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Sample records for repeated toxicity tests

  1. 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.

  2. [Twenty-eight days repeated dose toxicity test of N-(fluorodichloromethylthio)phthalimide in rats].

    Science.gov (United States)

    Matsushima, Y; Tsuda, M; Naito, K; Saitoh, M; Isama, K; Ikarashi, Y; Kawasaki, Y; Momma, J; Kitajima, S; Kaniwa, M

    1995-01-01

    N-(Fluorodichloromethylthio)phthalimide (Fluor-folpet) has been widely used as an anti-mold and anti-bacterial agent. In this study, 28 days repeated-dose oral toxicity study of fluor-folpet was carried out in Slc:Wistar rats. An oral toxicity study for fluor-folpet, the twenty-eight days test, repeated-dose, oral administration, was performed as follows: Five week-old rats, male and female, 10 rats, each/group, were treated with intragastric administration of fluor-folpet with a dose of 0 (1% Sodium CMC, control), 20, 80 and 320 mg/kg, body weight. Recovery test, for 14 days after the last treatment, was examined for the control and the 320 mg/kg groups. The 320 mg/kg groups, both males and females, showed significantly reduced their body-weight gain compared with the control group. In the 320 mg/kg group, five out of 20 male rats and four out of 20 female rats died from dyspnea during the treatment period. In the female rats in the 320 mg/kg group, serum ChE level was decreased to 50% of control level and gamma-GT was increased in a dose-dependent manner, but these serum levels recovered after 14 days non-treatment period. No histopathological change, relating to the treatment, in liver was observed. Increased weight of the kidney and vacuolation in renal tubules were found in both sexes of 320 mg/kg group. Hyperkeratosis and hyperplasia of the stomach epithelium were observed at the dose more than 80 mg/kg in male, and more than 20 mg/kg in female. A supplemental study, repeated-dose, oral administration in rats carried out to examine the dyspnea revealed that severe acute toxic damages in epithelium of nasal cavity and meatus nasopharyngeus were induced by intragastric administration of fluor-folpet. Fluor-folpet is shown to be cytotoxic. In conclusion, the no-observed-effect level (NOEL) for fluor-folpet was not found under the experimental conditions employed in this repeated-dose toxicity study.

  3. An abbreviated repeat dose and reproductive/developmental toxicity test for high production volume chemicals

    Energy Technology Data Exchange (ETDEWEB)

    Scala, R.A.; Bevan, C.; Beyer, B.K. (Exxon Biomedical Sciences, Inc., East Millstone, NJ (United States))

    1992-08-01

    A novel protocol is described for obtaining preliminary data on repeated dose systemic effects and reproductive/developmental toxicity. The test protocol was developed by a group of experts at the request of the U.S. Environmental Protection Agency (EPA) for use as part of a Screening Information Data Set on high production volume chemicals. Interest in this protocol is shared by several regulatory agencies, including the Organization for Economic Cooperation, the European Community, and the EPA. To validate the study protocol, ethylene glycol monomethyl ether (EGME) was used. After a dosing period of approximately 6 weeks, EGME showed both systemic and reproductive/developmental effects similar to those previously reported using standard protocols. Thus, this test protocol may be used as a screening tool for high production volume chemicals.

  4. Study of four week repeated dose toxic test of Sweet Bee Venom in Beagle Dogs

    Directory of Open Access Journals (Sweden)

    Jae-Seuk Park

    2010-12-01

    Full Text Available Objectives: This study was performed to analyse four week repeated dose toxicity of Sweet Bee Venom(Sweet BV extracted from the bee venom in Beagle dogs. Methods: All experiments were conducted under the regulations of Good Laboratory Practice (GLP at Biotoxtech Company, a non-clinical study authorized institution. Male and female Beagle dogs of 5-6 months old were chosen for the pilot study of four week repeated dose toxicity of Sweet BV which was administered at the level of 0.56㎎/㎏ body weight which is eighty times higher than the clinical application dosage as the high dosage, followed by 0.28 and 0.14㎎/㎏ as midium and low dosage, respectively. Equal amount of excipient(normal saline to the Sweet BV experiment groups was administered as the control group every day for four weeks. Results: 1. No mortality was witnessed in all of the experiment groups. 2. All experiment groups were appealed pain sense in the treating time compared to the control group, and hyperemia and movement disorder were observed around the area of administration in all experiment groups, and higher occurrence in the higher dosage treatment. 3. For weight measurement, Neither male nor female groups showed significant changes. 4. In the urine analysis, CBC and biochemistry didn't show any significant changes in the experiment groups compared with control group. 5. For weight measurement of organs, experiment groups didn't show any significant changes compared with control group. 6. To verify abnormalities of organs and tissues, thigh muscle which treated with Sweet BV, cerebrum, liver, lung, kidney, and spinal cords were removed and conducted histologocal observation with H-E staining. In the histologocal observation of thigh muscle, cell infiltration, inflammatory, degeneration, necrosis of muscle fiber, and fibrosis were found in both thigh tissue. And the changes were depend on the dose of Sweet BV. But another organs were not detected in any abnormalities. 7

  5. The ToxBank Data Warehouse: Supporting the Replacement of In Vivo Repeated Dose Systemic Toxicity Testing.

    Science.gov (United States)

    Kohonen, Pekka; Benfenati, Emilio; Bower, David; Ceder, Rebecca; Crump, Michael; Cross, Kevin; Grafström, Roland C; Healy, Lyn; Helma, Christoph; Jeliazkova, Nina; Jeliazkov, Vedrin; Maggioni, Silvia; Miller, Scott; Myatt, Glenn; Rautenberg, Michael; Stacey, Glyn; Willighagen, Egon; Wiseman, Jeff; Hardy, Barry

    2013-01-01

    The aim of the SEURAT-1 (Safety Evaluation Ultimately Replacing Animal Testing-1) research cluster, comprised of seven EU FP7 Health projects co-financed by Cosmetics Europe, is to generate a proof-of-concept to show how the latest technologies, systems toxicology and toxicogenomics can be combined to deliver a test replacement for repeated dose systemic toxicity testing on animals. The SEURAT-1 strategy is to adopt a mode-of-action framework to describe repeated dose toxicity, combining in vitro and in silico methods to derive predictions of in vivo toxicity responses. ToxBank is the cross-cluster infrastructure project whose activities include the development of a data warehouse to provide a web-accessible shared repository of research data and protocols, a physical compounds repository, reference or "gold compounds" for use across the cluster (available via wiki.toxbank.net), and a reference resource for biomaterials. Core technologies used in the data warehouse include the ISA-Tab universal data exchange format, REpresentational State Transfer (REST) web services, the W3C Resource Description Framework (RDF) and the OpenTox standards. We describe the design of the data warehouse based on cluster requirements, the implementation based on open standards, and finally the underlying concepts and initial results of a data analysis utilizing public data related to the gold compounds. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Repeated Intramuscular-dose Toxicity Test of Water-soluble Carthami Flos (WCF Pharmacopuncture in Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Yoo-min Choi

    2015-03-01

    Full Text Available Objectives: Water-soluble carthami flos (WCF is a new mixture of Carthami flos (CF pharmacopuncture. We conducted a 4-week toxicity test of repeated intramuscular injections of WCF in Sprague-Dawley rats. Methods: Forty male and 40 female rats were divided into 4 groups of 10 male and 10 female SD rats: The control group received 0.5 mL/animal/day of normal saline whereas the three experimental groups received WCF at doses of 0.125, 0.25, and 0.5 mL/animal/day, respectively. For 4 weeks, the solutions were injected into the femoral muscle of the rats alternating from side to side. Clinical signs, body weights, and food consumption were observed; opthalmological examinations and urinalyses were performed. On day 29, blood samples were taken for hematological and clinical chemistry analyses. Then, necropsy was conducted in all animals to observe weights and external and histopathological changes in the bodily organs. All data were tested using a statistical analysis system (SAS. Results: No deaths were observed. Temporary irregular respiration was observed in male rats of the experimental group for the first 10 days. Body weights, food consumptions, opthalmological examinations, urinalyses, clinical chemistry analyses, organ weights and necropsy produced no findings with toxicological meaning. In the hematological analysis, delay of prothrombin time (PT was observed in male rats of the 0.25- and the 0.5-mL/animal/day groups. In the histopathological test, a dose-dependent inflammatory cell infiltration into the fascia and panniculitis in perimuscular tissues was observed in all animals of the experimental groups. However, those symptoms were limited to local injection points. No toxicological meanings, except localized changes, were noted. Conclusion: WCF solution has no significant toxicological meaning, but does produce localized symptoms. No observed adverse effect level (NOAEL of WCF in male and female rats is expected for doses over 0.5 mL/animal/day.

  7. Construction of the Database of Rat Repeated-dose Toxicity Tests of Pesticides for the Toxicological Characterization of Hepatocyte Hypertrophy.

    Science.gov (United States)

    Masuda, Akane; Masuda, Miyabi; Kawano, Takuya; Kitsunai, Yoko; Nakayama, Haruka; Nakajima, Hiroyuki; Kojima, Hiroyuki; Kitamura, Shigeyuki; Uramaru, Naoto; Hosaka, Takuomi; Sasaki, Takamitsu; Yoshinari, Kouichi

    2017-01-01

     Liver and hepatocyte hypertrophy can be induced by exposure to chemical compounds, but the mechanisms and toxicological characteristics of these phenomena have not yet been investigated extensively. In particular, it remains unclear whether the hepatocyte hypertrophy induced by chemical compounds should be judged as an adaptive response or an adverse effect. Thus, understanding of the toxicological characteristics of hepatocyte hypertrophy is of great importance to the safety evaluation of pesticides and other chemical compounds. To this end, we have constructed a database of potentially toxic pesticides. Using risk assessment reports of pesticides that are publicly available from the Food Safety Commission of Japan, we extracted all observations/findings that were based on 90-day subacute toxicity tests and 2-year chronic toxicity and carcinogenicity tests in rats. Analysis of the database revealed that hepatocyte hypertrophy was observed for 37-47% of the pesticides investigated (varying depending on sex and testing period), and that centrilobular hepatocyte hypertrophy was the most frequent among the various types of hepatocyte hypertrophy in both the 90-day and 2-year studies. The database constructed in this study enables us to investigate the relationships between hepatocyte hypertrophy and other toxicological observations/findings, and thus will be useful for characterizing hepatocyte hypertrophy.

  8. Duct Leakage Repeatability Testing

    Energy Technology Data Exchange (ETDEWEB)

    Walker, Iain [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Sherman, Max [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2014-01-01

    Duct leakage often needs to be measured to demonstrate compliance with requirements or to determine energy or Indoor Air Quality (IAQ) impacts. Testing is often done using standards such as ASTM E1554 (ASTM 2013) or California Title 24 (California Energy Commission 2013 & 2013b), but there are several choices of methods available within the accepted standards. Determining which method to use or not use requires an evaluation of those methods in the context of the particular needs. Three factors that are important considerations are the cost of the measurement, the accuracy of the measurement and the repeatability of the measurement. The purpose of this report is to evaluate the repeatability of the three most significant measurement techniques using data from the literature and recently obtained field data. We will also briefly discuss the first two factors. The main question to be answered by this study is to determine if differences in the repeatability of these tests methods is sufficient to indicate that any of these methods is so poor that it should be excluded from consideration as an allowed procedure in codes and standards.

  9. Genes and pathways affected by CAG-repeat RNA-based toxicity in Drosophila.

    Science.gov (United States)

    Shieh, Shin-Yi; Bonini, Nancy M

    2011-12-15

    Spinocerebellar ataxia type 3 is one of the polyglutamine (polyQ) diseases, which are caused by a CAG-repeat expansion within the coding region of the associated genes. The CAG repeat specifies glutamine, and the expanded polyQ domain mutation confers dominant toxicity on the protein. Traditionally, studies have focused on protein toxicity in polyQ disease mechanisms. Recent findings, however, demonstrate that the CAG-repeat RNA, which encodes the toxic polyQ protein, also contributes to the disease in Drosophila. To provide insights into the nature of the RNA toxicity, we extracted brain-enriched RNA from flies expressing a toxic CAG-repeat mRNA (CAG100) and a non-toxic interrupted CAA/G mRNA repeat (CAA/G105) for microarray analysis. This approach identified 160 genes that are differentially expressed specifically in CAG100 flies. Functional annotation clustering analysis revealed several broad ontologies enriched in the CAG100 gene list, including iron ion binding and nucleotide binding. Intriguingly, transcripts for the Hsp70 genes, a powerful suppressor of polyQ and other human neurodegenerative diseases, were also upregulated. We therefore tested and showed that upregulation of heat shock protein 70 mitigates CAG-repeat RNA toxicity. We then assessed whether other modifiers of the pathogenic, expanded Ataxin-3 polyQ protein could also modify the CAG-repeat RNA toxicity. This approach identified the co-chaperone Tpr2, the transcriptional regulator Dpld, and the RNA-binding protein Orb2 as modifiers of both polyQ protein toxicity and CAG-repeat RNA-based toxicity. These findings suggest an overlap in the mechanisms of RNA and protein-based toxicity, providing insights into the pathogenicity of the RNA in polyQ disease.

  10. Evaluation of a repeated dose liver micronucleus assay in rats treated with two genotoxic hepatocarcinogens, dimethylnitrosamine and 2-acetylaminofluorene: the possibility of integrating micronucleus tests with multiple tissues into a repeated dose general toxicity study.

    Science.gov (United States)

    Takashima, Rie; Takasawa, Hironao; Kawasako, Kazufumi; Ohyama, Wakako; Okada, Emiko; Narumi, Kazunori; Fujiishi, Yohei; Wako, Yumi; Yasunaga, Katsuaki; Hattori, Akiko; Kawabata, Masayoshi; Nakadate, Kiyoko; Nakagawa, Munehiro; Hamada, Shuichi

    2015-03-01

    As part of a collaborative study by the Collaborative Study Group for Micronucleus Test (CSGMT) of the Mammalian Mutagenicity Study Group (MMS) in the Japanese Environmental Mutagen Society (JEMS), the present study evaluated the effectiveness of the repeated dose liver micronucleus (RDLMN) assay. Two genotoxic hepatocarcinogens, dimethylnitrosamine (DMN) and 2-acetylaminofluorene (2-AAF), were administered orally to male rats (6 weeks old at the initial dosing) once daily for 14 and 28 days to evaluate the micronucleus (MN) inducibility in the liver. In addition, these chemicals were evaluated for MN inducibility in the bone marrow (BM) and gastrointestinal (GI) tract, i.e. glandular stomach and colon of the same animals used in the RDLMN assay. As a result, both chemicals produced positive results in the liver, although a weak positive response was given by 2-AAF. DMN gave negative results in the tissues other than the liver. 2-AAF produced positive responses in the BM and glandular stomach, and a prominent response was particularly observed in the glandular stomach, which is directly exposed to the test chemicals by gavage. The present results suggest that the RDLMN assay is a useful method for detecting genotoxic hepatocarcinogens, and that it is especially effective for evaluating test chemicals, such as DMN, undetectable by the BM and GI tract MN assay. Moreover, the results in this investigation indicate that the use of multiple tissues in the study integrating the MN tests is more effective than using a single tissue, for detection of the MN induction produced by chemical exposure to rats, and helps to determine the characteristics of the test chemicals.

  11. Strengthening concept learning by repeated testing.

    Science.gov (United States)

    Wiklund-Hörnqvist, Carola; Jonsson, Bert; Nyberg, Lars

    2014-02-01

    The aim of this study was to examine whether repeated testing with feedback benefits learning compared to rereading of introductory psychology key-concepts in an educational context. The testing effect was examined immediately after practice, after 18 days, and at a five-week delay in a sample of undergraduate students (n = 83). The results revealed that repeated testing with feedback significantly enhanced learning compared to rereading at all delays, demonstrating that repeated retrieval enhances retention compared to repeated encoding in the short- and the long-term. In addition, the effect of repeated testing was beneficial for students irrespectively of working memory capacity. It is argued that teaching methods involving repeated retrieval are important to consider by the educational system.

  12. Evaluation of statistical tools used in short-term repeated dose administration toxicity studies with rodents.

    Science.gov (United States)

    Kobayashi, Katsumi; Pillai, K Sadasivan; Sakuratani, Yuki; Abe, Takemaru; Kamata, Eiichi; Hayashi, Makoto

    2008-02-01

    In order to know the different statistical tools used to analyze the data obtained from twenty-eight-day repeated dose oral toxicity studies with rodents and the impact of these statistical tools on interpretation of data obtained from the studies, study reports of 122 numbers of twenty-eight-day repeated dose oral toxicity studies conducted in rats were examined. It was found that both complex and easy routes of decision trees were followed for the analysis of the quantitative data. These tools include Scheffe's test, non-parametric type Dunnett's and Scheffe's tests with very low power. Few studies used the non-parametric Dunnett type test and Mann-Whitney's U test. Though Chi-square and Fisher's tests are widely used for analysis of qualitative data, their sensitivity to detect a treatment-related effect is questionable. Mann-Whitney's U test has better sensitivity to analyze qualitative data than the chi-square and Fisher's tests. We propose Dunnett's test for analysis of quantitative data obtained from twenty-eight-day repeated dose oral toxicity tests and for qualitative data, Mann-Whitney's U test. For both tests, one-sided test with p=0.05 may be applied.

  13. Why Do Students Repeat Admissions Tests?

    Science.gov (United States)

    Jones, Martha S.

    Attitudes and beliefs about the admissions process, especially the role of standardized testing in admissions, were examined for students who took a standardized admissions test more than once. Their attitudes were compared with those of students who did not repeat the test. About 200 preveterinary students who had taken the Veterinary Aptitude…

  14. Toxic Test Chambers

    Data.gov (United States)

    Federal Laboratory Consortium — Description/History: Hazardous material test facility Both facilities have 16,000 cubic foot chambers, equipped with 5000 CFM CBR filter systems with an air change...

  15. Distinct C9orf72-Associated Dipeptide Repeat Structures Correlate with Neuronal Toxicity

    Science.gov (United States)

    Krans, Amy; Sawaya, Michael R.; Paulson, Henry L.; Todd, Peter K.; Barmada, Sami J.; Ivanova, Magdalena I.

    2016-01-01

    Hexanucleotide repeat expansions in C9orf72 are the most common inherited cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The expansions elicit toxicity in part through repeat-associated non-AUG (RAN) translation of the intronic (GGGGCC)n sequence into dipeptide repeat-containing proteins (DPRs). Little is known, however, about the structural characteristics and aggregation propensities of the dipeptide units comprising DPRs. To address this question, we synthesized dipeptide units corresponding to the three sense-strand RAN translation products, analyzed their structures by circular dichroism, electron microscopy and dye binding assays, and assessed their relative toxicity when applied to primary cortical neurons. Short, glycine-arginine (GR)3 dipeptides formed spherical aggregates and selectively reduced neuronal survival compared to glycine-alanine (GA)3 and glycine-proline (GP)3 dipeptides. Doubling peptide length had little effect on the structure of GR or GP peptides, but (GA)6 peptides formed β-sheet rich aggregates that bound thioflavin T and Congo red yet lacked the typical fibrillar morphology of amyloids. Aging of (GA)6 dipeptides increased their β-sheet content and enhanced their toxicity when applied to neurons. We also observed that the relative toxicity of each tested dipeptide was proportional to peptide internalization. Our results demonstrate that different C9orf72-related dipeptides exhibit distinct structural properties that correlate with their relative toxicity. PMID:27776165

  16. Toxicity testing using Caenorhabditis elegans

    Energy Technology Data Exchange (ETDEWEB)

    Middendorf, P.J.; Dusenbery, D.B. [Georgia Institute of Technology, Atlanta, GA (United States); Williams, P.L. [Univ. of Georgia, Athens, GA (United States)

    1995-12-31

    Caenorhabditis elegans is a small free-living nematode that is representative of what may be the most abundant animal group. It has been promoted as a possible model organism for toxicity testing in the laboratory and in field evaluations in part because more is known about its biology than any other animal, Toxicity tests using C. elegans have been developed with lethality, reproduction, and behavior as end points. The tests have also been developed to varying degrees using standard laboratory media, water, and soil. The results of the tests when exposing C. elegans to a variety of metals, inorganic, and organic compounds indicate it is typically at least as sensitive as other species currently used, such as Daphnia and earthworms, and is generally much easier to maintain in the laboratory. The advantages and disadvantages of C. elegans and the state of development of the tests will be discussed.

  17. A Miniscale Algal Toxicity Test

    DEFF Research Database (Denmark)

    Arensberg, Pia; Hemmingsen, Vicky H.; Nyholm, Niels

    1995-01-01

    A simple miniscale (approx. 1 - 2.5 ml) toxicity test procedure with the freshwater green algaSelenastrum capricornutum is described. The procedure fulfils the validity criteria of the ISO (International Association for Standardization) standard test protocol. Practically identical concentration...... facilitates CO2 mass transfer. Uniform illumination of the individual units of a minitest setup is obtained readily due to the small area that has to be illuminated. Using the rapidly growing green alga S. capricornutum as test organism, it is proposed generally to reduce the standard test duration from 3...... and test volumes (down to 1 ml) could also be used. Tissue culture treated polystyrene microplates were found toxic to algae and thus unusable. pH control is achieved more easily in the minitest than in larger size shake flasks due to greater turbulence and a larger surface/volume ratio which both...

  18. Acute and repeated dose toxicity studies of different β-cyclodextrin-based nanosponge formulations.

    Science.gov (United States)

    Shende, Pravin; Kulkarni, Yogesh A; Gaud, R S; Deshmukh, Kiran; Cavalli, Roberta; Trotta, Francesco; Caldera, Fabrizio

    2015-05-01

    Nanosponges (NS) show promising results in different fields such as medicine, agriculture, water purification, fire engineering and so on. The present study was designed to evaluate toxicity of different NS formulations (namely, S1-S6) synthesized with different cross-linking agents such as carbonyl diimidazole, pyromellitic dianhydride and hexamethylene diisocynate; and preparation methods in experimental animals. Acute and repeated dose toxicity studies of formulations were carried out as per OECD guidelines 423 and 407, respectively. For acute toxicity study, formulations were administered to female rats at doses of 300 and 2000 mg/kg orally. The general behaviour of the rats was continuously monitored for 1 h after dosing, periodically during the first 24 h and daily thereafter for a total of 14 days. On day 14, animals were fasted overnight, weighed, and sacrificed. After sacrification, animals were subjected to necropsy. For repeated dose toxicity study, rats of either sex were orally administered with formulations at the dose of 300 mg/kg per day for a period of 28 days. The maximally tolerated dose of all formulations was found to be 2000 mg/kg. Repeated administration of formulations for 28 days did not show any significant changes in haematological and biochemical parameters in experimental animals. These results indicate that the formulations are safe, when tested in experimental animals.

  19. Strengths and limitations of using repeat-dose toxicity studies to predict effects on fertility.

    Science.gov (United States)

    Dent, M P

    2007-08-01

    The upcoming European chemicals legislation REACH (Registration, Evaluation, and Authorisation of Chemicals) will require the risk assessment of many thousands of chemicals. It is therefore necessary to develop intelligent testing strategies to ensure that chemicals of concern are identified whilst minimising the testing of chemicals using animals. Xenobiotics may perturb the reproductive cycle, and for this reason several reproductive studies are recommended under REACH. One of the endpoints assessed in this battery of tests is mating performance and fertility. Animal tests that address this endpoint use a relatively large number of animals and are also costly in terms of resource, time, and money. If it can be shown that data from non-reproductive studies such as in-vitro or repeat-dose toxicity tests are capable of generating reliable alerts for effects on fertility then some animal testing may be avoided. Available rat sub-chronic and fertility data for 44 chemicals that have been classified by the European Union as toxic to fertility were therefore analysed for concordance of effects. Because it was considered appropriate to read across data for some chemicals these data sets were considered relevant for 73 of the 102 chemicals currently classified as toxic to reproduction (fertility) under this system. For all but 5 of these chemicals it was considered that a well-performed sub-chronic toxicity study would have detected pathology in the male, and in some cases, the female reproductive tract. Three showed evidence of direct interaction with oestrogen or androgen receptors (linuron, nonylphenol, and fenarimol). The remaining chemicals (quinomethionate and azafenidin) act by modes of action that do not require direct interaction with steroid receptors. However, both these materials caused in-utero deaths in pre-natal developmental toxicity studies, and the relatively low NOAELs and the nature of the hazard identified in the sub-chronic tests provides an alert

  20. Comparison of the repeated dose toxicity of isomers of dinitrotoluene.

    Science.gov (United States)

    Lent, Emily May; Crouse, Lee C B; Quinn, Michael J; Wallace, Shannon M

    2012-03-01

    Dinitrotoluene (DNT) is a nitroaromatic explosive used in propellant mixtures and in the production of plastics. Isomers of DNT were administered daily via oral gavage to male Sprague-Dawley rats for 14 days to determine the subacute toxicity of individual isomers of DNT. The 3,5-DNT isomer was the most toxic isomer, inducing weight loss and mortality within 3 days. Cyanosis and anemia were observed for all isomers. Exposure to 2,4-, 2,6-, and 3,5-DNT resulted in decreased testes mass and degenerative histopathological changes. Increased splenic mass was observed for 2,4-, 2,6-, and 2,5-DNT. Extramedullary hematopoiesis of the spleen was noted for all isomers, while lymphoid hyperplasia of the spleen was noted for all isomers except 2,5-DNT. Increased liver mass was observed for 2,3-DNT and 3,4-DNT. Hepatocellular lesions were observed for 2,6-DNT and 2,4-DNT. Neurotoxic effects were noted for 3,4-DNT, 2,4-DNT, and 3,5-DNT.

  1. The OSIRIS Weight of Evidence approach: ITS for the endpoints repeated-dose toxicity (RepDose ITS)

    NARCIS (Netherlands)

    Tluczkiewicz, I.; Batke, M.; Kroese, D.; Buist, H.; Aldenberg, T.; Pauné, E.; Grimm, H.; Kühne, R.; Schüürmann, G.; Mangelsdorf, I.; Escher, S.E.

    2013-01-01

    In the FP6 European project OSIRIS, Integrated Testing Strategies (ITSs) for relevant toxicological endpoints were developed to avoid new animal testing and thus to reduce time and costs. The present paper describes the development of an ITS for repeated-dose toxicity called RepDose ITS which evalua

  2. Investigation of repeated dose (90 day oral toxicity, reproductive/developmental toxicity and mutagenic potential of ‘Calebin A’

    Directory of Open Access Journals (Sweden)

    Muhammed Majeed

    2015-01-01

    Full Text Available The present work investigated repeated dose and reproductive toxicity of Calebin A in Wistar rats. A study for assessing the mutagenic potential of Calebin A through an AMES test is also described. Calebin A was orally administered to groups of 10 male and/or 10 female Wistar rats each, assigned to three dose levels (20, 50 and 100 mg/kg/body weight once daily for 90 consecutive days. None of the animals in any of the treatment/control groups exhibited any abnormal clinical signs/behavioral changes, reproductive as well as developmental parameters, or gross and microscopic changes in both male and female rats. Calebin A was also evaluated for its ability to induce reverse mutations at selected loci of Salmonella typhimurium in the presence and absence of Aroclor 1254 induced rat liver S9 cell lines. In conclusion, 100 mg/kg/d of Calebin A is not likely to produce any significant toxic effects in male and female Wistar rats and no reproductive or developmental toxicity was observed at the same dose and hence Calebin A at 100 mg/kg was determined as “No Observed Adverse Effect Level (NOAEL” under the test conditions.

  3. Bacterial and enzymatic bioassays for toxicity testing in the environment.

    Science.gov (United States)

    Bitton, G; Koopman, B

    1992-01-01

    solvents may be used to extract the toxicants. Some of the solvents used for extraction of organic chemicals are themselves toxic to bacteria (e.g., dichloromethane), requiring exchange with a less toxic solvent (e.g., ethanol, methanol, DMSO). A modification of the Microtox test allows direct assay of solid-phase samples such as sediments. The toxicity reduction evaluation (TRE) must be carried out at wastewater treatment plants whose effluents fail toxicity standards. The TREs require numerous and repeated toxicity assays, thus favoring application of microbioassays. Presently, no single microbioassay can detect all categories of environmental toxicants with equal sensitivity. Therefore, a battery of tests approach is recommended. The differential sensitivity of alternative tests may, in fact, be exploited. Further research is needed to construct strains of genetically engineered microorganisms or isolate microorganisms or enzymes that respond to specific classes of toxicants. These can be combined into batteries appropriate for different environments or test objectives.

  4. Evaluation of 90 day repeated dose oral toxicity and reproductive/developmental toxicity of 3'-hydroxypterostilbene in experimental animals.

    Science.gov (United States)

    Majeed, Muhammed; Bani, Sarang; Natarajan, Sankaran; Pandey, Anjali; S, Naveed

    2017-01-01

    3'-Hydroxypterostilbene (3'-HPT) is one of the active constituents of Sphaerophysa salsula and Pterocarpus marsupium. Despite many proposed therapeutic applications, the safety profile of 3'-HPT has not been established. The present work investigated 90 day repeated oral dose and reproductive (developmental) toxicity of 3'-HPT as a test substance in rats as per OECD guidelines. 90 day toxicity was conducted in sixty Sprague Dawley rats of each sex (120 rats), grouped into six dosage groups of 0 (control), 0 (control recovery), 20 (low dose), 80 (mid dose), 200 (high dose) and 200 (high dose recovery) mg/kg bwt/day (body weight/day) respectively. For the reproductive toxicity study forty Wistar rats of each sex (80 rats) divided into four dosage groups received 0 (vehicle control), 20 (low dose), 100 (mid dose) and 200 (high dose) mg/kg bwt/day of 3'-HPT respectively for a period of two weeks while pre-mating, mating, on the day before sacrifice, in females during pregnancy and four days of lactation period. Results showed no significant differences in body weight, food intake, absolute organ weight, haematology, with no adverse effects (toxicity) on biochemical values nor any abnormal clinical signs or behavioural changes were observed in any of the control/treatment groups, including reproductive and developmental parameters, gross and histopathological changes. In conclusion, the results suggested a No-Observed-Adverse-Effect-Level (NOAEL) of 200 mg/kg bwt/day in rats after oral administration, implying 3'-HPT did not exhibit any toxicity under the study conditions employed.

  5. The Historical Development of Animal Toxicity Testing

    OpenAIRE

    Gertler, N

    1997-01-01

    This paper traces the historical development of animal toxicity testing, from its ancient origins through the period of standardization following World War II. It explores the roots of toxicity testing in physiology and experimental medicine, drug development, and the detection and identification of poisons. The discussion then turns to the shift in focus from acute to chronic toxicity which occurred around the turn of the century. The controversy over the potential toxicity of preservatives ...

  6. Genes and pathways affected by CAG-repeat RNA-based toxicity in Drosophila

    OpenAIRE

    Shieh, Shin-Yi; Bonini, Nancy M.

    2011-01-01

    Spinocerebellar ataxia type 3 is one of the polyglutamine (polyQ) diseases, which are caused by a CAG-repeat expansion within the coding region of the associated genes. The CAG repeat specifies glutamine, and the expanded polyQ domain mutation confers dominant toxicity on the protein. Traditionally, studies have focused on protein toxicity in polyQ disease mechanisms. Recent findings, however, demonstrate that the CAG-repeat RNA, which encodes the toxic polyQ protein, also contributes to the ...

  7. BIOEQUIVALENCE APPROACH FOR WHOLE EFFLUENT TOXICITY TESTING

    Science.gov (United States)

    Increased use of whole effluent toxicity (WET) tests in the regulatory arena has brought increased concern over the statistical analysis of WET test data and the determination of toxicity. One concern is the issue of statistical power. A number of WET tests may pass the current...

  8. Estimation of acute oral toxicity using the No Observed Adverse Effect Level (NOAEL) from the 28 day repeated dose toxicity studies in rats.

    Science.gov (United States)

    Bulgheroni, Anna; Kinsner-Ovaskainen, Agnieszka; Hoffmann, Sebastian; Hartung, Thomas; Prieto, Pilar

    2009-02-01

    Acute systemic toxicity is one of the areas of particular concern due to the 2009 deadline set by the 7th Amendment of the Cosmetics Directive (76/768/EEC), which introduces a testing and marketing ban of cosmetic products with ingredients tested on animals. The scientific community is putting considerable effort into developing and validating non-animal alternatives in this area. However, it is unlikely that validated and regulatory accepted alternative methods and/or strategies will be available in March 2009. Following the initiatives undertaken in the pharmaceutical industry to waive the acute oral toxicity testing before going to clinical studies by using information from other in vivo studies, we proposed an approach to identify non-toxic compounds (LD50>2000mg/kg) using information from 28 days repeated dose toxicity studies. Taking into account the high prevalence of non-toxic substances (87%) in the New Chemicals Database, it was possible to set a NOAEL threshold of 200mg/kg that allowed the correct identification of 63% of non-toxic compounds, while testing of cosmetic ingredients.

  9. Impact of Inclusion or Exclusion of Repeaters on Test Equating

    Science.gov (United States)

    Puhan, Gautam

    2011-01-01

    This study examined the effect of including or excluding repeaters on the equating process and results. New forms of two tests were equated to their respective old forms using either all examinees or only the first timer examinees in the new form sample. Results showed that for both tests used in this study, including or excluding repeaters in the…

  10. Repeated-dose liver micronucleus test of 4,4'-methylenedianiline using young adult rats.

    Science.gov (United States)

    Sanada, Hisakazu; Koyama, Naomi; Wako, Yumi; Kawasako, Kazufumi; Hamada, Shuichi

    2015-03-01

    Liver micronucleus (MN) tests using partial hepatectomized rats or juvenile rats have been shown to be useful for the detection of hepatic carcinogens. Moreover, Narumi et al. established the repeated-dose liver MN test using young adult rats for integration into general toxicity. In the present study, in order to examine the usefulness of the repeated-dose liver MN test, we investigated MN induction with a 14 or 28 day treatment protocol using young adult rats treated with 4,4′-methylenedianiline (MDA), a known hepatic carcinogen. MDA dose-dependently induced micronuclei in hepatocytes in 14- and 28-day repeated-dose tests. However, although statistically significant increases in micronuclei were observed in bone marrow cells at two dose levels in the 14-day study, there was no dose response and no increases in micronuclei in the 28-day study. These results indicate that the evaluation of genotoxic effects using hepatocytes is effective in cases where chromosomal aberrations are not clearly detectable in bone marrow cells. Moreover, the repeated-dose liver MN test allows evaluation at a dose below the maximum tolerable dose, which is required for the conventional MN test because micronucleated hepatocytes accumulate. The repeated-dose liver MN test employed in the present study can be integrated into the spectrum of general toxicity tests without further procedural modifications.

  11. Biological assays for aquatic toxicity testing

    CSIR Research Space (South Africa)

    Slabbert, JL

    1999-10-01

    Full Text Available A number of aquatic toxicity tests have been established for South African use, which include fish and Daphnia lethality tests, microbiotests, and short-term chronic tests. Studies on effluents and surface waters showed that all the tests have a...

  12. A comparison of standard acute toxicity tests with rapid-screening toxicity tests

    Energy Technology Data Exchange (ETDEWEB)

    Toussaint, M.W. [Geo-Centers, Inc., Fort Washington, MD (United States); Shedd, T.R. [Army Biomedical Research and Development Lab., Frederick, MD (United States); Schalie, W.H. van der [Environmental Protection Agency, Washington, DC (United States); Leather, G.R. [Hood Coll., Frederick, MD (United States). Dept. of Biology

    1995-05-01

    This study compared the relative sensitivity of five inexpensive, rapid toxicity tests to the sensitivity of five standard aquatic acute toxicity tests through literature review and testing. The rapid toxicity tests utilized organisms that require little culturing or handling prior to testing: a freshwater rotifer (Branchionus calyciflorus); brine shrimp (Artemia salina); lettuce (Lactuca sativa); and two microbial tests (Photobacterium phosphoreum--Microtox{reg_sign} test, and a mixture of bacterial species--the Polytox{reg_sign} test). Standard acute toxicity test species included water fleas (Daphnia magna and Ceriodaphnia dubia), green algae (Selenastrum capricornutum), fathead minnows (Pimephales promelas), and mysid shrimp (Mysidopsis bahia). Sensitivity comparisons between rapid and standard acute toxicity tests were based on LC50/EC50 data from 11 test chemicals. Individually, the lettuce and rotifer tests ranked most similar in sensitivity to the standard tests, while Microtox fell just outside the range of sensitivities represented by the group of standard acute toxicity tests. The brine shrimp and Polytox tests were one or more orders of magnitude different from the standard acute toxicity tests for most compounds. The lettuce, rotifer, and Microtox tests could be used as a battery for preliminary toxicity screening of chemicals. Further evaluation of complex real-world environmental samples is recommended.

  13. Comparison of standard acute toxicity tests with rapid-screening toxicity tests

    Energy Technology Data Exchange (ETDEWEB)

    Toussaint, M.W.; Shedd, T.R.; VanDerSchal, W.H.; Leather, G.R.

    1995-10-01

    This study compared the relative sensitivity of five inexpensive, rapid toxicity tests to the sensitivity of five standard aquatic acute toxicity tests through literature review and testing. The rapid toxicity tests utilized organisms that require little culturing or handling prior to testing: a freshwater rotifer (Branchionus ccalyciflorus); brine shrimp (Artemia salina); lettuce (Lactuca sativa); and two microbial tests (Photo bacterium phosphoreum - Microtox test, and a mixture of bacterial species - the polytox test). Standard acute toxicity test species included water fleas (Daphnia magna and Ceriadaphnta dubia), green algae (Setenastrum capricarnutum), fathead minnows (Pimephalespromelas), and mysid shrimp (Mysidopsis bahia). Sensitivity comparisons between rapid and standard acute toxicity tests were based on LC5O/EC50 data from 11 test chemicals. Individually, the lettuce and rotifer tests ranked most similar in sensitivity to the standard tests, while Microtox fell just outside the range of sensitivities represented by the group of standard acute toxicity tests. The brine shrimp and Polytox tests were one or more orders of magnitude different from the standard acute toxicity tests for most compounds. The lettuce, rotifer, and Microtox tests could be used as a battery for preliminary toxicity screening of chemicals. Further evaluation of complex real-world environmental samples is recommended.

  14. 40 CFR 799.9305 - TSCA Repeated dose 28-day oral toxicity study in rodents.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 31 2010-07-01 2010-07-01 true TSCA Repeated dose 28-day oral toxicity study in rodents. 799.9305 Section 799.9305 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... strains of young healthy adult animals should be employed. The females should be nulliparous and...

  15. Bioequivalence approach for whole effluent toxicity testing

    Energy Technology Data Exchange (ETDEWEB)

    Shukla, R.; Wang, Q.; Fulk, F.; Deng, C.; Denton, D.

    2000-01-01

    Increased use of whole effluent toxicity (WET) tests in the regulatory arena has brought increased concern over the statistical analysis of WET test data and the determination of toxicity. One concern is the issue of statistical power. A number of WET tests may pass the current hypothesis test approach because they lack statistical power to detect relevant toxic effects because of large within-test variability. Additionally, a number of WET tests may fail the current approach because they possess excessive statistical power, as a result of small within-test variability, and detect small differences that may not be biologically relevant. The strengths and limitations of both the traditional hypothesis test approach and the bioequivalence approach for use in the National Pollutant Discharge Elimination System program were evaluated. Data from 5,213 single-concentration, short-term chronic WET tests with Ceriodaphnia dubia provided the database for analysis. Comparison of results between the current approach and the bioequivalence approach indicates that the current approach to WET testing is generally sound but that adopting the proposed bioequivalence approach resolves concerns of statistical power. Specifically, within this data set, applying the bioequivalence approach resulted in failure for tests with relatively large test variability and a pass for tests with relatively small within-test variability.

  16. Implications of Animal Welfare on Toxicity Testing

    DEFF Research Database (Denmark)

    Meyer, Otto A.

    1993-01-01

    The testing strategy for chemical substances is discussed with regard to obtaining improved quality of data for health assessment while respecting the ethical responsibility for consideration of the welfare of the animals involved. Ensuring animal welfare without indulging too much...... in anthropomorphism leads to better research/testing. Current trends in toxicity testing will result in tests involving more sophisticated techniques, better quality of laboratory animals, and eventually the use of fewer animals....

  17. Corneal epithelial toxicity of antiglaucoma formulations: in vitro study of repeated applications

    Directory of Open Access Journals (Sweden)

    Meloni M

    2012-09-01

    Full Text Available Marisa Meloni,1 Giampiero Cattaneo,2 Barbara De Servi11VitroScreen In Vitro Research Laboratories, 2Thea Farma, Milan, ItalyBackground: By using a biologically relevant and sensitive three-dimensional model of human corneal epithelium and multiple endpoint analysis, assessment of the potential for eye irritation and long-term compatibility of four registered ophthalmological preparations, ie, Timolabak®, Timoptol®, Nyogel®, and Timogel®, was performed. This approach enables classification of the potential for irritation, discriminating between mildly irritant and non-irritant ocular substances.Methods: The exposure protocol included two time periods, ie, 24 hours (acute application and 72 hours (repeated applications twice daily. This approach allows assessment of not only the acute reaction but also possible recovery, as well as mimicking the potential cumulative effects associated with long-term application. Using benzalkonium chloride (BAK 0.01% as a positive control, the following parameters were quantified: cellular viability by MTT test, histological analysis by hematoxylin and eosin staining, passive release of interleukin-1a by enzyme-linked immunosorbent assay, and OCLN gene expression by quantitative real-time polymerase chain reaction.Results: Cell viability was reduced to under the 50% cutoff value after acute exposure (24 hours to BAK 0.01%, and after repeated application (72 hours of Timoptol and Nyogel. Histological analysis after acute exposure showed signs of superficial damage with all formulations, and severe changes after repeated applications of Timoptol, BAK 0.01%, and Nyogel. Timolabak and Timogel did not significantly alter the morphology of the human corneal epithelial cells after the different exposure times. Interleukin-1α release was greater than that for the negative control (>20 pg/mL and the positive control (BAK 0.01%, Nyogel, and Timoptol treatments and not different after treatment with Timolabak and

  18. The OSIRIS Weight of Evidence approach: ITS for the endpoints repeated-dose toxicity (RepDose ITS).

    Science.gov (United States)

    Tluczkiewicz, Inga; Batke, Monika; Kroese, Dinant; Buist, Harrie; Aldenberg, Tom; Pauné, Eduard; Grimm, Helvi; Kühne, Ralph; Schüürmann, Gerrit; Mangelsdorf, Inge; Escher, Sylvia E

    2013-11-01

    In the FP6 European project OSIRIS, Integrated Testing Strategies (ITSs) for relevant toxicological endpoints were developed to avoid new animal testing and thus to reduce time and costs. The present paper describes the development of an ITS for repeated-dose toxicity called RepDose ITS which evaluates the conditions under which in vivo non-guideline studies are reliable. In a tiered approach three aspects of these "non-guideline" studies are assessed: the documentation of the study (reliability), the quality of the study design (adequacy) and the scope of examination (validity). The reliability is addressed by the method "Knock-out criteria", which consists of four essential criteria for repeated-dose toxicity studies. A second tool, termed QUANTOS (Quality Assessment of Non-guideline Toxicity Studies), evaluates and weights the adequacy of the study by using intra-criterion and inter-criteria weighting. Finally, the Coverage approach calculates a probability that the detected Lowest-Observed-Effect-Level (LOEL) is similar to the LOEL of a guideline study dependent on the examined targets and organs of the non-guideline study. If the validity and adequacy of the non-guideline study are insufficient for risk assessment, the ITS proposes to apply category approach or the Threshold of Toxicological Concern (TTC) concept, and only as a last resort new animal-testing.

  19. Draft Test Guideline: Fish Acute Toxicity Test, Freshwater And Marine

    Science.gov (United States)

    The following draft test guideline is part of a series of test guidelines that have been developed by EPA for use in the testing of pesticides and toxic substances, and the development of test data for submission to the Agency for review.

  20. Repeat Testing Effects on Credentialing Exams: Are Repeaters Misinformed or Uninformed?

    Science.gov (United States)

    Feinberg, Richard A.; Raymond, Mark R.; Haist, Steven A.

    2015-01-01

    To mitigate security concerns and unfair score gains, credentialing programs routinely administer new test material to examinees retesting after an initial failing attempt. Counterintuitively, a small but growing body of recent research suggests that repeating the identical form does not create an unfair advantage. This study builds upon and…

  1. Animal alternatives for whole effluent toxicity testing ...

    Science.gov (United States)

    Since the 1940s, effluent toxicity testing has been utilized to varying degrees in many countries to assess potential ecological impacts and assist in determining necessary treatment options for environmental protection. However, it was only in the early 1980’s that toxicity based effluent assessments and subsequent discharge controls became globally important, when it was recognized that physical and chemical measurements alone did not protect the environment from potential impacts. Consequently, various strategies using different toxicity tests, whole effluent assessment techniques (incorporating bioaccumulation potential and persistence) plus supporting analytical tools have been developed over 30 years of practice. Numerous workshops and meetings have focused on effluent risk assessment through ASTM, SETAC, OSPAR, UK competent authorities, and EU specific country rules. Concurrent with this drive to improve effluent quality using toxicity tests, interest in reducing animal use has risen. The Health and Environmental Sciences Institute (HESI) organized and facilitated an international workshop in March 2016 to evaluate strategies for concepts, tools, and effluent assessments and update the toolbox of for effluent testing methods. The workshop objectives were to identify opportunities to use a suite of strategies for effluents, and to identify opportunities to reduce the reliance on animal tests and to determine barriers to implementation of new methodologie

  2. Animal alternatives for whole effluent toxicity testing ...

    Science.gov (United States)

    Since the 1940s, effluent toxicity testing has been utilized to varying degrees in many countries to assess potential ecological impacts and assist in determining necessary treatment options for environmental protection. However, it was only in the early 1980’s that toxicity based effluent assessments and subsequent discharge controls became globally important, when it was recognized that physical and chemical measurements alone did not protect the environment from potential impacts. Consequently, various strategies using different toxicity tests, whole effluent assessment techniques (incorporating bioaccumulation potential and persistence) plus supporting analytical tools have been developed over 30 years of practice. Numerous workshops and meetings have focused on effluent risk assessment through ASTM, SETAC, OSPAR, UK competent authorities, and EU specific country rules. Concurrent with this drive to improve effluent quality using toxicity tests, interest in reducing animal use has risen. The Health and Environmental Sciences Institute (HESI) organized and facilitated an international workshop in March 2016 to evaluate strategies for concepts, tools, and effluent assessments and update the toolbox of for effluent testing methods. The workshop objectives were to identify opportunities to use a suite of strategies for effluents, and to identify opportunities to reduce the reliance on animal tests and to determine barriers to implementation of new methodologie

  3. Toxicity test of a dental commercial composite

    Science.gov (United States)

    Ponce-Bravo, Santa; Martínez-Rivera, José-Luis; Garcés-Ortíz, Maricela

    2015-01-01

    Background International rules must be followed for testing biosecurity in dental materials. A new brand of restorative material appeared in the market and regulations indicated that it should be tested for toxicity. Objectives The aim of this study was to determine the 90-day sub chronic toxicity of one triethylene glycol dimethacrylate containing composite (MEDENTAL Light-Cure Composite™) orally administered to rats according to Organization for Economic Co-Operation and Development no. 48 guidelines and the requirements specified in the ISO 10993-11. Material and Methods Wistar rats ate the polymerized composite during 90 days and were observed to determine changes in their behavior, eye and skin signs and other attitudes such as aggressiveness, posture, walking and response to handling. After 90 days were sacrificed to ascertain blood alterations, we did special hematological tests and assessed microscopic slides from 33 different organs. Results We recorded no significant changes in clinical behavior of the animals. Microscopic review of the H&E stained slides obtained from the analyzed organs showed no abnormal inflammatory or cytological changes and all hematological special tests were within normal limits. Conclusions Results of this study show that under our experimental conditions the MEDENTAL Light-Cure Composite™ does not produce inflammatory or cytological changes suggestive of toxicity. Key words:Dental materials, composite resin, toxicity, inflammation, TEGDMA. PMID:26155348

  4. Repeated measures dose-finding design with time-trend detection in the presence of correlated toxicity data.

    Science.gov (United States)

    Yin, Jun; Paoletti, Xavier; Sargent, Daniel J; Mandrekar, Sumithra J

    2017-08-01

    Phase I trials are designed to determine the safety, tolerability, and recommended phase 2 dose of therapeutic agents for subsequent testing. The dose-finding paradigm has thus traditionally focused on identifying the maximum tolerable dose of an agent or combination therapy under the assumption that there is a non-decreasing relationship between dose-toxicity and dose-efficacy. The dose is typically determined based on the probability of severe toxicity observed during the first treatment cycle. A novel endpoint, the total toxicity profile, was previously developed to account for the multiple toxicity types and grades experienced in the first cycle. More recently, this was extended to a repeated measures design based on the total toxicity profile to account for longitudinal toxicities over multiple treatment cycles in the absence of within-patient correlation. In this work, we propose to extend the design in the presence of within-patient correlation. Furthermore, we provide a framework to detect a toxicity time trend (toxicity increasing, decreasing, or stable) over multiple treatment cycles. We utilize a linear mixed model in the Bayesian framework, with the addition of Bayesian risk functions for decision-making in dose assignment. The performance of this design was evaluated using simulation studies and real data from a phase I trial. We demonstrated that using available toxicity data from all cycles of treatment improves the accuracy of maximum tolerated dose identification and allows for the detection of a time trend. The performance is consistent regardless of the strength of the within-patient correlation. In addition, the use of a quasi-continuous total toxicity profile score significantly increased the power to detect time trends compared to when binary data only were used. The increased interest in molecularly targeted agents and immunotherapies in oncology necessitates innovative phase I study designs. Our proposed framework provides a tool to tackle

  5. Stages and conformations of the Tau repeat domain during aggregation and its effect on neuronal toxicity.

    Science.gov (United States)

    Kumar, Satish; Tepper, Katharina; Kaniyappan, Senthilvelrajan; Biernat, Jacek; Wegmann, Susanne; Mandelkow, Eva-Maria; Müller, Daniel J; Mandelkow, Eckhard

    2014-07-18

    Several neurodegenerative diseases are characterized by the aggregation and posttranslational modifications of Tau protein. Its "repeat domain" (TauRD) is mainly responsible for the aggregation properties, and oligomeric forms are thought to dominate the toxic effects of Tau. Here we investigated the conformational transitions of this domain during oligomerization and aggregation in different states of β-propensity and pseudo-phosphorylation, using several complementary imaging and spectroscopic methods. Although the repeat domain generally aggregates more readily than full-length Tau, its aggregation was greatly slowed down by phosphorylation or pseudo-phosphorylation at the KXGS motifs, concomitant with an extended phase of oligomerization. Analogous effects were observed with pro-aggregant variants of TauRD. Oligomers became most evident in the case of the pro-aggregant mutant TauRDΔK280, as monitored by atomic force microscopy, and the fluorescence lifetime of Alexa-labeled Tau (time-correlated single photon counting (TCSPC)), consistent with its pronounced toxicity in mouse models. In cell models or primary neurons, neither oligomers nor fibrils of TauRD or TauRDΔK280 had a toxic effect, as seen by assays with lactate dehydrogenase and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, respectively. However, oligomers of pro-aggregant TauRDΔK280 specifically caused a loss of spine density in differentiated neurons, indicating a locally restricted impairment of function. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  6. Stages and Conformations of the Tau Repeat Domain during Aggregation and Its Effect on Neuronal Toxicity*

    Science.gov (United States)

    Kumar, Satish; Tepper, Katharina; Kaniyappan, Senthilvelrajan; Biernat, Jacek; Wegmann, Susanne; Mandelkow, Eva-Maria; Müller, Daniel J.; Mandelkow, Eckhard

    2014-01-01

    Several neurodegenerative diseases are characterized by the aggregation and posttranslational modifications of Tau protein. Its “repeat domain” (TauRD) is mainly responsible for the aggregation properties, and oligomeric forms are thought to dominate the toxic effects of Tau. Here we investigated the conformational transitions of this domain during oligomerization and aggregation in different states of β-propensity and pseudo-phosphorylation, using several complementary imaging and spectroscopic methods. Although the repeat domain generally aggregates more readily than full-length Tau, its aggregation was greatly slowed down by phosphorylation or pseudo-phosphorylation at the KXGS motifs, concomitant with an extended phase of oligomerization. Analogous effects were observed with pro-aggregant variants of TauRD. Oligomers became most evident in the case of the pro-aggregant mutant TauRDΔK280, as monitored by atomic force microscopy, and the fluorescence lifetime of Alexa-labeled Tau (time-correlated single photon counting (TCSPC)), consistent with its pronounced toxicity in mouse models. In cell models or primary neurons, neither oligomers nor fibrils of TauRD or TauRDΔK280 had a toxic effect, as seen by assays with lactate dehydrogenase and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, respectively. However, oligomers of pro-aggregant TauRDΔK280 specifically caused a loss of spine density in differentiated neurons, indicating a locally restricted impairment of function. PMID:24825901

  7. Use of a statistical model to predict the potential for repeated dose and developmental toxicity of dermally administered crude oil and relation to reproductive toxicity.

    Science.gov (United States)

    McKee, Richard H; Nicolich, Mark; Roy, Timothy; White, Russell; Daughtrey, Wayne C

    2014-01-01

    Petroleum (commonly called crude oil) is a complex substance primarily composed of hydrocarbon constituents. Based on the results of previous toxicological studies as well as occupational experience, the principal acute toxicological hazards are those associated with exposure by inhalation to volatile hydrocarbon constituents and hydrogen sulfide, and chronic hazards are associated with inhalation exposure to benzene and dermal exposure to polycyclic aromatic compounds. The current assessment was an attempt to characterize the potential for repeated dose and/or developmental effects of crude oils following dermal exposures and to generalize the conclusions across a broad range of crude oils from different sources. Statistical models were used to predict the potential for repeated dose and developmental toxicity from compositional information. The model predictions indicated that the empirical data from previously tested crude oils approximated a "worst case" situation, and that the data from previously tested crude oils could be used as a reasonable basis for characterizing the repeated dose and developmental toxicological hazards of crude oils in general.

  8. Microfluidics for Antibiotic Susceptibility and Toxicity Testing

    Directory of Open Access Journals (Sweden)

    Jing Dai

    2016-10-01

    Full Text Available The recent emergence of antimicrobial resistance has become a major concern for worldwide policy makers as very few new antibiotics have been developed in the last twenty-five years. To prevent the death of millions of people worldwide, there is an urgent need for a cheap, fast and accurate set of tools and techniques that can help to discover and develop new antimicrobial drugs. In the past decade, microfluidic platforms have emerged as potential systems for conducting pharmacological studies. Recent studies have demonstrated that microfluidic platforms can perform rapid antibiotic susceptibility tests to evaluate antimicrobial drugs’ efficacy. In addition, the development of cell-on-a-chip and organ-on-a-chip platforms have enabled the early drug testing, providing more accurate insights into conventional cell cultures on the drug pharmacokinetics and toxicity, at the early and cheaper stage of drug development, i.e., prior to animal and human testing. In this review, we focus on the recent developments of microfluidic platforms for rapid antibiotics susceptibility testing, investigating bacterial persistence and non-growing but metabolically active (NGMA bacteria, evaluating antibiotic effectiveness on biofilms and combinatorial effect of antibiotics, as well as microfluidic platforms that can be used for in vitro antibiotic toxicity testing.

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

    DEFF Research Database (Denmark)

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

    and stakeholders, this study aims to develop innovative partial life-cycle tests on the reproduction of the freshwater gastropods Potamopyrgus antipodarum and Lymnaea stagnalis, which are relevant candidate species for the standardization of mollusc apical toxicity tests assessing reprotoxic effects of chemicals...... with P. antipodarum and L. stagnalis exposed to Cd are thus very encouraging. Results for BPA highlighted issues in controlling exposure concentrations, and possibly BPA leaching from test equipment. This study also highlighted that factors, such as e.g., snail origin, temperature and test chemical...... stability in water, must be controlled in mollusc toxicity tests to avoid data dispersion which may impede the interpretation of effects. Applicability and limitations of the SOP proposed for L. stagnalis will be assessed after completion of the on-going pre-validation work. In both cases, optimization...

  10. Repeating tests: different roles in research studies and clinical medicine.

    Science.gov (United States)

    Monach, Paul A

    2012-10-01

    Researchers often decide whether to average multiple results in order to produce more precise data, and clinicians often decide whether to repeat a laboratory test in order to confirm its validity or to follow a trend. Some of the major sources of variation in laboratory tests (analytical imprecision, within-subject biological variation and between-subject variation) and the effects of averaging multiple results from the same sample or from the same person over time are discussed quantitatively in this article. This analysis leads to the surprising conclusion that the strategy of averaging multiple results is only necessary and effective in a limited range of research studies. In clinical practice, it may be important to repeat a test in order to eliminate the possibility of a rare type of error that has nothing to do analytical imprecision or within-subject variation, and for this reason, paradoxically, it may be most important to repeat tests with the highest sensitivity and/or specificity (i.e., ones that are critical for clinical decision-making).

  11. Methyldibromoglutaronitrile allergy: relationship between patch test and repeated open application test thresholds

    DEFF Research Database (Denmark)

    Fischer, L.A.; Johansen, J.D.; Menne, T.

    2008-01-01

    a significant relationship between the patch test and the repeated open application test (ROAT) reactivity. Objectives To study the relationship between elicitation threshold doses at single occluded exposure and repeated open application, using MDBGN as the allergen. Methods Eighteen subjects allergic to MDBGN...

  12. The rise in carboxyhemoglobin from repeated pulmonary diffusing capacity tests.

    Science.gov (United States)

    Zavorsky, Gerald S

    2013-03-01

    The purpose of this study determined the rise in carboxyhemoglobin percentage (COHb) from repeated pulmonary diffusing capacity tests using 5 or 10s single breath-hold maneuvers. Five male and four female non-smokers [baseline COHb=1.2 (SD 0.5%)] performed repeated pulmonary diffusing capacity testing on two separate days. The days were randomized to either repeated 10s (0.28% CO), or 5s (0.28% CO, 55ppm NO) breath-hold maneuvers. Twenty-two 5s breath-hold maneuvers, each separated by 4min rest, raised COHb to 11.1 (1.4)% and minimally raised the methemoglobin percentage (METHb) by 0.3 (0.2)% to a value of 0.8 (0.2)%. After the 22nd test, pulmonary diffusing capacity for carbon monoxide (DLCO) was reduced by about 4mL/min/mmHg, equating to a 0.44% increase in COHb per 5s breath-hold maneuver and a concomitant 0.35mL/min/mmHg decrease in DLCO. Pulmonary diffusing capacity for nitric oxide (DLNO) was not altered after 22 tests. On another day, the 10s single breath-hold maneuver increased COHb by 0.64% per test, and reduced DLCO by 0.44mL/min/mmHg per test. In conclusion, 5s breath-hold maneuvers do not appreciably raise METHb or DLNO, and DLCO is only significantly reduced when COHb is at least 6%.

  13. Toxicity of Uranium Adsorbent Materials using the Microtox Toxicity Test

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jiyeon [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Jeters, Robert T. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Gill, Gary A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Kuo, Li-Jung [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Bonheyo, George T. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2015-10-01

    The Marine Sciences Laboratory at the Pacific Northwest National Laboratory evaluated the toxicity of a diverse range of natural and synthetic materials used to extract uranium from seawater. The uranium adsorbent materials are being developed as part of the U. S. Department of Energy, Office of Nuclear Energy, Fuel Resources Program. The goal of this effort was to identify whether deployment of a farm of these materials into the marine environment would have any toxic effects on marine organisms.

  14. Investigation of the toxicity of some organophosphorus pesticides in a repeated dose study in rats.

    Science.gov (United States)

    Baconi, Daniela Luiza; Bârcă, Maria; Manda, Gina; Ciobanu, Anne Marie; Bălălău, C

    2013-01-01

    The study aimed to the investigation of the toxicity of organophosphorus pesticides malathion (MLT) and diazinon (DZN) in Wistar rats in a repeated dose study for 35 days. MLT and DZN in corn oil vehicle were oral administered. Body and organs weights, plasma and brain cholinesterase activities, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities, histopathological changes in liver and kidney, and some parameters of the immune function, such as leukocyte formula, spleen weight and cellularity, spleen lymphocytes proliferation in response to concanavalin A (Con A) were investigated; the potential oxidative stress (malondialdehyde in plasma and brain, and blood catalase activity) was also evaluated. No clinical toxicity signs attributed to pesticides were noted; no significant changes in the organ weights have been found. Body weight tends slightly to increase, predominantly in DZN treated rats. The results suggest that plasma cholinesterase is more susceptible than brain cholinesterase to the inhibitory effect of DZN and MLT. Other serum biochemical parameters showed no significant difference. DZN produced a marked increase of the number of spleen lymphocytes without a significant gain of the relative spleen weight. The both pesticides produced an increase of the number of mononuclear cells÷weight spleen. The splenic lymphocyte proliferation has not been influenced by MLT or DZN treatment. Histopathological observations identified some changes (vasodilatation, microvacuoles, and granular dystrophy) in the liver, with MLT, inducing macrovacuolar steatosis. The study indicates that repeated exposure, at subclinical doses, to organophosphorus MLT and DZN causes some biochemical, histopathological and immune alterations in rats.

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

    Science.gov (United States)

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

    2015-04-01

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

  16. Developmental and reproductive toxicity testing of vaccines.

    Science.gov (United States)

    Barrow, Paul

    2012-03-01

    The majority of new preventative and therapeutic vaccines are now assessed for developmental toxicity according to guidelines issued by the FDA in 2006. Despite the absence of confirmed effects in humans, vaccines are frequently suspected of having adverse side-effects on the development of children. Such suspicions are perhaps unavoidable considering the extremely widespread use of vaccines. The preclinical developmental toxicology studies are designed to assess possible influences of each component of the vaccine formulation-and the induced antibodies-on the development of the conceptus, neonate and suckling organism. Immune modulation by a vaccine or an adjuvant could, for instance, affect the outcome of pregnancy by interfering with the natural shift in immune balance of the mother during gestation. Maternal immunoglobulins are transferred from the mother to the offspring in order to confer passive immunity during early life. This maternal antibody transport is prenatal in humans and monkeys, but tends to be delayed until after birth in other species. Therefore, a suitable model species needs to be chosen for preclinical studies in order to ensure exposure of the foetus to the induced maternal antibodies following vaccination. Rabbits are the best laboratory model for prenatal immunoglobulin transfer, but rodents are more practical for the necessary postnatal investigations. Non-human primates are the only appropriate models for the testing of vaccines that are not immunogenic in lower species. It is advisable to test new adjuvants separately according to the ICH S5(R2) guidelines. Preclinical paediatric investigations are not currently required for vaccines, even though most vaccines are given to children. Other areas of regulatory concern include developmental immunotoxicity and effects on the preimplantation embryo. Because of the limitations of the available animal models for developmental toxicity testing, pharmacovigilance is essential. Copyright © 2011

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

    DEFF Research Database (Denmark)

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

    and stakeholders, this study aims to develop innovative partial life-cycle tests on the reproduction of the freshwater gastropods Potamopyrgus antipodarum and Lymnaea stagnalis, which are relevant candidate species for the standardization of mollusc apical toxicity tests assessing reprotoxic effects of chemicals....... Draft standard operating procedures (SOPs) have been designed based upon literature and expert knowledge from project partners. Pre-validation studies have been implemented to validate the proposed test conditions and identify issues in performing the SOPs and analyzing test results. Pre-validation work...... with P. antipodarum and L. stagnalis exposed to Cd are thus very encouraging. Results for BPA highlighted issues in controlling exposure concentrations, and possibly BPA leaching from test equipment. This study also highlighted that factors, such as e.g., snail origin, temperature and test chemical...

  18. A Novel Method for Repeatable Failure Testing of Annulus Fibrosus.

    Science.gov (United States)

    Werbner, Benjamin; Zhou, Minhao; O'Connell, Grace

    2017-11-01

    Tears in the annulus fibrosus (AF) of the intervertebral disk can result in disk herniation and progressive degeneration. Understanding AF failure mechanics is important as research moves toward developing biological repair strategies for herniated disks. Unfortunately, failure mechanics of fiber-reinforced tissues, particularly tissues with fibers oriented off-axis from the applied load, is not well understood, partly due to the high variability in reported mechanical properties and a lack of standard techniques ensuring repeatable failure behavior. Therefore, the objective of this study was to investigate the effectiveness of midlength (ML) notch geometries in producing repeatable and consistent tissue failure within the gauge region of AF mechanical test specimens. Finite element models (FEMs) representing several notch geometries were created to predict the location of bulk tissue failure using a local strain-based criterion. FEM results were validated by experimentally testing a subset of the modeled specimen geometries. Mechanical testing data agreed with model predictions (∼90% agreement), validating the model's predictive power. Two of the modified dog-bone geometries ("half" and "quarter") effectively ensured tissue failure at the ML for specimens oriented along the circumferential-radial and circumferential-axial directions. The variance of measured mechanical properties was significantly lower for notched samples that failed at the ML, suggesting that ML notch geometries result in more consistent and reliable data. In addition, the approach developed in this study provides a framework for evaluating failure properties of other fiber-reinforced tissues, such as tendons and meniscus.

  19. Cardiovascular adjustments and pain during repeated cold pressor test.

    Science.gov (United States)

    Stancák, A; Yamamotová, A; Kulls, I P; Sekyra, I V

    1996-04-01

    The cold pressor test is used in the clinical testing of the autonomic nervous system. However, little is known about changes in the autonomic control of the cardiovascular system during repeated challenge with cold. Heart rate (HR), respiratory sinus arrhythmia (RSA), T-wave amplitude of ECG (TWA), blood pressure, body temperature and perceived pain were recorded in 18 male subjects during three CPTs which consisted of four minutes immersion of the left hand into cold water at 1 degree C. Breathing during CPT was either spontaneous or paced at 0.23 Hz or 0.1 Hz. Pain intensity and HR decreased and TWA increased during the cold immersion and in the resting period preceding cold in the second and third trials. Systolic and pulse blood pressure increased in resting periods in the third trial. RSA increased in the second and third cold challenge during paced breathing at 0.1 Hz only. A decrease in body temperature (0.48 degree C) at the end of the experiment correlated marginally with HR changes. Our study shows that sustained cardiovascular changes are induced by the first challenge with cold, and persist or increase with repeated cold pressor tests.

  20. Screening of repeated dose toxicity data present in SCC(NF)P/SCCS safety evaluations of cosmetic ingredients.

    Science.gov (United States)

    Vinken, Mathieu; Pauwels, Marleen; Ates, Gamze; Vivier, Manon; Vanhaecke, Tamara; Rogiers, Vera

    2012-03-01

    Alternative methods, replacing animal testing, are urgently needed in view of the European regulatory changes in the field of cosmetic products and their ingredients. In this context, a joint research initiative called SEURAT was recently raised by the European Commission and COLIPA, representing the European cosmetics industry, with the overall goal of developing an animal-free repeated dose toxicity testing strategy for human safety assessment purposes. Although cosmetic ingredients are usually harmless for the consumer, one of the initial tasks of this research consortium included the identification of organs that could potentially be affected by cosmetic ingredients upon systemic exposure. The strategy that was followed hereof is described in the present paper and relies on the systematic evaluation, by using a self-generated electronic databank, of published reports issued by the scientific committee of DG SANCO responsible for the safety of cosmetic ingredients. By screening of the repeated dose toxicity studies present in these reports, it was found that the liver is potentially the most frequently targeted organ by cosmetic ingredients when orally administered to experimental animals, followed by the kidney and the spleen. Combined listing of altered morphological, histopathological, and biochemical parameters subsequently indicated the possible occurrence of hepatotoxicity, including steatosis and cholestasis, triggered by a limited number of cosmetic compounds. These findings are not only of relevance for the in vitro modeling efforts and choice of compounds to be tested in the SEURAT project cluster, but also demonstrate the importance of using previously generated toxicological data through an electronic databank for addressing specific questions regarding the safety evaluation of cosmetic ingredients.

  1. Triplet repeat primed PCR simplifies testing for Huntington disease.

    Science.gov (United States)

    Jama, Mohamed; Millson, Alison; Miller, Christine E; Lyon, Elaine

    2013-03-01

    Diagnostic and predictive testing for Huntington disease (HD) requires an accurate determination of the number of CAG repeats in the Huntingtin (HHT) gene. Currently, when a sample appears to be homozygous for a normal allele, additional testing is required to confirm amplification from both alleles. If the sample still appears homozygous, Southern blot analysis is performed to rule out an undetected expanded HTT allele. Southern blot analysis is expensive, time-consuming, and labor intensive and requires high concentrations of DNA. We have developed a chimeric PCR process to help streamline workflow; true homozygous alleles are easily distinguished by this simplified method, and only very large expanded alleles still require Southern blot analysis. Two hundred forty-six HD samples, previously run with a different fragment analysis method, were analyzed with our new method. All samples were correctly genotyped, resulting in 100% concordance between the methods. The chimeric PCR assay was able to identify expanded alleles up to >150 CAG repeats. This method offers a simple strategy to differentiate normal from expanded CAG alleles, thereby reducing the number of samples reflexed to Southern blot analysis. It also provides assurance that expanded alleles are not routinely missed because of allele dropout.

