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Estimation of Tetrabromobisphenol A (TBBPA)percutaneous uptake in humans using the parallelogram method.
Citation:
Knudsen, G., M. Hughes, K. McIntosh, J. Sanders, AND L. Birnbaum. Estimation of Tetrabromobisphenol A (TBBPA)percutaneous uptake in humans using the parallelogram method. TOXICOLOGY AND APPLIED PHARMACOLOGY. Academic Press Incorporated, Orlando, FL, 289(2):323-329, (2015).
Impact/Purpose:
Experiments using the parallelogram approach to estimate human systemic exposure to the brominated flame retardant tetrabromobisphenol A following dermal application suggest that the compound is bioavailable. Overall, this study shows the importance of considering the contribution of the dermal route of exposure to TBBP A to provide a more complete evaluation of potential risk of adverse health outcomes.
Description:
Tetrabromobisphenol A (Tl3BPA) is currently the world's highest production volumebrominated flame retardant. Humans are frequently exposed to TBBPA by the dermal route. In the present study., a parallelogram approach was used to make predictions of internal dose in exposed humans. Human and rat skin samples received 100 nmol ofTBBPA/cm2 skin and absorption and penetrance were determined using a flow-throughin vitro system. TBBPA-derived [14C]-radioactivity was determined at 6 hour intervals in the media and at 24 hours post-dosing in the skin. The human skin and media contained an average of 3.4% and 0.2% of the total dose at the terminal time point,respectively, while the rat skin and media contained 9.3% and 3.5%, respectively. In the intact rat, 14% of a dermally-administered dose of -100 nmol/cm2 remained in the skin at the dosing site, with an additional 8% reaching systemic circulation by 24 hours post-dosing. Relative absorption and penetrance was less (10% total) at 24 hours following dermal administration of a ten-fold higher dose (-1,000 nmol/cm2) to rats. However, by 72 hours, 70% of this dose was either absorbed into the dosing-site skin or had reached systemic circulation. It is clear from these results that TBBPA can be absorbed by the skin and dermal contact with TBBPA may represent a small but important route of exposure. Together, these in vitro data in human and rat skin and in vivo data from rats may be used to predict TBBPA absorption in humans following dermal exposure. Based on this parallelogram calculation, up to 6% of dermally applied TBBPA may be bioavailable to humans exposed to TBBPA.
