Enantioselective formation of methyl sulfone metabolites of 2,2',3,3',4,6'-hexachlorobiphenyl in rat.
Several nonsymmetric polychlorinated biphenyl (PCB) congeners form atropisomers due to steric hindrance of free rotation around the phenyl-phenyl bond. It is evident from the literature that both chiral PCB congeners and their atropisomeric methylsulfonyl-PCB metabolites, formed in higher animals and in humans, are present in biota as nonracemic mixtures. Chiral methylsulfonyl-PCBs are strongly dominated by one of the atropisomers in mammalian tissues. The aim of the present study is to examine enantioselective metabolism, retention, and excretion of 2,2',3,3',4,6'-hexachlorobiphenyl (CB-132) in rat by administration of a CB-132 racemate and pure atropisomers. Chemical analysis of liver, lung, and adipose tissue from the rats showed a strong retention of one of the CB-132 atropisomers and a similar, but even more pronounced, accumulation of one of the atropisomers of the meta- and para-methylsulfonyl-substituted CB-132 metabolites in these tissues. Metabolites with R structures were predominately formed from one of the atropisomers of CB-132. The slower metabolism of the other atropisomer of CB-132 and its pronounced excretion in feces suggest an enantioselective metabolism. The results indicate enantio-selective formation of the methylsulfonyl-CB132 metabolites and confirm the critical role of stereochemistry of chemicals for their metabolism.
Norstrom
Karin
K
Department of Environmental Chemistry, Stockholm University, SE-106 91 Stockholm, Sweden.
Eriksson
Johan
J
Haglund
Johanna
J
Silvari
Virginia
V
Bergman
Ake
A
D000818:Animals; D002849:Chromatography, Gas; D002851:Chromatography, High Pressure Liquid; D004121:Dimethyl Sulfoxide / Q000493:pharmacokinetics*; D008297:Male; D011078:Polychlorinated Biphenyls / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism; D013450:Sulfones / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D013450:Sulfones; C094859:2,2',3,3',4,6'-hexachlorobiphenyl; C025910:dimethyl sulfone; D011078:Polychlorinated Biphenyls; D004121:Dimethyl Sulfoxide