title: Evaluation of 3D-human skin equivalents for assessment of human dermal absorption of some brominated flame retardants.
abstract: Ethical and technical difficulties inherent to studies in human tissues are impeding assessment of the dermal bioavailability of brominated flame retardants (BFRs). This is further complicated by increasing restrictions on the use of animals in toxicity testing, and the uncertainties associated with extrapolating data from animal studies to humans due to inter-species variations. To overcome these difficulties, we evaluate 3D-human skin equivalents (3D-HSE) as a novel in vitro alternative to human and animal testing for assessment of dermal absorption of BFRs. The percutaneous penetration of hexabromocyclododecanes (HBCD) and tetrabromobisphenol-A (TBBP-A) through two commercially available 3D-HSE models was studied and compared to data obtained for human ex vivo skin according to a standard protocol. No statistically significant differences were observed between the results obtained using 3D-HSE and human ex vivo skin at two exposure levels. The absorbed dose was low (less than 7%) and was significantly correlated with log Kow of the tested BFR. Permeability coefficient values showed increasing dermal resistance to the penetration of γ-HBCD>β-HBCD>α-HBCD>TBBPA. The estimated long lag times (>30 min) suggests that frequent hand washing may reduce human exposure to HBCDs and TBBPA via dermal contact.
authors.affiliation: Division of Environmental Health and Risk Management, College of Life and Environmental Sciences, University of Birmingham, Birmingham B15 2TT, United Kingdom; Department of Analytical Chemistry, Faculty of Pharmacy, Assiut University, 71526 Assiut, Egypt. Electronic address: mae_abdallah@yahoo.co.uk.
authors.forename: Mohamed Abou-Elwafa
authors.initials: MA
authors.lastname: Abdallah
authors.affiliation: Division of Environmental Health and Risk Management, College of Life and Environmental Sciences, University of Birmingham, Birmingham B15 2TT, United Kingdom.
authors.forename: Gopal
authors.initials: G
authors.lastname: Pawar
authors.affiliation: Division of Environmental Health and Risk Management, College of Life and Environmental Sciences, University of Birmingham, Birmingham B15 2TT, United Kingdom.
authors.forename: Stuart
authors.initials: S
authors.lastname: Harrad
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D000826:Animal Testing Alternatives; D000818:Animals; D001682:Biological Availability; D005260:Female; D005411:Flame Retardants / Q000493:pharmacokinetics* / Q000633:toxicity; D006801:Humans; D006842:Hydrocarbons, Brominated / Q000493:pharmacokinetics* / Q000633:toxicity; D066298:In Vitro Techniques; D011075:Polybrominated Biphenyls / Q000493:pharmacokinetics* / Q000633:toxicity; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption; D017768:Skin, Artificial
chemical_list: D005411:Flame Retardants; D006842:Hydrocarbons, Brominated; D011075:Polybrominated Biphenyls; C089796:hexabromocyclododecane; C020806:tetrabromobisphenol A
keywords: Dermal absorption; EPISKIN; HBCDs; Human ex vivo skin; Human skin equivalents; TBBPA