  2. Precise small-molecule recognition of a toxic CUG RNA repeat expansion.

    Science.gov (United States)

    Rzuczek, Suzanne G; Colgan, Lesley A; Nakai, Yoshio; Cameron, Michael D; Furling, Denis; Yasuda, Ryohei; Disney, Matthew D

    2017-02-01

    Excluding the ribosome and riboswitches, developing small molecules that selectively target RNA is a longstanding problem in chemical biology. A typical cellular RNA is difficult to target because it has little tertiary, but abundant secondary structure. We designed allele-selective compounds that target such an RNA, the toxic noncoding repeat expansion (r(CUG)(exp)) that causes myotonic dystrophy type 1 (DM1). We developed several strategies to generate allele-selective small molecules, including non-covalent binding, covalent binding, cleavage and on-site probe synthesis. Covalent binding and cleavage enabled target profiling in cells derived from individuals with DM1, showing precise recognition of r(CUG)(exp). In the on-site probe synthesis approach, small molecules bound adjacent sites in r(CUG)(exp) and reacted to afford picomolar inhibitors via a proximity-based click reaction only in DM1-affected cells. We expanded this approach to image r(CUG)(exp) in its natural context.

  3. Respiratory toxicity of repeated exposure to particles produced by traffic and sugar cane burning.

    Science.gov (United States)

    Mazzoli-Rocha, Flavia; Carvalho, Giovanna M C; Lanzetti, Manuella; Valença, Samuel S; Silva, Luiz F F; Saldiva, Paulo H N; Zin, Walter A; Faffe, Débora S

    2014-01-15

    We compared the toxicity of subchronic exposure to equivalent masses of particles from sugar cane burning and traffic. BALB/c mice received 3 intranasal instillations/week during 1, 2 or 4 weeks of either distilled water (C1, C2, C4) or particles (15μg) from traffic (UP1, UP2, UP4) or biomass burning (BP1, BP2, BP4). Lung mechanics, histology and oxidative stress were analyzed 24h after the last instillation. In all instances UP and BP groups presented worse pulmonary elastance, airway and tissue resistance, alveolar collapse, bronchoconstriction and macrophage influx into the lungs than controls. UP4, BP2 and BP4 presented more alveolar collapse than UP1 and BP1, respectively. UP and BP had worse bronchial and alveolar lesion scores than their controls; BP4 had greater bronchial lesion scores than UP4. Catalase was higher in UP4 and BP4 than in C4. In conclusion, biomass particles were more toxic than those from traffic after repeated exposures.

  4. Repeated exposure to iron oxide nanoparticles causes testicular toxicity in mice.

    Science.gov (United States)

    Sundarraj, Kiruthika; Manickam, Vijayprakash; Raghunath, Azhwar; Periyasamy, Madhivadhani; Viswanathan, Mangala Priya; Perumal, Ekambaram

    2017-02-01

    The aim of this study was to determine whether repeated exposure to iron oxide nanoparticles (Fe2 O3 -NPs) could be toxic to mice testis. Fe2 O3 -NPs (25 and 50 mg/kg) were intraperitoneally administered into mice once a week for 4 weeks. Our study showed that Fe2 O3 -NPs have the ability to cross the blood-testis barrier to get into the testis. The findings showed that exposure resulted in the accumulation of Fe2 O3 -NPs which was evidenced from the iron content and accumulation in the testis. Furthermore, 25 and 50 mg/kg Fe2 O3 -NPs administration increased the reactive oxygen species, lipid peroxidation, protein carbonyl content, glutathione peroxidase activity, and nitric oxide levels with a concomitant decrease in the levels of antioxidants-superoxide dismutase, catalase, glutathione, and vitamin C. Increased expression of Bax, cleaved-caspase-3, and cleaved-PARP confirms apoptosis. Serum testosterone levels increased with increased concentration of Fe2 O3 -NPs exposure. In addition, the histopathological lesions like vacuolization, detachment, and sloughing of germ cells were also observed in response to Fe2 O3 -NPs treatment. The data from our study entailed that testicular toxicity caused by Fe2 O3 -NPs exposure may be associated with Fe2 O3 -NPs accumulation leading to oxidative stress and apoptosis. Therefore, precautions should be taken in the safe use of Fe2 O3 -NPs to avoid complications in the fertility of males. Further research will unravel the possible molecular mechanisms on testicular toxicity of Fe2 O3 -NPs. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 594-608, 2017.

  5. Low patch test reactivity to nickel in unselected adolescents tested repeatedly with nickel in infancy

    DEFF Research Database (Denmark)

    Christiansen, Elisabeth Soegaard; Andersen, Klaus Ejner; Bindslev-Jensen, Carsten

    2016-01-01

    BACKGROUND: It is questionable how repeated patch tests with nickel sulphate in infancy affect nickel patch test reactivity at a later age. METHODS: The DARC cohort encompasses 562 infants invited to a clinical examination including patch tests with nickel sulphate 6 times during the first 36 mon...

  6. Repeat length and RNA expression level are not primary determinants in CUG expansion toxicity in Drosophila models.

    Directory of Open Access Journals (Sweden)

    Gwenn Le Mée

    Full Text Available Evidence for an RNA gain-of-function toxicity has now been provided for an increasing number of human pathologies. Myotonic dystrophies (DM belong to a class of RNA-dominant diseases that result from RNA repeat expansion toxicity. Specifically, DM of type 1 (DM1, is caused by an expansion of CUG repeats in the 3'UTR of the DMPK protein kinase mRNA, while DM of type 2 (DM2 is linked to an expansion of CCUG repeats in an intron of the ZNF9 transcript (ZNF9 encodes a zinc finger protein. In both pathologies the mutant RNA forms nuclear foci. The mechanisms that underlie the RNA pathogenicity seem to be rather complex and not yet completely understood. Here, we describe Drosophila models that might help unravelling the molecular mechanisms of DM1-associated CUG expansion toxicity. We generated transgenic flies that express inducible repeats of different type (CUG or CAG and length (16, 240, 480 repeats and then analyzed transgene localization, RNA expression and toxicity as assessed by induced lethality and eye neurodegeneration. The only line that expressed a toxic RNA has a (CTG(240 insertion. Moreover our analysis shows that its level of expression cannot account for its toxicity. In this line, (CTG(240.4, the expansion inserted in the first intron of CG9650, a zinc finger protein encoding gene. Interestingly, CG9650 and (CUG(240.4 expansion RNAs were found in the same nuclear foci. In conclusion, we suggest that the insertion context is the primary determinant for expansion toxicity in Drosophila models. This finding should contribute to the still open debate on the role of the expansions per se in Drosophila and in human pathogenesis of RNA-dominant diseases.

  7. 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

  8. Evaluation of arecoline hydrobromide toxicity after a 14-day repeated oral administration in Wistar rats.

    Directory of Open Access Journals (Sweden)

    Xiaojuan Wei

    Full Text Available A subchronic toxicity test was conducted in rats on the basis of a previous acute toxicity test to evaluate the safety of arecoline hydrobromide (Ah, to systematically study its pharmacological effects and to provide experimental support for a safe clinical dose. Eighty rats were randomly divided into four groups: a high-dose group (1000 mg/kg, medium-dose group (200 mg/kg, low-dose group (100mg/kg and blank control group. The doses were administered daily via gastric lavage for 14 consecutive days. There were no significant differences in the low-dose Ah group compared to the control group (P>0.05 with regard to body weight, organ coefficients, hematological parameters and histopathological changes. The high-dose of Ah influenced some of these parameters, which requires further study. The results of this study indicated that a long-term, continuous high dose of Ah was toxic. However, it is safe to use Ah according to the clinically recommended dosing parameters. The level of Ah at which no adverse effects were observed was 100 mg/kg/day under the present study conditions.

  9. Evaluation of arecoline hydrobromide toxicity after a 14-day repeated oral administration in Wistar rats.

    Science.gov (United States)

    Wei, Xiaojuan; Zhang, Jiyu; Niu, Jianrong; Zhou, Xuzheng; Li, Jianyong; Li, Bing

    2015-01-01

    A subchronic toxicity test was conducted in rats on the basis of a previous acute toxicity test to evaluate the safety of arecoline hydrobromide (Ah), to systematically study its pharmacological effects and to provide experimental support for a safe clinical dose. Eighty rats were randomly divided into four groups: a high-dose group (1000 mg/kg), medium-dose group (200 mg/kg), low-dose group (100mg/kg) and blank control group. The doses were administered daily via gastric lavage for 14 consecutive days. There were no significant differences in the low-dose Ah group compared to the control group (P>0.05) with regard to body weight, organ coefficients, hematological parameters and histopathological changes. The high-dose of Ah influenced some of these parameters, which requires further study. The results of this study indicated that a long-term, continuous high dose of Ah was toxic. However, it is safe to use Ah according to the clinically recommended dosing parameters. The level of Ah at which no adverse effects were observed was 100 mg/kg/day under the present study conditions.

  10. Correlation of inter-locus polyglutamine toxicity with CAG•CTG triplet repeat expandability and flanking genomic DNA GC content.

    Directory of Open Access Journals (Sweden)

    Colm E Nestor

    Full Text Available Dynamic expansions of toxic polyglutamine (polyQ-encoding CAG repeats in ubiquitously expressed, but otherwise unrelated, genes cause a number of late-onset progressive neurodegenerative disorders, including Huntington disease and the spinocerebellar ataxias. As polyQ toxicity in these disorders increases with repeat length, the intergenerational expansion of unstable CAG repeats leads to anticipation, an earlier age-at-onset in successive generations. Crucially, disease associated alleles are also somatically unstable and continue to expand throughout the lifetime of the individual. Interestingly, the inherited polyQ length mediating a specific age-at-onset of symptoms varies markedly between disorders. It is widely assumed that these inter-locus differences in polyQ toxicity are mediated by protein context effects. Previously, we demonstrated that the tendency of expanded CAG•CTG repeats to undergo further intergenerational expansion (their 'expandability' also differs between disorders and these effects are strongly correlated with the GC content of the genomic flanking DNA. Here we show that the inter-locus toxicity of the expanded polyQ tracts of these disorders also correlates with both the expandability of the underlying CAG repeat and the GC content of the genomic DNA flanking sequences. Inter-locus polyQ toxicity does not correlate with properties of the mRNA or protein sequences, with polyQ location within the gene or protein, or steady state transcript levels in the brain. These data suggest that the observed inter-locus differences in polyQ toxicity are not mediated solely by protein context effects, but that genomic context is also important, an effect that may be mediated by modifying the rate at which somatic expansion of the DNA delivers proteins to their cytotoxic state.

  11. Status and applications of echinoid (phylum echinodermata) toxicity test methods

    Energy Technology Data Exchange (ETDEWEB)

    Bay, S.; Burgess, R.; Nacci, D.

    1993-01-01

    The use of echinoderms for toxicity testing has focused primarily on sea urchins and sand dollars (Strongylocentrotus purpuratus, Arbacia punctulata, Lytechinus pictus, and Dendraster excentricus, for example). The status and relative sensitivity of various test methods are described. The most frequently used test methods consist of short-term exposures of sea urchin sperm or embryos; these tests can be easily conducted at all times of the year by using species with complementary spawning cycles or laboratory conditioned populations of a single species. Data from reference toxicant and effluent toxicity tests are summarized. Information on the precision and sensitivity of echinoid test methods are limited and preclude rigorous comparisons with other test methods. The available data indicate that the sensitivity and precision of these methods are comparable to short-term chronic methods for other marine invertebrates and fish. Recent application of the sperm test in toxicity identification evaluations (TIEs) and studies of effluent toxicity decay and sediment toxicity illustrate the versatility of this rapid (10 to 60 min exposure) test method. Embryo tests typically use a 48 to 96 h exposure period and measure the occurrence of embryo malformations. Most recent applications of the embryo test have been for the assessment of sediment elutriate toxicity. Adult echinoderms are not frequently used to assess effluent or receiving water toxicity. Recent studies have had success in using the adult life stage of urchins and sand dollars to assess the effects of contaminated sediment on growth, behavior, and bioaccumulation.

  12. Repeat associated non-ATG translation initiation: one DNA, two transcripts, seven reading frames, potentially nine toxic entities!

    Directory of Open Access Journals (Sweden)

    Christopher E Pearson

    2011-03-01

    Full Text Available Diseases associated with unstable repetitive elements in the DNA, RNA, and amino acids have consistently revealed scientific surprises. Most diseases are caused by expansions of trinucleotide repeats, which ultimately lead to diseases like Huntington's disease, myotonic dystrophy, fragile X syndrome, and a series of spinocerebellar ataxias. These repeat mutations are dynamic, changing through generations and within an individual, and the repeats can be bi-directionally transcribed. Unsuspected modes of pathogenesis involve aberrant loss of protein expression; aberrant over-expression of non-mutant proteins; toxic-gain-of-protein function through expanded polyglutamine tracts that are encoded by expanded CAG tracts; and RNA-toxic-gain-of-function caused by transcripts harboring expanded CUG, CAG, or CGG tracts. A recent advance reveals that RNA transcripts with expanded CAG repeats can be translated in the complete absence of a starting ATG, and this Repeat Associated Non-ATG translation (RAN-translation occurs across expanded CAG repeats in all reading frames (CAG, AGC, and GCA to produce homopolymeric proteins of long polyglutamine, polyserine, and polyalanine tracts. Expanded CTG tracts expressing CUG transcripts also show RAN-translation occurring in all three frames (CUG, UGC, and GCU, to produce polyleucine, polycysteine, and polyalanine. These RAN-translation products can be toxic. Thus, one unstable (CAG•(CTG DNA can produce two expanded repeat transcripts and homopolymeric proteins with reading frames (the AUG-directed polyGln and six RAN-translation proteins, yielding a total of potentially nine toxic entities. The occurrence of RAN-translation in patient tissues expands our horizons of modes of disease pathogenesis. Moreover, since RAN-translation counters the canonical requirements of translation initiation, many new questions are now posed that must be addressed. This review covers RAN-translation and some of the pertinent

  13. Toxicity from repeated doses of acetaminophen in children: assessment of causality and dose in reported cases.

    Science.gov (United States)

    Heard, Kennon; Bui, Alison; Mlynarchek, Sara L; Green, Jody L; Bond, G Randall; Clark, Richard F; Kozer, Eran; Koff, Raymond S; Dart, Richard C

    2014-01-01

    Liver injury has been reported in children treated with repeated doses of acetaminophen. The objective of this study was to identify and validate reports of liver injury or death in children younger than 6 years who were administered repeated therapeutic doses of acetaminophen. We reviewed US Poison Center data, peer-reviewed literature, US Food and Drug Administration Adverse Event Reports, and US Manufacturer Safety Reports describing adverse effects after acetaminophen administration. Reports that described hepatic abnormalities (description of liver injury or abnormal laboratory testing) or death after acetaminophen administration to children younger than 6 years were included. The identified reports were double abstracted and then reviewed by an expert panel to determine if the hepatic injury was related to acetaminophen and whether the dose of acetaminophen was therapeutic (≤75 mg/kg) or supratherapeutic. Our search yielded 2531 reports of adverse events associated with acetaminophen use. From these cases, we identified 76 cases of hepatic injury and 26 deaths associated with repeated acetaminophen administration. There were 6 cases of hepatic abnormalities and no deaths associated with what our panel determined to be therapeutic doses. A large proportion of cases could not be fully evaluated due to incomplete case reporting. Although we identified numerous examples of liver injury and death after repeated doses of acetaminophen, all the deaths and all but 6 cases of hepatic abnormalities involved doses more than 75 mg/kg per day. This study suggests that the doses of less than 75 mg/kg per day of acetaminophen are safe for children younger than 6 years.

  14. Test-retest repeatability of the Strain Index.

    Science.gov (United States)

    Stephens, John-Paul; Vos, Gordon A; Stevens, Edward M; Moore, J Steven

    2006-05-01

    Fifteen raters individually, and in five teams of three, evaluated the test-retest repeatability of published data collection and rating methods of the Strain Index by analyzing 61 job video files twice over a 5-month period. Raters estimated average and peak hand forces, measured Duration of Exertion, cycle time, and exertions per job cycle, calculated percent Duration of Exertion and Efforts per Minute, and assigned ratings for five of the six Strain Index task variables. Twelve additional jobs were analyzed to determine Strain Index Score and hazard classification. Intraclass correlation (ICC) coefficients for task variable ratings and accompanying data ranged from 0.66 to 0.95 for both individuals and teams. The Strain Index Score ICC(2,1) for individuals and teams were 0.56 and 0.82, respectively. Intra-rater reliability for the hazard classification was 0.81 for individuals and 0.88 for teams. The results indicate that the Strain Index has good test-retest reliability.

  15. Simple test guidelines for screening oilspill sorbents for toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Blenkinsopp, S.A.; Sergy, G. [Environment Canada, Edmonton, AB (Canada); Doe, K.; Jackman, P. [Environment Canada, Moncton, NB (Canada); Huybers, A. [Harris Industrial Testing Services Ltd., Milford, NS (Canada)

    1998-09-01

    Environment Canada`s Emergencies Science Division has established a program to develop a standard test method suitable for evaluating the toxicity of common sorbent materials. Sorbents are used to absorb or adsorb spilled oil and other hazardous materials. They vary widely in composition and packaging. They are often treated with oleophilic and hydrophobic compounds to improve performance and have been used in large quantities during oil spills. Until now, their potential toxicity has never been considered. Three tests have been evaluated to determine how appropriate they are in screening the toxicity of sorbents. Seven toxicity test recommendations for sorbents were presented. 7 refs., 3 tabs., 2 figs.

  16. Alteration in metabolism and toxicity of acetaminophen upon repeated administration in rats.

    Science.gov (United States)

    Kim, Sun J; Lee, Min Y; Kwon, Do Y; Kim, Sung Y; Kim, Young C

    2009-10-01

    Our previous studies showed that administration of a subtoxic dose of acetaminophen (APAP) to female rats increased generation of carbon monoxide from dichloromethane, a metabolic reaction catalyzed mainly by cytochrome P450 (CYP) 2E1. In this study we examined the changes in metabolism and toxicity of APAP upon repeated administration. An intraperitoneal dose of APAP (500 mg/kg) alone did not increase aspartate aminotransferase, alanine aminotransferase, or sorbitol dehydrogenase activity in serum, but was significantly hepatotoxic when the rats had been pretreated with an identical dose of APAP 18 h earlier. The concentrations and disappearance of APAP and its metabolites in plasma were monitored for 8 h after the treatment. APAP pretreatment reduced the elevation of APAP-sulfate, but increased APAP-cysteine concentrations in plasma. APAP or APAP-glucuronide concentrations were not altered. Administration of a single dose of APAP 18 h before sacrifice increased microsomal CYP activities measured with p-nitrophenol, p-nitroanisole, and aminopyrine as probes. Expression of CYP2E1, CYP3A, and CYP1A proteins in the liver was also elevated significantly. The results suggest that administration of APAP at a subtoxic dose may result in an induction of hepatic CYP enzymes, thereby altering metabolism and toxicological consequences of various chemical substances that are substrates for the same enzyme system.

  17. 78 FR 66700 - Toxic Substances Control Act Chemical Testing; Receipt of Test Data

    Science.gov (United States)

    2013-11-06

    ... Mammals; Bacterial Reverse Mutation Assay; Chromosomal Aberrations; Combined Repeated Dose Toxicity with... heat set, cold Study in Zebra Fish set, and sheet-fed (Brachydanio rerio). applications. Acute Toxicity Study in Daphnia Magna with C.I. Pigment Blue 61 (Static). Fresh Water Algal Growth 0442,...

  18. Toxicity Tests for Ensuring Succesful Industrial Wastewater Treatment Plant Operation

    Science.gov (United States)

    Cěbere, B.; Faltiņa, E.; Zelčāns, N.; Kalniņa, D.

    2009-01-01

    Industrial wastewaters are complex and can be polluted by non-biodegradable end toxic organic compounds and are a serious threat to the environment. Chemical procedure alone cannot provide sufficient information. A complete evaluation of wastewaters should include ecotoxicological tests too, especially concerning the complex wastewaters. In the literature review the authors attempted to establish which is the more promising and suitable aquatic toxicology test for sewage treatment plant influent toxicity monitoring. A variety of types of organisms representing different trophic levels and many different species are used for aquatic toxicity testing. Toxicity characterization would be needed both for influents and effluents of wastewater treatment plant. For the purpose of screening biological wastewater treatment influent, toxicity to activated sludge microorganisms is important and toxicology tests here used are respirometry and bioluminescence toxicology tests. Respirometry toxicity tests are easy, fast and inexpensive compared to other approaches. Bioluminescence has been widely used, the most thoroughly investigated test system is the Microtox. The toxicity tests have also been compared by different authors. International, national and regional authorities use these tools to meet various regulatory and legislative requirements. Importance of biotesting has been emphasized also in EU legislation.

  19. Microcomputer-based tests for repeated-measures: Metric properties and predictive validities

    Science.gov (United States)

    Kennedy, Robert S.; Baltzley, Dennis R.; Dunlap, William P.; Wilkes, Robert L.; Kuntz, Lois-Ann

    1989-01-01

    A menu of psychomotor and mental acuity tests were refined. Field applications of such a battery are, for example, a study of the effects of toxic agents or exotic environments on performance readiness, or the determination of fitness for duty. The key requirement of these tasks is that they be suitable for repeated-measures applications, and so questions of stability and reliability are a continuing, central focus of this work. After the initial (practice) session, seven replications of 14 microcomputer-based performance tests (32 measures) were completed by 37 subjects. Each test in the battery had previously been shown to stabilize in less than five 90-second administrations and to possess retest reliabilities greater than r = 0.707 for three minutes of testing. However, all the tests had never been administered together as a battery and they had never been self-administered. In order to provide predictive validity for intelligence measurement, the Wechsler Adult Intelligence Scale-Revised and the Wonderlic Personnel Test were obtained on the same subjects.

  20. A New Way in Deciding NOAEL Based on the Findings from GLP-Toxicity Test

    OpenAIRE

    Park, Yeong-Chul; Cho, Myung-Haing

    2011-01-01

    The FDA guidance focuses on the use of the NOAEL to establish the maximum recommended starting dose. The majority of NOAEL has been described inaccurately or incompletely in final reports for 90-days repeated dose toxicity test based on GLP (good laboratory practice) regulation. This is the most serious one of reasons for why most pharmaceutical companies targeting global markets have disregarded the final report produced from GLP facilities in Korea. The problems in deciding NOAEL reflected ...

  1. Rapid toxicity testing based on yeast respiratory activity

    Energy Technology Data Exchange (ETDEWEB)

    Haubenstricker, M.E. (Environmental Protection Agency, Ann Arbor, MI (USA)); Meier, P.G.; Mancy, K.H. (Univ. of Michigan, Ann Arbor (USA)); Brabec, M.J. (Eastern Michigan Univ., Ypsilanti (USA))

    1990-05-01

    Rapid and economical techniques are needed to determine the effects of environmental contaminants. At present, the main methods to assess the impact of pollutants are based on chemical analysis of the samples. Invertebrate and vertebrate exposures have been used over the last two decades in assessing acute and chronic toxicities. However, these tests are labor intensive and require several days to complete. An alternative to whole organism exposure is to determine toxic effects in monocellular systems. Another approach for assessing toxicity is to monitor sensitive, nonspecific, subcellular target sites such as mitochondria. Changes in mitochondrial function which could indicate a toxic effect can be demonstrated readily after addition of a foreign substance. In initial assessments of various chemicals, rat liver mitochondria (RLM) were evaluated as a biological sensor of toxicity. False toxicity assessments will result if these ions are present even though they are generally considered nontoxic. Because of these disadvantages, an alternative mitochondrial system, such as found in bakers yeast, was evaluated.

  2. Reference toxicants for toxicity testing using Caenorhabditis elegans in aquatic media

    Energy Technology Data Exchange (ETDEWEB)

    Cressman, C.P. III; Williams, P.L. [Univ. of Georgia, Athens, GA (United States)

    1997-09-01

    Caenorhabditis elegans aquatic toxicity assays were standardized with five common reference toxicants: CdCl{sub 2}, NaCl, KCl, sodium lauryl sulfate (SLS), and sodium pentachlorophenate (PCP). Aquatic toxicity testing was conducted in 3 media: a standard C. elegans medium; EPA moderately hard reconstituted water; and EPA moderately hard mineral water. Test duration in each medium was 24h without a food source, and 24h and 48h with Escherichia coli strain OP50 as a food source. Each test was replicated three times with each replicate having 6 wells per concentration, 10 worms per well. LC{sub 50} values were calculated using probit analysis. The average LC{sub 50}s for each set of replications were compared to assess sensitivity and reproducibility of the data, identifying expected variation between replicate tests. These reference toxicants increase the database for C. elegans and provide a benchmark for further application.

  3. Problems and solutions for the analysis of somatic CAG repeat expansion and their relationship to Huntington's disease toxicity.

    Science.gov (United States)

    Budworth, Helen; McMurray, Cynthia T

    2016-01-01

    Huntington's Disease is caused by inheritance of a single disease-length allele harboring an expanded CAG repeat, which continues to expand in somatic tissues with age. Whether somatic expansion contributed to toxicity was unknown. From extensive work from multiple laboratories, it has been made clear that toxicity depended on length of the inherited allele, but whether preventing or delaying somatic repeat expansion in vivo would be beneficial was unknown, since the inherited disease allele was still expressed. In Budworth et al., we provided definitive evidence that suppressing the somatic expansion in mice substantially delays disease onset in littermates that inherit the same disease-length allele. This key discovery opens the door for therapeutic approaches targeted at stopping or shortening the CAG tract during life. The analysis was difficult and, at times, non-standard. Here, we take the opportunity to discuss the challenges, the analytical solutions, and to address some controversial issues with respect to expansion biology.

  4. Bacterial and enzymatic bioassays for toxicity testing in the environment

    Energy Technology Data Exchange (ETDEWEB)

    Bitton, G.; Koopman, B. (Department of Environmental Engineering Sciences, University of Florida, Gainesville (United States))

    1992-01-01

    Microbioassays using bacteria or enzymes are increasingly applied to measure chemical toxicity in the environment. Attractive features of these assays may include low cost, rapid response to toxicants, high sample throughput, modest laboratory equipment and space requirements, low sample volume, portability, and reproducible responses. Enzymatic tests rely on measurement of either enzyme activity or enzyme biosynthesis. Dehydrogenases are the enzymes most used in toxicity testing. Assay of dehydrogenase activity is conveniently carried out using oxidoreduction dyes such as tetrazolium salts. Other enzyme activity tests utilize ATPases, esterases, phosphatases, urease, luciferase, beta-galactosidase, protease, amylase, or beta-glucosidase. Recently, the inhibition of enzyme (beta-galactosidase, tryptophanase, alpha-glucosidase) biosynthesis has been explored as a basis for toxicity testing. Enzyme biosynthesis was found to be generally more sensitive to organic chemicals than enzyme activity.107 references.

  5. Toxicity and Antioxidant Tests of Morinda citrifolia (noni Seed Extract

    Directory of Open Access Journals (Sweden)

    Brett J. West

    2011-08-01

    Full Text Available The aim of the current study was to evaluate Morinda citrifolia (noni seed extract, a food ingredient, for potential toxicity and antioxidant activity. Nitrates, nitrites, phytic acid, oxalic acid, as well as aflatoxins B1, B2, G1 and G2 were not detected in the extract. The extract was also non-cytoxic (LC50 > 1 mg/mL in the 24 and 40 h brine shrimp toxicity test. There were no symptoms of toxicity in a subacute (28 day oral toxicity test in Sprague-Dawley rats. Noni seed extract did not display any genotoxic potential in a primary DNA damage test in E. coli PQ37. The extract did exhibit significant antioxidant activity in the Oxygen Radical Absorbance Capacity (ORAC and Ferric Reducing Antioxidant Power (FRAP tests.

  6. Neutral red uptake cytotoxicity tests for estimating starting doses for acute oral toxicity tests.

    Science.gov (United States)

    Stokes, William S; Casati, Silvia; Strickland, Judy; Paris, Michael

    2008-05-01

    In vitro cytotoxicity assays can be used as alternative toxicity tests to reduce the total number of animals needed for acute oral toxicity tests. This unit describes two methods for determining the in vitro cytotoxicity of test substances using neutral red uptake (NRU) and using the in vitro data to determine starting doses for in vivo acute oral systemic toxicity tests, e.g., the up-and-down procedure or the acute toxic class method. The use of the NRU methods to determine starting doses for acute oral toxicity tests may reduce the number of animals required, and for relatively toxic substances, this approach may also reduce the number of animals that die or require humane euthanasia due to severe toxicity. An interlaboratory validation study has demonstrated that the methods are useful and reproducible for these purposes. Two standardized protocols provide details for performing NRU tests with rodent and human cells.

  7. Collaborative work on evaluation of ovarian toxicity. 2) Two- or four-week repeated dose studies and fertility study of mifepristone in female rats.

    Science.gov (United States)

    Tamura, Toru; Yokoi, Ryohei; Okuhara, Yuji; Harada, Chiho; Terashima, Yukari; Hayashi, Morimichi; Nagasawa, Tatsuya; Onozato, Tomoya; Kobayashi, Kazuo; Kuroda, Junji; Kusama, Hiroshi

    2009-01-01

    In order to assess ovarian pathological changes and their relationship to changes in female fertility parameters, mifepristone, a progesterone receptor antagonist, was selected as the test article and was administered orally to female rats at dose levels of 0, 0.8, 4, 20 and 100 mg/kg for 2 or 4 weeks in repeated dose-toxicity studies and in a female fertility study at dose levels of 0, 0.8, 4 and 20 mg/kg from > 2 weeks before copulation to postcoital day 7. In the repeated dose toxicity studies, persistent estrus was seen in the vaginal smears, and multiple cysts in the ovaries at necropsy, increases in luteinized cysts and hypertrophy of previously formed corpora lutea were observed in the histopathological examination of ovaries in rats receiving 20 mg/kg or more for 2 or 4 weeks. In female fertility studies, persistent vaginal cornification was also observed at 20 mg/kg and the precoital interval was significantly shortened. All of the animals were completely infertile when dosed with 20 mg/kg during the post-coital period. An increase in pre-implantation losses was observed in the animals treated with 20 mg/kg during the pre-coital phase, while treatment with 4 mg/kg mifepristone during the post-coital phase induced an increase in post-implantation losses. These results suggested that a 2-week administration period would be sufficient to detect the ovarian toxicity of mifepristone in repeated dose toxicity study and the pathological findings in the ovaries would reflect the alterations in female reproductive endpoints in the female fertility study.

  8. Repeated-Doses Toxicity Study of the Essential Oil of Hyptis martiusii Benth. (Lamiaceae in Swiss Mice

    Directory of Open Access Journals (Sweden)

    Germana Freire Rocha Caldas

    2013-01-01

    Full Text Available Hyptis martiusii Benth. (Lamiaceae is found in abundance in Northeastern Brazil where it is used in traditional medicine to treat gastric disorders. Since there are no studies reporting the toxicity and safety profile of this species, we investigated repeated-doses toxicity of the essential oil of Hyptis martiusii (EOHM. Swiss mice of both sexes were orally treated with EOHM (100 and 500 mg/kg for 30 days, and biochemical, hematological, and morphological parameters were determined. No toxicity signs or deaths were recorded during the treatment with EOHM. The body weight gain was not affected, but there was an occasional variation in water and food consumption among mice of both sexes treated with both doses. The hematological and biochemical profiles did not show significant differences except for a decrease in the MCV and an increase in albumin, but these variations are within the limits described for the species. The microscopic analysis showed changes in liver, kidneys, lungs, and spleen; however, these changes do not have clinical relevance since they varied among the groups, including the control group. The results indicate that the treatment of repeated-doses with the essential oil of Hyptis martiusii showed low toxicity in mice.

  9. Zinc oxide nanoparticles: a 90-day repeated-dose dermal toxicity study in rats

    Directory of Open Access Journals (Sweden)

    Ryu HJ

    2014-12-01

    Full Text Available Hwa Jung Ryu,1,* Mu Yeb Seo,2,* Sung Kyu Jung,1 Eun Ho Maeng,2 Seung-Young Lee,2 Dong-Hyouk Jang,2 Taek-Jin Lee,2 Ki-Yeon Jo,2 Yu-Ri Kim,3 Kyu-Bong Cho,4 Meyoung-Kon Kim,3 Beom Jun Lee,5 Sang Wook Son1 1Department of Dermatology, Korea University College of Medicine, Seoul, 2Korea Testing and Research Institute, Gyunggido, 3Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul, 4Department of Clinical Laboratory Science, Shinheung College, Uijeongbu, 5College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic of Korea *These authors contributed equally to this work and both should be considered first authors Abstract: Zinc oxide (ZnO works as a long-lasting, broad-spectrum physical sunblock, and can prevent skin cancer, sunburn, and photoaging. Nanosized ZnO particles are used often in sunscreens due to consumer preference over larger sizes, which appear opaque when dermally applied. Although the US Food and Drug Administration approved the use of nanoparticles (NPs in sunscreens in 1999, there are ongoing safety concerns. The aim of this study was to evaluate the subchronic toxicity of ZnO NPs after dermal application according to the Organization for Economic Cooperation and Development Test Guidelines 411 using Good Laboratory Practice. Sprague Dawley rats were randomly divided into eight (one control, one vehicle control, three experimental, and three recovery groups. Different concentrations of ZnO NPs were dermally applied to the rats in the experimental groups for 90 days. Clinical observations as well as weight and food consumption were measured and recorded daily. Hematology and biochemistry parameters were determined. Gross pathologic and histopathologic examinations were performed on selected tissues from all animals. Analyses of tissue were undertaken to determine target organ tissue distribution. There was no increased mortality in the experimental group. Although there

  10. Rapid Field Toxicity Test for Water Supplies

    Science.gov (United States)

    1994-02-28

    of trichothecenes (2). The correlation of the novel method with the Mysid trichothecenes paper described a perfect qualitative shrimp test, using fresh...test designed for human or animal consumption. organisms in a standard time LED light emitting diode CONCLUSION ml milliliter ppm parts per million A...potassium. of Trichothecenes ," Naval Research Laboratory Memorwdm Report 5738 (March 1986) Logistics dictate a day or so to test field samples in the

  11. Evaluating the zebrafish embryo toxicity test for pesticide hazard screening.

    Science.gov (United States)

    Glaberman, Scott; Padilla, Stephanie; Barron, Mace G

    2016-10-04

    Given the numerous chemicals used in society, it is critical to develop tools for accurate and efficient evaluation of potential risks to human and ecological receptors. Fish embryo acute toxicity tests are 1 tool that has been shown to be highly predictive of standard, more resource-intensive, juvenile fish acute toxicity tests. However, there is also evidence that fish embryos are less sensitive than juvenile fish for certain types of chemicals, including neurotoxicants. The utility of fish embryos for pesticide hazard assessment was investigated by comparing published zebrafish embryo toxicity data from pesticides with median lethal concentration 50% (LC50) data for juveniles of 3 commonly tested fish species: rainbow trout, bluegill sunfish, and sheepshead minnow. A poor, albeit significant, relationship (r(2 ) = 0.28; p zebrafish embryo and juvenile fish toxicity when pesticides were considered as a single group, but a much better relationship (r(2)  = 0.64; p pesticide mode of action was factored into an analysis of covariance. This discrepancy is partly explained by the large number of neurotoxic pesticides in the dataset, supporting previous findings that commonly used fish embryo toxicity test endpoints are particularly insensitive to neurotoxicants. These results indicate that it is still premature to replace juvenile fish toxicity tests with embryo-based tests such as the Organisation for Economic Co-operation and Development Fish Embryo Acute Toxicity Test for routine pesticide hazard assessment, although embryo testing could be used with other screening tools for testing prioritization. Environ Toxicol Chem 2016;9999:1-6. © 2016 SETAC.

  12. Organophosphorus insecticides: Toxic effects and bioanalytical tests for evaluating toxicity during degradation processes

    Directory of Open Access Journals (Sweden)

    Čolović Mirjana B.

    2013-01-01

    Full Text Available Organophosphorus insecticides have been the most applied group of insecticides for the last two decades. Their main toxic effects are related to irreversible inactivation of acetylcholinesterase (AChE. Actually, they covalently bind to serine OH group in the enzyme active site forming phosphorylated enzyme that cannot hydrolyze acetylcholine. Organophosphorus insecticides in the environment undergo the natural degradation pathway including mainly homogeneous and heterogeneous hydrolysis (especially at high pH generating non-inhibiting products. Additionally, thio organophosphates are easily oxidized by naturally present oxidants and UV light, forming more toxic and stable oxons. Thus, oxidative degradation procedures, generally referred as advanced oxidation processes (AOP, have been applied for their efficient removal from contaminated waters. The most applied bioassays to monitor the organophosphate toxicity i.e. the detoxification degree during AOP are Vibrio fischeri and AChE bioassays. Vibrio fischeri toxicity test exploits bioluminescence as the measure of luciferase activity of this marine bacterium, whereas AChE bioassay is based on AChE activity inhibition. Both bioanalytical techniques are rapid (several minutes, simple, sensitive and reproducible. Vibrio fischeri test seems to be a versatile indicator of toxic compounds generated in AOP for organophosphorus insecticides degradation. However, detection of neurotoxic AChE inhibitors, which can be formed in AOP of some organophosphates, requires AChE bioassays. Therefore, AChE toxicity test is more appropriate for monitoring the degradation processes of thio organophosphates, because more toxic oxo organophosphates might be formed and overlooked by Vibrio fischeri bioluminescence inhibition. In addition, during organophosphates removal by AOP, compounds with strong genotoxic potential may be formed, which cannot be detected by standard toxicity tests. For this reason, determination of

  13. Changes of lead speciation and microbial toxicity in soil treated with repeated Pb exposure in the presence of BDE209.

    Science.gov (United States)

    Zhang, Rong; Zhang, Wei; Liu, Gao; Lin, Kuangfei; Fu, Rongbing

    2016-03-01

    Lead (Pb) and decabromodiphenyl ether (BDE209) are main pollutants at electric waste (e-waste) recycling sites (EWRSs), and their joint toxicological effects have received extensive attention. Frequently, soil pollution at EWRSs usually results from the occurrence of repeated single or multiple pollution events, with continuous impacts on soil microorganisms. Therefore, a laboratory incubation study was conducted to determine Pb bioavailability and microbial toxicity in repeated Pb-polluted soil in the presence of BDE209 for the first time. We evaluated the impacts of repetitive exposure trials on chemical fractions of Pb, and the results showed that repeated single Pb pollution event resulted in an increase of carbonates fraction of Pb, which was different from one-off single Pb exposure. Moreover, one-off Pb-treated groups exhibited higher I R (reduced partition index) values on day 30 and all treatments remained the same I R level at the end of incubation period. The parameters of microbial toxicity were well reflected by soil enzymes. During the entire incubation, the dehydrogenase and urease activities were significantly inhibited by Pb (P soil enzymes were clearly observed (P < 0.05 or 0.01). Such observations would provide useful information for ecological effects of Pb and BDE209 at EWRSs.

  14. Unnecessary repeat requesting of tests: an audit in a government hospital immunology laboratory.

    Science.gov (United States)

    Kwok, J; Jones, B

    2005-05-01

    Unnecessary repeat requesting of tests can make up a large proportion of a laboratory's workload. This audit set out to establish the size of this problem and to identify the circumstances under which these repeat requests were made in a government tertiary hospital immunology laboratory. The numbers of tests for immunoglobulin measurement, common autoantibodies, and tumour markers that were repeated over a 12 month period were analysed by interrogating the Delphic laboratory computer system using a management information system for raw data enquiry protocol. Repeat requests within 12 weeks of a previous request made up 16.78% of the total workload. The total cost of the tests was estimated at 132 151 US dollars. The waste of technician time and reagents as a result of unnecessary repeat testing is excessive. Many of these tests might be eliminated with the use of interventions such as computerised reminders.

  15. Unique evolutionary trajectories in repeated adaptation to hydrogen sulphide-toxic habitats of a neotropical fish (Poecilia mexicana).

    Science.gov (United States)

    Pfenninger, Markus; Patel, Simit; Arias-Rodriguez, Lenin; Feldmeyer, Barbara; Riesch, Rüdiger; Plath, Martin

    2015-11-01

    Replicated ecological gradients are prime systems to study processes of molecular evolution underlying ecological divergence. Here, we investigated the repeated adaptation of the neotropical fish Poecilia mexicana to habitats containing toxic hydrogen sulphide (H2 S) and compared two population pairs of sulphide-adapted and ancestral fish by sequencing population pools of >200 individuals (Pool-Seq). We inferred the evolutionary processes shaping divergence and tested the hypothesis of increase of parallelism from SNPs to molecular pathways. Coalescence analyses showed that the divergence occurred in the face of substantial bidirectional gene flow. Population divergence involved many short, widely dispersed regions across the genome. Analyses of allele frequency spectra suggest that differentiation at most loci was driven by divergent selection, followed by a selection-mediated reduction of gene flow. Reconstructing allelic state changes suggested that selection acted mainly upon de novo mutations in the sulphide-adapted populations. Using a corrected Jaccard index to quantify parallel evolution, we found a negligible proportion of statistically significant parallel evolution of Jcorr  = 0.0032 at the level of SNPs, divergent genome regions (Jcorr  = 0.0061) and genes therein (Jcorr  = 0.0091). At the level of metabolic pathways, the overlap was Jcorr  = 0.2545, indicating increasing parallelism with increasing level of biological integration. The majority of pathways contained positively selected genes in both sulphide populations. Hence, adaptation to sulphidic habitats necessitated adjustments throughout the genome. The largely unique evolutionary trajectories may be explained by a high proportion of de novo mutations driving the divergence. Our findings favour Gould's view that evolution is often the unrepeatable result of stochastic events with highly contingent effects.

  16. Neurobehavioral toxicity of a repeated exposure (14 days to the airborne polycyclic aromatic hydrocarbon fluorene in adult Wistar male rats.

    Directory of Open Access Journals (Sweden)

    Julie Peiffer

    Full Text Available Fluorene is one of the most abundant polycyclic aromatic hydrocarbons in air and may contribute to the neurobehavioral alterations induced by the environmental exposure of humans to PAHs. Since no data are available on fluorene neurotoxicity, this study was conducted in adult rats to assess the behavioral toxicity of repeated fluorene inhalation exposure. Male rats (n = 18/group were exposed nose-only to 1.5 or 150 ppb of fluorene 6 hours/day for 14 consecutive days, whereas the control animals were exposed to non-contaminated air. At the end of the exposure, animals were tested for activity and anxiety in an open-field and in an elevated-plus maze, for short-term memory in a Y-maze, and for spatial learning in an eight-arm maze. The results showed that the locomotor activity and the learning performances of the animals were unaffected by fluorene. In parallel, the fluorene-exposed rats showed a lower level of anxiety than controls in the open-field, but not in the elevated-plus maze, which is probably due to a possible difference in the aversive feature of the two mazes. In the same animals, increasing blood and brain levels of fluorene monohydroxylated metabolites (especially the 2-OH fluorene were detected at both concentrations (1.5 and 150 ppb, demonstrating the exposure of the animals to the pollutant and showing the ability of this compound to be metabolized and to reach the cerebral compartment. The present study highlights the possibility for a 14-day fluorene exposure to induce some specific anxiety-related behavioral disturbances, and argues in favor of the susceptibility of the adult brain when exposed to volatile fluorene.

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

    Science.gov (United States)

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

    2014-01-01

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

  18. A Mini-Nitrification Test for Toxicity Screening, Minntox

    DEFF Research Database (Denmark)

    Arvin, Erik; Dyreborg, Søren; Menck, C.

    1994-01-01

    There is a high demand for a rapid, simple, and inexpensive test for screening of the toxicity of wastewater, polluted groundwater and chemicals in order to protect sewage treatment plants and aquatic and terrestrial recipients. The mini-nitrification test, MINNTOX, presented here, fulfils...

  19. Repeated dose liver micronucleus assay using adult mice with multiple genotoxicity assays concurrently performed as a combination test.

    Science.gov (United States)

    Hagio, Soichiro; Furukawa, Satoshi; Abe, Masayoshi; Kuroda, Yusuke; Hayashi, Seigo; Ogawa, Izumi

    2014-06-01

    Recently, the liver micronucleus (MN) assay using young adult rats with repeated administrations has been investigated by employing a new method without partial hepatectomy or in situcollagenase perfusion as the repeated dose liver MN (RDLMN) assay by Narumi et al. (2012). In our study, in order to investigate the possibility of the RDLMN assay using young adult mice instead of rats and the feasibility of employing some genotoxicity assays along with the RDLMN assay as a combination test, two genotoxic carcinogens (N,N-diethylnitrosoamine (DEN) and cisplatin (CIS)) and a nongenotoxic carcinogen (phenobarbital sodium (PHE)) were administered to mice for 15 or 29 days. Then, the liver MN assay, peripheral blood (PB) MN assay and comet assay using the liver and kidney were concurrently performed as a combination test. DEN showed positive responses to all endpoints except MN induction in PB after 15 days of repeat administration. A cross-linking agent, CIS, showed MN induction in liver after 29 days of repeat administration, and in PB after 15 and 29 days of repeat administration, although the comet assay yielded negative responses for both organs at both sampling times. PHE yielded negative responses for all endpoints. In conclusion, it is suggested that the RDLMN assay using mice is a feasible method to be integrated into the general repeated toxicity test along with the combination assays, i.e., comet assay or PB MN assay, which would help in risk assessment for carcinogenicity by comparing the results of combination assays with each other.

  20. Toxic PR poly-dipeptides encoded by the C9orf72 repeat expansion target LC domain polymers

    Science.gov (United States)

    Lin, Yi; Mori, Eiichiro; Kato, Masato; Xiang, Siheng; Wu, Leeju; Kwon, Ilmin; McKnight, Steven L.

    2016-01-01

    Summary Two complementary approaches were used in search of the intracellular targets of the toxic PR poly-dipeptide encoded by the repeat sequences expanded in the C9orf72 form of amyotrophic lateral sclerosis. The top categories of PRn-bound proteins include constituents of non-membrane invested cellular organelles and intermediate filaments. PRn targets are enriched for the inclusion of low complexity (LC) sequences. Evidence is presented indicating that LC sequences represent the direct target of PRn binding, and that interaction between the PRn poly-dipeptide and LC domains is polymer-dependent. These studies indicate that PRn-mediated toxicity may result from broad impediments to the dynamics of cell structure and information flow from gene to message to protein. PMID:27768897

  1. Toxic PR Poly-Dipeptides Encoded by the C9orf72 Repeat Expansion Target LC Domain Polymers.

    Science.gov (United States)

    Lin, Yi; Mori, Eiichiro; Kato, Masato; Xiang, Siheng; Wu, Leeju; Kwon, Ilmin; McKnight, Steven L

    2016-10-20

    Two complementary approaches were used in search of the intracellular targets of the toxic PR poly-dipeptide encoded by the repeat sequences expanded in the C9orf72 form of amyotrophic lateral sclerosis. The top categories of PRn-bound proteins include constituents of non-membrane invested cellular organelles and intermediate filaments. PRn targets are enriched for the inclusion of low complexity (LC) sequences. Evidence is presented indicating that LC sequences represent the direct target of PRn binding and that interaction between the PRn poly-dipeptide and LC domains is polymer-dependent. These studies indicate that PRn-mediated toxicity may result from broad impediments to the dynamics of cell structure and information flow from gene to message to protein.

  2. Use of blue crab (Callinectes sapidus) embryos for toxicity testing

    Energy Technology Data Exchange (ETDEWEB)

    Lee, R.; O`Malley, K. [Skidaway Inst. of Oceanography, Savannah, GA (United States)

    1995-12-31

    After fertilization, blue crab embryos develop in egg sacs attached to the female pleopods, often referred to as the sponge. Lipovitellin and lipid droplets in the egg sacs provide energy and nutrition for the developing embryos. Embryos were removed from the sponge and transferred to 24 well culture plates containing sea water with or without toxicants, Each well contained 10 embryos. After 7 to 10 days, embryos hatched to swimming zoea. The effects of toxicants at various concentrations on hatching were determined and the EC{sub 50} calculated. For example, the EC{sub 50} for tributyltin, fenvalerate and mercuric chloride were 50, 30 and 90 ng/liter, respectively. The hatching success of control embryos ranged from 95 to 98%. Formation of the heart, eyespot formation, appendage formation and utilization rate of lipovitellin were also effected by exposure to toxicants. At a low concentration of mercuric ion (30ng/liter) the heart formed, but there was no heart beat. Eyespot formation was abnormal in the presence of high concentrations of cadmium (2 {micro}g/liter) and zinc (5 {micro}g/liter), Crab embryos offer many advantages for toxicity testing of pure compounds or mixtures in water, including toxicity testing of sediment pore water. The crab embryos may also serve as models to understand the effect of specific toxicants on the heart and eye spots of crustaceans.

  3. Modal Testing Repeatability of a Population of Spherical Shells

    Energy Technology Data Exchange (ETDEWEB)

    Robertson, A. [HYTEC, Inc., Boulder, CO (United States); Hemez, F. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Salazar, I. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Duffey, T. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2004-05-01

    In this study, we investigated the variability in modal frequencies obtained from testing a set of hollow, almost spherical marine floats. We investigated four sources of variability: unit-to-unit variability, operator-to-operator variability, test repetition, and accelerometer placement. Because we measured the excitation and response of the marine floats, we were able to estimate impulse response and frequency response functions. Variability is assessed by measuring the deviation of each frequency response function from the mean curve for its test group.

  4. The genomic landscape of rapid, repeated evolutionary rescue from toxic pollution in wild fish

    Science.gov (United States)

    Several populations of Atlantic killifish (Fundulus heteroclitus) in contaminated Atlantic coast estuaries have evolved resistance to the toxic effects of PCBs, dioxins, and PAHs. However, the genetic mechanisms of resistance and whether they are shared among populations is not known. We sequenced t...

  5. Validity and repeatability of a new test for aniseikonia

    OpenAIRE

    Antona Peñalba, Beatriz; Barra Lázaro, Francisco; Barrio de Santos, Ana Rosa; González Díaz-Obregón, Enrique; Sánchez Pérez, Isabel

    2007-01-01

    PURPOSE. The Aniseikonia Inspector 1.1 (AI) is a new software product to measure aniseikonia using red-green anaglyphs. The purpose of this study was to test whether the AI is a valid and reliable test. METHODS. There were two groups of sample subjects: one at risk of aniseikonia, with anisometropia greater than or equal to 1.00 D (n = 29), and a control group (n = 45). The validity was studied by comparing the measured aniseikonia with the aniseikonia simulated with size lenses. The reli...

  6. Functional toxicology: tools to advance the future of toxicity testing

    Directory of Open Access Journals (Sweden)

    Brandon David Gaytán

    2014-05-01

    Full Text Available The increased presence of chemical contaminants in the environment is an undeniable concern to human health and ecosystems. Historically, by relying heavily upon costly and laborious animal-based toxicity assays, the field of toxicology has often neglected examinations of the cellular and molecular mechanisms of toxicity for the majority of compounds – information that, if available, would strengthen risk assessment analyses. Functional toxicology, where cells or organisms with gene deletions or depleted proteins are used to assess genetic requirements for chemical tolerance, can advance the field of toxicity testing by contributing data regarding chemical mechanisms of toxicity. Functional toxicology can be accomplished using available genetic tools in yeasts, other fungi and bacteria, and eukaryotes of increased complexity, including zebrafish, fruit flies, rodents, and human cell lines. Underscored is the value of using less complex systems such as yeasts to direct further studies in more complex systems such as human cell lines. Functional techniques can yield (1 novel insights into chemical toxicity; (2 pathways and mechanisms deserving of further study; and (3 candidate human toxicant susceptibility or resistance genes.

  7. Review of the use of Ceramium tenuicorne growth inhibition test for testing toxicity of substances, effluents, products sediment and soil

    Science.gov (United States)

    Eklund, Britta

    2017-08-01

    A growth inhibition test has been developed based on two clones of the red macroalga Ceramium tenuicorne, one originating from 7 PSU and the other from 20 PSU. The species can be adapted to different salinities and the test can be carried out between 4 and 32 PSU. This test became an ISO standard in 2010 (ISO 107 10) for testing of chemicals and water effluents. In this study new and published data has been compiled on toxicity of single substances, waste waters from pulp mills, leachates from antifouling paints, harbour sediments and soil used for maintenance of leisure boats. The results show that the alga is sensitive to both metals and organic compounds and to biocides used in antifouling paints. By testing leachates from antifouling paints these could be ranked according to their toxicity. Similarly, the toxicity of waste waters from pulp mills was determined and the efficiency of secondary treatment evaluated. Further, the test method proved useful to test the toxicity in sediment samples. Sediments from small town harbours and ship lanes were shown to be harmful and compounds originating from antifouling paints were responsible for a large part of the inhibiting effect. The alga proved to be sensitive to contaminants leaking from boat yard soil. The growth inhibition test is a robust test that has high repeatability and reproducibility and easily can be applied on water, soil and sediment samples without being too costly. The species is found worl-wide in temperate waters, which makes the results relevant for large areas. In the Baltic Sea C. tenuicorne is the most common red alga species and is thus particularly relevant for this area. The overall results show that contaminants from boat activities and the use of antifouling paints in particular pose a threat to the environment.

  8. Scanning respirometer for toxicity tests using micro-organisms

    Science.gov (United States)

    Zhang, Min-Quan; Li, Xiang-Ming; Wong, Yuk-Shan; Kwan, FolkYear

    1995-09-01

    A novel respirometer is developed for microbial toxicity tests. The respirometer is based on luminescent quenching of oxygen to measure the concentration of dissolved oxygen in cell vessels and evaluate the toxicity of chemicals by monitoring the effect of toxicants on cell respiration of micro-organisms. The oxygen sensing element is ruthenium complex absorbed on the surface of silica particles followed by immobilizing on a silicone rubber film. The oxygen sensing film is coated on the inner bottom of a transparent cell vessel. A sensing device scanning under the cell vessel is used for remote monitoring of the oxygen concentration inside the cell vessels so that a large number of samples can be handled in one batch. The sensing device includes the excitation light sources and an optical cable connected to a filter and a photomultiplier tube for detecting the luminescence in the cell vessel which can then be related to the dissolved oxygen concentration inside the cell vessel. The movement of the sensing device and data acquisition are controlled by a personal computer. The toxicity of heavy metals to activated sludge, soil bacteria and E. coli were tested using the present device. The scanning respirometer provides a new alternative for fast and large scale screening and monitoring of toxicants using micro-organisms.

  9. Repeated dose oral toxicity of inorganic mercury in wistar rats: biochemical and morphological alterations

    Directory of Open Access Journals (Sweden)

    M. D. Jegoda

    2013-06-01

    Full Text Available Aim: The study was conducted to find out the possible toxic effect of mercuric chloride (HgCl2 at the histological, biochemical, and haematological levels in the wistar rats for 28 days. Materials and Methods: The biochemical and hematological alteration were estimated in four groups of rat (each group contain ten animals, which were treated with 0 (control, 2, 4, and 8 mg/kg body weight of HgCl2 through oral gavage. At the end of study all rats were sacrificed and subjected for histopathology. Result: A significantly (P < 0.05 higher level of serum alanine amino transferase (ALT, gamma Glutamyle Transferase, and creatinine were recorded in treatment groups, while the level of alkaline phosphtase (ALP was significantly decreased as compared to the control group. The toxic effect on hematoclogical parameter was characterized by significant decrease in hemoglobin, packed cell volume, total erythrocytes count, and total leukocyte count. Gross morphological changes include congestion, severe haemorrhage, necrosis, degenerative changes in kidneys, depletion of lymphocyte in spleen, decrease in concentration of mature spermatocyte, and edema in testis. It was notable that kidney was the most affected organ. Conclusion: Mercuric chloride (HgCl caused dose-dependent toxic effects on blood parameters and kidney. [Vet World 2013; 6(8.000: 563-567

  10. Clinical Characteristics of Patients Who Test Positive for Clostridium difficile by Repeat PCR

    Science.gov (United States)

    Stotler, Brie; Jackman, Dana; Whittier, Susan; Della-Latta, Phyllis

    2014-01-01

    The high sensitivity of PCR assays for diagnosing Clostridium difficile infection (CDI) has greatly reduced the need for repeat testing after a negative result. Nevertheless, a small subset of patients do test positive within 7 days of a negative test. The aim of this study was to evaluate the clinical characteristics of these patients to determine when repeat testing may be appropriate. The results of all Xpert C. difficile PCR (Cepheid, Sunnyvale CA) tests performed in the clinical microbiology laboratory at New York-Presbyterian Hospital, Columbia University Medical Center (NYPH/CUMC) from 1 May 2011 through 6 September 2013, were reviewed. A retrospective case-control study was performed, comparing patients who tested positive within 7 days of a negative test result to a random selection of 50 controls who tested negative within 7 days of a negative test result. During the study period, a total of 14,875 tests were performed, of which 1,066 were repeat tests (7.2%). Eleven of these repeat tests results were positive (1.0%). The only risk factor independently associated with repeat testing positive was history of a prior CDI (odds ratio [OR], 19.6 [95% confidence interval {CI}, 4.0 to 19.5], P < 0.001). We found that patients who test positive for C. difficile by PCR within 7 days of a negative test are more likely to have a history of CDI than are patients who test negative with repeat PCR. This finding may be due to the high rate of disease relapse or the increased likelihood of empirical therapy leading to false-negative results in these patients. PMID:25122866

  11. Clinical characteristics of patients who test positive for Clostridium difficile by repeat PCR.

    Science.gov (United States)

    Green, Daniel A; Stotler, Brie; Jackman, Dana; Whittier, Susan; Della-Latta, Phyllis

    2014-11-01

    The high sensitivity of PCR assays for diagnosing Clostridium difficile infection (CDI) has greatly reduced the need for repeat testing after a negative result. Nevertheless, a small subset of patients do test positive within 7 days of a negative test. The aim of this study was to evaluate the clinical characteristics of these patients to determine when repeat testing may be appropriate. The results of all Xpert C. difficile PCR (Cepheid, Sunnyvale CA) tests performed in the clinical microbiology laboratory at New York-Presbyterian Hospital, Columbia University Medical Center (NYPH/CUMC) from 1 May 2011 through 6 September 2013, were reviewed. A retrospective case-control study was performed, comparing patients who tested positive within 7 days of a negative test result to a random selection of 50 controls who tested negative within 7 days of a negative test result. During the study period, a total of 14,875 tests were performed, of which 1,066 were repeat tests (7.2%). Eleven of these repeat tests results were positive (1.0%). The only risk factor independently associated with repeat testing positive was history of a prior CDI (odds ratio [OR], 19.6 [95% confidence interval {CI}, 4.0 to 19.5], P PCR within 7 days of a negative test are more likely to have a history of CDI than are patients who test negative with repeat PCR. This finding may be due to the high rate of disease relapse or the increased likelihood of empirical therapy leading to false-negative results in these patients.

  12. Polymorphisms in the CAG repeat--a source of error in Huntington disease DNA testing.

    Science.gov (United States)

    Yu, S; Fimmel, A; Fung, D; Trent, R J

    2000-12-01

    Five of 400 patients (1.3%), referred for Huntington disease DNA testing, demonstrated a single allele on CAG alone, but two alleles when the CAG + CCG repeats were measured. The PCR assay failed to detect one allele in the CAG alone assay because of single-base silent polymorphisms in the penultimate or the last CAG repeat. The region around and within the CAG repeat sequence in the Huntington disease gene is a hot-spot for DNA polymorphisms, which can occur in up to 1% of subjects tested for Huntington disease. These polymorphisms may interfere with amplification by PCR, and so have the potential to produce a diagnostic error.

  13. Freshwater toxicity testing using rehydrated Philodina sp. (Rotifera) as test animals.

    Science.gov (United States)

    Snell, Terry W; Johnston, Rachel K; Matthews, Amelia B

    2017-10-01

    Rotifers have become widely used in aquatic toxicology as a rapid screening test for toxicity. The commercial availability of diapausing embryos (cysts) have facilitated their popularity because test animals can be obtained without having to master the details of culturing. Other rotifer species have life stages capable of surviving desiccation and also could be used in non-culture systems for toxicity assessment. In this article, we describe a system for toxicity testing in freshwater based on rehydrating desiccated bdelloid rotifers in the genus Philodina. These animals can remain in this anhydrobiotic state for more than one year and then rehydrate within hours to provide animals for toxicity tests. We describe three endpoints: a 1.5 h ingestion test, a 24 h mortality test, and a five day reproductive test. The latter test requires feeding and a method using a dried commercial product is explained. Using desiccated rotifers and dried food in toxicity tests make this system especially attractive because of its flexibility and low threshold of biological expertise required to execute the tests. The use of the Philodina toxicity test is illustrated with four metals: copper, lead, mercury and cadmium. Reproduction generally was the most sensitive endpoint, with EC50s of 0.33, 0.44, 0.60, and 0.12 mg/L, respectively. Ingestion was a close second with EC50s of 0.13, 1.64, 0.64, and 6.26 mg/L, respectively. © 2017 Wiley Periodicals, Inc.

  14. Toxicity evaluation of zinc aluminium levodopa nanocomposite via oral route in repeated dose study

    Science.gov (United States)

    Kura, Aminu Umar; Cheah, Pike-See; Hussein, Mohd Zobir; Hassan, Zurina; Tengku Azmi, Tengku Ibrahim; Hussein, Nor Fuzina; Fakurazi, Sharida

    2014-05-01

    Nanotechnology, through nanomedicine, allowed drugs to be manipulated into nanoscale sizes for delivery to the different parts of the body, at the same time, retaining the valuable pharmacological properties of the drugs. However, efficient drug delivery and excellent release potential of these delivery systems may be hindered by possible untoward side effects. In this study, the sub-acute toxicity of oral zinc aluminium nanocomposite with and without levodopa was assessed using the Organization for Economic Co-operation and Development guidelines. No sign or symptom of toxicity was observed in orally treated rats with the nanocomposite at 5 and 500 mg/kg concentrations. Body weight gain, feeding, water intake, general survival and organosomatic index were not significantly different between control and treatment groups. Aspartate aminotransferase (AST) in 500 mg/kg levodopa nanocomposite (169 ± 30 U/L), 5 mg/kg levodopa nanocomposite (172 ± 49 U/L), and 500 mg/kg layered double hydroxides (LDH) nanocomposite (175 ± 25 U/L) were notably elevated compared to controls (143 ± 05 U/L); but the difference were not significant ( p > 0.05). However, the differences in aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio of 500 mg/kg levodopa nanocomposite (0.32 ± 0.12) and 500 mg/kg LDH nanocomposite (0.34 ± 0.12) were statistically significant ( p brain was found to be of similar morphology in both control and experimental groups. The kidneys of 500-mg/kg-treated rats with levodopa nanocomposite and LDH nanocomposite were found to have slight inflammatory changes, notably leukocyte infiltration around the glomeruli. The ultra-structure of the neurons from the substantia nigra of nanocomposite-exposed group was similar to those receiving only normal saline. The observed result has suggested possible liver and renal toxicity in orally administered levodopa intercalated nanocomposite; it is also dose-dependent that needs further assessment.

  15. Metal availability and soil toxicity after repeated croppings of Thlaspi caerulescens in metal contaminated soils

    Energy Technology Data Exchange (ETDEWEB)

    Keller, Catherine; Hammer, Daniel

    2004-09-01

    Metal phytoextraction with hyperaccumulating plants could be a useful method to decontaminate soils, but it is not fully validated yet. In order to quantify the efficiency of Cd and Zn extraction from a calcareous soil with and without Fe amendment and an acidic soil, we performed a pot experiment with three successive croppings of Thlaspi caerulescens followed by 3 months without plant and 7 weeks with lettuce. We used a combined approach to assess total extraction efficiency (2 M HNO{sub 3}-extractable metals), changes in metal bio/availability (0.1 M NaNO{sub 3}-extractable metals and lettuce uptake) and toxicity (lettuce biomass and the BIOMETreg] biosensor). The soil solution was monitored over the whole experiment. In the calcareous soil large Cu concentrations were probably responsible for chlorosis symptoms observed on T. caerulescens. When this soil was treated with Fe, the amount of extracted metal by T. caerulescens increased and metal availability and soil toxicity decreased when compared to the untreated soil. In the acidic soil, T. caerulescens was most efficient: Cd and Zn concentrations in plants were in the range of hyperaccumulation and HNO{sub 3}-extractable Cd and Zn, metal bio/availability, soil toxicity, and Cd and Zn concentrations in the soil solution decreased significantly. However, a reduced Cd concentration measured in the third T. caerulescens cropping indicated a decrease in metal availability below a critical threshold, whereas the increase of dissolved Cd and Zn concentrations after the third cropping may be the early sign of soil re-equilibration. This indicates that phytoextraction efficiency must be assessed by different approaches in order not to overlook any potential hazard and that an efficient phytoextraction scheme will have to take into account the different dynamics of the soil-plant system.

  16. The impact of toxicity testing costs on nanomaterial regulation.

    Science.gov (United States)

    Choi, Jae-Young; Ramachandran, Gurumurthy; Kandlikar, Milind

    2009-05-01

    Information about the toxicity of nanoparticles is important in determining how nanoparticles will be regulated. In the U.S., the burden of collecting this information and conducting risk assessment is placed on regulatory agencies without the budgetary means to carry out this mandate. In this paper, we analyze the impact of testing costs on society's ability to gather information about nanoparticle toxicity and whether such costs can reasonably be borne by an emerging industry. We show for the United States that costs for testing existing nanoparticles ranges from $249 million for optimistic assumptions about nanoparticle hazards (i.e., they are primarily safe and mainly require simpler screening assays) to $1.18 billion for a more comprehensive precautionary approach (i.e., all nanomaterials require long-term in vivo testing). At midlevel estimates of total corporate R&D spending, and assuming plausible levels of spending on hazard testing, the time taken to complete testing is likely to be very high (34-53 years) if all existing nanomaterials are to be thoroughly tested. These delays will only increase with time as new nanomaterials are introduced. The delays are considerably less if less-stringent yet risk-averse perspectives are used. Our results support a tiered risk-assessment strategy similar to the EU's REACH legislation for regulating toxic chemicals.

  17. Repeat testing is essential when estimating chronic kidney disease prevalence and associated cardiovascular risk.

    Science.gov (United States)

    Brook, M O; Bottomley, M J; Mevada, C; Svistunova, A; Bielinska, A-M; James, T; Kalachik, A; Harden, P N

    2012-03-01

    Investigations into chronic kidney disease (CKD) and cardiovascular disease in the CKD population may be misleading as they are often based on a single test of kidney function. To determine whether repeat testing at 3 months to confirm a diagnosis of CKD impacts on the estimated prevalence of CKD and the estimated 10-year general cardiovascular risk of the CKD population. Blood and urine samples from presumed healthy volunteers were analysed for evidence of CKD on recruitment and again 3 months later. Estimated 10-year cardiovascular risk was calculated using criteria determined by the Framingham study. Preliminary study: 512 volunteers were screened for CKD. Of the initial results, 206 indicated CKD or eGFR within one standard deviation of abnormal, and 142 (69%) of these were retested. Validation study: 528 volunteers were recruited and invited to return for repeat testing. A total of 214 (40.5%) participants provided repeat samples. A single test indicating CKD had a positive predictive value of 0.5 (preliminary) and 0.39 (validation) for repeat abnormalities 3 months later. Participants with CKD confirmed on repeat testing had a significant increase in estimated 10-year cardiovascular risk over the population as a whole (preliminary: 16.5 vs. 11.9%, P risk. Repeat testing for CKD after 3 months significantly reduces the estimated prevalence of disease and identifies a population with true CKD and a cardiovascular risk significantly in excess of the general population.

  18. Use of neomysis mercedis (crustacea: mysidacea) for estuarine toxicity tests

    Energy Technology Data Exchange (ETDEWEB)

    Brandt, O.M.; Fujimura, R.W.; Finlayson, B.J. (Aquatic Toxicology Laboratory, Elk Grove, CA (United States))

    1993-03-01

    The mysid Neomysis mercedis was examined as a test organism for use in acute toxicity tests at intermediate salinities characteristic of estuarine waters. Several sensitive invertebrate species are available for marine assessments (mysids) and freshwater tests (cladocerans), but few are available for estuarine toxicity tests. Observations in the laboratory indicate that Neomysis mercedis can be reared successfully at a temperature of 17[degrees]C, a salinity of 2%, and a population density less than 5/L. Brine shrimp nauplii Artemia salina, algae, and commercial foods were used to sustain mysid cultures. Neomysis mercedis is vivaparous and can complete its life cycle in 3-4 months. Neomysis mercedis is as sensitive as or more sensitive to toxicants than the marine mysid Mysidopsis bahia and the freshwater cladocerans Daphnia magna, Ceriodaphnia dubia, and Simocephalus serrulatus. The mean 96-h LC50 values (concentrations lethal to half the test animals) for N. mercedis, in increasing order, were 0.20 [mu]g/L for thiobencarb, and for malathion, 14 [mu]g/L for carbofuran, 150 [mu]g/L for copper sulfate, 280 [mu]g/L for thiobencarb, and 1,600 [mu]g/L for molinate. Neonates (5 d postrelease) were generally more sensitive than older juveniles. Coefficients of variation (100[center dot]SD/mean) of LC50 values varied from 21 to 35%. 37 refs., 2 figs., 7 tabs.

  19. The development of a test of repeated-sprint ability for elite women's soccer players.

    Science.gov (United States)

    Gabbett, Tim J

    2010-05-01

    The purpose of this study was to develop a game-specific test of repeated-sprint ability for elite women's soccer players. Nineteen elite women's soccer players (mean +/- SD; age, 18.1 +/- 2.9 y) participated in this study. After familiarization, players completed a repeated-sprint test consisting of 6 x 20-m maximal effort sprints, on a 15-second cycle. At the completion of each sprint, players performed a 10-m deceleration and a 10-m active jog recovery. Ten elite female soccer players performed the test on 2 occasions, 1 week apart, to determine the reliability of the test. In addition, the validity of the repeated-sprint test to discriminate among players of different playing ability was evaluated by testing national (n = 11) and state (n = 8) women's soccer players. Heart rate and blood lactate concentration were recorded to determine the physiological responses to the test. The total sprint time proved to be highly reproducible (intraclass correlation coefficient = 0.91; typical error of measurement = 1.5%). However, the percentage decrement was less reliable (intraclass correlation coefficient = 0.14, typical error of measurement = 19.5%). The repeated-sprint test was valid in discriminating between national- and state-level players, with national players having significantly lower (p repeated-sprint times than state players (20.9 +/- 0.5 s vs. 23.3 +/- 0.4 s). The mean (+/-SD) heart rate and blood lactate concentration were 182 +/- 6 beats/min and 9.3 +/- 2.0 mmol/L, respectively. The results of this study demonstrate that the developed repeated-sprint test discriminates players of higher and lesser skill levels and offers a reliable method of assessing repeated-sprint ability in elite women's soccer players when results are expressed as the total sprint time.

