Prenatal chlordane exposure: effects on plasma corticosterone concentrations over the lifespan of mice

Developmental exposure to nonteratogenic doses of the organochlorine pesticide Chlordane has been reported to alter endocrine function of apparently normal offspring evaluated at 101 days of age (J.S. Cranmer, D.L. Avery, R.R. Grady, and J.S. Kitay, 1978, J. Environ. Pathol. Toxicol. 2, 357-369). The long-term study reported here was conducted in cohort groups of identically treated mice to determine if prenatal exposure to Chlordane had a persistent effect on endocrine function over the lifespan of the exposed offspring as determined by alterations in plasma concentrations of corticosterone at 400 and 800 days of age. Dihybrid female mice were exposed throughout gestation to 0.16 or 8.00 mg/kg/day Chlordane and endocrine function of offspring was evaluated at three timepoints in their lifespan. Adrenal production and liver reduction capacity for corticosterone (the primary glucocorticoid in rodents) and plasma concentration of corticosterone were measured at 101 days. In this and three previous studies, changes in plasma levels of corticosterone proved to be a reliable indicator of changes in adrenal and/or liver function, thus, only plasma concentrations of corticosterone were determined at 400 and 800 days of age. Plasma corticosterone concentrations of male mice prenatally exposed to the lower Chlordane dose were significantly (P less than 0.01) elevated when measured at 101 days of age. This abnormal elevation (P less than 0.05) was recorded in both dose groups when male mice were examined at 400 days of age. At 800 days of age, no differences from control were found for male offspring in the lower dose group; insufficient numbers of offspring in the higher dose group survived to be evaluated. An effect of Chlordane on corticosterone metabolism in female offspring was observed only in the 0.16 mg/kg dose group at 400 days of age when plasma concentrations of corticosterone were significantly (P less than 0.05) increased. Results suggest that prenatal exposure to nonteratogenic doses of Chlordane (1) had a significant effect on endocrine function (corticosterone control), (2) affected males more than females, and (3) produced changes (increased plasma corticosterone levels) which were detectable at adulthood and persisted into middle age. The mechanisms responsible for these persistent changes in corticosterone metabolism remain to be elucidated.