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Epidemiology (Cambridge, Mass.) Sep 2019Brominated flame retardants, including polybrominated biphenyls (PBB), are persistent compounds reported to affect sex hormones in animals; less is known about potential...
BACKGROUND
Brominated flame retardants, including polybrominated biphenyls (PBB), are persistent compounds reported to affect sex hormones in animals; less is known about potential effects in humans. An industrial accident in 1973-1974 exposed Michigan residents to PBB through contaminated food. We examined whether this exposure to PBB had long-term effects on menstrual cycle function.
METHODS
In 2004-2006, we recruited reproductive-aged women in the Michigan PBB Registry who were not pregnant, lactating, or taking hormonal medications. Participants kept daily diaries and provided daily urine samples for up to 6 months. We assayed the urine samples for estrone 3-glucuronide (E13G), pregnanediol 3-glucuronide (Pd3G), and follicle stimulating hormone (FSH). We fit linear mixed models among women aged 35-42 years to describe the relation between serum PBB levels and log-transformed, creatinine-adjusted daily endocrine levels among women who were premenarchal during the exposure incident in 1973-1974 (n = 70).
RESULTS
We observed that high (>3.0 parts per billion [ppb]) and medium (>1.0-3.0 ppb) PBB exposure were associated with lower E13G levels across the menstrual cycle and lower FSH levels during the follicular phase, compared with low PBB exposure (≤1.0 ppb). High PBB exposure was also associated with lower Pd3G levels across the cycle compared with low PBB exposure, whereas Pd3G levels were similar in women with medium and low PBB exposure.
CONCLUSION
Our results are consistent with a hypothesized effect of exposure to an exogenous estrogen agonist but the modest sample size of the study requires cautious interpretation.
Topics: Accidents, Occupational; Adolescent; Adult; Biomarkers; Environmental Exposure; Environmental Pollutants; Female; Flame Retardants; Humans; Menstrual Cycle; Michigan; Middle Aged; Polybrominated Biphenyls; Prospective Studies; Young Adult
PubMed: 31180930
DOI: 10.1097/EDE.0000000000001045 -
Reviews of Environmental Contamination... 1995Data on two classes of brominated polyaromatic flame retardants are reviewed with emphasis on analytical aspects, occurrence, fate, and toxicity in the environment.... (Review)
Review
Data on two classes of brominated polyaromatic flame retardants are reviewed with emphasis on analytical aspects, occurrence, fate, and toxicity in the environment. Concentrations of brominated fire retardants are quantified as equivalents of commercial mixtures. Because different congeners behave differently in the environment and show large differences in toxicity, future studies would benefit from the availability of analytical standards of individual congeners. The main environmental properties and mechanisms of toxicity of the PBBs and PBDEs are similar to those of the structurally related PCBs and dibenzodioxins. Although the present concentrations of brominated fire retardants do not yet appear to represent a major environmental risk in marine food chains, their replacement by environmentally less harmful alternatives is recommended.
Topics: Animals; Cytochrome P-450 Enzyme System; Environmental Pollutants; Flame Retardants; Halogenated Diphenyl Ethers; Hydrocarbons, Brominated; Phenyl Ethers; Polybrominated Biphenyls
PubMed: 7886253
DOI: 10.1007/978-1-4612-2530-0_1 -
Environmental Research Nov 2022In 1973-74, a polybrominated biphenyl (PBB) flame retardant mixture was shipped to Michigan livestock feed mills in place of a nutritional supplement and contaminated...
