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Clearance of Polychlorinated Biphenyl Atropisomers is Enantioselective in Female C57Bl/6 Mice
Journal article   Peer reviewed

Clearance of Polychlorinated Biphenyl Atropisomers is Enantioselective in Female C57Bl/6 Mice

Izabela Kania-Korwel, Mohammed H.M.E El-Komy, Peter Veng-Pedersen and Hans-Joachim Lehmler
Environmental science & technology, Vol.44(8), pp.2828-2835
04/15/2010
DOI: 10.1021/es901781p
PMCID: PMC2855138
PMID: 20384376

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Abstract

Changes in the enantiomer composition of polychlorinated biphenyls (PCBs) can not only be used to investigate environmental and biological transport processes, but also has 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 C57Bl/6 mice after oral administration of a mixture of several PCBs, including racemic PCBs 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 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 towards enantioselective biotransformation processes as the origin of PCB’s enantiomeric enrichment in mammals and, possibly, humans.
atropisomers chiral accumulation factor Polychlorinated biphenyls pharmacokinetics clearance half-life

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