In vitro hepatic metabolism of 2,2′,4,4′,5-pentabromodiphenyl ether (BDE 99) in Chinook Salmon (Onchorhynchus tshawytscha)

Abstract

Polybrominated diphenyl ethers (PBDEs) are brominated flame retardants that persist in the environment and are present in geographically widespread fish species. PBDE concentrations can be particularly high in resident Chinook salmon (Onchorhynchus tshawytscha) in the Puget Sound, Washington. Although PBDE residues in salmon and other fish are often dominated by lower brominated congeners, these congeners are not produced commercially in the greatest quantity, suggesting bioaccumulation of the lower molecular weight PBDEs or debromination of more fully brominated congeners. We determined the capacity of Chinook liver fractions to debrominate 2,2′, 4,4′,5-pentabromodiphenyl ether (BDE 99), a model PBDE congener readily debrominated by common carp (Cyprinus caprio). Liver subcellular fractions from two strains of Chinook were incubated with BDE 99 prior to liquid/liquid extraction followed by gas chromatography/mass spectrometry analysis (GC/MS analysis) to identify metabolites and debromination products. In contrast to common carp, debromination of BDE 99 to BDE 47 (2,2′,4,4′-tetrabromodiphenyl ether) was not observed in microsomal fractions from either strain of Chinook salmon. However, Chinook salmon liver microsomes from both Chinook strains slowly debrominated BDE 99 to BDE 49 (2,2′, 4,5′-tetrabromodiphenyl ether), a unique debromination product whose formation has not been reported in other fish. Three-year old males belonging to a Rapid River Spring Chinook salmon genetic strain showed a somewhat greater microsomal debromination capacity than older hatchery returning male Chinook, but were still inefficient in the debromination of BDE 99 relative to carp. Microsomal debromination of BDE 99 to BDE 49 was not NADPH-dependent, indicating a lack of cytochrome P450 involvement. By contrast, omission of the reductant dithiothreitol (DTT) from Chinook microsomal preparations resulted in a lack of BDE 99 debromination, suggesting the involvement of a microsomal reductase(s) or deiodinase (DI). Cytosolic fractions from Chinook salmon and Common carp debrominated BDE 99 to BDE 49 in vitro. However, carp cytosolic enzymes preferentially formed BDE 47. In summary, our data indicate significant differences among teleosts with respect to efficiency and metabolite profiles of BDE 99 debromination, and suggest that Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access

Major sources of MeO/OH-BDEs in the East China Sea elucidated from their records and phytoplankton biomarkers

“…These compounds were initially considered as metabolites or by-products of anthropogenic PBDEs because of the similarities in their structure (Haglund et al, 1997;Marsh et al, 2006). Some in vivo and in vitro studies have reported the biotransformation of OH-BDEs from various PBDEs (Erratico et al, 2010;Hakk et al, 2009;Malmberg et al, 2005;Qiu et al, 2007;Stapleton et al, 2009) despite the absence of OH-BDE formation in other PBDE exposure experiments (Benedict et al, 2007;Browne et al, 2009;Stapleton et al, 2006;Wan et al, 2009). However, concentrations of detected OH-BDEs were markedly lower than PBDEs, with a conversion ratio of w3% (Erratico et al, 2010;Hamers et al, 2008;Malmberg et al, 2005;Stapleton et al, 2009).…”

Experimental exposure of eggs to polybrominated diphenyl ethers BDE‐47 and BDE‐99 in red‐eared sliders (Trachemys scripta elegans) and snapping turtles (Chelydra serpentina) and possible species‐specific differences in debromination

“…Although early embryonic development of red-eared sliders and snapping turtles is similar [42,43], species-specific differences are likely in enzymatic systems potentially responsible for differential capacities for debromination, as has been shown in fish exposed to BDE-99 [7,10]. Several studies of fish have shown debromination of BDE-99 to BDE-47 in carp, but other species such as Chinook salmon and rainbow trout demonstrate different reductive metabolite products and slower formation rates [6,7,9,10]. Deiodinase enzymes (DIs)-which are responsible for the removal of iodine atoms from thyroid hormones, resulting in activation or deactivation of the hormones-have been suggested as the primary enzymatic system for debromination of BDE-99 to BDE-47 in fish, particularly in carp [7,9,10].…”

“…McKernan et al [8] reported the presence of several PBDE congeners in the egg contents of several species of birds that had been injected with DE-71 but were not detected in the dosing solution or control eggs. Although early embryonic development of red-eared sliders and snapping turtles is similar [42,43], species-specific differences are likely in enzymatic systems potentially responsible for differential capacities for debromination, as has been shown in fish exposed to BDE-99 [7,10]. Several studies of fish have shown debromination of BDE-99 to BDE-47 in carp, but other species such as Chinook salmon and rainbow trout demonstrate different reductive metabolite products and slower formation rates [6,7,9,10].…”

“…Several studies of fish have shown debromination of BDE-99 to BDE-47 in carp, but other species such as Chinook salmon and rainbow trout demonstrate different reductive metabolite products and slower formation rates [6,7,9,10]. Deiodinase enzymes (DIs)-which are responsible for the removal of iodine atoms from thyroid hormones, resulting in activation or deactivation of the hormones-have been suggested as the primary enzymatic system for debromination of BDE-99 to BDE-47 in fish, particularly in carp [7,9,10]. Preliminary data suggest higher DI activity in red-eared sliders than in snapping turtles, suggesting that the DIs may be a hypothetical metabolic pathway for reductive debromination in red-eared sliders [44].…”

“…The lower brominated congeners, including BDE-47, -99, -100, and -153, are most widely detected and usually in the greatest quantity, which has been attributed to metabolism of the higher brominated congeners through debromination [4,5] as well as exposures to the penta-BDE commercial mixture present in older products that remain in use. There is evidence that in fish, rats, and birds, reductive debromination is a potential pathway for metabolism of PBDEs [6][7][8][9][10][11]. The environmental persistence of PBDEs as well as metabolism to the more bioaccumulative and toxic lower brominated congeners suggests that they are likely to remain contaminants of concern despite recently imposed restrictions on use.…”