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Estimation of human percutaneous bioavailability for two novel brominated flame retardants, 2-ethylhexyl tetrabromobenzoate (EH-TBB) and bis(2-ethylhexyl) tetrabromophthalate (BEH-TEBP), using the parallelogram approach
Knudsen, G., M. Hughes, J. Sanders, S. Hall, AND L. Birnbaum. Estimation of human percutaneous bioavailability for two novel brominated flame retardants, 2-ethylhexyl tetrabromobenzoate (EH-TBB) and bis(2-ethylhexyl) tetrabromophthalate (BEH-TEBP), using the parallelogram approach. TOXICOLOGY AND APPLIED PHARMACOLOGY. Academic Press Incorporated, Orlando, FL, 311:117-127, (2016).
Experiments using the parallelogram approach to estimate human systemic exposure to the brominated flame retardants 2-ethylhexyl tetrabromobenzoate (EH-TBB) and bis(2-ethylhexyl) tetrabromophthalate (BEH-TEBP) following dermal application suggest that these compounds are bioavailable. Overall, this study shows the importance of considering the contribution of the dermal route of exposure to EH-TBB and BEH-TEBP and provides a more complete evaluation of potential risk of adverse health outcomes.
2-ethylhexyltetrabromobenzoate (EH-TBB) and bis(2-ethylhexyl)tetrabromophthalate (BEH-TEBP) are novel brominated flame retardants (FRs). BEH-TEBP is used alone as a plasticizer or with EH-TBB in polyurethane foams; both are contaminants in the indoor and outdoor environments. In the present study, a parallelogram approach was used to predict internal doses for dermally exposed humans. [14C]-EH-TBB or [14C]-BEH-TEBP was applied in toluene to human or rat skin at 100 nmol/cm2 using a flow-through diffusion cell system. Intact rats received a similar dose by dermal application to a dorsal skin site. At the conclusion of each experiment, treated skin was washed and tape-stripped to remove unabsorbed [14C]-radioactivity. The absorbed dose was then quantified within the skin and perfusion media in the in vitro system and in the excreta, tissues, and dosed skin site of rats. Human skin retained 12% of the total dose of EH-TBB while 0.2% was recovered in the perfusion media. Rat skin was more absorptive (36%) and permeable (2%). In dermally-exposed rats, 10% of the total dose remained within the application site and 13% had reached systemic circulation by 24 h post-dosing. BEH-TEBP was poorly absorbed in the in vitro system, with 29% of the total dose recovered in the skin and <0.01% recovered in the perfusion media. In vivo, dosed skin contained 8% of applied BEH-TEBP with 1.2% reaching systemic circulation. EH-TBB was completely metabolized in rat and human skin to tetrabromobenzoic acid (TBBA). The low amount of BEH-TEBP-derived [14C]-radioactivity in the perfusion media could not be characterized. Based on these data, ~7% of EH-TBB and ~1% of BEH-TEBP may be dermally bioavailable to humans.
Record Details:Record Type: DOCUMENT (JOURNAL/PEER REVIEWED JOURNAL)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY
INTEGRATED SYSTEMS TOXICOLOGY DIVISION