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DISTRIBUTION OF PCB 84 ENANTIOMERS IN C56BL/6 MICE
Citation:
Lehmler, H. J., D. J. Price, A W. Garrison, AND L. W. Robertson. DISTRIBUTION OF PCB 84 ENANTIOMERS IN C56BL/6 MICE. Presented at 2nd PCB Workshop: "Recent Advances in the Environmental Toxicology and Health Effects of PCBs", Brno, Czech Republic, May 7-11, 2002.
Impact/Purpose:
Extend existing model technologies to accommodate the full range of transport, fate and food chain contamination pathways, and their biogeographical variants, present in agricultural landscapes and watersheds. Assemble the range of datasets needed to execute risk assessments with appropriate geographic specificity in support of pesticide safety evaluations. Develop software integration technologies, user interfaces, and reporting capabilities for direct application to the EPA risk assessment paradigm in a statistical and probabilistic decision framework.
Description:
At room temperature, nineteen of the 209 possible PCB congeners exist as pairs of stable rotational isomers that are enantiomeric to each other. A racemic mixture of each of these PCB atropisomers is present in technical mixtures, thus raising concerns about enantioselective distribution, metabolism, and disposition processes. An understanding of these processes in combination with knowledge of different biological effects of pure PCB enantiomers is necessary to calculate the overall risk of exposure to chiral PCB congeners. This study investigates the distribution and enantiomeric fractions (EF) of PCB 84 in several organs in uninduced female C57BL/6 mice. Methods: PCB 84 (EF = 0.513 0.003) was injected intraperitoneally (600 mmol/kg body weight), and organs (liver, brain, lung, heart, spleen and kidney) were removed after three and six days, respectively. The PCB enantiomers were separated by GC on a chiral phase composed of 20% tert-butyldimethylsilylated-b-cyclodextrin (BGB 172 chiral column, BGB Analytik AG, Anwil, Switzerland) and detected with a mass selective detector. With this chiral phase, the (-)-enantiomer of PCB 84 elutes first. Resolution of the enantiomers of PCB 84 was R = 0.8 (n = 3). Because there were no interfering peaks in the samples, this ratio was sufficient for the determination of enantiomer fractions. Results: The EFs in brain, liver, lung and heart were significantly different from the racemic PCB 84 standard at days three and six, with an enrichment of (+)-PCB 84 in all four tissues. A significant enrichment of (+)-PCB 84 in the kidney was observed for day six. No significant difference was observed for the spleen. Tissue EFs for the brain showed the highest EF, whereas the EFs in the spleen were almost identical with the PCB 84 standard. The EFs did not change significantly between day three and six. Conclusions: There is a significant enrichment of (+)-PCB 84 in several tissues (brain, liver, lung, heart and kidney) three and/or six days after administration of a racemic mixture of PCB 84. This enrichment may be due to enantioselective metabolism in these tissues and/or enantioselective distribution or disposition of PCB 84. Our findings suggest that the risk assessment of PCB 84 and, possibly, other atropisomeric PCB congeners should take enantioselective processes into account.