Dynamic changes of α-hexachlorocyclohexane and its enantiomers in various tissues of Japanese Rabbits (Oyctolagus cuniculus) after oral or dermal exposure

Japanese Rabbits (Oyctolagus cuniculus) were exposed to α-hexachlorocyclohexane (α-HCH) either orally or dermally and concentrations of α-HCH and its two enantiomers were measured at different time intervals in the blood, intestine, liver, kidney, fat, brain, and muscle. The time trends were quantified using toxicokinetic models. It was found that absorption and elimination of α-HCH in blood were first-order processes which can be characterized by a single compartmental kinetic model. The absorption of dermally exposed α-HCH in blood was more than one order of magnitude faster than that of orally exposed α-HCH. The transport of α-HCH from the blood to other tissues was characterized using a two-compartment model. The accumulation rates were different among tissues depending on blood flow rate and fat content. Significant correlation was revealed between α-HCH concentration and fat content for various tissues either before or 1 d after the exposure. However, there was no such correlation at 10 min immediately after the exposure. The enantiomeric fraction (EF) of α-HCH in rabbit blood was nearly racemic before the exposure and increased to 0.73 and 0.82 after oral or dermal exposure, respectively. The result of a toxicokinetic modeling suggested that the strong enantioenrichment of (+)-α-HCH was primarily because the elimination rate of (−)-α-HCH was more than two times higher than that of (+)-α-HCH. The EFs for other tissues also increased dramatically after the exposure and the EFs in brain reached as high as 0.99 due to enantioselective transport across the blood brain barrier.