  20. Toxicity assessment of repeated intravenous injections of arginine–glycine–aspartic acid peptide conjugated CdSeTe/ZnS quantum dots in mice

    Directory of Open Access Journals (Sweden)

    Wang YW

    2014-10-01

    Full Text Available You-Wei Wang, Kai Yang, Hong Tang, Dan Chen, Yun-Long Bai Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China Background: Nanotechnology-based near-infrared quantum dots (NIR QDs have many excellent optical properties, such as high fluorescence intensity, good fluorescence stability, and strong tissue-penetrating ability. Integrin αvß3 is highly and specifically expressed in tumor angiogenic vessel endothelial cells of almost all carcinomas. Recent studies have shown that NIR QDs linked to peptides containing the arginine–glycine–aspartic acid (RGD sequence (NIR QDs-RGD can specifically target integrin αvß3 expressed in endothelial cells of tumor angiogenic vessels in vivo, and they offer great potential for early cancer diagnosis, in vivo tumor imaging, and tumor individualized therapy. However, the toxicity profile of NIR QDs-RGD has not been reported. This study was conducted to investigate the toxicity of NIR QDs-RGD when intravenously administered to mice singly and repeatedly at the dose required for successful tumor imaging in vivo.Materials and methods: A NIR QDs-RGD probe was prepared by linking NIR QDs with the maximum emission wavelength of 800 nm (QD800 to the RGD peptide (QD800-RGD. QD800-RGD was intravenously injected to BALB/C mice once or twice (200 pmol equivalent of QD800 for each injection. phosphate-buffered saline solution was used as control. Fourteen days postinjection, toxicity tests were performed, including complete blood count (white blood cell, red blood cell, hemoglobin, platelets, lymphocytes, and neutrophils and serum biochemical analysis (total protein, albumin, albumin/globulin, aspartate aminotransferase, alanine aminotransferase, and blood urea nitrogen. The coefficients of liver, spleen, kidney, and lung weight to body weight were measured, as well as their oxidation and antioxidation indicators, including

  1. Rapid testing methods for food contaminants and toxicants

    Institute of Scientific and Technical Information of China (English)

    Jiachi Chiou; Arthur Ho Hon Leung; Hang Wai Lee; Wing-tak Wong

    2015-01-01

    Food safety is one of the major concerns in every country regardless of the economic and social development. The frequent occurrence of food scandals in the world has led the Chinese government to implement several strategies to fortify the food supply system to a high food safety standard. This relies heavily on laboratory testing services but conventional methods for detection of food contaminants and toxicants are limited by sophisticated sample preparation procedures, long analysis time, large instruments and professional personnel to meet the increasing demands. In this review, we have incorporated most of the current and potential rapid detection methods for many notorious food contaminants and toxicants including microbial agents, toxic ions, pesticides, veterinary drugs and preservatives, as wel as detection of geneticaly modiifed food genes and adulterated edible oil. Development of rapid, accurate, easy-to-use and affordable testing methods could urge food handlers and the public to actively screen for food contaminants and toxicants instead of passively relying on monitoring by the government examination facility. This review also provides several recommendations including how to encourage the public to engage in the food safety management system and provide optimal education and ifnancial assistance that may improve the current Chinese food safety control system.

  2. Utility and necessity of repeat testing of critical values in the clinical chemistry laboratory.

    Directory of Open Access Journals (Sweden)

    Aijun Niu

    Full Text Available CONTEXT: Routine repeat testing of critical values is a long-standing practice in many clinical laboratories; however, its usefulness and necessity remain to be empirically established and no regulatory requirements yet exist for verification of the critical value results obtained by repeat analysis. OBJECTIVE: To determine whether repeat testing of critical values is useful and necessary in a clinical chemistry laboratory. METHODS: A total of 601 chemistry critical values (potassium, n = 255; sodium, n = 132; calcium, n = 108; glucose, n = 106 obtained from 72,259 routine clinical chemistry specimens were repeat tested. The absolute value and the percentage of difference between the two testing runs were calculated for each of the four critical values and then compared with the allowable error limit put forth in the College of American Pathologists (CAP. RESULTS: Among the repeat data for the 601 critical values, a total of 24 showed large differences between the initial result and the repeated result which exceeded the CAP limits for allowable error. The number and rates (% of large differences for within and outside the analytical measurement range (AMR were 12 (2.1% and 12 (41.4%, respectively. For the 572 critical values within the AMR for each test category, the mean absolute difference (mmol/L and difference(% between the two testing runs were: potassium, 0.1 mmol/L (2.7%; sodium, 2.1 mmol/L (1.7%; calcium, 0.05 mmol/L (3.0%; glucose, 0.18 mmol/L (2.6%. CONCLUSIONS: When the initial chemistry critical values are within the AMR, repeated testing does not improve accuracy and is therefore unnecessary. When the initial chemistry critical values are outside the AMR, however, the benefit of repeated testing justifies its performance and makes it necessary. Performing repeat clinical testing on a case-by-case, rather than routine, basis can improve patient care by delivering critical values more rapidly while providing savings

  3. Antioxidant, Antimicrobial Activity and Toxicity Test of Pilea microphylla

    Directory of Open Access Journals (Sweden)

    Amir Modarresi Chahardehi

    2010-01-01

    Full Text Available A total of 9 plant extracts were tested, using two different kinds of extracting methods to evaluate the antioxidant and antimicrobial activities from Pilea microphylla (Urticaceae family and including toxicity test. Antioxidant activity were tested by using DPPH free radical scavenging, also total phenolic contents and total flavonoid contents were determined. Toxicity assay carried out by using brine shrimps. Methanol extract of method I (ME I showed the highest antioxidant activity at 69.51±1.03. Chloroform extract of method I (CE I showed the highest total phenolic contents at 72.10±0.71 and chloroform extract of method II (CE II showed the highest total flavonoid contents at 60.14±0.33. The antimicrobial activity of Pilea microphylla extract was tested in vitro by using disc diffusion method and minimum inhibitory concentration (MIC. The Pilea microphylla extract showed antibacterial activity against some Gram negative and positive bacteria. The extracts did not exhibit antifungal and antiyeast activity. The hexane extract of method I (HE I was not toxic against brine shrimp (LC50 value was 3880 μg/ml. Therefore, the extracts could be suitable as antimicrobial and antioxidative agents in food industry.

  4. Amiodarone lung toxicity: role of pulmonary function tests.

    Science.gov (United States)

    Foresti, V; Carini, L; Lovagnini-Scher, C A; Parisio, E; Scolari, N; Pozzi, G; Clini, V

    1987-01-01

    Forty-three patients treated with amiodarone hydrochloride with an average daily dose of 204.7 +/- 79.4 mg/day for a mean period of 37.1 +/- 25.3 months, were studied by clinical examination, chest roentgenograms, pulmonary function tests and blood gas analyses. The habits of cigarette smoking were also recorded and expressed as cigarette pack/years. Pulmonary function tests did not show any differences from control subjects and no correlation was found between exposure to drug and lung function. However, one patient developed abnormalities in the chest X-ray (interstitial type) and a reduction of carbon monoxide diffusion capacity as a possible manifestation of amiodarone lung toxicity. Nine patients (22%) had a 20% decrease from normal in carbon monoxide diffusion capacity and three (7%) had a 15% decrease in total lung capacity. More treated patients had interstitial abnormalities in the chest X-ray (14%) than controls (5.5%). Although pulmonary function test abnormalities could be detected in patients taking amiodarone, they were not usually severe enough to interfere with gas exchange. Our results confirm the rarity of amiodarone lung toxicity when a low dosage is used, and suggest the advisability of periodical monitoring, including clinical examination, chest X-ray and pulmonary function tests in order to detect the earliest signs of amiodarone lung toxicity.

  5. Drosophila melanogaster As a Model Organism to Study RNA Toxicity of Repeat Expansion-Associated Neurodegenerative and Neuromuscular Diseases

    Science.gov (United States)

    Koon, Alex C.; Chan, Ho Yin Edwin

    2017-01-01

    For nearly a century, the fruit fly, Drosophila melanogaster, has proven to be a valuable tool in our understanding of fundamental biological processes, and has empowered our discoveries, particularly in the field of neuroscience. In recent years, Drosophila has emerged as a model organism for human neurodegenerative and neuromuscular disorders. In this review, we highlight a number of recent studies that utilized the Drosophila model to study repeat-expansion associated diseases (READs), such as polyglutamine diseases, fragile X-associated tremor/ataxia syndrome (FXTAS), myotonic dystrophy type 1 (DM1) and type 2 (DM2), and C9ORF72-associated amyotrophic lateral sclerosis/frontotemporal dementia (C9-ALS/FTD). Discoveries regarding the possible mechanisms of RNA toxicity will be focused here. These studies demonstrate Drosophila as an excellent in vivo model system that can reveal novel mechanistic insights into human disorders, providing the foundation for translational research and therapeutic development. PMID:28377694

  6. 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.

  7. Undetected Toxicity Risk in Pharmacogenetic Testing for Dihydropyrimidine Dehydrogenase

    Directory of Open Access Journals (Sweden)

    Felicia Stefania Falvella

    2015-04-01

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

  8. Lesser Neural Pattern Similarity across Repeated Tests Is Associated with Better Long-Term Memory Retention.

    Science.gov (United States)

    Karlsson Wirebring, Linnea; Wiklund-Hörnqvist, Carola; Eriksson, Johan; Andersson, Micael; Jonsson, Bert; Nyberg, Lars

    2015-07-01

    Encoding and retrieval processes enhance long-term memory performance. The efficiency of encoding processes has recently been linked to representational consistency: the reactivation of a representation that gets more specific each time an item is further studied. Here we examined the complementary hypothesis of whether the efficiency of retrieval processes also is linked to representational consistency. Alternatively, recurrent retrieval might foster representational variability--the altering or adding of underlying memory representations. Human participants studied 60 Swahili-Swedish word pairs before being scanned with fMRI the same day and 1 week later. On Day 1, participants were tested three times on each word pair, and on Day 7 each pair was tested once. A BOLD signal change in right superior parietal cortex was associated with subsequent memory on Day 1 and with successful long-term retention on Day 7. A representational similarity analysis in this parietal region revealed that beneficial recurrent retrieval was associated with representational variability, such that the pattern similarity on Day 1 was lower for retrieved words subsequently remembered compared with those subsequently forgotten. This was mirrored by a monotonically decreased BOLD signal change in dorsolateral prefrontal cortex on Day 1 as a function of repeated successful retrieval for words subsequently remembered, but not for words subsequently forgotten. This reduction in prefrontal response could reflect reduced demands on cognitive control. Collectively, the results offer novel insights into why memory retention benefits from repeated retrieval, and they suggest fundamental differences between repeated study and repeated testing. Repeated testing is known to produce superior long-term retention of the to-be-learned material compared with repeated encoding and other learning techniques, much because it fosters repeated memory retrieval. This study demonstrates that repeated memory

  9. Field assessments in conjunction with whole effluent toxicity testing

    Energy Technology Data Exchange (ETDEWEB)

    La Point, T.W.; Waller, W.T.

    2000-01-01

    Whole effluent toxicity (WET) tests are widely used to assess potential effects of wastewater discharges on aquatic life. This paper represents a summary of chapters in a 1996 Society of Environmental Toxicology and Chemistry-sponsored workshop and a literature review concerning linkages between WET testing and associated field biomonitoring. Most published studies thus far focus primarily on benthic macroinvertebrates and on effluent-dominated stream systems in which effluents demonstrate little or no significant acute toxicity. Fewer studies examine WET test predictability in other aquatic ecosystems (e.g., wetlands, estuaries, large rivers) or deal with instream biota such as fish and primary producers. Published results indicate that standards for the usual WET freshwater test species, Ceriodaphnia dubia and Pimephales promelas, may not always protect most of the species inhabiting a receiving stream. Although WET tests are useful in predicting aquatic individual responses, they are not meant to directly measure natural population or community responses. Further, they do not address bioconcentration or bioaccumulation of hydrophobic compounds; do not assess eutrophication effects in receiving systems; and lastly, do not reflect genotoxic effects or function to test for endocrine-disrupting chemicals. Consequently, a more direct evaluation of ecosystem health, using bioassessment techniques, may be needed to properly evaluate aquatic systems affected by wastewater discharges.

  10. Reliability of specific on-ice repeated-sprint ability test for ice-hockey players

    Directory of Open Access Journals (Sweden)

    Karel Hůlka

    2014-06-01

    Full Text Available Background: Repeated sprint ability tests are today widely used to evaluate the performance capability in team sports. Objective: The aim of this study was to determine the reliability of a specific ice hockey test, which indicates the agility and repeated-sprint ability of the players. Methods: Twenty four highly trained junior ice hockey players (age = 17.68 ± 1.52 years; BMI = 23.8 ± 1.92 kg . m-2 participated in the study. Each participant was assessed for specific on-ice repeated-sprint ability test 12 × 54 m with 30 s rest. Intraclass correlation coefficient (association between two repeated measurements and coefficient of variation were calculated to assess the reliability of the test. Results: All intraclass correlation coefficients were .78 for sprint decrement and .98 for total time and the best time, the coefficient of variation was 1.52% for best sprint time, 1.31% for total time and 19.3% for sprint decrement variable. Conclusions: The results suggest the high reliability of the ice hockey agility test expressed by the best sprint time and repeated-sprint ability by the total time and less reliability of sprint decrement.

  11. REPEATABILITY OF THE SUGAR ABSORPTION TEST, USING LACTULOSE AND MANNITOL, FOR MEASURING INTESTINAL PERMEABILITY FOR SUGARS

    NARCIS (Netherlands)

    VANELBURG, RM; UIL, JJ; KOKKE, FTM; MULDER, AM; VANDEBROEK, WGM; MULDER, CJJ; HEYMANS, HSA

    1995-01-01

    Differential sugar-absorption tests for measuring intestinal permeability for sugars have been studied in a variety of gastrointestinal diseases. Their use in general practice has been hampered by a lack of data on reference values and repeatability of the test and the laboratory assay. In this stud

  12. Integral toxicity test of sea waters by an algal biosensor.

    Science.gov (United States)

    Tonnina, Daniele; Campanella, Luigi; Sammartino, Maria Pia; Visco, Giovanni

    2002-04-01

    An integral toxicity test, based on an algal biosensor and suitable to be used in sea water, is presented. The biosensor was designed and built by coupling a Clark oxygen electrode as transducer and the marine alga Spirulina subsalsa as biological mediator; it constitutes the "core" in a lab-scale prototype of a flow apparatus suitable to continuously monitor, in sea water, the photosynthetic activity of the alga and, from its variation, the marine pollution from the toxicological point of view. Inorganic pollutants (heavy metals) were tested in previous researches while organic ones (chlorophenols, pesticides and surfactants) are the object of the present paper.

  13. Reliability and criterion-related validity of a new repeated agility test

    Directory of Open Access Journals (Sweden)

    MS Fessi

    2016-04-01

    Full Text Available The study aimed to assess the reliability and the criterion-related validity of a new repeated sprint T-test (RSTT that includes intense multidirectional intermittent efforts. The RSTT consisted of 7 maximal repeated executions of the agility T-test with 25 s of passive recovery rest in between. Forty-five team sports players performed two RSTTs separated by 3 days to assess the reliability of best time (BT and total time (TT of the RSTT. The intra-class correlation coefficient analysis revealed a high relative reliability between test and retest for BT and TT (>0.90. The standard error of measurement (<0.50 showed that the RSTT has a good absolute reliability. The minimal detectable change values for BT and TT related to the RSTT were 0.09 s and 0.58 s, respectively. To check the criterion-related validity of the RSTT, players performed a repeated linear sprint (RLS and a repeated sprint with changes of direction (RSCD. Significant correlations between the BT and TT of the RLS, RSCD and RSTT were observed (p<0.001. The RSTT is, therefore, a reliable and valid measure of the intermittent repeated sprint agility performance. As this ability is required in all team sports, it is suggested that team sports coaches, fitness coaches and sports scientists consider this test in their training follow-up.

  14. TRACKING PYRETHROID TOXICITY IN SURFACE WATER SAMPLES: EXPOSURE DYNAMICS AND TOXICITY IDENTIFICATION TOOLS FOR LABORATORY TESTS WITH HYALELLA AZTECA (AMPHIPODA).

    Science.gov (United States)

    Deanovic, Linda A; Stillway, Marie; Hammock, Bruce G; Fong, Stephanie; Werner, Inge

    2017-09-09

    Pyrethroid insecticides are commonly used in pest control and are present at toxic concentrations in surface waters of agricultural and urban areas worldwide. Monitoring is challenging due to their high hydrophobicity and low toxicity thresholds, which often fall below the detection limits of analytical methods. Standard daphnid bioassays used in surface water monitoring are not sensitive enough to protect more susceptible invertebrate species such as the amphipod, Hyalella azteca, and chemical loss during toxicity testing is of concern. In this study, we quantified toxicity loss during storage and testing, using both natural and synthetic water, and present a tool to enhance toxic signal strength for improved sensitivity of H. azteca toxicity tests. The average half-life during storage in LDPE cubitainers at 4°C of five pyrethroids (permethrin, bifenthrin, lambda-cyhalothrin, cyfluthrin, esfenvalerate) and one organophosphate (chlorpyrifos; used as reference) was 1.4 d, and piperonyl butoxide (PBO) proved an effective tool to potentiate toxicity. We conclude that toxicity tests on ambient water samples containing these hydrophobic insecticides are likely to underestimate toxicity present in the field, and mimic short pulse rather than continuous exposures. Where these chemicals are of concern, the addition of PBO during testing can yield valuable information on their presence or absence. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  15. Development of methodology for community level toxicity testing using the fathead minnow seven day survival-growth impairment test

    OpenAIRE

    Lauth, John Robert

    1990-01-01

    Single species toxicity tests are widely used to assess the potential effects of a toxicant on aquatic life. Increasingly, it is necessary to understand how the results of these tests relate to toxicant effects in natural communities. This dissertation presents the methodology and validation for a community level toxicity test that bridges the gap between single species tests and natutal community responses. The research involved control of environmental parameters, improvement...

  16. Establishing relative sensitivities of various toxicity testing organisms to ammonia

    Energy Technology Data Exchange (ETDEWEB)

    Karle, L.M.; Mayhew, H.L.; Barrows, M.E.; Karls, R.K. [Battelle/Marine Sciences Lab., Sequim, WA (United States)

    1994-12-31

    The toxicity of ammonia to various organisms was examined to develop a baseline for mortality in several commonly used testing species. This baseline data will assist in choosing the proper test species and in interpreting results as they pertain to ammonia. Responses for two juvenile fish species, three marine amphipods, and two species of mysid shrimp were compared for their sensitivity to levels of ammonia. All mortality caused by ammonia in the bottom-dwelling Citharichthys stigmaeus occurred within 24 h of exposure, whereas mortality in the silverside, Menidia beryllina, occurred over the entire 96-h test duration. Responses to ammonia varied among the amphipods Rhepoxynius abronius, Ampelisca abdita, and Eohaustorius estuarius. R. abronius and A. abdita showed similar sensitivity to ammonia at lower concentrations; A. abdita appeared more sensitive than R. abronius at levels above 40 mg/L. Concentrations of ammonia required to produce significant mortality in the amphipod E. estuarius were far higher than the other species examined (> 100 mg/L NH{sub 3}). A comparison of ammonia toxicity with two commonly used invertebrates, Holmesimysis sculpts and Mysidopsis bahia, suggest that these two species of mysid have similar sensitivities to ammonia. Further studies with ammonia that examine sensitivity of different organisms should be conducted to assist regulatory and environmental agencies in determining appropriate test species and in interpreting toxicological results as they may be affected by levels of ammonia.

  17. Repeated patch testing to nickel during childhood do not induce nickel sensitization

    DEFF Research Database (Denmark)

    Søgaard Christiansen, Elisabeth

    2014-01-01

    Background: Previously, patch test reactivity to nickel sulphate in a cohort of unselected infants tested repeatedly at 3-72 months of age has been reported. A reproducible positive reaction at 12 and 18 months was selected as a sign of nickel sensitivity, provided a patch test with an empty Finn...... chamber was negative. The objective of this study is to follow-up on infants with suspected nickel sensitivity. Methods: A total of 562 infants were included in the cohort and patch tested with nickel sulphate. The 26 children with a positive patch test to nickel sulphate at 12 and 18 months were offered...... repeated patch test to nickel sulphate at 3 (36 months), 6 (72 months) and 14 years of age. Results: At 3 years, 24 of 26 nickel sensitive children were retested and a positive reaction was seen in 7 children, a negative reaction in 16 and 1 child was excluded due to reaction to both nickel and the empty...

  18. A maximal cycle test with good validity and high repeatability in adults of all ages

    DEFF Research Database (Denmark)

    Eriksen, L; Tolstrup, J S; Larsen, Steen

    2014-01-01

    In 11 680 individuals (18-85 years) maximal oxygen consumption (VO2max) was estimated indirectly in a maximal cycle test using a prediction model developed in a young population (15-28 years). A subsample of 182 individuals (23-77 years) underwent 2 maximal cycle tests with VO2max estimated...... we suggest a new prediction model of VO2max. The maximal cycle test was highly repeatable....

  19. Combinatorial QSAR modeling of chemical toxicants tested against Tetrahymena pyriformis.

    Science.gov (United States)

    Zhu, Hao; Tropsha, Alexander; Fourches, Denis; Varnek, Alexandre; Papa, Ester; Gramatica, Paola; Oberg, Tomas; Dao, Phuong; Cherkasov, Artem; Tetko, Igor V

    2008-04-01

    Selecting most rigorous quantitative structure-activity relationship (QSAR) approaches is of great importance in the development of robust and predictive models of chemical toxicity. To address this issue in a systematic way, we have formed an international virtual collaboratory consisting of six independent groups with shared interests in computational chemical toxicology. We have compiled an aqueous toxicity data set containing 983 unique compounds tested in the same laboratory over a decade against Tetrahymena pyriformis. A modeling set including 644 compounds was selected randomly from the original set and distributed to all groups that used their own QSAR tools for model development. The remaining 339 compounds in the original set (external set I) as well as 110 additional compounds (external set II) published recently by the same laboratory (after this computational study was already in progress) were used as two independent validation sets to assess the external predictive power of individual models. In total, our virtual collaboratory has developed 15 different types of QSAR models of aquatic toxicity for the training set. The internal prediction accuracy for the modeling set ranged from 0.76 to 0.93 as measured by the leave-one-out cross-validation correlation coefficient ( Q abs2). The prediction accuracy for the external validation sets I and II ranged from 0.71 to 0.85 (linear regression coefficient R absI2) and from 0.38 to 0.83 (linear regression coefficient R absII2), respectively. The use of an applicability domain threshold implemented in most models generally improved the external prediction accuracy but at the same time led to a decrease in chemical space coverage. Finally, several consensus models were developed by averaging the predicted aquatic toxicity for every compound using all 15 models, with or without taking into account their respective applicability domains. We find that consensus models afford higher prediction accuracy for the

  20. Beryllium toxicity testing in the suspension culture of mouse fibroblasts.

    Science.gov (United States)

    Rössner, P; Bencko, V

    1980-01-01

    Suspension culture of mouse fibroblast cell line L-A 115 was used to test beryllium toxicity in the presence of magnesium ions. Beryllium added to the MEM cultivation medium was bound in a complex with sulphosalicylic acid BeSSA complex, because the use of beryllium chloride turned out to yield ineffective beryllium phosphate that formed macroscopically detectable insoluble opacities. The BeSSA complex was used in the concentration range: 10(-3)--10(-9)M, magnesium was used in 3 concentrations: 10(-1)M, 5 x 10(-2)M and 10(-2)M. Growth curve analysis revealed pronounced beryllium toxicity at the concentration of 10(-3)M, magnesium-produced toxic changes were observed only at the concentration of 10(-1)M. No competition between the beryllium and magnesium ions was recorded. It is assumed that the possible beryllium-magnesium competition was significantly modified by the use of BeSSA complex-bound beryllium.

  1. In situ toxicity testing of Lake Orta sediments

    Directory of Open Access Journals (Sweden)

    Monica BELTRAMI

    2001-08-01

    Full Text Available The use of in situ assays, which was initially proposed by Nebeker et al. (1984, is presently recognised as an effective tool to study the effects of contaminated sediments (Burton 1992. The placement of caged organisms to study short-term effects of exposure to contaminated environments has been employed for a number of aquatic species, both fish and invertebrate. This paper describes the application of this techniques to study the toxicity of Lake Orta sediments using both resident (Daphnia obtusa, D. longispina and non-resident (D. magna, Echinogammarus stammeri invertebrate species. In each of the selected stations, a group of four chambers, each containing 10 individuals, were deployed by scuba divers at 10 m depth and collected after 48 h. For each chamber, the surviving animals were counted, transferred to the laboratory and kept in Lake Orta water until their death. The number of neonates produced by each female in the laboratory was recorded daily in order to determine if the short exposure period could affect the reproductive behaviour of the animals. The technique and results reported here indicate the utility of in situ testing and suggest that, under certain conditions, this method of testing may yield results which are more representative of actual environmental conditions by avoiding the sample manipulation required for traditional laboratory toxicity tests.

  2. International Conference on Harmonisation; guidance on the duration of chronic toxicity testing in animals (rodent and nonrodent toxicity testing); availability. Notice. Food and Drug Administration, HHS.

    Science.gov (United States)

    1999-06-25

    The Food and Drug Administration (FDA) is publishing a guidance entitled "S4A Duration of Chronic Toxicity Testing in Animals (Rodent and Nonrodent Toxicity Testing)." The guidance was prepared under the auspices of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) and is intended to provide guidance on the duration of chronic toxicity testing in rodents and nonrodents as part of the safety evaluation of a drug product. FDA is also noting circumstances in which it may accept durations of chronic toxicity testing in nonrodents that differ from the duration generally recommended by ICH.

  3. Acute toxicity testing of chemicals-Opportunities to avoid redundant testing and use alternative approaches.

    Science.gov (United States)

    Creton, Stuart; Dewhurst, Ian C; Earl, Lesley K; Gehen, Sean C; Guest, Robert L; Hotchkiss, Jon A; Indans, Ian; Woolhiser, Michael R; Billington, Richard

    2010-01-01

    Assessment of the acute systemic oral, dermal, and inhalation toxicities, skin and eye irritancy, and skin sensitisation potential of chemicals is required under regulatory schemes worldwide. In vivo studies conducted to assess these endpoints can sometimes be associated with substantial adverse effects in the test animals, and their use should always be scientifically justified. It has been argued that while information obtained from such acute tests provides data needed to meet classification and labelling regulations, it is of limited value for hazard and risk assessments. Inconsistent application of in vitro replacements, protocol requirements across regions, and bridging principles also contribute to unnecessary and redundant animal testing. Assessment of data from acute oral and dermal toxicity testing demonstrates that acute dermal testing rarely provides value for hazard assessment purposes when an acute oral study has been conducted. Options to waive requirements for acute oral and inhalation toxicity testing should be employed to avoid unnecessary in vivo studies. In vitro irritation models should receive wider adoption and be used to meet regulatory needs. Global requirements for sensitisation testing need continued harmonisation for both substance and mixture assessments. This paper highlights where alternative approaches or elimination of tests can reduce and refine animal use for acute toxicity requirements.

  4. A roadmap for the development of alternative (non-animal) methods for systemic toxicity testing - t4 report*.

    Science.gov (United States)

    Basketter, David A; Clewell, Harvey; Kimber, Ian; Rossi, Annamaria; Blaauboer, Bas; Burrier, Robert; Daneshian, Mardas; Eskes, Chantra; Goldberg, Alan; Hasiwa, Nina; Hoffmann, Sebastian; Jaworska, Joanna; Knudsen, Thomas B; Landsiedel, Robert; Leist, Marcel; Locke, Paul; Maxwell, Gavin; McKim, James; McVey, Emily A; Ouédraogo, Gladys; Patlewicz, Grace; Pelkonen, Olavi; Roggen, Erwin; Rovida, Costanza; Ruhdel, Irmela; Schwarz, Michael; Schepky, Andreas; Schoeters, Greet; Skinner, Nigel; Trentz, Kerstin; Turner, Marian; Vanparys, Philippe; Yager, James; Zurlo, Joanne; Hartung, Thomas

    2012-01-01

    Systemic toxicity testing forms the cornerstone for the safety evaluation of substances. Pressures to move from traditional animal models to novel technologies arise from various concerns, including: the need to evaluate large numbers of previously untested chemicals and new products (such as nanoparticles or cell therapies), the limited predictivity of traditional tests for human health effects, duration and costs of current approaches, and animal welfare considerations. The latter holds especially true in the context of the scheduled 2013 marketing ban on cosmetic ingredients tested for systemic toxicity. Based on a major analysis of the status of alternative methods (Adler et al., 2011) and its independent review (Hartung et al., 2011), the present report proposes a roadmap for how to overcome the acknowledged scientific gaps for the full replacement of systemic toxicity testing using animals. Five whitepapers were commissioned addressing toxicokinetics, skin sensitization, repeated-dose toxicity, carcinogenicity, and reproductive toxicity testing. An expert workshop of 35 participants from Europe and the US discussed and refined these whitepapers, which were subsequently compiled to form the present report. By prioritizing the many options to move the field forward, the expert group hopes to advance regulatory science.

  5. Reliability and criterion-related validity of a new repeated agility test

    Science.gov (United States)

    Makni, E; Jemni, M; Elloumi, M; Chamari, K; Nabli, MA; Padulo, J; Moalla, W

    2016-01-01

    The study aimed to assess the reliability and the criterion-related validity of a new repeated sprint T-test (RSTT) that includes intense multidirectional intermittent efforts. The RSTT consisted of 7 maximal repeated executions of the agility T-test with 25 s of passive recovery rest in between. Forty-five team sports players performed two RSTTs separated by 3 days to assess the reliability of best time (BT) and total time (TT) of the RSTT. The intra-class correlation coefficient analysis revealed a high relative reliability between test and retest for BT and TT (>0.90). The standard error of measurement (repeated linear sprint (RLS) and a repeated sprint with changes of direction (RSCD). Significant correlations between the BT and TT of the RLS, RSCD and RSTT were observed (prepeated sprint agility performance. As this ability is required in all team sports, it is suggested that team sports coaches, fitness coaches and sports scientists consider this test in their training follow-up. PMID:27274109

  6. 30 CFR 250.522 - When do I have to repeat casing diagnostic testing?

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 2 2010-07-01 2010-07-01 false When do I have to repeat casing diagnostic testing? 250.522 Section 250.522 Mineral Resources MINERALS MANAGEMENT SERVICE, DEPARTMENT OF THE INTERIOR OFFSHORE OIL AND GAS AND SULPHUR OPERATIONS IN THE OUTER CONTINENTAL SHELF Oil and Gas...

  7. TOXICITY TESTING IN THE 21ST CENTURY: A VISION AND A STRATEGY

    DEFF Research Database (Denmark)

    Krewski, D.; Acosta, D.; Andersen, M.

    2010-01-01

    With the release of the landmark report Toxicity Testing in the 21st Century: A Vision and a Strategy, the U. S. National Academy of Sciences, in 2007, precipitated a major change in the way toxicity testing is conducted. It envisions increased efficiency in toxicity testing and decreased animal ...

  8. Non-animal methodologies within biomedical research and toxicity testing.

    Science.gov (United States)

    Knight, Andrew

    2008-01-01

    Laboratory animal models are limited by scientific constraints on human applicability, and increasing regulatory restrictions, driven by social concerns. Reliance on laboratory animals also incurs marked - and in some cases, prohibitive - logistical challenges, within high-throughput chemical testing programmes, such as those currently underway within Europe and the US. However, a range of non-animal methodologies is available within biomedical research and toxicity testing. These include: mechanisms to enhance the sharing and assessment of existing data prior to conducting further studies, and physicochemical evaluation and computerised modelling, including the use of structure-activity relationships and expert systems. Minimally-sentient animals from lower phylogenetic orders or early developmental vertebral stages may be used, as well as microorganisms and higher plants. A variety of tissue cultures, including immortalised cell lines, embryonic and adult stem cells, and organotypic cultures, are also available. In vitro assays utilising bacterial, yeast, protozoal, mammalian or human cell cultures exist for a wide range of toxic and other endpoints. These may be static or perfused, and may be used individually, or combined within test batteries. Human hepatocyte cultures and metabolic activation systems offer potential assessment of metabolite activity and organ-organ interaction. Microarray technology may allow genetic expression profiling, increasing the speed of toxin detection, well prior to more invasive endpoints. Enhanced human clinical trials utilising micro- dosing, staggered dosing, and more representative study populations and durations, as well as surrogate human tissues, advanced imaging modalities and human epidemiological, sociological and psycho- logical studies, may increase our understanding of illness aetiology and pathogenesis, and facilitate the development of safe and effective pharmacologic interventions. Particularly when human tissues

  9. Photosynthesis tests as an alternative to growth tests for hazard assessment of toxicant

    DEFF Research Database (Denmark)

    Petersen, S.; Kusk, Kresten Ole

    2000-01-01

    Acute (3- and 6-h) toxic responses toward Cu, linear alkylbenzene sulfonate (LAS), and tributyltin (TBT) of lightsaturated and unsaturated photosynthesis were investigated for Rhodomonas salina and Skeletonema costatum obtained from exponentially growing batch cultures and from chemostat cultures...... limited by either nitrogen or phosphorus. The sensitivity of the photosynthesis tests were compared to standardized growth tests applied to the same species and toxicants. For Cu and S. costatum the photosynthesis test was up to 300 times more sensitive at light saturation than at light limitation....... For the remaining photosynthesis tests no dependence on light condition were found. The photosynthesis tests with Cu and S. costatum were up to 10 times as sensitive as the growth test and most sensitive when the algae were obtained from a phosphatelimited chemostate. For the other photosynthesis tests...

  10. Duration of postoperative immunosuppression assessed by repeated delayed type hypersensitivity skin tests

    DEFF Research Database (Denmark)

    Hammer, J H; Nielsen, Hans Jørgen; Moesgaard, F;

    1992-01-01

    The duration of postoperative impairment in cell-mediated immunity was assessed by repeated skin testing with seven delayed type common antigens in 15 patients undergoing major elective abdominal surgery compared to a similar testing regimen in 10 healthy volunteers. All were skin tested four times......, with 72-hour intervals, and in the surgical patients the first test was applied 2 days before surgery, followed by tests on postoperative days 1, 4 and 7. The tests were read after 48 h. Postoperatively, the skin test area decreased on day 3 (p less than 0.01) and recurred to preoperative levels on day 9....... In contrast, the skin test area in the volunteers increased from test to test (p less than 0.001) during the study, confirming a previous finding of a vaccination effect. These results suggest that the postoperative immunosuppression is maintained for about 6-9 days....

  11. Testing procedures to determine the toxicity of blast fumes

    Energy Technology Data Exchange (ETDEWEB)

    Carbonel, P.; Bigourd, J. (Centre d' Etudes et Recherches des Charbonnages de France (CERCHAR), 60 - Verneuil-en-Halatte:

    1980-05-01

    Several methods are available in CERCHAR to determine the production of toxic gases from a shot of explosives: blasting of 50 g or 100 g of explosives in a 115 l bomb usually in the presence of sand and in a nitrogen atmosphere, blasting from 0.5 kg to 1 kg of explosive in a 15 m/sup 3/ chamber in the presence of air, under variable confinement (suspended charge or charge in a test mortar with or without stemming and possibly with a sheath). The test results show that the production of toxic gases depends to a great extent on the blasting conditions: type of detonation of the explosive, work done by the fumes, possible reactions of the fumes with atmospheric oxygen or with materials in contact with the explosive (cartridge material, stemming, sheath). It appears that the method consisting in blasting of explosives in a steel mortar with stemming in the 15 m/sup 3/ chamber gives results most closely related to those obtained in underground blasting. Therefore this method seems prefereble.

  12. Statistical testing and distribution for lead chloride toxicity

    Institute of Scientific and Technical Information of China (English)

    John H. Lange

    2005-01-01

    @@ Dear Sir, Graca et al. [1] provided an interesting investigation on the toxicity of lead chloride and sperm development in mice. However, I would like to make a comment on the statistical analysis presented. Table 1 and its results suggest that a comparison of treated (experiment) and control mice were undertaken using the t-test. The authors indicate that they used the t-test along with complementation of ANOVA analysis. It appears that the t-test was used for analysis in Table 1 and ANOVA, as indicated,for Table 2. Use of t-test for comparing three of more groups is not appropriate since this may result in a multiple comparison problem (increasing the type I error rate)[2, 3]. Multiple comparisons can result in the reporting of a P value that is significant (or of lower value) when in actuality it is not. It is better to use, for example, a one-way ANOVA followed by a post-test (post-hoc)which can take into account all comparisons. Other statistical testing can also be employed to control the overall type I error, such as Tukey-HSD (honest significant difference), Scheffe's and Bonferroni-Dunn methods [2].

  13. Aquatic toxicity testing for hazard identification of engineered nanoparticles

    DEFF Research Database (Denmark)

    Sørensen, Sara Nørgaard

    in aqueous media. Moreover, ENPs undergo time-dependent transformation processes of agglomeration, dissolution, sedimentation, and interactions with organisms and their exudates. Together, these processes challenge the establishment of traditional concentration-response data by affecting both the exposure...... to exposure control and response mechanisms in aquatic toxicity tests with ENPs are addressed through: 1) Exposure timing measures to minimize the transformation processes of ENPs during test incubation, and 2) Multi-dimensional approaches including investigations of other organisms responses than...... the traditionally applied, and determination of different exposure fractions such as the concentration of dissolved ions from ENPs and body burdens. Although these approaches are scientifically exploratory by nature, the aim is to generate data applicable for regulatory hazard identification of ENPs. The focus has...

  14. Relationships Among Two Repeated Activity Tests and Aerobic Fitness of Volleyball Players.

    Science.gov (United States)

    Meckel, Yoav; May-Rom, Moran; Ekshtien, Aya; Eisenstein, Tamir; Nemet, Dan; Eliakim, Alon

    2015-08-01

    The purpose of the study was to determine performance indices of a repeated sprint test (RST) and to examine their relationships with performance indices of a repeated jump test (RJT) and with aerobic fitness among trained volleyball players. Sixteen male volleyball players performed RST (6 × 30 m sprints), RJT (6 sets of 6 consecutive jumps), and an aerobic power test (20-m Shuttle Run Test). Performance indices for the RST and the RJT were (a) the ideal 30-m run time (IS), the total run time (TS) of the 6 sprints, and the performance decrement (PD) during the test and (b) the ideal jump height (IJ), the total jump height (TJ) of all the jumps, and the PD during the test, respectively. No significant correlations were found between performance indices of the RST and RJT. Significant correlations were found between PD, IS, and TS in the RST protocol and predicted peak V[Combining Dot Above]O2 (r = -0.60, -0.75, -0.77, respectively). No significant correlations were found between performance indices of the RJT (IJ, TJ, and PD) and peak V[Combining Dot Above]O2. The findings suggest that a selection of repeated activity test protocols should acknowledge the specific technique used in the sport, and that a distinct RJT, rather than the classic RST, is more appropriate for assessing the anaerobic capabilities of volleyball players. The findings also suggest that aerobic fitness plays only a minor role in performance maintenance throughout characteristic repeated jumping activity of a volleyball game.

  15. Re-examining repeated testing and teacher effects in a remedial mathematics course.

    Science.gov (United States)

    Martinez, J G; Martinez, N C

    1992-11-01

    This study examined the impact of repeated testing and teachers' effects on student achievement in a remedial mathematics course. A 2 x 2 completely randomised factorial design was used, with final examination performance the dependent variable and testing attempts and the teacher factor the independent variables. The study found no main effects for teacher but a main effect for testing attempts and a teacher-factor/testing-attempt interaction. Post hoc findings qualified a direct interpretation of the main effect. The implications for further research and application are discussed, giving special attention to teacher effects, the needs of remedial mathematics instruction, and the claims of mastery-learning pedagogies.

  16. [Repeated measurement of memory with valenced test items: verbal memory, working memory and autobiographic memory].

    Science.gov (United States)

    Kuffel, A; Terfehr, K; Uhlmann, C; Schreiner, J; Löwe, B; Spitzer, C; Wingenfeld, K

    2013-07-01

    A large number of questions in clinical and/or experimental neuropsychology require the multiple repetition of memory tests at relatively short intervals. Studies on the impact of the associated exercise and interference effects on the validity of the test results are rare. Moreover, hardly any neuropsychological instruments exist to date to record the memory performance with several parallel versions in which the emotional valence of the test material is also taken into consideration. The aim of the present study was to test whether a working memory test (WST, a digit-span task with neutral or negative distraction stimuli) devised by our workgroup can be used with repeated measurements. This question was also examined in parallel versions of a wordlist learning paradigm and an autobiographical memory test (AMT). Both tests contained stimuli with neutral, positive and negative valence. Twenty-four participants completed the memory testing including the working memory test and three versions of a wordlist and the AMT at intervals of a week apiece (measuring points 1. - 3.). The results reveal consistent performances across the three measuring points in the working and autobiographical memory test. The valence of the stimulus material did not influence the memory performance. In the delayed recall of the wordlist an improvement in memory performance over time was seen. The tests on working memory presented and the parallel versions for the declarative and autobiographical memory constitute informal economic instruments within the scope of the measurement repeatability designs. While the WST and AMT are appropriate for study designs with repeated measurements at relatively short intervals, longer intervals might seem more favourable for the use of wordlist learning paradigms. © Georg Thieme Verlag KG Stuttgart · New York.

  17. Influence of coefficient of variation in determining significant difference of quantitative values obtained from 28-day repeated-dose toxicity studies in rats.

    Science.gov (United States)

    Kobayashi, Katsumi; Sakuratani, Yuki; Abe, Takemaru; Yamazaki, Kazuko; Nishikawa, Satoshi; Yamada, Jun; Hirose, Akihiko; Kamata, Eiichi; Hayashi, Makoto

    2011-01-01

    In order to understand the influence of coefficient of variation (CV) in determining significant difference of quantitative values of 28-day repeated-dose toxicity studies, we examined 59 parameters of 153 studies conducted in accordance with Chemical Substance Control Law in 12 test facilities. Sex difference was observed in 12 parameters and 10 parameters showed large CV in females. The minimum CV was 0.74% for sodium. CV of electrolytes was comparatively small, whereas enzymes had large CV. Large differences in CV were observed for major parameters among 7-8 test facilities. The changes in CV were grossly classified into 11. Our study revealed that a statistical significant difference is usually detected if there is a difference of 7% in mean values between the groups and the groups have a CV of about 7%. A parameter with a CV as high as 30% may be significantly different, if the difference of the mean between the groups is 30%. It would be ideal to use median value to assess the treatment-related effect, rather than mean, when the CV is very high. We recommend using CV of the body weight as a standard to judge the adverse effect level.

  18. Study of Optimal Perimetric Testing in Children (OPTIC: Feasibility, Reliability and Repeatability of Perimetry in Children.

    Directory of Open Access Journals (Sweden)

    Dipesh E Patel

    Full Text Available To investigate feasibility, reliability and repeatability of perimetry in children.A prospective, observational study recruiting 154 children aged 5-15 years, without an ophthalmic condition that affects the visual field (controls, identified consecutively between May 2012 and November 2013 from hospital eye clinics. Perimetry was undertaken in a single sitting, with standardised protocols, in a randomised order using the Humphrey static (SITA 24-2 FAST, Goldmann and Octopus kinetic perimeters. Data collected included test duration, subjective experience and test quality (incorporating examiner ratings on comprehension of instructions, fatigue, response to visual and auditory stimuli, concentration and co-operation to assess feasibility and reliability. Testing was repeated within 6 months to assess repeatability.Overall feasibility was very high (Goldmann=96.1%, Octopus=89% and Humphrey=100% completed the tests. Examiner rated reliability was 'good' in 125 (81.2% children for Goldmann, 100 (64.9% for Octopus and 98 (63.6% for Humphrey perimetry. Goldmann perimetry was the most reliable method in children under 9 years of age. Reliability improved with increasing age (multinomial logistic regression (Goldmann, Octopus and Humphrey, p<0.001. No significant differences were found for any of the three test strategies when examining initial and follow-up data outputs (Bland-Altman plots, n=43, suggesting good test repeatability, although the sample size may preclude detection of a small learning effect.Feasibility and reliability of formal perimetry in children improves with age. By the age of 9 years, all the strategies used here were highly feasible and reliable. Clinical assessment of the visual field is achievable in children as young as 5 years, and should be considered where visual field loss is suspected. Since Goldmann perimetry is the most effective strategy in children aged 5-8 years and this perimeter is no longer available, further

  19. Biosolid Soil Application: Toxicity Tests under Laboratory Conditions

    Directory of Open Access Journals (Sweden)

    Cintya Ap. Christofoletti

    2012-01-01

    Full Text Available A large volume of generated sewage sludge makes its disposal a problem. The usage of sludge in agriculture is highlighted by a number of advantages. However, heavy metals and other toxic compounds may exercise harmful effects to soil organisms. This study evaluated the possible toxic effects of a biosolid sample, under laboratory conditions, for 30 days, using diplopods Rhinocricus padbergi and plants Allium cepa (onion as test organisms. The data obtained demonstrated that the biosolid raw sample had genotoxic potential for Allium cepa root tip cells. In the diplopods exposed to biosolid sample, epithelium disorganization in the midgut and a reduction of the volume of the hepatic cells were observed after 7 days of exposure. After 30 days, the animals still showed a reduction of the volume of the hepatic cells, but in minor intensity. Allium cepa analysis showed genotoxicity, but this effect was reduced after 30 days of bioprocessing by diplopods. This study was important to know the effects as well as to determine how this waste could be applied concerning the soil living organisms and plants.

  20. Repeat HIV testing during pregnancy and delivery: missed opportunities in a rural district hospital in Zambia.

    Science.gov (United States)

    Heemelaar, Steffie; Habets, Nicole; Makukula, Ziche; van Roosmalen, Jos; van den Akker, Thomas

    2015-03-01

    To assess coverage of repeat HIV testing among women who delivered in a Zambian hospital. HIV testing of pregnant women and repeat testing every 3 months during pregnancy and breastfeeding is the recommended policy in areas of high HIV prevalence. A prospective implementation study in a second-level hospital in rural Zambia. Included were all pregnant women who delivered in hospital during May and June 2012. Data regarding antenatal visits and HIV testing were collected by two investigators using a standardised form. Of 401 women who delivered in hospital, sufficient antenatal data could be retrieved for 322 (80.3%) women. Of these 322 women, 301 (93.5%) had attended antenatal care (ANC) at least once. At the time of discharge after delivery in hospital, 171 (53.1%) had an unclear HIV status because their negative test result was more than 3 months ago or of an unknown date, or because they had not been tested at all during pregnancy or delivery. An updated HIV status was present for 151 (46.9%) women: 25 (7.8%) were HIV positive and 126 (39.1%) had tested negative within the last 3 months. In this last group, 79 (24.5%) had been tested twice or more during pregnancy. During the study period, none of the women was tested during admission for delivery. Despite high ANC coverage, opportunities for repeat HIV testing were missed in almost half of all women who delivered in this hospital in a high-prevalence HIV setting. © 2014 John Wiley & Sons Ltd.

  1. Toxicity of 100 nm zinc oxide nanoparticles: a report of 90-day repeated oral administration in Sprague Dawley rats

    Directory of Open Access Journals (Sweden)

    Kim YR

    2014-12-01

    Full Text Available Yu-Ri Kim,1,* Jong-Il Park,2,* Eun Jeong Lee,1 Sung Ha Park,3 Nak-won Seong,2 Jun-Ho Kim,2 Geon-Yong Kim,2 Eun-Ho Meang,2 Jeong-Sup Hong,2 Su-Hyon Kim,2 Sang-Bum Koh,2 Min-Seok Kim,2 Cheol-Su Kim,4 Soo-Ki Kim,4 Sang Wook Son,5 Young Rok Seo,6 Boo Hyon Kang,7 Beom Seok Han,8 Seong Soo A An,9 Hyo-In Yun,9 Meyoung-Kon Kim1 1Department of Biochemistry and Molecular Biology, Korea University Medical School and College, Seoul, Korea; 2General Toxicology Team, Korea Testing and Research Institute, Seoul, Korea; 3Department of Biochemistry, University of Bath, Bath, UK; 4Department of Microbiology, Wonju College of Medicine, Yonsei University, Wonju-si, Gangwon, Korea; 5Department of Life Science, Institute of Environmental Medicine for Green Chemistry, Dongguk University, Seoul, Korea; 6Nonclinical Research Institute, Chemon Inc., Yongin, Gyeonggi, Korea; 7Toxicological Research Center, Hoseo University, Ansan, Chungnam, Korea; 8Department of Bionanotechnology, Gachon University, Seongnam, Gyeonggi, Korea; 9College of Veterinary Medicine, Chungnam National University, Daejon, Korea  *These authors contributed equally to this work Abstract: Nanoparticles (NPs are used commercially in health and fitness fields, but information about the toxicity and mechanisms underlying the toxic effects of NPs is still very limited. The aim of this study is to investigate the toxic effect(s of 100 nm negatively (ZnOAE100[-] or positively (ZnOAE100[+] charged zinc oxide (ZnO NPs administered by gavage in Sprague Dawley rats, to establish a no observed adverse effect level, and to identify target organ(s. After verification of the primary particle size, morphology, hydrodynamic size, and zeta potential of each test article, we performed a 90-day study according to Organisation for Economic Co-operation and Development test guideline 408. For the 90-day study, the high dose was set at 500 mg/kg and the middle and low doses were set at 125 mg/kg and 31.25 mg

  2. The 14-day repeated dose liver micronucleus test with methapyrilene hydrochloride using young adult rats.

    Science.gov (United States)

    Inoue, Kenji; Ochi, Akimu; Koda, Akira; Wako, Yumi; Kawasako, Kazufumi; Doi, Takaaki

    2015-03-01

    The repeated dose liver micronucleus (RDLMN) assay using young adult rats has the potential to detect genotoxic hepatocarcinogens that can be integrated into a general toxicity study. The assay methods were thoroughly validated by 19 Japanese facilities. Methapyrilene hydrochloride (MP), known to be a non-genotoxic hepatocarcinogen, was examined in the present study. MP was dosed orally at 10, 30 and 100mg/kg/day to 6-week-old male Crl:CD (SD) rats daily for 14 days. Treatment with MP resulted in an increase in micronucleated hepatocytes (MNHEPs) with a dosage of only 100mg/kg/day. At this dose level, cytotoxicity followed by regenerative cell growth was noted in the liver. These findings suggest that MP may induce clastogenic effects indirectly on the liver or hepatotoxicity of MP followed by regeneration may cause increase in spontaneous incidence of MNHEPs.

  3. Exploring discrepancies in the TOEFL iBT scores of repeat test takers

    OpenAIRE

    2011-01-01

    Students choosing to study abroad either independently or as a component of a local degree must first demonstrate their language proficiency by achieving the required score of their destination institution in a TOEFL iBT or IELTS examination. With such high stakes, many candidates opt to repeat the test a number of times before the submission date in the hope that one of the tests will yield a sufficiently high score. This study analyzed the test results of twenty-five students who, toward th...

  4. Twenty-eight-day repeated inhalation toxicity study of nano-sized lanthanum oxide in male sprague-dawley rats.

    Science.gov (United States)

    Shin, Seo-Ho; Lim, Cheol-Hong; Kim, Yong-Soon; Lee, Yong-Hoon; Kim, Sung-Hwan; Kim, Jong-Choon

    2017-04-01

    Although the use of lanthanum has increased in field of high-tech industry worldwide, potential adverse effects to human health and to the environment are largely unknown. The present study aimed to investigate the potential toxicity of nano-sized lanthanum oxide (La2 O3 ) following repeated inhalation exposure in male Sprague-Dawley rats. Male rats were exposed nose-only to nano-sized La2 O3 for 28 days (5 days/week) at doses of 0, 0.5, 2.5, and 10 mg/m(3) . In the experimental period, we evaluated treatment-related changes including clinical signs, body weight, hematology, serum biochemistry, necropsy findings, organ weight, and histopathology findings. We also analyzed lanthanum distribution in the major organs and in the blood, bronchoalveolar lavage fluids (BALF), and oxidative stress in lung tissues. Lanthanum level was highest in lung tissues and showed a dose-dependent relation. Alveolar proteinosis was observed in all treatment groups and was accompanied by an increase in lung weight; moreover, lung inflammation was observed in the 2.5 mg/m(3) and higher dose groups and was accompanied by an increase in white blood cells. In the BALF, total cell counts including macrophages and neutrophils, lactate dehydrogenase, albumin, nitric oxide, and tumor necrosis factor-alpha increased significantly in all treatment groups. Furthermore, these changes tended to deteriorate in the 10 mg/m(3) group at the end of the recovery period. In the present experimental conditions, we found that the lowest-observed-adverse-effect level of nano-sized La2 O3 was 0.5 mg/m(3) in male rats, and the target organ was the lung. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1226-1240, 2017. © 2016 Wiley Periodicals, Inc.

  5. Influence of repeated maximal exercise testing on biomarkers and fatigue in sarcoidosis.

    Science.gov (United States)

    Braam, A W E; de Haan, S N; Vorselaars, A D M; Rijkers, G T; Grutters, J C; van den Elshout, F J J; Korenromp, I H E

    2013-10-01

    Fatigue in the immune mediated inflammatory disease sarcoidosis is thought to be associated with impaired exercise tolerance. This prospective study assessed fatigue and recuperative capacity after repeated exercise, and examined whether changing concentrations in biomarkers upon exercise are associated with fatigue. Twenty sarcoidosis patients and 10 healthy volunteers performed maximal cardiopulmonary exercise tests on two successive days. Concentrations of cytokines, stress hormones, ACE and CK were assessed before and after the two exercise tests, and 3 days thereafter. All participants completed a sleep diary. Severely fatigued patients showed significant lower VO2 max (p=0.038, p=0.022) and maximal workload (p=0.034, p=0.028) on both exercise tests compared to healthy controls. No impairment of maximal exercise testing was demonstrated during the second cycling test in any group. Fatigue was not correlated with changes in concentrations of biomarkers upon exercise. Severely fatigued patients rated both tests as significantly more fatiguing, and reported significant lower mean subjective night sleeping time during the testing period. Fatigue in sarcoidosis patients cannot be objectified by reduction of exercise capacity after repeated maximal exercise testing, and is not correlated with significant changes in biomarkers. Severe fatigue is only and consistently featured by patient reported outcomes. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Custom-designed nanomaterial libraries for testing metal oxide toxicity.

    Science.gov (United States)

    Pokhrel, Suman; Nel, André E; Mädler, Lutz

    2013-03-19

    Advances in aerosol technology over the past 10 years have enabled the generation and design of ultrafine nanoscale materials for many applications. A key new method is flame spray pyrolysis (FSP), which produces particles by pyrolyzing a precursor solution in the gas phase. FSP is a highly versatile technique for fast, single-step, scalable synthesis of nanoscale materials. New innovations in particle synthesis using FSP technology, including variations in precursor chemistry, have enabled flexible, dry synthesis of loosely agglomerated, highly crystalline ultrafine powders (porosity ≥ 90%) of binary, ternary, and mixed-binary-and-ternary oxides. FSP can fulfill much of the increasing demand, especially in biological applications, for particles with specific material composition, high purity, and high crystallinity. In this Account, we describe a strategy for creating nanoparticle libraries (pure or Fedoped ZnO or TiO₂) utilizing FSP and using these libraries to test hypotheses related to the particles' toxicity. Our innovation lies in the overall integration of the knowledge we have developed in the last 5 years in (1) synthesizing nanomaterials to address specific hypotheses, (2) demonstrating the electronic properties that cause the material toxicity, (3) understanding the reaction mechanisms causing the toxicity, and (4) extracting from in vitro testing and in vivo testing in terrestrial and marine organisms the essential properties of safe nanomaterials. On the basis of this acquired knowledge, we further describe how the dissolved metal ion from these materials (Zn²⁺ in this Account) can effectively bind with different cell constituents, causing toxicity. We use Fe-S protein clusters as an example of the complex chemical reactions taking place after free metal ions migrate into the cells. As a second example, TiO₂ is an active material in the UV range that exhibits photocatalytic behavior. The induction of electron-hole (e⁻/h⁺) pairs followed by

  7. Implementation of repeat HIV testing during pregnancy in Kenya: a qualitative study.

    Science.gov (United States)

    Rogers, Anna Joy; Weke, Elly; Kwena, Zachary; Bukusi, Elizabeth A; Oyaro, Patrick; Cohen, Craig R; Turan, Janet M

    2016-07-11

    Repeat HIV testing in late pregnancy has the potential to decrease rates of mother-to-child transmission of HIV by identifying mothers who seroconvert after having tested negative for HIV in early pregnancy. Despite being national policy in Kenya, the available data suggest that implementation rates are low. We conducted 20 in-depth semi-structured interviews with healthcare providers and managers to explore barriers and enablers to implementation of repeat HIV testing guidelines for pregnant women. Participants were from the Nyanza region of Kenya and were purposively selected to provide variation in socio-demographics and job characteristics. Interview transcripts were coded and analyzed in Dedoose software using a thematic analysis approach. Four themes were identified a priori using Ferlie and Shortell's Framework for Change and additional themes were allowed to emerge from the data. Participants identified barriers and enablers at the client, provider, facility, and health system levels. Key barriers at the client level from the perspective of providers included late initial presentation to antenatal care and low proportions of women completing the recommended four antenatal visits. Barriers to offering repeat HIV testing for providers included heavy workloads, time limitations, and failing to remember to check for retest eligibility. At the facility level, inconsistent volume of clients and lack of space required for confidential HIV retesting were cited as barriers. Finally, at the health system level, there were challenges relating to the HIV test kit supply chain and the design of nationally standardized antenatal patient registers. Enablers to improving the implementation of repeat HIV testing included client dissemination of the benefits of antenatal care through word-of-mouth, provider cooperation and task shifting, and it was suggested that use of an electronic health record system could provide automatic reminders for retest eligibility. This study

  8. Sympathetic enhancement in futsal players but not in football players after repeated sprint ability test

    OpenAIRE

    Chen, Yung-Sheng; Liao, Chih-Jung; Lu, Wan-An; Kuo, Cheng-Deng

    2015-01-01

    Background Heart rate variability (HRV) can disclose the specific adaptation of sympathovagal modulation to exercise. This study investigated the change in HRV measures after anaerobic and aerobic intermittent exercises in university football and futsal players. Method 36 male university students with physically active lifestyle (n=14), football (n=12), and futsal (n=10) participated in this study. The participants completed the repeated sprint ability (RSA) test and Yo-Yo (YY) intermittent r...

  9. Developmental toxicity, acute toxicity and mutagenicity testing in freshwater snails Biomphalaria glabrata (Mollusca: Gastropoda) exposed to chromium and water samples.

    Science.gov (United States)

    Tallarico, Lenita de Freitas; Borrely, Sueli Ivone; Hamada, Natália; Grazeffe, Vanessa Siqueira; Ohlweiler, Fernanda Pires; Okazaki, Kayo; Granatelli, Amanda Tosatte; Pereira, Ivana Wuo; Pereira, Carlos Alberto de Bragança; Nakano, Eliana

    2014-12-01

    A protocol combining acute toxicity, developmental toxicity and mutagenicity analysis in freshwater snail Biomphalaria glabrata for application in ecotoxicological studies is described. For acute toxicity testing, LC50 and EC50 values were determined; dominant lethal mutations induction was the endpoint for mutagenicity analysis. Reference toxicant potassium dichromate (K2Cr2O7) was used to characterize B. glabrata sensitivity for toxicity and cyclophosphamide to mutagenicity testing purposes. Compared to other relevant freshwater species, B. glabrata showed high sensitivity: the lowest EC50 value was obtained with embryos at veliger stage (5.76mg/L). To assess the model applicability for environmental studies, influent and effluent water samples from a wastewater treatment plant were evaluated. Gastropod sensitivity was assessed in comparison to the standardized bioassay with Daphnia similis exposed to the same water samples. Sampling sites identified as toxic to daphnids were also detected by snails, showing a qualitatively similar sensitivity suggesting that B. glabrata is a suitable test species for freshwater monitoring. Holding procedures and protocols implemented for toxicity and developmental bioassays showed to be in compliance with international standards for intra-laboratory precision. Thereby, we are proposing this system for application in ecotoxicological studies.

  10. Toxicity testing: the search for an in vitro alternative to animal testing.

    Science.gov (United States)

    May, J E; Xu, J; Morse, H R; Avent, N D; Donaldson, C

    2009-01-01

    Prior to introduction to the clinic, pharmaceuticals must undergo rigorous toxicity testing to ensure their safety. Traditionally, this has been achieved using in vivo animal models. However, besides ethical reasons, there is a continual drive to reduce the number of animals used for this purpose due to concerns such as the lack of concordance seen between animal models and toxic effects in humans. Adequate testing to ensure any toxic metabolites are detected can be further complicated if the agent is administered in a prodrug form, requiring a source of cytochrome P450 enzymes for metabolism. A number of sources of metabolic enzymes have been utilised in in vitro models, including cell lines, primary human tissue and liver extracts such as S9. This review examines current and new in vitro models for toxicity testing, including a new model developed within the authors' laboratory utilising HepG2 liver spheroids within a co-culture system to examine the effects of chemotherapeutic agents on other cell types.

  11. Effects of Repeated Testing on Short- and Long-Term Memory Performance across Different Test Formats

    Science.gov (United States)

    Stenlund, Tova; Sundström, Anna; Jonsson, Bert

    2016-01-01

    This study examined whether practice testing with short-answer (SA) items benefits learning over time compared to practice testing with multiple-choice (MC) items, and rereading the material. More specifically, the aim was to test the hypotheses of "retrieval effort" and "transfer appropriate processing" by comparing retention…

  12. Dredged Material Evaluations: Review of Zooplankton Toxicity Test Methods for Marine Water Quality Evaluations

    Science.gov (United States)

    2016-09-01

    for elutriate toxicity tests are fish , invertebrates (crustaceans), and zooplankton. Freshwater evaluations (following CWA regulations) use standard...is not a limiting factor in cultures. However, it is appropriate to investigate lower feeding rations, or absence of food, in toxicity testing to...2012. Standard guide for selection of resident species as test organisms for aquatic and sediment toxicity tests. Designation: E1850 − 04.West

  13. Modes-of-Action Related to Repeated Dose Toxicity: Tissue-Specific Biological Roles of PPARγ Ligand-Dependent Dysregulation in Nonalcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Merilin Al Sharif

    2014-01-01

    Full Text Available Comprehensive understanding of the precise mode of action/adverse outcome pathway (MoA/AOP of chemicals becomes a key step towards superseding the current repeated dose toxicity testing methodology with new generation predictive toxicology tools. The description and characterization of the toxicological MoA leading to non-alcoholic fatty liver disease (NAFLD are of specific interest, due to its increasing incidence in the modern society. Growing evidence stresses on the PPARγ ligand-dependent dysregulation as a key molecular initiating event (MIE for this adverse effect. The aim of this work was to analyze and systematize the numerous scientific data about the steatogenic role of PPARγ. Over 300 papers were ranked according to preliminary defined criteria and used as reliable and significant sources of data about the PPARγ-dependent prosteatotic MoA. A detailed analysis was performed regarding proteins which PPARγ-mediated expression changes had been confirmed to be prosteatotic by most experimental evidence. Two probable toxicological MoAs from PPARγ ligand binding to NAFLD were described according to the Organisation for Economic Cooperation and Development (OECD concepts: (i PPARγ activation in hepatocytes and (ii PPARγ inhibition in adipocytes. The possible events at different levels of biological organization starting from the MIE to the organ response and the connections between them were described in details.

  14. Assessment of pose repeatability and specimen repositioning of a robotic joint testing platform.

    Science.gov (United States)

    El Daou, H; Lord, B; Amis, A; Rodriguez Y Baena, F

    2017-09-01

    This paper describes the quantitative assessment of a robotic testing platform, consisting of an industrial robot and a universal force-moment sensor, via the design of fixtures used to hold the tibia and femur of cadaveric knees. This platform was used to study the contributions of different soft tissues and the ability of implants and reconstruction surgeries to restore normal joint functions, in previously published literature. To compare different conditions of human joints, it is essential to reposition specimens with high precision after they have been removed for a surgical procedure. Methods and experiments carried out to determine the pose repeatability and measure errors in repositioning specimens are presented. This was achieved using an optical tracking system (fusion Track 500, Atracsys Switzerland) to measure the position and orientation of bespoke rigid body markers attached to the tibial and femoral pots after removing and reinstalling them inside the rigs. The pose repeatability was then evaluated by controlling the robotic platform to move a knee joint repeatedly to/from a given pose while tracking the position and orientation of a rigid body marker attached to the tibial fixture. The results showed that the proposed design ensured a high repeatability in repositioning the pots with standard deviations for the computed distance and angle between the pots at both ends of the joint equal to 0.1mm, 0.01mm, 0.13° and 0.03° for the tibial and femoral fixtures respectively. Therefore, it is possible to remove and re-setup a joint with high precision. The results also showed that the errors in repositioning the robotic platform (that is: specimen path repeatability) were 0.11mm and 0.12°, respectively. Copyright © 2017. Published by Elsevier Ltd.

  15. Toxicity testing of NCSRP priority substances for the development of soil quality criteria

    Energy Technology Data Exchange (ETDEWEB)

    Cureton, P.M. [Environment Canada, Ottawa, Ontario (Canada). Evaluation and Interpretation Branch; Balch, G.; Lintott, D.; Poirrier, K.; Goudey, S. [HydroQual Labs. Ltd., Calgary, Alberta (Canada)

    1994-12-31

    The effects of 14 National Contaminated Sites Remediation Program (NCSRP) priority substances was measured on emergence and root elongation in lettuce (Lactuca saliva) and radish (Raphanus saliva) and on survival of the earthworm Eisenia foetida. The worm and seedling emergence tests were conducted in an artificial soil mixture composed of 10% peat moss, 20% kaolinite clay, and 70% silica sand (70 mesh) spiked with the contaminant. The root elongation tests were conducted on filter paper moistened with the contaminant solution. The following endpoints were derived on nominal and measured concentrations: NOEC, LOEC, the LC{sub 50} and LC{sub 25} for earthworm mortality and the EC{sub 50} and EC{sub 25} for emergence and root elongation. The contaminants tested included: arsenic, cadmium, chromium, copper, lead, mercury, zinc, vanadium, benzo(a)pyrene, cyanide, naphthalene, ethylene glycol, pentachlorophenol, and phenol. Each test was repeated three times using different batches of freshly prepared soil, seed lots and worm cultures. The authors will present the findings and discuss the application of toxicity test results in developing generic soil quality criteria.

  16. Preliminary evaluation of a micro-based repeated measures testing system

    Science.gov (United States)

    Kennedy, Robert S.; Wilkes, Robert L.; Lane, Norman E.

    1985-01-01

    A need exists for an automated performance test system to study the effects of various treatments which are of interest to the aerospace medical community, i.e., the effects of drugs and environmental stress. The ethics and pragmatics of such assessment demand that repeated measures in small groups of subjects be the customary research paradigm. Test stability, reliability-efficiency and factor structure take on extreme significance; in a program of study by the U.S. Navy, 80 percent of 150 tests failed to meet minimum metric requirements. The best is being programmed on a portable microprocessor and administered along with tests in their original formats in order to examine their metric properties in the computerized mode. Twenty subjects have been tested over four replications on a 6.0 minute computerized battery (six tests) and which compared with five paper and pencil marker tests. All tests achieved stability within the four test sessions, reliability-efficiencies were high (r greater than .707 for three minutes testing), and the computerized tests were largely comparable to the paper and pencil version from which they were derived. This computerized performance test system is portable, inexpensive and rugged.

  17. Neuro-mechanical and metabolic adjustments to the repeated anaerobic sprint test in professional football players.

    Science.gov (United States)

    Brocherie, Franck; Millet, Gregoire P; Girard, Olivier

    2015-05-01

    This study aimed to determine the neuro-mechanical and metabolic adjustments in the lower limbs induced by the running anaerobic sprint test (the so-called RAST). Eight professional football players performed 6 × 35 m sprints interspersed with 10 s of active recovery on artificial turf with their football shoes. Sprinting mechanics (plantar pressure insoles), root mean square activity of the vastus lateralis (VL), rectus femoris (RF), and biceps femoris (BF) muscles (surface electromyography, EMG) and VL muscle oxygenation (near-infrared spectroscopy) were monitored continuously. Sprint time, contact time and total stride duration increased from the first to the last repetition (+17.4, +20.0 and +16.6 %; all P 0.05), decreased over sprint repetitions and were correlated with the increase in running time (r = -0.82 and -0.90; both P sprint repetitions, players with a better repeated-sprint performance (lower cumulated times) also displayed faster muscle de- (during sprints) and re-oxygenation (during recovery) rates (r = -0.74 and -0.84; P repeated anaerobic sprint test leads to substantial alterations in stride mechanics and leg-spring behaviour. Our results also strengthen the link between repeated-sprint ability and the change in neuromuscular activation as well as in muscle de- and re-oxygenation rates.

