title: Estimation of tetrabromobisphenol A (TBBPA) percutaneous uptake in humans using the parallelogram method.
abstract: 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 [(14)C]-radioactivity was determined at 6h intervals in the media and at 24h 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/cm(2) remained in the skin at the dosing site, with an additional 8% reaching systemic circulation by 24h post-dosing. Relative absorption and penetrance were less (10% total) at 24h following dermal administration of a ten-fold higher dose (~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.
authors.affiliation: NCI at NIEHS, 111 T W Alexander Dr., Research Triangle Park, NC, USA. Electronic address: gabriel.knudsen@nih.gov.
authors.forename: Gabriel A
authors.initials: GA
authors.lastname: Knudsen
authors.affiliation: Integrated Systems Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Hughes
authors.affiliation: NCI at NIEHS, 111 T W Alexander Dr., Research Triangle Park, NC, USA.
authors.forename: Katelyn L
authors.initials: KL
authors.lastname: McIntosh
authors.affiliation: NCI at NIEHS, 111 T W Alexander Dr., Research Triangle Park, NC, USA.
authors.forename: J Michael
authors.initials: JM
authors.lastname: Sanders
authors.affiliation: NCI at NIEHS, 111 T W Alexander Dr., Research Triangle Park, NC, USA.
authors.forename: Linda S
authors.initials: LS
authors.lastname: Birnbaum
mesh_terms: D000279:Administration, Cutaneous; D000368:Aged; D000818:Animals; D001682:Biological Availability; D001822:Body Burden; D004781:Environmental Exposure; D005260:Female; D005411:Flame Retardants / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics / Q000633:toxicity; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008954:Models, Biological; D011075:Polybrominated Biphenyls / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics / Q000633:toxicity; D017208:Rats, Wistar; D018570:Risk Assessment; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption
chemical_list: D005411:Flame Retardants; D011075:Polybrominated Biphenyls; C020806:tetrabromobisphenol A
keywords: Brominated flame retardant; Dermal bioavailability; Parallelogram method; Persistent organic pollutant; Tetrabromobisphenol A; Tetrabromobisphenol A (PubChem CID: 6618)