions...

  8. Toxicity of energy drinks.

    Science.gov (United States)

    Wolk, Brian J; Ganetsky, Michael; Babu, Kavita M

    2012-04-01

    'Energy drinks', 'energy shots' and other energy products have exploded in popularity in the past several years; however, their use is not without risk. Caffeine is the main active ingredient in energy drinks, and excessive consumption may acutely cause caffeine intoxication, resulting in tachycardia, vomiting, cardiac arrhythmias, seizures, and death. The effects of chronic high-dose caffeine intake in children and adolescents are unknown. Caffeine may raise blood pressure, disrupt adolescent sleep patterns, exacerbate psychiatric disease, cause physiologic dependence, and increase the risk of subsequent addiction. Coingestion of caffeine and ethanol has been associated with increased risk-taking behaviors, harm to adolescent users, impaired driving, and increased use of other illicit substances. The toxicity of ingredients often present in energy drinks, such as taurine, niacin, and pyridoxine, is less well defined. Recent and significant literature describing adverse events associated with energy drink use are reviewed. Although prior studies have examined the effects of caffeine in adolescents, energy drinks should be considered a novel exposure. The high doses of caffeine, often in combination with ingredients with unknown safety profiles, mandates urgent research on the safety of energy drink use in children and adolescents. Regulation of pediatric energy drink use may be a necessary step once the health effects are further characterized.

  9. Overcoming ammonium toxicity.

    Science.gov (United States)

    Bittsánszky, András; Pilinszky, Katalin; Gyulai, Gábor; Komives, Tamas

    2015-02-01

    Ammonia (ammonium ion under physiological conditions) is one of the key nitrogen sources in cellular amino acid biosynthesis. It is continuously produced in living organisms by a number of biochemical processes, but its accumulation in cells leads to tissue damage. Current knowledge suggests that a few enzymes and transporters are responsible for maintaining the delicate balance of ammonium fluxes in plant tissues. In this study we analyze the data in the scientific literature and the publicly available information on the dozens of biochemical reactions in which endogenous ammonium is produced or consumed, the enzymes that catalyze them, and the enzyme and transporter mutants listed in plant metabolic and genetic databases (Plant Metabolic Network, TAIR, and Genevestigator). Our compiled data show a surprisingly high number of little-studied reactions that might influence cellular ammonium concentrations. The role of ammonium in apoptosis, its relation to oxidative stress, and alterations in ammonium metabolism induced by environmental stress need to be explored in order to develop methods to manage ammonium toxicity. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  10. Macroevolutionary developmental biology: Embryos, fossils, and phylogenies.

    Science.gov (United States)

    Organ, Chris L; Cooper, Lisa Noelle; Hieronymus, Tobin L

    2015-10-01

    The field of evolutionary developmental biology is broadly focused on identifying the genetic and developmental mechanisms underlying morphological diversity. Connecting the genotype with the phenotype means that evo-devo research often considers a wide range of evidence, from genetics and morphology to fossils. In this commentary, we provide an overview and framework for integrating fossil ontogenetic data with developmental data using phylogenetic comparative methods to test macroevolutionary hypotheses. We survey the vertebrate fossil record of preserved embryos and discuss how phylogenetic comparative methods can integrate data from developmental genetics and paleontology. Fossil embryos provide limited, yet critical, developmental data from deep time. They help constrain when developmental innovations first appeared during the history of life and also reveal the order in which related morphologies evolved. Phylogenetic comparative methods provide a powerful statistical approach that allows evo-devo researchers to infer the presence of nonpreserved developmental traits in fossil species and to detect discordant evolutionary patterns and processes across levels of biological organization. © 2015 Wiley Periodicals, Inc.