  18. Gain of Toxicity from ALS/FTD-Linked Repeat Expansions in C9ORF72 Is Alleviated by Antisense Oligonucleotides Targeting GGGGCC-Containing RNAs.

    Science.gov (United States)

    Jiang, Jie; Zhu, Qiang; Gendron, Tania F; Saberi, Shahram; McAlonis-Downes, Melissa; Seelman, Amanda; Stauffer, Jennifer E; Jafar-Nejad, Paymaan; Drenner, Kevin; Schulte, Derek; Chun, Seung; Sun, Shuying; Ling, Shuo-Chien; Myers, Brian; Engelhardt, Jeffery; Katz, Melanie; Baughn, Michael; Platoshyn, Oleksandr; Marsala, Martin; Watt, Andy; Heyser, Charles J; Ard, M Colin; De Muynck, Louis; Daughrity, Lillian M; Swing, Deborah A; Tessarollo, Lino; Jung, Chris J; Delpoux, Arnaud; Utzschneider, Daniel T; Hedrick, Stephen M; de Jong, Pieter J; Edbauer, Dieter; Van Damme, Philip; Petrucelli, Leonard; Shaw, Christopher E; Bennett, C Frank; Da Cruz, Sandrine; Ravits, John; Rigo, Frank; Cleveland, Don W; Lagier-Tourenne, Clotilde

    2016-05-04

    Hexanucleotide expansions in C9ORF72 are the most frequent genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia. Disease mechanisms were evaluated in mice expressing C9ORF72 RNAs with up to 450 GGGGCC repeats or with one or both C9orf72 alleles inactivated. Chronic 50% reduction of C9ORF72 did not provoke disease, while its absence produced splenomegaly, enlarged lymph nodes, and mild social interaction deficits, but not motor dysfunction. Hexanucleotide expansions caused age-, repeat-length-, and expression-level-dependent accumulation of RNA foci and dipeptide-repeat proteins synthesized by AUG-independent translation, accompanied by loss of hippocampal neurons, increased anxiety, and impaired cognitive function. Single-dose injection of antisense oligonucleotides (ASOs) that target repeat-containing RNAs but preserve levels of mRNAs encoding C9ORF72 produced sustained reductions in RNA foci and dipeptide-repeat proteins, and ameliorated behavioral deficits. These efforts identify gain of toxicity as a central disease mechanism caused by repeat-expanded C9ORF72 and establish the feasibility of ASO-mediated therapy.

  19. Effects of nicotine gum on repeated administration of the Stroop test.

    Science.gov (United States)

    Provost, S C; Woodward, R

    1991-01-01

    Using a double-blind procedure, 24 non-smoking subjects chewed either 2 mg nicorette gum or a placebo for 20 min, before completing a Stroop test on three occasions. Colour-word reading and simple colour naming times were consistent across repeats, and were unaffected by nicotine. However, the time taken to name the colour of incongruous colour word stimuli declined across trials. This increase in speed across repeats was significantly greater in those subjects who had received nicotine. These data are consistent with previous reports of a decreased Stroop effect following nicotine administration, but are not compatible with a simple model which assumes that nicotine alters the way in which information is filtered by selective attentional mechanisms. The present results can be explained by postulating that nicotine influences either the rate at which colour naming become more automatic, or changes the way in which resources are allocated to non-automatic processes.

  20. Repeated anticonvulsant testing: contingent tolerance to diazepam and clobazam in kindled rats.

    Science.gov (United States)

    Tietz, E I

    1992-04-01

    The acute anticonvulsant efficacy of diazepam (1.5 mg/kg, i.p.) was evaluated by repeated test injection in kindled rats subcutaneously implanted with diazepam-filled or empty silastic tubes for 3 weeks. Tolerance developed to acute test injections in both diazepam- and sham-implanted rats. Tolerance developed to a lesser extent in another group of diazepam-implanted rats which did not receive acute intermittent anticonvulsant tests. The hypothesis that contingent tolerance had developed to the anticonvulsant actions of benzodiazepines (diazepam, 1.5 mg/kg, i.p. and clobazam, 10 mg/kg, i.p.) in kindled rats given acute intermittent injections was investigated using a 'before-after' design. Significant contingent tolerance developed in rats which received intermittent benzodiazepine treatment before, but not after, amygdala stimulation. Tolerance developed to different extents depending on the seizure measure evaluated (forelimb clonus duration, amygdala afterdischarge duration, motor seizure latency and duration, and seizure stage). Contingent tolerance to both benzodiazepines developed at a similar rate. The findings suggest that contingent tolerance may contribute a sizeable component to the overall functional benzodiazepine tolerance measured in long-term anticonvulsant drug studies in kindled rats. Several questions regarding contingent tolerance phenomena are posed and the implications of these findings for studies using repeated anticonvulsant testing are discussed.

  1. Reliability, usefulness, and validity of a repeated sprint and jump ability test.

    Science.gov (United States)

    Buchheit, Martin; Spencer, Matt; Ahmaidi, Said

    2010-03-01

    Two studies involving 122 handball players were conducted to assess the reliability, usefulness, and validity of a repeated shuttle-sprint and jump ability (RSSJA) test. The test consisted of 6x(2x12.5-m) sprints departing on 25 s, with a countermovement jump performed during recovery between sprints. For the reliability and usefulness study, 14 well-trained male handball players performed the RSSJA test 7 d apart. Reliability of the test variables was assessed by the typical error of measurement, expressed as a coefficient of variation (CV). The minimal changes likely to be "real" in sprint time and jump power were also calculated. For the validity study, players of seven teams (national to international levels, women and men) performed the RSSJA test. CV values for best and mean sprint time were 1.0% (90% CL, 0.7 to 1.6) and 1.0% (90% CL, 0.7 to 1.4). CV values for best and mean jump peak power were 1.7% (90% CL, 1.2 to 2.7) and 1.5% (90% CL, 1.1 to 2.5). The percent sprint and jump decrements were less reliable, with CVs of 22.3% (90% CL, 15.7 to 38.3) and 34.8% (90% CL, 24.2 to 61.8). Minimal changes likely to be "real" for mean sprint time and jumping peak power were -2.6% and 4.8%. Qualitative analysis revealed that the majority of between-team differences were rated as "almost certain" (ie, 100% probability that the true differences were meaningful) for mean sprint and jump performances. The RSSJA test is reliable and valid to assess repeated explosive effort sequences in team sports such as handball. Test results are likely to be representative of gender and competition level; thus the test could be used to discriminate across playing standards and monitor fitness levels.

  2. Methods For Collecting , Culturing And Performing Toxicity Tests With Daphnia ambigua

    Energy Technology Data Exchange (ETDEWEB)

    Specht, Winona L.

    2005-07-01

    Toxicity tests conducted on water collected from impacted locations in SRS streams often failed chronic toxicity tests and sometimes failed acute toxicity tests (Specht 1995). These findings prompted SRS to determine the cause of the failures. Some SRS NPDES outfalls were also failing chronic toxicity tests, even though no toxicant could be identified and when TIEs were performed, none of the TIE treatments removed the toxicity. Ultimately, it was determined that the failures were due to the low hardness of SRS surface waters, rather than to the presence of a toxicant. The species of cladoceran that the EPA recommends for toxicity testing, Ceriodaphnia dubia, is stressed by the very low hardness of SRS waters. SRS developed an alternate species toxicity test that is similar to the EPA test, but uses an indigenous cladoceran, Daphnia ambigua (Specht and Harmon, 1997; Harmon et al., 2003). In 2001, SCDHEC approved the use of D. ambigua for toxicity testing at SRS, contingent upon approval by EPA Region 4. In 2002, EPA Region 4 approved the use of this species for compliance toxicity testing at SRS. Ultimately, the use of this species demonstrated that SRS effluents were not toxic, and most toxicity testing requirements were removed from the NPDES permit that was issued in December 2003, with the exception of one round of chronic definitive testing on outfalls A-01, A-11, and G-10 just before the next NPDES permit application is submitted to SCDHEC. Although the alternate species test was developed at SRS (1996-1998), the culture was transferred to a contract toxicity testing lab (ETT Environmental) located in Greer, SC in 1998. ETT Environmental became certified by SCDHEC to perform toxicity tests using D. ambigua in 2002, and at this time is the only laboratory certified by SCDHEC to perform tests with this species. Because of the expense associated with maintaining the D. ambigua culture for several years when no toxicity testing is required, SRS decided to suspend

  3. Implementing Lecane quadridentata acute toxicity tests to assess the toxic effects of selected metals (Al, Fe and Zn).

    Science.gov (United States)

    Guzmán, Félix Torres; González, Francisco Javier Avelar; Martínez, Roberto Rico

    2010-03-01

    An environmental study revealed that three metals (Al, Fe and Zn) are common in the San Pedro River (SPR) (Aguascalientes, Mexico). Regrettably, in many samples the concentrations of these metals exceeded the maximum allowed toxicant concentrations levels as defined in by Mexican legislation. The highest concentrations of the three metals were found during the 2005 dry season, with elevated Al concentrations present along the entire river. Not surprisingly, the highest concentrations for all three metals came from locations adjacent to industrial areas. Estimates of the contribution of these metals to total toxicity revealed that these three metals are important contaminants of the river and responsible for most of the lethal toxicity found in environmental samples. To assess the importance of these reports, we conducted acute toxicity tests to determine LC50 for Al, Fe and Zn on the freshwater rotifer Lecane quadridentata. This permitted us to estimate the contribution of these metals to total toxicity during 2005-2006. Based on LC50 values, all three metals should be considered very toxic, with the zinc LC50 value (0.12 mg L(-1)) making it the most toxic metal for L. quadridentata. This approach can be applied to other sites with similar concentrations of these metals. (c) 2009 Elsevier Inc. All rights reserved.

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

    DEFF Research Database (Denmark)

    Charles, Sandrine; Ducrot, Virginie; Azam, Didier

    2016-01-01

    This paper presents the results from two ring-tests addressing the feasibility, robustness and reproducibility of a reproduction toxicity test with the freshwater gastropod Lymnaea stagnalis (RENILYS strain). Sixteen laboratories (from inexperienced to expert laboratories in mollusc testing) from...

  5. Repeatability of contrast sensitivity testing in patients with age-related macular degeneration, glaucoma, and cataract

    Directory of Open Access Journals (Sweden)

    Selcuk Kara

    Full Text Available ABSTRACT Purpose: To analyze the intrasession and intersession repeatability of contrast sensitivity (CS measurements in patients with glaucoma, cataract, or age-related macular degeneration (AMD and healthy controls. Methods: CS measurements were performed using the OPTEC-Functional Vision Analyzer (FVA, which uses a standardized and closed (view-in system. Measurements for patients with glaucoma, cataract, or AMD and healthy controls were repeated within 30 minutes (intrasession and during two sessions (intersession, separated by one week to one month. Test-retest reliability and correlation were measured using the intraclass correlation coefficient (ICC and coefficient of repeatability (COR. Results: Ninety subjects (90 eyes with visual acuity of 0.17 logMAR or higher in the cataract group or 0.00 logMAR in the other groups were included. During the first session, the ICC values were 0.87, 0.90, 0.76, and 0.69, and COR values were 0.24, 0.20, 0.38, and 0.25 for the control, glaucoma, cataract, and AMD groups, respectively. The reliability scores significantly improved during the second session, except in the glaucoma group. There was an acceptable floor effect and no ceiling effect at higher frequencies in the glaucoma and AMD groups. Conclusion: In subjects with good visual acuity, the FVA system is useful for evaluating CS and demonstrates good repeatability, as shown by ICC and COR. Because there is no ceiling effect, this system is beneficial for evaluation of early changes in CS, particularly in patients with glaucoma or AMD.

  6. Characterization of robotic system passive path repeatability during specimen removal and reinstallation for in vitro knee joint testing.

    Science.gov (United States)

    Goldsmith, Mary T; Smith, Sean D; Jansson, Kyle S; LaPrade, Robert F; Wijdicks, Coen A

    2014-10-01

    Robotic testing systems are commonly utilized for the study of orthopaedic biomechanics. Quantification of system error is essential for reliable use of robotic systems. Therefore, the purpose of this study was to quantify a 6-DOF robotic system's repeatability during knee biomechanical testing and characterize the error induced in passive path repeatability by removing and reinstalling the knee. We hypothesized removing and reinstalling the knee would substantially alter passive path repeatability. Testing was performed on four fresh-frozen cadaver knees. To determine repeatability and reproducibility, the passive path was collected three times per knee following the initial setup (intra-setup), and a single time following two subsequent re-setups (inter-setup). Repeatability was calculated as root mean square error. The intra-setup passive path had a position repeatability of 0.23 mm. In contrast, inter-setup passive paths had a position repeatability of 0.89 mm. When a previously collected passive path was replayed following re-setup of the knee, resultant total force repeatability across the passive path increased to 28.2N (6.4N medial-lateral, 25.4N proximal-distal, and 10.5 N anterior-posterior). This study demonstrated that removal and re-setup of a knee can have substantial, clinically significant changes on our system's repeatability and ultimately, accuracy of the reported results. Copyright © 2014 IPEM. Published by Elsevier Ltd. All rights reserved.

  7. Repeated open application test with methyldibromo glutaronitrile, a multicentre study within the EECDRG.

    Science.gov (United States)

    Gruvberger, B; Andersen, K E; Brandão, F M; Bruynzeel, D P; Bruze, M; Frosch, P J; Goossens, A; Lahti, A; Maibach, H I; Menné, T; Orton, D; Seidenari, S

    2005-01-01

    Contact allergy to and allergic contact dermatitis from methyldibromo glutaronitrile (MDBGN) have frequently been reported. This study was initiated to help determine the optimal patch test preparation for MDBGN. In 51 patients with a doubtful or a positive patch test reaction to at least 1 of 4 test preparations with MDBGN in petrolatum at 1.0% w/w, 0.5%, 0.3% and 0.1%, a repeated open application test (ROAT) with moisturizers with and without MDBGN at 0.03% w/w was performed on the upper arms for 2 weeks. 18 of the 51 (35.3%) patients developed a positive ROAT. In all patients, there was a positive ROAT only to the moisturizer with MDBGN (P < 0.001). A statistically significant association was also found between the patch test reactivity (PTRL) and the outcome of the ROAT (P < 0.001). If only considering those with a PTRL above 0.3%, thus with negative or doubtful test reactions to 0.1% and 0.3%, there were still statistically significantly more patients with a positive ROAT to the moisturizer with MDBGN than to the moisturizer without MDBGN. The study demonstrates that patch testing with MDBGN at 0.3% and 0.1% will miss clinically relevant patch test reactions to MDBGN.

  8. OECD validation study to assess intra- and inter-laboratory reproducibility of the zebrafish embryo toxicity test for acute aquatic toxicity testing.

    Science.gov (United States)

    Busquet, François; Strecker, Ruben; Rawlings, Jane M; Belanger, Scott E; Braunbeck, Thomas; Carr, Gregory J; Cenijn, Peter; Fochtman, Przemyslaw; Gourmelon, Anne; Hübler, Nicole; Kleensang, André; Knöbel, Melanie; Kussatz, Carola; Legler, Juliette; Lillicrap, Adam; Martínez-Jerónimo, Fernando; Polleichtner, Christian; Rzodeczko, Helena; Salinas, Edward; Schneider, Katharina E; Scholz, Stefan; van den Brandhof, Evert-Jan; van der Ven, Leo T M; Walter-Rohde, Susanne; Weigt, Stefan; Witters, Hilda; Halder, Marlies

    2014-08-01

    The OECD validation study of the zebrafish embryo acute toxicity test (ZFET) for acute aquatic toxicity testing evaluated the ZFET reproducibility by testing 20 chemicals at 5 different concentrations in 3 independent runs in at least 3 laboratories. Stock solutions and test concentrations were analytically confirmed for 11 chemicals. Newly fertilised zebrafish eggs (20/concentration and control) were exposed for 96h to chemicals. Four apical endpoints were recorded daily as indicators of acute lethality: coagulation of the embryo, lack of somite formation, non-detachment of the tail bud from the yolk sac and lack of heartbeat. Results (LC50 values for 48/96h exposure) show that the ZFET is a robust method with a good intra- and inter-laboratory reproducibility (CV30%) for some very toxic or volatile chemicals, and chemicals tested close to their limit of solubility. The ZFET is now available as OECD Test Guideline 236. Considering the high predictive capacity of the ZFET demonstrated by Belanger et al. (2013) in their retrospective analysis of acute fish toxicity and fish embryo acute toxicity data, the ZFET is ready to be considered for acute fish toxicity for regulatory purposes. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  9. Exploring repeat HIV testing among men who have sex with men in Cape Town and Port Elizabeth, South Africa.

    Science.gov (United States)

    Siegler, Aaron J; Sullivan, Patrick S; de Voux, Alex; Phaswana-Mafuya, Nancy; Bekker, Linda-Gail; Baral, Stefan D; Winskell, Kate; Kose, Zamakayise; Wirtz, Andrea L; Brown, Ben; Stephenson, Rob

    2015-01-01

    Despite the high prevalence of HIV among men who have sex with men (MSM) - and the general adult population - in South Africa, there is little data regarding the extent to which MSM seek repeat testing for HIV. This study explores reported histories of HIV testing, and the rationales for test seeking, among a purposive sample of 34 MSM in two urban areas of South Africa. MSM participated in activity-based in-depth interviews that included a timeline element to facilitate discussion. Repeat HIV testing was limited among participants, with three-quarters having two or fewer lifetime HIV tests, and over one-third of the sample having one or fewer lifetime tests. For most repeat testers, the time gap between their HIV tests was greater than the one-year interval recommended by national guidelines. Analysis of the reasons for seeking HIV testing revealed several types of rationale. The reasons for a first HIV test were frequently one-time occurrences, such as a requirement prior to circumcision, or motivations likely satisfied by a single HIV test. For MSM who reported repeat testing at more timely intervals, the most common rationale was seeking test results with a sex partner. Results indicate a need to shift HIV test promotion messaging and programming for MSM in South Africa away from a one-off model to one that frames HIV testing as a repeated, routine health maintenance behavior.

  10. Pyrrolizidine Alkaloids: Testing for Toxic Constituents of Comfrey.

    Science.gov (United States)

    Vollmer, John J.; And Others

    1987-01-01

    Discusses the possibilities of toxins present in medicinal herbs. Describes an experiment in which toxic constituents can be selectively detected by thin-layer chromatography and NMR spectroscopy. (TW)

  11. Toxicity test of xanthone from mangosteen on zebrafish embryos

    Science.gov (United States)

    Noordin, Muhammad Akram Mohd; Noor, Mahanem Mat; Kamaruddin, Wan Mohd Aizat Wan; Lazim, Azwan Mat; Fazry, Shazrul

    2016-11-01

    Xanthone is a chemical compound identified in mangosteen pericarp. A previous study showed that xanthone has anti-proliferating effect on cancer cells. In this study we investigate the toxicity level of xanthone in zebrafish embryo to for future reference on other animal model. We employed Fish Embryo Toxicity (FET) assay to determine the toxicity level of different concentrations of xanthone. Embryos were observed at 24, 48 and 72 hours post fertilization (hpf) under microscope at 4× magnification. The extract showed toxicity effect on embryo at concentrations of 250, 125 and 62.5 µg/mL. Concentrations at 15.63, 7.81 and 3.91 µg / mL of xanthone did not harm the embryos and showed 100% of survival.

  12. Applicability of ambient toxicity testing to national or regional water-quality assessment

    Science.gov (United States)

    Elder, John F.

    1990-01-01

    Comprehensive assessment of the quality of natural waters requires a multifaceted approach. Descriptions of existing conditions may be achieved by various kinds of chemical and hydrologic analyses, whereas information about the effects of such conditions on living organisms depends on biological monitoring. Toxicity testing is one type of biological monitoring that can be used to identify possible effects of toxic contaminants. Based on experimentation designed to monitor responses of organisms to environmental stresses, toxicity testing may have diverse purposes in water-quality assessments. These purposes may include identification of areas that warrant further study because of poor water quality or unusual ecological features, verification of other types of monitoring, or assessment of contaminant effects on aquatic communities. Toxicity-test results are most effective when used as a complement to chemical analyses, hydrologic measurements, and other biological monitoring. However, all toxicity-testing procedures have certain limitations that must be considered in developing the methodology and applications of toxicity testing in any large-scale water-quality-assessment program. A wide variety of toxicity-test methods have been developed to fulfill the needs of diverse applications. The methods differ primarily in the selections made relative to four characteristics: (1) test species, (2) endpoint (acute or chronic), (3) test-enclosure type, and (4) test substance (toxicant) that functions as the environmental stress. Toxicity-test approaches vary in their capacity to meet the needs of large-scale assessments of existing water quality. Ambient testing, whereby the test organism is exposed to naturally occurring substances that contain toxicant mixtures in an organic or inorganic matrix, is more likely to meet these needs than are procedures that call for exposure of the test organisms to known concentrations of a single toxicant. However, meaningful

  13. A test strategy for the assessment of additive attributed toxicity of tobacco products.

    Science.gov (United States)

    Kienhuis, Anne S; Staal, Yvonne C M; Soeteman-Hernández, Lya G; van de Nobelen, Suzanne; Talhout, Reinskje

    2016-08-01

    The new EU Tobacco Product Directive (TPD) prohibits tobacco products containing additives that are toxic in unburnt form or that increase overall toxicity of the product. This paper proposes a strategy to assess additive attributed toxicity in the context of the TPD. Literature was searched on toxicity testing strategies for regulatory purposes from tobacco industry and governmental institutes. Although mainly traditional in vivo testing strategies have been applied to assess toxicity of unburnt additives and increases in overall toxicity of tobacco products due to additives, in vitro tests combined with toxicogenomics and validated using biomarkers of exposure and disease are most promising in this respect. As such, tests are needed that are sensitive enough to assess additive attributed toxicity above the overall toxicity of tobacco products, which can associate assay outcomes to human risk and exposure. In conclusion, new, sensitive in vitro assays are needed to conclude whether comparable testing allows for assessment of small changes in overall toxicity attributed to additives. A more pragmatic approach for implementation on a short-term is mandated lowering of toxic emission components. Combined with risk assessment, this approach allows assessment of effectiveness of harm reduction strategies, including banning or reducing of additives.

  14. Repeated Assessment and Practice Effects of the Written Symbol Digit Modalities Test Using a Short Inter-Test Interval.

    Science.gov (United States)

    Pereira, Diana R; Costa, Patrício; Cerqueira, João J

    2015-08-01

    The Symbol Digit Modalities Test (SDMT) is a widely used instrument to assess information processing speed, attention, visual scanning, and tracking. Considering that repeated evaluations are a common need in neuropsychological assessment routines, we explored test-retest reliability and practice effects of two alternate SDMT forms with a short inter-assessment interval. A total of 123 university students completed the written SDMT version in two different time points separated by a 150-min interval. Half of the participants accomplished the same form in both occasions, while the other half filled different forms. Overall, reasonable test-retest reliabilities were found (r = .70), and the subjects that completed the same form revealed significant practice effects (p University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  15. Mutations of short tandem repeat loci in cases of paternity testing in Chinese.

    Science.gov (United States)

    Sun, Mao; Zhang, XiaoNan; Wu, Dan; Shen, Qi; Wu, YuanMing; Fu, ShanMin

    2016-09-01

    In order to find out the characteristics of genetic mutations in 15 short tandem repeat (STR) loci, 3734 parentage cases were analyzed using AmpFlSTR Sinofiler kit. The allele source, mutation rate, and mutation rule of the STR loci were determined. Seventy mutations were observed in all cases for paternity testing. Among 15 STR loci, the highest mutation rate was observed in D12S391 (0.21 %), but the D5S818 gene mutation rate was relatively low (0.02 %). One-step mutation cases accounted for 95.7 % of all of the cases monitored. And the mutations in this study mainly showed paternal mutation (64/70). The research results are of great significance for identification and paternity tests and for the improvement of genetic studies on Chinese population in the future.

  16. Behavioral momentum and resurgence: Effects of time in extinction and repeated resurgence tests.

    Science.gov (United States)

    Sweeney, Mary M; Shahan, Timothy A

    2013-12-01

    Resurgence is an increase in a previously extinguished operant response that occurs if an alternative reinforcement introduced during extinction is removed. Shahan and Sweeney (2011) developed a quantitative model of resurgence based on behavioral momentum theory that captures existing data well and predicts that resurgence should decrease as time in extinction and exposure to the alternative reinforcement increases. Two experiments tested this prediction. The data from Experiment 1 suggested that without a return to baseline, resurgence decreases with increased exposure to alternative reinforcement and to extinction of the target response. Experiment 2 tested the predictions of the model across two conditions, one with constant alternative reinforcement for five sessions, and the other with alternative reinforcement removed three times. In both conditions, the alternative reinforcement was removed for the final test session. Experiment 2 again demonstrated a decrease in relapse across repeated resurgence tests. Furthermore, comparably little resurgence was observed at the same time point in extinction in the final test, despite dissimilar previous exposures to alternative reinforcement removal. The quantitative model provided a good description of the observed data in both experiments. More broadly, these data suggest that increased exposure to extinction may be a successful strategy to reduce resurgence. The relationship between these data and existing tests of the effect of time in extinction on resurgence is discussed.

  17. Anodonta imbecillis copper sulfate reference toxicant test, Clinch River - Environmental Restoration Program (CR-ERP)

    Energy Technology Data Exchange (ETDEWEB)

    Simbeck, D.J.

    1997-06-01

    Reference toxicant testing using juvenile freshwater mussels was conducted as part of the CR-ERP biomonitoring study of Clinch River sediments to assess the sensitivity of test organisms and the overall performance of the test. Tests were conducted using moderately hard synthetic water spiked with known concentrations of copper as copper sulfate. Toxicity testing of copper sulfate reference toxicant was conducted from May 12-21, 1993. The organisms used for testing were juvenile fresh-water mussels (Anodonta imbecillis). Results from this test showed an LC{sub 50} value of 1.12 mg Cu/L which is lower than the value of 2.02 mg Cu/L obtained in a previous test. Too few tests have been conducted with copper as the toxicant to determine a normal range of values.

  18. Allium-test as a tool for toxicity testing of environmental radioactive-chemical mixtures

    Science.gov (United States)

    Oudalova, A. A.; Geras'kin, S. A.; Dikareva, N. S.; Pyatkova, S. V.

    2017-01-01

    Bioassay-based approaches have been propagated to assess toxicity of unknown mixtures of environmental contaminants, but it was rarely applied in cases of chemicals with radionuclides combinations. Two Allium-test studies were performed to assess environmental impact from potential sources of combined radioactive-chemical pollution. Study sites were located at nuclear waste storage facilities in European and in Far-Eastern parts of Russia. As environmental media under impact, waters from monitor wells and nearby water bodies were tested. Concentrations of some chemicals and radionuclides in the samples collected enhanced the permitted limits. Cytogenetic and cytotoxic effects were used as biological endpoints, namely, frequency and spectrum of chromosome aberrations and mitotic abnormalities in anatelophase cells as well as mitotic activity in Allium root tips. Sample points were revealed where waters have an enhanced mutagenic potential. The findings obtained could be used to optimize monitoring system and advance decision making on management and rehabilitation of industrial sites. The Allium-test could be recommended and applied as an effective tool for toxicity testing in case of combined contamination of environmental compartments with radionuclides and chemical compounds.

  19. Enhancing the applicability and predictability of the embryonic stem cell test for developmental toxicity

    NARCIS (Netherlands)

    de Jong, E.

    2012-01-01

    Within the full risk assessment of a chemical, developmental toxicity testing is one of the endpoints that require the highest percentage of experimental animals. With the high number of experimental animals, cost and time involved in in vivo developmental toxicity testing there is an urgent need

  20. The Adverse Outcome Pathway: A conceptual framework to support toxicity testing in the 21st century

    Science.gov (United States)

    The field of regulatory toxicity testing is at a turning point. The U.S. National Research Council (NRC) envisioned a shift away from traditional toxicity testing and towards a focused effort to explore and understand pathways perturbed by biologically active substances or their ...

  1. Acute toxicity of copper oxide nanoparticles to Daphnia magna under different test conditions

    DEFF Research Database (Denmark)

    Thit, Amalie; Huggins, Krista; Selck, Henriette

    2017-01-01

    The acute toxicity of monodispersed 6 nm and Daphnia magna was assessed using 48 h immobilization tests. CuSO4 was used as a reference. Four different exposure conditions were tested, to study whether the toxicity of the nanoparticle...

  2. Evaluation of critical rest interval determined from repeated sprint ability testing.

    Science.gov (United States)

    LA Monica, Michael B; Fukuda, David H; Beyer, Kyle S; Hoffman, Mattan W; Miramonti, Amelia A; Fragala, Maren S; Stout, Jeffrey R; Hoffman, Jay R

    2016-10-01

    To test if the critical power (CP) concept can be utilized to determine the critical rest interval (CRI) using repeated sprint ability (RSA) testing with varying work-to-rest ratios. Twelve recreationally trained men (mean±SD; age 24.1±3.6 years) completed a graded exercise test and three RSA protocols with 6-second maximal sprints and varying rest intervals (12-36 s) on a cycle ergometer to determine CRI. Intermittent critical power (ICP) was calculated through the linear total work (TW) and time-to-exhaustion (TTE) relationship, whereas CRI was estimated using average work per sprint and ICP. Validation trials above and below CRI were conducted to evaluate physiological response. Repeated measures analysis of variance were used to analyze variables from RSA trials and changes in blood lactate, oxygen uptake (V̇O2), heart rate (HR), peak power, and TW throughout the validation trials. Blood lactate, average V̇O2, V̇O2peak, and heart rate were significantly greater below CRI (8.94±4.89 mmol/L, 2.05±0.36 L/min, 2.84±0.48 L/min, and 151.14±18.46 bpm, respectively) when compared to above CRI (6.56±3.45 mmol/L, 1.78±0.26 L/min, 2.61±0.43 L/min, and 138.14±17.51 bpm). Significant interactions were found between above and below CRI for minimal V̇O2 response and maximal HR response, which were consistent with the heavy and severe exercise intensity domains. The use of the work-time relationship determined from RSA testing with varying rest intervals can be used to determine CRI and may distinguish between physiological responses related to exercise intensity domains.

  3. Improving toxicity assessment of pesticide mixtures: the use of polar passive sampling devices extracts in microalgae toxicity tests

    Directory of Open Access Journals (Sweden)

    Sandra KIM TIAM

    2016-09-01

    Full Text Available Complexity of contaminants exposure needs to be taking in account for an appropriate evaluation of risks related to mixtures of pesticides released in the ecosystems. Toxicity assessment of such mixtures can be made through a variety of toxicity tests reflecting different level of biological complexity. This paper reviews the recent developments of passive sampling techniques for polar compounds, especially Polar Organic Chemical Integrative Samplers (POCIS and Chemcatcher® and the principal assessment techniques using microalgae in laboratory experiments. The progresses permitted by the coupled use of such passive samplers and ecotoxicology testing as well as their limitations are presented. Case studies combining passive sampling devices (PSD extracts and toxicity assessment toward microorganisms at different biological scales from single organisms to communities level are presented. These case studies, respectively aimed i at characterizing the toxic potential of waters using dose-response curves, and ii at performing microcosm experiments with increased environmental realism in the toxicant exposure in term of cocktail composition and concentration. Finally perspectives and limitations of such approaches for future applications in the area of environmental risk assessment are discussed.

  4. Improving Toxicity Assessment of Pesticide Mixtures: The Use of Polar Passive Sampling Devices Extracts in Microalgae Toxicity Tests

    Science.gov (United States)

    Kim Tiam, Sandra; Fauvelle, Vincent; Morin, Soizic; Mazzella, Nicolas

    2016-01-01

    Complexity of contaminants exposure needs to be taking in account for an appropriate evaluation of risks related to mixtures of pesticides released in the ecosystems. Toxicity assessment of such mixtures can be made through a variety of toxicity tests reflecting different level of biological complexity. This paper reviews the recent developments of passive sampling techniques for polar compounds, especially Polar Organic Chemical Integrative Samplers (POCIS) and Chemcatcher® and the principal assessment techniques using microalgae in laboratory experiments. The progresses permitted by the coupled use of such passive samplers and ecotoxicology testing as well as their limitations are presented. Case studies combining passive sampling devices (PSD) extracts and toxicity assessment toward microorganisms at different biological scales from single organisms to communities level are presented. These case studies, respectively, aimed (i) at characterizing the “toxic potential” of waters using dose-response curves, and (ii) at performing microcosm experiments with increased environmental realism in the toxicant exposure in term of cocktail composition and concentration. Finally perspectives and limitations of such approaches for future applications in the area of environmental risk assessment are discussed. PMID:27667986

  5. Predicting the future: opportunities and challenges for the chemical industry to apply 21st-century toxicity testing.

    Science.gov (United States)

    Settivari, Raja S; Ball, Nicholas; Murphy, Lynea; Rasoulpour, Reza; Boverhof, Darrell R; Carney, Edward W

    2015-03-01

    Interest in applying 21st-century toxicity testing tools for safety assessment of industrial chemicals is growing. Whereas conventional toxicology uses mainly animal-based, descriptive methods, a paradigm shift is emerging in which computational approaches, systems biology, high-throughput in vitro toxicity assays, and high-throughput exposure assessments are beginning to be applied to mechanism-based risk assessments in a time- and resource-efficient fashion. Here we describe recent advances in predictive safety assessment, with a focus on their strategic application to meet the changing demands of the chemical industry and its stakeholders. The opportunities to apply these new approaches is extensive and include screening of new chemicals, informing the design of safer and more sustainable chemical alternatives, filling information gaps on data-poor chemicals already in commerce, strengthening read-across methodology for categories of chemicals sharing similar modes of action, and optimizing the design of reduced-risk product formulations. Finally, we discuss how these predictive approaches dovetail with in vivo integrated testing strategies within repeated-dose regulatory toxicity studies, which are in line with 3Rs principles to refine, reduce, and replace animal testing. Strategic application of these tools is the foundation for informed and efficient safety assessment testing strategies that can be applied at all stages of the product-development process.

  6. 78 FR 69414 - Toxic Substances Control Act Chemical Testing; Receipt of Test Data

    Science.gov (United States)

    2013-11-19

    ... pigments; Toxicity to Algae; Acute emulsion polymerization in Inhalation Toxicity in paper, textile, fiber, and Rats; Bacterial Reverse adhesives industries. Mutation; In Vitro Mammalian Chromosome...

  7. Statistical tools for analysing the data obtained from repeated dose toxicity studies with rodents: a comparison of the statistical tools used in Japan with that of used in other countries.

    Science.gov (United States)

    Kobayashi, Katsumi; Pillai, K Sadasivan; Guhatakurta, Soma; Cherian, K M; Ohnishi, Mariko

    2011-01-01

    In the present study, an attempt was made to compare the statistical tools used for analysing the data of repeated dose toxicity studies with rodents conducted in 45 countries, with that of Japan. The study revealed that there was no congruence among the countries in the use of statistical tools for analysing the data obtained from the above studies. For example, to analyse the data obtained from repeated dose toxicity studies with rodents, Scheffé's multiple range and Dunnett type (joint type Dunnett) tests are commonly used in Japan, but in other countries use of these statistical tools is not so common. However, statistical techniques used for testing the above data for homogeneity of variance and inter-group comparisons do not differ much between Japan and other countries. In Japan, the data are generally not tested for normality and the same is true with the most of the countries investigated. In the present investigation, out of 127 studies examined, data of only 6 studies were analysed for both homogeneity of variance and normal distribution. For examining homogeneity of variance, we propose Levene's test, since the commonly used Bartlett's test may show heterogeneity in variance in all the groups, if a slight heterogeneity in variance is seen any one of the groups. We suggest the data may be examined for both homogeneity of variance and normal distribution. For the data of the groups that do not show heterogeneity of variance, to find the significant difference among the groups, we recommend Dunnett's test, and for those show heterogeneity of variance, we recommend Steel's test.

  8. Developing a list of reference chemicals for testing alternatives to whole fish toxicity tests.

    Science.gov (United States)

    Schirmer, Kristin; Tanneberger, Katrin; Kramer, Nynke I; Völker, Doris; Scholz, Stefan; Hafner, Christoph; Lee, Lucy E J; Bols, Niels C; Hermens, Joop L M

    2008-11-11

    This paper details the derivation of a list of 60 reference chemicals for the development of alternatives to animal testing in ecotoxicology with a particular focus on fish. The chemicals were selected as a prerequisite to gather mechanistic information on the performance of alternative testing systems, namely vertebrate cell lines and fish embryos, in comparison to the fish acute lethality test. To avoid the need for additional experiments with fish, the U.S. EPA fathead minnow database was consulted as reference for whole organism responses. This database was compared to the Halle Registry of Cytotoxicity and a collation of data by the German EPA (UBA) on acute toxicity data derived from zebrafish embryos. Chemicals that were present in the fathead minnow database and in at least one of the other two databases were subject to selection. Criteria included the coverage of a wide range of toxicity and physico-chemical parameters as well as the determination of outliers of the in vivo/in vitro correlations. While the reference list of chemicals now guides our research for improving cell line and fish embryo assays to make them widely applicable, the list could be of benefit to search for alternatives in ecotoxicology in general. One example would be the use of this list to validate structure-activity prediction models, which in turn would benefit from a continuous extension of this list with regard to physico-chemical and toxicological data.

  9. Collaborative work on evaluation of ovarian toxicity. 17) Two- or four-week repeated-dose studies and fertility study of sulpiride in female rats.

    Science.gov (United States)

    Ishii, Shun-ichiro; Ube, Masayuki; Okada, Miyoko; Adachi, Tamiko; Sugimoto, Jiro; Inoue, Yoshimi; Uno, Yoshifumi; Mutai, Mamoru

    2009-01-01

    To find the appropriate dosing period to detect ovarian toxicity, sulpiride, a D2 antagonist was orally dosed to female rats at dose levels of 1, 10, and 100 mg/kg/day daily for 2 or 4 weeks in repeated-dose toxicity studies. In addition, sulpiride at the same dose levels was given to female rats daily during the pre-mating period, mating period, and Days 0-7 of gestation to assess its effect on fertility. In ovarian histology in the 2-week study, increases in atretic follicle were seen at 1 mg/kg or more and increases in follicular cysts at 10 mg/kg or more. In the 4-week study, these findings were seen at 1 mg/kg or more, and a decrease in large follicles was seen at 10 mg/kg or more. Increased body weight gain was observed at 10 mg/kg or more in the 2- and 4-week studies. The females in these groups exhibited development of mammary alveolus by sulpiride-induced hyperprolactinemia. In the fertility study, sulpiride-treated females showing persistent diestrus resulted in successful mating, and almost all females got pregnant. However, increased implantation loss was observed at 10 mg/kg or more, which was considered to be caused by the adverse effect of sulpiride on oocyte development. From these results, sulpiride-induced ovarian toxicity was seen at 1 mg/kg or more in the 2- and 4-week repeated-dose toxicity studies, and the observed ovarian changes were considered to be related to adverse effects on female fertility.

  10. Reliability characteristics and applicability of a repeated sprint ability test in male young soccer players.

    Science.gov (United States)

    Castagna, Carlo; Francini, Lorenzo; Krustrup, Peter; Fenarnandes-da-Silva, Juliano; Póvoas, Susana C A; Bernardini, Andrea; D'Ottavio, Stefano

    2017-07-28

    The aim of this study was to examine the usefulness and reliability characteristics of a repeated sprint ability test considering 5 line sprints of 30-m interspersed with 30-s of active recovery in non-elite outfield young male soccer players. Twenty-six (age 14.9±1.2 years, height 1.72±0.12 cm, body mass 62.2±5.1 kg) players were tested 48 hours and 7 days apart for 5x30-m performance over 5 trials (T1-T5). Short- (T1-T2) and long-term reliability (T1-T3-T4-T5) were assessed with Intraclass Correlation Coefficient (ICC) and with typical error for measurement (TEM). Short- and long-term reliability ICCs and TEMs for total sprint time and best sprint performance were nearly perfect and satisfactory, respectively. Usefulness (as smallest worthwhile change and TEM ratio) resulted acceptable (i.e =1) and good (i.e >1) for total sprint time and best sprint performance, respectively. The present study revealed that the 5x30-m sprint test is a reliable field test in the short and long-term when the sum of sprint times and the best sprint performance are considered as outcome variables. Sprint performance decrements variables showed large variability across trials.

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

    Directory of Open Access Journals (Sweden)

    Sudin Bhattacharya

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

  12. Tests for bioequivalence of control media and test media in studies of toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Erickson, W.P.; McDonald, L.L. [Western EcoSystems Technology, Inc., Cheyenne, WY (United States)

    1995-07-01

    Statistical tests of the classical (null) hypothesis--that there is no difference in effects of control media and tested--are commonly used to make statistical inferences toward the no-observed-adverse-effect concentration. However, failing to rejects this hypothesis is not considered as scientific proof the hypothesis is true. An effect may exist, but high variation due to inadequate replication, variation in experimental units, or imprecise measurement techniques may yield data for which the hypothesis is not rejected. An experiment may also be too precise, yielding effects that are statistically significant but not biologically important. The authors propose the use of tests of bioequivalence of control media and test media to alleviate these unsatisfactory characteristics of tests and of the classical hypotheses for regulatory decisions. They review and illustrate the test for bioequivalence using acute and chronic toxicity data. They also define a procedure for determining the level of effect at which there will be high power to refute the hypothesis that there is a lack of bioequivalence if in fact the biological response in the control media is identical to the responses in the test media.

  13. The utility of repeat enzyme immunoassay testing for the diagnosis of Clostridium difficile infection: A systematic review of the literature

    Directory of Open Access Journals (Sweden)

    P S Garimella

    2012-01-01

    Full Text Available Over the last 20 years, the prevalence of healthcare-associated Clostridium difficile (C. diff disease has increased. While multiple tests are available for the diagnosis of C. diff infection, enzyme immunoassay (EIA testing for toxin is the most used. Repeat EIA testing, although of limited utility, is common in medical practice. To assess the utility of repeat EIA testing to diagnose C. diff infections. Systematic literature review. Eligible studies performed >1 EIA test for C. diff toxin and were published in English. Electronic searches of MEDLINE and EMBASE were performed and bibliographies of review articles and conference abstracts were hand searched. Of 805 citations identified, 32 were reviewed in detail and nine were included in the final review. All studies except one were retrospective chart reviews. Seven studies had data on number of participants (32,526, and the overall reporting of test setting and patient characteristics was poor. The prevalence of C. diff infection ranged from 9.1% to 18.5%. The yield of the first EIA test ranged from 8.4% to 16.6%, dropping to 1.5-4.7% with a second test. The utility of repeat testing was evident in outbreak settings, where the yield of repeat testing was 5%. Repeat C. diff testing for hospitalized patients has low clinical utility and may be considered in outbreak settings or when the pre-test probability of disease is high. Future studies should aim to identify patients with a likelihood of disease and determine the utility of repeat testing compared with empiric treatment.

  14. The utility of repeat enzyme immunoassay testing for the diagnosis of Clostridium difficile infection: a systematic review of the literature.

    Science.gov (United States)

    Garimella, P S; Agarwal, R; Katz, A

    2012-01-01

    Over the last 20 years, the prevalence of healthcare-associated Clostridium difficile (C. diff) disease has increased. While multiple tests are available for the diagnosis of C. diff infection, enzyme immunoassay (EIA) testing for toxin is the most used. Repeat EIA testing, although of limited utility, is common in medical practice. To assess the utility of repeat EIA testing to diagnose C. diff infections. Systematic literature review. Eligible studies performed >1 EIA test for C. diff toxin and were published in English. Electronic searches of MEDLINE and EMBASE were performed and bibliographies of review articles and conference abstracts were hand searched. Of 805 citations identified, 32 were reviewed in detail and nine were included in the final review. All studies except one were retrospective chart reviews. Seven studies had data on number of participants (32,526), and the overall reporting of test setting and patient characteristics was poor. The prevalence of C. diff infection ranged from 9.1% to 18.5%. The yield of the first EIA test ranged from 8.4% to 16.6%, dropping to 1.5-4.7% with a second test. The utility of repeat testing was evident in outbreak settings, where the yield of repeat testing was 5%. Repeat C. diff testing for hospitalized patients has low clinical utility and may be considered in outbreak settings or when the pre-test probability of disease is high. Future studies should aim to identify patients with a likelihood of disease and determine the utility of repeat testing compared with empiric treatment.

  15. Toxicity tests in the ecological risk assessment (ERA) process: Is there ecological relevance?

    Energy Technology Data Exchange (ETDEWEB)

    Saban, L.B. [Roy F. Weston, Inc., Seattle, WA (United States)

    1995-12-31

    There are a number of ways to evaluate risks to potential receptors. Screening level assessments often compare toxicity reference values from the literature to doses or concentrations from a particular site. Toxicity testing and biological monitoring are also performed to further evaluate potential effects. In many situations, a ``weight-of-evidence`` approach is used to determine deleterious ecological effects. Much of the time the results are often contradictory, further complicating the decision process and adding uncertainty to the risk estimate. There are many factors that contribute to this uncertainty, including physical parameters, organism and species sensitivity, bioavailability, power, and test conditions. These factors are evaluated from multiple case studies to provide a means to decrease the uncertainty associated with toxicity testing. This discussion focuses on the results of sediment toxicity testing, variability within and between tests, relating cause to effect, and applicability of toxicity testing to the ecological risk assessment process. Recommendations are given to reduce uncertainty in relating toxicity testing to ERA`s and to increase the ecological relevance associated with toxicity testing.

  16. Nutrient and toxic element soil concentrations during repeated mineral and compost fertilization treatments in a Mediterranean agricultural soil.

    Science.gov (United States)

    Baldantoni, Daniela; Morra, Luigi; Saviello, Giovanni; Alfani, Anna

    2016-12-01

    Agricultural soils of semi-arid Mediterranean areas are often subjected to depletion of their chemical, physical, and biological properties. In this context, organic fertilization, in addition to providing nutrients for a longer time in respect to mineral fertilization, improves many other characteristics related to soil fertility. Moreover, the combined use of organic and mineral fertilizers may promote a more sustainable crop production. However, a concern on the long-term use of organic fertilizers arises in relation to the possible accumulation of toxic elements in soil and their transfer to human beings. For this reason, a long-term study on nutrient and toxic element total concentrations and availabilities during fertilization treatments was carried out. In particular, mineral NPK fertilized soils, soils amended with biowaste compost, soils amended with biowaste compost plus mineral nitrogen, and unfertilized soils were analyzed for 11 chemical elements. The results highlighted that temporal variations in total and bioavailable concentrations of both nutrients and toxic elements, occurring also in unfertilized soils, are wider than those related to fertilization treatments. Anyway, soil amendments with biowaste compost, alone or in combination with mineral fertilizers, reduce Cu bioavailability but improve K, Fe, Mn, and Zn availabilities, excluding at the same time a long-term accumulation in soil. Total and bioavailable toxic element concentrations (apart from available Cd) do not vary in relation to fertilization treatments.

  17. (1)H NMR-based metabolomics study on repeat dose toxicity of fine particulate matter in rats after intratracheal instillation.

    Science.gov (United States)

    Zhang, Yannan; Hu, Hejing; Shi, Yanfeng; Yang, Xiaozhe; Cao, Lige; Wu, Jing; Asweto, Collins Otieno; Feng, Lin; Duan, Junchao; Sun, Zhiwei

    2017-07-01

    Systemic metabolic effects and toxicity mechanisms of ambient fine particulate matter (PM2.5) remain uncertain. In order to investigate the mechanisms in PM2.5 toxicity, we explored the endogenous metabolic changes and possible influenced metabolic pathways in rats after intratracheal instillation of PM2.5 by using a (1)H nuclear magnetic resonance (NMR)-based metabolomics approach. Liver and kidney histopathology examinations were also performed. Chemical characterization demonstrated that PM2.5 was a complex mixture of elements. Histopathology showed cellular edema in liver and glomerulus atrophy of the PM2.5 treated rats. We systematically analyzed the metabolites changes of serum and urine in rats using (1)H NMR techniques in combination with multivariate statistical analysis. Significantly reduced levels of lactate, alanine, dimethylglycine, creatine, glycine and histidine in serum, together with increased levels of citrate, arginine, hippurate, allantoin and decreased levels of allthreonine, lactate, alanine, acetate, succinate, trimethylamine, formate in urine were observed of PM2.5 treated rats. The mainly affected metabolic pathways by PM2.5 were glycine, serine and threonine metabolism, glyoxylate and dicarboxylate metabolism, citrate cycle (TCA cycle), nitrogen metabolism and methane metabolism. Our study provided important information on assessing the toxicity of PM2.5 and demonstrated that metabolomics approach can be employed as a tool to understand the toxicity mechanism of complicated environmental pollutants. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Concentration-time data in toxicity tests and resulting relationships

    Science.gov (United States)

    Hilado, C. J.; Brauer, D. P.

    1979-01-01

    Periodic analyses for carbon monoxide and methane in the animal exposure chamber during pyrolysis of polyethylene at 800 C without forced air flow showed that the concentrations of these compounds increased with exposure time. These observations, and similar observations for polyurethane flexible foam, permitted the calculation of carbon monoxide toxicity in terms of a DP (Death Product Concentration) value, in addition to flammability in terms of HC (Hydro Carbon) value. Observed DP values exceeding the critical DP(CO) value of 47,200 ppm-min for carbon monoxide may indicate that lethal exposures were reached earlier but not immediately manifested because of the time delay involved in physiological processes. On the basis of this DP(CO) value, carbon monoxide could have been the sole toxicant in the case of polyethylene, polypropylene, polyoxymethylene, polystyrene, polycarbonate, ethylene propylene diene rubber, and wood.

  19. Development of a Chronic Toxicity Testing Method for Daphnia pulex

    Science.gov (United States)

    2015-08-01

    handling (Lewis 1985). Both acute and chronic Daphnia exposures have been used to determine the short-term toxicity of many aquatic contaminants, and...sublethal effects. Vincon vinyl clear tubing (1/4 in. inside diameter) (Pentair Aquatic Ecosystems, Part # TP30, Apopka, FL) was used to siphon the D...pipette. Exercise care not to damage the organism by minimizing turbulence. When transferring the organism to the fresh beaker, the tip ERDC/EL SR

  20. Gamma Radiation Reduced Toxicity of Azoxystrobin Tested on Artemia franciscana.

    Science.gov (United States)

    Dvorak, P; Zdarsky, M; Benova, K; Falis, M; Tomko, M

    2016-06-01

    Fungicide azoxystrobin toxicity was monitored by means of a 96-h biotest with Artemia franciscana nauplius stages after exposure to solutions with concentrations of 0.2, 0.4, 0.6 and 0.8 mg L(-1) irradiated with (60)Co gamma radiation with doses of 1, 2.5, 5 and 10 kGy. The effects of ionization radiation on azoxystrobin toxicity were mainly manifested by a statistically significant reduction of lethality after 72- and 96-h exposure. A maximum reduction of lethality of 72 % was achieved using doses of 1-5 kGy for an azoxystrobin initial concentration of 0.4 mg L(-1) and after 72 h of exposure. At a 96-h exposure, a difference of lethal effects reached up to 70 % for a dose of 10 kGy. The observed effect of gamma ionizing radiation on azoxystrobin toxicity suggest that this approach can be applied as an alternative for a reduction of azoxystrobin residua in food.

  1. The embryonic stem cell test combined with toxicogenomics as an alternative testing model for the assessment of developmental toxicity.

    Science.gov (United States)

    van Dartel, Dorien A M; Piersma, Aldert H

    2011-09-01

    One of the most studied in vitro alternative testing methods for identification of developmental toxicity is the embryonic stem cell test (EST). Although the EST has been formally validated, the applicability domain as well as the predictability of the model needs further study to allow successful implementation of the EST as an alternative testing method in regulatory toxicity testing. Genomics technologies have already provided a proof of principle of their value in identification of toxicants such as carcinogenic compounds. Also within the EST, gene expression profiling has shown its value in the identification of developmental toxicity and in the evaluation of factors critical for risk assessment, such as dose and time responses. It is expected that the implementation of genomics into the EST will provide a more detailed end point evaluation as compared to the classical morphological scoring of differentiation cultures. Therefore, genomics may contribute to improvement of the EST, both in terms of definition of its applicability domain as well as its predictive capacity. In the present review, we present the progress that has been made with regard to the prediction of developmental toxicity using the EST combined with transcriptomics. Furthermore, we discuss the developments of additional aspects required for further optimization of the EST, including kinetics, the use of human embryonic stem cells (ESC) and computational toxicology. Finally, the current and future use of the EST model for prediction of developmental toxicity in testing strategies and in regulatory toxicity evaluations is discussed. Copyright © 2011 Elsevier Inc. All rights reserved.

  2. Development of a New Toxicity Test Method Using a Bio-dipstick

    Science.gov (United States)

    2013-11-12

    For this reason, most toxicity test methods cannot be performed in the petroleum laboratory. The bio -dipstick is a formation of agar medium and was...designed to monitoring of microbial contamination in various industrial environments. Recently, this bio -dipstick has been also successfully used for...was studied using a bio -dipstick. The test results showed that the proposed test method was able to differentiate the toxicity level of lubricants and

  3. Sympathetic enhancement in futsal players but not in football players after repeated sprint ability test.

    Science.gov (United States)

    Chen, Yung-Sheng; Liao, Chih-Jung; Lu, Wan-An; Kuo, Cheng-Deng

    2015-01-01

    Heart rate variability (HRV) can disclose the specific adaptation of sympathovagal modulation to exercise. This study investigated the change in HRV measures after anaerobic and aerobic intermittent exercises in university football and futsal players. 36 male university students with physically active lifestyle (n=14), football (n=12), and futsal (n=10) participated in this study. The participants completed the repeated sprint ability (RSA) test and Yo-Yo (YY) intermittent recovery test level 1 in randomised order. ECG signals of the participants were recorded in supine position 15 min before and 30 min after exercises. Before exercise, and 5 and 30 min after exercise, the blood pressures were also taken. In the RSA protocol, the percentage changes in normalised high-frequency power (nHFP) were significantly decreased, while the percentage changes in the very low/high frequency power ratio (VLHR) and low/high frequency power ratio (LHR) were significantly increased in futsal players after exercise, as compared with the controls. No significant changes in all HRV indices were found in the YY protocol, except the respiratory frequency. After exercise, the percent decrease in vagal modulation in futsal players was significantly reduced, while the percentage increase in sympathetic modulation in futsal players was significantly enhanced in the RSA test, but not in the YY test, as compared with the control group. The increase in sympathetic activity and the decrease in vagal activity in the futsal players were greater than the corresponding increase and decrease in the football players in the RSA test.

  4. Passive Dosing in Chronic Toxicity Tests with the Nematode Caenorhabditis elegans.

    Science.gov (United States)

    Fischer, Fabian; Böhm, Leonard; Höss, Sebastian; Möhlenkamp, Christel; Claus, Evelyn; Düring, Rolf-Alexander; Schäfer, Sabine

    2016-09-01

    In chronic toxicity tests with Caenorhabditis elegans, it is necessary to feed the nematode with bacteria, which reduces the freely dissolved concentration (Cfree) of hydrophobic organic chemicals (HOCs), leading to poorly defined exposure with conventional dosing procedures. We examined the efficacy of passive dosing of polycyclic aromatic hydrocarbons (PAHs) using silicone O-rings to control exposure during C. elegans toxicity testing and compared the results to those obtained with solvent spiking. Solid-phase microextraction and liquid-liquid extraction were used to measure Cfree and the chemicals taken up via ingestion. During toxicity testing, Cfree decreased by up to 89% after solvent spiking but remained constant with passive dosing. This led to a higher apparent toxicity on C. elegans exposed by passive dosing than by solvent spiking. With increasing bacterial cell densities, Cfree of solvent-spiked PAHs decreased while being maintained constant with passive dosing. This resulted in lower apparent toxicity under solvent spiking but an increased apparent toxicity with passive dosing, probably as a result of the higher chemical uptake rate via food (CUfood). Our results demonstrate the utility of passive dosing to control Cfree in routine chronic toxicity testing of HOCs. Moreover, both chemical uptake from water or via food ingestion can be controlled, thus enabling the discrimination of different uptake routes in chronic toxicity studies.

  5. 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

  6. 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 thei

  7. Application of Neomysis awatschensis as a standard marine toxicity test organism in China

    Institute of Scientific and Technical Information of China (English)

    YAN Tian; ZHOU Ming-jiang; TAN Zhi-jun; LI Zheng-yan; LI Jun; YU Ren-cheng; WANG Li-ping

    2003-01-01

    The small mysid crustacean Neomysis awatschensis was collected in the west coast of Jiaozhou Bay, Qingdao, China in 1992 and acclimated and cultured in laboratory conditions since then. Standard acute toxicity tests using 4-6 d juvenile mysids of this species were conducted and the results were compared with Mysidopsis bahia, a standard toxicity test organism used in the US in terms of their sensitivities to reference toxins, as well as their taxonomy, morphology and geographic distributions. Because of its wide distribution along the Chinese coast, similar sensitivity to pollutants as M. bahia, short life history, small size and the ease of handling, this study intended to use N.awatschensis as one of the standard marine organisms for toxicity testing in China. The species were applied to acute toxicity evaluations of drilling fluid and its additives, organotin TPT and toxic algae, and to chronic ( life cycle) toxicity assays of organotin TPT and a toxic dinofalgellate Alexandrium tamarense, respectively. Using N. awatschensis as a standard toxicity testing organism in marine pollution assessment in China is suggested.

  8. Toxicity Tests of Whole Sediment Samples Using the Hyallella (H. azteca) Survival and Growth Tests (ASTM E 1283-93)

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — 10-day toxicity tests using Hyalella azteca were conducted with sediment samples collected by the U.S. Fish & Wildlife Service, Bloomington, Indiana facility to...

  9. Promoting the 3Rs to enhance the OECD fish toxicity testing framework.

    Science.gov (United States)

    Hutchinson, Thomas H; Wheeler, James R; Gourmelon, Anne; Burden, Natalie

    2016-04-01

    Fish toxicity testing has been conducted since the 1860's in order to help define safe levels of chemical contaminants in lakes, rivers and coastal waters. The historical emphasis on acute lethality testing of chemicals has more recently focussed on long term sublethal effects of chemicals on fish and their prey species. Fish toxicity testing is now embedded in much environment legislation on chemical safety while it is recognized that animal use should be Replaced, Reduced and Refined (the 3Rs) where possible. The OECD Fish Toxicity Testing Framework provides a useful structure with which to address the needs of environmental safety assessment whilst implementing the 3Rs. This commentary aims to promote the implementation of the recommendations of the OECD Fish Toxicity Testing Framework. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. The extended statistical analysis of toxicity tests using standardised effect sizes (SESs: a comparison of nine published papers.

    Directory of Open Access Journals (Sweden)

    Michael F W Festing

    Full Text Available The safety of chemicals, drugs, novel foods and genetically modified crops is often tested using repeat-dose sub-acute toxicity tests in rats or mice. It is important to avoid misinterpretations of the results as these tests are used to help determine safe exposure levels in humans. Treated and control groups are compared for a range of haematological, biochemical and other biomarkers which may indicate tissue damage or other adverse effects. However, the statistical analysis and presentation of such data poses problems due to the large number of statistical tests which are involved. Often, it is not clear whether a "statistically significant" effect is real or a false positive (type I error due to sampling variation. The author's conclusions appear to be reached somewhat subjectively by the pattern of statistical significances, discounting those which they judge to be type I errors and ignoring any biomarker where the p-value is greater than p = 0.05. However, by using standardised effect sizes (SESs a range of graphical methods and an over-all assessment of the mean absolute response can be made. The approach is an extension, not a replacement of existing methods. It is intended to assist toxicologists and regulators in the interpretation of the results. Here, the SES analysis has been applied to data from nine published sub-acute toxicity tests in order to compare the findings with those of the author's. Line plots, box plots and bar plots show the pattern of response. Dose-response relationships are easily seen. A "bootstrap" test compares the mean absolute differences across dose groups. In four out of seven papers where the no observed adverse effect level (NOAEL was estimated by the authors, it was set too high according to the bootstrap test, suggesting that possible toxicity is under-estimated.

  11. TPK Sarimukti, Cipatat, West Bandung compost toxicity test using Allium test

    Science.gov (United States)

    Wardini, Trimurti Hesti; Notodarmojo, Peni Astrini

    2015-09-01

    TPK Sarimukti, Cipatat, West Bandung produced 2 kinds of compost from traditional market waste, liquid and solid compost. The aim of this research is to evaluate toxicity of compost produced in TPK Sarimukti using shallots (Allium cepa). Tests carried out by treated shallots with liquid compost (2,5%, 5%, 10% and 12,5% (w/v)) or solid compost (25%, 50%, 75% and 100% (w/v)) for 48 hours. Results showed reduced root growth rate and mitotic index (MI) in accordance with increased concentrations of compost. Sub lethal concentrations are liquid compost 5% and 10% and solid compost 75%. Lethal concentrations are liquid compost 12,5 % and solid compost 100%. Micronuclei (MN) increased with increase in liquid compost concentration. MN found at very high frequencies in highest solid compost concentration (100%), but very low at lower concentrations. Cells with binuclei and cell necrosis increased with increasing concentrations of given compost. Nuclear anomalies (NA) found in high frequency in 75% and 100% solid compost. Based on research, we can conclude that liquid compost is more toxic because it can reduce MI and root growth rate at lower concentrations than solid compost. Both types of compost have genotoxic properties because it can induce chromosome aberration (CA), MN, binuclei and NA formation.

  12. TPK Sarimukti, Cipatat, West Bandung compost toxicity test using Allium test

    Energy Technology Data Exchange (ETDEWEB)

    Wardini, Trimurti Hesti; Notodarmojo, Peni Astrini [Biology Study Program, School of Life Science and Technology, Bandung Institute of Technology (Indonesia)

    2015-09-30

    TPK Sarimukti, Cipatat, West Bandung produced 2 kinds of compost from traditional market waste, liquid and solid compost. The aim of this research is to evaluate toxicity of compost produced in TPK Sarimukti using shallots (Allium cepa). Tests carried out by treated shallots with liquid compost (2,5%, 5%, 10% and 12,5% (w/v)) or solid compost (25%, 50%, 75% and 100% (w/v)) for 48 hours. Results showed reduced root growth rate and mitotic index (MI) in accordance with increased concentrations of compost. Sub lethal concentrations are liquid compost 5% and 10% and solid compost 75%. Lethal concentrations are liquid compost 12,5 % and solid compost 100%. Micronuclei (MN) increased with increase in liquid compost concentration. MN found at very high frequencies in highest solid compost concentration (100%), but very low at lower concentrations. Cells with binuclei and cell necrosis increased with increasing concentrations of given compost. Nuclear anomalies (NA) found in high frequency in 75% and 100% solid compost. Based on research, we can conclude that liquid compost is more toxic because it can reduce MI and root growth rate at lower concentrations than solid compost. Both types of compost have genotoxic properties because it can induce chromosome aberration (CA), MN, binuclei and NA formation.

  13. Toxicity tests of soil contaminated by recycling of scrap plastics.

    Science.gov (United States)

    Wong, M H; Chui, V W

    1990-03-01

    The present investigation studied the toxicity of soil contaminated by untreated discharge from a factory that recycles used plastics. The nearby agricultural areas and freshwater fish ponds were polluted with high concentrations of Cu, Ni, and Mn. Water extracts from the contaminated soil retarded root growth of Brassica chinensis (Chinese white cabbage) and Cynodon dactylon (Bermuda grass) where their seeds were obtained commercially. The contaminated populations of C. dactylon, Panicum repen (panic grass), and Imperata cylindrica (wooly grass) were able to withstand higher concentrations of Cu, Ni, and Mn, especially C. dactylon, when compared with their uncontaminated counterparts.

  14. INDUSTRIAL ROBOT REPEATABILITY TESTING WITH HIGH SPEED CAMERA PHANTOM V2511

    Directory of Open Access Journals (Sweden)

    Jerzy Józwik

    2016-12-01

    Full Text Available Apart from accuracy, one of the parameters describing industrial robots is positioning accuracy. The parameter in question, which is the subject of this paper, is often the decisive factor determining whether to apply a given robot to perform certain tasks or not. Articulated robots are predominantly used in such processes as: spot weld-ing, transport of materials and other welding applications, where high positioning repeatability is required. It is therefore essential to recognise the parameter in question and to control it throughout the operation of the robot. This paper presents methodology for robot positioning accuracy measurements based on vision technique. The measurements were conducted with Phantom v2511 high-speed camera and TEMA Motion software, for motion analysis. The object of the measurements was a 6-axis Yaskawa Motoman HP20F industrial robot. The results of measurements obtained in tests provided data for the calculation of positioning accuracy of the robot, which was then juxtaposed against robot specifications. Also analysed was the impact of the direction of displacement on the value of attained pose errors. Test results are given in a graphic form.

  15. The case for using the repeatability coefficient when calculating test-retest reliability.

    Directory of Open Access Journals (Sweden)

    Sharmila Vaz

    Full Text Available The use of standardised tools is an essential component of evidence-based practice. Reliance on standardised tools places demands on clinicians to understand their properties, strengths, and weaknesses, in order to interpret results and make clinical decisions. This paper makes a case for clinicians to consider measurement error (ME indices Coefficient of Repeatability (CR or the Smallest Real Difference (SRD over relative reliability coefficients like the Pearson's (r and the Intraclass Correlation Coefficient (ICC, while selecting tools to measure change and inferring change as true. The authors present statistical methods that are part of the current approach to evaluate test-retest reliability of assessment tools and outcome measurements. Selected examples from a previous test-retest study are used to elucidate the added advantages of knowledge of the ME of an assessment tool in clinical decision making. The CR is computed in the same units as the assessment tool and sets the boundary of the minimal detectable true change that can be measured by the tool.

  16. The assessment of sewage sludge gasification by-products toxicity by ecotoxicologial test.

    Science.gov (United States)

    Werle, Sebastian; Dudziak, Mariusz

    2015-08-01

    The process of gasification of sewage sludge generates by-products, which may be contaminated with toxic and hazardous substances, both organic and inorganic. It is therefore important to assess the environmental risk associated with this type of waste. The feasibility of using an ecotoxicological tests for this purpose was determined in the presented study. The applied tests contained indicator organisms belonging to various biological groups (bacteria, crustaceans, plants). The subject of the study were solid (ash, char) and liquid (tar) by-products generated during gasification (in a fixed bed reactor) of dried sewage sludge from various wastewater treatment systems. The tested samples were classified based on their toxic effect. The sensitivity of the indicator organisms to the tested material was determined. In-house procedures for the preparation for toxicity analysis of both sewage sludge and by-products generated during the gasification were presented. The scope of work also included the determination of the effect of selected process parameters (temperature, amount of gasifying agent) on the toxicity of gasification by-products depending on the sewage sludge source. It was shown that both the type of sewage sludge and the parameters of the gasification process affects the toxicity of the by-products of gasification. However, the results of toxicity studies also depend on the type of ecotoxicological test used, which is associated with a different sensitivity of the indicator organisms. Nevertheless, it may be concluded that the by-products formed during the gasification of the low toxicity sewage sludge can be regarded as non-toxic or low toxic. However, the results analysis of the gasification of the toxic sludge were not conclusive, which leads to further research needs in this area. © The Author(s) 2015.

  17. Whole sediment toxicity tests for metal risk assessments: on the importance of equilibration and test design to increase ecological relevance.

    Science.gov (United States)

    Vandegehuchte, Michiel B; Nguyen, Lien T H; De Laender, Frederik; Muyssen, Brita T A; Janssen, Colin R

    2013-04-01

    Current laboratory-based approaches for predicting metal toxicity in sediments exhibit a number of limitations. The most important are (1) a lack of sufficient equilibration resulting in unrealistically low pH values or unnaturally high porewater metal concentrations and (2) an inadequate test design regarding the metal concentrations selected for spiking. The present study illustrates that by explicitly accounting for these limitations, one obtains reliable and environmentally realistic toxicity data, thus advancing the metal risk assessments of sediments. To this end, a toxicity test design with natural sediments was developed in which the administered metal concentrations were selected to comprise a range of the difference between the molar concentration of simultaneously extracted metals and acid volatile sulfides (SEM-AVS) closely surrounding zero. In addition, the test design presented includes a 35- or 40-d equilibration period with overlying water renewal during which conductivity, pH, and metal concentrations in the overlying water are monitored. This allows toxicity testing to start after equilibrium for these parameters has been reached. This test design was applied to Ephoron virgo (Olivier, 1791), Gammarus pulex (Linnaeus, 1758), and Lumbriculus variegatus (Mueller, 1774) exposed to Zn and Pb. These tests indicated that the general concept of absence of toxicity when SEM-AVS<0 could not be rejected. However, the onset of Zn toxicity occurred at lower concentrations than generally assumed.

  18. Collaborative work to evaluate toxicity on male reproductive organs by repeated dose studies in rats 22). Effects of 2- and 4-week administration of theobromine on the testis.

    Science.gov (United States)

    Funabashi, H; Fujioka, M; Kohchi, M; Tateishi, Y; Matsuoka, N

    2000-10-01

    The effects of theobromine, a xanthine derivative, on the testis were compared between rats dosed for 2 and 4 weeks to determine whether a 2-week dosing period is long enough to detect toxicity. Theobromine was administered orally to male Sprague-Dawley rats at dose levels of 250 and 500 mg/kg for 2 weeks starting at the age of 6 or 8 weeks, and for 4 weeks from the age of 6 weeks. Histopathological examination of reproductive organs revealed toxic findings in the testis at 500 mg/kg after 2 weeks of dosing at both ages, and at 250 and 500 mg/kg after 4 weeks of dosing. The primary findings were degeneration/necrosis and desquamation of spermatids and spermatocytes, vacuolization of seminiferous tubules, and multinucleated giant cell formation. These findings were present mainly in stages I-VI and XII-XIV. From these results, it is concluded that the toxic effects of theobromine on the testis can be detected by repeated dosing for 2 weeks as well as for 4 weeks.

