The effects of chlordane exposure during pre- and postnatal periods at environmentally relevant levels on sex steroid-mediated behaviors and functions in the rat.

Technical chlordane is a mixture of four main isomers (i.e., heptachlor, cis-chlordane, trans-chlordane, and trans-non-achlor) found in meat and dairy products as well as in indoor air of houses treated for termites. These isomers are metabolized to more potent epoxides (heptachlor epoxide and oxychlordane) which accumulate in lipid compartments of tissues and have been shown to reduce chloride influx through GABAA receptor complex channels and to alter steroid levels. However, considering the almost universal human exposure and the potential for accumulation of these agents, very little is known about how chronic, low-level exposures during development affect adult behavior and steroid-mediated processes. Time-pregnant Sprague-Dawley dams (Day 4 of gestation through Day 21 of lactation) and offspring (Day 22 of age through Day 80) were exposed to three levels of technical chlordane (100, 500, or 5000 ng/g) on a daily schedule. The low-exposure level generated heptachlor epoxide and oxychlordane plasma levels in the dam (Day 20) and in the offspring (Day 80) representative of those found in the U.S. populace. Chlordane-dosed offspring exhibited sex- and dose-dependent effects on testosterone levels, behavioral tests, and body weight conducted between postnatal Days 77 and 85. Chlordane-dosed females, but not males, had significant decreases in testosterone levels, significant improvements in spatial abilities (i.e., decreases in Cincinnati maze errors, navigation times, and failures to escape), and significant increases in body weight and in auditory startle-evoked responses. In two other tests, only males were used. These chlordane-dosed males showed significant increases in male-typical mating behaviors and decreases in 36Cl- uptake into brain microsacs. For all behavioral and body weight measurements, dose-response effects were observed for the 100 and 500 ng/g dosed groups. However, the 5000 ng/g dose group responses were closer to those of control values. These results suggest that these cyclodienes masculinize sexually dimorphic functions and behaviors by mimicking sex steroids and/or changing their levels.