Enantioselective and Gender-Dependent Depletion of Chlordane Compounds from Rat Tissues

Abstract

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.

Chirality as an Environmental Forensics Tool

“…Both sexes preferentially depleted (À)-trans-chlordane, as well as (þ)-oxychlordane in organisms individually exposed to oxychlordane, trans-chlordane, or achiral trans-nonachlor. These results supported the hypothesis that although CYP3A induction in rats was not sex-dependent, CYP1A1 induction was [272]. More research remains to be done to elucidate the stereoselectivity of CYP induction and its effects on the metabolism of POPs.…”

“…Female rats initially metabolized trans-chlordane to racemic oxychlordane, which later became enriched in the (À)-enantiomer post-exposure [272]. On the other hand, male rats immediately degraded trans-chlordane enantioselectively to (À)-oxychlordane [272].…”

“…Female rats initially metabolized trans-chlordane to racemic oxychlordane, which later became enriched in the (À)-enantiomer post-exposure [272]. On the other hand, male rats immediately degraded trans-chlordane enantioselectively to (À)-oxychlordane [272]. Both sexes preferentially depleted (À)-trans-chlordane, as well as (þ)-oxychlordane in organisms individually exposed to oxychlordane, trans-chlordane, or achiral trans-nonachlor.…”

Effect of Pregnancy on the Disposition of 2,2′,3,5′,6-Pentachlorobiphenyl (PCB 95) Atropisomers and Their Hydroxylated Metabolites in Female Mice

“…For example, changes in the hepatic P450 enzyme composition have been shown to alter OH-PCB profiles in in vitro metabolism studies 53, 54 and affect chiral signatures of other chiral environmental pollutants, such as chlordanes. 55, 56 Several animal studies have shown that physiological changes during pregnancy alter the enantioselective disposition of chiral bronchodilators 25 or antidepressants. 26 Moreover, PCBs absorbed from the diet may avoid the atropselective hepatic first-pass metabolism due to differences in the lipoprotein transport during pregnancy, 49 which could also contribute to differences in EF values.…”

Chlordane and Heptachlor Are Metabolized Enantioselectively by Rat Liver Microsomes

“…Treatment-dependent differences in the direction of the enantiomeric enrichment of OXY have been reported previously in rats. 21 In this in vivo study, an enrichment of (+)-OXY was observed in female rats treated for 28 days with trans -nonachlor or T-CHLORD. In contrast, (-)-OXY was enriched in females rats dosed for 28 days, followed by a 28 or 56 day depuration period.…”