  19. Developmental toxicity testing for safety assessment: new approaches and technologies.

    Science.gov (United States)

    Knudsen, Thomas B; Kavlock, Robert J; Daston, George P; Stedman, Donald; Hixon, Mary; Kim, James H

    2011-10-01

    The ILSI Health and Environmental Sciences Institute's Developmental and Reproductive Toxicology Technical Committee held a 2-day workshop entitled "Developmental Toxicology-New Directions" in April 2009. The fourth session of this workshop focused on new approaches and technologies for the assessment of developmental toxicology. This session provided an overview of the application of genomics technologies for developmental safety assessment, the use of mouse embryonic stem cells to capture data on developmental toxicity pathways, dynamical cell imaging of zebrafish embryos, the use of computation models of development pathways and systems, and finally, high-throughput in vitro approaches being utilized by the EPA ToxCast program. Issues discussed include the challenges of anchoring in vitro predictions to relevant in vivo endpoints and the need to validate pathway-based predictions with targeted studies in whole animals. Currently, there are 10,000 to 30,000 chemicals in world-wide commerce in need of hazard data for assessing potential health risks. The traditional animal study designs for assessing developmental toxicity cannot accommodate the evaluation of this large number of chemicals, requiring that alternative technologies be utilized. Though a daunting task, technologies are being developed and utilized to make that goal reachable. © 2011 Wiley Periodicals, Inc.

  20. Interlaboratory Evaluation of Hyalella Azteca and Chironomus Tentans Short-term and Long-term Sediment Toxicity Tests

    Science.gov (United States)

    This paper presents the results of interlaboratory toxicity tests on sediment toxicity methods for use in routine testing and this data has been presented in an EPA report and this is a summary of that data.

  1. Interlaboratory Evaluation of Hyalella Azteca and Chironomus Tentans Short-term and Long-term Sediment Toxicity Tests

    Science.gov (United States)

    This paper presents the results of interlaboratory toxicity tests on sediment toxicity methods for use in routine testing and this data has been presented in an EPA report and this is a summary of that data.

  2. Evaluation of the sensitivity of freshwater organisms used in toxicity tests of wastewater from explosives company.

    Science.gov (United States)

    Ribeiro, Elaine Nolasco; da Silva, Flávio Teixeira; de Paiva, Teresa Cristina Brazil

    2012-10-01

    Explosives industries are a source of toxic discharge. The aim of this study was to compare organisms sensitivity (Daphnia similis, Danio rerio, Escherichia coli and Pseudomonas putida) in detecting acute toxicity in wastewater from two explosives, 2,4,6-TNT (TNT) and nitrocellulose. The samples were collected from an explosives company in the Paraiba Valley, São Paulo, Brazil. The effluents from TNT and nitrocellulose production were very toxic for tested organisms. Statistical tests indicated that D. similis and D. rerio were the most sensitive organisms for toxicity detection in effluents from 2,4,6-TNT and nitrocellulose production. The P. putida bacteria was the organism considered the least sensitive in indicating toxicity in effluents from nitrocellulose.

  3. Development and application of a marine sediment pore-water toxicity test using Ulva fasciata zoospores

    Science.gov (United States)

    Hooten, R.L.; Carr, R.S.

    1998-01-01

    An acute (96 h) pore-water toxicity test protocol using germination and growth of Ulva fasciata zoospores as endpoints was developed to test the toxicity of marine and estuarine sediment pore-water samples. Tests with an organic toxicant (sodium dodecyl sulfate; SDS), three metals (Cd, Cu, and Zn), and ammonia (NH3) were conducted to determine zoospore sensitivity. Zoospore germination and gametophyte growth were as sensitive to SDS as sea urchin (Arbacia punctulata) fertilization and embryological development. Zoospore sensitivity to metals was greater than or comparable to that of adult macroalgae. Zoospores were less sensitive to NH3 than were other commonly used toxicity test organisms. Test results using this algal assay with sediment pore-water samples with high NH3 concentrations were compared with results from sea urchin fertilization and embryological development tests for the same samples. Ulva fasciata zoospore germination was not affected by samples with high NH3 concentrations that were toxic in both sea urchin tests. Zoospore tolerance of NH3 and sensitivity to other contaminants indicate that their response may be useful in toxicity identification evaluation studies with pore-water samples that contain high concentrations of unionized NH3.

  4. Modifying Foods and Feeding Regimes to Optimize the Performance of Hyalella azteca during Chronic Toxicity Tests

    Science.gov (United States)

    The amphipod Hyalella azteca is commonly used to assess the toxicity of sediments and waters. However, laboratories have reported varying success in maintaining healthy cultures and in obtaining consistent growth and reproduction (where applicable), especially during tests...

  5. Modifying Foods and Feeding Regimes to Optimize the Performance of Hyalella azteca during Chronic Toxicity Tests

    Science.gov (United States)

    The amphipod Hyalella azteca is commonly used to assess the toxicity of sediments and waters. However, laboratories have reported varying success in maintaining healthy cultures and in obtaining consistent growth and reproduction (where applicable), especially during tests...

  6. Toxic Substances Control Act Test Submissions 2.0 (TSCATS 2.0)

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Toxic Substances Control Act Test Submissions 2.0 (TSCATS 2.0) tracks the submissions of health and safety data submitted to the EPA either as required or...

  7. Suboptimal performance on neuropsychological tests in patients with suspected chronic toxic encephalopathy

    NARCIS (Netherlands)

    van Hout, MSE; Schmand, B; Wekking, EM; Hageman, G; Deelman, BG

    2003-01-01

    Suboptimal performance during neuropsychological testing can seriously complicate assessment in behavioral neurotoxicology. We present data on the prevalence of suboptimal performance in a group of Dutch patients with suspected chronic toxic encephalopathy (CTE) after long-term occupational exposure

  8. Comparative use of bacterial, algal and protozoan tests to study toxicity of azo- and anthraquinone dyes.

    Science.gov (United States)

    Novotný, Cenek; Dias, Nicolina; Kapanen, Anu; Malachová, Katerina; Vándrovcová, Marta; Itävaara, Merja; Lima, Nelson

    2006-06-01

    Toxicity of two azo dyes (Reactive Orange 16 (RO16); Congo Red (CR)) and two anthraquinone dyes (Remazol Brilliant Blue R (RBBR); Disperse Blue 3 (DB3)) were compared using bacterium Vibrio fischeri, microalga Selenastrum capricornutum and ciliate Tetrahymena pyriformis. The following respective endpoints were involved: acute toxicity measured as bacterial luminescence inhibition, algal growth inhibition, and the effects on the protozoa including viability, growth inhibition, grazing effect and morphometric effects. In addition, mutagenicity of the dyes was determined using Ames test with bacterium Salmonella typhimurium His(-). DB3 dye was the most toxic of all dyes in the bacterial, algal and protozoan tests. In contrast to other dyes, DB3 exhibited mutagenic effects after metabolic activation in vitro in all S. typhimurium strains used. Of the methods applied, the algal test was the most sensitive to evaluate toxicity of the dyes tested.

  9. EP-toxicity test of saturated GT-73 resin and resin in grout

    Energy Technology Data Exchange (ETDEWEB)

    Bibler, J.P.

    1985-04-24

    The results of EP-toxicity tests on mercury saturated Duolite{reg_sign} GT-73 cation exchange resin clarify options for the ultimate disposal of spent resin. Samples of GT-73 saturated with mercury passed the EP-toxicity test, indicating that fully spent resin may be classifed as ``solid``-not``hazardous``-waste and stored or disposed-of as such. Samples of GT-73 resin saturated with mercury and then incorporated into Portland Type 1 cement did not pass the EP-toxicity test and fall into the ``hazardous waste`` category. Samples of GT-73 resin less-than-saturated with mercury which were in corporated in Portland Type 1 cement passed the EP-toxicity test and may be classified as ``solid waste.`` Other commercially available materials are being investigated for incorporating fully spent GT-73 resin in a solid waste form.

  10. 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...

  11. Integrating the fish embryo toxicity test as triad element for sediment toxicity assessment based on the water framework directive approach

    Energy Technology Data Exchange (ETDEWEB)

    Bartzke, Mariana [Dept. Aquatic Ecotoxicology, Goethe Univ. Frankfurt am Main (Germany); Gobio GmbH, Aarbergen/Kettenbach (Germany); Dept. Bioanalytical Ecotoxicology, Helmholtz Centre for Environmental Research, UFZ, Leipzig (Germany); Delov, Vera [Dept. Aquatic Ecotoxicology, Goethe Univ. Frankfurt am Main (Germany); Gobio GmbH, Aarbergen/Kettenbach (Germany); Ecotoxicology, Fraunhofer Inst. for Molecular Biology and Applied Ecology IME, Aachen (Germany); Stahlschmidt-Allner, Petra; Allner, Bernhard [Gobio GmbH, Aarbergen/Kettenbach (Germany); Oehlmann, Joerg [Dept. Aquatic Ecotoxicology, Goethe Univ. Frankfurt am Main (Germany)

    2010-04-15

    Purpose: The objective of this study was to complement analyses according to the European Union Water Framework Directive (WFD) with a sediment toxicity analysis as part of an integrated river assessment. To this end, Hessian water courses were analyzed using the sediment quality triad concept according to Chapman with chemical analyses, in situ effect evaluations, and ecotoxicological assessments. For the ecotoxicological assessment (fish embryo toxicity test with Danio rerio), a new evaluation scheme was developed, the fish teratogenicity index (FTI), that allows for a classification of sediments into ecological quality classes compliant to the WFD. Materials and methods sediment and macrozoobenthos samples were taken from tributaries of the rivers Fulda and Lahn. Sediments were characterized regarding particle size, carbon, heavy metals, and polyaromatic hydrocarbon content. Macroinvertebrate samples were taken via multi-habitat sampling. The fish embryo toxicity test with D. rerio was conducted as a contact assay on the basis of DIN 38415-6. Results and discussion The integrated assessment indicated a significant influence of heavy metals and carbon content on macroinvertebrate communities. The bioaccessibility of sediment pollutants were clearly demonstrated by the FTI, which showed a wide range of adverse effects. A significant linear relationship between metals and the FTI was detected. However, there was no statistically significant evidence that macroinvertebrate communities were affected by the hydromorphological quality clements at the sampling sites. Conclusions The new scheme for the assessment of fish embryo toxicity test was successfully applied. The results suggest that sediment compounds impact macroinvertebrate communities and early development of fish. It demonstrates that the quality of sediments should be evaluated on a routine basis as part of an integrated river assessment. (orig.)

  12. 40 CFR 797.1050 - Algal acute toxicity test.

    Science.gov (United States)

    2010-07-01

    ... concentration may be pooled into one sample. An aliquot of the pooled sample may then be taken and the... centrifuging or filtering the remaining pooled sample and measure the test substance concentration in the algal... perform this test include: a growth chamber or a controlled environment room that can hold the test...

  13. 40 CFR 797.1400 - Fish acute toxicity test.

    Science.gov (United States)

    2010-07-01

    ... handled and stored in a manner which minimizes loss of test substance through microbial degradation... solution. Glass or stainless steel filter holders are best for organic test substances, while plastic... concentration range to be used in the test. (D) An analytical method is not acceptable if likely degradation...

  14. Repeated dose 28-days oral toxicity study of Carica papaya L. leaf extract in Sprague Dawley rats.

    Science.gov (United States)

    Afzan, Adlin; Abdullah, Noor Rain; Halim, Siti Zaleha; Rashid, Badrul Amini; Semail, Raja Hazlini Raja; Abdullah, Noordini; Jantan, Ibrahim; Muhammad, Hussin; Ismail, Zakiah

    2012-04-10

    Carica papaya L. leaves have been used in ethnomedicine for the treatment of fevers and cancers. Despite its benefits, very few studies on their potential toxicity have been described. The aim of the present study was to characterize the chemical composition of the leaf extract from 'Sekaki' C. papaya cultivar by UPLC-TripleTOF-ESI-MS and to investigate the sub-acute oral toxicity in Sprague Dawley rats at doses of 0.01, 0.14 and 2 g/kg by examining the general behavior, clinical signs, hematological parameters, serum biochemistry and histopathology changes. A total of twelve compounds consisting of one piperidine alkaloid, two organic acids, six malic acid derivatives, and four flavonol glycosides were characterized or tentatively identified in the C. papaya leaf extract. In the sub-acute study, the C. papaya extract did not cause mortality nor were treatment-related changes in body weight, food intake, water level, and hematological parameters observed between treatment and control groups. Some biochemical parameters such as the total protein, HDL-cholesterol, AST, ALT and ALP were elevated in a non-dose dependent manner. Histopathological examination of all organs including liver did not reveal morphological alteration. Other parameters showed non-significant differences between treatment and control groups. The present results suggest that C. papaya leaf extract at a dose up to fourteen times the levels employed in practical use in traditional medicine in Malaysia could be considered safe as a medicinal agent.

  15. Comparison of toxicity values across zebrafish early life stages and mammalian studies: Implications for chemical testing.

    Science.gov (United States)

    Ducharme, Nicole A; Reif, David M; Gustafsson, Jan-Ake; Bondesson, Maria

    2015-08-01

    With the high cost and slow pace of toxicity testing in mammals, the vertebrate zebrafish has become a tractable model organism for high throughput toxicity testing. We present here a meta-analysis of 600 chemicals tested for toxicity in zebrafish embryos and larvae. Nineteen aggregated and 57 individual toxicity endpoints were recorded from published studies yielding 2695 unique data points. These data points were compared to lethality and reproductive toxicology endpoints analyzed in rodents and rabbits and to exposure values for humans. We show that although many zebrafish endpoints did not correlate to rodent or rabbit acute toxicity data, zebrafish could be used to accurately predict relative acute toxicity through the rat inhalation, rabbit dermal, and rat oral exposure routes. Ranking of the chemicals based on toxicity and teratogenicity in zebrafish, as well as human exposure levels, revealed that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), benzo(a)pyrene, and chlorpyrifos ranked in the top nine of all chemicals for these three categories, and as such should be considered high priority chemicals for testing in higher vertebrates.

  16. Quantitative patch and repeated open application testing in methyldibromo glutaronitrile-sensitive patients.

    Science.gov (United States)

    Schnuch, A; Kelterer, D; Bauer, A; Schuster, Ch; Aberer, W; Mahler, V; Katzer, K; Rakoski, J; Jappe, U; Krautheim, A; Bircher, A; Koch, P; Worm, M; Löffler, H; Hillen, U; Frosch, P J; Uter, W

    2005-04-01

    Contact allergy to methyldibromo glutaronitrile (MDBGN), often combined with phenoxyethanol (PE) (e.g., Euxyl K 400), increased throughout the 1990s in Europe. Consequently, in 2003, the European Commission banned its use in leave-on products, where its use concentration was considered too high and the non-sensitizing use concentration as yet unknown. The 2 objectives of the study are (a) to find a maximum non-eliciting concentration in a leave-on product in MDBGN/PE-sensitized patients, which could possibly also be considered safe regarding induction and (b) to find the best patch test concentration for MDBGN. We, therefore, performed a use-related test (ROAT) in patients sensitized to MDBGN/PE (n = 39) with 3 concentrations of MDBGN/PE (50, 100 and 250 p.p.m. MDBGN, respectively). A subset of these patients (n = 24) was later patch-tested with various concentrations (0.1, 0.2, 0.3 and 0.5% MDBGN, respectively). 15 patients (38%, 95% confidence interval (CI) = 23-55%) had a negative and 24 (62%; 95% CI = 45-77%) a positive overall repeated open application test (ROAT) result. 13 reacted to the lowest (50 p.p.m.), 8 to the middle (100 p.p.m.) and 3 to the highest concentration (250 p.p.m.) only. In those 13 reacting to the lowest ROAT concentration, dermatitis developed within a few days (1-7). The strength of the initial and the confirmatory patch test result, respectively, and the outcome of the ROAT were positively associated. Of the 24 patients with a use and confirmatory patch test, 15 reacted to 0.1% MDBGN, 16 to 0.2%, 17 to 0.3% and 22 to 0.5%. With the patch test concentration of 0.5%, the number of ROAT-negative patients but patch-test-positive patients increases considerably, particularly due to + reactions. A maximum sensitivity of 94% (95% CI = 70-100%) is reached with a patch test concentration of 0.2%, and is not further improved by increasing the concentration. However, the specificity decreases dramatically from 88 (95% CI = 47-100%) with 0.2% to a

  17. Acute toxicity tests on raw leachate from a Malaysian dumping site.

    Science.gov (United States)

    Sujá, Fatihah; Yusof, Arij; Osman, Md Anuar

    2010-01-01

    Leachate samples collected from the Ampar Tenang open dumping site at Dengkil, Malaysia, were analyzed for acute toxicity. Two in vivo toxicity tests, Acute Oral Toxicity (AOT) and Primary Skin Irritation (PSI), were performed using Sprague Dawley rats and New Zealand Albino rabbits, respectively. The leachate samples were also analyzed chemically for nitrate and phosphate, ammonia-nitrogen, Kjeldahl-nitrogen and Chemical Oxygen Demand (COD). Results from both the AOT and PSI tests showed that the leachate did not contribute to acute toxicity. The AOT test yielded a negative result: no effect was observed in at least half of the rat population. The PSI test on rabbits produced effects only at a leachate concentration of 100%. However, the skin irritation was minor, and the test returned a negative result. The four chemical tests showed high levels of nutrient pollution in the leachate. The nitrate and phosphate concentrations were 2.1 mg/L and 23.6 mg/L, respectively. Further, the ammonia-nitrogen concentration was 1,000 mg NH(3)-N/L the Kjeldahl-nitrogen level was 446 mg NH(3)-N/L, and the Chemical Oxygen Demand was 1,300 mg/L. The in vivo toxicity and chemical analyses showed that the leachate is polluted but not acutely toxic to organisms.

  18. On the possibility of using biological toxicity tests to monitor the work of wastewater treatment plants

    Directory of Open Access Journals (Sweden)

    Zorić Jelena

    2008-01-01

    Full Text Available The aim of this study was to ascertain the possibility of using biological toxicity tests to monitor influent and effluent wastewaters of wastewater treatment plants. The information obtained through these tests is used to prevent toxic pollutants from entering wastewater treatment plants and discharge of toxic pollutants into the recipient. Samples of wastewaters from the wastewater treatment plants of Kragujevac and Gornji Milanovac, as well as from the Lepenica and Despotovica Rivers immediately before and after the influx of wastewaters from the plants, were collected between October 2004 and June 2005. Used as the test organism in these tests was the zebrafish Brachydanio rerio Hamilton - Buchanon (Cyprinidae. The acute toxicity test of 96/h duration showed that the tested samples had a slight acutely toxic effect on B. rerio, except for the sample of influent wastewater into the Cvetojevac wastewater treatment plant, which had moderately acute toxicity, indicating that such water should be prevented from entering the system in order to eliminate its detrimental effect on the purification process.

  19. Alternative methods for toxicity assessments in fish: comparison of the fish embryo toxicity and the larval growth and survival tests in zebrafish and fathead minnows.

    Science.gov (United States)

    Jeffries, Marlo K Sellin; Stultz, Amy E; Smith, Austin W; Rawlings, Jane M; Belanger, Scott E; Oris, James T

    2014-11-01

    An increased demand for chemical toxicity evaluations has resulted in the need for alternative testing strategies that address animal welfare concerns. The fish embryo toxicity (FET) test developed for zebrafish (Danio rerio) is one such alternative, and the application of the FET test to other species such as the fathead minnow (Pimephales promelas) has been proposed. In the present study, the performances of the FET test and the larval growth and survival (LGS; a standard toxicity testing method) test in zebrafish and fathead minnows were evaluated. This required that testing methods for the fathead minnow FET and zebrafish LGS tests be harmonized with existing test methods and that the performance of these testing strategies be evaluated by comparing the median lethal concentrations of 2 reference toxicants, 3,4-dicholoraniline and ammonia, obtained via each of the test types. The results showed that procedures for the zebrafish FET test can be adapted and applied to the fathead minnow. Differences in test sensitivity were observed for 3,4-dicholoraniline but not ammonia; therefore, conclusions regarding which test types offer the least or most sensitivity could not be made. Overall, these results show that the fathead minnow FET test has potential as an alternative toxicity testing strategy and that further analysis with other toxicants is warranted in an effort to better characterize the sensitivity and feasibility of this testing strategy. © 2014 SETAC.

  20. Instability in the COPD Diagnosis upon Repeat Testing Vary with the Definition of COPD

    Science.gov (United States)

    Perez-Padilla, Rogelio; Wehrmeister, Fernando C.; Montes de Oca, Maria; Lopez, Maria Victorina; Jardim, Jose R.; Muino, Adriana; Valdivia, Gonzalo; Pertuze, Julio; Menezes, Ana Maria B.

    2015-01-01

    Background A low FEV1/FVC from post-bronchodilator spirometry is required to diagnose COPD. Both the FEV1 and the FVC can vary over time; therefore, individuals can be given a diagnosis of mild COPD at one visit, but have normal spirometry during the next appointment, even without an intervention. Methods We analyzed two population-based surveys of adults with spirometry carried out for the same individuals 5-9 years after their baseline examination. We determined the factors associated with a change in the spirometry interpretation from one exam to the next utilizing different criteria commonly used to diagnose COPD. Results The rate of an inconsistent diagnosis of mild COPD was 11.7% using FEV1/FVC <0.70, 5.9% using FEV1/FEV6 repeating the test in patients with borderline results. PMID:25811461

  1. Alternative methods in toxicity testing: the current approach

    OpenAIRE

    Araújo,Gabrielle Luck de; Campos,Maria Augusta Amaral; Valente,Maria Anete Santana; Silva,Sarah Cristina Teixeira; França,Flávia Dayrell; Chaves,Miriam Martins; Tagliati, Carlos Alberto

    2014-01-01

    Alternative methods are being developed to reduce, refine, and replace (3Rs) animals used in experiments, aimed at protecting animal welfare. The present study reports alternative tests which are based on the principles of the 3Rs and the efforts made to validate these tests. In Europe, several methodologies have already been implemented, such as tests of irritability, cell viability, and phototoxicity as well as in vitro mathematical models together with the use of in silico tools. This is a...

  2. Assessment of Jatropha curcas L. biodiesel seed cake toxicity using the zebrafish (Danio rerio) embryo toxicity (ZFET) test.

    Science.gov (United States)

    Hallare, Arnold V; Ruiz, Paulo Lorenzo S; Cariño, J C Earl D

    2014-05-01

    Consequent to the growing demand for alternative sources of energy, the seeds from Jatropha curcas remain to be the favorite for biodiesel production. However, a significant volume of the residual organic mass (seed cake) is produced during the extraction process, which raises concerns on safe waste disposal. In the present study, we assessed the toxicity of J. curcas seed cake using the zebrafish (Danio rerio) embryotoxicity test. Within 1-h post-fertilization (hpf), the fertilized eggs were exposed to five mass concentrations of J. curcas seed cake and were followed through 24, 48, and 72 hpf. Toxicity was evaluated based on lethal endpoints induced on zebrafish embryos namely egg coagulation, non-formation of somites, and non-detachment of tail. The lowest concentration tested, 1 g/L, was not able to elicit toxicity on embryos whereas 100 % mortality (based also on lethal endpoints) was recorded at the highest concentration at 2.15 g/L. The computed LC50 for the J. curcas seed cake was 1.61 g/L. No further increase in mortality was observed in the succeeding time points (48 and 72 hpf) indicating that J. curcas seed cake exerted acute toxicity on zebrafish embryos. Sublethal endpoints (yolk sac and pericardial edema) were noted at 72 hpf in zebrafish embryos exposed to higher concentrations. The observed lethal endpoints induced on zebrafish embryos were discussed in relation to the active principles, notably, phorbol esters that have remained in the seed cake even after extraction.

  3. Field Validation of Toxicity Tests to Evaluate the Potential for Beneficial Use of Produced Water

    Energy Technology Data Exchange (ETDEWEB)

    Joseph Bidwell; Jonathan Fisher; Naomi Cooper

    2008-03-31

    This study investigated potential biological effects of produced water contamination derived from occasional surface overflow and possible subsurface intrusion at an oil production site along the shore of Skiatook Lake, Oklahoma. We monitored basic chemistry and acute toxicity to a suite of standard aquatic test species (fathead minnow-Pimephales promelas, Daphnia pulex, Daphnia magna, and Ceriodaphnia dubia) in produced water and in samples taken from shallow groundwater wells on the site. Toxicity identification evaluations and ion toxicity modeling were used to identify toxic constituents in the samples. Lake sediment at the oil production site and at a reference site were also analyzed for brine intrusion chemically and by testing sediment toxicity using the benthic invertebrates, Chironomus dilutus, and Hyallela azteca. Sediment quality was also assessed with in situ survival and growth studies with H. azteca and the Asian clam, Corbicula fluminea, and by benthic macroinvertebrate community sampling. The produced water was acutely toxic to the aquatic test organisms at concentrations ranging from 1% to 10% of the whole produced water sample. Toxicity identification evaluation and ion toxicity modeling indicated major ion salts and hydrocarbons were the primary mixture toxicants. The standardized test species used in the laboratory bioassays exhibited differences in sensitivity to these two general classes of contaminants, which underscores the importance of using multiple species when evaluating produced water toxicity. Toxicity of groundwater was greater in samples from wells near a produced water injection well and an evaporation pond. Principle component analyses (PCA) of chemical data derived from the groundwater wells indicated dilution by lake water and possible biogeochemical reactions as factors that ameliorated groundwater toxicity. Elevated concentrations of major ions were found in pore water from lake sediments, but toxicity from these ions was

  4. Effect of reference foods in repeated acceptability tests: testing familiar and novel foods using 2 acceptability scales.

    Science.gov (United States)

    El Dine, A Nasser; Olabi, A

    2009-03-01

    Hedonic tests are routinely used to assess the acceptance of food products. However, these single tests may not be the best approach for predicting long-term use. The objectives of this study were, first, to check whether a difference from reference score is more sensitive to changes in hedonic scores, second, to assess whether the labeled affective scale (LAM) is more sensitive to differences than the 9-point scale, and third, to assess the effect of repeated exposure on the hedonic scores of neophilic and neophobic panelists for familiar and novel foods. Two groups of 41 panelists were tested with either the 9-point hedonic scale or LAM scale. Panelists received a food neophobia questionnaire and were subsequently classified to neophobic, neophilic, or neutral. Ten foods, including 5 novel and 5 familiar, were used. In each session, 5 to 6 foods were served twice/week for 4 wk. Serving frequency ranged between 1 and 8 times (1, 2, 4, 6, 8). Data analyses were performed 3 times, using either absolute acceptability scores or relative scores, that is, the difference between absolute scores and scores for either the reference (cracker, RELFAM) or a novel food (pickled-ginger, RELNOV) served in every session. The 3 analyses (absolute, RELFAM, and RELNOV) generated similar results with respect to the number of significant differences between foods. There was no major drift in acceptability scores with sessions. A significant food effect was obtained (P food x neophobia (P foods, pickled ginger, and lychee, whereby neophobic panelists were less accepting of them. Both scales were equally sensitive with some advantages for LAM over the 9-point hedonic scale.

  5. Cross-Sector Review of Drivers and Available 3Rs Approaches for Acute Systemic Toxicity Testing

    Science.gov (United States)

    Seidle, Troy; Robinson, Sally; Holmes, Tom; Creton, Stuart; Prieto, Pilar; Scheel, Julia; Chlebus, Magda

    2010-01-01

    Acute systemic toxicity studies are carried out in many sectors in which synthetic chemicals are manufactured or used and are among the most criticized of all toxicology tests on both scientific and ethical grounds. A review of the drivers for acute toxicity testing within the pharmaceutical industry led to a paradigm shift whereby in vivo acute toxicity data are no longer routinely required in advance of human clinical trials. Based on this experience, the following review was undertaken to identify (1) regulatory and scientific drivers for acute toxicity testing in other industrial sectors, (2) activities aimed at replacing, reducing, or refining the use of animals, and (3) recommendations for future work in this area. PMID:20484382

  6. PAH toxicity at aqueous solubility in the fish embryo test with Danio rerio using passive dosing

    DEFF Research Database (Denmark)

    Fernqvist, Margit; Mayer, Philipp; Smith, Kilian

    2014-01-01

    As part of the risk assessment process within REACh, prior to manufacturing and distribution of chemical substances their (eco)toxicological impacts have to be investigated. The fish embryo toxicity test (FET) with the zebrafish Danio rerio has gained a high significance as an in vitro alternative...... to animal testing in (eco)toxicology. However, for hydrophobic organic chemicals it remains a technical challenge to ensure constant freely dissolved concentration at the maximum exposure level during such biotests. Passive dosing with PDMS silicone was thus applied to control the freely dissolved...... further data to support the close relationship between the chemical activity and the toxicity of hydrophobic organic compounds. Passive dosing from PDMS silicone enabled reliable toxicity testing of (highly) hydrophobic substances at aqueous solubility, providing a practical way to control toxicity...

  7. Ecotoxicity of engineered nanoparticles to aquatic invertebrates: a brief review and recommendations for future toxicity testing

    DEFF Research Database (Denmark)

    Baun, Anders; Hartmann, Nanna Isabella Bloch; Grieger, Khara Deanne

    2008-01-01

    Based on a literature review and an overview of toxic effects of engineered nanoparticles in aquatic invertebrates, this paper proposes a number of recommendations for the developing field of nanoecotoxicology by highlighting the importance of invertebrates as sensitive and relevant test organisms...... Daphnia magna as the test organism. To date, the limited number of studies has indicated acute toxicity in the low mgl(-1) range and higher of engineered nanoparticles to aquatic invertebrates, although some indications of chronic toxicity and behavioral changes have also been described at concentrations...... in the high mu gl(-1) range. Nanoparticles have also been found to act as contaminant carriers of co-existing contaminants and this interaction has altered the toxicity of specific chemicals towards D. magna. We recommend that invertebrate testing is used to advance the level of knowledge in nanoecotoxicology...

  8. 40 CFR 797.1930 - Mysid shrimp acute toxicity test.

    Science.gov (United States)

    2010-07-01

    ... exposure over a specified period of time. (4) “Loading” means the ratio of test organisms biomass (grams... as hydrolysis and oxidation products, give positive or negative interferences which cannot be..., pH, etc.) and a description of any pretreatment. (2) Detailed information about the test...

  9. 40 CFR 797.1300 - Daphnid acute toxicity test.

    Science.gov (United States)

    2010-07-01

    ... ratio of daphnid biomass (grams, wet weight) to the volume (liters) of test solution in a test chamber... oxidation products, give positive or negative interferences which cannot be systematically identified and...., conductivity, hardness, pH, etc.) and a description of any pretreatment. (4) Detailed information about...

  10. 40 CFR 797.1950 - Mysid shrimp chronic toxicity test.

    Science.gov (United States)

    2010-07-01

    ...) “Loading” means the ratio of test organism biomass (gram, wet weight) to the volume (liters) of test... substance, such as hydrolysis and oxidation products, give positive or negative interferences which cannot... characteristics (e.g., salinity, pH, etc.) and a description of any pretreatment. (2) Detailed information...

  11. Toxicity assessing for chlorpyrifos-contaminated soil with three different earthworm test methods

    Institute of Scientific and Technical Information of China (English)

    ZHOU Shi-ping; DUAN Chang-qun; FU Hui; CHEN Yu-hui; WANG Xue-hua; YU Ze-fen

    2007-01-01

    Earthworm toxicity tests are useful tools for terrestrial risk assessment but require a hierarchy of test designs that differ in effect levels (behavior, sublethal, lethal). In this study, the toxicity of chlorpyrifos contaminated soil on earthworms was assessed. In addition to the acute and chronic tests, an avoidance response test was applied. Earthworms were exposed to sublethal and lethal concentration of chlorpyrifos, and evaluated for acute toxicity, growth, fecundity and avoidance response after a certain exposure period. The test methods covered all important ecological relevant endpoints (acute, chronic, behavioral). Concentration of 78.91 mg/kg, chlorpyrifos caused significant toxic effects in all test methods, but at lower test concentrations, only significant chronic toxic effects could be observed. In the present study, chlorpyrifos had adverse effect on growth and fecundity in earthworm exposed to 5 mg/kg chlorpyrifos after eight weeks. The avoidance response test, however, showed significant repellent effects concentration of 40 mg/kg chlorpyrifos. For chlorpyrifos, concentration affecting avoidance response was far greater than growth and fecundity, it seemed likely that earthworms were not able to escape from pesticide-contaminated soil into the clean soil in field and hence were exposed continuously to elevated concentrations of pesticides.

  12. Assigning ethical weights to clinical signs observed during toxicity testing.

    Science.gov (United States)

    Ringblom, Joakim; Törnqvist, Elin; Hansson, Sven Ove; Rudén, Christina; Öberg, Mattias

    2017-01-01

    Reducing the number of laboratory animals used and refining experimental procedures to enhance animal welfare are fundamental questions to be considered in connection with animal experimentation. Here, we explored the use of cardinal ethical weights for clinical signs and symptoms in rodents by conducting trade-off interviews with members of Swedish Animal Ethics Committees in order to derive such weights for nine typical clinical signs of toxicity. The participants interviewed represent researchers, politically nominated political nominees and representatives of animal welfare organizations. We observed no statistically significant differences between these groups with respect to the magnitude of the ethical weights assigned, though the political nominees tended to assign lower weights. Overall, hunched posture was considered the most severe clinical sign and body weight loss the least severe. The ethical weights assigned varied considerably between individuals, from zero to infinite value, indicating discrepancies in prioritization of reduction and refinement. Cardinal ethical weights may be utilized to include both animal welfare refinement and reduction of animal use in designing as well as in retrospective assessment of animal experiments. Such weights may also be used to estimate ethical costs of animal experiments.

  13. Acute toxicity testing with the tropical marine copepod Acartia sinjiensis: optimisation and application.

    Science.gov (United States)

    Gissi, F; Binet, M T; Adams, M S

    2013-11-01

    Globally there is limited toxicity data for tropical marine species, and there has been a call for further research and development in the area of tropical marine ecotoxicology. An increase in developmental pressures in northern tropical Australia is causing a higher demand for toxicity test protocols with ecologically relevant species. Copepods are a diverse group of zooplankton that are major components of marine food webs. The calanoid copepod Acartia sinjiensis is widely distributed across tropical and sub-tropical brackish to marine waters of Australia and was identified in a recent comprehensive review of marine tropical toxicity testing in Australia as a suitable test organism. Through a number of optimisation steps including feeding trials, changes to culture and test conditions; a 48-h acute toxicity test with A. sinjiensis was modified to become a highly reliable and reproducible standard test protocol. Control mobility was improved significantly, and the sensitivity of A. sinjiensis to copper (EC50 of 33µg/L), ammonia (EC50 of 10mg/L) and phenol (EC50 of 13mg/L) fell within the ranges of those reported previously, indicating that the modifications did not alter its sensitivity. In a comprehensive literature search we found that this species was the most sensitive to copper out of a range of marine copepods. The test was also successfully applied in toxicity assessments of four environmental samples: two produced formations waters (PFWs) and two mine tailing liquors (MTLs). The toxicity assessments utilised toxicity data from a suite of marine organisms (bacteria, microalgae, copepods, sea urchins, oysters, prawns, and fish). For the PFWs, which were predominantly contaminated with organic chemicals, A. sinjiensis was the most sensitive species (EC50 value 2-17 times lower than for any other test species). For the predominantly metal-contaminated mine tailing liquors, its sensitivity was similar to that of other test species used. The modified 48-h acute

  14. Establishment of quality assurance procedures for aquatic toxicity testing with the nematode Caenorhabditis elegans

    Energy Technology Data Exchange (ETDEWEB)

    Freeman, M.N.; Marse, T.J.; Williams, P.L. [Univ. of Georgia, Athens, GA (United States). Environmental Health Science Program

    1998-12-31

    In this study initial data were generated to develop laboratory control charts for aquatic toxicity testing using the nematode Caenorhabditis elegans. Tests were performed using two reference toxicants: CdCl{sub 2} and CuCl{sub 2}. All tests were performed for 24 h without a food source and of 48 h with a food source in a commonly used nematode aquatic medium. Each test was replicated 6 times with each replicate having 6 wells per concentration with 10 {+-} 1 worms per well. Probit analysis was used to estimate LC{sub 50} values for each test. The data were used to construct a mean ({bar x}) laboratory control chart for each reference toxicant. The coefficient of variation (CV) for three of the four reference toxicant tests was less than 20%, which demonstrates an excellent degree of reproducibility. These CV values are well within suggested standards for determination of organism sensitivity and overall test system credibility. A standardized procedure for performing 24 h and 48 h aquatic toxicity studies with C. elegans is proposed.

  15. Triage of Women with Low-Grade Cervical Lesions - HPV mRNA Testing versus Repeat Cytology

    Science.gov (United States)

    Sørbye, Sveinung Wergeland; Arbyn, Marc; Fismen, Silje; Gutteberg, Tore Jarl; Mortensen, Elin Synnøve

    2011-01-01

    Background In Norway, women with low-grade squamous intraepithelial lesions (LSIL) are followed up after six months in order to decide whether they should undergo further follow-up or be referred back to the screening interval of three years. A high specificity and positive predictive value (PPV) of the triage test is important to avoid unnecessary diagnostic and therapeutic procedures. Materials and Methods At the University Hospital of North Norway, repeat cytology and the HPV mRNA test PreTect HPV-Proofer, detecting E6/E7 mRNA from HPV types 16, 18, 31, 33 and 45, are used in triage of women with ASC-US and LSIL. In this study, women with LSIL cytology in the period 2005–2008 were included (n = 522). Two triage methods were evaluated in two separate groups: repeat cytology only (n = 225) and HPV mRNA testing in addition to repeat cytology (n = 297). Histologically confirmed cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) was used as the study endpoint. Results Of 522 women with LSIL, 207 had biopsies and 125 of them had CIN2+. The sensitivity and specificity of repeat cytology (ASC-US or worse) were 85.7% (95% confidence interval (CI): 72.1, 92.2) and 54.4 % (95% CI: 46.9, 61.9), respectively. The sensitivity and specificity of the HPV mRNA test were 94.2% (95% CI: 88.7, 99.7) and 86.0% (95% CI: 81.5, 90.5), respectively. The PPV of repeat cytology was 38.4% (95% CI: 29.9, 46.9) compared to 67.0% (95% CI: 57.7, 76.4) of the HPV mRNA test. Conclusion HPV mRNA testing was more sensitive and specific than repeat cytology in triage of women with LSIL cytology. In addition, the HPV mRNA test showed higher PPV. These data indicate that the HPV mRNA test is a better triage test for women with LSIL than repeat cytology. PMID:21918682

  16. Recreating the seawater mixture composition of HOCs in toxicity tests with Artemia franciscana by passive dosing

    Energy Technology Data Exchange (ETDEWEB)

    Rojo-Nieto, E., E-mail: elisa.rojo@uca.es [Andalusian Centre of Marine Science and Technology (CACYTMAR), Department of Environmental Technologies, University of Cadiz, 11510 Puerto Real (Spain); Smith, K.E.C. [Department of Environmental Science, Aarhus University, DK-4000 Roskilde (Denmark); Perales, J.A. [Andalusian Centre of Marine Science and Technology (CACYTMAR), Department of Environmental Technologies, University of Cadiz, 11510 Puerto Real (Spain); Mayer, P. [Department of Environmental Science, Aarhus University, DK-4000 Roskilde (Denmark)

    2012-09-15

    The toxicity testing of hydrophobic organic compounds (HOCs) in aquatic media is generally challenging, and this is even more problematic for mixtures. The hydrophobic properties of these compounds make them difficult to dissolve, and subsequently to maintain constant exposure concentrations. Evaporative and sorptive losses are highly compound-specific, which can alter not only total concentrations, but also the proportions between the compounds in the mixture. Therefore, the general aim of this study was to explore the potential of passive dosing for testing the toxicity of a PAH mixture that recreates the mixture composition found in seawater from a coastal area of Spain, the Bay of Algeciras. First, solvent spiking and passive dosing were compared for their suitability to determine the acute toxicity to Artemia franciscana nauplii of several PAHs at their respective solubility limits. Second, passive dosing was applied to recreate the seawater mixture composition of PAHs measured in a Spanish monitoring program, to test the toxicity of this mixture at different levels. HPLC analysis was used to confirm the reproducibility of the dissolved exposure concentrations for the individual PAHs and mixtures. This study shows that passive dosing has some important benefits in comparison with solvent spiking for testing HOCs in aquatic media. These include maintaining constant exposure concentrations, leading to higher reproducibility and a relative increase in toxicity. Passive dosing is also able to faithfully reproduce real mixtures of HOCs such as PAHs, in toxicity tests, reproducing both the levels and proportions of the different compounds. This provides a useful approach for studying the toxicity of environmental mixtures of HOCs, both with a view to investigating their toxicity but also for determining safety factors before such mixtures result in detrimental effects.

  17. Stability of relative oxygen pulse curve during repeated maximal cardiopulmonary testing in professional soccer players

    Directory of Open Access Journals (Sweden)

    R.R. Perim

    2011-07-01

    Full Text Available During cardiopulmonary exercise testing (CPET, stroke volume can be indirectly assessed by O2 pulse profile. However, for a valid interpretation, the stability of this variable over time should be known. The objective was to analyze the stability of the O2 pulse curve relative to body mass in elite athletes. VO2, heart rate (HR, and relative O2 pulse were compared at every 10% of the running time in two maximal CPETs, from 2005 to 2010, of 49 soccer players. Maximal values of VO2 (63.4 ± 0.9 vs 63.5 ± 0.9 mL O2•kg-1•min-1, HR (190 ± 1 vs188 ± 1 bpm and relative O2 pulse (32.9 ± 0.6 vs 32.6 ± 0.6 mL O2•beat-1•kg-1 were similar for the two CPETs (P > 0.05, while the final treadmill velocity increased from 18.5 ± 0.9 to 18.9 ± 1.0 km/h (P < 0.01. Relative O2 pulse increased linearly and similarly in both evaluations (r² = 0.64 and 0.63 up to 90% of the running time. Between 90 and 100% of the running time, the values were less stable, with up to 50% of the players showing a tendency to a plateau in the relative O2 pulse. In young healthy men in good to excellent aerobic condition, the morphology of the relative O2 pulse curve is consistent up to close to the peak effort for a CPET repeated within a 1-year period. No increase in relative O2pulse at peak effort could represent a physiologic stroke volume limitation in these athletes.

  18. Controlling silver nanoparticle exposure in algal toxicity testing - A matter of timing

    DEFF Research Database (Denmark)

    Sørensen, Sara Nørgaard; Baun, Anders

    2015-01-01

    The aquatic ecotoxicity testing of nanoparticles is complicated by unstable exposure conditions resulting from various transformation processes of nanoparticles in aqueous suspensions. In this study, we investigated the influence of exposure timing on the algal test response to silver nanoparticles......) in a standard algal growth inhibition test (ISO 8692:2004) for 48 h and a short-term (2 h) 14C-assimilation test. For AgNO3, similar responses were obtained in the two tests, whereas freshly prepared suspensions of citrate stabilized AgNPs were less toxic in the 2-h tests compared to the 48-h tests. The 2-h...... and reproducibility increased. Prolonged aging to 48 h increased toxicity in the 2-h tests whereas aging beyond 48 h reduced toxicity. Our results demonstrate that the outcome of algal toxicity testing of AgNPs is highly influenced not only by the test duration, but also by the time passed from the moment Ag...

  19. Alternative approaches for identifying acute systemic toxicity: Moving from research to regulatory testing.

    Science.gov (United States)

    Hamm, Jon; Sullivan, Kristie; Clippinger, Amy J; Strickland, Judy; Bell, Shannon; Bhhatarai, Barun; Blaauboer, Bas; Casey, Warren; Dorman, David; Forsby, Anna; Garcia-Reyero, Natàlia; Gehen, Sean; Graepel, Rabea; Hotchkiss, Jon; Lowit, Anna; Matheson, Joanna; Reaves, Elissa; Scarano, Louis; Sprankle, Catherine; Tunkel, Jay; Wilson, Dan; Xia, Menghang; Zhu, Hao; Allen, David

    2017-06-01

    Acute systemic toxicity testing provides the basis for hazard labeling and risk management of chemicals. A number of international efforts have been directed at identifying non-animal alternatives for in vivo acute systemic toxicity tests. A September 2015 workshop, Alternative Approaches for Identifying Acute Systemic Toxicity: Moving from Research to Regulatory Testing, reviewed the state-of-the-science of non-animal alternatives for this testing and explored ways to facilitate implementation of alternatives. Workshop attendees included representatives from international regulatory agencies, academia, nongovernmental organizations, and industry. Resources identified as necessary for meaningful progress in implementing alternatives included compiling and making available high-quality reference data, training on use and interpretation of in vitro and in silico approaches, and global harmonization of testing requirements. Attendees particularly noted the need to characterize variability in reference data to evaluate new approaches. They also noted the importance of understanding the mechanisms of acute toxicity, which could be facilitated by the development of adverse outcome pathways. Workshop breakout groups explored different approaches to reducing or replacing animal use for acute toxicity testing, with each group crafting a roadmap and strategy to accomplish near-term progress. The workshop steering committee has organized efforts to implement the recommendations of the workshop participants. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Higher Drop in Speed during a Repeated Sprint Test in Soccer Players Reporting Former Hamstring Strain Injury.

    Science.gov (United States)

    Røksund, Ola D; Kristoffersen, Morten; Bogen, Bård E; Wisnes, Alexander; Engeseth, Merete S; Nilsen, Ann-Kristin; Iversen, Vegard V; Mæland, Silje; Gundersen, Hilde

    2017-01-01

    Aim: Hamstring strain injury is common in soccer. The aim of this study was to evaluate the physical capacity of players who have and have not suffered from hamstring strain injury in a sample of semi-professional and professional Norwegian soccer players in order to evaluate characteristics and to identify possible indications of insufficient rehabilitation. Method: Seventy-five semi-professional and professional soccer players (19 ± 3 years) playing at the second and third level in the Norwegian league participated in the study. All players answered a questionnaire, including one question about hamstring strain injury (yes/no) during the previous 2 years. They also performed a 40 m maximal sprint test, a repeated sprint test (8 × 20 m), a countermovement jump, a maximal oxygen consumption (VO2max) test, strength tests and flexibility tests. Independent sample t-tests were used to evaluate differences in the physical capacity of the players who had suffered from hamstring strain injury and those who had not. Mixed between-within subject's analyses of variance was used to compare changes in speed during the repeated sprint test between groups. Results: Players who reported hamstring strain injury during the previous two years (16%) had a significantly higher drop in speed (0.07 vs. 0.02 s, p = 0.007) during the repeated sprint test, compared to players reporting no previous hamstring strain injury. In addition, there was a significant interaction (groups × time) (F = 3.22, p = 0.002), showing that speed in the two groups changed differently during the repeated sprint test. There were no significant differences in relations to age, weight, height, body fat, linear speed, countermovement jump height, leg strength, VO2max, or hamstring flexibility between the groups. Conclusion: Soccer players who reported hamstring strain injury during the previous 2 years showed significant higher drop in speed during the repeated sprint test compared to players with no hamstring

  1. Higher Drop in Speed during a Repeated Sprint Test in Soccer Players Reporting Former Hamstring Strain Injury

    Science.gov (United States)

    Røksund, Ola D.; Kristoffersen, Morten; Bogen, Bård E.; Wisnes, Alexander; Engeseth, Merete S.; Nilsen, Ann-Kristin; Iversen, Vegard V.; Mæland, Silje; Gundersen, Hilde

    2017-01-01

    Aim: Hamstring strain injury is common in soccer. The aim of this study was to evaluate the physical capacity of players who have and have not suffered from hamstring strain injury in a sample of semi-professional and professional Norwegian soccer players in order to evaluate characteristics and to identify possible indications of insufficient rehabilitation. Method: Seventy-five semi-professional and professional soccer players (19 ± 3 years) playing at the second and third level in the Norwegian league participated in the study. All players answered a questionnaire, including one question about hamstring strain injury (yes/no) during the previous 2 years. They also performed a 40 m maximal sprint test, a repeated sprint test (8 × 20 m), a countermovement jump, a maximal oxygen consumption (VO2max) test, strength tests and flexibility tests. Independent sample t-tests were used to evaluate differences in the physical capacity of the players who had suffered from hamstring strain injury and those who had not. Mixed between-within subject's analyses of variance was used to compare changes in speed during the repeated sprint test between groups. Results: Players who reported hamstring strain injury during the previous two years (16%) had a significantly higher drop in speed (0.07 vs. 0.02 s, p = 0.007) during the repeated sprint test, compared to players reporting no previous hamstring strain injury. In addition, there was a significant interaction (groups × time) (F = 3.22, p = 0.002), showing that speed in the two groups changed differently during the repeated sprint test. There were no significant differences in relations to age, weight, height, body fat, linear speed, countermovement jump height, leg strength, VO2max, or hamstring flexibility between the groups. Conclusion: Soccer players who reported hamstring strain injury during the previous 2 years showed significant higher drop in speed during the repeated sprint test compared to players with no hamstring

  2. Improving the reliability of aquatic toxicity testing of hydrophobic chemicals via equilibrium passive dosing - A multiple trophic level case study on bromochlorophene.

    Science.gov (United States)

    Stibany, Felix; Ewald, Franziska; Miller, Ina; Hollert, Henner; Schäffer, Andreas

    2017-01-28

    The main objective of the present study was to improve the reliability and practicability of aquatic toxicity testing of hydrophobic chemicals based upon the model substance bromochlorophene (BCP). Therefore, we adapted a passive dosing format to test the toxicity of BCP at different concentrations and in multiple test systems with aquatic organisms of various trophic levels. At the same time, the method allowed for the accurate determination of exposure concentrations (i.e., in the presence of exposed organisms; Ctest) and freely dissolved concentrations (i.e., without organisms present; Cfree) of BCP in all tested media. We report on the joint adaptation of three ecotoxicity tests - algal growth inhibition, Daphnia magna immobilization, and fish-embryo toxicity - to a silicone O-ring based equilibrium passive dosing format. Effect concentrations derived by passive dosing methods were compared with corresponding effect concentrations derived by standard co-solvent setups. The passive dosing format led to EC50-values in the lower μgL(-1) range for algae, daphnids, and fish embryos, whereas increased effect concentrations were measured in the co-solvent setups for algae and daphnids. This effect once more shows that passive dosing might offer advantages over standard methods like co-solvent setups when it comes to a reliable risk assessment of hydrophobic substances. The presented passive dosing setup offers a facilitated, practical, and repeatable way to test hydrophobic chemicals on their toxicity to aquatic organisms, and is an ideal basis for the detailed investigation of this important group of chemicals.

  3. Toxics testing performance evaluation for GB and GD

    Energy Technology Data Exchange (ETDEWEB)

    O`Neill, H.J.; Schneider, J.F.; Brubaker, K.L.; Kimmell, T.A.; Anderson, A.W.

    1997-10-01

    Residues resulting from demilitarization, treatment, cleanup, and testing of military chemical agents at Dugway Proving Ground (DPG), Utah, are currently listed as hazardous wastes by the State of Utah Department of Environmental Quality. The US Army Test and Evaluation Command believes that certain categories of waste generated at DPG are not hazardous. To demonstrate this, analytical methods capable of quantitatively measuring the concentrations of chemical agents, including GB and GD, in the different waste media must be available. Argonne National Laboratory has developed methods to analyze metal substrate, spent hypochlorite decontamination fluid, and soil matrices for GB and GD. These methods involve the use of sorbent cartridge preconcentration and thermal desorption combined with gas chromatography using flame photometric detection to achieve the desired sensitivity and specificity. This report describes the methods and presents results for these three common waste matrices. The test results indicate that these methods can be used to quantitatively determine concentrations of GB and GD in the low parts-per-billion range in all sample media tested.

  4. 40 CFR 797.1330 - Daphnid chronic toxicity test.

    Science.gov (United States)

    2010-07-01

    ... daphnids except for minor activity of the appendages. (7) Loading means the ratio of daphnid biomass (grams... acceptable if likely degradation products of the test substance, such as hydrolysis and oxidation products..., pH), and a description of any pretreatment. (4) Detailed information about the daphnids used...

  5. A Correction for the Epsilon Approximate Test in Repeated Measures Designs with Two or More Independent Groups.

    Science.gov (United States)

    Lecoutre, Bruno

    1991-01-01

    The routine epsilon approximate test in repeated measures designs when the condition of circularity is unfulfilled uses an erroneous formula in the case of two or more groups. Because this may lead to underestimation of the deviation from circularity when the subject number is small, a correction is proposed. (Author/SLD)

  6. NMSBA: Aken Technologies Final Report: Toxicity Testing of Liquidoff

    Energy Technology Data Exchange (ETDEWEB)

    Ruffing, Anne [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Jensen, Travis [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Strickland, Lucas [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2015-02-01

    To determine the effect of Liquidoff on bacteria, three bacterial strains were tested: Escherichia coli DH5α, Synechococcus sp. PCC 7002, and Synechococcus elongatus PCC 7942. E. coli DH5α is a Gram-negative, aerobic bacterium that is often found in normal gut flora and is commonly used the laboratory due to its fast growth rate. Synechococcus sp. PCC 7002 and S. elongatus PCC 7942 are Gram-negative, aquatic, autophototrophic cyanobacteria. Synechococcus sp. PCC 7002 is a marine cyanobacterium isolated from ‘fish pens’ on Magueyes Island, Puerto Rico in 1962, while S. elongatus PCC 7942 is a freshwater cyanobacterium. It should be noted that no Gram-positive bacterium was tested in this study.

  7. NMSBA: Aken Technologies. Final Report: Toxicity Testing of Liquidoff

    Energy Technology Data Exchange (ETDEWEB)

    Ruffing, Anne [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Jensen, Travis J. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Strickland, Lucas Marshall [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Rader, Nadeya C. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Carson, Bryan [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2015-01-01

    To determine the effect of Liquidoff on bacteria, three bacterial strains were tested: Escherichia coli DH5α, Synechococcus sp. PCC 7002, and Synechococcus elongatus PCC 7942. E. coli DH5α is a Gramnegative, aerobic bacterium that is often found in normal gut flora and is commonly used the laboratory due to its fast growth rate. Synechococcus sp. PCC 7002 and S. elongatus PCC 7942 are Gram-negative, aquatic, autophototrophic cyanobacteria. Synechococcus sp. PCC 7002 is a marine cyanobacterium isolated from ‘fish pens’ on Magueyes Island, Puerto Rico in 1962, while S. elongatus PCC 7942 is a freshwater cyanobacterium. It should be noted that no Gram-positive bacterium was tested in this study.

  8. Anaerobic degradation and toxicity of commercial cationic surfactants in anaerobic screening tests.

    Science.gov (United States)

    García, M T; Campos, E; Sánchez-Leal, J; Ribosa, I

    2000-09-01

    Anaerobic biodegradability and toxicity on anaerobic bacteria of di(hydrogenated tallow) dimethyl ammonium chloride (DHTDMAC) and two esterquats have been investigated. A batch test system containing municipal digester solids as a source of anaerobic bacteria, based on the method proposed by the ECETOC, has been applied. To evaluate the potential toxicity of such surfactants on anaerobic sludge, a co-substrate, an easily biodegradable compound in anaerobic conditions, has been added to the samples to test and the effects on biogas production have been determined. For the esterquats studied high biodegradation levels were obtained and no toxic effects on anaerobic bacteria were observed even at the highest concentrations tested, 100 and 200 mg C/l, respectively. On the contrary, DHTDMAC was not degradated at the same test conditions. However, no inhibitory effects on the biogas production were detected for this surfactant at concentrations <100 mg C/l.

  9. The Use of Physarum for Testing of Toxicity/Mutagenicity

    Science.gov (United States)

    1984-04-19

    Salmonella-mammalian microsome mutagenicity test. Mutat, Res. 31, 347-364. Anderson, R. 1977. A plasmodial colour mutation in the myxomycete Physarum... myxomycete Physarum polycephalum. Genet. Res., Camb. 29, 21-34. Arescaldino, I. 1968. Determination de l’age optimum d’aptitude a la sporula- tion chez... Myxomycetes ) au cours de la sporulation. Comptes Rendus, Ser. D., 273, 398-401. Back, K. C., and A. A. Thomas. 1964. A study of the mechanism of

  10. Dispersed oil toxicity tests with biological species indigenous to the Gulf of Mexico. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Fucik, K.W.; Carr, K.A.; Balcom, B.J.

    1994-08-01

    Static and flowthrough aquatic acute toxicity testing protocols were utilized on eggs and larvae of seven commercially important invertebrates and fishes from the Gulf of Mexico. Test organisms were exposed to Central and Western Gulf oils, dispersed oil, and Corexit 9527. Species included brown shrimp (Penaeus aztecus), white shrimp (Penaeus setiferus), blue crab (Callinectes sapidus), eastern oyster (Crassostrea virginica), red drum (Sciaenops ocellatus), inland silverside (Menidia berylina), and spot (Leiosomus xanthurus). Atlantic menhaden (Brevoortia tyrannus) was also tested because gulf menhaden were not available. Mysids (Mysidopsis bahia) were evaluated as part of a chronic toxicity assessment.

  11. Prediction of the carcinogenic potential of human pharmaceuticals using repeated dose toxicity data and their pharmacological properties

    Directory of Open Access Journals (Sweden)

    Jan Willem Van Der Laan

    2016-10-01

    Full Text Available In an exercise designed to reduce animal use, we analysed the results of rat sub-chronic toxicity studies from 289 pharmaceutical compounds with the aim to predict the tumour outcome of carcinogenicity studies in this species. The results were obtained from the assessment reports available at the Medicines Evaluation Board of the Netherlands for 289 pharmaceutical compounds that had been shown to be non-genotoxic. One hundred and forty-three of the 239 compounds not inducing putative preneoplastic lesions in the sub-chronic study did not induce tumours in the carcinogenicity study (True Negatives - TN, whereas 96 compounds were categorised as False Negatives (FN, because tumours were observed in the carcinogenicity study. For the remaining 50 compounds, 31 showed preneoplastic lesions in the subchronic study and tumours in the carcinogenicity study (True positives - TP, and 19 only showed preneoplastic lesions in subchronic studies but no tumours in the carcinogenicity study (False positives - FP. In addition, we then re-assessed the prediction of the tumour outcome by integrating the pharmacological properties of these compounds. These pharmacological properties were evaluated with respect to the presence or absence of a direct or indirect proliferative action. We found support for the absence of cellular proliferation for 204 compounds (TN. For 67 compounds the presence of cellular hyperplasia as evidence for proliferative action could be found (TP. Therefore, this approach resulted in an ability to predict non-carcinogens at a success rate of 92 % and the ability to detect carcinogens at 98 %. The combined evaluation of pharmacological and histopathological endpoints eventually led to only 18 unknown outcomes (17 categorised as FN. 1 as FP, thereby enhancing both the negative and positive predictivity of an evaluation based upon histopathological evaluation only. The data show the added value of a consideration of the pharmacological

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

    OpenAIRE

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

    2014-01-01

    Since March 2013, animal use for cosmetics testing for the European market has been banned. This requires a renewed view on risk assessment in this field. However, in other fields as well, traditional animal experimentation does not always satisfy requirements in safety testing, as the need for human-relevant information is ever increasing. A general strategy for animal-free test approaches was outlined by the US National Research Council`s vision document for Toxicity Testing in the 21st Cen...

  13. Acute aquatic toxicity of heavy fuel oils. Summary of relevant test data

    Energy Technology Data Exchange (ETDEWEB)

    Comber, M.I.H.; Den Haan, K.; Djemel, N.; Eadsforth, C.V.; King, D.; Parkerton, T.; Paumen, M.L.; Dmytrasz, B.

    2011-12-15

    This report describes the experimental procedures and results obtained in acute ecotoxicity tests on several heavy fuel oil (HFO) samples. Water accommodated fractions (WAFs) of these samples were tested for toxicity to the rainbow trout (Oncorhynchus mykiss), the crustacean zooplankter (Daphnia magna) and green algae (Selenastrum capricornutum). These results assist in determining the environmental hazard from heavy fuel oil.

  14. Acute and chronic aquatic toxicity of aromatic extracts. Summary of relevant test data

    Energy Technology Data Exchange (ETDEWEB)

    Comber, M.I.H.; Den Haan, K.; Djemel, N.; Eadsforth, C.V.; King, D.; Parkerton, T.; Leon Paumen, M.; Dmytrasz, B.; Del Castillo, F.

    2013-09-15

    This report describes the experimental procedures and the results obtained in acute and chronic ecotoxicity tests on several aromatic extracts samples. The samples were tested for toxicity to the rainbow trout (Oncorhynchus mykiss), the crustacean zooplankter, Daphnia magna and the algae, Selenastrum capricornutum using water accommodated fractions. These results assist in determining the environmental hazard posed by aromatic extracts.

  15. Evaluation of an alternative in vitro test battery for detecting reproductive toxicants in a grouping context

    NARCIS (Netherlands)

    Kroese, E. Dinant; Bosgra, Sieto; Buist, Harrie E.; Lewin, Geertje; van der Linden, Sander C.; Man, Hai-yen; Piersma, Aldert H.; Rorije, Emiel; Schulpen, Sjors H. W.; Schwarz, Michael; Uibel, Frederik; van Vugt-Lussenburg, Barbara M. A.; Wolterbeek, Andre P. M.; van der Burg, Bart

    2015-01-01

    Previously we showed a battery consisting of CALUX transcriptional activation assays, the ReProGlo assay, and the embryonic stem cell test, and zebrafish embryotoxicity assay as 'apical' tests to correctly predict developmental toxicity for 11 out of 12 compounds, and to explain the one false negati

  16. Acute marine sediment toxicity: a potential new test with the amphipod Gammarus locusta.

    Science.gov (United States)

    Costa, F O; Correia, A D; Costa, M H

    1998-01-01

    Although amphipod toxicity tests have been successfully used in the United States to assess coastal sediment toxicity, few tests have been developed with European species. The authors have been working with the amphipod Gammarus locusta, a widely spread species along European coastal areas that is particularly abundant in the Portuguese Sado estuary. This amphipod fulfills the most important requirements of a test species. It can be easily reproduced in laboratory and it is tolerant to a broad range of sediment types. A series of tests demonstrated its sensitivity to copper and gamma-hexachlorocyclohexane (lindane) in the sediment (LC50 = 6.8 mg Cu/dry kg, 0.9% total volatile solids; LC50 = 60.5 micrograms HCH/dry kg, 2% total volatile solids) and to some heavily contaminated field sediments. After assessment of the species sensitivity to several noncontaminant variables, an experimental protocol was designed to conduct acute sediment toxicity tests that are briefly described. Proposed is a 10-day static toxicity test at 15 degrees C and 33-34/1000 salinity, with laboratory-produced juveniles and mortality as the endpoint. General assay performance is identical to the American Society for Testing and Materials (ASTM) standard for sediment toxicity tests with marine and estuarine amphipods. The results previously obtained revealed a strong potential for this amphipod to be used in toxicological testing. Considering the wide geographic distribution of this species and its amenability for culturing, it may be an alternative or complementary test for ecotoxicological studies in other European coastal systems where the existing tests cannot be applied or do not offer a definitive solution.

  17. Toxicity Testing of Pristine and Aged Silver Nanoparticles in Real Wastewaters Using Bioluminescent Pseudomonas putida

    Directory of Open Access Journals (Sweden)

    Florian Mallevre

    2016-03-01

    Full Text Available Impact of aging on nanoparticle toxicity in real matrices is scarcely investigated due to a lack of suitable methodologies. Herein, the toxicity of pristine and aged silver nanoparticles (Ag NPs to a bioluminescent Pseudomonas putida bioreporter was measured in spiked crude and final wastewater samples (CWs and FWs, respectively collected from four wastewater treatment plants (WWTPs. Results showed lower toxicity of pristine Ag NPs in CWs than in FWs. The effect of the matrix on the eventual Ag NP toxicity was related to multiple physico-chemical parameters (biological oxygen demand (BOD, chemical oxygen demand (COD, total suspended solids (TSS pH, ammonia, sulfide and chloride based on a multivariate analysis. However, no collection site effect was concluded. Aged Ag NPs (up to eight weeks were found less toxic than pristine Ag NPs in CWs; evident increased aggregation and decreased dissolution were associated with aging. However, Ag NPs exhibited consistent toxicity in FWs despite aging; comparable results were obtained in artificial wastewater (AW simulating effluent. The study demonstrates the potency of performing nanoparticle acute toxicity testing in real and complex matrices such as wastewaters using relevant bacterial bioreporters.

  18. Implementation of population screening for colorectal cancer by repeated Fecal Immunochemical Test (FIT: third round

    Directory of Open Access Journals (Sweden)

    Stegeman Inge

    2012-06-01

    Full Text Available Abstract Background Colorectal cancer (CRC is the most common cancer in Europe with a mortality rate of almost 50%. The prognosis of patients is largely determined by the clinical and pathological stage at the time of diagnosis. Population screening has been shown to reduce CRC-related mortality rate. Most screening programs worldwide rely on fecal immunochemical testing (FIT. The effectiveness of a FIT screening program is not only influenced by initial participation rate, but also by program adherence during consecutive screening rounds. We aim to evaluate the participation rate in and yield of a third CRC screening round using FIT. Methods and design Four years after the first screening round and two years after the second round, a total number of approximately 11,000 average risk individuals (50 to 75 years of age will be invited to participate in a third round of FIT-based CRC screening. We will select individuals in the same target area as in the previous screening rounds, using the electronic database of the regional municipal administration registrations. We will invite all FIT-negatives and all non-participants in previous screening rounds, as well as eligible first time invitees who have moved into the area or have become 50 years of age. FITs will be analyzed in the special technique laboratory of the Academic Medical Center of the University of Amsterdam. All FIT-positives will be invited for a consultation at the outpatient clinic. In the absence of contra-indications, a colonoscopy will follow at the Academic Medical Center or at the Flevohospital. The primary outcome measures are the participation rate, defined as the proportion of invitees that return a FIT in this third round of FIT-screening, and the diagnostic yield of the program. Implications This study will provide precise data on the participation in later FIT screening rounds. This enables to estimate the effectiveness of CRC screening programs that rely on repeated

  19. Boar spermatozoa successfully predict mitochondrial modes of toxicity: implications for drug toxicity testing and the 3R principles.

    Science.gov (United States)

    Vicente-Carrillo, A; Edebert, I; Garside, H; Cotgreave, I; Rigler, R; Loitto, V; Magnusson, K E; Rodríguez-Martínez, H

    2015-04-01

    Replacement of animal testing by in vitro methods (3-R principles) requires validation of suitable cell models, preferably obtained non-invasively, defying traditional use of explants. Ejaculated spermatozoa are highly dependent on mitochondrial production and consumption of ATP for their metabolism, including motility display, thus becoming a suitable model for capturing multiple modes of action of drugs and other chemicals acting via mitochondrial disturbance. In this study, a hypothesis was tested that the boar spermatozoon is a suitable cell type for toxicity assessment, providing a protocol for 3R-replacement of animals for research and drug-testing. Boar sperm kinetics was challenged with a wide variety of known frank mito-toxic chemicals with previously shown mitochondrial effects, using a semi-automated motility analyser allied with real-time fluorescent probing of mitochondrial potential (MitoTracker & JC-1). Output of this sperm assay (obtained after 30 min) was compared to cell viability (ATP-content, data obtained after 24-48 h) of a hepatome-cell line (HepG2). Results of compound effects significantly correlated (Psperm variables and for most variables in (HepG2). Dose-dependent decreases of relative ATP content in HepG2 cells correlated to sperm speed (r=0.559) and proportions of motile (r=0.55) or progressively motile (r=0.53) spermatozoa. The significance of the study relies on the objectivity of computerized testing of sperm motility inhibition which is comparable albeit of faster output than somatic cell culture models. Sperm suspensions, easily and painlessly obtained from breeding boars, are confirmed as suitable biosensors for preclinical toxicology screening and ranking of lead compounds in the drug development processes.

  20. Embryonic stem cells: An alternative approach to developmental toxicity testing

    Directory of Open Access Journals (Sweden)

    S Tandon

    2012-01-01

    Full Text Available Stem cells in the body have a unique ability to renew themselves and give rise to more specialized cell types having functional commitments. Under specified growth conditions, these cell types remain unspecialized but can be triggered to become specific cell type of the body such as heart, nerve, or skin cells. This ability of embryonic stem cells for directed differentiation makes it a prominent candidate as a screening tool in revealing safer and better drugs. In addition, genetic variations and birth defects caused by mutations and teratogens affecting early human development could also be studied on this basis. Moreover, replacement of animal testing is needed because it involves ethical, legal, and cost issues. Thus, there is a strong requirement for validated and reliable, if achievable, human stem cell-based developmental assays for pharmacological and toxicological screening.

  1. Embryonic stem cells: An alternative approach to developmental toxicity testing.

    Science.gov (United States)

    Tandon, S; Jyoti, S

    2012-04-01

    Stem cells in the body have a unique ability to renew themselves and give rise to more specialized cell types having functional commitments. Under specified growth conditions, these cell types remain unspecialized but can be triggered to become specific cell type of the body such as heart, nerve, or skin cells. This ability of embryonic stem cells for directed differentiation makes it a prominent candidate as a screening tool in revealing safer and better drugs. In addition, genetic variations and birth defects caused by mutations and teratogens affecting early human development could also be studied on this basis. Moreover, replacement of animal testing is needed because it involves ethical, legal, and cost issues. Thus, there is a strong requirement for validated and reliable, if achievable, human stem cell-based developmental assays for pharmacological and toxicological screening.

