The Polybrominated Diphenyl Ether Mixture DE-71 Is Mildly Estrogenic

Mercado-Feliciano, Minerva; Bigsby, Robert M.

doi:10.1289/ehp.10643

Cited by 71 publications

(42 citation statements)

References 61 publications

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“…35 This concept is supported by the experimental observations that microsomal metabolism of DE-71 increased its estrogenic activity. 19,45 Accordingly, it is possible that the observed biological activity of DE-71 resulted from the activities of metabolite products but not the PBDE congeners.…”

Section: Estrogen Receptor Pathwaymentioning

confidence: 99%

Molecular toxicology of polybrominated diphenyl ethers: nuclear hormone receptor mediated pathways

Ren

Guo

2013

Environ. Sci.: Processes Impacts

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Polybrominated diphenyl ethers (PBDEs) are used in large quantities as flame retardant additives in commercial products. Bio-monitoring data show that PBDE concentrations have increased rapidly in the bodies of wildlife and human over the last few decades. Based on the studies on experimental animals, the toxicological endpoints of exposure to PBDEs are likely to be thyroid homeostasis disruption, neurodevelopmental deficits, reproductive ineffectiveness and even cancer. Unfortunately, the available molecular toxicological evidence for these endpoints is still very limited. This review focuses on the recent studies on the molecular mechanisms of PBDE toxicities carried out through the hormone receptor pathways, including thyroid hormone receptor, estrogen receptor, androgen receptor, progesterone receptor and aryl hydrocarbon receptor pathways. The general approach in the mechanistic investigation is to examine the in vitro direct binding of a PBDE with a receptor, the in vitro recruitment of a co-activator or co-repressor by the ligand-bound receptor, and the participation of the ligand in the receptor-mediated transcription pathways in cells. It is hoped that further studies in this area would provide more insights into the potential risks of PBDEs to human health. Environmental impactPBDEs are a class of chemicals used as ame retardant additives in a wide variety of industrial and commercial products. Rising levels of PBDEs have been detected in the human body. The toxicological endpoints of exposure to PBDEs are likely to be thyroid homeostasis disruption, neuro-developmental decits, reproductive ineffectiveness and even cancer. However, the available molecular toxicological evidence for these endpoints is still very limited. This review focuses on the recent studies on the molecular mechanisms of PBDE toxicities carried out through the hormone receptor pathways, including thyroid hormone receptor, estrogen receptor, androgen receptor, progesterone receptor and aryl hydrocarbon receptor pathways.

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Section: Estrogen Receptor Pathwaymentioning

confidence: 99%

Molecular toxicology of polybrominated diphenyl ethers: nuclear hormone receptor mediated pathways

Ren

Guo

2013

Environ. Sci.: Processes Impacts

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“…In general, previous studies of PBDEs in vitro have incorporated micromolar (lM) levels in the culture media, although several reports have used nanomolar (nM) levels (Barber et al, 2006;Cantón et al, 2006;Dingemans et al, 2007Dingemans et al, , 2008Fery et al, 2009;Giordano et al, 2008Giordano et al, , 2009He et al, 2008aHe et al, ,b, 2009Hu et al, 2007;Madia et al, 2004;Mercado-Feliciano and Bigsby, 2008;Peters et al, 2004Peters et al, , 2006Stavenes Andersen et al, 2009;Song et al, 2009;Stapleton et al, 2009;Tagliaferri et al, 2010;Zhang et al, 2007). None of these studies measured the cellular PBDE concentrations but it is assumed that the concentrations used may not be environmentally relevant because they are much higher than the picomolar (pM) or lower levels typically found in environmental water or body fluids (Frederiksen et al, 2009;Gill et al, 2004;Streets et al, 2006;Wu et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Determination of environmentally relevant exposure concentrations of polybrominated diphenyl ethers for in vitro toxicological studies

Wei

Zhao

Liu

et al. 2010

Toxicology in Vitro

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a b s t r a c tToxicological studies at environmentally relevant concentrations are essential for understanding ecotoxic and health risks of pollutants such as polybrominated diphenyl ethers (PBDEs). However, no information is available on what exposure levels of PBDEs in vitro studies are environmentally relevant. We exposed MCF-7, HepG2, H295R and PC12 cells to BDE-47, and measured BDE-47 concentrations in the cells after exposure. We also used the percentile method to summarize literature data on environmental exposure levels of biotic tissues to PBDEs. The exposure concentration that resulted in a BDE-47 burden in cells close to the 90th percentile of PBDEs levels in tissues was assigned as the upper limit for the environmentally relevant concentration. Exposure to 1 nM BDE-47 resulted in PBDEs burdens in MCF-7, HepG2 and H295R cells close to the 90th percentile but PBDEs burdens in PC12 cells were higher than the 90th percentile. In consideration of the high exposure levels in PBDE-polluted areas, we concluded that the highest environmentally relevant exposure concentration of PBDEs in culture media should be approximately 10 nM for MCF-7, HepG2 and H295R cells, and <10 nM for PC12 cells. These results provide an approximate reference for setting environmentally relevant exposure concentrations of PBDEs for studies in vitro.

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“…PBDEs may have different actions on endocrine homeostasis depending on the tissues and the life stages. In particular, the lower-brominated PBDEs can bind and activate estrogen receptors [47,48,49]. The hydroxylated PBDE metabolites are more potent agonists of estrogen receptors than parent PBDEs and methoxylated metabolites [11].…”

Section: Discussionmentioning

confidence: 99%

Serum Levels of Polybrominated Diphenyl Ethers in Girls with Premature Thelarche

et al. 2016

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Background/Aims: Polybrominated diphenyl ethers (PBDEs) are widely used as flame retardants and have shown endocrine disruption properties in experimental studies. The aim of this study was to investigate the association between the exposure to PBDEs and alterations of puberty in girls referred for idiopathic central precocious puberty (ICPP) and premature thelarche (PT). Methods: A case-control study was conducted in 124 girls: 37 girls with ICPP (mean age 7.4 ± 0.9 years), 56 with PT (mean age 5.7 ± 2.1 years) and 31 controls (mean age 5.4 ± 1.9 years). PBDE serum concentrations, hormone levels and anthropometry were assessed. PBDE concentrations were corrected for total serum lipid content. Individual exposure to PBDEs was evaluated through ad hoc questionnaires. Results: PBDE serum concentrations corrected for total lipid content were significantly higher in girls with PT (mean 1.49 ± 0.63 log ng/g) than in controls (mean 1.23 ± 0.54 log ng/g; p < 0.05). PT girls showed higher levels of PBDE than ICPP girls (1.49 ± 0.63 vs. 1.37 ± 0.49 log ng/g), though this was not significant. An analysis of the questionnaires revealed no significant differences in exposure between the three groups. Conclusion: Our findings suggest that higher concentrations of serum PBDEs are associated with PT in girls.

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The Polybrominated Diphenyl Ether Mixture DE-71 Is Mildly Estrogenic

Cited by 71 publications

References 61 publications

Molecular toxicology of polybrominated diphenyl ethers: nuclear hormone receptor mediated pathways

Molecular toxicology of polybrominated diphenyl ethers: nuclear hormone receptor mediated pathways

Determination of environmentally relevant exposure concentrations of polybrominated diphenyl ethers for in vitro toxicological studies

Serum Levels of Polybrominated Diphenyl Ethers in Girls with Premature Thelarche

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