Enantioselective Accumulation Dynamics Of α-hexachlorocyclohexane And Chlordanes In Various Tissues Of Japanese Rabbits (Oyctolagus Cuniculus) And Chicken (Gallus Gallus)

Japanese Rabbits (Oyctolagus Cuniculus) were exposed toα-hexachlorocyclohexane (α-HCH) either orally or dermally and concentrations ofα-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 ofα-HCH in blood were first-order processes which can be characterized by a single compartmental kinetic model. The absorption of dermally exposedα-HCH in blood was more than one order of magnitude faster than that of orally exposedα-HCH. The transport ofα-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 betweenα-HCH and fat content for various tissues either before or 1 d after the exposure. However, there was no such correlation at 10 minutes immediately after the exposure.The enantiomeric fraction (EF) ofα-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.After a single oral exposure of technical chlordane, levels of CC, TC, HEP, HEPX and OXY were determined in gastrointestinal residues, droppings and various tissues of Chicken(Gallus gallus) at the time of 60, 120, 160, 200, 300, 500, 1000 and 2000 min. Interestingly, over 98% of CC and TC were bioaccessible for chicken, while only approximately 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 rate in the whole body, while TC showed a slight more rapid elimination rate, with half-life of 13.4h for CC and 12.5h for TC. The metabolites of HEPX and OXY appeared as soon as 60 min after exposure, and were mainly accumulated in fat and liver tissues. Concentrations of CC, TC and HEP in chicken tissues roughly followed orders as fat > intestine > skin > liver > brain > muscle > blood. Levels of CC, TC and HEP in various tissues showed significant correlation with lipid content (p<0.05) since 500 min after exposure. A multi-compartment toxicokinetic model was developed to characterize the accumulation dynamics of CC and TC in the various tissues respectively.Tissues of chicken all enantioselectively accumulated (-)-CC and (+)-TC, while fat, skin and liver tissues showed relatively stronger capacity of enantio-enrichments. The EFs of droppings remained nearly racemic at first, but gradually decreased less than 0.5 for CC and increased more than 0.5 for TC, which could rule out the enantioselective absorption and excretion of CC and TC in chicken. The one-compartment toxicokinetic model was applied for the individual enantiomers of CC and TC, respectively, and different elimination rates but similar absorption rates were observed between the enantiomers for both CC and TC. Compared with other tissues, brain tissues of chicken didn't showed accumulated (-)-CC and (+)-TC to any different extent.