  2. Visual attention to repeated print advertising : A test of scanpath theory

    NARCIS (Netherlands)

    Pieters, R; Rosbergen, E; Wedel, M

    1999-01-01

    The authors examine consumers' visual attention during repeated exposures to print advertisements using eye-tracking methodology. The authors propose a statistical model comprising submodels for two key measures of visual attention to elements of the advertisement: attention duration and inter- and

  3. Cross-trimester repeated measures testing for Down's syndrome screening: an assessment.

    LENUS (Irish Health Repository)

    Wright, D

    2010-07-01

    To provide estimates and confidence intervals for the performance (detection and false-positive rates) of screening for Down\\'s syndrome using repeated measures of biochemical markers from first and second trimester maternal serum samples taken from the same woman.

  4. Damage evolution in GLARE fibre-metal laminate under repeated low-velocity impact tests

    NARCIS (Netherlands)

    Morinière, F.D.; Alderliesten, R.C.; Tooski, M.Y.; Benedictus, R.

    2012-01-01

    An experimental study was performed on the repeated low-velocity impact behaviour of GLARE. Damage evolution in the material constituents was characterised with successive number of impacts. Records were correlated with visual inspection, ultrasound C-scan and chemical etching. The stiffness of the

  5. The flight test of Pi-SAR(L) for the repeat-pass interferometric SAR

    Science.gov (United States)

    Nohmi, Hitoshi; Shimada, Masanobu; Miyawaki, Masanori

    2006-09-01

    This paper describes the experiment of the repeat pass interferometric SAR using Pi-SAR(L). The air-borne repeat-pass interferometric SAR is expected as an effective method to detect landslide or predict a volcano eruption. To obtain a high-quality interferometric image, it is necessary to make two flights on the same flight pass. In addition, since the antenna of the Pi-SAR(L) is secured to the aircraft, it is necessary to fly at the same drift angle to keep the observation direction same. We built a flight control system using an auto pilot which has been installed in the airplane. This navigation system measures position and altitude precisely with using a differential GPS, and the PC Navigator outputs a difference from the desired course to the auto pilot. Since the air density is thinner and the speed is higher than the landing situation, the gain of the control system is required to be adjusted during the repeat pass flight. The observation direction could be controlled to some extent by adjusting a drift angle with using a flight speed control. The repeat-pass flight was conducted in Japan for three days in late November. The flight was stable and the deviation was within a few meters for both horizontal and vertical direction even in the gusty condition. The SAR data were processed in time domain based on range Doppler algorism to make the complete motion compensation. Thus, the interferometric image processed after precise phase compensation is shown.

  6. Inhalation method for delivery of nanoparticles to the Drosophila respiratory system for toxicity testing

    Energy Technology Data Exchange (ETDEWEB)

    Posgai, Ryan; Ahamed, Maqusood [Department of Biology, University of Dayton, Dayton, OH, 45469-2320 (United States); Hussain, Saber M. [Applied Biotechnology Branch, Human Effectiveness Directorate Air Force Research Laboratory/RHBP, Wright-Patterson Air Force Base, OH, 45433 (United States); Rowe, John J. [Department of Biology, University of Dayton, Dayton, OH, 45469-2320 (United States); Nielsen, Mark G., E-mail: Mark.Nielsen@notes.udayton.edu [Department of Biology, University of Dayton, Dayton, OH, 45469-2320 (United States)

    2009-12-20

    The growth of the nanotechnology industry and subsequent proliferation of nanoparticle types present the need to rapidly assess nanoparticle toxicity. We present a novel, simple and cost-effective nebulizer-based method to deliver nanoparticles to the Drosophila melanogaster respiratory system, for the purpose of toxicity testing. FluoSpheres (registered) , silver, and CdSe/ZnS nanoparticles of different sizes were effectively aerosolized, showing the system is capable of functioning with a wide range of nanoparticle types and sizes. Red fluorescent CdSe/ZnS nanoparticles were successfully delivered to the fly respiratory system, as visualized by fluorescent microscopy. Silver coated and uncoated nanoparticles were delivered in a toxicity test, and induced Hsp70 expression in flies, confirming the utility of this model in toxicity testing. This is the first method developed capable of such delivery, provides the advantage of the Drosophila health model, and can serve as a link between tissue culture and more expensive mammalian models in a tiered toxicity testing strategy.

  7. Critical evaluation of current developmental toxicity testing strategies: a case of babies and their bathwater.

    Science.gov (United States)

    Carney, Edward W; Ellis, Amy L; Tyl, Rochelle W; Foster, Paul M D; Scialli, Anthony R; Thompson, Kary; Kim, James

    2011-10-01

    This review is the second in a series of four papers emanating from a workshop entitled "Developmental Toxicology-New Directions," which was sponsored by the ILSI Health and Environmental Sciences Institute's (HESI) Developmental and Reproductive Toxicology Technical Committee. The present review analyzes the strengths and weaknesses of current developmental safety testing approaches in an effort to identify those strengths that should be retained in the future versus the weaknesses that should be eliminated. Workshop participants considered the following to be key strengths of current testing approaches: the integrated biology of pregnant animal models including pharmacokinetic and pharmacodynamic processes, the ability to detect low incidence malformations as well as maternally mediated toxicity, and the long history of use coupled with extensive historical data. A number of weaknesses were related to the resource-intensive nature of developmental toxicity testing (e.g., large number of animals, high costs, low throughput, the inability to keep pace with the demand for more toxicity data). Other weaknesses included the use of very high dose levels that often far exceed human exposure levels, the confounding influence of maternal toxicity, sparse understanding of basic developmental mechanisms and genetics of standard animal models relative to mouse or lower organisms, difficulties interpreting low incidence findings, and issues surrounding the interpretation of minor skeletal variations. An appreciation of these strengths and weaknesses is critical for the design of new approaches to developmental toxicity testing in the 21st century. © 2011 Wiley Periodicals, Inc.

  8. A limitation of the Microtox{reg_sign} test for toxicity measurements of nonionic surfactants

    Energy Technology Data Exchange (ETDEWEB)

    Sherrard, K.B.; Marriott, P.J.; McCormick, M.J. [Royal Melbourne Inst. of Tech. (Australia). Dept. of Applied Chemistry; Millington, K. [CSIRO, Belmont (Australia). Div. of Wool Technology

    1996-07-01

    Qualitative and quantitative analysis of the components of wastewaters is a necessary step towards determining the nature of aqueous effluents. However, toxicity levels of the effluents and receiving waters should also be determined to obtain a more comprehensive understanding of the effects the discharges may have on aquatic environments. The Microtox{reg_sign} test was successfully used to measure EC50 values of nonionic polyethoxylate surfactants. However, toxicity measurements of real samples that contain surfactants above a particular concentration, termed the critical toxicity concentration (CTC) are not valid. These samples require dilution before the test is performed, and because the relationship between toxicity and concentration is not linear above the CTC, the EC50 cannot be extrapolated back to give the toxicity of the original concentrated sample and a true estimation of toxicity is therefore not possible. This phenomenon may be related to the minimum surface tension requirement of the bacteria or other physical properties of the surfactant such as the tendency to assemble at interfaces and surfaces and the tendency to form micelles.

  9. Quick, portable toxicity testing of marine or terrigenous fluids, sediments, or chemicals with bioluminescent organism

    Energy Technology Data Exchange (ETDEWEB)

    Sabate, R.W.; Stiffey, A.V.; Dewailly, E.L. [Lumitox Gulf L.C., New Orleans, LA (United States)

    1995-12-31

    A hand-held, battery-operated instrument, which measures bioluminescence inhibition of the microscopic marine dinoflagellate Pyrocystis lunula, is capable of field-testing substances for toxicity. The organism is sensitive to ppb of strong toxicants. It tolerates some solvents in concentrations necessary for testing lipophylic samples. A test consumes only micrograms of sample. This method requires no adjustments for salinity, pH, color, or turbidity. It has been used successfully to test oil-well drilling fluids, brines produced with oil, waters and sediments from streams and lakes and petroleum-plant effluents containing contaminants such as benzene. The test is non-specific; however, if the substance is known, the end-point effects a direct measurement of its concentration. One-hour toxicity screening tests in the field produce results comparable to the standard four-hour laboratory test. Keeping the sample in the dark during incubation and testing, together with shortness of the overall procedure, eliminates anomalies from light-sensitive substances. Day-to-day variation, as well as among test replicates, is less than 10%. This quick method yields results comparable with a quick test that uses Photobacterium phosphoria, and with 96-hour tests that use Mysidopsis bahia, Artemia salina, Gonyaulax polyedra, Pimephales promelas, Ceriodaphnia dubia, and Cyprinodon variegatus.

  10. Marine microalgae toxicity test for linear alkylbenzene sulfonate (LAS) and alkylphenol ethoxylate (APEO).

    Science.gov (United States)

    Moreno-Garrido, I; Hampel, M; Lubián, L M; Blasco, J

    2001-10-01

    Different microalgal species have been used in growth-inhibition tests to determine the toxic concentrations of anionic and non-ionic surfactants to phytoplankton. The species used were selected from different taxonomic groups, all of considerable ecological relevance to marine environments. The toxicity of the C13 LAS homologue to the microalgal species selected was usually one order of magnitude greater than that of the C11 homologue. The toxicity of a commercial LAS mixture to different microalgal species was also checked. For this material and C. gracilis, cellular counting by means of a Neubauer chamber and by use of a flow cytometer were compared; differences between the two methods were insignificant. The toxicity of decaethoxylated nonylphenol non-ionic surfactant to C. gracilis was also checked; the EC50 value for this compound was 1.0 mg L(-1).

  11. User’s Guide for T.E.S.T. (version 4.2) (Toxicity Estimation Software Tool) A Program to Estimate Toxicity from Molecular Structure

    Science.gov (United States)

    The user's guide describes the methods used by TEST to predict toxicity and physical properties (including the new mode of action based method used to predict acute aquatic toxicity). It describes all of the experimental data sets included in the tool. It gives the prediction res...

  12. Handbook of acute toxicity of chemicals to fish and aquatic invertebrates : summaries of toxicity tests conducted at Columbia National Fisheries Research Laboratory, 1965-78

    Science.gov (United States)

    Johnson, W. Waynon; Finley, Mack T.

    1980-01-01

    Acute toxicity is a major subject of research at Columbia National Fisheries Research Laboratory for evaluating the impact of toxic chemicals on fishery resources. The Laboratory has played a leading role in developing research technology for toxicity testing and data interpretation. In 1965-78, more than 400 chemicals were tested against a variety of invertebrates and fish species representative of both cold- and warm-water climates.The use of acute toxicity tests for assessing the potential hazard of chemical contaminants to aquatic organisms is well documented (Boyd 1957; Henderson et al. 1960; Sanders and Cope 1966; Macek and McAllister 1970). Static acute toxicity tests provide rapid and (within limits) reproducible concentration-response curves for estimating toxic effects of chemicals on aquatic organisms. These tests provide a database for determining relative toxicity of a large number of chemicals to a variety of species and for estimating acute effects of chemical spills on natural aquatic systems; they also assist in determining priority and design of additional toxicity studies.Acute toxicity tests usually provide estimates of the exposure concentration causing 50% mortality (LC50) to test organisms during a specified period of time. For certain invertebrates, the effective concentration is based on immobilization, or some other identifiable endpoint, rather than on lethality. The application of the LC50 has gained acceptance among toxicologists and is generally the most highly rated test for assessing potential adverse effects of chemical contaminants to aquatic life (Brungs and Mount 1978; American Institute for Biological Sciences 1978a).The literature contains numerous papers dealing with the acute toxicity of chemicals to freshwater organisms. However, there is a tremendous need for a concise compendium of toxicity data covering a large variety of chemicals and test species. This Handbook is a compilation of a large volume of acute toxicity data

  13. 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.

  14. Differential toxicity of Disperse Red 1 and Disperse Red 13 in the Ames test, HepG2 cytotoxicity assay, and Daphnia acute toxicity test.

    Science.gov (United States)

    Ferraz, E R A; Umbuzeiro, G A; de-Almeida, G; Caloto-Oliveira, A; Chequer, F M D; Zanoni, M V B; Dorta, D J; Oliveira, D P

    2011-10-01

    Azo dyes are of environmental concern due to their degradation products, widespread use, and low-removal rate during conventional treatment. Their toxic properties are related to the nature and position of the substituents with respect to the aromatic rings and amino nitrogen atom. The dyes Disperse Red 1 and Disperse Red 13 were tested for Salmonella mutagenicity, cell viability by annexin V, and propidium iodide in HepG2 and by aquatic toxicity assays using daphnids. Both dyes tested positive in the Salmonella assay, and the suggestion was made that these compounds induce mainly frame-shift mutations and that the enzymes nitroreductase and O-acetyltransferase play an important role in the observed effect. In addition, it was shown that the presence of the chlorine substituent in Disperse Red 13 decreased the mutagenicity about 14 times when compared with Disperse Red 1, which shows the same structure as Disperse Red 13, but without the chlorine substituent. The presence of this substituent did not cause cytotoxicity in HepG2 cells, but toxicity to the water flea Daphnia similis increased in the presence of the chlorine substituent. These data suggest that the insertion of a chlorine substituent could be an alternative in the design of dyes with low-mutagenic potency, although the ecotoxicity should be carefully evaluated.

  15. Reduction and technical simplification of testing protocol for walking based on repeatability analyses: An Interreg IVa pilot study

    Directory of Open Access Journals (Sweden)

    Nejc Sarabon

    2010-12-01

    Full Text Available The aim of this study was to define the most appropriate gait measurement protocols to be used in our future studies in the Mobility in Ageing project. A group of young healthy volunteers took part in the study. Each subject carried out a 10-metre walking test at five different speeds (preferred, very slow, very fast, slow, and fast. Each walking speed was repeated three times, making a total of 15 trials which were carried out in a random order. Each trial was simultaneously analysed by three observers using three different technical approaches: a stop watch, photo cells and electronic kinematic dress. In analysing the repeatability of the trials, the results showed that of the five self-selected walking speeds, three of them (preferred, very fast, and very slow had a significantly higher repeatability of the average walking velocity, step length and cadence than the other two speeds. Additionally, the data showed that one of the three technical methods for gait assessment has better metric characteristics than the other two. In conclusion, based on repeatability, technical and organizational simplification, this study helped us to successfully define a simple and reliable walking test to be used in the main study of the project.

  16. Earthworm nano‐ecotoxicology: Towards an integrated approach in toxicity testing of metal nanoparticles

    DEFF Research Database (Denmark)

    Hayashi, Yuya; Pedersen, Henrik; Wang, Jing

    Manufactured nanoparticles (NPs) belong to an emerging class of potential environmental pollutants. Of particular interest are the characteristics of NP toxicity under different exposure conditions e.g. cell culture, aquatic or soil media. NPs are thought to behave differently depending...... are versatile indicator organisms that can be tested in a wide range of different exposure media providing the possibility for a mechanistic insight into exposure testing of NPs. Here we report characterisation of Ag-NPs and their toxicity to the earthworm Eisenia fetida based on soil and aquatic exposures...

  17. Preimplantation Genetic Screening: An Effective Testing for Infertile and Repeated Miscarriage Patients?

    Directory of Open Access Journals (Sweden)

    Ning Wang

    2010-01-01

    Full Text Available Aneuploidy in pregnancy is known to increase with advanced maternal age (AMA and associate with repeated implantation failure (RIF, and repeated miscarriage (RM. Preimplantation genetic screening (PGS has been introduced into clinical practice, screening, and eliminating aneuploidy embryos, which can improve the chance of conceptions for infertility cases with poor prognosis. These patients are a good target group to assess the possible benefit of aneuploidy screening. Although practiced widely throughout the world, there still exist some doubts about the efficacy of this technique. Recent randomized trials were not as desirable as we expected, suggesting that PGS needs to be reconsidered. The aim of this review is to discuss the efficacy of PGS.

  18. Testing the fireball/blastwave model by monitoring afterglows from soft gamma repeaters

    OpenAIRE

    Huang, Y. F.

    2005-01-01

    The popular fireball/blastwave model of classical gamma-ray bursts is applied to soft gamma-ray bursts. It is found that X-ray afterglows from strong events may be above their quiescent levels for 40 -- 400 seconds. Optical afterglows may also be detectable. By monitoring the three repeaters, we will have an ideal way to check the fireball/blastwave model.

  19. Repeatability of testing a small broadband sensor in the Albuquerque Seismological Laboratory Underground Vault

    Science.gov (United States)

    Ringler, Adam; Holland, Austin; Wilson, David

    2017-01-01

    Variability in seismic instrumentation performance plays a fundamental role in our ability to carry out experiments in observational seismology. Many such experiments rely on the assumed performance of various seismic sensors as well as on methods to isolate the sensors from nonseismic noise sources. We look at the repeatability of estimating the self‐noise, midband sensitivity, and the relative orientation by comparing three collocated Nanometrics Trillium Compact sensors. To estimate the repeatability, we conduct a total of 15 trials in which one sensor is repeatedly reinstalled, alongside two undisturbed sensors. We find that we are able to estimate the midband sensitivity with an error of no greater than 0.04% with a 99th percentile confidence, assuming a standard normal distribution. We also find that we are able to estimate mean sensor self‐noise to within ±5.6  dB with a 99th percentile confidence in the 30–100‐s‐period band. Finally, we find our relative orientation errors have a mean difference in orientation of 0.0171° from the reference, but our trials have a standard deviation of 0.78°.

  20. Toxicity of Aqueous Fullerene nC60 to Activated Sludge: Nitrification Inhibition and Microtox Test

    Directory of Open Access Journals (Sweden)

    Yongkui Yang

    2012-01-01

    Full Text Available The increasing production and use of fullerene nanomaterials raised their exposure potential to the activated sludge during biological wastewater treatment process. In this study, the toxicity of aqueous nanoscaled C60 (nC60 to activated sludge was investigated using nitrification inhibition and Microtox test. The test solutions of nC60 were prepared using two methods: long stirring (Stir/nC60 and toluene exchange (Tol/nC60. The nC60 aggregation in test medium was also evaluated for toxicity assessment. The results showed that the nC60 aggregation behaved differently in two test mediums during the incubation periods. The nC60 toxicity was greatly influenced by the preparation method. Stir/nC60 presented no significant toxicity to both the nitrification sludge and bioluminescent bacteria at the maximum concentration studied. In contrast, the EC20 of Tol/nC60 was obtained to be 4.89 mg/L (3 h for the nitrification inhibition and 3.44 mg/L (30 min for Microtox test, respectively.

  1. Evaluation of 90-day Repeated Dose Oral Toxicity, Glycometabolism, Learning and Memory Ability, and Related Enzyme of Chromium Malate Supplementation in Sprague-Dawley Rats.

    Science.gov (United States)

    Feng, Weiwei; Wu, Huiyu; Li, Qian; Zhou, Zhaoxiang; Chen, Yao; Zhao, Ting; Feng, Yun; Mao, Guanghua; Li, Fang; Yang, Liuqing; Wu, Xiangyang

    2015-11-01

    Our previous study showed that chromium malate improved the regulation of blood glucose in mice with alloxan-induced diabetes. The present study was designed to evaluate the 90-day oral toxicity of chromium malate in Sprague-Dawley rats. The present study inspected the effect of chromium malate on glycometabolism, glycometabolism-related enzymes, lipid metabolism, and learning and memory ability in metabolically healthy Sprague-Dawley rats. The results showed that all rats survived and pathological, toxic, feces, and urine changes were not observed. Chromium malate did not cause measurable damage on liver, brain, and kidney. The fasting blood glucose, serum insulin, insulin resistance index, C-peptide, hepatic glycogen, glucose-6-phosphate dehydrogenase, glucokinase, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglyceride levels of normal rats in chromium malate groups had no significant change when compared with control group and chromium picolinate group under physiologically relevant conditions. The serum and organ content of Cr in chromium malate groups had no significant change compared with control group. No significant changes were found in morris water maze test and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and true choline esterase (TChE) activity. The results indicated that supplementation with chromium malate did not cause measurable toxicity and has no obvious effect on glycometabolism and related enzymes, learning and memory ability, and related enzymes and lipid metabolism of female and male rats. The results of this study suggest that chromium malate is safe for human consumption.

  2. Earthworm nano‐ecotoxicology: Towards an integrated approach in toxicity testing of metal nanoparticles

    DEFF Research Database (Denmark)

    Hayashi, Yuya; Pedersen, Henrik; Wang, Jing

    Manufactured nanoparticles (NPs) belong to an emerging class of potential environmental pollutants. Of particular interest are the characteristics of NP toxicity under different exposure conditions e.g. cell culture, aquatic or soil media. NPs are thought to behave differently depending on the me......Manufactured nanoparticles (NPs) belong to an emerging class of potential environmental pollutants. Of particular interest are the characteristics of NP toxicity under different exposure conditions e.g. cell culture, aquatic or soil media. NPs are thought to behave differently depending...... are versatile indicator organisms that can be tested in a wide range of different exposure media providing the possibility for a mechanistic insight into exposure testing of NPs. Here we report characterisation of Ag-NPs and their toxicity to the earthworm Eisenia fetida based on soil and aquatic exposures...

  3. PAH toxicity at aqueous solubility in the fish embryo test with Danio rerio using passive dosing

    DEFF Research Database (Denmark)

    Seiler, Thomas-Benjamin; Best, Nina; Fernqvist, Margit Møller

    2014-01-01

    to animal testing in (eco)toxicology. However, for hydrophobic organic chemicals it remains a technical challenge to ensure constant freely dissolved concentration at the maximum exposure level during such biotests. Passive dosing with PDMS silicone was thus applied to control the freely dissolved...... further data to support the close relationship between the chemical activity and the toxicity of hydrophobic organic compounds. Passive dosing from PDMS silicone enabled reliable toxicity testing of (highly) hydrophobic substances at aqueous solubility, providing a practical way to control toxicity...... without direct contact to the silicone surface showed similar mortalities as those exposed with direct contact to the silicone. Silicone oil overlaying the water phase as a novel passive dosing phase had no observable effects on the development of the fish embryos until hatching. This study provides...

  4. Artemia salina as test organism for assessment of acute toxicity of leachate water from landfills.

    Science.gov (United States)

    Svensson, B M; Mathiasson, L; Mårtensson, L; Bergström, S

    2005-03-01

    Artemia salina has, for the first time, been used as test organism for acute toxicity of leachate water from three landfills (the municipal landfills at Kristianstad, Sweden and Siauliai, Lithuania, and an industrial landfill at Stena fragmenting AB, Halmstad, as well as for leachate from Kristianstad treated in different ways in a pilot plan). Artemia can tolerate the high concentrations of chloride ions found in such waters. Large differences in toxicities were found, the leachate from Siauliai being the most toxic one. To increase the selectivity in the measurements, a fractionation was done by using ion exchange to separate ammonium/ammonia and metal ions from the leachate, and activated carbon adsorbents for organic pollutants. The influence of some metals and phenol compounds on the toxicity was investigated separately. It was found that most of the toxicity emanated from the ammonium/ammonia components in the leachate. However, there was also a significant contribution n from organic pollutants, other than phenol compounds, since separate experiments had in this latter case indicated negligible impact. The concentrations of metals were at a level, shown by separate experiments, where only small contribution to the toxicity could be expected.

  5. Acute toxicity tests and meta-analysis identify gaps in tropical ecotoxicology for amphibians.

    Science.gov (United States)

    Ghose, Sonia L; Donnelly, Maureen A; Kerby, Jacob; Whitfield, Steven M

    2014-09-01

    Amphibian populations are declining worldwide, particularly in tropical regions where amphibian diversity is highest. Pollutants, including agricultural pesticides, have been identified as a potential contributor to decline, yet toxicological studies of tropical amphibians are very rare. The present study assesses toxic effects on amphibians of 10 commonly used commercial pesticides in tropical agriculture using 2 approaches. First, the authors conducted 8-d toxicity assays with formulations of each pesticide using individually reared red-eyed tree frog (Agalychnis callidryas) tadpoles. Second, they conducted a review of available data for the lethal concentration to kill 50% of test animals from the US Environmental Protection Agency's ECOTOX database to allow comparison with their findings. Lethal concentration estimates from the assays ranged over several orders of magnitude. The nematicides terbufos and ethoprophos and the fungicide chlorothalonil were very highly toxic, with evident effects within an order of magnitude of environmental concentrations. Acute toxicity assays and meta-analysis show that nematicides and fungicides are generally more toxic than herbicides yet receive far less research attention than less toxic herbicides. Given that the tropics have a high diversity of amphibians, the findings emphasize the need for research into the effects of commonly used pesticides in tropical countries and should help guide future ecotoxicological research in tropical regions.

  6. Development of methods for laboratory culture and toxicity testing of the endangered desert pupfish, Cyprinodon macularius, and evaluation of the acute toxicity of selenium

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — We conducted a series of studies to evaluate methods for laboratory culture and toxicity testing with the endangered desert pupfish, Cyprinodon macularius. This...

  7. Comparison of random regression and repeatability models to predict breeding values from test-day records of Norwegian goats.

    Science.gov (United States)

    Andonov, S; Ødegård, J; Svendsen, M; Ådnøy, T; Vegara, M; Klemetsdal, G

    2013-03-01

    One aim of the research was to challenge a previously selected repeatability model with 2 other repeatability models. The main aim, however, was to evaluate random regression models based on the repeatability model with lowest mean-squared error of prediction, using Legendre polynomials up to third order for both animal additive genetic and permanent environmental effects. The random regression and repeatability models were compared for model fit (using likelihood-ratio testing, Akaike information criterion, and the Bayesian information criterion) and the models' mean-squared errors of prediction, and by cross-validation. Cross-validation was carried out by correlating excluded observations in one data set with the animals' breeding values as predicted from the pedigree only in the remaining data, and vice versa (splitting proportion: 0.492). The data was from primiparous goats in 2 closely tied buck circles (17 flocks) in Norway, with 11,438 records for daily milk yield and 5,686 to 5,896 records for content traits (fat, protein, and lactose percentages). A simple pattern was revealed; for daily milk yield with about 5 records per animal in first lactation, a second-order random regression model should be chosen, whereas for content traits that had only about 3 observations per goat, a first-order polynomial was preferred. The likelihood-ratio test, Akaike information criterion, and mean-squared error of prediction favored more complex models, although the results from the latter and the Bayesian information criterion were in the direction of those obtained with cross-validation. As the correlation from cross-validation was largest with random regression, genetic merit was predicted more accurate with random regression models than with the repeatability model.

  8. Static renewal tests using Anodonta imbecillus (freshwater mussels). Anodonta imbecillis copper sulfate reference toxicant test, Clinch River-Environmental Restoration Program (CR-ERP)

    Energy Technology Data Exchange (ETDEWEB)

    Simbeck, D.J.

    1993-12-31

    Reference toxicant testing using juvenile freshwater mussels was conducted as part of the CR-ERP biomonitoring study of Clinch River sediments to assess the sensitivity of test organisms and the overall performance of the test. Tests were conducted using moderately hard synthetic water spiked with known concentrations of copper as copper sulfate. Toxicity testing of copper sulfate reference toxicant was conducted from May 12--21, 1993. The organisms used for testing were juvenile fresh-water mussels (Anodonta imbecillis). Results from this test showed an LC{sub 50} value of 1.12 mg Cu/L which is lower than the value of 2.02 mg Cu/L obtained in a previous test. Too few tests have been conducted with copper as the toxicant to determine a normal range of values. Attachments to this report include: Toxicity test bench sheets and statistical analyses; Copper analysis request and results; and Personnel training documentation.

  9. Predicting aquatic toxicities of chemical pesticides in multiple test species using nonlinear QSTR modeling approaches.

    Science.gov (United States)

    Basant, Nikita; Gupta, Shikha; Singh, Kunwar P

    2015-11-01

    In this study, we established nonlinear quantitative-structure toxicity relationship (QSTR) models for predicting the toxicities of chemical pesticides in multiple aquatic test species following the OECD (Organization for Economic Cooperation and Development) guidelines. The decision tree forest (DTF) and decision tree boost (DTB) based QSTR models were constructed using a pesticides toxicity dataset in Selenastrum capricornutum and a set of six descriptors. Other six toxicity data sets were used for external validation of the constructed QSTRs. Global QSTR models were also constructed using the combined dataset of all the seven species. The diversity in chemical structures and nonlinearity in the data were evaluated. Model validation was performed deriving several statistical coefficients for the test data and the prediction and generalization abilities of the QSTRs were evaluated. Both the QSTR models identified WPSA1 (weighted charged partial positive surface area) as the most influential descriptor. The DTF and DTB QSTRs performed relatively better than the single decision tree (SDT) and support vector machines (SVM) models used as a benchmark here and yielded R(2) of 0.886 and 0.964 between the measured and predicted toxicity values in the complete dataset (S. capricornutum). The QSTR models applied to six other aquatic species toxicity data yielded R(2) of >0.92 (DTF) and >0.97 (DTB), respectively. The prediction accuracies of the global models were comparable with those of the S. capricornutum models. The results suggest for the appropriateness of the developed QSTR models to reliably predict the aquatic toxicity of chemicals and can be used for regulatory purpose.

  10. Morphine Sulphate Toxicity on Liver Function Tests in Fructose-Induced Insulin Resistant Male Rats

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Shahraki

    2014-02-01

    Full Text Available Background: Since liver is a gland which has an important role in drug metabolism, the present study was conducted to evaluate the effect of a single dose and repeated administration of morphine on LFT, blood sugar and fasting insulin resistance index in fructose- fed male rats. Materials and Methods: The experiment was performed on 36 Wistar-Albino male rats, which were divided into a control (A and three tests groups (B, C and D. The control group consumed tap water, but the test groups consumed fructose-enriched water (10%, w/v and received null, single, and repeated doses of morphine, respectively. At the end, animals were anesthetized and blood samples were collected. Liver enzymes, insulin and insulin resistance were measured. Data were analyzed by SPSS-11, using ANOVA and Tukey tests as post hoc test. Results were expressed as mean±SD and Statistical differences were recognized significant by p<0.05. Results: The results showed that all test groups were insulin resistant; alanine aminotransferase (ALT and asparatate aminotransferase (AST activity values in group D significantly increased compared to other groups while its plasma glucose and insulin values showed a significant decrease in comparison to other test groups. Conclusion: It seems that repeated morphine administration can affect liver function test (LFT and fasting Insulin resistance index (FIRI in fructose- fed male rats.

  11. In-vitro cervical mucus-sperm penetration tests and outcome of infertility treatments in couples with repeatedly negative post-coital tests.

    Science.gov (United States)

    Farhi, J; Valentine, A; Bahadur, G; Shenfield, F; Steele, S J; Jacobs, H S

    1995-01-01

    The results of in-vitro cervical mucus-sperm penetration tests and cross-hostility tests in 178 couples with repeatedly negative post-coital tests were recorded. Using a protocol of three cycles with intra-uterine inseminations (IUI) followed by three cycles with ovulation induction + IUI, the association between the cause of infertility, results of the in-vitro tests and the outcome of infertility treatment was investigated. We found that repeatedly negative post-coital tests are a good indicator of a cervical mucus-sperm penetration problem. The cross-hostility test clearly differentiates the abnormal factor in this interaction, and a good performance of the donors' spermatozoa in the cervical mucus correlates with increased pregnancy rate. In male factor infertility, failure of the husbands' spermatozoa to penetrate cervical mucus was not indicative of a deficient fertilization potential in vivo. In these patients a serious attempt should therefore be made to reverse the infertility by treatment with IUI or ovulation induction + IUI before attempting assisted reproduction. Women with polycystic ovaries and repeatedly negative post-coital tests should be investigated for sperm receptivity of the cervical mucus. Low receptivity of the cervical mucus may imply that endometrial receptivity and oocyte quality are also low. Ovulation induction and not IUI alone should therefore be used as the preferred mode of treatment to improve pregnancy rate.

  12. Prospective evaluation of potential toxicity of repeated doses of Thymus vulgaris L. extracts in rats by means of clinical chemistry, histopathology and NMR-based metabonomic approach.

    Science.gov (United States)

    Benourad, Fouzia; Kahvecioglu, Zehra; Youcef-Benkada, Mokhtar; Colet, Jean-Marie

    2014-10-01

    In the field of natural extracts, research generally focuses on the study of their biological activities for food, cosmetic, or pharmacological purposes. The evaluation of their adverse effects is often overlooked. In this study, the extracts of Thymus vulgaris L. were obtained by two different extraction methods. Intraperitoneal injections of both extracts were given daily for four days to male Wistar Han rats, at two different doses for each extract. The evaluation of the potential toxic effects included histopathological examination of liver, kidney, and lung tissues, as well as serum biochemistry of liver and kidney parameters, and (1)H-NMR-based metabonomic profiles of urine. The results showed that no histopathological changes were observed in the liver and kidney in rats treated with both extracts of thyme. Serum biochemical investigations revealed significant increases in blood urea nitrogen, creatinine, and uric acid in animals treated with polyphenolic extract at both doses. In these latter groups, metabonomic analysis revealed alterations in a number of urine metabolites involved in the energy metabolism in liver mitochondria. Indeed, the results showed alterations of glycolysis, Krebs cycle, and β-oxidative pathways as evidenced by increases in lactate and ketone bodies, and decreases in citrate, α-ketoglutarate, creatinine, hippurate, dimethylglycine, and dimethyalanine. In conclusion, this work showed that i.p. injection of repeated doses of thyme extracts causes some disturbances of intermediary metabolism in rats. The metabonomic study revealed interesting data which could be further used to determine the cellular pathways affected by such treatments.

  13. 26-week repeated oral dose toxicity study of UP446, a combination of defined extracts of Scutellaria baicalensis and Acacia catechu, in beagle dogs.

    Science.gov (United States)

    Yimam, Mesfin; Lee, Young Chul; Jia, Qi

    2016-07-01

    The needs for relatively safe botanical alternatives to relieve symptoms associated to arthritis have continued to grow in parallel with the ageing population. UP446, a standardized bioflavonoid composition from the roots of Scutellaria baicalensis and the heartwoods of Acacia catechu, has been used as over the counter joint care dietary supplements and a prescription medical food. Significant safety data have been documented in rodents and human for this composition. Here we evaluated the potential adverse effects of orally administered UP446 in beagle dogs following a 26-week repeated oral dose toxicity study. UP446 at doses of 250, 500 and 1000 mg/kg/day were administered orally to beagle dogs for 26 weeks. A 4-week recovery group from the high dose (1000 mg/kg) and vehicle treated groups were included. No morbidity or mortality was observed for the duration of the study. No significant differences between groups in body weights, food consumption, ophthalmological examinations, electrocardiograms, urinalysis, hematology, clinical chemistry, organ weights, gross pathology and histopathology were documented. Emesis, loose feces and diarrhea were noted in both genders at the 1000 mg/kg treatment groups. These clinical signs were considered to be reversible as they were not evident in the recovery period. In conclusion, the no-observed-adverse-effect-level (NOAEL) of UP446 was considered to be 500 mg/kg/day both in male and female beagle dogs.

  14. Studies with the USF/NASA toxicity screening test method - Exercise wheels and oxygen replenishment

    Science.gov (United States)

    Hilado, C. J.; Cumming, H. J.

    1977-01-01

    Continuing efforts to improve the University of San Francisco/NASA toxicity screening test method have included the addition of exercise wheels to provide a different measure of incapacitation, and oxygen replenishment to offset any effect of oxygen depletion by the test animals. The addition of exercise wheels limited the number of animals in each test and doubled the required number of tests without any significant improvement in reproducibility. Oxygen replenishment appears to have an effect on survival in the last 5 minutes of the 30-minute test, but the effect is expected to be similar for most materials.

  15. A high throughput passive dosing format for the Fish Embryo Acute Toxicity test

    DEFF Research Database (Denmark)

    Vergauwen, Lucia; Nørgaard Schmidt, Stine; Stinckens, Evelyn

    2015-01-01

    High throughput testing according to the Fish Embryo Acute Toxicity (FET) test (OECD Testing Guideline 236) is usually conducted in well plates. In the case of hydrophobic test substances, sorptive and evaporative losses often result in declining and poorly controlled exposure conditions. Therefore......, our objective was to improve exposure conditions in FET tests by evaluating a passive dosing format using silicone O-rings in standard 24-well polystyrene plates. We exposed zebrafish embryos to a series of phenanthrene concentrations until 120 h post fertilization (hpf), and obtained a linear...

  16. Animal alternatives for whole effluent toxicity testing: Perspectives from a global workshop

    Science.gov (United States)

    Since the 1940’s, effluent toxicity testing has been utilized to varying degrees in many countries to assess potential ecological impacts and assist in determining necessary treatment options for environmental protection. However, it was only in the early 1980’s that ...

  17. Animal alternatives for whole effluent toxicity testing: Perspectives from a global workshop (presentation)

    Science.gov (United States)

    Since the 1940s, effluent toxicity testing has been utilized to varying degrees in many countries to assess potential ecological impacts and assist in determining necessary treatment options for environmental protection. However, it was only in the early 1980’s that toxicit...

  18. Aquatic toxicity testing of liquid hydrophobic chemicals – Passive dosing exactly at the saturation limit

    DEFF Research Database (Denmark)

    Stibany, Felix; Nørgaard Schmidt, Stine; Schäffer, Andreas

    2017-01-01

    The aims of the present study were (1) to develop a passive dosing approach for aquatic toxicity testing of liquid substances with very high Kow values and (2) to apply this approach to the model substance dodecylbenzene (DDB, Log Kow = 8.65). The first step was to design a new passive dosing for...

  19. Animal alternatives for whole effluent toxicity testing: Perspectives from a global workshop

    Science.gov (United States)

    Since the 1940’s, effluent toxicity testing has been utilized to varying degrees in many countries to assess potential ecological impacts and assist in determining necessary treatment options for environmental protection. However, it was only in the early 1980’s that ...

  20. Animal alternatives for whole effluent toxicity testing: Perspectives from a global workshop (presentation)

    Science.gov (United States)

    Since the 1940s, effluent toxicity testing has been utilized to varying degrees in many countries to assess potential ecological impacts and assist in determining necessary treatment options for environmental protection. However, it was only in the early 1980’s that toxicit...

  1. 40 CFR Appendix 2 to Subpart A of... - Drilling Fluids Toxicity Test

    Science.gov (United States)

    2010-07-01

    ... System, Cary, North Carolina, 1982) was used to analyze these data. The 96-hour LC50 adjusted for the... are designed to minimize sample contamination and alteration of the physical or chemical properties of... toxicity testing provided that proper containers are used and proper condition are maintained. II...

  2. Development of a standard acute dietary toxicity test for the silkworm (Bombyx mori L.)

    NARCIS (Netherlands)

    Sun, X.; Valk, H.; Jiang, H.; Wang, X.; Yuan, S.; Zhang, Y.; Roessink, I.; Gao, X.

    2012-01-01

    Larvae of the silkworm (Bombyx mod L.) may be exposed to pesticide residues on the leaves of their food plant, the mulberry tree (Morus spp.), which can lead to adverse effects on silk production. A new acute dietary toxicity test method was evaluated as the basis for pesticide risk assessment. A se

  3. 40 CFR 799.9355 - TSCA reproduction/developmental toxicity screening test.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 31 2010-07-01 2010-07-01 true TSCA reproduction/developmental toxicity screening test. 799.9355 Section 799.9355 Protection of Environment ENVIRONMENTAL PROTECTION... developmental defects should not be used. Healthy virgin animals, not subjected to previous...

  4. ISSUES IN DEVELOPING A TWO-GENERATION AVIAN TOXICITY TEST WITH JAPANESE QUAIL

    Science.gov (United States)

    As a subgroup of the OECD Expert Group on Assessment of Endocrine Disrupting Effects in Birds, we reviewed unresolved methodological issures important for the development of a two-generation toxicity test, discussed advantages and disadvantages of alternative approaches, and prop...

  5. Compound-specific effects of diverse neurodevelopmental toxicants on global gene expression in the neural embryonic stem cell test (ESTn)

    NARCIS (Netherlands)

    Theunissen, P.T.; Robinson, J.F.; Pennings, J.L.A.; van Herwijnen, M.; Kleinjans, J.C.S.; Piersma, A.H.

    2012-01-01

    Alternative assays for developmental toxicity testing are needed to reduce animal use in regulatory toxicology. The in vitro murine neural embryonic stem cell test (ESTn) was designed as an alternative for neurodevelopmental toxicity testing. The integration of toxicogenomic-based approaches may fur

  6. Human Short Tandem Repeat (STR Markers for Paternity Testing in Pig-Tailed Macaques

    Directory of Open Access Journals (Sweden)

    DYAH PERWITASARI-FARAJALLAH

    2007-06-01

    Full Text Available This study investigated the use of human short tandem repeat (STR or microsatellite loci markers for assessing paternity and genetic structure of pig-tailed macaques (Macaca nemestrina breeding colony. Four human microsatellite primer pairs located at human map position D1S548, D3S1768, D5S820, and D2S1777, were amplified by polymerase chain reaction (PCR for pig-tailed macaques. Four loci were found to be clearly and reliably amplified, and three loci exhibited high levels of genetic heterogeneity. These loci were sufficiently informative to differentiate discretely between related and unrelated pairs.

  7. The Effects of Repeated Cooperative Testing in an Introductory Statistics Course.

    Science.gov (United States)

    Giraud, Gerald; Enders, Craig

    Cooperative testing seems a logical complement to cooperative learning, but it is counter to traditional testing procedures and is viewed by some as an opportunity for cheating and freeloading on the efforts of other test takers. This study examined the practice of cooperative testing in introductory statistics. Findings indicate that students had…

  8. Paradoxical effects of testing: repeated retrieval attempts enhance the likelihood of later accurate and false recall.

    Science.gov (United States)

    McDermott, Kathleen B

    2006-03-01

    The testing effect is the finding that taking an initial test enhances the likelihood of later recall. The present report examines the extent to which this benefit of testing comes with a cost: an enhanced likelihood of erroneously recalling incorrect information. Subjects were given short lists of semantic associates (e.g., hill, valley, climb); each list converged upon a related nonpresented word (e.g., mountain). After presentation of some lists, the subjects received no initial test; after others, one initial free recall test; and after others, three successive free recall tests. The probabilities of final free recall (and the probability of reporting vivid recollection of the moment of encoding) of both studied and related, nonstudied words (e.g., mountain) were highest when three initial tests had been taken, intermediate following one initial test, and lowest when no initial test had occurred. The beneficial effects of testing carry the cost of increases in erroneous memory for related information.

  9. Duration of Acute and Chronic Toxicity Testing in Animals (ICH S4A and S4B)

    DEFF Research Database (Denmark)

    Spindler, Per; Van Cauteren, Herman

    2013-01-01

    for the ICH S4B guideline regarding the duration of non-rodent repeated dose toxicity studies is explained and lessons learned are discussed. Since the guideline was issued in 1997 changes occurred in e.g. the language of the European legislation, and the requirements for non-clinical studies to support...

  10. Acute toxicity of metals and reference toxicants to a freshwater ostracod, Cypris subglobosa Sowerby, 1840 and correlation to EC{sub 50} values of other test models

    Energy Technology Data Exchange (ETDEWEB)

    Khangarot, B.S., E-mail: bkhangarot@hotmail.com [Ecotoxicology Division, Indian Institute of Toxicology Research (Formerly: Industrial Toxicology Research Centre), Post Box No. 80, Mahatma Gandhi Marg, Lucknow 226001 (India); Das, Sangita [Ecotoxicology Division, Indian Institute of Toxicology Research (Formerly: Industrial Toxicology Research Centre), Post Box No. 80, Mahatma Gandhi Marg, Lucknow 226001 (India)

    2009-12-30

    The ostracod Cypris subglobosa Sowerby, 1840 static bioassay test on the basis of a 48 h of 50% of immobilization (EC{sub 50}) has been used to measure the toxicity of 36 metals and metalloids and 12 reference toxicants. Among the 36 metals and metalloids, osmium (Os) was found to be the most toxic in the test while boron (B), the least toxic. The EC{sub 50} values of this study revealed positive linear relationship with the established test models of cladoceran (Daphnia magna), sludge worm (Tubifex tubifex), chironomid larvae (Chironomus tentans), protozoan (Tetrahymena pyriformis), fathead minnow (Pimephales promelas), bluegill sunfish (Lepomis macrochirus), and aquatic macrophyte duckweed (Lemna minor). Correlation coefficients (r{sup 2}) for 17 physicochemical properties of metals or metal ions and EC{sub 50}s (as pM) were examined by linear regression analysis. The electronegativity, ionization potential, melting point, solubility product of metal sulfides (pK{sub sp}), softness parameter and some other physicochemical characteristics were significantly correlated with EC{sub 50}s of metals to C. subglobosa. The reproducibility of toxicity test was determined using 12 reference toxicants. The coefficient of variability of the EC{sub 50}s ranged from 6.95% to 55.37% and variability was comparable to that noticed for D. magna and other aquatic test models. The study demonstrated the need to include crustacean ostracods in a battery of biotests to detect the presence of hazardous chemicals in soils, sewage sludges, sediments and aquatic systems.

  11. Comprehensive In Vitro Toxicity Testing of a Panel of Representative Oxide Nanomaterials: First Steps towards an Intelligent Testing Strategy.

    Directory of Open Access Journals (Sweden)

    Lucian Farcal

    Full Text Available Nanomaterials (NMs display many unique and useful physico-chemical properties. However, reliable approaches are needed for risk assessment of NMs. The present study was performed in the FP7-MARINA project, with the objective to identify and evaluate in vitro test methods for toxicity assessment in order to facilitate the development of an intelligent testing strategy (ITS. Six representative oxide NMs provided by the EC-JRC Nanomaterials Repository were tested in nine laboratories. The in vitro toxicity of NMs was evaluated in 12 cellular models representing 6 different target organs/systems (immune system, respiratory system, gastrointestinal system, reproductive organs, kidney and embryonic tissues. The toxicity assessment was conducted using 10 different assays for cytotoxicity, embryotoxicity, epithelial integrity, cytokine secretion and oxidative stress. Thorough physico-chemical characterization was performed for all tested NMs. Commercially relevant NMs with different physico-chemical properties were selected: two TiO2 NMs with different surface chemistry - hydrophilic (NM-103 and hydrophobic (NM-104, two forms of ZnO - uncoated (NM-110 and coated with triethoxycapryl silane (NM-111 and two SiO2 NMs produced by two different manufacturing techniques - precipitated (NM-200 and pyrogenic (NM-203. Cell specific toxicity effects of all NMs were observed; macrophages were the most sensitive cell type after short-term exposures (24-72h (ZnO>SiO2>TiO2. Longer term exposure (7 to 21 days significantly affected the cell barrier integrity in the presence of ZnO, but not TiO2 and SiO2, while the embryonic stem cell test (EST classified the TiO2 NMs as potentially 'weak-embryotoxic' and ZnO and SiO2 NMs as 'non-embryotoxic'. A hazard ranking could be established for the representative NMs tested (ZnO NM-110 > ZnO NM-111 > SiO2 NM-203 > SiO2 NM-200 > TiO2 NM-104 > TiO2 NM-103. This ranking was different in the case of embryonic tissues, for which TiO2

  12. Evaluation of ability of reference toxicity tests to identify stress in laboratory populations of the amphipod Hyalella azteca

    Science.gov (United States)

    McNulty, E.W.; Dwyer, F.J.; Ellersieck, Mark R.; Greer, E.I.; Ingersoll, C.G.; Rabeni, C.F.

    1999-01-01

    Standard methods for conducting toxicity tests imply that the condition of test organisms can be established using reference toxicity tests. However, only a limited number of studies have evaluated whether reference toxicity tests can actually be used to determine if organisms are in good condition at the start of a test. We evaluated the ability of reference toxicants to identify stress associated with starvation in laboratory populations of the amphipod Hyalella azteca using acute toxicity tests and four reference toxicants: KCl, CdCl2, sodium pentachlorophenate (NaPCP), and carbaryl. Stress associated with severe starvation was observed with exposure of amphipods to carbaryl or NaPCP but not with exposure to KCl or CdCl2 (i.e., lower LC50 with severe starvation). Although the LC50s for NaPCP and carbaryl were statistically different between starved and fed amphipods, this difference may not be biologically significant given the variability expected in acute lethality tests. Stress associated with sieving, heat shock, or cold shock of amphipods before the start of a test was not evident with exposure to carbaryl or KCl as reference toxicants. The chemicals evaluated in this study provided minimal information about the condition of the organisms used to start a toxicity test. Laboratories should periodically perform reference toxicity tests to assess the sensitivity of life stages or strains of test organisms. However, use of other test acceptability criteria required in standard methods such as minimum survival, growth, or reproduction of organisms in the control treatment at the end of a test, provides more useful information about the condition of organisms used to start a test compared to data generated from reference toxicity tests.

  13. Evaluation of ability of reference toxicity tests to identify stress in laboratory populations of the amphipod Hyalella azteca

    Energy Technology Data Exchange (ETDEWEB)

    McNulty, E.W.; Ellersieck, M.R.; Rabeni, C.F. [Univ. of Missouri, Columbia, MO (United States); Dwyer, F.J.; Greer, E.I.; Ingersoll, C.G. [Geological Survey, Columbia, MO (United States). Columbia Environmental Research Center

    1999-03-01

    Standard methods for conducting toxicity tests imply that the condition of test organisms can be established using reference toxicity tests. However, only a limited number of studies have evaluated whether reference toxicity tests can actually be used to determine if organisms are in good condition, at the start of a test. The authors evaluated the ability of reference toxicants to identify stress associated with starvation in laboratory populations of the amphipod Hyalella azteca using acute toxicity tests and four reference toxicants: KCl, CdCl{sub 2}, sodium pentachlorophenate (NaPCP), and carbaryl. Stress associated with severe starvation was observed with exposure of amphipods to carbaryl or NaPCP but not with exposure to KCl or CdCl{sub 2} (i.e., lower LC50 with severe starvation). Although the LC50s for NaPCP and carbaryl were statistically different between starved and fed amphipods, this difference may not be biologically significant given the variability expected in acute lethality tests. Stress associated with sieving, heat shock, or cold shock of amphipods before the start of a test was not evident with exposure to carbaryl or KCl as reference toxicants. The chemicals evaluated in this study provided minimal information about the condition of the organisms used to start a toxicity test. Laboratories should periodically perform reference toxicity tests to assess the sensitivity of life stages or strains of test organisms. However, use of other test acceptability criteria required in standard methods, such as minimum survival, growth, or reproduction of organisms in the control treatment at the end of a test, provides more useful information about the condition of organisms used to start a test compared to data generated from reference toxicity tests.

  14. Developmental toxicity of thyroid-active compounds in a zebrafish embryotoxicity test.

    Science.gov (United States)

    Jomaa, Barae; Hermsen, Sanne A B; Kessels, Maurijn Y; van den Berg, Johannes H J; Peijnenburg, Ad A C M; Aarts, Jac M M J G; Piersma, Aldert H; Rietjens, Ivonne M C M

    2014-01-01

    Zebrafish embryos were exposed to concentration ranges of selected thyroid-active model compounds in order to assess the applicability of zebrafish-based developmental scoring systems withinan alternative testing strategy to detect the developmental toxicity ofthyroid-active compounds. Model compounds tested included triiodothyronine (T3), propylthiouracil (PTU), methimazole (MMI), sodium perchlorate (NaClO4) and amiodarone hydrochloride (AMI), selected to represent different modes of action affecting thyroid activity. Tested time windows included 48-120 hours post fertilization (hpf), 0-72 hpf and 0-120 hpf. All tested compounds resulted in developmental changes, with T3 being the most potent. The developmental parameters affected included reflective iridophores, beat and glide swimming, inflated swim bladders, as well as resorbed yolk sacs. These effects are only evident by 120 hpf and therefore an existing General Morphology Score (GMS) system was extended to create a General Developmental Score(GDS) that extends beyond the 72 hpfscoring limit of GMS and includes additional parameters that are affected by exposure to model thyroid-active compounds. Moreover, the GDS is cumulative as it includes not only the scoring of developmental morphologies but also integrates developmental dysmorphologies. Exposures from 48-120 hpf did not provide additional information to exposures from 0-120 hpf. The results indicate that the zebrafish GDS can detect the developmental toxicity of thyroid toxicants and may be of use in an integrated testing strategy to reduce, refine and in certain cases replace animal testing.

  15. Toxicity testing with constant or decreasing concentrations of chemically dispersed oil

    Energy Technology Data Exchange (ETDEWEB)

    Kiesser, S.L.; Fleishmann, M.L.; McQuerry, D.L.; Riley, R.G.

    1982-10-01

    An exposure system and method of quantitating toxicity have been developed to provide an estimate of the effects of dispersed oil on marine organisms under a variety of exposure conditions. Results of constant concentration exposures (for hours or days) can be compared to those of diluting exposures (decreasing to zero in 8 or 24 h) on a basis of the ''toxicity index.'' This index is equal to the total exposure when time in hours or days is multiplied by the concentration at each hour (ppm h or ppm days). Tests have been conducted with shrimp (Pandalus danae), two oils (Prudhoe Bay crude and a light Arabian crude), and two dispersants. There is a seasonal pattern to the tolerance of the shrimp. Tests in the colder months (fall/winter) produce toxicity indices approximately three times higher than summer/spring values. During tests in summer, there was also little difference observed when the toxicity of the light Arabian oil was compared to that of Prudhoe Bay crude (2.3 and 3.4 ppm days, respectively). The usefulness of our methods is that in addition to the comparisons already noted, it is possible to predict the outcome of dispersant application under varying environmental conditions.

  16. Application of a novel integrated toxicity testing strategy incorporating "3R" principles of animal research to evaluate the safety of a new agrochemical sulfoxaflor.

    Science.gov (United States)

    Terry, Claire; Rasoulpour, Reza J; Saghir, Shakil; Marty, Sue; Gollapudi, B Bhaskar; Billington, Richard

    2014-05-01

    Plant protection products (PPPs) and the active substance(s) contained within them are rigorously and comprehensively tested prior to registration to ensure that human health is not impacted by their use. In recent years, there has been a widespread drive to have more relevant testing strategies (e.g., ILSI/HESI-ACSA and new EU Directives), which also take account of animal welfare, including the 3R (replacement, refinement, and reduction) principles. The toxicity potential of one such new active substance, sulfoxaflor, a sulfoximine insecticide (CAS #946578-00-3), was evaluated utilizing innovative testing strategies comprising: (1) an integrated testing scheme to optimize information obtained from as few animals as possible (i.e., 3R principles) through modifications of standard protocols, such as enhanced palatability study design, to include molecular endpoints, additional neurotoxicity and immunotoxicity parameters in a subchronic toxicity study, and combining multiple test guidelines into one study protocol; (2) generation of toxicokinetic data across dose levels, sexes, study durations, species, strains and life stages, without using satellite animals, which was a first for PPP development, and (3) addition of prospective mode of action (MoA) endpoints within repeat dose toxicity studies as well as proactive inclusion of specific MoA studies as an integral part of the development program. These novel approaches to generate key data early in the safety evaluation program facilitated informed decision-making on the need for additional studies and contributed to a more relevant human health risk assessment. This supplement also contains papers which describe in more detail the approach taken to establish the MoA and human relevance framework related to toxicities elicited by sulfoxaflor in the mammalian toxicology studies: developmental toxicity in rats mediated via the fetal muscle nicotinic acetylcholine receptor (nAChR) ( Ellis-Hutchings et al. 2014 ); liver

  17. Critique on the use of the standardized avian acute oral toxicity test for first generation anticoagulant rodenticides

    Science.gov (United States)

    Vyas, Nimish B.; Rattner, Barnett A.

    2012-01-01

    Avian risk assessments for rodenticides are often driven by the results of standardized acute oral toxicity tests without regards to a toxicant's mode of action and time course of adverse effects. First generation anticoagulant rodenticides (FGARs) generally require multiple feedings over several days to achieve a threshold concentration in tissue and cause adverse effects. This exposure regimen is much different than that used in the standardized acute oral toxicity test methodology. Median lethal dose values derived from standardized acute oral toxicity tests underestimate the environmental hazard and risk of FGARs. Caution is warranted when FGAR toxicity, physiological effects, and pharmacokinetics derived from standardized acute oral toxicity testing are used for forensic confirmation of the cause of death in avian mortality incidents and when characterizing FGARs' risks to free-ranging birds.

  18. Acute toxicity assessment of ANAMMOX substrates and antibiotics by luminescent bacteria test.

    Science.gov (United States)

    Ding, Shuang; Wu, Junwei; Zhang, Meng; Lu, Huifeng; Mahmood, Qaisar; Zheng, Ping

    2015-12-01

    Acute toxicities of anaerobic ammonia oxidation (ANAMMOX) substrates and four antibiotics from pharmaceutical wastewaters on ANAMMOX process were reported. Individual and joint acute toxicity assays were performed using 50% inhibitory concentration (IC50). Results showed that IC50 values and their 95% confidence interval of ammonium chloride (A), sodium nitrite (B), penicillin G-Na (C), polymyxin B sulfate (D), chloramphenicol (E) and kanamycin sulfate (F) were 2708.9 (2247.9-3169.9), 1475.4 (1269.9-1680.9), 5114.4 (4946.4-5282.4), 10.2 (1.8-18.6), 409.9 (333.7-486.1) and 5254.1 (3934.4-6573.8) mgL(-1) respectively, suggesting toxicities were in the order of D>E>B>A>C>F. Joint acute toxicities of bicomponent mixtures A and B, C and D, C and F, D and F were independent; D and E, E and F were additive while C and E were synergistic. Joint acute toxicities of multicomponent mixtures were synergistic or additive. Luminescent bacteria test is an easy and robust method for forecasting the feasibility of ANAMMOX process for pharmaceutical wastewater treatment.

  19. Attentional and visual demands for sprint performance in non-fatigued and fatigued conditions: reliability of a repeated sprint test

    Directory of Open Access Journals (Sweden)

    Diercks Ron L

    2010-05-01

    Full Text Available Abstract Background Physical performance measures are widely used to assess physical function, providing information about physiological and biomechanical aspects of motor performance. However they do not provide insight into the attentional and visual demands for motor performance. A figure-of-eight sprint test was therefore developed to measure the attentional and visual demands for repeated-sprint performance. The aims of the study were: 1 to assess test-retest reliability of the figure-of-eight sprint test, and 2 to study the attentional and visual demands for sprint performance in a non-fatigued and fatigued condition. Methods Twenty-seven healthy athletes were included in the study. To determine test-retest reliability, a subgroup of 19 athletes performed the figure-of-eight sprint test twice. The figure-of-eight sprint test consisted of nine 30-second sprints. The sprint test consisted of three test parts: sprinting without any restriction, with an attention-demanding task, and with restricted vision. Increases in sprint times with the attention-demanding task or restricted vision are reflective of the attentional and visual demands for sprinting. Intraclass correlation coefficients (ICCs and mean difference between test and retest with 95% confidence limits (CL were used to assess test-retest reliability. Repeated-measures ANOVA were used for comparisons between the sprint times and fatigue measurements of the test parts in both a non-fatigued and fatigued condition. Results The figure-of-eight sprint test showed good test-retest reliability, with ICCs ranging from 0.75 to 0.94 (95% CL: 0.40-0.98. Zero lay within the 95% CL of the mean differences, indicating that no bias existed between sprint performance at test and retest. Sprint times during the test parts with attention-demanding task (P = 0.01 and restricted vision (P Conclusions High ICCs and the absence of systematic variation indicate good test-retest reliability of the figure

  20. Leachates draining from controlled municipal solid waste landfill: Detailed geochemical characterization and toxicity tests.

    Science.gov (United States)

    Mavakala, Bienvenu K; Le Faucheur, Séverine; Mulaji, Crispin K; Laffite, Amandine; Devarajan, Naresh; Biey, Emmanuel M; Giuliani, Gregory; Otamonga, Jean-Paul; Kabatusuila, Prosper; Mpiana, Pius T; Poté, John

    2016-09-01

    Management of municipal solid wastes in many countries consists of waste disposal into landfill without treatment or selective collection of solid waste fractions including plastics, paper, glass, metals, electronic waste, and organic fraction leading to the unsolved problem of contamination of numerous ecosystems such as air, soil, surface, and ground water. Knowledge of leachate composition is critical in risk assessment of long-term impact of landfills on human health and the environment as well as for prevention of negative outcomes. The research presented in this paper investigates the seasonal variation of draining leachate composition and resulting toxicity as well as the contamination status of soil/sediment from lagoon basins receiving leachates from landfill in Mpasa, a suburb of Kinshasa in the Democratic Republic of the Congo. Samples were collected during the dry and rainy seasons and analyzed for pH, electrical conductivity, dissolved oxygen, soluble ions, toxic metals, and were then subjected to toxicity tests. Results highlight the significant seasonal difference in leachate physicochemical composition. Affected soil/sediment showed higher values for toxic metals than leachates, indicating the possibility of using lagoon system for the purification of landfill leachates, especially for organic matter and heavy metal sedimentation. However, the ecotoxicity tests demonstrated that leachates are still a significant source of toxicity for terrestrial and benthic organisms. Therefore, landfill leachates should not be discarded into the environment (soil or surface water) without prior treatment. Interest in the use of macrophytes in lagoon system is growing and toxic metal retention in lagoon basin receiving systems needs to be fully investigated in the future. This study presents useful tools for evaluating landfill leachate quality and risk in lagoon systems which can be applied to similar environmental compartments.

  1. Damage evolution in GLARE fibre-metal laminate under repeated low-velocity impact tests

    Science.gov (United States)

    Morinière, Freddy; Alderliesten, René; Tooski, Mehdi; Benedictus, Rinze

    2012-12-01

    An experimental study was performed on the repeated low-velocity impact behaviour of GLARE. Damage evolution in the material constituents was characterised with successive number of impacts. Records were correlated with visual inspection, ultrasound C-scan and chemical etching. The stiffness of the plate varied when cumulating the number of impacts. Damage accumulation was limited thanks to the synthesis of unidirectional composite and metal. The glass/epoxy plies with high elastic tensile strength could withstand several impacts before perforation despite delamination growth in the vicinity of the impacted area. The damage tolerant aluminium layers prevented the penetration of the projectile and avoided the expansion of delamination. This efficient mechanism preserved the structural integrity of GLARE until first aluminium cracking at the non-impacted side. Among the different failure modes, plate deformation absorbed most of the impact energy. The findings will support the development of a generic quasi-static analytical model and numerical methods.

  2. Comparison of feeding strategies in acute toxicity tests of crude oil and commercial bioremediation agents

    Energy Technology Data Exchange (ETDEWEB)

    Cavender, R.C.; Cherry, D.S.; Yeager, M.M. [Virginia Polytechnic Inst. and State Univ., Blacksburg, VA (United States). Biology Dept.; Bidwell, J.R. [Univ. of South Australia, Adelaide (Australia). School of Pharmacy and Medical Sciences

    1995-12-31

    Proposed modifications to the National Oil and Hazardous Substance Pollution Contingency Plan have prompted examinations of the methodology used in toxicity testing of the water soluble fraction (WSF) of oil, commercial bioremediation agents (CBA), and a combination of the two. The organisms currently used in acute (96 hr) testing of these agents are the inland silverside, Menidia beryllina, and an estuarine mysid, Mysidopsis bahia. The mysid is a carnivorous species that must be fed during a test in order to prevent predation within the test chambers. Currently proposed methodology for silverside testing also includes feeding. The high oxygen demand of CBAs and the WSF of oil causes dissolved oxygen to be a factor in toxicity. This effect can be intensified by the addition of brine shrimp (Artemia sp.) to the test chambers. The purpose of this study was to compare the toxicity of CBAs in combination with the WSF of oil to silversides with and without the addition of food. Tests were conducted using both 24-hour and 14-day spinning times for the CBA/WSF mixture. With the 24-hour spinning time, LC50 values from each day of the 4-day test were consistently lower in the Artemia fed test (47.8--22.6%) as compared to the unfed test (72.1--43.0%). A similar trend was seen in the 24 and 48 hour LC50`s in the 14-day spinning time. Overall, low dissolved oxygen was found to be most relevant at the highest CBA/WSF concentrations where D.O. dropped below 2 mg/l in Artemia fed tests.

  3. Toxicity of uranium, molybdenum, nickel, and arsenic to Hyalella azteca and Chironomus dilutus in water-only and spiked-sediment toxicity tests.

    Science.gov (United States)

    Liber, Karsten; Doig, Lorne E; White-Sobey, Suzanne L

    2011-07-01

    A series of laboratory spiked-sediment toxicity tests with the amphipod Hyalella azteca and the midge Chironomus dilutus were undertaken to determine acute and chronic toxicity thresholds for uranium (U), molybdenum (Mo), nickel (Ni), and arsenic (As) based on both whole-sediment (total) and pore water exposure concentrations. Water-only toxicity data were also generated from separate experiments to determine the toxicities of these metals/metalloids under our test conditions and to help evaluate the hypothesis that pore water metal concentrations are better correlated with sediment toxicity to benthic organisms than whole-sediment metal concentrations. The relative toxicity of the four elements tested differed depending on which test species was used and whether whole-sediment or pore water metal concentrations were correlated with effects. Based on measured whole-sediment concentrations, Ni and As were the two most acutely toxic elements to H. azteca with 10-d LC50s of 521 and 532 mg/kg d.w., respectively. Measured pore water concentrations indicated that U and Ni were the two most acutely toxic elements, with 10-d LC50s to H. azteca of 2.15 and 2.05 mg/L, respectively. Based on pore water metal concentrations, the no-observed-effect concentrations (NOECs) for growth were (H. azteca and C. dilutus, respectively) 0.67 and 0.21 mg/L for U, azteca and C. dilutus, respectively) 2.99 and 0.48 mg/L for U, 0.37 and 2.33 mg/L for Ni, and 58.99 and 0.42 mg/L for As. For U and Ni, results from 96-h water-only acute toxicity tests correlated well with pore water metal concentrations in acutely toxic metal-spiked sediment. This was not true for As where metalloid concentrations in overlying water (diffusion from sediment) may have contributed to toxicity. The lowest whole-sediment LOEC reported here for As was 6.6- and 4-fold higher than the Canadian Council of Ministers of the Environment interim sediment quality guideline and the Canadian Nuclear Safety Commission (CNSC

  4. Altering Work to Rest Ratios Differentially Influences Fatigue Indices During Repeated Sprint Ability Testing.

    Science.gov (United States)

    La Monica, Michael B; Fukuda, David H; Beyer, Kyle S; Hoffman, Mattan W; Miramonti, Amelia A; Riffe, Josh J; Baker, Kayla M; Fragala, Maren S; Hoffman, Jay R; Stout, Jeffrey R

    2016-02-01

    This study examined the influence of recovery time on fatigue indices, performance (total work [TW], peak power [PP], and mean power [MP]), and oxygen consumption during repeated sprint ability (RSA) on a cycle ergometer. Eight recreationally-trained men performed 3 RSA protocols consisting of 10 × 6 s sprints with 12 s, 18 s, and 24 s rest intervals between each sprint. Fatigue indices were determined as percent decrement (%Dec) and rate of decline using either a log transform method or standard slope approach for TW, PP, and MP during respective RSA protocols. The maximal VO2 value in response to given sprint intervals and the minimal VO2 value in response to given rest periods (VO2 work and VO2 rest, respectively) were recorded. A repeated measures analysis of variance was used to analyze all variables. Average VO2 work was not different among rest interval trials. Average VO2 rest with 12 s rest was greater than 18 s and 24 s (2.16 ± 0.17 L · min(-1), 1.91 ± 0.18 L · min(-1), 1.72 ± 0.15 L · min(-1), respectively), while 18 s was greater than 24 s. Average TW and MP were greater with 24 s rest than 12 s (4,604.44 ± 915.98 J vs. 4,305.46 ± 727.17 J, respectively), with no differences between RSA protocols for PP. No differences in %Dec were observed. Both methods of calculating rates of decline per sprint for PP and TW were greater during 12 s than 18 s or 24 s. Since changes were only noted between the 12 s and 24 s protocols, a 6 s differential in rest intervals may not be enough to elicit alterations in TW, PP, MP, or %Dec in RSA performance. Rate of decline may be a more sensitive measure of fatigue than %Dec.

  5. Toxicity testing and chemical analyses of recycled fibre-based paper for food contact

    DEFF Research Database (Denmark)

    Binderup, Mona-Lise; Pedersen, Gitte Alsing; Vinggaard, Anne

    2002-01-01

    Food-contact materials, including paper, have to comply with a basic set of criteria concerning safety. This means that paper for food contact should not give rise to migration of components, which can endanger human health. The objectives of this pilot study were, first, to compare paper...... of different qualities as food-contact materials and to Perform a preliminary evaluation of their suitability from a safety point of view, and, second, to evaluate the use of different in vitro toxicity tests for screening of paper and board. Paper produced from three different categories of recycled fibres (B......-D) and a raw material produced from virgin fibres (A) were obtained from industry, and extracts were examined by chemical analyses and diverse in vitro toxicity test systems. The products tested were either based on different raw materials or different treatments were applied. Paper category B was made from 40...

  6. Application of the tukey trend test procedure to assess developmental and reproductive toxicity. I. Measurement data.

    Science.gov (United States)

    Antonello, J M; Clark, R L; Heyse, J F

    1993-07-01

    Developmental and reproductive (DAR) toxicity studies typically include a series of increasing doses of a compound and a zero dose control. Given this framework, Tukey et al. (Biometrics, 41, 295-301, 1985) proposed a procedure (referred to as either the Tukey trend or TCH test procedure) for detecting a nonzero trend in response to increasing doses of the test compound. The procedure considers three candidate dosage scalings to ensure high power against relatively common dose-response patterns and appreciable power against most reasonable patterns. For toxicologic effects with near monotonic dose-response patterns, simulation studies have shown the TCH test to be overall more powerful than pairwise comparison procedures. The TCH test can be applied sequentially, eliminating the highest dose each time a statistically significant trend is observed, until a no-statistical-significance-of-trend dose is reached. This is the highest dose through which there is no statistically trustworthy evidence of the compound's impact on the response. Since DAR toxicity usually exhibits a progressive (monotonic) dose-response, we advocate routine use of Tukey's trend test for the evaluation of treatment effects in these studies. In this article, we discuss the procedure in detail and apply it to fetal body weight, a continuous measurement variable, from a developmental toxicity study.

