Abstract
The Life Sciences Research Office (LSRO) of the Federation of American Societies for Experimental Biology (FASEB) is conducting this symposium under contract with the Center for Food Safety and Applied Nutrition (CFSAN) of the Food and Drug Administration (FDA). The FDA has requested information on the strengths and weaknesses of current interspecies extrapolation methods using metabolic and pharmacokinetic data, identity of data for these methods, bases for choice of extrapolation method and selection of data base, validity and uniformity of interspecies extrapolation from target organ data, and nature and completeness of supporting data. Definitions and basic concepts of dose scaling are addressed and questions regarding appropriate units of measurement (e.g., mg/kg body weight, mg/m3 respired air, mg/m2 surface area) are raised. The use of DNA damage as a marker or end point upon which to scale carcinogenic potency is considered. Genotoxic mechanisms of carcinogenesis are emphasized because the roles of DNA adducts and DNA repair processes in initiation and promotion are much better defined than the mechanism for nongenotoxic carcinogenesis. The problems encountered in evaluating the human carcinogenicity of trichloroethylene are reviewed. The broad objectives of the symposium are discussed and the development of a structured format for the presentation of invited papers is presented.
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Elcombe C. R. Species differences in carcinogenicity and peroxisome proliferation due to trichloroethylene: a biochemical human hazard assessment. Arch Toxicol Suppl. 1985;8:6–17. doi: 10.1007/978-3-642-69928-3_2. [DOI] [PubMed] [Google Scholar]
- Green T., Prout M. S. Species differences in response to trichloroethylene. II. Biotransformation in rats and mice. Toxicol Appl Pharmacol. 1985 Jul;79(3):401–411. doi: 10.1016/0041-008x(85)90138-3. [DOI] [PubMed] [Google Scholar]
- Hoel D. G., Kaplan N. L., Anderson M. W. Implication of nonlinear kinetics on risk estimation in carcinogenesis. Science. 1983 Mar 4;219(4588):1032–1037. doi: 10.1126/science.6823565. [DOI] [PubMed] [Google Scholar]
- Jones C. A., Marlino P. J., Lijinsky W., Huberman E. The relationship between the carcinogenicity and mutagenicity of nitrosamines in a hepatocyte-mediated mutagenicity assay. Carcinogenesis. 1981;2(10):1075–1077. doi: 10.1093/carcin/2.10.1075. [DOI] [PubMed] [Google Scholar]
- Jones H. B., Grendon A. Environmental factors in the origin of cancer and estimation of the possible hazard to man. Food Cosmet Toxicol. 1975 Apr;13(2):251–268. doi: 10.1016/s0015-6264(75)80012-5. [DOI] [PubMed] [Google Scholar]
- Langenbach R., Gingell R., Kuszynski C., Walker B., Nagel D., Pour P. Mutagenic activities of oxidized derivatives of N-nitrosodipropylamine in the liver cell-mediated and Salmonella typhimurium assays. Cancer Res. 1980 Oct;40(10):3463–3467. [PubMed] [Google Scholar]
- Schwartz A. G., Moore C. J. Inverse correlation between species life span and capacity of cultured fibroblasts to metabolize polycyclic hydrocarbon carcinogens. Fed Proc. 1979 May;38(6):1989–1992. [PubMed] [Google Scholar]
- Yanysheva N. Y., Antomonov Y. G. Predicting the risk of tumor occurrence under the effect of small doses of carcinogens. Environ Health Perspect. 1976 Feb;13:95–99. doi: 10.1289/ehp.761395. [DOI] [PMC free article] [PubMed] [Google Scholar]