  11. Developmental milestones among Aboriginal children in Canada.

    Science.gov (United States)

    Findlay, Leanne; Kohen, Dafna; Miller, Anton

    2014-05-01

    Windows of achievement provide age ranges for the attainment of early developmental skills. Group-specific research is warranted given that development may be influenced by social or cultural factors. To examine developmental milestones for Inuit, Métis and off-reserve First Nation children in Canada, based on developmental domains collected from the 2006 Aboriginal Children's Survey. Sociodemographic and health predictors of risk for developmental delay were also examined. The ranges in which children achieve certain developmental milestones are presented. Gross motor and self-help skills were found to be achieved earlier (across the three Aboriginal groups), whereas language skills were achieved slightly later than in Canadian children in general. Furthermore, health factors (eg, low birth weight, chronic health conditions) were associated with late achievement of developmental outcomes even when sociodemographic characteristics were considered. Findings suggest that the timing of milestone achievement may differ for Aboriginal children, highlighting the importance of establishing culturally specific norms and standards rather than relying on those derived from general populations. This information may be useful for practitioners and parents interested in identifying the age ranges for development, as well as age ranges indicating potential for developmental risk and opportunities for early intervention among Aboriginal children.

  12. Comparative toxicities of benzene, chlorobenzene, and dichlorobenzenes to sea urchin embryos and sperm

    Energy Technology Data Exchange (ETDEWEB)

    Pagano, G.; Cipollaro, M.; Corsale, G.; Esposito, A.; Giordano, G.G.; Ragucci, E.; Trieff, N.M.

    1988-04-01

    The leukemogenicity and myelotoxicity of benzene are well-known and the major cause of benzene's banning from most industrial applications. Various benzene derivatives such as alkylbenzenes and chlorobenzenes, however, continue to be used as chemical intermediates, solvents, pesticides, etc. in spite of incomplete knowledge of their chronic toxicity. This study was designed to obtain comparative data on developmental, genetic and reproductive toxicities of benzene (B), chlorobenzene (CB) and dichlorobenzenes (o-, m-, and p-DCB) in the sea urchin bioassay. This test system, permits observation of a number of biological endpoints on mitotic activity, embryogenesis and fertilization, and thus provides multi-parametric toxicological data on xenobiotics.

  13. Non-animal Replacements for Acute Toxicity Testing.

    Science.gov (United States)

    Barker-Treasure, Carol; Coll, Kevin; Belot, Nathalie; Longmore, Chris; Bygrave, Karl; Avey, Suzanne; Clothier, Richard

    2015-07-01

    Current approaches to predicting adverse effects in humans from acute toxic exposure to cosmetic ingredients still heavily necessitate the use of animals under EU legislation, particularly in the context of the REACH system, when cosmetic ingredients are also destined for use in other industries. These include the LD50 test, the Up-and-Down Procedure and the Fixed Dose Procedure, which are regarded as having notable scientific deficiencies and low transferability to humans. By expanding on previous in vitro tests, such as the animal cell-based 3T3 Neutral Red Uptake (NRU) assay, this project aims to develop a truly animal-free predictive test for the acute toxicity of cosmetic ingredients in humans, by using human-derived cells and a prediction model that does not rely on animal data. The project, funded by Innovate UK, will incorporate the NRU assay with human dermal fibroblasts in animal product-free culture, to generate an in vitro protocol that can be validated as an accepted replacement for the currently available in vivo tests. To date, the project has successfully completed an assessment of the robustness and reproducibility of the method, by using sodium lauryl sulphate (SLS) as a positive control, and displaying analogous results to those of the original studies with mouse 3T3 cells. Currently, the testing of five known ingredients from key groups (a surfactant, a preservative, a fragrance, a colour and an emulsifier) is under way. The testing consists of initial range-finding runs followed by three valid runs of a main experiment with the appropriate concentration ranges, to generate IC50 values. Expanded blind trials of 20 ingredients will follow. Early results indicate that this human cell-based test holds the potential to replace aspects of in vivo animal acute toxicity testing, particularly with reference to cosmetic ingredients. 2015 FRAME.