  7. Measurement and reduction of porewater ammonia in 10-day sediment toxicity tests with marine amphipods

    Energy Technology Data Exchange (ETDEWEB)

    Kohn, N.P.; Karls, R.K.; Barrows, M.E. [Battelle/Marine Sciences Lab., Sequim, WA (United States)

    1994-12-31

    Ammonia is recognized as a potential contributor to amphipod toxicity in sediment bioassays, such as those required for dredged material testing. Measurement of ammonia in sediment porewater prior to testing and monitoring of ammonia during testing have not been routinely performed. The U.S. Environmental Protection Agency (EPA) and U.S. Army Corps of Engineers (USACE) have recently provided guidance for reducing sediment porewater ammonia by aeration and by exchange of overlying water prior to introducing test animals. In this study, two amphipod species, Rhepoxynius abronius and Eohaustorius estuarius, were exposed to eight sediment treatments in 10-day solid-phase static bioassays. Ammonia in sediment porewater was measured prior to testing; treatments with > 70 mg/L total ammonia were manipulated to reduce porewater ammonia in the test chambers to {<=}30 mg/L, following procedures in a memorandum by EPA and USACE. Porewater ammonia was also measured {approximately}24 h after test set up (when animals would normally be added), each day of manipulation before animals were added, and also on Days 5 and 9 for the E. estuarius test. The treatment with the highest porewater ammonia concentration was tested with and without manipulation. Reduction of porewater ammonia required up to 2 days. Toxicity was reduced in the manipulated sediments, but was statistically significant relative to control and reference treatments.

  8. Toxicity Testing of Restorative Dental Materials Using Brine Shrimp Larvae (Artemia salina

    Directory of Open Access Journals (Sweden)

    Manar M. Milhem

    2008-08-01

    Full Text Available This study investigated the effect of extracts of different composites, glass ionomer cement (GICs and compomers on the viability of brine shrimp larvae. Ethanolic extracts of four dental composites (Z-100; Solitaire 2; Filtek P60 and Synergy, a conventional GIC (Ketac-Fil, a resin-modified glass ionomer cement (Vitremer, two compomers (F2000; Dyract AP, and a flowable compomer (Dyract Flow were prepared from each material. Following evaporation of the ethanol, the extracts were resuspended in distilled water, which was then used to test the effects on the viability of brine shrimp larvae. For the composites, the extract of Synergy was the least toxic (88% viability followed by the extracts of Solitaire 2, Z100 and P60 (75%, 67.5% and 50% viability, respectively. One-way ANOVA revealed highly significant differences between the resin composite materials (p<0.001. Follow-up comparison between the composite groups by Tukey's pairwise multiple-comparison test (α =0.05 showed that the extract of Synergy was significantly less toxic than the extracts of all the other materials except that of Solitaire 2. The compomers showed 100% lethality, while the percentage of viable larvae for the extracts of Ketac-Fil, and Vitremer were 32.3%, and 37.0%, respectively. One-way ANOVA revealed highly significant differences between the groups of materials (p<0.001. Follow-up comparison between the groups by Tukey's test (α = 0.05 showed that the toxic effect of the extracts of the compomers were significantly greater than that of Ketac-Fil, and Vitremer. The differences in the toxic effects of Vitremer and Ketac-Fil were not statistically significant. In conclusion, the toxicity of composite materials varied according to their chemical composition. Compomers were the most lethal materials to brine shrimp larvae followed by GICs and then composites.

  9. Cardiopulmonary exercise testing early after stroke using feedback-controlled robotics-assisted treadmill exercise: test-retest reliability and repeatability.

    Science.gov (United States)

    Stoller, Oliver; de Bruin, Eling D; Schindelholz, Matthias; Schuster-Amft, Corina; de Bie, Rob A; Hunt, Kenneth J

    2014-10-11

    Exercise capacity is seriously reduced after stroke. While cardiopulmonary assessment and intervention strategies have been validated for the mildly and moderately impaired populations post-stroke, there is a lack of effective concepts for stroke survivors suffering from severe motor limitations. This study investigated the test-retest reliability and repeatability of cardiopulmonary exercise testing (CPET) using feedback-controlled robotics-assisted treadmill exercise (FC-RATE) in severely motor impaired individuals early after stroke. 20 subjects (age 44-84 years, stroke) with severe motor limitations (Functional Ambulatory Classification 0-2) were selected for consecutive constant load testing (CLT) and incremental exercise testing (IET) within a powered exoskeleton, synchronised with a treadmill and a body weight support system. A manual human-in-the-loop feedback system was used to guide individual work rate levels. Outcome variables focussed on standard cardiopulmonary performance parameters. Relative and absolute test-retest reliability were assessed by intraclass correlation coefficients (ICC), standard error of the measurement (SEM), and minimal detectable change (MDC). Mean difference, limits of agreement, and coefficient of variation (CoV) were estimated to assess repeatability. Peak performance parameters during IET yielded good to excellent relative reliability: absolute peak oxygen uptake (ICC =0.82), relative peak oxygen uptake (ICC =0.72), peak work rate (ICC =0.91), peak heart rate (ICC =0.80), absolute gas exchange threshold (ICC =0.91), relative gas exchange threshold (ICC =0.88), oxygen cost of work (ICC =0.87), oxygen pulse at peak oxygen uptake (ICC =0.92), ventilation rate versus carbon dioxide output slope (ICC =0.78). For these variables, SEM was 4-13%, MDC 12-36%, and CoV 0.10-0.36. CLT revealed high mean differences and insufficient test-retest reliability for all variables studied. This study presents first evidence on

  10. Optimizing the performance of Hyalella azteca in chronic toxicity tests: Results of feeding studies with various foods and feeding regimes

    Science.gov (United States)

    The freshwater amphipod Hyalella azteca is a common organism used for sediment toxicity testing in the United States and elsewhere. Standard methods for 10-d and 42-d toxicity tests with H. azteca were last revised and published by USEPA/ASTM in 2000. Under the methods in the man...

  11. Optimizing the performance of Hyalella azteca in chronic toxicity tests: Results of feeding studies with various foods and feeding regimes

    Science.gov (United States)

    The freshwater amphipod Hyalella azteca is a common organism used for sediment toxicity testing in the United States and elsewhere. Standard methods for 10-d and 42-d toxicity tests with H. azteca were last revised and published by USEPA/ASTM in 2000. Under the methods in the man...

  12. Interpreting Variations in Groundwater Flows from Repeated Distributed Thermal Perturbation Tests.

    Science.gov (United States)

    Hausner, Mark B; Kryder, Levi; Klenke, John; Reinke, Richard; Tyler, Scott W

    2016-07-01

    To better understand the groundwater resources of southern Nye County, Nevada, a multipart distributed thermal perturbation sensing (DTPS) test was performed on a complex of three wells. These wells penetrate an alluvial aquifer that drains the Nevada National Security Site, and characterizing the hydraulic properties and flow paths of the regional groundwater flow system has proven very difficult. The well complex comprised one pumping well and two observation wells, both located 18 m from the pumping well. Using fiber-optic cables and line heaters, DTPS tests were performed under both stressed and unstressed conditions. Each test injects heat into the water column over a period of one to two days, and observes the rising temperature during heat injection and falling temperatures after heating ceases. Aquifer thermal properties are inferred from temperature patterns in the cased section of the wells, and fluxes through the 30-m screened section are estimated based on a model that incorporates conductive and advective heat fluxes. Vertical variations in flux are examined on a scale of tens of cm. The actively flowing zones of the aquifer change between the stressed and unstressed test, and anisotropy in the aquifer permeability is apparent from the changing fluxes between tests. The fluxes inferred from the DTPS tests are compared to solute tracer tests previously performed on the same site. The DTPS-based fluxes are consistent with the fastest solute transport observed in the tracer test, but appear to overestimate the mean flux through the system.

  13. Repeated open application test with methyldibromo glutaronitrile, a multicentre study within the EECDRG

    DEFF Research Database (Denmark)

    Gruvberger, B; Andersen, Klaus Ejner; Brandão, F M

    2005-01-01

    Contact allergy to and allergic contact dermatitis from methyldibromo glutaronitrile (MDBGN) have frequently been reported. This study was initiated to help determine the optimal patch test preparation for MDBGN. In 51 patients with a doubtful or a positive patch test reaction to at least 1 of 4 ...

  14. Late presenters, repeated testing, and missed opportunities in a Danish nationwide HIV cohort

    DEFF Research Database (Denmark)

    Helleberg, Marie; Engsig, Frederik N; Kronborg, Gitte

    2012-01-01

    . After 2002 the proportion of men who have sex with men with a negative HIV test prior to diagnosis increased (incidence rate ratio (IRR) 1.3, 95% CI 1.1?1.6), coinciding with a reduction in IR of presentation with advanced HIV. Mortality rates were increased the first 2 y following presentation...... to guidelines for targeted HIV testing....

  15. Modified whole effluent toxicity test to assess and decouple wastewater effects from environmental gradients.

    Directory of Open Access Journals (Sweden)

    Sebastián Sauco

    Full Text Available Environmental gradients and wastewater discharges produce aggregated effects on marine populations, obscuring the detection of human impact. Classical assessment methods do not include environmental effects in toxicity tests designs, which could lead to incorrect conclusions. We proposed a modified Whole Effluent Toxicity test (mWET that includes environmental gradients in addition to effluent dilutions, together with the application of Generalized Linear Mixed Models (GLMM to assess and decouple those effects. We tested this approach, analyzing the lethal effects of wastewater on a marine sandy beach bivalve affected by an artificial canal freshwater discharge used for rice crops irrigation. To this end, we compared bivalve mortality between canal water dilutions (CWd and salinity controls (SC: without canal water. CWd were prepared by diluting the water effluent (sampled during the pesticide application period with artificial marine water. The salinity gradient was included in the design by achieving the same final salinities in both CWd and SC, allowing us to account for the effects of salinity by including this variable as a random factor in the GLMM. Our approach detected significantly higher mortalities in CWd, indicating potential toxic effects of the effluent discharge. mWET represents an improvement over the internationally standardized WET tests, since it considers environmental variability and uses appropriate statistical analyses.

  16. Is repeated-sprint ability of soccer players predictable from field-based or laboratory physiological tests?

    Science.gov (United States)

    Psotta, R; Bunc, V; Hendl, J; Tenney, D; Heller, J

    2011-03-01

    The aim of this study was to investigate multiple regression models with prediction equations that would enable a valid estimate of running repeated-sprint ability (RSA) in soccer players from the variables measured in field and laboratory physiological tests. Adolescent soccer players (N=33) performed five field performance tests and two laboratory tests for assessment of muscle strength of legs, sprint ability, anaerobic power and capacity, aerobic power and capacity, and running economy. These tests served as potential predictors of RSA. RSA was assessed by a intermittent anaerobic running test (IAnRT) consisted of ten 20 m sprints. Multiple regression analysis revealed that the mean speed in the 20 m sprint test and the 2 km endurance running test accounted for 89% of total variation in the mean running speed in the IAnRT (VIAnRT) as the indicator of capacity for multiple sprint work (R2=0.89, SEM=0.09 m.s-1). Using the variables from the laboratory tests, the best prediction of the VIAnRT was obtained from the running speed at the ventilatory threshold level (VVT) and anaerobic power (Pmax.kg-1) (R2=0.49, SEM=0.21 m.s-1). Performance in the multiple-sprint exercise as an indicator of RSA can be estimated by the regression equation with two predictors - mean speed in the 20 m sprint and 2 km running test with an error of 4%.

  17. Testing the Deployment Repeatability of a Precision Deployable Boom Prototype for the Proposed SWOT Karin Instrument

    Science.gov (United States)

    Agnes, Gregory S.; Waldman, Jeff; Hughes, Richard; Peterson, Lee D.

    2015-01-01

    NASA's proposed Surface Water Ocean Topography (SWOT) mission, scheduled to launch in 2020, would provide critical information about Earth's oceans, ocean circulation, fresh water storage, and river discharge. The mission concept calls for a dual-antenna Ka-band radar interferometer instrument, known as KaRIn, that would map the height of water globally along two 50 km wide swaths. The KaRIn antennas, which would be separated by 10 meters on either side of the spacecraft, would need to be precisely deployable in order to meet demanding pointing requirements. Consequently, an effort was undertaken to design build and prototype a precision deployable Mast for the KaRIn instrument. Each mast was 4.5-m long with a required dilitation stability of 2.5 microns over 3 minutes. It required a minimum first mode of 7 Hz. Deployment repeatability was less than +/- 7 arcsec in all three rotation directions. Overall mass could not exceed 41.5 Kg including any actuators and thermal blanketing. This set of requirements meant the boom had to be three times lighter and two orders of magnitude more precise than the existing state of the art for deployable booms.

  18. 氟氯氰菊酯亚急性吸入毒性实验研究%Inhalation toxicity of cyfluthrin for 28-day repeated dose in rats

    Institute of Scientific and Technical Information of China (English)

    秦珩; 乔善磊; 顾军; 钟义红; 杨洪宝; 王玉邦; 施爱民

    2012-01-01

    Objective To determine the inhalation toxicity and find the non -observed adverse effect level (NOAEL) of cyfluthrin for a 28-day repeated dose in rats. Methods Clean-grade SD rats were randomly divided into 5 groups with 5 females and 5 males in each. The animals inhaled DMSO or cyfluthrin at the concentration of 0, 7. 81 , 9. 05 and 18. 98 mg/m for 4 weeks (6 h/d, 5 d/w). At the end of inhalation , all the animals were kindly sacrificed. Their organs were collected for histopathological examination . Blood samples were collected for analysis of complete blood count , biochemistry and coagulation. Results The animals in 18. 98 mg/m3 group were found scratching repeatedly around the mouth, listless, fidgeting, trembling, discharging blood around the mouth and nose . However, symptoms in females were less serious than in males. Furthermore , the body mass , feed efficiency , weight of kidney of animals in this dose male group were found decreased compared with the control group . Biochemistry detection revealed that serum AST was elevated markedly in both genders of 18. 98 mg/m3 group and in males of 9. 05 mg/m3 group. No obvious abnormity was found in 7.81 mg/m3 group or control group. Conclusion Based on the results above, the non-observed adverse effect level (NOAEL) of cyfluthrin in SD rats is 7. 81 mg/m3 for 28 d repeated inhalation in this study.%目的 观察氟氯氰菊酯染毒大鼠亚急性吸入毒性.方法 7周龄清洁级SD大鼠随机分成5组,每组雌雄各5只,分别吸入氟氯氰菊酯0,7.81,9.05,18.98 mg/m3及溶剂二甲亚砜,每天6 h,每周5 d,共28 d.实验结束时取血液做常规生化指标、血细胞指标、血凝学指标检测.取心、肝、脾等8种主要脏器称重并做病理组织学检查.结果 18.98 mg/m3组动物在染毒中呈现反复抓挠口周、烦躁不安、鼻有血性分泌物、颤抖,染毒结束后呈现萎靡、蜂腰、四肢无力的体征.雌性动物的毒性表现较雄性低.与溶剂对照组相

  19. The 2.5-minute loaded repeated jump test: evaluating anaerobic capacity in alpine ski racers with loaded countermovement jumps.

    Science.gov (United States)

    Patterson, Carson; Raschner, Christian; Platzer, Hans-Peter

    2014-09-01

    The purposes of this study were to test the reproducibility of the 2.5-minute loaded repeated jump test (LRJT) and to test the effectiveness of general preparation period (GPP) training on anaerobic fitness of elite alpine ski racers with the LRJT. Thirteen male volunteers completed 2 LRJTs to examine reliability. Nine male Austrian elite junior racers were tested in June and October 2009. The LRJT consisted of 60 loaded countermovement jumps (LCMJs) with a loaded barbell equivalent to 40% bodyweight. Before the LRJT, the power (P) of a single LCMJ was determined. Power was calculated from ground reaction forces. The mean P was calculated for the complete test and for each 30-second interval. The interclass correlation coefficients (between 0.88 and 0.99) for main variables of the LRJT demonstrated a high reliability. A repeated-measures analysis of variance indicated that anaerobic capacity was significantly higher in October (p ≤ 0.05). The ski racers' single LCMJ P increased from 37.0 ± 1.2 W·kg to 39.0 ± 1.4 W·kg. The mean P of the total test improved from 33.6 ± 1.2 W·kg to 35.8 ± 1.3 W·kg, but relative effect of fatigue did not change. The GPP training improved the athletes' ability to produce and maintain muscular power. The LRJT is a reliable anaerobic test suitable for all alpine ski racing events because the 60 jumps simulate the approximate number of gates in slalom and giant slalom races and the 2.5 minutes is equivalent to the duration of the longest downhill race.

  20. Handbook of acute toxicity of chemicals to fish and aquatic invertebrates : summaries of toxicity tests conducted at Columbia National Fisheries Research Laboratory, 1965-78

    Science.gov (United States)

    Johnson, W. Waynon; Finley, Mack T.

    1980-01-01

    Acute toxicity is a major subject of research at Columbia National Fisheries Research Laboratory for evaluating the impact of toxic chemicals on fishery resources. The Laboratory has played a leading role in developing research technology for toxicity testing and data interpretation. In 1965-78, more than 400 chemicals were tested against a variety of invertebrates and fish species representative of both cold- and warm-water climates. The use of acute toxicity tests for assessing the potential hazard of chemical contaminants to aquatic organisms is well documented (Boyd 1957; Henderson et al. 1960; Sanders and Cope 1966; Macek and McAllister 1970). Static acute toxicity tests provide rapid and (within limits) reproducible concentration-response curves for estimating toxic effects of chemicals on aquatic organisms. These tests provide a database for determining relative toxicity of a large number of chemicals to a variety of species and for estimating acute effects of chemical spills on natural aquatic systems; they also assist in determining priority and design of additional toxicity studies. Acute toxicity tests usually provide estimates of the exposure concentration causing 50% mortality (LC50) to test organisms during a specified period of time. For certain invertebrates, the effective concentration is based on immobilization, or some other identifiable endpoint, rather than on lethality. The application of the LC50 has gained acceptance among toxicologists and is generally the most highly rated test for assessing potential adverse effects of chemical contaminants to aquatic life (Brungs and Mount 1978; American Institute for Biological Sciences 1978a). The literature contains numerous papers dealing with the acute toxicity of chemicals to freshwater organisms. However, there is a tremendous need for a concise compendium of toxicity data covering a large variety of chemicals and test species. This Handbook is a compilation of a large volume of acute toxicity

  1. The effects of repeat testing, malingering, and traumatic brain injury on visuospatial memory span

    Directory of Open Access Journals (Sweden)

    David L Woods

    2016-01-01

    Full Text Available Spatial span tests such as the Corsi Block Test (CBT and the spatial span test of the Wechsler Memory Scale are widely used to assess deficits in spatial working memory. We conducted three experiments to evaluate the test-retest reliability and clinical sensitivity of a new computerized spatial span test (C-SST that incorporates psychophysical methods to improve the precision of spatial span measurement. In Experiment 1, we analyzed C-SST test-retest reliability in 49 participants who underwent three test sessions at weekly intervals. Intraclass correlation coefficients (ICC were higher for a psychophysically derived mean span (MnS metric (0.83 than for the maximal span and total correct metrics used in traditional spatial-span tests. Response times (ReTs also showed high ICCs (0.93 that correlated negatively with MnS scores and correlated positively with response-time latencies from other tests of processing speed. Learning effects were insignificant. Experiment 2 examined the performance of Experiment 1 participants when instructed to feign symptoms of traumatic brain injury: 57% showed abnormal MnS z-scores. A MnS z-score cutoff of 3.0 correctly classified 36% of simulated malingerers and 91% of the subgroup of 11 control participants with abnormal spans. Malingerers also made more substitution errors than control participants with abnormal spans (sensitivity = 43%, specificity = 91%. In addition, malingerers showed no evidence of ReT slowing, in contrast to significant abnormalities seen on other malingered tests of processing speed. As a result, differences between ReT z-scores and z-scores on other processing speed tests showed very high sensitivity and specificity in distinguishing malingering and control participants with either normal or abnormal spans. Experiment 3 examined C-SST performance in a group of patients with predominantly mild traumatic brain injury (TBI: neither MnS nor ReT z-scores showed significant group

  2. Does behavioral response to novelty influence paw withdrawal latencies in repeated Hargreaves test?

    OpenAIRE

    Tvrdeić, Ante; Kočevski, Dragana

    2008-01-01

    Background and Purpose: Only recently, we have reported that single retesting session significantly decreases rat paw withdrawal latencies (PWL) in Hargreaves tests.We wondered, whether decrease in PWL values obtained during reexposure toHargreaves testmight be associated with reaction to the new environment. Therefore, we investigated PWL together with the open field behavior in an enclosure of the Hargreaves test device during the period of 3 subsequent days. Materials and Methods: Ten...

  3. The Hidden Burden of Outpatient Repeat PSA Testing in a Prospective Cohort

    LENUS (Irish Health Repository)

    Browne, E

    2017-05-01

    PSA testing is widespread throughout Europe for diagnostic purposes and follow up. We performed a prospective outpatient cohort study of 250 men (2013-2015) in two hospital sites. Included were those men being followed up by urology with PSA blood testing. First appointments and those men in whom non-PSA tests were ordered by urology were excluded. The median age was 67.2yrs (46-88). Eighty-one point two percent of samples had a combination of 21 different serology tests at an added cost of >€18,000. Abnormal serology resulted in 53 referrals. Twenty-six-six percentof correspondence referenced abnormal serology other than PSA. Follow up of non-PSA test results poses a challenge in an outpatient setting with failure to appropriately follow-up on abnormal results, increased costs, and medico-legal implications. There is currently no Irish legislature in place to safeguard hospital physicians. This study quantifies the levels of expenditure, resources and risk associated with ambulant PSA testing.

  4. Is There a Space-Based Technology Solution to Problems with Preclinical Drug Toxicity Testing?

    OpenAIRE

    Hammond, Timothy; Allen, Patricia; Birdsall, Holly

    2016-01-01

    Even the finest state-of-the art preclinical drug testing, usually in primary hepatocytes, remains an imperfect science. Drugs continue to be withdrawn from the market due to unforeseen toxicity, side effects, and drug interactions. The space program may be able to provide a lifeline. Best known for rockets, space shuttles, astronauts and engineering, the space program has also delivered some serious medical science. Optimized suspension culture in NASA’s specialized suspension culture device...

  5. Statistical studies of animal response data from USF toxicity screening test method

    Science.gov (United States)

    Hilado, C. J.; Machado, A. M.

    1978-01-01

    Statistical examination of animal response data obtained using Procedure B of the USF toxicity screening test method indicates that the data deviate only slightly from a normal or Gaussian distribution. This slight departure from normality is not expected to invalidate conclusions based on theoretical statistics. Comparison of times to staggering, convulsions, collapse, and death as endpoints shows that time to death appears to be the most reliable endpoint because it offers the lowest probability of missed observations and premature judgements.

  6. Methods used for testing toxicity of industrial chemicals and the need of their international unification.

    Science.gov (United States)

    Vyskocil, A; Tusl, M

    1989-01-01

    The work presented here provides a demonstration of approaches in testing chemical substances in the world, comparison of various guidelines, shows differences in them with the aim to unify them as much as possible and thus to achieve their international comparability. First chapter includes a comparison of American and European approaches to Good Laboratory Practice (GLP). Some parts of American GLP seem to be specific for the USA only and thus they are not suitable for application on the international level where countries having different systems of government and various levels of their economy would have to observe them. GLP published in OECD and ECETOC guidelines seem to be most beneficial for needs of socialist countries. OECD, EEC, EPA/FIFRA, EPA/TSCA, Japan/MAFF and UK/HSC guidelines are compared in subsequent chapters and recommendations given by ECETOC and the authors of this work for unification of the guidelines are presented as well. Some parts of OECD guidelines are specified in detail there especially those which are most suitable for CMEA countries. Differences or supplements contained in CMEA recommendations are presented in the end of each chapter. Acute, subchronic and chronic toxicity tests were compared as well as carcinogenicity, combined carcinogenicity/chronic toxicity studies and reproductive toxicity tests.

  7. SORPTION PERFORMANCE OF QUERCUS CERRIS CORK WITH POLYCYCLIC AROMATIC HYDROCARBONS AND TOXICITY TESTING

    Directory of Open Access Journals (Sweden)

    M. Àngels Olivella

    2011-06-01

    Full Text Available Quercus cerris is an important oak species extended in large areas of Eastern Europe and Minor Asia that has a thick bark which is not utilized at all. The sorption performance of cork from Quercus cerris bark with four polycyclic aromatic hydrocarbons (PAHs (acenaphthene, fluorene, phenanthrene, and anthracene was investigated. Quercus cerris cork was characterized for elemental analysis, acidic groups, and summative chemical composition, and the results were compared with Quercus suber cork. A Microtox® test was carried out to test for the release of any toxic compounds into the solution. All isotherms fit the Freundlich model and displayed linear n values. Quercus cerris exhibited a high efficiency for sorption of PAHs for the studied concentrations (5 to 50 µg/L with 80-96% removal, while the desorption isotherms showed a very low release of the adsorbed PAHs (<2%. In relation to Quercus suber cork, KF values of Quercus cerris cork are about three times lower. The quantity of Quercus cerris cork required to reduce water pollution by PAHs was estimated to be less than twice the quantity of other adsorbents such as aspen wood and leonardite. Toxicity tests indicated that non-toxic compounds were released into the solution by the Quercus cerris and Quercus suber cork samples. Overall the results indicate the potential use of Quercus cerris cork and of Quercus suber cork as effective and economical biosorbents for the treatment of PAH-contaminated waters.

  8. Estuarine sediment acute toxicity testing with the European amphipod Corophium multisetosum Stock, 1952.

    Science.gov (United States)

    Ré, Ana; Freitas, Rosa; Sampaio, Leandro; Rodrigues, Ana Maria; Quintino, Victor

    2009-09-01

    This study assessed the use of the European amphipod Corophium multisetosum Stock [Stock, J.H., 1952. Some notes on the taxonomy, the distribution and the ecology of four species of the genus Corophium (Crustacea, Malacostraca). Beaufortia 21, 1-10] in estuarine sediment acute toxicity testing. The sensitivity of adults to the reference toxicant CdCl(2) was determined in water-only 96 h exposures in salinity 2. LC(50) values ranged from 0.33mgCd(2+)L(-1) at 22 degrees C to 0.57mgCd(2+)L(-1) at 15 degrees C. Adult survival was studied in control sediment with water salinity from 0 to 36 and with fine particles content (Tagus Estuary, western Portugal. A major flood event in winter 2000-2001 induced detectable alterations in sediment baseline descriptors (grain-size, redox potential and total volatile solids), organic contaminants (PAHs, PCBs, DDT metabolites and gamma-HCH) and the macrofauna benthic community. Mortality of the amphipod diminished significantly from the before to the after flood period, in close agreement with diminishing sediment contamination and increasing benthic fauna diversity, in the same time period. C. multisetosum is suitable to conduct acute sediment toxicity tests and presents good potential for the development of a full life-cycle sediment test, due to its amenability to laboratory culture and high survival in the control sediment.

  9. Toxicity minimization of pipelines hydrostatic tests fluids, stage I: laboratory essays

    Energy Technology Data Exchange (ETDEWEB)

    Lacerda, Jorge A.S.; Penna, Monica de O.; Portela, Daniele B.; Christino, Fernando P.; Silva, Joao L.B. da; Geraldo, Lucia M.L. [Petroleo do Brasileiro S.A. (PETROBRAS), Rio de Janeiro, RJ (Brazil); Mota, Vanessa V.C. [Fundacao Gorceix, Ouro Preto, MG (Brazil); Cravo Junior, Walter [Pontificia Univ. Catolica do Rio de Janeiro (PUC-Rio), RJ (Brazil)

    2009-07-01

    This paper presents the results of the laboratory essays stage of the project for toxicity minimization of pipelines hydrostatic tests fluids. The hydrostatic-hibernation fluid composition most used by PETROBRAS in offshore operations is seawater added with sodium bis sulfite, fluorescein, alquildimetilbenzilamonium chloride, and tetrakis-hydroxymethyl-phosphonium sulfate (THPS). In order to reduce the toxicity of the fluid used in hydrostatic tests, the use of lesser concentrations of THPS was attempted with UV radiation application as a disinfection technique prior to the adding of the fluid's components. The compositions were evaluated in different conditions of temperature use of UV radiation or not and oxygen scavenger adding (presence and absence). The fluids were kept hibernating for 120 days. All the parameters tested after hibernation were compared to fresh from preparation samples (zero time samples). The fluid's characteristics were evaluated by microbiological control and toxicity as well as the THPS residual. Results showed that the UV treatment was more effective in the absence of oxygen scavenger. The temperature acts as a microbial growth control agent, as expected. To large scale operations, a water quality monitoring must be performed previously to any field operations, in order to determinate the best treatment to be used in each case. (author)

  10. Long-term repeatability of the skin prick test is high when supported by history or allergen-sensitivity tests

    DEFF Research Database (Denmark)

    Bodtger, U; Jacobsen, C R; Poulsen, Lars K.

    2003-01-01

    Long-term reproducibility of the skin-prick test (SPT) has been questioned. The aim of the study was to investigate the clinical relevance of SPT changes.......Long-term reproducibility of the skin-prick test (SPT) has been questioned. The aim of the study was to investigate the clinical relevance of SPT changes....

  11. Evaluation of the toxicity of Araribá (Centrolobium tomentosum using brine Shrimp test

    Directory of Open Access Journals (Sweden)

    Roberto Carlos de Sá Silva

    2013-12-01

    Full Text Available Since the dawn of medicine, man has used natural products for the treatment of disease. There has been a recent increase in studies of the therapeutic characteristics plants in popular use in many places of the world. In this context, the species Centrolobium tomentosum, Fabaceae, known popularly as Araribá or Araruva, is used in Brazilian folk medicine as an astringent for wound treatment and bruises due to the large amount of tannins contained in the bark. This work used toxicity tests to assess the biological activity of ethanolic extracts from C. tomentosum with the specific objectives of obtaining concentrated extracts from the bark and wood of this species and determining the total phenols and tannins present in these extracts. We collected araribá samples in order to obtain ethanolic extracts through the percolation process. We then made a qualitative chemical identification of hydrolysable tannins and condensed tannins. We used the Folin-Ciocalteu method for the phenols quantification and the casein precipitation method for the tannins determination. The toxicity of extracts was evaluated using the brine shrimp bioassay (Artemia salina, in which the C. tomentosum bark extract showed moderate toxicity, with estimated LC50 = 416 μg.ml-1, whereas the leaves and wood extracts of this species showed low toxicity with LC50 = 537 μg.ml-1 and 826 μg.ml-1, respectively.

  12. Monitoring the effectiveness of remediation techniques using sediment toxicity tests with the amphipod Eohaustorius estuarius

    Energy Technology Data Exchange (ETDEWEB)

    Doe, K.G.; Jackman, P.M. [Environment Canada, Moncton, NB (Canada); Lee, K. [Department of Fisheries and Oceans Canada, Dartmouth, NS (Canada)

    2002-07-01

    The results of a controlled oil release experiment of weathered crude oil was presented. The released oil was applied to a tidal saltwater marsh at Conrod's Beach, Nova Scotia, Canada. The study included 3 replicate blocks which included 2 unoiled treatments and 4 oiled treatments for each block. One unoiled site had no treatment, the second unoiled site had nutrient addition to examine the effect of nutrients. The oiled treatments included natural attenuation, nutrient addition, nutrient addition with plants, and nutrient addition with a garden aerator to introduce oxygen. A standard lab procedure was used to analyze the sediments to determine the effectiveness of the technique as well as the toxic effects on the survival of the amphipod Eohaustorius estuarius. Test results indicated that the unoiled sites were non-toxic, with a slight decrease in survival in the treatment with nutrient addition. All the oiled sites were very toxic at first, but toxicity decreased gradually with time. Treatment with nutrient addition with a garden aerator proved to be the most complete and fastest detoxification method. 8 refs., 4 tabs., 2 figs.

  13. Major Phytochemical as γ-Sitosterol Disclosing and Toxicity Testing in Lagerstroemia Species

    Science.gov (United States)

    Sirikhansaeng, Prapaparn

    2017-01-01

    Medicinal plants in genus Lagerstroemia were investigated for phytochemical contents by GC-MS and HPLC with ethanol and hexane extracts and their toxicity MTT and comet assay on human peripheral blood mononuclear cells (PBMCs). γ-Sitosterol is the major component found in all species at 14.70–34.44%. All of the extracts, except for L. speciosa ethanol extract, showed high percentages of cell viability. The IC50 value, 0.24 mg/mL, of ethanol L. speciosa extract predicted an LD50 of 811.78 mg/kg, which belongs to WHO Class III of toxic chemicals. However, in-depth toxicity evaluation by the comet assay showed that the four tested species induced significant (p < 0.05) DNA damage in PBMCs. γ-Sitosterol was previously reported to possess antihyperglycemic activity by increasing insulin secretion in response to glucose. Nonetheless, consumers should consider its toxicity, and the amount of consumption should be of concern.

  14. Current strategies to minimize toxicity of oxaliplatin: selection of pharmacogenomic panel tests.

    Science.gov (United States)

    Di Francia, Raffaele; Siesto, Raffaella Stefania; Valente, Daniela; Del Buono, Andrea; Pugliese, Sergio; Cecere, Sabrina; Cavaliere, Carla; Nasti, Guglielmo; Facchini, Gaetano; Berretta, Massimiliano

    2013-11-01

    Oxaliplatin is an anticancer drug routinely used to treat colorectal, gastroesophageal, ovarian, breast, head/neck, and genitourinary cancers. Discontinuation of oxaliplatin treatment is mostly because of peripheral neuropathy, more often than for tumor progression, potentially compromising patient benefit. Several strategies to prevent neurotoxicity have so far been investigated. To overcome this life-threatening side effect, while taking advantage of the antineoplastic activities of oxaliplatin, we describe in detail recent findings on the underlying mechanisms of genetic variants associated with toxicity and resistance to oxaliplatin-based chemotherapy in colorectal cancer. A comprehensive panel of eight polymorphisms, previously validated as significant markers related to oxaliplatin toxicity, is proposed and discussed. In addition, the most common available strategies or methods to prevent/minimize the toxicity were described in detail. Moreover, an early outline evaluation of the genotyping costs and methods was taken in consideration. With the availability of individual pharmacogenomic profiles, the oncologists will have new means to make treatment decisions for their patients that maximize benefit and minimize toxicity. With this purpose in mind, the clinician and lab manager should cooperate to evaluate the advantages and limitations, in terms of costs and applicability, of the most appropriate pharmacogenomic tests for routine incorporation into clinical practice.

  15. Robot-Assisted End-Effector-Based Stair Climbing for Cardiopulmonary Exercise Testing: Feasibility, Reliability, and Repeatability

    Science.gov (United States)

    Stoller, Oliver; Schindelholz, Matthias; Hunt, Kenneth J.

    2016-01-01

    Background Neurological impairments can limit the implementation of conventional cardiopulmonary exercise testing (CPET) and cardiovascular training strategies. A promising approach to provoke cardiovascular stress while facilitating task-specific exercise in people with disabilities is feedback-controlled robot-assisted end-effector-based stair climbing (RASC). The aim of this study was to evaluate the feasibility, reliability, and repeatability of augmented RASC-based CPET in able-bodied subjects, with a view towards future research and applications in neurologically impaired populations. Methods Twenty able-bodied subjects performed a familiarisation session and 2 consecutive incremental CPETs using augmented RASC. Outcome measures focussed on standard cardiopulmonary performance parameters and on accuracy of work rate tracking (RMSEP−root mean square error). Criteria for feasibility were cardiopulmonary responsiveness and technical implementation. Relative and absolute test-retest reliability were assessed by intraclass correlation coefficients (ICC), standard error of the measurement (SEM), and minimal detectable change (MDC). Mean differences, limits of agreement, and coefficients of variation (CoV) were estimated to assess repeatability. Results All criteria for feasibility were achieved. Mean V′O2peak was 106±9% of predicted V′O2max and mean HRpeak was 99±3% of predicted HRmax. 95% of the subjects achieved at least 1 criterion for V′O2max, and the detection of the sub-maximal ventilatory thresholds was successful (ventilatory anaerobic threshold 100%, respiratory compensation point 90% of the subjects). Excellent reliability was found for peak cardiopulmonary outcome measures (ICC ≥ 0.890, SEM ≤ 0.60%, MDC ≤ 1.67%). Repeatability for the primary outcomes was good (CoV ≤ 0.12). Conclusions RASC-based CPET with feedback-guided exercise intensity demonstrated comparable or higher peak cardiopulmonary performance variables relative to

  16. Robot-Assisted End-Effector-Based Stair Climbing for Cardiopulmonary Exercise Testing: Feasibility, Reliability, and Repeatability.

    Directory of Open Access Journals (Sweden)

    Oliver Stoller

    Full Text Available Neurological impairments can limit the implementation of conventional cardiopulmonary exercise testing (CPET and cardiovascular training strategies. A promising approach to provoke cardiovascular stress while facilitating task-specific exercise in people with disabilities is feedback-controlled robot-assisted end-effector-based stair climbing (RASC. The aim of this study was to evaluate the feasibility, reliability, and repeatability of augmented RASC-based CPET in able-bodied subjects, with a view towards future research and applications in neurologically impaired populations.Twenty able-bodied subjects performed a familiarisation session and 2 consecutive incremental CPETs using augmented RASC. Outcome measures focussed on standard cardiopulmonary performance parameters and on accuracy of work rate tracking (RMSEP-root mean square error. Criteria for feasibility were cardiopulmonary responsiveness and technical implementation. Relative and absolute test-retest reliability were assessed by intraclass correlation coefficients (ICC, standard error of the measurement (SEM, and minimal detectable change (MDC. Mean differences, limits of agreement, and coefficients of variation (CoV were estimated to assess repeatability.All criteria for feasibility were achieved. Mean V'O2peak was 106±9% of predicted V'O2max and mean HRpeak was 99±3% of predicted HRmax. 95% of the subjects achieved at least 1 criterion for V'O2max, and the detection of the sub-maximal ventilatory thresholds was successful (ventilatory anaerobic threshold 100%, respiratory compensation point 90% of the subjects. Excellent reliability was found for peak cardiopulmonary outcome measures (ICC ≥ 0.890, SEM ≤ 0.60%, MDC ≤ 1.67%. Repeatability for the primary outcomes was good (CoV ≤ 0.12.RASC-based CPET with feedback-guided exercise intensity demonstrated comparable or higher peak cardiopulmonary performance variables relative to predicted values, achieved the criteria for V'O2

  17. Robot-Assisted End-Effector-Based Stair Climbing for Cardiopulmonary Exercise Testing: Feasibility, Reliability, and Repeatability.

    Science.gov (United States)

    Stoller, Oliver; Schindelholz, Matthias; Hunt, Kenneth J

    2016-01-01

    Neurological impairments can limit the implementation of conventional cardiopulmonary exercise testing (CPET) and cardiovascular training strategies. A promising approach to provoke cardiovascular stress while facilitating task-specific exercise in people with disabilities is feedback-controlled robot-assisted end-effector-based stair climbing (RASC). The aim of this study was to evaluate the feasibility, reliability, and repeatability of augmented RASC-based CPET in able-bodied subjects, with a view towards future research and applications in neurologically impaired populations. Twenty able-bodied subjects performed a familiarisation session and 2 consecutive incremental CPETs using augmented RASC. Outcome measures focussed on standard cardiopulmonary performance parameters and on accuracy of work rate tracking (RMSEP-root mean square error). Criteria for feasibility were cardiopulmonary responsiveness and technical implementation. Relative and absolute test-retest reliability were assessed by intraclass correlation coefficients (ICC), standard error of the measurement (SEM), and minimal detectable change (MDC). Mean differences, limits of agreement, and coefficients of variation (CoV) were estimated to assess repeatability. All criteria for feasibility were achieved. Mean V'O2peak was 106±9% of predicted V'O2max and mean HRpeak was 99±3% of predicted HRmax. 95% of the subjects achieved at least 1 criterion for V'O2max, and the detection of the sub-maximal ventilatory thresholds was successful (ventilatory anaerobic threshold 100%, respiratory compensation point 90% of the subjects). Excellent reliability was found for peak cardiopulmonary outcome measures (ICC ≥ 0.890, SEM ≤ 0.60%, MDC ≤ 1.67%). Repeatability for the primary outcomes was good (CoV ≤ 0.12). RASC-based CPET with feedback-guided exercise intensity demonstrated comparable or higher peak cardiopulmonary performance variables relative to predicted values, achieved the criteria for V'O2max

  18. THE BAFFLED FLASK TEST FOR DISPERSANT EFFECTIVENESS: A ROUND ROBIN EVALUATION OF REPRODUCIBILITY AND REPEATABILITY

    Science.gov (United States)

    After two previous investigations demonstrated that the Baffled Flask Test (BFT) was an effective and reproducible method for screening the effectiveness of dispersant products in the laboratory, the USEPA decided that before the new protocol cold be considered for replacement of...

  19. Reference values and repeatability of the Schirmer tear tests I and II in domesticated, clinically normal dromedary camels (Camelus dromedarius).

    Science.gov (United States)

    Marzok, Mohamed A; Badawy, Adel M; El-Khodery, Sabry A

    2017-05-01

    To determine the normal values and repeatability for Schirmer tear test (STT) in clinically normal dromedary camels and to analyze the influence of the age and gender on these values. Thirty clinically normal dromedary camels of different ages (calves, immature, and mature). Schirmer tear tests I and II were performed using commercial STT strips. Three measurements were obtained from each eye over three consecutive weeks, and the variance of these measurements was determined. Mean values and coefficient of variation of STT I and STT II for the right and left eyes varied significantly among camel groups (P STT I, the most frequently recorded values were >14-18, > 22-26, and >30-34 mm/min in calves, immature camels, and mature camels, respectively. For STT II, however, the most frequently recorded values were 7-14, >10-18, and >26-30 mm/min, respectively. The interassay coefficients of variation were 1.7-14.4% and were significantly lower in mature camels than in calves and immature camels (P STT I (r = 0.81) and STT II values (r = 0.88). No significant variations were found between genders. This preliminary study reports STT I and II values and repeatability in normal dromedary camels. This information may assist veterinary practitioners in complete ophthalmic examinations and in accurate diagnosis of ocular surface diseases affecting the tear film in this species. © 2016 American College of Veterinary Ophthalmologists.

  20. Behavioral momentum and resurgence: Effects of time in extinction and repeated resurgence tests

    OpenAIRE

    Sweeney, Mary M.; Shahan, Timothy A

    2013-01-01

    Resurgence is an increase in a previously extinguished operant response that occurs if an alternative reinforcement introduced during extinction is removed. Shahan and Sweeney (2011) developed a quantitative model of resurgence based on behavioral momentum theory that captures existing data well and predicts that resurgence should decrease as time in extinction and exposure to the alternative reinforcement increases. Two experiments tested this prediction. The data from Experiment 1 suggested...

  1. Toxicity test using medaka (Oryzias latipes) early fry and concentrated sample water as an index of aquatic habitat condition.

    Science.gov (United States)

    Yamashita, H; Haribowo, R; Sekine, M; Oda, N; Kanno, A; Shimono, Y; Shitao, W; Higuchi, T; Imai, T; Yamamoto, K

    2011-08-01

    The aim of the present study was to show a relationship between toxicity of 100-fold concentrated water and aquatic habitat conditions. Environmental waters are 100-fold concentrated with solid-phase extraction. Medaka early fry was exposed in these waters for 48 h. The number of death and disorder was counted at 1, 2, 3, 6, 12, 24, and 48 h; toxicity was expressed using inverse median effect time and median lethal time (ET (50)(-1), LT (50)(-1)). Average score per taxon (ASPT) for benthic animals and Index of Biotic Integrity (IBI) for fish were applied as indices of aquatic habitat conditions. The results of toxicity test were compared using ASPT and IBI. The different levels of toxicity were detected in the seawater of Japan. At the Husino River area, toxicity cannot be detected. In rivers, high toxicity appeared at urban districts without sewerage. By Spearman coefficient, the relationship between toxicity and high biochemical oxygen demand (BOD) were obtained. BOD household wastewater contains hydrophobic toxic matters; otherwise, seawater in industrial area does not show clear relationship between toxicity and chemical oxygen demand. Gas chromatography to mass spectrometry simultaneous analysis database may give an answer for the source of toxicity, but further test is required. Ratio of clear stream benthic animal sharply decreased over 0.25 of LT (50)(-1) or 0.5 of ET (50)(-1). Tolerant fish becomes dominant over 0.3 of LT (50)(-1) or 0.5-1.0 of ET (50)(-1). By Pearson product-moment correlation coefficient, correlation coefficient between toxicity and ASPT was obtained at -0.773 (ET (50)(-1)) and -0.742 (LT (50)(-1)) at 1 % level of significance with a high negative correlation. Toxicity (LT (50)(-1) ) has strong correlation with the ratio of tolerant species. By Pearson product-moment correlation coefficient, correlation coefficient between toxicity and IBI obtained were -0.155 (ET (50)(-1)) and -0.190 (LT (50)(-1)) at 1 % level of significance and has a

  2. USEFULNESS AND METABOLIC IMPLICATIONS OF A 60-SECOND REPEATED JUMPS TEST AS A PREDICTOR OF ACROBATIC JUMPING PERFORMANCE IN GYMNASTS

    Directory of Open Access Journals (Sweden)

    Ferran Antoni Rodriguez

    2013-01-01

    Full Text Available Gymnastics floor exercises are composed of a set of four to five successive acrobatic jumps usually called a �series�. The aims of the study were: 1 to relate the acrobatic gymnastics performance of these series with a repeated jumps test of similar duration (R60, 2 to study the relation between R60 and physiological parameters (heart rate and blood lactate, and the performance obtained in different kinds of jumps, 3 to confirm whether R60, executed without a damped jumping technique, can be considered an anaerobic lactic power test. Twenty male and twenty-four female gymnasts performed three repeated jumps tests for 5 s (R5, 10 s (R10 and 60 s (R60 and vertical jumps, such as drop jumps (DJ, squat jumps (SJ and countermovement jumps (CMJ. We assessed heart rate (HR and blood lactate during R10 and R60. The average values of the maximal blood lactate concentration (Lmax after R10 (males = 2.5±0.6 mmol.l-1; females = 2.1±0.8 mmol.l-1 confirm that anaerobic glycolysis is not activated to a high level. In R60, the Lmax (males = 7.5±1.7 mmol.l-1; females = 5.9±2.1 mmol.l-1 that was recorded does not validate R60 as an anaerobic lactic power test. We confirmed the relation between the average power obtained in R60 (R60Wm and the acrobatic performance on the floor. The inclusion in the multiple regression equation of the best power in DJ and the best flight-contact ratio (FC in R5 confirms the influence of other non-metabolic components on the variability in R60 performance, at least in gymnasts.

  3. Use of sublethal endpoints in sediment toxicity tests with the amphipod Hyalella azteca

    Science.gov (United States)

    Ingersoll, Chris G.; Brunson, Eric L.; Dwyer, F. James; Hardesty, Douglas K.; Kemble, Nile E.

    1998-01-01

    Short-term sediment toxicity tests that only measure effects on survival can be used to identify high levels of contamination but may not be able to identify marginally contaminated sediments. The objective of the present study was to develop a method for determining the potential sublethal effects of contaminants associated with sediment on the amphipod Hyalella azteca (e.g., reproduction). Exposures to sediment were started with 7- to 8-d-old amphipods. On day 28, amphipods were isolated from the sediment and placed in water-only chambers where reproduction was measured on day 35 and 42. Typically, amphipods were first in amplexus at about day 21 to 28 with release of the first brood between day 28 to 42. Endpoints measured included survival (day 28, 35, and 42), growth (as length and weight on day 28 and 42), and reproduction (number of young/female produced from day 28 to 42). This method was used to evaluate a formulated sediment and field-collected sediments with low to moderate concentrations of contaminants. Survival of amphipods in these sediments was typically >85% after the 28-d sediment exposures and the 14-d holding period in water to measure reproduction. Reproduction was more variable than growth; hence, more replicates might be needed to establish statistical differences among treatments. Previous studies have demonstrated that growth of H. azteca in sediment tests often provides unique information that can be used to discriminate toxic effects of exposure to contaminants. Either length or weight can be measured in sediment tests with H. azteca. However, additional statistical options are available if length is measured on individual amphipods, such as nested analysis of variance that can account for variance in length within replicates. Ongoing water-only studies testing select contaminants will provide additional data on the relative sensitivity and variability of sublethal endpoints in toxicity tests with H. azteca.

  4. Some biological aspects of Mysidopsis juniae (Crustacea:Mysidacea) and its use in chronic toxicity tests

    Energy Technology Data Exchange (ETDEWEB)

    Badaro-Pedroso, C. [USP, Sao Paulo (Brazil)] Nipper, M.G. [NIWA, Hamilton (New Zealand)

    1995-12-31

    As part of the joint effort to develop marine toxicity tests with organisms abundant at the Brazilian coast, some aspects for the laboratory culture of M. juniae and its sensitivity to single chemicals were studied. Organisms fed a mixture of brine shrimp (Artemia sp.) nauplii and the microalgae Isochrysis galbana reached sexual maturity 10 days before animals fed brine shrimp nauplii only. Under best conditions, sexual maturity was reached on the 9th--11th day and newborn mysids hatched on the 16th--18th day, Short-term chronic toxicity tests were initiated with 7-day old mysids and exposure time was 11 days, with growth (length and dry weight) as test endpoints. Experiments were undertaken with zinc, copper, and ammonia. Zinc did not affect the organisms at concentrations between 0.018 and 0.1 mg/L, which were one order of magnitude lower than the average 96-h; LC50 value. The NOEC and LOEC values were the same for length and weight in some tests with copper and ammonia (Cu: 0.006 and 0.015 mg/L; NH{sub 3}: 0.32 and 0.87 mg/L, respectively), but revealed length as a more sensitive endpoint than weight in others (length NOEC and LOEC: 0.23 and 0.53 mgNH{sub 3}/L; weight: 0.53 and 0.99 mgNH{sub 3}/L, respectively). The authors speculate that this could be caused by time-dependent variations in the lipid content of the organisms. Length would be a steadier and more reliable endpoint for chronic toxicity tests with M. juniae. The results show that the method has potential applications for the evaluation and monitoring of contaminated marine systems along the Brazilian coast.

  5. Evaluation of Factors Affecting Repeatability and Accuracy of Turbine Rig Test Results.

    Science.gov (United States)

    1980-06-01

    RESOLUTION TEST CHART ( TABLE A-III (Cont’d) m In 0 wNw I- 0 10 O + WVN-4 119 Jb ( TABLE A-IV PROGRAM4 TTR2" IIw + co In N I LL I CC\\OIa CDa N we In t...CL Q) I- mW 0 0 Q U . X CL~ W CC) -W- I-- w - I-LUi L) W U- ~~~ LULLI Uzoct LU = LA- I- CL M C CXWW 0- U) W~W W CLU U) LUU _ aci~ L III.J 00 M𔃺 W

  6. Tolerance of freshwater test organisms to formulated sediments for use as control materials in whole-sediment toxicity tests

    Energy Technology Data Exchange (ETDEWEB)

    Kemble, N.E.; Dwyer, F.J.; Ingersoll, C.G. [Geological Survey, Columbia, MO (United States). Environmental and Contaminants Research Center; Dawson, T.D. [Integrated Laboratory Systems, Duluth, MN (United States); Norberg-King, T.J. [Environmental Protection Agency, Duluth, MN (United States). Mid-Continent Ecological Div.

    1999-02-01

    A method is described for preparing formulated sediments for use in toxicity testing. Ingredients used to prepare formulated sediments included commercially available silt, clay, sand, humic acid, dolomite, and {alpha}-cellulose (as a source of organic carbon). {alpha}-Cellulose was selected as the source of organic carbon because it is commercially available, consistent from batch to batch, and low in contaminant concentrations. The tolerance of freshwater test organisms to formulated sediments for use as control materials in whole-sediment toxicity testing was evaluated. Sediment exposures were conducted for 10 d with the amphipod Hyalella azteca, the midges Chironomus riparius and C. tentans, and the oligochaete Lumbriculus variegatus and for 28 d with H. azteca. Responses of organisms in formulated sediments was compared with a field-collected control sediment that has routinely been used to determine test acceptability. Tolerance of organisms to formulated sediments was evaluated by determining responses to varying levels of {alpha}-cellulose, to varying levels of grain size, to evaluation of different food types, or to evaluation of different sources of overlying water. In the 10-d exposures, survival of organisms exposed to the formulated sediments routinely met or exceeded the responses of test organisms exposed to the control sediment and routinely met test acceptability criteria required in standard methods. Growth of amphipods and oligochaetes in 10-d exposures with formulated sediment was often less than growth of organisms in the field-collected control sediment. Additional research is needed, using the method employed to prepare formulated sediment, to determine if conditioning formulated sediments before starting 10-d tests would improve the growth of amphipods. In the 28-d exposures, survival of H. azteca was low when reconstituted water was used as the source of overlying water. However, when well water was used as the source of overlying water in

  7. Characterization of sewage sludge and the use of brine shrimp for toxicity test

    Energy Technology Data Exchange (ETDEWEB)

    Pun, K.C.; Cheung, R.Y.H. [City Univ. of Hong Kong (Hong Kong). Dept. of Biology and Chemistry; Wong, M.H. [Hong Kong Baptist Univ. (Hong Kong). Dept. of Biology

    1995-12-31

    Heavy metal contents (Cd, Cr, Cu, Pb, Ni and Zn) of digested sludges, collected from 4 sewage treatment works in Hong Kong were analyzed using atomic absorption spectrophotometry, after sequentially extracted by 1 M KNO{sub 3}, 0.5 M KF, 0.1 M Na{sub 4}, P{sub 2}, O{sub 7} 0.1 M EDTA and 6 M HNO{sub 3} It was found that the major forms of Cu, Pb, Ni and Zn were in the sulfide phase, organically bound phase, adsorbed phase and carbonate phase respectively. Nauplii larvae of brine shrimp (Artemia franciscana) was then used as bioindicator to test the toxicity, of the digested sludges. 20 individuals were placed into 1 liter seawater containing whole sample of the types of digested sludges at different concentrations, The toxicity of the 4 sludges, according to 48h-LC 50, were ranked as follows YL > TP > ST > SWH.

  8. Toxicity tests with crustaceans for detecting sublethal effects of potential endocrine disrupting chemicals

    DEFF Research Database (Denmark)

    Wollenberger, Leah

    /antagonistic activity with the ecdysteroid-responsive Drosophila melanogaster BII cell line 6) to draft an OECD guideline proposal for testing of chemicals based on the experimental work performed within this study In preliminary investigations with A. tonsa were studied various parameters related to processes...... regulated by hormones such as growth, molting, sexual maturation and reproduction. The primary endpoints were larval development ratio, egg production and sex ratio. Exposure experiments were conducted with naturally occurring and synthetic vertebrate and invertebrate hormones as well as compounds known...... contribution of the present work with BFRs was to establish data on their (sub)chronic toxicity towards marine copepods. To discriminate between general toxicological and endocrine-mediated toxic effects, the model compounds were assessed in vitro for ecdysteroid agonistic/antagonistic activity using...

  9. Relative sensitivities of toxicity test protocols with the amphipods Eohaustorius estuarius and Ampelisca abdita.

    Science.gov (United States)

    Anderson, Brian S; Lowe, Sarah; Phillips, Bryn M; Hunt, John W; Vorhees, Jennifer; Clark, Sara; Tjeerdema, Ronald S

    2008-01-01

    A series of dose-response experiments was conducted to compare the relative sensitivities of toxicity test protocols using the amphipods Ampelisca abdita and Eohaustorius estuarius. A. abdita is one of the dominant infaunal species in the San Francisco Estuary, and E. estuarius is the primary sediment toxicity species used in the San Francisco Estuary Regional Monitoring Program. Experiments were conducted with a formulated sediment spiked with copper, fluoranthene, chlorpyrifos, and the three pyrethroid pesticides permethrin, bifenthrin, and cypermethrin, all chemicals of concern in this Estuary. The results showed that the protocol with A. abdita was more sensitive to fluoranthene and much more sensitive to copper, while E. estuarius was more sensitive to chlorpyrifos, and much more sensitive to the pyrethroid pesticides. These results, considered in conjunction with those from previous spiking studies [Weston, D.P., 1995. Further development of a chronic Ampelisca abdita bioassay as an indicator of sediment toxicity: summary and conclusions. In: Regional Monitoring Program for Trace Substances Annual Report. San Francisco Estuary Institute, Oakland, CA, pp 108-115; DeWitt, T.E., Swartz, R.C., Lamberson, J.O., 1989. Measuring the acute toxicity of estuarine sediments. Environ. Toxicol. Chem. 8: 1035-1048; DeWitt, T.H.E., Pinza, M.R., Niewolny, L.A., Cullinan, V.I., Gruendell, B.D., 1997. Development and evaluation of a standard marine/estuarine chronic sediment toxicity method using Leptocheirus plumulosus. Draft report prepared for the US Environmental Protection Agency, Office of Science and Technology, Washington DC, under contract DE-AC06-76RLO 1830 by Batelle Marine Science Laboratory, Battelle Memorial Institute, Pacific Northwest Division, Richland, WA], suggest that, in general, A. abdita is more sensitive to metals, E. estuarius is more sensitive to pesticides, and both protocols have roughly comparable sensitivities to hydrocarbons. The preponderance of

  10. The use of portable NIRS to measure muscle oxygenation and haemodynamics during a repeated sprint running test.

    Science.gov (United States)

    Jones, Ben; Hesford, Catherine M; Cooper, Chris E

    2013-01-01

    Portable near-infrared spectroscopy (NIRS) devices were originally developed for use in exercise and sports science by Britton Chance in the 1990s (the RunMan and microRunman series). However, only recently with the development of more robust, and wireless systems, has the routine use in elite sport become possible. As with the medical use of NIRS, finding applications of the technology that are relevant to practitioners is the key issue. One option is to use NIRS to track exercise training-induced adaptations in muscle. Portable NIRS devices enable monitoring during the normal 'field' routine uses to assess fitness, such as repeat sprint shuttle tests. Knowledge about the acute physiological responses to these specific tests has practical applications within team sport training prescription, where development of both central and peripheral determinants of high-intensity intermittent exercise needs to be considered. The purpose of this study was to observe NIRS-detected parameters during a repeat sprint test. We used the PortaMon, a two wavelength spatially resolved NIR spectrometer manufactured by Artinis Inc., to assess NIR changes in the gastrocnemius muscle of both the left and right leg during high-intensity running. Six university standard rugby players were assessed (age 20 ± 1.5 years; height 183 ± 1.0 cm; weight 89.4 ± 5.8 kg; body fat 12.2 ± 3.0 %); the subjects completed nine repeated shuttle runs, which incorporated forward, backward and change of direction movements. Individual sprint time, total time to complete test, blood lactate response (BL), heart rate values (HR) and haemoglobin variables (ΔHHb, ΔtHb, ΔHbO2 and ΔTSI%) were measured. Total time to complete the test was 260 ± 20 s, final blood lactate was 14.3 ± 2.8 mM, and maximal HR 182 ± 5 bpm. NIRS variables displayed no differences between right and left legs. During the test, the group-averaged data showed a clear decrease in HbO2 (max. decrease 11.41 ± 4.95 μM), increase in HHb

  11. Comprehensive In Vitro Toxicity Testing of a Panel of Representative Oxide Nanomaterials: First Steps towards an Intelligent Testing Strategy

    Science.gov (United States)

    Farcal, Lucian; Torres Andón, Fernando; Di Cristo, Luisana; Rotoli, Bianca Maria; Bussolati, Ovidio; Bergamaschi, Enrico; Mech, Agnieszka; Hartmann, Nanna B.; Rasmussen, Kirsten; Riego-Sintes, Juan; Ponti, Jessica; Kinsner-Ovaskainen, Agnieszka; Rossi, François; Oomen, Agnes; Bos, Peter; Chen, Rui; Bai, Ru; Chen, Chunying; Rocks, Louise; Fulton, Norma; Ross, Bryony; Hutchison, Gary; Tran, Lang; Mues, Sarah; Ossig, Rainer; Schnekenburger, Jürgen; Campagnolo, Luisa; Vecchione, Lucia; Pietroiusti, Antonio; Fadeel, Bengt

    2015-01-01

    Nanomaterials (NMs) display many unique and useful physico-chemical properties. However, reliable approaches are needed for risk assessment of NMs. The present study was performed in the FP7-MARINA project, with the objective to identify and evaluate in vitro test methods for toxicity assessment in order to facilitate the development of an intelligent testing strategy (ITS). Six representative oxide NMs provided by the EC-JRC Nanomaterials Repository were tested in nine laboratories. The in vitro toxicity of NMs was evaluated in 12 cellular models representing 6 different target organs/systems (immune system, respiratory system, gastrointestinal system, reproductive organs, kidney and embryonic tissues). The toxicity assessment was conducted using 10 different assays for cytotoxicity, embryotoxicity, epithelial integrity, cytokine secretion and oxidative stress. Thorough physico-chemical characterization was performed for all tested NMs. Commercially relevant NMs with different physico-chemical properties were selected: two TiO2 NMs with different surface chemistry – hydrophilic (NM-103) and hydrophobic (NM-104), two forms of ZnO – uncoated (NM-110) and coated with triethoxycapryl silane (NM-111) and two SiO2 NMs produced by two different manufacturing techniques – precipitated (NM-200) and pyrogenic (NM-203). Cell specific toxicity effects of all NMs were observed; macrophages were the most sensitive cell type after short-term exposures (24-72h) (ZnO>SiO2>TiO2). Longer term exposure (7 to 21 days) significantly affected the cell barrier integrity in the presence of ZnO, but not TiO2 and SiO2, while the embryonic stem cell test (EST) classified the TiO2 NMs as potentially ‘weak-embryotoxic’ and ZnO and SiO2 NMs as ‘non-embryotoxic’. A hazard ranking could be established for the representative NMs tested (ZnO NM-110 > ZnO NM-111 > SiO2 NM-203 > SiO2 NM-200 > TiO2 NM-104 > TiO2 NM-103). This ranking was different in the case of embryonic tissues, for

  12. Testing Accuracy and Repeatability of UAV Blocks Oriented with GNSS-Supported Aerial Triangulation

    Directory of Open Access Journals (Sweden)

    Francesco Benassi

    2017-02-01

    Full Text Available UAV Photogrammetry today already enjoys a largely automated and efficient data processing pipeline. However, the goal of dispensing with Ground Control Points looks closer, as dual-frequency GNSS receivers are put on board. This paper reports on the accuracy in object space obtained by GNSS-supported orientation of four photogrammetric blocks, acquired by a senseFly eBee RTK and all flown according to the same flight plan at 80 m above ground over a test field. Differential corrections were sent to the eBee from a nearby ground station. Block orientation has been performed with three software packages: PhotoScan, Pix4D and MicMac. The influence on the checkpoint errors of the precision given to the projection centers has been studied: in most cases, values in Z are critical. Without GCP, the RTK solution consistently achieves a RMSE of about 2–3 cm on the horizontal coordinates of checkpoints. In elevation, the RMSE varies from flight to flight, from 2 to 10 cm. Using at least one GCP, with all packages and all test flights, the geocoding accuracy of GNSS-supported orientation is almost as good as that of a traditional GCP orientation in XY and only slightly worse in Z.

  13. Long-term repeatability of the skin prick test is high when supported by history or allergen-sensitivity tests

    DEFF Research Database (Denmark)

    Bødtger, Uffe; Jacobsen, C R; Poulsen, L K;

    2003-01-01

    BACKGROUND: Long-term reproducibility of the skin-prick test (SPT) has been questioned. The aim of the study was to investigate the clinical relevance of SPT changes. METHODS: SPT to 10 common inhalation allergens was performed annually from 1999 to 2001 in 25 nonsensitized and 21 sensitized...

  14. Chronic exercise prevents repeated restraint stress-provoked enhancement of immobility in forced swimming test in ovariectomized mice.

    Science.gov (United States)

    Han, Tae-Kyung; Lee, Jang-Kyu; Leem, Yea-Hyun

    2015-06-01

    We assessed whether chronic treadmill exercise attenuated the depressive phenotype induced by restraint stress in ovariectomized mice (OVX). Immobility of OVX in the forced swimming test was comparable to that of sham mice (CON) regardless of the postoperative time. Immobility was also no difference between restrained mice (exposure to periodic restraint for 21 days; RST) and control mice (CON) on post-exposure 2nd and 9th day, but not 15th day. In contrast, the immobility of ovariectomized mice with repeated stress (OVX + RST) was profoundly enhanced compared to ovariectomized mice-alone (OVX), and this effect was reversed by chronic exercise (19 m/min, 60 min/day, 5 days/week for 8 weeks; OVX + RST + Ex) or fluoxetine administration (20 mg/kg, OVX + RST + Flu). In parallel with behavioral data, the immunoreactivity of Ki-67 and doublecortin (DCX) in OVX was significantly decreased by repeated stress. However, the reduced numbers of Ki-67- and DCX-positive cells in OVX + RST were restored in response to chronic exercise (OVX + RST + Ex) and fluoxetine (OVX + RST + Flu). In addition, the expression pattern of cAMP response element-binding protein (CREB) and calcium-calmodulin-dependent kinase IV (CaMKIV) was similar to that of the hippocampal proliferation and neurogenesis markers (Ki-67 and DCX, respectively). These results suggest that menopausal depression may be induced by an interaction between repeated stress and low hormone levels, rather than a deficit in ovarian secretion alone, which can be improved by chronic exercise.

  15. Microbial community-level toxicity testing of linear alkylbenzene sulfonates in aquatic microcosms.

    Science.gov (United States)

    Brandt, Kristian K; Jørgensen, Niels O G; Nielsen, Tommy H; Winding, Anne

    2004-08-01

    Complex microbial communities may serve as ideal and ecologically relevant toxicity indicators. We here report an assessment of frequently used methods in microbial ecology for their feasibility to detect toxic effects of the environmentally important surfactant linear alkylbenzene sulfonate (LAS) on microbial communities in lake water and treated waste water. The two microbial communities were evaluated for changes in community structure and function over a period of 7 weeks in replicated aquatic microcosms amended with various levels of LAS (0, 0.1, 1, 10 or 100 mg l(-1)) and inorganic nutrients. In general, the two communities behaved similarly when challenged with LAS. Following lag periods of 1-3 weeks, LAS was degraded to non-toxic substances. Denaturing gradient gel electrophoresis of 16S rRNA gene fragments and [3H]leucine incorporation were the most sensitive assays with effect levels of 0-1 and 1-10 mg LAS l(-1), respectively. Community-level physiological profiles and pollution-induced community tolerance determinations using Biolog microplates demonstrated less sensitivity with effect levels of 10-100 mg LAS l(-1). Total cell counts and net uptake of inorganic N and P were unaffected even at 100 mg LAS l(-1). Interestingly, different microbial communities developed in some replicate microcosms, indicating the importance of stochastic events for community succession. We conclude that microbial community-level toxicity testing holds great promise and suggest a polyphasic approach involving a range of independent methods targeting both the structure and function of the tested microbial communities.

  16. [TEFREP: repeating sentences Test in France and Quebec. Development, validation and standardization].

    Science.gov (United States)

    Bourgeois-Marcotte, Josiane; Wilson, Maximiliano A; Forest, Martin; Monetta, Laura

    2015-09-01

    Sentence repetition is part of the assessment tasks used to better characterise aphasic patients' oral production. Moreover, impaired sentence and phrase repetition is a core feature of the logopenic variant of primary progressive aphasia. The aim of this study is to present the TEFREP (TEst Français de RÉpétition de Phrases), a French sentence repetition task that manipulates psycholinguistic variables known to affect the performance of aphasic patients. The final version of the TEFREP consists of 24 sentences in which length, semantic reversibility and type of sentence have been manipulated. The task shows good psychometric properties (validity and reliability). Norms according to age and education level have been developed from a sample of 80 healthy adults and older adults. In conclusion, the TEFREP fulfills the current need for a reliable assessment tool of sentence repetition in Canadian French-speaking populations and contributes to the differential diagnosis of language impairment.

  17. Aquatic toxicity testing of silver nanoparticles – a matter of timing

    DEFF Research Database (Denmark)

    Sørensen, Sara Nørgaard; Owsianiak, Mikolaj; Engelbrekt, Christian

    In recent years, the ecotoxicity of silver nanoparticles (AgNPs) has been studied intensively due to their high toxicity and extensive use in consumer products. However, the field of aquatic nanotoxicology is generally challenged by poor reproducibility, lack of dose-response relationships......, and difficulties in controlling and/or describing the characteristics of the tested NPs. These issues may be related to the widespread approach of using freshly prepared stock solutions for ecotoxicity testing, as the introduction of NPs into aqueous media initiates time-dependent processes that possibly interfere......NPs with a nominal size of 30 nm, the resulting dose-response relationships from tests without (A) and with (B) the pre-suspension step are illustrated in figure 1. Without the pre-suspension step, poorly reproducible results were obtained and it was not possible to produce comparable EC50 values from the three test...

  18. Toxicity of sediments from lead-zinc mining areas to juvenile freshwater mussels (Lampsilis siliquoidea) compared to standard test organisms.

