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2,4,6-Tribromophenol disposition and kinetics in rodents: effects of dose, route, sex, and species
Citation:
Knudsen, G., A. Trexler, A. Richiards, M. Hughes, AND L. Birnbaum. 2,4,6-Tribromophenol disposition and kinetics in rodents: effects of dose, route, sex, and species. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 169(1):167-179, (2019). https://doi.org/10.1093/toxsci/kfz044
Impact/Purpose:
2,4,6-Tribromophenol (TBP, CAS No. 118-79-6) is a widely used brominated flame retardant (BFR), precursor for other BFRs, and wood antifungal agent. TBP is found as a naturally-occurring bromophenol in marine organisms and contributes to the ‘shrimp’ flavor in processed foodstuff. Biotic degradation of tetrabromobisphenol A or other brominated phenolic chemicals results in the formation of TBP and other phenolic byproducts. Due to this wide variety of natural and anthropogenic sources, TBP is a frequently detected (60-100% detection frequency) contaminant in environmental matrices and biota, including human breast milk, placenta, and serum. This study examined the disposition and kinetics of TBP in rodents. The study focused on the effects of dose, route, sex, and species. Ex vivo dermal absorption studies were done with human to estimate human in vivo dermal absorption. TBP was readily absorbed at all doses and routes tested with an oral bioavailability of 23-27%; 49% of TBP is expected to be dermally bioavailable in humans. TBP did not appear to bioaccumulate or alter its own metabolism after repeated administration. From these data we conclude that humans are likely to have significant systemic exposure when TBP is encountered in the workplace, home, or outside environment. This data would be of interest to the Office of Pollution Prevention and Toxics and state and local agencies that regulate brominated flame retardants.
Description:
2,4,6-tribromophenol (TBP, CAS No. 118-79-6) is widely used as a brominated flame retardant and wood antifungal agent. TBP is frequently detected in environmental matrices, biota, and humans. In female SD rats, systemically available TBP (10 µmol/kg, IV) was rapidly excreted primarily via urine, with ~61% of the dose recovered after 4h, and 89-94% in 24h; 5% was recovered in feces and 1-2% in blood/tissues. TBP administered to female SD rats (0.1-1000 µmol/kg) by gavage was well absorbed, with ~25% eliminated via urine after 4h and ~88% after 24h. Approximately 11% of a single oral dose was recovered in bile. Male SD rats and B6C3F1/J mice of both sexes had similar disposition profiles when administered a single oral dose of TBP (10 µmol/kg). Following administration, fecal recoveries varied only slightly by dose, sex, or species. TBP readily passed unchanged through both human (ex vivo only) and rat skin. Concentrations of TBP in blood fit a two-compartment model after IV-dosing and a one-compartment model after oral dosing. Urine contained a mixture of TBP, TBP-glucuronide, and TBP-sulfate. Fecal extracts contained only parent TBP while bile contained only TBP-glucuronide. TBP did not appear to bioaccumulate or alter its own metabolism after repeated administration. TBP was readily absorbed at all doses and routes tested with an oral bioavailability of 23-27%; 49% of TBP is expected to be dermally bioavailable in humans. From these data we conclude that humans are likely to have significant systemic exposure when TBP is encountered in the workplace, home, or outside environment.
URLs/Downloads:
DOI: 2,4,6-Tribromophenol disposition and kinetics in rodents: effects of dose, route, sex, and species
https://academic.oup.com/toxsci/article/169/1/167/5320422