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

被引:21
作者
Knudsen, Gabriel A. [1 ]
Hughes, Michael F. [2 ]
McIntosh, Katelyn L. [1 ]
Sanders, J. Michael [1 ]
Birnbaum, Linda S. [1 ]
机构
[1] NIEHS, NCI, Res Triangle Pk, NC 27709 USA
[2] US EPA, Integrated Syst Toxicol Div, Natl Hlth & Environm Effects Res Lab, Off Res & Dev, Res Triangle Pk, NC 27711 USA
关键词
Dermal bioavailability; Brominated flame retardant; Tetrabromobisphenol A; Parallelogram method; Persistent organic pollutant; VITRO DERMAL ABSORPTION; SPRAGUE-DAWLEY RATS; IN-VITRO; FLAME RETARDANTS; BISPHENOL-A; HOUSE-DUST; EXPOSURE; SKIN; DISPOSITION; VIVO;
D O I
10.1016/j.taap.2015.09.012
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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/cm(2) skin and absorption and penetrance were determined using a flow-through in vitro system. TBBPA-derived [C-14]-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 similar to 100 nmol/cm(2) 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 (similar to 1000 nmol/cm(2)) 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. Published by Elsevier Inc.
引用
收藏
页码:323 / 329
页数:7
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