Two-generation reproduction toxicity study in rats with methoxychlor.

A two-generation reproduction toxicity study was conducted in rats with a reference estrogenic pesticide, methoxychlor, to validate the sensitivity and competency of current guidelines recommended by the United States Environmental Protection Agency; Japanese Ministry of Agriculture, Forestry and Fisheries; and Organisation for Economic Co-operation and Development for predicting reproductive toxicity of the test compound based on estrogenic endocrine disrupting effects. Both sexes of SD rats were exposed to methoxychlor in the diet at concentrations of 0, 10, 500 and 1500 ppm for two successive generations. The present study has successfully detected estrogenic activities and reproductive toxicities of methoxychlor, as well as its systemic toxicity. Body weights, body weight gains and food consumption of both sexes of animals were suppressed significantly in the 500 and 1500 ppm groups. Typical reproductive toxicities observed in females of these groups included, but were not limited to, prolonged estrous cycle, reduced fertility, decreased numbers of implantation sites and newborns, decreased ovary weights and/or increased incidences of cystic ovary. Uterine weights of weanlings increased significantly in these groups, suggesting that the sensitivity of this parameter for predicting estrogenic ability of the test compound is comparable to that of the uterotrophic assay. Reproductive toxicities of methoxychlor seemed less potent in males than in females. Methoxychlor delayed preputial separation and significantly reduced sperm counts and reproductive organ weights of males of the 500 and/or 1500 ppm groups; however, most males that failed to impregnate females in the same group showed normal fertility when they were re-mated with untreated females. Neither systemic nor reproductive toxicities appeared in the 10 ppm group.