Estimation of tetrabromobisphenol A (TBBPA) percutaneous uptake in humans using the parallelogram method

• Tetrabromobisphenol A is the brominated flame retardant with highest global production volumes.
• Humans are frequently exposed to TBBPA by the dermal route, especially via contaminated dust.
• Human and rat skin data were integrated using a parallelogram method to predict human absorption.
• TBBPA was dermally absorbed and skin contact may represent a small but important route of exposure.
• Up to 6% of dermally applied TBBPA may be bioavailable to humans exposed to TBBPA.

Tetrabromobisphenol A (TBBPA) is currently the world's highest production volume brominated 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 of TBBPA/cm2 skin and absorption and penetrance were determined using a flow-through in vitro system. TBBPA-derived [14C]-radioactivity was determined at 6 h intervals in the media and at 24 h 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 h post-dosing. Relative absorption and penetrance were less (10% total) at 24 h following dermal administration of a ten-fold higher dose (~ 1000 nmol/cm2) to rats. However, by 72 h, 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.