The fate of technical-grade chlordane in mice fed a high-fat diet and its roles as a candidate obesogen.
After a single oral exposure of technical chlordane, levels of cis-chlordane (CC), trans-chlordane (TC), heptachlor (HEP), heptachlorepoxide (HEPX), and oxychlordane (OXY) were determined in gastrointestinal residues, droppings, and various tissues of cockerels at times of 60, 120, 160, 200, 300, 500, 1000, and 2000 min. Over 98% of CC and TC were found to be bioaccessible; only 1.1% of CC and TC were directly excreted through droppings without further biotransformation. According to the single-compartment toxicokinetic modeling, CC and TC shared similar absorption rates in the whole body while TC showed a slightly more rapid elimination rate, with a half-life of 13.4 h for CC and 12.5 h for TC. The metabolites HEPX and OXY appeared quickly in tissues 60 min after exposure and were mainly accumulated in fat and liver tissues. Concentrations of CC, TC, and HEP in cockerel tissues roughly followed the order as fat > intestine > skin > liver> brain > muscle > blood. Levels of CC, TC, and HEP in various tissues showed significant correlation with the lipid contents of the tissues (p < 0.05) for samples beginning 500 min after exposure. A multicompartment toxicokinetic model was developed to characterize the accumulation dynamics of CC and TC in the various tissues. All tissues of cockerels enantioselectively accumulated (-)-CC and (+)-TC, and fat, skin, and liver tissues showed a relatively stronger capacity of enantioenrichment. The enantiomer fractions (EFs) of droppings remained nearly racemic at first but gradually decreased to less than 0.5 for CC and increased to more than 0.5 for TC, which could rule out enantioselective absorption and excretion of CC and TC in cockerels. The one-compartment toxicokinetic model was applied to the individual enantiomers of CC and TC. Different elimination rates but similar absorption rates were observed between the enantiomers for both CC and TC.