Residual effects of polybrominated biphenyls following perinatal exposure in rats

McCormack, K. M.; Braselton, W. Emmett; Sanger, V. L.; Hook, Jerry B.

doi:10.1016/0041-008x(80)90387-7

Cited by 16 publications

(6 citation statements)

References 29 publications

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“…PBB-associated CpGs were more likely to be in transcription factor binding sites for a member of the AHR pathway, and many of the significantly associated CpGs were in members of the cytochrome P450 family. This finding is consistent with early studies in rat models that found that PBB increased activity of other members of the AHR pathway like the aryl hydrocarbon hydroxylase (AHH) and members of the cytochrome P-450 enzyme family [60][61][62]. Additionally, PBB-associated CpGs were more likely to be near nuclear hormone receptor transcription factor binding sites.…”

Section: Discussionsupporting

confidence: 90%

Exposure to polybrominated biphenyl (PBB) associates with genome-wide DNA methylation differences in peripheral blood

et al. 2019

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In 1973, Michigan residents were exposed to polybrominated biphenyl (PBB) when it was accidentally added to farm animal feed. Highly exposed individuals and their children have experienced endocrine-related health problems, though the underlying mechanism behind these remains unknown. We investigated whether PBB exposure is associated with variation in DNA methylation in peripheral blood samples from 658 participants of the Michigan PBB registry using the MethylationEPIC BeadChip, as well as investigated what the potential function of the affected regions are and whether these epigenetic marks are known to associate with endocrine system pathways. After multiple test correction (FDR <0.05), 1890 CpG sites associated with total PBB levels. These CpGs were not enriched in any particular biological pathway, but were enriched in enhancer and insulator regions, and depleted in regions near the transcription start site or in CpG islands (p < 0.05). They were also more likely to be in ARNT and ESR2 transcription factor binding sites (p = 3.27e-23 and p = 1.62e-6, respectively), and there was significant overlap between CpGs associated with PBB and CpGs associated with estrogen (p < 2.2e-16). PBBassociated CpGs were also enriched for CpGs known to be associated with gene expression in blood (eQTMs) (p < 0.05). These eQTMs were enriched for pathways related to immune function and endocrine-related autoimmune disease (FDR <0.05). These results indicate that exposure to PBB is associated with differences in epigenetic marks that suggest that it is acting similarly to estrogen and is associated with dysregulated immune system pathways. ARTICLE HISTORY

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Section: Discussionsupporting

confidence: 90%

Exposure to polybrominated biphenyl (PBB) associates with genome-wide DNA methylation differences in peripheral blood

et al. 2019

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“…This increased vacuolation was most prominent soon after exposure. The livers of exposed rat pups also had retained bile, slight necrosis and cellular swelling [ 20 ].…”

Section: Effects Of Pbbs In Animal Modelsmentioning

confidence: 99%

“…Besides the overt physical changes, rats exposed to PBBs have altered enzyme activity compared with control rats. They showed increased microsomal enzyme activity in both the liver and kidneys [ 20 , 21 ]. Both pregnant rats and their offspring had a tenfold increase in AHH activity and threefold increase in EH activity in their livers.…”

Section: Effects Of Pbbs In Animal Modelsmentioning

confidence: 99%

“…The authors mentioned that exposure to dioxin, a well-known lipophilic carcinogen and environmental pollutant, caused a similar increase in EH activity, but in the rats’ lung and skin tissue, suggesting that PBB, like PCB, could be dioxin-like [ 21 ]. Offspring of rats exposed to 100 ppm diet metabolized the anesthetic, pentobarbital, more quickly (duration was only 1% that of controls) and had 57% less vitamin A in their livers, suggesting that PBB exposure can affect the metabolism of naturally occurring compounds and xenobiotics for an extended period [ 19 , 20 ]. Further, the different congeners of PBB induce different responses in rat livers.…”

Section: Effects Of Pbbs In Animal Modelsmentioning

confidence: 99%

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Intergenerational Effects of Endocrine-Disrupting Compounds: A Review of the Michigan Polybrominated Biphenyl Registry

et al. 2018

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Endocrine-disrupting compounds (EDCs) are a broad class of chemicals present in many residential products that can disrupt hormone signaling and cause health problems in humans. Multigenerational cohorts, like the Michigan polybrominated biphenyl registry, are ideal for studying the effects of intergenerational exposure. Registry participants report hormone-related health problems, particularly in those exposed before puberty or those in the second generation exposed through placental transfer or breastfeeding. However, more research is needed to determine how EDCs cause health problems and the mechanisms underlying intergenerational exposure. Utilizing existing data in this registry, along with genetic and epigenetic approaches, could provide insight to how EDCs cause human disease and help to determine the risk to exposed populations and future generations.

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“…McCormack et al (1980) fed a diet containing 0 and 100 mg/kg b.w. FireMaster BP-6 from the eighth day of pregnancy through 28 days post partum.…”

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confidence: 99%

Scientific Opinion on Polybrominated Biphenyls (PBBs) in Food

2010

EFSA Journal

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EFSA was asked by the European Commission to deliver a scientific opinion on polybrominated biphenyls (PBBs) in food. PBBs are additive flame retardants which were applied in synthetic fibres and polymers. PBBs are present in the environment at low concentrations and likewise in biota and in food and feed. Data from the analysis of 16 PBB congeners in 794 food samples were provided to EFSA by 6 Member States, covering the period from 2003 to 2009. Toxicity studies were carried out with technical PBB mixtures of which the exact congener composition is not known. Main targets were the liver, thyroid hormone homeostasis and the reproductive, nervous and immune systems. PBBs are not directly genotoxic. The Panel on Contaminants in the Food Chain (CONTAM Panel) selected the hepatic carcinogenic effects as the critical effect, with a no‐observed‐effect level (NOEL) of 0.15 mg/kg body weight (b.w.). Since this NOEL was obtained in a study with a technical PBB mixture, the congener profile of which differs from that currently found in food, the CONTAM Panel concluded that it was inappropriate to use this NOEL to derive a health based guidance value. The intake of PBBs by high and frequent consumers of fatty fish, the subgroup with the highest dietary exposure, was approximately 6 orders of magnitude less than this NOEL. Exposure for high consuming breast‐fed infants is 5 orders of magnitude less than this NOEL. Therefore the CONTAM Panel concluded that the risk to the European population from exposure to PBBs through the diet is of no concern. Since PBBs are no longer produced or used in Europe and taking into account low and declining environmental concentrations, the CONTAM Panel concluded that PBBs are a low priority for further research or monitoring efforts.

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Residual effects of polybrominated biphenyls following perinatal exposure in rats

Cited by 16 publications

References 29 publications

Exposure to polybrominated biphenyl (PBB) associates with genome-wide DNA methylation differences in peripheral blood

Exposure to polybrominated biphenyl (PBB) associates with genome-wide DNA methylation differences in peripheral blood

Intergenerational Effects of Endocrine-Disrupting Compounds: A Review of the Michigan Polybrominated Biphenyl Registry

Scientific Opinion on Polybrominated Biphenyls (PBBs) in Food

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