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CARCINOGENICITY AND PESTICIDES: BIOLOGICAL ISSUES IN EXTRAPOLATION
Citation:
Yang, R., J. Huff, D. Germolec, M. Luster, J. Simmons, AND J. Seely. CARCINOGENICITY AND PESTICIDES: BIOLOGICAL ISSUES IN EXTRAPOLATION. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/D-90/038 (NTIS PB90220799).
Description:
Approximately 41% (26/63) of the pesticides evaluated in the chronic toxicity and carcinogen lofty studies of the National Toxicology Program (NTP) showed varying degrees of carcinogenicity. Since those chemicals nominated to the NTP for carcinogenicity studies usually represent a sampling of potentially "problem" chemicals, this ratio (i.e. 41%) does not implicate the actual percentage of carcinogenic chemicals among all pesticides. n general, results from epidemiological studies are of limited value in prevention and have been done on few pesticides. Furthermore, it is impossible to conduct chronic toxicity/carcinogenicity studies in humans. herefore, laboratory animals must be utilized as surrogates, at least for the foreseeable future. o assess potential risks of chemicals to humans, extrapolation of the findings in laboratory animals to possible health effects in humans is inevitable. everal important biological issues must be considered in such a process; these include extrapolation between doses, species (including strain and sex), routes of administration and exposure regimens (e.g., intermittent vs. constant rate). hile there is no perfect surrogate for humans in the evaluation of carcinogenic potential and other toxicities of chemicals and other agents, rodents still represent the best models. ny imperfection in such a process (e.e.. hazard identification and risk assessment of any given chemical or other agent) must be taken into consideration during extrapolation. he state-of-the-art technique or tools, such as physiologically based pharmacokinetics/computer modeling, should be considered and utilized judiciously to minimize the intrinsic imperfections in the process. he continuing refinement and improvement of the entire process (from selection of chemicals for testing, experimental design and conduct. Interpretation and analysis of data, interpolation and extrapolation, to risk assessment) is essential as scientific advances are made in these areas.
