2,4,6-Tribromophenol disposition and kinetics: effects of dose, route, sex, and species
Citation:
Knudsen, G., A. Trexler, A. Richards, S. Hall, M. Hughes, AND L. Birnbaum. 2,4,6-Tribromophenol disposition and kinetics: effects of dose, route, sex, and species. Society of Toxicology, Baltimore, Maryland, March 10 - 14, 2019.
Impact/Purpose:
2,4,6-Tribromophenol (TBP) is a widely used brominated flame retardant and wood antifungal agent. It is routinely detected in the environment and in humans. This study examined the disposition of TBP following oral, intravenous and dermal administration in rodents. Human skin in vitro was also used to assess dermal absorption. The data suggests that humans are likely to have significant systemic exposure when TBP is encountered in the workplace, home or outside environment.
Description:
2,4,6-tribromophenol (TBP, CAS No. 118-79-6) is a naturally-occurring bromophenol that is widely used as a brominated flame retardant and wood antifungal. TBP is found in soil, dust, wild-caught seafood, and humans. TBP in vivo studies of oral and dermal disposition were conducted in rats and mice. Human dermal disposition was estimated based on studies of ex vivo split-thickness human and rat skin. Following intravenous administration, TBP was rapidly excreted in urine, with 89-94% recovered in urine, 5% in feces and 1-2% in blood/tissues after 24h. TBP administered to female SD rats (0.1-1000 µmol/kg) by gavage was well absorbed, with ~88% eliminated via urine after 24h, 11% in bile, and 5% in feces. Male and female SD rats and B6C3F1/J mice had similar disposition profiles when administered a single oral dose of TBP (10 µmol/kg), with urine and fecal recoveries varying only slightly by sex or species. TBP kinetics were linear across a range of doses in short-term studies (500 nmol/kg, 4 h). Urine contained TBP, TBP-glucuronide, and TBP-sulfate while bile contained TBP-glucuronide and fecal extracts contained only parent TBP. TBP did not appear to bioaccumulate after single or 5 repeated oral administrations. TBP was readily absorbed at all doses and routes tested with an oral bioavailability of 23-27%. TBP readily passed unchanged through both human and rat skin with 49% expected to be dermally bioavailable in humans. We conclude from these data that humans are likely to have significant systemic exposure when TBP is encountered in the workplace, home, or outside environment. (This abstract does not necessarily represent U.S. EPA policy.)