The Flame Retardants, Polybrominated Diphenyl Ethers, Are Pregnane X Receptor Activators

Pacyniak, Erik; Cheng, Xinjian; Cunningham, Michael L.; Crofton, Kevin M.; Klaassen, Curtis D.; Guo, Grace L.

doi:10.1093/toxsci/kfm025

Cited by 134 publications

(100 citation statements)

References 47 publications

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“…The present results are in line with other studies showing that CYP2B gene expression is inducible and might be involved in the metabolism of BDE-209 (Meerts et al., 2000; Pacyniak et al, 2007). These results are similar to our study in which BDE-209 significantly induced CYP1A2 and CYP3A1 expression in the liver.…”

Section: Discussionsupporting

confidence: 94%

Evaluation of liver and thyroid toxicity in Sprague-Dawley rats after exposure to polybrominated diphenyl ether BDE-209

et al. 2010

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Section: Discussionsupporting

confidence: 94%

Evaluation of liver and thyroid toxicity in Sprague-Dawley rats after exposure to polybrominated diphenyl ether BDE-209

et al. 2010

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“…CYP3A isozymes are involved in the first phase of the xenobiotic metabolism by means of introducing reactive or polar groups into the xenobiotics, thus modifying their chemical structure. Contaminants that have been shown to induce the transcription of CYP3A isozymes include PCBs (Schuetz et al, 1998), dioxins (Tseng et al, 2005) and PBDEs (Pacyniak et al, 2007). In addition, we also identified one transcriptionally upregulated gene involved in the second phase of the xenobiotic metabolism, glutathione S-transferase pi (GSTP1), previously described in many fish species including the European eel (GenBank accession number AAS01601).…”

Section: Parallel Transcriptional Detoxification Response To Pollutantsmentioning

confidence: 81%

Detecting genome-wide gene transcription profiles associated with high pollution burden in the critically endangered European eel

et al. 2013

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a b s t r a c tThe European eel illustrates an example of a critically endangered fish species strongly affected by human stressors throughout its life cycle, in which pollution is considered to be one of the factors responsible for the decline of the stock. The objective of our study was to better understand the transcriptional response of European eels chronically exposed to pollutants in their natural environment. A total of 42 pre-migrating (silver) female eels from lowly, highly and extremely polluted environments in Belgium and, for comparative purposes, a lowly polluted habitat in Italy were measured for polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs) and brominated flame retardants (BFRs). Multipollutant level of bioaccumulation was linked to their genome-wide gene transcription using an eel-specific array of 14,913 annotated cDNAs. Shared responses to pollutant exposure were observed when comparing the highly polluted site in Belgium with the relatively clean sites in Belgium and Italy. First, an altered pattern of transcription of genes was associated with detoxification, with a novel European eel CYP3A gene and gluthatione S-transferase transcriptionally up-regulated. Second, an altered pattern of transcription of genes associated with the oxidative phosphorylation pathway, with the following genes involved in the generation of ATP being transcriptionally down-regulated in individuals from the highly polluted site: NADH dehydrogenase, succinate dehydrogenase, ubiquinol-cytochrome c reductase, cytochrome c oxidase and ATP synthase. Although we did not measure metabolism directly, seeing that the transcription level of many genes encoding enzymes involved in the mitochondrial respiratory chain and oxidative phosphorylation were down-regulated in the highly polluted site suggests that pollutants may have a significant effect on energy metabolism in these fish.

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“…PBDEs have been reported, similar to non-dioxin-like PCBs, as inducer of CAR-and PXR-mediated gene expression in vitro (Pacyniak et al, 2007;Wahl et al, 2008;Fery et al, 2009) as well as in vivo (Sanders et al, 2005;Fery et al, 2009;Szabo et al, 2009). BDE-47, -99 and -209 induced PXRdependent gene expression in mice.…”

Section: Activation Of Car and Pxr Receptorsmentioning

confidence: 94%

Scientific Opinion on Polybrominated Diphenyl Ethers (PBDEs) in Food

2011

EFS2

195

147

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EFSA was asked by the European Commission to deliver a scientific opinion on polybrominated diphenyl ethers (PBDEs) in food. PBDEs are additive flame retardants which are applied in plastics, textiles, electronic castings and circuitry. PBDEs are ubiquitously present in the environment and likewise in biota and in food and feed. Data from the analysis of 19 PBDE congeners in 3,971 food samples were provided to EFSA by 11 European countries. Eight congeners were considered by the Panel on Contaminants in the Food Chain (CONTAM Panel) to be of primary interest: . The highest dietary exposure is to . Toxicity studies were carried out with technical PBDE mixtures or individual congeners. Main targets were the liver, thyroid hormone homeostasis and the reproductive and nervous system. PBDEs cause DNA damage through the induction of reactive oxygen species. The Panel identified effects on neurodevelopment as the critical endpoint, and derived benchmark doses (BMDs) and their corresponding lower 95 % confidence limit for a benchmark response of 10 %, BMDL 10 s, for a number of PBDE congeners: BDE-47, 309 μg/kg b.w.; BDE-99, 12 μg/kg b.w.; BDE-153, 83 μg/kg b.w.; BDE-209, 1,700 μg/kg b.w. Due to the limitations and uncertainties in the current database, the Panel concluded that it was inappropriate to use these BMDLs to establish health based guidance values, and instead used a margin of exposure (MOE) approach for the health risk assessment. Since elimination characteristics of PBDE congeners in animals and humans differ considerably, the Panel used the body burden as starting point for the MOE approach. The CONTAM Panel concluded that for BDE-47, -153 and -209 current dietary exposure in the EU does not raise a health concern. For BDE-99 there is a potential health concern with respect to current dietary exposure. 4 The term "intra-species" has been replaced by "inter-species" in the Summary and in Chapter 9.1. The chemical stability of the PBDE congeners varies with the individual structure. In general PBDE congeners with up to three bromine substituents and those with nine or ten bromine substituents are more sensitive to abiotic transformations. PBDE congeners with four to eight bromine substituents show the highest stability. PBDE congeners are particularly susceptible to photolysis, reductive debromination and radical reactions whereas they are less susceptible to oxidation and hydrolysis. In general, PBDE congeners are persistent and bioaccumulative with the exception of BDE-209 bioaccumulative properties of which seem to be species dependent. BDE-209 undergoes debromination reactions both in the abiotic environment and in biota, leading to formation of PBDE congeners containing seven to nine bromine atoms. © European Food SafetyBased on the composition of the technical PBDE mixtures, occurrence in the environment and in food, the Panel on Contaminants in the Food Chain (CONTAM Panel) considered the following eight PBDE congeners to be of primary interest: which are relevant for dietary PBDE exposur...

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The Flame Retardants, Polybrominated Diphenyl Ethers, Are Pregnane X Receptor Activators

Cited by 134 publications

References 47 publications

Evaluation of liver and thyroid toxicity in Sprague-Dawley rats after exposure to polybrominated diphenyl ether BDE-209

Evaluation of liver and thyroid toxicity in Sprague-Dawley rats after exposure to polybrominated diphenyl ether BDE-209

Detecting genome-wide gene transcription profiles associated with high pollution burden in the critically endangered European eel

Scientific Opinion on Polybrominated Diphenyl Ethers (PBDEs) in Food

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