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ANIMAL MODELS FOR ASSESSING DEVELOPMENTAL TOXICITY
Citation:
Kimmel, C., R. Kavlock, AND E. Francis. ANIMAL MODELS FOR ASSESSING DEVELOPMENTAL TOXICITY. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/D-91/137 (NTIS PB91219154), 1991.
Description:
Developmental effects may result from toxic agent exposure of parental gametes prior to conception, during the prenatal period or postnatally up to the time of sexual maturation. hese effects are not predictable from the assessment of adult exposures to the same agent. umber of animal models have been used to evaluate the developmental effects of exposure to toxicants, and several of these are exemplified by the standard protocols used by regulatory agencies. thers have been developed to evaluate the effects of toxicants on particular target organs or organ systems. nimal models and principles for the interpretation of data from studies Involving prenatal exposure are much further advanced than those Involving postnatal exposure. n those experimental animal studies that assess the effects of prenatal exposure, the developing organism is exposed secondarily via the maternal organism which intervenes in the absorption, metabolism and distribution to the embryo/fetal compartment. n postnatal exposure studies, exposure of the developing offspring may also be indirect via maternal milk or direct by dosing of pups. n addition, exposure may occur unintentionally via contaminants on maternal fur or skin, in excretory products following exposure, and/or by access to dosed food or drinking water before weaning. umber of factors may influence the response of pups to toxicant exposure either prenatally or postnatally, e.g., the influence of litter, litter size, handling of pups, maternal care and maternal/infant Interactions, and the effects of maternal infant separation during exposure. tudies designed to compare the sensitivity of developing animals and adults must consider the above factors along with these that more directly influence sensitivity, e.g., metabolic capability, growth and repair processes, functional maturity, or genetic differences in susceptibility. o illustrate the complexity of postnatal studies, examples derived from developmental neurotoxicity and renal developmental toxicity are presented. n these examples, it can be seen clearly that each organ or functional system has its own unique ontogenetic maturation sequence and the pattern of organ maturation varies across species. hus, there can be no single laboratory animal model that is most appropriate for predicting the effects of toxicants in the developing human. t is possible, however, to utilize existing data on comparative developmental morphology and physiology to study effects of toxic agents in laboratory animal models for use in human risk assessment, and target organ toxicity in the developing organism should be evaluated in light of these patterns.