Decabromodiphenyl Ether in the Rat: Absorption, Distribution, Metabolism, and Excretion

Abstract

This article is available online at http://dmd.aspetjournals.org ABSTRACT:Among the group of polybrominated diphenyl ethers used as flame-retardants, the fully brominated diphenyl ether, decabromodiphenyl ether (decaBDE), is the most commonly used. Despite the large usage of decaBDE, neither the metabolic pathways nor the absorption have been addressed, and there are very few studies on its toxicology. In this work, it is shown that after a single oral dose of 14 C-labeled decaBDE to rats, at least 10% of the decaBDE dose is absorbed. The major excretion route in conventional rats is via feces that contained 90% of the decaBDE dose. The excretion in bile was close to 10% of the dose and represented mainly metabolites. It cannot be excluded that greater than 10% of the oral dose had been absorbed since 65% of the radioactivity excreted in feces was metabolites. The highest concentrations on a lipid weight basis were found in plasma and blood-rich tissues, and the adipose tissue had the lowest concentration of decaBDE. After derivatization of a phenolic fraction, gas chromatography-mass spectrometry (GC/MS) analyses indicated that metabolites with five to seven bromine atoms had formed, and they possessed a guaiacol structure (a hydroxy and a methoxy group) in one of the rings. In addition, traces of nonabrominated diphenyl ethers and monohydroxylated metabolites were found by GC/MS. Metabolites, characterized by their chemical properties, were interpreted to be covalently bound to macromolecules, either proteins or lipids. In addition, water solubility was suggested. The metabolic pathway was indicated to include a reactive intermediate.

Developmental neurotoxicity of polybrominated diphenyl ether (PBDE) flame retardants

“…The half-life of tetra-to hexa-PBDEs has been shown to range in mice and rats between 20 and 120 days (Hakk and Letcher, 2003;Geyer et al 2004), with an increase proportional to the degree of bromination. In contrast, BDE-209 appears to be excreted more rapidly (Morck et al 2003;Hakk and Letcher, 2003), though a half-life of 75 days has been reported in another study (Huwe and Smith, 2007).…”

“…BDE-47, BDE-99, BDE-153) are usually well absorbed following oral exposure (Orn and Klasson-Wehler, 1998;Hakk et al 2002;Staskal et al 2006b). In contrast, absorption of decaBDE is much lower (10% of the dose) (Morck et al 2003). PBDEs distribute to several tissues including the brain, and highest and more persistent concentrations are found in adipose tissue (Hakk and Letcher, 2003), however, this is not the case for BDE-209 (Morck et al 2003).…”

“…PBDEs distribute to several tissues including the brain, and highest and more persistent concentrations are found in adipose tissue (Hakk and Letcher, 2003), however, this is not the case for BDE-209 (Morck et al 2003). Tetra-and pentaBDEs are metabolized by mixed function oxidases to mono-and di-hydroxylated metabolites (Hakk et al 2002;Hakk and Letcher, 2003;Malmberg et al 2005;Marsh et al 2004), while decaBDE is metabolized to lower brominated congeners (nona-and octaBDE) (Morck et al 2003;Huwe and Smith, 2007). There appears to be a species difference in the rate of excretion, with a higher urinary excretion in mice (Orn and Klasson-Wehler, 1998).…”

Debrominated and methoxylated polybrominated diphenyl ether metabolites in rainbow trout (Oncorhynchus mykiss) after exposure to decabromodiphenyl ether

“…Two tetra-MeO-BDEs were reported from green turtle and marine mammals from the Southern Hemisphere (Vetter, 2001;Vetter et al, 2002). Moreover, MeO-BDE metabolites containing 6-7 bromine atoms also have been shown in rats exposed to BDE209 (Mörck et al, 2003).…”

Toxicokinetics and the related metabolites in rainbow trout (Oncorhynchus mykiss) after exposure to decabromodiphenyl ether

“…Furthermore, debromination of BDE209 by juvenile carp following dietary exposure was also observed, and several hexa-through octa-BDE metabolites were found to be more bioavailable than BDE209 itself [24]. In addition to debrominated diphenyl ether metabolites, methoxylated brominated diphenyl ethers (MeO-BDEs) were also regarded as the BDE metabolites in organisms [25][26][27][28]. However, the majority of those studies attributed the MeOBDEs in biota samples to naturally biogenetic processes in marine sponges and algae [29], while very limited studies about MeO-BDEs metabolites of PBDEs were available.…”