  14. Mitochondrial fusion, fission, and mitochondrial toxicity.

    Science.gov (United States)

    Meyer, Joel N; Leuthner, Tess C; Luz, Anthony L

    2017-08-05

    Mitochondrial dynamics are regulated by two sets of opposed processes: mitochondrial fusion and fission, and mitochondrial biogenesis and degradation (including mitophagy), as well as processes such as intracellular transport. These processes maintain mitochondrial homeostasis, regulate mitochondrial form, volume and function, and are increasingly understood to be critical components of the cellular stress response. Mitochondrial dynamics vary based on developmental stage and age, cell type, environmental factors, and genetic background. Indeed, many mitochondrial homeostasis genes are human disease genes. Emerging evidence indicates that deficiencies in these genes often sensitize to environmental exposures, yet can also be protective under certain circumstances. Inhibition of mitochondrial dynamics also affects elimination of irreparable mitochondrial DNA (mtDNA) damage and transmission of mtDNA mutations. We briefly review the basic biology of mitodynamic processes with a focus on mitochondrial fusion and fission, discuss what is known and unknown regarding how these processes respond to chemical and other stressors, and review the literature on interactions between mitochondrial toxicity and genetic variation in mitochondrial fusion and fission genes. Finally, we suggest areas for future research, including elucidating the full range of mitodynamic responses from low to high-level exposures, and from acute to chronic exposures; detailed examination of the physiological consequences of mitodynamic alterations in different cell types; mechanism-based testing of mitotoxicant interactions with interindividual variability in mitodynamics processes; and incorporating other environmental variables that affect mitochondria, such as diet and exercise. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. The developmental genetics of biological robustness.

    Science.gov (United States)

    Mestek Boukhibar, Lamia; Barkoulas, Michalis

    2016-04-01

    Living organisms are continuously confronted with perturbations, such as environmental changes that include fluctuations in temperature and nutrient availability, or genetic changes such as mutations. While some developmental systems are affected by such challenges and display variation in phenotypic traits, others continue consistently to produce invariable phenotypes despite perturbation. This ability of a living system to maintain an invariable phenotype in the face of perturbations is termed developmental robustness. Biological robustness is a phenomenon observed across phyla, and studying its mechanisms is central to deciphering the genotype-phenotype relationship. Recent work in yeast, animals and plants has shown that robustness is genetically controlled and has started to reveal the underlying mechinisms behind it. Studying biological robustness involves focusing on an important property of developmental traits, which is the phenotypic distribution within a population. This is often neglected because the vast majority of developmental biology studies instead focus on population aggregates, such as trait averages. By drawing on findings in animals and yeast, this Viewpoint considers how studies on plant developmental robustness may benefit from strict definitions of what is the developmental system of choice and what is the relevant perturbation, and also from clear distinctions between gene effects on the trait mean and the trait variance. Recent advances in quantitative developmental biology and high-throughput phenotyping now allow the design of targeted genetic screens to identify genes that amplify or restrict developmental trait variance and to study how variation propagates across different phenotypic levels in biological systems. The molecular characterization of more quantitative trait loci affecting trait variance will provide further insights into the evolution of genes modulating developmental robustness. The study of robustness mechanisms in

  16. Specific Developmental Disorders of Scholastic Skills

    Directory of Open Access Journals (Sweden)

    Beena Johnson

    2015-07-01

    Full Text Available Several factors contribute to scholastic backwardness in children. Causes include specific developmental disorders of scholastic skills, low intelligence, chronic illnesses, family dysfunction, social problems, attention deficits, and emotional disorders. Children with specific developmental disorders of scholastic skills experience significant impairment in the acquisition of reading, writing and mathematical skills. If not remedied at the earliest, these children are at risk of developing severe stress related disorders. There is high comorbidity of behaviour disorders and emotional disorders in these children. Hence early intensive remedial education is essential in the management of children with specific developmental disorders of scholastic skills.

