Enantioselective and gender-dependent depletion of chlordane compounds from rat tissues

Isomers and metabolites of the organochlorine pesticide chlordane persist in the environment and bioaccumulate in Arctic marine food webs. Rodent studies indicate that there are gender-related differences in trans-nonachlor and oxychlordane metabolism. Thus, comparative tissue depletion studies were undertaken in male and female rats exposed to trans-nonachlor, oxychlordane, or trans-chlordane at 2.5 mg/kg body weight/d by gavage for 28 d followed by two consecutive 28-d depletion periods. None of the test chemicals were overtly toxic at this dose, although increased liver weights in some groups were consistent with microsomal enzyme induction. The metabolite oxychlordane accumulated in tissues from rats exposed to trans-nonachlor and trans-chlordane. Trans-Nonachlor and oxychlordane residue levels were highest in tissues from female rats at each time point; however, trans-chlordane was completely eliminated from males and females by the end of the study. Body burden calculations showed no significant clearance of oxychlordane in females over 56 d postdosing, whereas males lost approximately half their oxychlordane body burden in the same period. For the chiral contaminants oxychlordane and trans-chlordane, tissues from male and female rats were selectively depleted of the (+)-enantiomer; however, there were gender-related differences in enantiomer depletion patterns over time. In general, residue analyses confirmed that gender-related metabolic differences and contaminant structural properties, including chirality, influenced chlordane contaminant elimination from rat tissues. The study points to a need for similar knowledge of gender-related responses in humans in order to provide relevant dietary recommendations for populations exposed to chlordane-related contaminants in foods.