M8 PM Chiral Chemistry: Toxicology of Environmental Contaminants and Phase Transfer
Monday, 14 November 2005: 1:50 PM - 5:30 PM in 337-338

(LEH-1117-807098) PCB 84: Disposition and Toxicity.

Lehmler, H.¹, Price, D.², Birge, W.², Robertson, L.¹, Garrison, A.³, ¹ University of Iowa, Department of Occupational and Environmental Health, Iowa City, Iowa, USA² University of Kentucky, School of Biological Sciences, Lexington, Kentucky, USA³ National Exposure Research Laboratory, US Environmental Protection Agency, Athens, Georgia, USA

ABSTRACT- Nineteen of the 209 possible polychlorinated biphenyl (PCB) congeners exist as pairs of stable rotational isomers that are enantiomeric to each other. Although a racemic mixture of chiral PCBs is present in technical PCB mixtures, enantioselective processes may result in an enantiomeric enrichment of these PCBs in the environment. The enantiomeric enrichment of chiral PCB congeners has been reported in tissue and blood samples from wildlife and humans, but only limited information about the enantioselective disposition of individual, chiral PCB congeners is available for laboratory animals. Intraperitoneal administration of racemic 2,2',3,3',6-pentachlorobiphenyl (PCB 84) in untreated female C57Bl/6 mice resulted in a statistically significant enrichment of (+)-PCB 84 in brain, liver, lung, kidney and heart tissues six days after administration, whereas no enantiomeric enrichment was observed in the spleen. The highest enantiomeric fractions were found in the brain, an observation that is of particular concern because PCB 84 enantiomers are known to have different potencies in in vitro neurotoxicity studies. Both (+)- and (-)-PCB 84 increased [³H]phorobol ester binding in a concentration-dependent manner with (-)-PCB 84 being slightly more potent. Both PCB 84 enantiomers also inhibited microsomal ⁴⁵Ca²⁺ uptake in a concentration-dependent manner, but no significant difference in the potency of the enantiomers was observed. These findings may have important implications for understanding the mechanism of neurotoxicity of chiral PCB congeners and further investigations of the disposition and toxicity of chiral PCBs are warranted (Supported by ES 012475 and ES 07380 from NIH; this abstract does not necessarily reflect USEPA policy).

Key words: PCB 84, Disposition, Neurotoxicity, Enantiomeric fraction