    Science.gov (United States)

    Besser, John M; Ingersoll, Christopher G; Brumbaugh, William G; Kemble, Nile E; May, Thomas W; Wang, Ning; MacDonald, Donald D; Roberts, Andrew D

    2015-03-01

    Sediment toxicity tests compared chronic effects on survival, growth, and biomass of juvenile freshwater mussels (28-d exposures with Lampsilis siliquoidea) to the responses of standard test organisms-amphipods (28-d exposures with Hyalella azteca) and midges (10-d exposures with Chironomus dilutus)-in sediments from 2 lead-zinc mining areas: the Tri-State Mining District and Southeast Missouri Mining District. Mussel tests were conducted in sediments sieved to toxic responses (reduced 10% or more relative to reference sites) in Tri-State sediments was greatest for amphipod survival (25% of samples), midge biomass (20%), and mussel survival (14%). In southeast Missouri sediments, the frequency of highly toxic samples was greatest for mussel biomass (25%) and amphipod biomass (13%). Thresholds for metal toxicity to mussels, expressed as hazard quotients based on probable effect concentrations, were lower for southeast Missouri sediments than for Tri-State sediments. Southeast Missouri sites with toxic sediments had 2 or fewer live mussel taxa in a concurrent mussel population survey, compared with 7 to 26 taxa at reference sites. These results demonstrate that sediment toxicity tests with juvenile mussels can be conducted reliably by modifying existing standard methods; that the sensitivity of mussels to metals can be similar to or greater than standard test organisms; and that responses of mussels in laboratory toxicity tests are consistent with effects on wild mussel populations.

  19. Use of power analysis to develop detectable significance criteria for sea urchin toxicity tests

    Science.gov (United States)

    Carr, R.S.; Biedenbach, J.M.

    1999-01-01

    When sufficient data are available, the statistical power of a test can be determined using power analysis procedures. The term “detectable significance” has been coined to refer to this criterion based on power analysis and past performance of a test. This power analysis procedure has been performed with sea urchin (Arbacia punctulata) fertilization and embryological development data from sediment porewater toxicity tests. Data from 3100 and 2295 tests for the fertilization and embryological development tests, respectively, were used to calculate the criteria and regression equations describing the power curves. Using Dunnett's test, a minimum significant difference (MSD) (β = 0.05) of 15.5% and 19% for the fertilization test, and 16.4% and 20.6% for the embryological development test, for α ≤ 0.05 and α ≤ 0.01, respectively, were determined. The use of this second criterion reduces type I (false positive) errors and helps to establish a critical level of difference based on the past performance of the test.

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

    DEFF Research Database (Denmark)

    Lagadic, Laurent; Holbech, Henrik; hutchinson, tom

    Framework. The guideline project is led by a consortium of experts (Germany/United- Kingdom/France/Denmark) from academia, industry and government stakeholders. To date, expert knowledge has been gathered and formed the basis of draft standard operating procedures (SOPs) for the culture and test...... in 2014 for both species based upon the consolidated SOPs....

  1. Antimicrobial PVK:SWNT nanocomposite coated membrane for water purification: performance and toxicity testing.

    Science.gov (United States)

    Ahmed, Farid; Santos, Catherine M; Mangadlao, Joey; Advincula, Rigoberto; Rodrigues, Debora F

    2013-08-01

    This study demonstrated that coated nitrocellulose membranes with a nanocomposite containing 97% (wt%) of polyvinyl-N-carbazole (PVK) and 3% (wt%) of single-walled carbon nanotubes (SWNTs) (97:3 wt% ratio PVK:SWNT) achieve similar or improved removal of bacteria when compared with 100% SWNTs coated membranes. Membranes coated with the nanocomposite exhibited significant antimicrobial activity toward Gram-positive and Gram-negative bacteria (≈ 80-90%); and presented a virus removal efficiency of ≈ 2.5 logs. Bacterial cell membrane damage was considered a possible mechanism of cellular inactivation since higher efflux of intracellular material (Deoxyribonucleic acid, DNA) was quantified in the filtrate of PVK-SWNT and SWNT membranes than in the filtrate of control membranes. To evaluate possible application of these membrane filters for drinking water treatment, toxicity of PVK-SWNT was tested against fibroblast cells. The results demonstrated that PVK-SWNT was non toxic to fibroblast cells as opposed to pure SWNT (100%). These results suggest that it is possible to synthesize antimicrobial nitrocellulose membranes coated with SWNT based nanocomposites for drinking water treatment. Furthermore, membrane filters coated with the nanocomposite PVK-SWNT (97:3 wt% ratio PVK:SWNT) will produce more suitable coated membranes for drinking water than pure SWNTs coated membranes (100%), since the reduced load of SWNT in the nanocomposite will reduce the use of costly and toxic SWNT nanomaterial on the membranes.

  2. Genotoxicity test and subchronic toxicity study with Superba™ krill oil in rats

    Directory of Open Access Journals (Sweden)

    Bruce Robertson

    2014-01-01

    Full Text Available The safety of krill oil was assessed in a subchronic toxicity study and in a genotoxicity test. In a 13-week study, rats were fed krill oil or control diets. There were no differences noted in body weight, food consumption or in the functional observation battery parameters in either gender. Differences in both haematology and clinical chemistry values were noted in the krill oil-treated groups. However these findings were of no toxicological significance. Significant decreases in absolute and covariant heart weight in some krill oil-treated animals were noted although no corresponding histological changes were observed. In addition, periportal microvesicular hepatocyte vacuolation was noted histologically in males fed 5% krill oil. This finding was not associated with other indications of hepatic dysfunction. Given that the effects of the 13-week toxicity study were non-toxic in nature, the no observed adverse effect level (NOAEL for the conditions of this study was considered to be 5% krill oil. The genotoxicity experiments documented no mutagenicity of krill oil in bacteria.

  3. Green Tea Protects Testes against Atrazine-induced Toxicity in Rat

    Directory of Open Access Journals (Sweden)

    Reza Kheirandish

    2017-06-01

    Full Text Available Background: Atrazine (ATZ is a common herbicide in agriculture for control of grass and broad-leaved weeds. It persists in the environment and causes reproductive problems in both human and animals. The present study was aimed at protective effect of green tea against ATZ toxicity in the reproductive system of male rats. Methods: The present study was performed in Veterinary School, Shahid Bahonar University of Kerman in 2016. ATZ and treatment groups received ATZ daily 200 mg/kg BW orally for 14 d. In addition, 0.2% methanolic green tea extract was administrated in the treatment group. Results: In histopathologic investigation, number of germinal layers reduced in the most seminiferous tubules in the ATZ group and spermatids were absence. Necrotic spermatocytes, spermatids, and spermatozoa were evident in the testicular tubules. In the morphometric measurements, tubular diameter, germinal epithelium height, and meiosis index decreased significantly. Conclusion: Green tea extract had reduced testicular toxicity of atrazine significantly. ATZ induces toxicity through oxidative damage and green tea extract can protect the testes due to antioxidant activity of its polyphenols especially flavonoids.

  4. Fourier-transform infrared spectroscopy as a novel approach to providing effect-based endpoints in duckweed toxicity testing.

    Science.gov (United States)

    Hu, Li-Xin; Ying, Guang-Guo; Chen, Xiao-Wen; Huang, Guo-Yong; Liu, You-Sheng; Jiang, Yu-Xia; Pan, Chang-Gui; Tian, Fei; Martin, Francis L

    2017-02-01

    Traditional duckweed toxicity tests only measure plant growth inhibition as an endpoint, with limited effects-based data. The present study aimed to investigate whether Fourier-transform infrared (FTIR) spectroscopy could enhance the duckweed (Lemna minor L.) toxicity test. Four chemicals (Cu, Cd, atrazine, and acetochlor) and 4 metal-containing industrial wastewater samples were tested. After exposure of duckweed to the chemicals, standard toxicity endpoints (frond number and chlorophyll content) were determined; the fronds were also interrogated using FTIR spectroscopy under optimized test conditions. Biochemical alterations associated with each treatment were assessed and further analyzed by multivariate analysis. The results showed that comparable x% of effective concentration (ECx) values could be achieved based on FTIR spectroscopy in comparison with those based on traditional toxicity endpoints. Biochemical alterations associated with different doses of toxicant were mainly attributed to lipid, protein, nucleic acid, and carbohydrate structural changes, which helped to explain toxic mechanisms. With the help of multivariate analysis, separation of clusters related to different exposure doses could be achieved. The present study is the first to show successful application of FTIR spectroscopy in standard duckweed toxicity tests with biochemical alterations as new endpoints. Environ Toxicol Chem 2017;36:346-353. © 2016 SETAC.

  5. Repeated high-dose (5 × 10(8) TCID50) toxicity study of a third generation smallpox vaccine (IMVAMUNE) in New Zealand white rabbits.

    Science.gov (United States)

    Tree, Julia A; Hall, Graham; Rees, Peter; Vipond, Julia; Funnell, Simon G P; Roberts, Allen D

    2016-07-01

    Concern over the release of variola virus as an agent of bioterrorism remains high and a rapid vaccination regimen is desirable for use in the event of a confirmed release of virus. A single, high-dose (5×10(8) TCID50) of Bavarian Nordic's IMVAMUNE was tested in a Phase-II clinical trial, in humans, as a substitute for the standard (1×10(8) TCID50), using a 2-dose, 28-days apart regimen. Prior to this clinical trial taking place a Good Laboratory Practice, repeated high-dose, toxicology study was performed using IMVAMUNE, in New Zealand white rabbits and the results are reported here. Male and female rabbits were dosed twice, subcutaneously, with 5×10(8) TCID50 of IMVAMUNE (test) or saline (control), 7-days apart. The clinical condition, body-weight, food consumption, haematology, blood chemistry, immunogenicity, organ-weight, and macroscopic and microscopic pathology were investigated. Haematological investigations indicated changes within the white blood cell profile that were attributed to treatment with IMVAMUNE; these comprised slight increases in neutrophil and monocyte numbers, on study days 1-3 and a marginal increase in lymphocyte numbers on day 10. Macroscopic pathology revealed reddening at the sites of administration and thickened skin in IMVAMUNE, treated animals. After the second dose of IMVAMUNE 9/10 rabbits seroconverted, as detected by antibody ELISA on day 10, by day 21, 10/10 rabbits seroconverted. Treatment-related changes were not detected in other parameters. In conclusion, the subcutaneous injection of 2 high-doses of IMVAMUNE, to rabbits, was well tolerated producing only minor changes at the site of administration. Vaccinia-specific antibodies were raised in IMVAMUNE-vaccinated rabbits only.

  6. Antibacterial, antioxidant and acute toxicity tests on flavonoids extracted from some medicinal plants

    Directory of Open Access Journals (Sweden)

    Akroum Souâd

    2010-01-01

    Full Text Available Flavonoids are well-known for their many therapeutic and pharmaceutical effects. In this study, we tested the antibacterial activity of 11 flavonoids extracted from some medicinal plants by the agar diffusion method. Then, we measured their antioxidant activity using the DPPH (2,2′-diphenyl-1-picrylhydrazyl radical assay and we also tested their acute toxicity effect on mice. The results showed that apigenin-7-O-glucoside was more active against the Gram-positive bacteria and quercetin was more active against the Gram-negative ones. Also, quercetin and diosmin showed the best antioxidant activity. Quercetin, apigenin-7-O-glucoside, luteolin-7-O-glucoside and luteolin-3′-O-glucuronide gave the best acute toxicity values. It can be concluded that quercetin was the most interesting compound for all the tested activities. Also, we observed that the presence or the absence of substitutions in flavonoids influenced significantly the results obtained, whereas the substitution type had a low impact.

  7. Microfluidic devices for stem-cell cultivation, differentiation and toxicity testing

    Science.gov (United States)

    Becker, Holger; Hansen-Hagge, Thomas; Kurtz, Andreas; Mrowka, Ralf; Wölfl, Stefan; Gärtner, Claudia

    2017-02-01

    The development of new drugs is time-consuming, extremely expensive and often promising drug candidates fail in late stages of the development process due to the lack of suitable tools to either predict toxicological effects or to test drug candidates in physiologically relevant environments prior to clinical tests. We therefore try to develop diagnostic multiorgan microfluidic chips based on patient specific induced pluripotent stem cell (iPS) technology to explore liver dependent toxic effects of drugs on individual human tissues such as liver or kidney cells. Based initially on standardized microfluidic modules for cell culture, we have developed integrated microfluidic devices which contain different chambers for cell/tissue cultivation. The devices are manufactured using injection molding of thermoplastic polymers such as polystyrene or cyclo-olefin polymer. In the project, suitable surface modification methods of the used materials had to be explored. We have been able to successfully demonstrate the seeding, cultivation and further differentiation of modified iPS, as shown by the use of differentiation markers, thus providing a suitable platform for toxicity testing and potential tissue-tissue interactions.

  8. Low malathion concentrations influence metabolism in Chironomus sancticaroli (Diptera, Chironomidae in acute and chronic toxicity tests

    Directory of Open Access Journals (Sweden)

    Débora Rebechi

    2014-09-01

    Full Text Available Low malathion concentrations influence metabolism in Chironomus sancticaroli (Diptera, Chironomidae in acute and chronic toxicity tests. Organophosphate compounds are used in agro-systems, and in programs to control pathogen vectors. Because they are continuously applied, organophosphates often reach water sources and may have an impact on aquatic life. The effects of acute and chronic exposure to the organophosphate insecticide malathion on the midge Chironomus sancticaroli are evaluated. To that end, three biochemical biomarkers, acetylcholinesterase (AChE, alpha (EST-α and beta (EST-β esterase were used. Acute bioassays with five concentrations of malathion, and chronic bioassays with two concentrations of malathion were carried out. In the acute exposure test, AChE, EST-α and EST-β activities declined by 66, 40 and 37%, respectively, at 0.251 µg L-1 and more than 80% at 1.37, 1.96 and 2.51 µg L-1. In chronic exposure tests, AChE and EST-α activities declined by 28 and 15% at 0.251 µg L-1. Results of the present study show that low concentrations of malathion can influence larval metabolism, indicating high toxicity for Chironomus sancticaroli and environmental risk associated with the use of organophosphates.

  9. Toxicity tests with crustaceans for detecting sublethal effects of potential endocrine disrupting chemicals

    DEFF Research Database (Denmark)

    Wollenberger, Leah

    of effective concentrations (ECx). After having demonstrated that larval development of A. tonsa was a very sensitive endpoint for evaluating effects of chemicals that might interfere with the endocrine system of crustaceans, the larval development test has been applied to two groups of emerging environmental...... of in vitro assays and (sub)chronic copepod tests, as applied in this study, is a valuable tool when screening chemicals suspected to be specifically toxic, in particular, to interfere with the endocrine system. The results of the experimental work as well as the literature survey demonstrated clearly......New and updated test methods to detect and characterise endocrine disrupting chemicals are urgently needed for the purpose of environmental risk assessment. Although endocrine disruption in invertebrates has not been studied as extensive as in vertebrates, in particular in fish, numerous reports...

  10. Toxicity tests based on predator-prey and competitive interactions between freshwater macroinvertebrates

    Energy Technology Data Exchange (ETDEWEB)

    Taylor, E.J.; Blockwell, S.J.; Pascoe, D. [Univ. of Wales Coll. of Cardiff (United Kingdom)

    1994-12-31

    Simple multi-species toxicity tests based on the predation of Daphnia magna Straus by Hydra oligactis (Pallas) and competition between Gammarus pulex (L.) and Asellus aquaticus (L.) were used to determine the effects of three reference chemicals. Criteria examined included functional responses; time to first captures; handling times (predator/prey systems) and co-existence and growth. The tests which proved most practicable and sensitive (lowest observed effects 0.1, 21, and 80 {micro}g/l for lindane, copper and 3,4 dichloroaniline, respectively) were: (1) predator-prey tests: determining changes in the size-structure of predated D. magna populations and (2) competition tests: measuring the feeding rate of G. pulex competing with A. aquaticus, using a bioassay based on the time-response analysis of the consumption of Artemia salina eggs. The concentration of a chemical which affected particular response criteria was fond to depend on the test system employed. Results of the tests indicated that effects were often not dose-related and that a given criterion could be variously affected by different test concentrations. The complex pattern of responses may be explained in terms of the differential sensitivity of the interacting species and perhaps subtle alteration in strategies. The sensitivity of the bioassay endpoints is compared to those of a range of single species tests, and their value for predicting the impact pollutants may have upon natural freshwater ecosystems is discussed.

  11. Suitability and repeatability of a photostress recovery test device, the macular test device, macular degeneration TEST DEVICE, detector (MDD-2), for diabetes and diabetic retinopathy assessment

    LENUS (Irish Health Repository)

    Loughman, James

    2013-10-16

    Diabetic retinopathy can result in impaired photostress recovery time despite normal visual acuity and fundoscopic appearance. The Macular Degeneration Detector (MDD-2) is a novel flash photostress recovery time device. In this study, we examine the repeatability of the MDD-2 in normal and diabetic subjects.

  12. Acute effects of two different initial heart rates on testing the Repeated Sprint Ability in young soccer players.

    Science.gov (United States)

    Ruscello, B; Briotti, G; Tozzo, N; Partipilo, F; Taraborelli, M; Zeppetella, A; Padulo, J; D'Ottavio, S

    2015-10-01

    The aim of this paper was to investigate the acute effects of two different initial heart rates intensities when testing the repeated sprint ability (RSA) performances in young soccer players. Since there are many kinds of pre-match warm-ups, we chose to take as an absolute indicator of internal load the heart rate reached at the end of two different warm-up protocols (60 vs. 90% HRmax) and to compare the respective RSA performances. The RSA tests were performed on fifteen male soccer players (age: 17.9±1.5 years) with two sets of ten shuttle-sprints (15+15 m) with a 1:3 exercise to rest ratio, in different days (randomized order) with different HR% (60 & 90% HRmax). In order to compare the different sprint performances a Fatigue Index (FI%) was computed, while the blood lactate concentrations (BLa-) were measured before and after testing, to compare metabolic demand. Significant differences among trials within each sets (P4 mmol/L(-1)).

  13. A 28-day repeat dose toxicity study of steroidal glycoalkaloids, alpha-solanine and alpha-chaconine in the Syrian Golden hamster

    DEFF Research Database (Denmark)

    Langkilde, Søren; Mandimika, T.; Schrøder, Malene

    2009-01-01

    Glycoalkaloids alpha-solanine and alpha-chaconine are naturally present toxicants in the potato plant (Solanum tuberosum). Human intake of high doses of glycoalkaloids has led to acute intoxication, in severe cases coma and death. Previous studies have indicated that the ratio of alpha-solanine...... to alpha-chaconine may determine the degree and nature of the glycoalkaloid toxicity in potatoes, as the toxicity of the two alkaloids act synergistically. The aim of the present study was to investigate whether an altered ratio of alpha-solanine and alpha-chaconine would reduce the toxicity...... of the glycoalkaloids. The Syrian Golden hamster was given daily doses of alpha-solanine and alpha-chaconine by gavage for 28 days. Doses of up to 33.3 mg total glycoalkaloids/kg body weight were applied in ratios of 1:3.7 and 1:70 (alpha-solanine:alpha-chaconine). Administration of the highest doses of both ratios...

  14. Refining methods for conducting long-term sediment and water toxicity tests with Chironomus dilutus: Formation of a midge chronic testing work group

    Science.gov (United States)

    Standard methods have been established by USEPA, ASTM International, Environment Canada and Organization for Economic Cooperation and Development for conducting sediment toxicity tests with various species of midges including Chironomus dilutus. Short-term 10-day exposures are ty...

  15. Assessment of Grape, Plum and Orange Synthetic Food Flavourings Using in vivo Acute Toxicity Tests

    Directory of Open Access Journals (Sweden)

    Ila Monize Sousa Sales

    2017-01-01

    Full Text Available The present study evaluates the acute toxicity of synthetic grape, plum and orange flavourings in root meristem cells of Allium cepa at the doses of 3.5, 7.0 and 14.0 mL/kg and exposure times of 24 and 48 h, and in bone marrow erythrocytes of mice treated orally for seven days with 0.5, 1.0, 2.0, 5.0 and 10.0 mL/kg of flavouring. The results of the plant test showed that grape, plum and orange flavourings, at both exposure times, inhibited cell division and promoted the formation of a significant number of micronuclei and mitotic spindle changes. These alterations were observed in at least one exposure time analysed, demonstrating a significant cytotoxic, genotoxic and mutagenic activity. In mouse bioassay, animals treated with 2.0, 5.0 and 10.0 mL/kg of flavouring died before the seventh day of treatment. The amounts of 0.5 and 1.0 mL/kg of the three additives were cytotoxic to erythrocytes, and treatment with the grape flavouring significantly induced the formation of micronucleated cells in the bone marrow of animals. Therefore, under the study conditions, the grape, plum and orange flavouring additives promoted significant toxicity to cells of the test systems used.

  16. Field and laboratory tests on acute toxicity of cadmium to freshwater crayfish

    Energy Technology Data Exchange (ETDEWEB)

    1986-09-01

    Environmental regulatory standards for cadmium (EPA 1980), like those for most pollutants, are based on acute, laboratory toxicity tests of single species. Such tests can be conducted rapidly and inexpensively in comparison to acute or chronic field studies, but their validity has often been questioned. Laboratory-based criteria are subject to two criticisms: (1) chemical and physical conditions differ greatly in degree and variability from laboratory to field, and (2) species are not isolated, but live in an ecosystem of interacting taxa and biofeedback. To investigate the validity of basing field toxicity standards on laboratory data, the authors subjected the freshwater crayfish Orconectes immunis for 96 h to various levels of cadmium in laboratory aquaria and experimental ponds. The study was designed to evaluate in part the first criticism of lab-based criteria. The studies were conducted concurrently with similar short-term experiments on the fathead minnow, Pimephales promelas, and coincided with studies of chronic cadmium stress on fathead minnows in experimental ponds.

  17. Laboratory Rodent Diets Contain Toxic Levels of Environmental Contaminants: Implications for Regulatory Tests.

    Directory of Open Access Journals (Sweden)

    Robin Mesnage

    Full Text Available The quality of diets in rodent feeding trials is crucial. We describe the contamination with environmental pollutants of 13 laboratory rodent diets from 5 continents. Measurements were performed using accredited methodologies. All diets were contaminated with pesticides (1-6 out of 262 measured, heavy metals (2-3 out of 4, mostly lead and cadmium, PCDD/Fs (1-13 out of 17 and PCBs (5-15 out of 18. Out of 22 GMOs tested for, Roundup-tolerant GMOs were the most frequently detected, constituting up to 48% of the diet. The main pesticide detected was Roundup, with residues of glyphosate and AMPA in 9 of the 13 diets, up to 370 ppb. The levels correlated with the amount of Roundup-tolerant GMOs. Toxic effects of these pollutants on liver, neurodevelopment, and reproduction are documented. The sum of the hazard quotients of the pollutants in the diets (an estimator of risk with a threshold of 1 varied from 15.8 to 40.5. Thus the chronic consumption of these diets can be considered at risk. Efforts toward safer diets will improve the reliability of toxicity tests in biomedical research and regulatory toxicology.

  18. Design, construction and testing of a system for detection of toxic gases based on piezoelectric crystals.

    Science.gov (United States)

    Leyva, J A; de Cisneros, J L; de Barreda, D G; Becerra, A J

    1994-01-01

    A system for static operation of toxic gas sensors based on piezoelectric crystals was constructed as a preliminary step in the development of this type of sensor. The sensing part of the setup consists of a twin oscillating circuit assembled from commercially available electronic parts mounted on a motherboard. The oscillating circuits can accommodate two piezoelectric crystals, of which one or both can be coated with different materials, or a single one, as required. The sensing assembly (crystals plus oscillating circuits) is placed in a customized test chamber that allows one to control and reproduce its internal environment. Once assembled and fine-tuned, the proposed setup was used to test a commercially available piezoelectric crystal for sensing formaldehyde in order to expand available information on this type of sensor.

  19. Anodonta imbecillis copper sulfate reference toxicant/food test, Clinch River - Environmental Restoration Program (CR-ERP)

    Energy Technology Data Exchange (ETDEWEB)

    Simbeck, D.J.

    1997-06-01

    Reference toxicant testing using juvenile freshwater mussels was conducted as part of the CR-ERP biomonitoring study of Clinch River sediments to assess the sensitivity of test organisms and the overall performance of the test. Tests were conducted using moderately hard synthetic water spiked with known concentrations of copper as copper sulfate. Two different foods, phytoplankton and YCT-Selenastrum (YCT-S), were tested in side by side tests to compare food quality. Toxicity testing of copper sulfate reference toxicant was conducted from July 6-15, 1993. The organisms used for testing were juvenile fresh-water mussels (Anodonta imbecillis). Results from this test showed LC{sub 50} values of 0.97 and 0.84 mg Cu/L for phytoplankton and YCT-S, respectively. Previously obtained values for phytoplankton tests are 2.02 and 1.12 mg Cu/L. Too few tests have been conducted with copper as the toxicant to determine a normal range of values. Although significant reduction in growth, compared to the phytoplankton control, was seen in all treatments, including the YCT-S Control, the consequence of this observation has not been established. Ninety-day testing of juvenile mussels exhibited large variations in growth within treatment and replicate groups.

  20. Toxicity of two imidazolium ionic liquids, [bmim][BF4] and [omim][BF4], to standard aquatic test organisms: Role of acetone in the induced toxicity.

    Science.gov (United States)

    Tsarpali, Vasiliki; Dailianis, Stefanos

    2015-07-01

    The main goal of this study was to investigate the toxicity of the imidazolium-based ionic liquids (ILs), [bmim][BF4] (1-butyl-3-methylimidazolium tetrafluoroborate) and [omim][BF4] (1-octyl-3-methylimidazolium tetrafluoroborate), in battery of standard aquatic toxicity test organisms. Specifically, exposure of the algae Scenedesmus rubescens, crustaceans Thamnocephalus platyurus and Artemia franciscana, rotifers Brachionus calyciflorus and Brachionus plicatilis and bivalve Mytilus galloprovincialis to different concentrations of [bmim][BF4], [omim][BF4] and/or a binary mixture of [bmim][BF4]-[omim][BF4] (1:1) with or without acetone (carrier solvent), revealed that solvent can differentially mediate ILs' toxic profile. Acetone's ability to differentially affect ILs' cation's alkyl chain length, as well as the hydrolysis of [BF4(-)] anions was evident. Given that the toxic potency of the tested ILs seemed to be equal or even higher (in some cases) than those of conventional organic solvents, the present study revealed that the characterization of imidazolium-based ILs as "green solvents" should not be generalized, at least in case of their natural occurrence in mixtures with organic solvents, such as acetone.

  1. Test-retest repeatability of the pupil light response to blue and red light stimuli in normal human eyes using a novel pupillometer

    DEFF Research Database (Denmark)

    Herbst, Kristina; Sander, Birgit; Milea, Dan

    2011-01-01

    In this study, we evaluated the repeatability of pupil responses to colored light stimuli in healthy subjects using a prototype chromatic pupillometer. One eye of 10 healthy subjects was tested twice in the same day using monochromatic light exposure at two selected wavelengths (660 and 470¿nm......, we have developed a novel prototype of color pupillometer which demonstrates good repeatability in evoking and recording the pupillary response to a bright blue and red light stimulus....

  2. Test-retest repeatability of strength capacity, aerobic power and pericranial tenderness of neck and shoulder muscles in children - relevant for tension-type headache

    DEFF Research Database (Denmark)

    Tornøe, Birte; Andersen, Lars L; Skotte, J H

    2013-01-01

    Frequent or chronic tension-type headache in children is a prevalent and debilitating condition for the child, often leading to medication overuse. To explore the relationship between physical factors and tension-type headache in children, the quality of repeated measures was examined. The aim...... of the present study was to determine the test-retest repeatability of parameters determining isometric neck and shoulder strength and stability, aerobic power, and pericranial tenderness in children....

  3. A chronic toxicity test for the tropical marine snail Nassarius dorsatus to assess the toxicity of copper, aluminium, gallium, and molybdenum.

    Science.gov (United States)

    Trenfield, Melanie A; van Dam, Joost W; Harford, Andrew J; Parry, David; Streten, Claire; Gibb, Karen; van Dam, Rick A

    2016-07-01

    Chronic toxicity test methods for assessing the toxicity of contaminants to tropical marine organisms are generally lacking. A 96-h chronic growth rate toxicity test was developed for the larval stage of the tropical dogwhelk, Nassarius dorsatus. Growth rates of N. dorsatus larvae were assessed following exposures to copper (Cu), aluminium (Al), gallium (Ga), and molybdenum (Mo). Exposure to Cu at 28 °C validated the sensitivity of the test method, with 10% (EC10) and 50% (EC50) effect concentrations of 4.2 μg/L and 7.3 μg/L Cu, respectively. The EC10 and EC50 values for Al (toxicity of Cu and Al was also assessed at 24 °C and 31 °C, representing average year-round water temperatures for subtropical and tropical Australian coastal environments. At 24 °C, the growth rate of control larvae was reduced by 52% compared with the growth rate at 28 °C and there was an increase in sensitivity to Cu (EC50 = 4.7 μg/L) but a similar sensitivity to Al (EC50 = 180 μg/L). At 31 °C the control growth rate increased by 35% from that measured at 28 °C and there was reduced sensitivity to both Cu and Al (EC50s = 8.5 μg/L and 642 μg/L, respectively). There was minimal toxicity resulting from Ga (EC50 = 4560 μg/L) and Mo (no effect at ≤7000 μg/L Mo). Environ Toxicol Chem 2016;35:1788-1795. © 2015 SETAC.

  4. Combining autosomal and Y-chromosomal short tandem repeat data in paternity testing with male child: methods and application.

    Science.gov (United States)

    Ayadi, Imen; Mahfoudh-Lahiani, Nadia; Makni, Hafedh; Ammar-Keskes, Leila; Rebaï, Ahmed

    2007-09-01

    Paternity testing is being increasingly requested with the aim of challenging presumptive fatherhood. The ability to establish the biological father is usually based on the genotyping of autosomal short tandem repeat (STR) in alleged father, mother and child, but the use of Y-chromosomal STR has gained interest in the last few years. In this work, we propose a new probabilistic approach that combines autosomal and Y-chromosomal STR data in paternity testing with father/son pairs taking into account mutation events. We also suggest a new two-stage approach where we first type Y-STRs and possibly autosomal STR for the putative father and son, conditional on Y-STR results. We applied this approach to 22 cases. Our results show that Y-STRs can identify nonpaternity cases with high accuracy but need to be validated with autosomal STR to establish paternity. Moreover, the two-stage approach is less costly than the standard approach and is very useful in motherless cases.

  5. A CA-repeat polymorphism close to the adenomatous polyposis coli (APC) gene offers improved diagnostic testing for familial APC

    Energy Technology Data Exchange (ETDEWEB)

    Spirio, L.; Nelson, L.; Ward, K.; Burt, R.; White, R.; Leppert, M. (Univ. of Utah, Salt Lake City (United States))

    1993-02-01

    Presymptomatic genetic testing for the presence of a mutant allele causing familial adenomatous polyposis coli (APC) has been difficult to perform effectively in the past because DNA markers surrounding the APC gene on chromosome 5q have not been very informative. The authors report results of genetic linkage studies on both research families and clinical families by using D5S346, a highly polymorphic dinucleotide (CA)-repeat locus 30-70 kb from the APC gene. Linkage analysis with this marker in a large APC pedigree showed an increase of at least 9.0 LOD units, in likelihood of linkage of the disease-causing allele to the APC locus, when compared with the highest LOD score attained with any other closely linked marker. When the first 14 APC families that requested genotypic analysis by the DNA Diagnostic Laboratory at the University of Utah were tested with D5S346, 20 of the 31 at-risk individuals were identified as either carriers or noncarriers of an APC-predisposing allele. The authors see this marker as an important tool for research studies and for the presymptomatic diagnosis of APC. 28 refs., 3 figs., 2 tabs.

  6. Influence of enrichment on behavioral and neurogenic effects of antidepressants in Wistar rats submitted to repeated forced swim test.

    Science.gov (United States)

    Possamai, Fernanda; dos Santos, Juliano; Walber, Thais; Marcon, Juliana C; dos Santos, Tiago Souza; Lino de Oliveira, Cilene

    2015-04-01

    Repeated forced swimming test (rFST) may detect gradual effects of antidepressants in adult rats. Antidepressants, as enrichment, affected behavior and neurogenesis in rats. However, the influence of enrichment on behavioral and neurogenic effects of antidepressants is unknown. Here, effects of antidepressants on rFST and hippocampal neurogenesis were investigated in rats under enriched conditions. Behaviors of male Wistar rats, housed from weaning in standard (SE) or enriched environment (EE), were registered during rFST. The rFST consisted of 15min of swimming (pretest) followed by 5min of swimming in the first (test), seventh (retest 1) and fourteenth (retest 2) days after pretest. One hour before the test, rats received an intraperitoneal injection of saline (1ml/kg), fluoxetine (2.5mg/kg) or imipramine (2.5 or 5mg/kg). These treatments were performed daily until the day of the retest 2. After retest 2, rats were euthanized for the identification of markers for neurogenesis in the hippocampus. Fluoxetine or imipramine decreased immobility in retests 1 and 2, as compared to saline. EE abolished these differences. In EE, fluoxetine or imipramine (5mg/kg) reduced immobility time in retest 2, as compared to the test. Independent of the housing conditions, fluoxetine and imipramine (5mg/kg) increased the ratio of immature neurons per progenitor cell in the hippocampus. In summary, antidepressants or enrichment counteracted the high immobility in rFST. Enrichment changed the effects of antidepressants in rFST depending on the type, and the dose of a substance but failed to change neurogenesis in control or antidepressant treated-rats. Effects of antidepressants and enrichment on rFST seemed neurogenesis-independent.

  7. Testing of the estrogenic activity and toxicity of Stephania venosa herb in ovariectomized rats.

    Science.gov (United States)

    Gomuttapong, Sarawoot; Pewphong, Rangsima; Choeisiri, Sucha; Jaroenporn, Sukanya; Malaivijitnond, Suchinda

    2012-07-01

    Stephania venosa Spreng is a traditional herb which has been used for cancer treatment as well as an aphrodisiac. The scientific literature strongly supports its in vitro antiproliferative effects on cancer cell lines and has suggested developing this plant as a potential anticancer drug. However, the in vivo steroidogenic activity and toxicity of this plant have never been tested. We analyzed the levels of five key isoflavones in the plant extract by quantitative HPLC and then evaluated the in vivo estrogenic activity and toxicity in ovariectomized rats, in comparison with the phytoestrogen-rich plant, Pueraria mirifica. Twenty rats were first ovariectomized, and then seven days later divided into four groups and gavaged daily with 0, 10 and 100 mg/kg body weight/day of S. venosa, or 100 mg/kg body weight/day of P. mirifica for 28 days. A trace amount of puerarin, daidzin and daidzein with a subtle amount of genistein and genistin were isolated from the S. venosa tuber extract. S. venosa tuber powder, at both doses, did not exhibit any detectable estrogenic activity in ovariectomized rats, as assessed by the vaginal cytology and uterotropic assays, whilst P. mirifica induced a remarkable vaginal and uterine proliferation. S. venosa induced a toxicological effect on the hematological values and histopathological appearance of metabolic organs. Taken together, these results suggest that S. venosa has no discernable estrogenic activity but that it is toxic, at least to ovariectomized rats. Thus, the use of this plant for anticancer treatment needs to be reassessed or used with caution.

  8. Screening for ovarian cancer in women with varying levels of risk, using annual tests, results in high recall for repeat screening tests

    Directory of Open Access Journals (Sweden)

    Nobbenhuis Marielle AE

    2011-11-01

    Full Text Available Abstract Background We assessed ovarian cancer screening outcomes in women with a positive family history of ovarian cancer divided into a low-, moderate- or high-risk group for development of ovarian cancer. Methods 545 women with a positive family history of ovarian cancer referred to the Ovarian Screening Service at the Royal Marsden Hospital, London from January 2000- December 2008 were included. They were stratified into three risk-groups according to family history (high-, moderate- and low-risk of developing ovarian cancer and offered annual serum CA 125 and transvaginal ultrasound screening. The high-risk group was offered genetic testing. Results The median age at entry was 44 years. The number of women in the high, moderate and low-risk groups was 397, 112, and 36, respectively. During 2266 women years of follow-up two ovarian cancer cases were found: one advanced stage at her fourth annual screening, and one early stage at prophylactic bilateral salpingo-oophorectomy (BSO. Prophylactic BSO was performed in 138 women (25.3%. Forty-three women had an abnormal CA125, resulting in 59 repeat tests. The re-call rate in the high, moderate and low-risk group was 14%, 3% and 6%. Equivocal transvaginal ultrasound results required 108 recalls in 71 women. The re-call rate in the high, moderate, and low-risk group was 25%, 6% and 17%. Conclusion No early stage ovarian cancer was picked up at annual screening and a significant number of re-calls for repeat screening tests was identified.

  9. 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

  10. Studies with the USF/NASA toxicity screening test method - Effect of air flow and effect of fabric dye

    Science.gov (United States)

    Hilado, C. J.; Lopez, M. T.

    1976-01-01

    One sample each of commercial polyurethane and polychloroprene flexible foams were evaluated using the USF/NASA toxicity screening test method. Air flow rates of 0, 0.16, 16, and 48 ml/sec were used to determine the effect of air flow on relative toxicity. Time to first sign of incapacitation and time to death were substantially reduced with both polyurethane and polychloroprene flexible foams by the introduction of 16 to 48 ml/sec air flow. The relative toxicity rankings of these materials were not altered by changes in air flow. Under these test conditions, the polyurethane foam consistently appeared more toxic than the polychloroprene foam. Samples of six different colors from the same fabric were evaluated separately, using the USF/NASA toxicity screening test method, to determine the effect of fabric dye, if any. The material was an upholstery fabric, consisting of 46 percent cotton, 33 percent wool, and 21 percent nylon. There appeared to be no significant effect of fabric dye on relative toxicity, for this material under these test conditions.

  11. A field assessment of long-term laboratory sediment toxicity tests with the amphipod Hyalella azteca

    Science.gov (United States)

    Ingersoll, Christopher G.; Wang, Ning; Hayward, Jeannie M. R.; Jones, John R.; Jones, Susan B.; Ireland, D. Scott

    2005-01-01

    Response of the amphipod Hyalella azteca exposed to contaminated sediments for 10 to 42 d in laboratory toxicity tests was compared to responses observed in controlled three-month invertebrate colonization exposures conducted in a pond. Sediments evaluated included a sediment spiked with dichlorodiphenyldichloroethane (DDD) or dilutions of a field sediment collected from the Grand Calumet River (GCR) in Indiana (USA) (contaminated with organic compounds and metals). Consistent effects were observed at the highest exposure concentrations (400 ??g DDD/goc [DDD concentrations normalized to grams of organic carbon (goc) in sedimentl or 4% GCR sediment) on survival, length, and reproduction of amphipods in the laboratory and on abundance of invertebrates colonizing sediments in the field. Effect concentrations for DDD observed for 10-d length and 42-d reproduction of amphipods (e.g., chronic value [ChV] of 66 ??g DDD/goc and 25% inhibition concentration [IC25] of 68 ??g DDD/goc for reproduction) were similar to the lowest effect concentrations for DDD measured on invertebrates colonizing sediment the field. Effect concentrations for GCR sediment on 28-d survival and length and 42-d reproduction and length of amphipods (i.e., ChVs of 0.20-0.66% GCR sediment) provided more conservative effect concentrations compared to 10-d survival or length of amphipods in the laboratory or the response of invertebrates colonizing sediment in the field (e.g., ChVs of 2.2% GCR sediment). Results of this study indicate that use of chronic laboratory toxicity tests with H. azteca and benthic colonization studies should be used to provide conservative estimates of impacts on benthic communities exposed to contaminated sediments. Bioaccumulation of DDD by oligochaetes colonizing the DDD-spiked sediment was similar to results of laboratory sediment tests previously conducted with the oligochaete Lumbriculus variegates, confirming that laboratory exposures can be used to estimate

  12. Furan toxicity on testes and protective role of lycopene in diabetic rats

    Science.gov (United States)

    Kara, Özlem; Baş, Hatice; Pandır, Dilek

    2016-01-01

    Objective Furan (C4H4O) is a heat-induced food contaminant that is utilized as an industrial chemical agent. Lycopene is a natural substance that is produced by plants and tomatoes. We aimed to evaluate the toxicity of furan on testes and the protective effect of lycopene in diabetic rats. Material and Methods Male Wistar albino rats were divided into five groups: Group 1 (control group) received 1 mL/kg corn oil. Group 2 (diabetic control group) received 55 mg/kg STZ and 1 mL/kg corn oil. Group 3 (diabetic lycopene group) received 55 mg/kg STZ and 4 mg/kg lycopene. Group 4 (diabetic furan group) received 55 mg/kg STZ and 40 mg/kg furan. Group 5 (diabetic furan + lycopene group) received 55 mg/kg STZ, 40 mg/kg furan, and 4 mg/kg lycopene. After 28 days, the testes were extirpated in all groups. In the testicular tissue samples, the level of malondialdehyde (MDA) and the activities of catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), and reducted glutathione (GST) were studied. Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone levels were measured. Histopathologic examination was performed by light microscope. Results The MDA level and the activities of CAT, GPx, SOD, and GST were found to be higher in the furan group than in the control and diabetic control groups (p<0.05). The MDA level and the activities of CAT, GPx, SOD, and GST were significantly lower in the furan + lycopene group than in the furan group (p<0.05). Conclusion The low blood testosterone level in the rats who received furan suggested the presence of endocrinological defects and cellular degenerative changes. Lycopene may be effective to reverse furan toxicity in diabetic rat testes. PMID:27990087

  13. An Exploratory Analysis of Stream Teratogenicity and Human Health Using Zebrafish Whole-Sediment Toxicity Test

    Directory of Open Access Journals (Sweden)

    Matthew Dellinger

    2014-02-01

    Full Text Available This study demonstrates a novel application of effect-based toxicity testing for streams that may provide indications of co-perturbation to ecological and human health. For this study, a sediment contact assay using zebrafish (Danio rerio embryos was adapted to serve as an indicator of teratogenic stress within river sediments. Sediment samples were collected from Lake Michigan tributary watersheds. Sediment contact assay responses were then compared to prevalence of congenital heart disease (CHD and vital statistic birth indicators aggregated from civil divisions associated with the watersheds. Significant risk relationships were detected between variation in early life-stage (ELS endpoints of zebrafish embryos 72 h post-fertilization and the birth prevalence of human congenital heart disease, low birthweight and infant mortality. Examination of principal components of ELS endpoints suggests that variance related to embryo heart and circulatory malformations is most closely associated with human CHD prevalence. Though toxicity assays are sometimes used prospectively, this form of investigation can only be conducted retrospectively. These results support the hypothesis that bioassays normally used for ecological screening can be useful as indicators of environmental stress to humans and expand our understanding of environmental–human health linkages.

  14. The effect of repeated measurements and working memory on the most comfortable level in the ANL test

    DEFF Research Database (Denmark)

    Brännström, K Jonas; Olsen, Steen Østergaard; Holm, Lucas

    2014-01-01

    interleaved methodology during one session using a non-semantic version. Phonological (PWM) and visuospatial working memory (VSWM) was measured. STUDY SAMPLE: Thirty-two normal-hearing adults. RESULTS: Repeated measures ANOVA, intraclass correlations, and the coefficient of repeatability (CR) were used...

  15. Repeated Strains, Social Control, Social Learning, and Delinquency: Testing an Integrated Model of General Strain Theory in China

    Science.gov (United States)

    Bao, Wan-Ning; Haas, Ain; Chen, Xiaojin; Pi, Yijun

    2014-01-01

    In Agnew's general strain theory, repeated strains can generate crime and delinquency by reducing social control and fostering social learning of crime. Using a sample of 615 middle-and high-school students in China, this study examines how social control and social learning variables mediate the effect of repeated strains in school and at home on…

  16. The SOS-LUX-TOXICITY-Test on the International Space Station.

    Science.gov (United States)

    Rabbow, Elke; Stojicic, Nevena; Walrafen, David; Baumstark-Khan, Christa; Rettberg, Petra; Schulze-Varnholt, Dirk; Franz, Markus; Reitz, Günther

    2006-01-01

    For the safety of astronauts and to ensure the stability and integrity of the genome of microorganisms and plants used in bioregenerative life support systems, it is important to improve our knowledge of the combined action of (space) radiation and microgravity. The SOS-LUX-TOXICITY test, as part of the TRIPLE-LUX project (accepted for flight at Biolab in Columbus on the International Space Station, (ISS)), will provide an estimation of the health risk resulting from exposure of astronauts to the radiation environment of space in microgravity. The project will: (i) increase our knowledge of biological/health threatening action of space radiation and enzymatic DNA repair; (ii) uncover cellular mechanisms of synergistic interaction of microgravity and space radiation; (iii) provide specified biosensors for spacecraft milieu examination; and (iv) provide experimental data on stability and integrity of bacterial DNA in spacecrafts. In the bacterial biosensor "SOS-LUX-Test" developed at DLR (patent), bacteria are transformed with the pBR322-derived plasmid pPLS-1 or the similar, advanced plasmid SWITCH, both carrying the promoterless lux operon of Photobacterium leiognathi as the reporter element controlled by a DNA damage-dependent SOS promoter as sensor element. A short description of the space experiment is given, and the current status of adaptation of the SOS-LUX-Test to the ISS, i.e. first results of sterilization, biocompatibility and functional tests performed with the already available hardware and bread board model of the automated space hardware under development, is described here.

  17. Thermal Stress and Toxicity

    Science.gov (United States)

    Elevating ambient temperature above thermoneutrality exacerbates toxicity of most air pollutants, insecticides, and other toxic chemicals. On the other hand, safety and toxicity testing of toxicants and drugs is usually performed in mice and rats maintained at subthermoneutral te...

  18. Highly Effective DNA Extraction Method for Nuclear Short Tandem Repeat Testing of Skeletal Remains from Mass Graves

    Science.gov (United States)

    Davoren, Jon; Vanek, Daniel; Konjhodzić, Rijad; Crews, John; Huffine, Edwin; Parsons, Thomas J.

    2007-01-01

    Aim To quantitatively compare a silica extraction method with a commonly used phenol/chloroform extraction method for DNA analysis of specimens exhumed from mass graves. Methods DNA was extracted from twenty randomly chosen femur samples, using the International Commission on Missing Persons (ICMP) silica method, based on Qiagen Blood Maxi Kit, and compared with the DNA extracted by the standard phenol/chloroform-based method. The efficacy of extraction methods was compared by real time polymerase chain reaction (PCR) to measure DNA quantity and the presence of inhibitors and by amplification with the PowerPlex 16 (PP16) multiplex nuclear short tandem repeat (STR) kit. Results DNA quantification results showed that the silica-based method extracted on average 1.94 ng of DNA per gram of bone (range 0.25-9.58 ng/g), compared with only 0.68 ng/g by the organic method extracted (range 0.0016-4.4880 ng/g). Inhibition tests showed that there were on average significantly lower levels of PCR inhibitors in DNA isolated by the organic method. When amplified with PP16, all samples extracted by silica-based method produced 16 full loci profiles, while only 75% of the DNA extracts obtained by organic technique amplified 16 loci profiles. Conclusions The silica-based extraction method showed better results in nuclear STR typing from degraded bone samples than a commonly used phenol/chloroform method. PMID:17696302

  19. A 28-day repeat dose toxicity study of steroidal glycoalkaloids a-solanine and a-chaconine in the Syrian Golden Hamster

    NARCIS (Netherlands)

    Langkilde, S.; Mandimika, T.; Schroder, M.; Meyer, O.; Slob, W.; Peijnenburg, A.A.C.M.; Poulsen, M.

    2009-01-01

    Glycoalkaloids ¿-solanine and ¿-chaconine are naturally present toxicants in the potato plant (Solanum tuberosum). Human intake of high doses of glycoalkaloids has led to acute intoxication, in severe cases coma and death. Previous studies have indicated that the ratio of ¿-solanine to ¿-chaconine m

  20. Toxicity testing of restorative dental materials using brine shrimp larvae (Artemia salina).

    Science.gov (United States)

    Milhem, Manar M; Al-Hiyasat, Ahmad S; Darmani, Homa

    2008-01-01

    This study investigated the effect of extracts of different composites, glass ionomer cement (GIC)s and compomers on the viability of brine shrimp larvae. Ethanolic extracts of four dental composites (Z-100; Solitaire 2; Filtek P60 and Synergy), a conventional GIC (Ketac-Fil), a resin-modified glass ionomer cement (Vitremer), two compomers (F2000; Dyract AP), and a flowable compomer (Dyract Flow) were prepared from each material. Following evaporation of the ethanol, the extracts were resuspended in distilled water, which was then used to test the effects on the viability of brine shrimp larvae. For the composites, the extract of Synergy was the least toxic (88% viability) followed by the extracts of Solitaire 2, Z100 and P60 (75%, 67.5% and 50% viability, respectively). One-way ANOVA revealed highly significant differences between the resin composite materials (pbrine shrimp larvae followed by GICs and then composites.

  1. Static renewal tests using Anodonta imbecillis (freshwater mussels). Anodonta imbecillis copper sulfate reference toxicant/food test, Clinch River-Environmental Restoration Program (CR-ERP)

    Energy Technology Data Exchange (ETDEWEB)

    Simbeck, D.J.

    1993-12-31

    Reference toxicant testing using juvenile freshwater mussels was conducted as part of the CR-ERP biomonitoring study of Clinch River sediments to assess the sensitivity of test organisms and the overall performance of the test. Tests were conducted using moderately hard synthetic water spiked with known concentrations of copper as copper sulfate. Two different foods, phytoplankton and YCT-Selenastrum (YCT-S), were tested in side by side tests to compare food quality. Toxicity testing of copper sulfate reference toxicant was conducted from July 6--15, 1993. The organisms used for testing were juvenile fresh-water mussels (Anodonta imbecillis). Although significant reduction in growth, compared to the phytoplankton control, was seen in all treatments, including the YCT-S Control, the consequence of this observation has not been established. Ninety-day testing of juvenile mussels exhibited large variations in growth within treatment and replicate groups. Attachments to this report include: Toxicity test bench sheets and statistical analyses; and Copper analysis request and results.

  2. Bio-testing integral toxicity of corrosion inhibitors, biocides and oil hydrocarbons in oil-and gas-processing industry

    Energy Technology Data Exchange (ETDEWEB)

    Chugunov, V.A.; Kholodenko, V.P.; Irkhina, I.A.; Fomchenkov, V.M.; Novikov, I.A. [State Research Center for Applied Microbiology, Obolensk, Moscow (Russian Federation)

    2004-07-01

    In recent years bioassays have been widely used for assessing levels of contamination of the environment. This is due to the fact that test-organisms provide a general response to toxicants present in samples. Based on microorganisms as test objects, it is possible to develop cheap, sensitive and rapid assays to identify environmental xenobiotics and toxicants. The objective of the research was to develop different microbiological assays for assessing integral toxicity of water environments polluted with corrosion inhibitors, biocides and hydrocarbons in oil- and gas-processing industry. Bio-luminescent, electro-orientational, osmo-optic and microorganism reducing activity assays were used for express evaluation of integral toxicity. They are found to determine promptly integral toxicity of water environments containing various pollutants (oil, oil products, corrosion inhibitors, biocides). Results conclude that the assays may be used for analyzing integral toxicity of water polluted with hydrocarbons, as well as for monitoring of water changes as a result of biodegradation of pollutants by microorganisms and their associations. Using a kit of different assays, it is also possible to evaluate ecological safety of biocides, corrosion inhibitors, and their compositions. Bioassays used as a kit are more effective than each assay individually, allowing one to get complete characterization of a reaction of bacterial test organisms to different environments. (authors)

  3. The SOS-LUX-LAC-FLUORO-Toxicity-test on the International Space Station (ISS)

    Science.gov (United States)

    Rabbow, E.; Rettberg, P.; Baumstark-Khan, C.; Horneck, G.

    In the 21 st century, an increasing number of astronauts will visit the International Space Station (ISS) for prolonged times. Therefore it is of utmost importance to provide necessary basic knowledge concerning risks to their health and their ability to work on the station and during extravehicular activities (EVA) in free space. It is the aim of one experiment of the German project TRIPLE-LUX (to be flown on the ISS) to provide an estimation of health risk resulting from exposure of the astronauts to the radiation in space inside the station as well as during extravehicular activities on one hand, and of exposure of astronauts to unavoidable or as yet unknown ISS-environmental genotoxic substances on the other. The project will (i) provide increased knowledge of the biological action of space radiation and enzymatic repair of DNA damage, (ii) uncover cellular mechanisms of synergistic interaction of microgravity and space radiation and (iii) examine the space craft milieu with highly specific biosensors. For these investigations, the bacterial biosensor SOS-LUX-LAC-FLUORO-Toxicity-test will be used, combining the SOS-LUX-Test invented at DLR Germany (Patent) with the commercially available LAC-FLUORO-Test. The SOS-LUX-Test comprises genetically modified bacteria transformed with the pBR322-derived plasmid pPLS-1. This plasmid carries the promoterless lux operon of Photobacterium leiognathi as a reporter element under control of the DNA-damage dependent SOS promoter of ColD as sensor element. This system reacts to radiation and other agents that induce DNA damages with a dose dependent measurable emission of bioluminescence of the transformed bacteria. The analogous LAC-FLUORO-Test has been developed for the detection of cellular responses to cytotoxins. It is based on the constitutive expression of green fluorescent protein (GFP) mediated by the bacterial protein expression vector pGFPuv (Clontech, Palo Alto, USA). In response to cytotoxic agents, this system

  4. Rapid and cost-effective multiparameter toxicity tests for soil microorganisms.

    Science.gov (United States)

    Carbonell, G; Pablos, M V; García, P; Ramos, C; Sánchez, P; Fernández, C; Tarazona, J V

    2000-03-20

    Three biochemical parameters, DNA quantification in soil samples and two enzymatic activities, beta-galactosidase and dehydrogenase have been assessed as potential end-points for the use in cost-effective toxicity tests on soil microorganisms. The assessment included the development of a classical dose-response 24-h assay and the incorporation of measurements of the effects on microbial activities in soil column leaching studies and multispecies miniaturised terrestrial systems (MTS). Four different chemicals, copper, a new herbicide, thiabendazole and fenthion were studied. A rapid fluorescence DNA quantification technique did not produce adequate responses. The efforts to quantify DNA after extraction and clean-up procedures failed due to the presence of humic acids. From the protocol of the technique one could see that the technical procedure is time-consuming and expensive and, for this reason, not suitable for use as a parameter in rapid and cost-effective tests. However, the enzymatic activities showed their potential as toxicity end-points. Copper produced a concentration/response inhibition of beta-galactosidase and dehydrogenase with EC50 values of 78.39 and 24.77 mg Cu/kg soil, respectively. In the soil column study, these endpoints allowed the measurement of the microbial activities through the column. The effects of the new herbicide on beta-galactosidase and dehydrogenase activities were statistically significant for the highest application dose (40 g/ha). Thiabendazole affected the microbial activity when mixed within the soil, but no effects were observed when this fungicide was applied on the soil surface. Fenthion produced effects when applied either in the soil or on the soil surface. These results can be explained by the low mobility of thiabendazole. The results show the capabilities of these biochemical parameters to be included as endpoints in cost-effective bioassays.

  5. Is strength of handedness reliable over repeated testing? An examination of typical development and Autism Spectrum Disorder.

    Directory of Open Access Journals (Sweden)

    Sara Marie Scharoun

    2015-02-01

    Full Text Available Despite a lack of agreement concerning the age at which adult-like patterns of handedness emerge, it is generally understood that hand preference presents early in life and development is variable. Young children (ages 3-5 years are described as having weak hand preference; however, older children (ages 7-10 years display stronger patterns. Here, strength of hand preference refers to reliable use of the preferred hand. In comparison to their typically-developing (TD peers, individuals with Autism Spectrum Disorder (ASD are described as having a weak hand preference. This study aimed to extend the literature to assess three measures of handedness (Waterloo Handedness Questionnaire – WHQ, Annett Pegboard – AP and WatHand Cabinet Test – WHCT in two repeated sessions. The first research question aimed to delineate if the strength of hand use changes across testing sessions as a function of age in typical development. Right-handed children reported a reliable preference for the right hand on the WHQ, similar to adults. A marginally significant difference was revealed between 3- to 4- and 5- to 6-year-olds on the AP. This was attributed to weak lateralization in 3- to 4-year-olds, where the establishment of hand preference by age 6 leads to superior performance with the preferred hand in 5- to 6-year-olds. Finally, for the WHCT, 3- to 4-year-olds had the highest bimanual score, indicating use of the same hand to lift the cabinet door and retrieve an object. It is likely that the task was not motorically complex enough to drive preferred hand selection for older participants. The second research question sought to determine if there is difference between typically-developing children and children with ASD. No differences were revealed; however, children with ASD did display variable AP performance, providing partial support for previous literature. Findings will be discussed in light of relevant literature.

  6. Influence of developmental stage, salts and food presence on various end points using Caenorhabditis elegans for aquatic toxicity testing

    Energy Technology Data Exchange (ETDEWEB)

    Donkin, S.G.; Williams, P.L. [Univ. of Georgia, Athens, GA (United States)

    1995-12-01

    This study used a randomized block design to investigate the importance of several variables in using the free-living soil nematode, Caenorhabditis elegans, for aquatic toxicity testing. Concentration-response data were obtained on nematodes of various developmental stages exposed to four metals (Cd, Pb, Cu, and Hg) and a water-soluble organic toxicant, sodium pentachlorophenate (PCP), under conditions of varied solvent medium (with or without salts and with or without a bacterial food source). The end points measured were 24- and 96-h mortality LC50 value, as well as development of larval stages to adulthood and evidence of reproduction. The results suggest that nematodes of various ages respond similarity to a given toxicant for all end points measured, although adults cultured from eggs appeared more sensitive than adults cultured from dauer larvae. The most important environmental variable in determining toxicity was the medium in which the tests were conducted. The presence of potassium and sodium salts in the medium significantly (p < 0.05) reduced the toxicity of many test samples. The presence of bacteria had little effect on 24-h tests with salts, but was important in 96-h survival and development. Based on sensitivity and ease of handling, adults cultured from eggs are recommended in both 24h and 96-h tests.

  7. Leach and EP (extraction procedure) toxicity tests on grouted waste from Tank 106-AN

    Energy Technology Data Exchange (ETDEWEB)

    Serne, R.J.; Martin, W.J.; Lokken, R.O.; LeGore, V.L.; Lindenmeier, C.W.; Martin, P.F.C.

    1989-09-01

    Pacific Northwest Laboratory is conducting laboratory experiments to produce leach rate data for various waste species that will be contained in grout at Hanford. In the work reported here, grout made from Tank 106-AN liquid waste was used to produce empirical leach rate data for several radionuclides ({sup 60}Co, {sup 90}Sr, {99}Tc, {129}I, {137}Cs, and {sup 241}Am), stable major components (NO{sub 3}{sup {minus}}, NO{sub 2}{sup {minus}}, F, Cl, and Na), and trace metals (Cr, Mo, and Ni). Two types of tests were used to produce leach rate data: an intermittent replacement leach test (ANS 16.1 leach test) and a static leach test. Measured effective diffusivities of key species are as follows: 4 to 6 {times} 10{sup {minus}8} cm{sup 2}/sec for {sup 99}Tc, 3 to 7 {times} 10{sup {minus}8} cm{sup 2}/sec for {sup 129}I, 4 to 6 {times} 10{sup {minus}9} cm{sup 2}/sec for nitrate, and 6 to 7 {times} 10{sup {minus}9} cm{sup 2}/sec for nitrite. The leach indices of all species studied are above (more favorable than) the waste form criteria. The leach indices for {sup 99}Tc and {sup 129}I are 7.4 {plus minus} 1.2 and 7.6 {plus minus} 0.4, respectively, and are being further investigated in continuing studies of double-shell slurry feed grouts. An Extraction Procedure (EP) toxicity test was also conducted and the grouted water is considered nontoxic per this test protocol. 19 refs., 9 figs., 8 tabs.

  8. Risk of sensitization in healthy adults following repeated administration of rdESAT-6 skin test reagent by the Mantoux injection technique

    DEFF Research Database (Denmark)

    Lillebaek, Troels; Bergstedt, Winnie; Tingskov, Pernille N;

    2009-01-01

    1 open clinical trial was to assess the sensitization risk and safety of repeated administration of rdESAT-6 reagent in 31 healthy adult volunteers. Three groups of volunteers received two fixed doses of 0.1 microg rdESAT-6 28, 56 or 112 days apart, respectively. After the second injection......Limited specificity of the tuberculin skin test incited the development of the intradermal Mycobacterium tuberculosis-specific rdESAT-6 skin test. Animal studies have shown, however, that there is a possible risk of sensitization when repeated injections of rdESAT-6 are given. The aim of this phase...

  9. Effect-based interpretation of toxicity test data using probability and comparison with alternative methods of analysis

    Energy Technology Data Exchange (ETDEWEB)

    Gully, J.R.; Baird, R.B.; Markle, P.J.; Bottomley, J.P.

    2000-01-01

    A methodology is described that incorporates the intra- and intertest variability and the biological effect of bioassay data in evaluating the toxicity of single and multiple tests for regulatory decision-making purposes. The single- and multiple-test regulatory decision probabilities were determined from t values (n {minus} 1, one-tailed) derived from the estimated biological effect and the associated standard error at the critical sample concentration. Single-test regulatory decision probabilities below the selected minimum regulatory decision probability identify individual tests as noncompliant. A multiple-test regulatory decision probability is determined by combining the regulatory decision probability of a series of single tests. A multiple-test regulatory decision probability is determined by combining the regulatory decision probability of a series of single tests. A multiple-test regulatory decision probability below the multiple-test regulatory decision minimum identifies groups of tests in which the magnitude and persistence of the toxicity is sufficient to be considered noncompliant or to require enforcement action. Regulatory decision probabilities derived from the t distribution were compared with results based on standard and bioequivalence hypothesis tests using single- and multiple-concentration toxicity test data from an actual national pollutant discharge incorporated the precision of the effect estimate into regulatory decisions at a fixed level of effect. Also, probability-based interpretation of toxicity tests provides incentive to laboratories to produce, and permit holders to use, high-quality, precise data, particularly when multiple tests are used in regulatory decisions. These results are contrasted with standard and bioequivalence hypothesis tests in which the intratest precision is a determining factor in setting the biological effect used for regulatory decisions.

  10. Replacing animal experiments in developmental toxicity testing of phenols by combining in vitro assays with physiologically based kinetic (PBK) modelling

    NARCIS (Netherlands)

    Strikwold, Marije

    2016-01-01

    Many efforts have been undertaken over the past decades to develop in vitro tests for a wide range of toxicological endpoints as an alternative to animal testing. The principle application of in vitro toxicity assays still lies in the hazard assessment and the prioritisation of chemicals for further

  11. Using a Sequence Homology-Based Predictive Strategy to Address Current Demands for Focused Toxicity Testing in Ecological Risk Assessment

    Science.gov (United States)

    The lack of resources available for comprehensive toxicity testing, international interest in limiting the quantity of animals used in testing, and a mounting list of anthropogenic chemicals produced world-wide have led to the exploration of innovative means for identifying chemi...

  12. An assessment of Hyalella azteca burrowing activity under laboratory sediment toxicity testing conditions.

    Science.gov (United States)

    Doig, Lorne E; Liber, Karsten

    2010-09-01

    Burrowing of the freshwater amphipod Hyalella azteca was evaluated under laboratory conditions similar to those recommended for standard sediment toxicity testing in Canada (EPS 1/RM/33; Environment Canada, 1997) and the United States (EPA/600/R-99/064; US EPA, 2000). Sediment type, time of day (light versus dark), size of animal, and the presence or absence of food were varied to assess their effects on burrowing activity. Hyalella azteca were found to burrow rapidly in fine, organic-rich sediments, but were slower to burrow in a sandy sediment. There was no increase in the number of animals occupying the sediment surface of a fine, organic-rich sediment after 4h of darkness compared to the previous 4h of light. Over a 9- to 10-d duration, a higher percentage of animals occupied the surface of the sandy sediment. The addition of food promoted burrowing in sandy sediment, as did using smaller animals. Overall, longer-duration tests involving older animals and coarse sediments may require formal observation to confirm burrowing and ensure adequate sediment exposure. The addition of food during a test may promote the burrowing of larger animals in coarse sediments, but may not be necessary in field-collected sediments that are not excessively sandy.

  13. Status of the SOS-LUX-Toxicity-Test on the International Space Station

    Science.gov (United States)

    Rabbow, E.; Rettberg, Petra; Baumstark-Khan, Christa; Schulze-Varnholt, Dirk; Franz, Markus; Reitz, Gunther

    2005-08-01

    For the safety of astronauts and to ensure stability and integrity of the genome of microorganisms and plants used in bioregenerative life support systems it is important to improve our knowledge on the combined action of (space) radiation and microgravity. The SOS-LUX- Toxicity Test as part of the TRIPLE-LUX project (accepted for flight in Biolab in Columbus on ISS) will provide an estimation of the health risk resulting from exposure of astronauts to the radiation environment of space in microgravity. The project will (i) increase knowledge of biological/health threatening action of space radiation and enzymatic DNA repair, (ii) uncover cellular mechanisms of synergistic interaction of microgravity and space radiation, (iii) provide specified biosensors for spacecraft milieu examination and (iv) provide experimental data on stability and integrity of bacterial DNA in spacecrafts. In the bacterial biosensor "SOS-LUX-Test" developed at DLR (patent), bacteria are transformed with the pBR322- derived plasmid pPLS-1 or the similar advanced plasmid Switch, both carrying the promoterless lux operon of Photobacterium leiognathi as reporter element controlled by a DNA-damage dependent SOS promoter as sensor element. A short description of the space experiment and first results of tests with the bread board model of the automated space hardware under development are given.

  14. Amphipod and Sea Urchin tests to assess the toxicity of Mediterranean sediments: the case of Portmán Bay

    Directory of Open Access Journals (Sweden)

    A. Cesar

    2004-04-01

    Full Text Available The sediment formed by the tailings of an abandoned mine, which discharged into Portmán Bay, Murcia, SE-Spain, was tested to establish a possible gradient of heavy metals. The results were compared with tolerance limits of what was calculated from control sites. Whole sediment toxicity tests were performed on two amphipod species, Gammarus aequicauda and Microdeutopus gryllotalpa, while sediment-water interface and porewater toxicity tests were performed on three sea urchins species, Arbacia lixula, Paracentrotus lividus and Sphaerechinus granularis. The sensitivity of these marine organisms was evaluated by exposure tests using the reference substances: ammonium chloride (NH4Cl, cadmium chloride (CdCl2, potassium dichromate (K2Cr2O7, sodium dodecyl sulfate (C12H25NaO4S and zinc sulfate (ZnSO4. The concentration of heavy metals decreased along the pollution gradient. Amphipod 10 day acute toxicity tests clearly demonstrated the gradient of toxicity. The sediment-water interface tests conducted with sea urchins also pointed to a pollution gradient and were more sensitive than the tests involving amphipods.

  15. A 28-day repeat dose toxicity study of steroidal glycoalkaloids, alpha-solanine and alpha-chaconine in the Syrian Golden hamster.

    Science.gov (United States)

    Langkilde, Søren; Mandimika, Tafadzwa; Schrøder, Malene; Meyer, Otto; Slob, Wout; Peijnenburg, Ad; Poulsen, Morten

    2009-06-01

    Glycoalkaloids alpha-solanine and alpha-chaconine are naturally present toxicants in the potato plant (Solanumtuberosum). Human intake of high doses of glycoalkaloids has led to acute intoxication, in severe cases coma and death. Previous studies have indicated that the ratio of alpha-solanine to alpha-chaconine may determine the degree and nature of the glycoalkaloid toxicity in potatoes, as the toxicity of the two alkaloids act synergistically. The aim of the present study was to investigate whether an altered ratio of alpha-solanine and alpha-chaconine would reduce the toxicity of the glycoalkaloids. The Syrian Golden hamster was given daily doses of alpha-solanine and alpha-chaconine by gavage for 28 days. Doses of up to 33.3 mg total glycoalkaloids/kg body weight were applied in ratios of 1:3.7 and 1:70 (alpha-solanine:alpha-chaconine). Administration of the highest doses of both ratios resulted in distended and fluid filled small intestines and stomach. Animals receiving the ratio with the reduced content of alpha-solanine were less affected compared to those receiving the other ratio. Gene expression profiling experiments were conducted using RNA from epithelial scrapings from the small intestines of the hamsters administered the highest doses of the glycoalkaloid treatments. In general, more differential gene expression was observed in the epithelial scrapings of the hamsters fed the ratio of 1:3.7. Mostly, pathways involved in lipid and energy metabolism were affected by the ratio of 1:3.7.

  16. Automated Lab-on-a-Chip Technology for Fish Embryo Toxicity Tests Performed under Continuous Microperfusion (μFET).

    Science.gov (United States)

    Zhu, Feng; Wigh, Adriana; Friedrich, Timo; Devaux, Alain; Bony, Sylvie; Nugegoda, Dayanthi; Kaslin, Jan; Wlodkowic, Donald

    2015-12-15

    The fish embryo toxicity (FET) biotest has gained popularity as one of the alternative approaches to acute fish toxicity tests in chemical hazard and risk assessment. Despite the importance and common acceptance of FET, it is still performed in multiwell plates and requires laborious and time-consuming manual manipulation of specimens and solutions. This work describes the design and validation of a microfluidic Lab-on-a-Chip technology for automation of the zebrafish embryo toxicity test common in aquatic ecotoxicology. The innovative device