Enhanced one-generation reproductive toxicity study in rats for detecting endocrine-disrupting effects of chemicals

Abstract

An enhanced one-generation reproductive toxicity study in rats without adjusting a litter size during the lactation period is proposed as a rapid and reliable bioassay for providing the data concerning adverse and/or low-dose effects of suspected endocrine disruptors. In this study, pregnant females are treated with the test substance from gestation day 0 through lactation day 21, in principle. F1 offspring from one-half of the litters in each dose group are killed and necropsied at weaning, while those from the remaining litters are examined for sexual maturation, estrous cyclicity, and/or sperm production. A series of pilot studies with ethynylestradiol as a reference chemical have suggested that the exposure of estrogenic chemicals during the early gestation period is critical for detecting effects on fertilization and/or implantation of eggs and survival of implants, and that expression of some genes including AR in the prostate and IGF-1 in the uterus of F1 offspring may be sensitive markers for monitoring potential estrogenic effects of the test compound.