  17. Information Propagation in Developmental Enhancers

    Science.gov (United States)

    Jena, Siddhartha; Levine, Michael

    Rather than encoding information about protein sequence, certain lengths of noncoding DNA, called enhancers, interact with protein machinery such as transcription factors to precisely regulate gene expression. Enhancers have been studied extensively in the fruit fly Drosophila melanogaster, where they regulate the expression of developmental genes that establish the blueprint of the adult fly. It has been suggested that enhancer sequences possess a specific but unknown syntax with regards to the placement and strength of transcription factor binding sites. Moreover, studies in divergent fly species have shown that compensatory evolution allows for maintenance of enhancer functionality despite considerable variation in primary DNA sequence. Here, the possible role of enhancers as signal processing modules is studied as a way of explaining these two findings. We first demonstrate how this framework can be used to explain the fine-tuned spatiotemporal dynamics of gene expression. We then explore the evolutionary pressure on enhancer sequences and the resulting emergence of enhancers that are linked by compensatory mutations. This study provides a possible mechanism for the function of multiple enhancers linked to a single gene.

  18. Executive Functions in Developmental Dyslexia

    Directory of Open Access Journals (Sweden)

    Pamela eVarvara

    2014-03-01

    Full Text Available The present study was aimed at investigating different aspects of Executive Functions (EF in children with Developmental Dyslexia (DD.A neuropsychological battery tapping verbal fluency, spoonerism, attention, verbal shifting, short-term and working memory was used to assess 60 children with DD and 65 with typical reading abilities.Compared to their controls, children with DD showed deficits in several EF domains such as verbal categorical and phonological fluency, visual-spatial and auditory attention, spoonerism, verbal and visual short-term memory, and verbal working memory. Moreover, exploring predictive relationships between EF measures and reading, we found that spoonerism abilities better explained word and non-word reading deficits. Although to a lesser extent, auditory and visual-spatial attention also explained the increased percentage of variance related to reading deficit.EF deficits found in DD are interpreted as an expression of a deficient functioning of the Central Executive System and are discussed in the context of the recent temporal sampling theory.

  19. Epidemiology of pervasive developmental disorders.

    Science.gov (United States)

    Fombonne, Eric

    2009-06-01

    This article reviews the results of 43 studies published since 1966 that provided estimates for the prevalence of pervasive developmental disorders (PDDs), including autistic disorder, Asperger disorder, PDD not otherwise specified, and childhood disintegrative disorder. The prevalence of autistic disorder has increased in recent surveys and current estimates of prevalence are around 20/10,000, whereas the prevalence for PDD not otherwise specified is around 30/10,000 in recent surveys. Prevalence of Asperger disorder is much lower than that for autistic disorder and childhood disintegrative disorder is a very rare disorder with a prevalence of about 2/100,000. Combined all together, recent studies that have examined the whole spectrum of PDDs have consistently provided estimates in the 60-70/10,000 range, making PDD one of the most frequent childhood neurodevelopmental disorders. The meaning of the increase in prevalence in recent decades is reviewed. There is evidence that the broadening of the concept, the expansion of diagnostic criteria, the development of services, and improved awareness of the condition have played a major role in explaining this increase, although it cannot be ruled out that other factors might have also contributed to that trend.

  20. Pervasive Developmental Disorder with Age?

    Directory of Open Access Journals (Sweden)

    M. Balfe

    2011-01-01

    Full Text Available A survey was undertaken to investigate the prevalence of high-functioning pervasive developmental disorder (HFPDD in a community sample of teenagers and adults aged 13 and above in the city of Sheffield, UK. 112 possible and definite cases were found, of whom 65 (57% had a previous diagnosis. The detected prevalence of possible or definite HFPDD was found to be 0.24 per 1000 of the population of Sheffield city aged 13 or over, but the prevalence by year of age fell from a maximum of 1.1 per 1000 in the group aged 13 to 14 years old (1 young adult in every 900 in this age group to 0.03 per 1000 in the over 60s (1 person in every 38500 in this age group. The results of this study are preliminary and need follow-up investigation in larger studies. We suggest several explanations for the findings, including reduced willingness to participate in a study as people get older, increased ascertainment in younger people, and increased mortality. Another contributory factor might be that the prevalence of high-functioning pervasive development disorder may decline with age. This raises the possibility that AS symptoms might become subclinical in adulthood in a proportion of people with HFPDD.