ToxSci Advance Access published online on February 15, 2006
Toxicological Sciences, doi:10.1093/toxsci/kfj132
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1 Department of Toxicology, University of Würzburg, Versbacherstr. 9, 97078 Würzburg, Germany
* To whom correspondence should be addressed. Tetrabromobisphenol A (TBBPA) is widely used as a flame retardant and is suspected to be stable in the environment with possible widespread human exposures. This study reports the characterization of the toxicokinetics of TBBPA in human subjects and in rats. A single oral dose of 0.1 mg/kg TBBPA was administered to 5 human subjects. Rats were administered a single oral dose of 300 mg TBBPA/kg bw. Urine and blood concentrations of TBBPA and its metabolites were determined by LC/MS-MS. TBBPA-glucuronide and TBBPA-sulfate were identified as metabolites of TBBPA in blood and urine of the human subjects and rats. In blood, TBBPA-glucuronide was detected in all human subjects, whereas TBBPA-sulfate was only present in blood from two individuals. Maximum plasma concentrations of TBBPA-glucuronide (16 nmol/l) were obtained within four hours after administration. In two individuals where TBBPA-sulfate was present in blood, maximum concentrations were obtained at the 4 h sampling point, the concentrations rapidly declined to reach the limit of detection after 8 hours. Parent TBBPA was not present in detectable concentrations in any of the human plasma samples. TBBPA-glucuronide was slowly eliminated in urine to reach the limit of detection 124 hours after administration. In rats, TBBPA-glucuronide and TBBPA-sulfate were also the major metabolites of TBBPA present in blood; in addition, a diglucuronide of TBBPA, a mixed glucuronide-sulfate conjugate of TBBPA, tribromobisphenol A, and the glucuronide of tribromobisphenol A were also present in low concentrations. TBBPA plasma concentrations peaked at 103 micromol/l 3 h after administration and thereafter declined with a half-life of 13 h; maximal concentrations of TBBPA-glucuronide (25 micromol/l) were also observed 3 h after administration. Peak plasma concentrations of TBBPA-sulfate (694 micromol/l) were reached within 6 h after administration. The obtained results suggest absorption of TBBPA from the gastrointestinal tract and rapid metabolism of the absorbed TBBPA by conjugation resulting in a low systemic bioavailability of TBBPA. The authors certify that all research involving human subjects was done under full compliance with all government policies and the Helsinki Declaration.
Received December 22, 2005
Accepted February 7, 2006
Biotransformation and Toxicokinetics
Toxicokinetics of Tetrabromobisphenol A in Humans and Rats After Oral Administration
Ute M. D. Schauer 1,
Wolfgang Völkel 1,
and
Wolfgang Dekant 1 *
Wolfgang Dekant, E-mail: dekant{at}toxi.uni-wuerzburg.de
Abstract
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