Disposition of 2,2′,4,4′,5,5′-hexabromodiphenyl ether (BDE153) and its interaction with other polybrominated diphenyl ethers (PBDEs) in rodents

Abstract

1.The disposition of the 14 C-labeled polybrominated diphenyl ether (PBDE), 2,2′,4,4′,5,5′-hexaBDE (BDE153) was investigated in rodents following single and multiple doses and in a mixture with radiolabeled 2,2′,4,4′-tetraBDE (BDE47) and 2,2′,4,4′,5-pentaBDE (BDE99). 2.In single exposure studies, there was little or no effect of dose on BDE153 disposition in male rats in the range of 1-100 µmol/kg. No major sex or species differences in the in vivo fate of BDE153 were detected. BDE153 was: 1) approximately 70% absorbed in rats or mice following gavage. 2) retained in tissues. 3) poorly metabolized and slowly excreted. 3.Mixture studies indicated that, relative to each other, more BDE47 was distributed to adipose tissue, more BDE153 accumulated in liver, and BDE99 was metabolized to the greatest extent. BDE153 was probably retained in liver due to minimal metabolism and elimination after "first pass" distribution to the tissue following gavage.

Scientific Opinion on Polybrominated Diphenyl Ethers (PBDEs) in Food

“…Additional studies performed in rodents with 14 C-BDE-47 confirmed that the majority of residues were contained in adipose tissue (Darnerud and Risberg, 2006;Sanders et al, 2006). Sanders et al (2006) examined the impact of repeat dosing on the disposition of BDE-47 in male rats. Doses of 0.1 μmol/kg (approximately 0.05 mg/kg) of 14 C-BDE-47 were administered for 1, 5, or 10 consecutive days.…”

“…They were 2'-hydroxy-2,4,4'-triBDE, 3'-hydroxy-2,4,4'-triBDE, 4'-hydroxy-2,2',4-triBDE, 6-hydroxy-2,2',4,4'-tetraBDE, 2'-hydroxy-2,3',4,4'-tetraBDE, 3-hydroxy-2,2',4,4'-tetraBDE, 5-hydroxy-2,2',4,4'-tetraBDE, 4'-hydroxy-2,2',4,5'-tetraBDE and 4-hydroxy-2,2',3,4'-tetraBDE. Analysis of biliary metabolites collected from rats receiving 1 μmol/kg (ca 0.5 mg/kg) 14 C-BDE-47 intravenously (Sanders et al, 2006), resulted in the identification of two glutathione conjugates, namely 5-(glutathion-S-yl)-2,2',4,4'-tetraBDE and 6-(glutathion-S-yl)-2,2',4,4'-tetraBDE. In the metabolic pathway proposed by the authors the glutathione conjugates were formed through an arene oxide intermediate.…”

“…Mixture studies indicated that, relative to each other, more BDE-47 was distributed to adipose tissue, more BDE-153 accumulated in the liver, and BDE-99 was metabolized to the greatest extent (Sanders et al, 2006). Reistad et al (2006) investigated the distribution of PBDE congeners in rats after a single intraperitoneal injection (13.2 ± 0.7 mg/kg b.w.)…”

Exposure of Americans to polybrominated diphenyl ethers

“…Orn and Klasson-Wehler (1998) found that BDE 47 was persistent in the rat, but rapidly excreted in urine in mice. In a recent study, Sanders et al (2006) found that BDE 99 was the most rapidly metabolized congener of BDEs 47, 99, and 153 following single and multiple doses of radiolabelled mixtures of these three congeners administered by gavage to rodents (rats and mice). This contradicts the extrapolation by Geyer et al (2004) which resulted in a more rapid half-life for BDE 47.…”

PBDE flame retardants

“…Studies in rodents have likewise measured absorption of BDE-47, -99, -100, -153, and -154 in the range of ~70-90%. [53][54][55] However, other studies that have exposed fish to unlabeled PBDEs through the diet have measured lower assimilation efficiencies of some congeners, including BDE-99, BDE-153, BDE-183, and BDE-209 suggesting species-specific differences in assimilation efficiencies of PBDEs possibly due to differences in metabolic enzyme systems. [56][57][58] For instance, BDE-209 absorption in some teleost fishes has been shown to occur at a slow rate, which may allow for greater metabolism and elimination than seen in terrestrial species.…”