Using the parallelogram approach to estimate human percutaneous bioavailability for novel & legacy brominated flame retardants

Authors

• GA Knudsen
• MF Hughes
• JM Sanders
• SM Hall
• LS Birnbaum

Abstract

Humans, especially children, are commonly exposed to flame retardants (FRs) in contaminated dust. Tetrabromobisphenol-A (TBBPA) is a FR used a reactive and additive FR. 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (EH-TBB), bis(2-ethylhexyl) tetrabromophthalate (BEH-TEBP), and decabromodiphenylethane (DBDPE) are novel brominated FRs used to replace banned polybrominated diphenyl ethers. In the present study, a parallelogram approach was used predict internal dose for dermally exposed humans. Human or rat skin received 100 nmol of [14C]-TBBPA, -TBB, -TBPH/cm2 or 2.5 nmol DBDPE/cm2. Treated skin was washed and tape-stripped prior to quantification of [14C]-radioactivity in dosed skin and media (in vitro) or excreta, tissues, and skin (in vivo). Human skin and media contained an average of 3.4% and 0.2% of TBBPA after 24h, respectively, while the in vitro rat skin and media contained 9.3% and 3.5% (in vivo: 14% and 8%), respectively. Up to 6% of dermally applied TBBPA may be bioavailable dermally. Dermal flux values for human skin continuously exposed to EH-TBB or BEH-TEBP were estimated to be 14±4 and 8±4 pmol-eq/cm2/h, respectively. EH-TBB was moderately absorbed dermally and hydrolyzed to tetrabromobenzoic acid while BEH-TEBP penetrance was low and metabolism was not seen. The dermis acted as a depot for dermally applied DBDPE; dermal flux for in vivo human skin was expected to reach 2±0.4 pmol-eq/cm2/h. Penetration for these studies was flux-limited; however, these data demonstrate skin contact with BFRs represents a small but important route of exposure. This work was supported by the extramural program of NCI/NIH. (This abstract does not represent U.S. EPA policy.)

Scientific Focus Area: Chemical Biology

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