Clearance of Polychlorinated Biphenyl Atropisomers is Enantioselective in Female C57BI/6 Mice

摘要

Changes in the enantiomeric composition of polychlorinated biphenyls (PCBs) can not only be used to investigate environmental and biological transport processes, but also have human health implications because of enantiospecific adverse health effects. To further understand differences in the disposition of PCB atropisomers in vivo, the present study investigates the toxicokinetics of PCB atropisomers in female C57BI/6 mice after oral administration of a mixture of several PCBs, including racemic PCBs 91,95,132,136,149,174, and 176. On the Chirasil-Dex column, an enrichment of the second eluting atropisomers was generally observed, whereas only the first eluting atropisomers E1-PCB 95, (-)-PCB 132, and (-)-PCB 149 had half-lives that were distinctively longer compared to the second eluting atropisomers. The bioavailability normalized clearance of first eluting atropisomers in blood was faster compared to that of second eluting atropisomers. The opposite trend was observed for the accumulation factors in adipose tissue, which is consistent with the slower clearance of the first eluting atropisomer. The only exception was PCB 174, which showed no differences in the toxicokinetic parameters of both atropisomers. Together, the differences in the toxicokinetics of PCB atropisomers point toward enantioselective biotransformation processes as the origin of PCB's enantiomeric enrichment in mammals and, possibly, humans.