Absorption of [14C]-tetrabromodiphenyl ether (TeBDE) through human and rat skin in vitro.
The skin is the largest organ in the human body and has the potential to come into contact with a variety of xenobiotics both intentionally (e.g., drugs and cosmetics) or accidentally (e.g., agrochemicals and industrial chemicals). These chemicals may then cross the skin barrier (the stratum corneum) and enter into the systemic circulation where they may produce a desired or an undesired effect, or even no systemic effect at all. Tetrabromodiphenyl ether (TeBDE) is one congener in a mixture of polybrominated diphenyl ethers that makes up a flame-retardant commercial product called pentabromodiphenyl ether (PeBDE). TeBDE was used as a surrogate to assess the potential dermal absorption of this product. The physicochemical properties, including lipophilicity, of TeBDE and PeBDE are similar. Operator exposure of PeBDE product to human skin is possible during production and use. However, during these activities, operators wear protective clothing to protect from or minimize exposure. This study was designed to assess the rate and extent of absorption of [14C]-tetrabromodiphenyl ether ([14C]-TeBDE) through human and rat skin in vitro. [14C]-TeBDE was applied to human and rat split thickness skin membranes in vitro in a single test preparation: [14C]-TeBDE in acetone (ca. 20%, w/v). Dermal delivery and absorbed dose of TeBDE applied to human skin was 3.13% (313 microg equiv/cm(2)) and 1.94% (194 microg equiv/cm(2)) of the applied dose, respectively. Dermal delivery and absorbed dose of TeBDE applied to rat skin was 17.94% (1804 microg equiv/cm(2)) and 14.81% (1489 microg equiv/cm(2)) of the applied dose, respectively. These results confirm that the risk of systemic exposure due to external dermal exposure of the PeBDE product is low in the human. Consequently, based on the toxicological profile of these materials, the potential for undesirable effects is also quite low. The results also confirm that the rat is a conservative model overpredicting human absorption about eight fold.
Roper
Clive S
CS
Charles River Laboratories, Tranent, Edinburgh, Scotland. clive.roper@eur.crl.com
Simpson
Andrew G
AG
Madden
Stephen
S
Serex
Tessa L
TL
Biesemeier
John A
JA
D000096:Acetone; D000287:Administration, Topical; D000328:Adult; D000818:Animals; D002626:Chemistry, Pharmaceutical; D015194:Diffusion Chambers, Culture; D005260:Female; D005411:Flame Retardants / Q000493:pharmacokinetics*; D055768:Halogenated Diphenyl Ethers; D006801:Humans; D006842:Hydrocarbons, Brominated / Q000493:pharmacokinetics*; D066298:In Vitro Techniques; D008297:Male; D008566:Membranes / Q000378:metabolism; D008875:Middle Aged; D016273:Occupational Exposure; D010647:Phenyl Ethers / Q000493:pharmacokinetics*; D011075:Polybrominated Biphenyls; D051381:Rats; D017207:Rats, Sprague-Dawley; D012869:Skin Absorption; D012997:Solvents
D005411:Flame Retardants; D055768:Halogenated Diphenyl Ethers; D006842:Hydrocarbons, Brominated; D010647:Phenyl Ethers; D011075:Polybrominated Biphenyls; D012997:Solvents; C511295:2,2',4,4'-tetrabromodiphenyl ether; D000096:Acetone