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United States Department of Agriculture

Agricultural Research Service

Research Project: DIOXINS AND OTHER ENVIRONMENTAL CONTAMINANTS IN FOOD

Location: Animal Metabolism-Agricultural Chemicals Research

Title: In Vivo Stereoisomerization of HBCD Gamma and Alpha Is Tissue and Stereoisomer Specific

Authors
item Hakk, Heldur
item Huwe, Janice
item Szabo, David -
item Diliberto, Janet -
item Birnbaum, Linda -

Submitted to: Dioxin Meeting
Publication Type: Proceedings
Publication Acceptance Date: July 13, 2010
Publication Date: August 30, 2010
Citation: Hakk, H., Huwe, J.K., Szabo, D., Diliberto, J., Birnbaum, L.S. 2010. In vivo stereoisomerization of HBCD gamma and alpha is tissue and stereoisomer specific. 30th International Symposium on Halogenated Persistant Organic Pollutants (POPs), September 12-17, 2010, San Antonio, TX. Available: http://www.xcdtech.com/dioxin2010/pdf/1436.pdf.

Interpretive Summary: Hexabromocyclododecane (HBCD) is a high production volume flame-retardant used primarily in thermal insulation, and the commercial mixture is made of three diastereomers (a, ß, and '). The present mouse metabolism studies were conducted to investigate the possible stereoisomerization of individual diastereomers that has been hypothesized to lead to the predominance of a-HBCD seen in environmental samples. Based on HBCD diastereomer standards, no parent or stereoisomerized products were detected in the urine, only a very polar metabolite(s). All three diastereoisomers, a-, ß- and '-HBCD were detected in the feces after a '-[14C]HBCD oral dose. In the liver only '-HBCD and ß-HBCD were detected, and the fat contained all three diastereomers, while the brain contained only ß-HBCD. Stereoisomerization levels were calculated for feces, liver, fat and brain, and for feces and liver were less that half of the excreta/tissue radioactivity. These data are in contrast to those obtained for the a-[14C]HBCD. No stereoisomerized products of a-HBCD were detected in the feces and liver; more than half and about a third of the radioactivity in the liver and feces, respectively, was parent compound. As seen before with '-HBCD, no parent compound was detected in the urine, blood or bile of a-HBCD dosed mice. In conclusion, differences in the metabolic rates exist between '-HBCD and a-HBCD ('-HBCD is more quickly metabolized in mice) and, in vivo stereoisomerization of '-HBCD to a- and ß- is occurring. Both observation undoubtedly contribute to the observed diastereomer patterns seen in environmental samples.

Technical Abstract: Hexabromocyclododecane (HBCD) is a flame-retardant used in thermal insulation, plastics and textiles, and the present mouse metabolism studies were initiated to investigate the possible stereoisomerization of individual diastereomers present in the commercial mixture (a, ß, and ') that has been hypothesized to lead to the shifted patterns seen in environmental samples. Based on HBCD diastereomer standards, no parent or stereoisomerized products were detected in the urine by TLC, only a very polar metabolite(s). All three diastereoisomers, a-, ß- and '-HBCD were detected in the feces after a '-[14C]HBCD oral dose by LC/MS analyses. 11% of the feces [14C] was either a- or ß-HBCD, while 4% was '-parent. In the liver only '-HBCD and ß-HBCD were detected, while the fat contained all three diastereomers, and the brain contained only ß-HBCD. 15% of the radioactivity present in the liver was stereoisomerized ß-HBCD and 6% was the parent '-HBCD, while 16% of the fat radioactive content consisted of stereoisomers. These data are in contrast to those obtained for the a-[14C]HBCD. No stereoisomerized products of a-HBCD were detected in the feces and liver; 62 and 34% of the radioactivity in the liver and feces was a-HBCD parent compound, respectively, the rest consisted of metabolites. As with '-HBCD, no parent compound was detected in the urine, blood or bile of a-HBCD dosed mice. In conclusion, differences in the metabolic rates exist between the two HBCD diastereomers and, in vivo stereoisomerization of '-HBCD to a- and ß- is occurring. Both observations are suspected to contribute to the diastereomeric patterns seen in environmental samples.

Last Modified: 7/24/2014
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