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  • 1
    Electronic Resource
    Electronic Resource
    Summary of the Workshop on Issues in Risk Assessment: Quantitative Methods for Developmental Toxicology (1994)
    Oxford, UK : Blackwell Publishing Ltd
    Risk analysis 14 (1994), S. 0 
    Details
    ISSN: 1539-6924
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Notes: This report summarizes the proceedings of a conference on quantitative methods for assessing the risks of developmental toxicants. The conference was planned by a subcommittee of the National Research Council's Committee on Risk Assessment Methodology/〉 in conjunction with staff from several federal agencies, including the U.S. Environmental Protection Agency, U.S. Food and Drug Administration, U.S. Consumer Products Safety Commission, and Health and Welfare Canada. Issues discussed at the workshop included computerized techniques for hazard identification, use of human and animal data for defining risks in a clinical setting, relationships between end points in developmental toxicity testing, reference dose calculations for developmental toxicology, analysis of quantitative dose-response data, mechanisms of developmental toxicity, physiologically based pharmacokinetic models, and structure-activity relationships. Although a formal consensus was not sought, many participants favored the evolution of quantitative techniques for developmental toxicology risk assessment, including the replacement of lowest observed adverse effect levels (LOAELs) and no observed adverse effect levels (NOAELs) with the benchmark dose methodology.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1539-6924.1994.tb00273.x
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  • 2
    Electronic Resource
    Electronic Resource
    Structural Determinants of Developmental Toxicity (1994)
    Oxford, UK : Blackwell Publishing Ltd
    Risk analysis 14 (1994), S. 0 
    Details
    ISSN: 1539-6924
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Notes: Developmental toxicity, an area of public concern, suffers from the lack of accessible, reliable, peer-reviewed compilations of data and substantial gaps in testing. These deficits frequently make it necessary for regulatory agencies to use other toxicological end points to regulate developmental toxicants. We have utilized a database of chemicals identified as developmental toxicants in rats, mice, rabbits, and humans and an expert system which learns the association between molecular structure and biological response (Computer Automated Structure Evaluation; CASE) to explore structure-activity relationships in developmental toxicity. Developmental toxicity was defined as death, growth retardation, or structural or functional malformations. In analyzing the data CASE selects its own molecular descriptors from a learning set of active and inactive molecules. Using randomly constructed learner and tester sets, the concordance of the predictions with the actual data was between 77 and 82%. CASE identified 13 major structural fragments associated with developmental toxicity in mice, IS in rats, 9 in rabbits, and 7 in humans. These analyses indicate that there is indeed a structural basis for developmental toxicity which may be used to predict the developmental hazard of untested or inadequately tested chemicals.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1539-6924.1994.tb00278.x
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Degeneration of mouse oocytes in response to polycyclic aromatic hydrocarbons (1979)
    New York, NY [u.a.] : Wiley-Blackwell
    The @Anatomical Record 193 (1979), S. 863-881 
    Details
    ISSN: 0003-276X
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Destruction of mouse oocytes in primordial and small primary follicles in response to treatment with 3-methylcholanthrene (MC) was studied at the ultrastructural level. Four-week old C57Bl/6N (B6) strain mice received a single injection of 80 mg/Kg MC in corn oil intraperitoneally. Controls received only corn oil. Ovaries from animals were prepared for light and electron microscopic examination at specified intervals after treatment. The number of primordial follicles remained constant in control animals. In contrast, their number decreased significantly (P 〈 0.01) by three days, and they were depleted by seven days after MC treatment. Subtle degenerative modifications were noted in the ooplasm of primordial follicles two days after treatment. These changes consisted of vesiculation of mitochondrial cristae, increased electron density of the mitochondrial matrix, myelin structures in lipid droplets and in mitochondria. More advanced stages of degeneration of primordial follicles were characterized by further vesiculation or disappearance of mitochondrial cristae, chromatin clumping, and increased density of the ooplasm. Small primary follicles had undergone similar initial degeneration as primordial follicles. In more advanced stages of degeneration nuclear and cytoplasmic contents condensed, endoplasmic reticulum, Golgi complex and mitochondria swelled, small vesicles and multivesicular bodies appeared. In the most advanced stages of degeneration of small primary follicles it appeared that small portions of the oocyte were engulfed by the surrounding follicular cells. It is concluded that exposure of B6 mice to a single dose of MC results in atresia of oocytes in primordial and small primary follicles. Ultrastructurally, these degenerating oocytes of treated mice looked much like the spontaneously atretic oocytes in untreated animals.
    Additional Material: 1 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/ar.1091930409
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  • 4
    Electronic Resource
    Electronic Resource
    Benzo(a)pyrene inhibits ovulation in C57BL/6N mice (1985)
    New York, NY [u.a.] : Wiley-Blackwell
    The @Anatomical Record 212 (1985), S. 268-276 
    Details
    ISSN: 0003-276X
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Successful female reproductive function requires follicle growth, ovulation, and formation of the corpus luteum. Treatment of C57BL/6N mice with a single intraperitoneal injection of benzo(a)pyrene in doses ranging from 1 to 500 mg/kg produced a dose- and time-dependent decreaśe in the number of corpora lutea. This effect on the number of corpora lutea is most pronounced at 1 week after treatment, with a threshold of about 1 mg/kg, and an ED50 of 1.6 mg/kg. By 2 weeks after treatment partial recovery of follicle growth and ovulation occurred, as indicated by an increase in the ED50 to 20 mg/kg. Complete recovery of normal corpora lutea number occurs in mice treated with less than 100 mg/kg by 3 weeks after treatment, with little change in the ED50 noted between 3 and 4 weeks posttreatment, 78 mg/kg at both times. Mice treated with 100 or 500 mg/kg did not recover normal corpora lutea number over the course of this experiment. These data indicate that acute exposure to benzo(a)pyrene, and perhaps other polycyclic aromatic hydrocarbons, may have a transient adverse effect on follicle growth, ovulation, or formation of corpora lutea. A consequence of this effect, transient infertility, has been observed previously when exploring the effect of polycyclic aromatic hydrocarbons on murine reproduction.
    Additional Material: 9 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/ar.1092120308
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