In 1973-74, a polybrominated biphenyl (PBB) flame retardant mixture was shipped to Michigan livestock feed mills in place of a nutritional supplement and contaminated the food supply. Following the accident, the Michigan PBB Registry was established to study the long-term health effects of halogenated compounds and is now led by a community-academic partnership. PBB exposure is associated with altered DNA methylation in sperm, which may lead to adverse birth outcomes in children whose fathers have increased levels of serum PBB or polychlorinated biphenyl (PCB). Paternal PBB and PCB levels of men enrolled in the Michigan PBB Registry (n = 155) were analyzed against matched offspring birthweight and gestational age (n = 336). Birthweight and gestational age were dichotomized at the 25th percentile and 37 weeks, respectively, and paternal PBB and PCB levels were examined as continuous measures and divided into tertiles. Associations of offspring birthweight and gestational age with paternal PBB and PCB serum concentrations were modeled using multivariable linear spline and log-risk regression, adjusting for family clustering, paternal health and lifestyle factors, maternal PBB, and PCB serum concentrations, sex, and offspring gestational age (for birthweight). Fathers in the middle and upper PBB and PCB tertiles had increased risks for lowest quartile birthweight compared to the first tertile, with adjusted risk ratios (aRR) = 1.67 (95% CI: 0.93, 2.99) and aRR = 2.06 (95% CI: 1.12, 3.79) for PBB, and aRR = 1.47 (95% CI: 0.79, 2.75) and aRR = 1.34 (95% CI: 0.70, 2.54) for PCB, respectively. Elevated paternal PBB levels were not associated with an increased risk for preterm birth, while PCB levels were associated with a small, but not significant, decrease in gestational age, β = -0.37 (95% CI: -0.76, 0.03) weeks per log unit increase PCB. The findings suggest that increased paternal PBB and PCB levels negatively impact offspring birthweight, and paternal PCB levels may negatively impact gestational age.
Topics: Birth Weight; Child; Environmental Pollutants; Fathers; Female; Humans; Infant; Infant, Newborn; Male; Polybrominated Biphenyls; Polychlorinated Biphenyls; Premature Birth; Semen
PubMed: 36041536
DOI: 10.1016/j.envres.2022.114215 -
Epigenomics May 2020Michigan residents were exposed to polybrominated biphenyls (PBBs) when it was accidentally added to the food supply. Highly exposed individuals report sex-specific...
Michigan residents were exposed to polybrominated biphenyls (PBBs) when it was accidentally added to the food supply. Highly exposed individuals report sex-specific health problems, but the underlying biological mechanism behind these different health risks is not known. DNA methylation in blood from 381 women and 277 men with PBB exposure was analyzed with the MethylationEPIC BeadChip. 675 CpGs were associated with PBBs levels in males, while only 17 CpGs were associated in females (false discovery rate <0.05). No CpGs were associated in both sexes. These CpGs were enriched in different functional regions and transcription factor binding sites in each sex. Exposure to PBBs may have sex-specific effects on the epigenome that may underlie sex-specific adverse health outcomes.
Topics: Adult; Aged; Aged, 80 and over; Binding Sites; CpG Islands; DNA Methylation; Environmental Exposure; Female; Humans; Male; Middle Aged; Polybrominated Biphenyls; Sex Characteristics; Transcription Factors; Young Adult
PubMed: 32496131
DOI: 10.2217/epi-2019-0179 -
Environmental Science & Technology May 2019Eleven polybrominated diphenyl ether (tri- to deca-BDE) congeners and 2,2',4,4',5,5'-hexabromobiphenyl (BB153) have been measured in pooled serum samples from the...
Eleven polybrominated diphenyl ether (tri- to deca-BDE) congeners and 2,2',4,4',5,5'-hexabromobiphenyl (BB153) have been measured in pooled serum samples from the National Health and Nutrition Examination Survey (NHANES) for one decade (from survey years 2005/06 through 2013/14). The pools, which are representative of the general noninstitutionalized population of the United States, encompassed thirty-two demographic groups defined by sex, race/ethnicity (Mexican American, non-Hispanic black, non-Hispanic white, and all other race/ethnicities), and age (12-19, >20-39, >40-59, and ≥60 years). The adjusted geometric means were determined in a multiple linear regression model for the six congeners (BDE28, BDE47, BDE99, BDE100, BDE153, and BB153) with detectable concentrations in at least 60% of pools in each of the thirty-two demographic groups; the level of significance for all statistical comparisons thereof were determined. BDE154 and BDE209 were detected in 60% of the NHANES 2011/12 and 2013/14 pools; only these two survey periods were evaluated for these congeners. The percent change in concentration by a 2-year survey period was calculated. All examined PBDEs reported in five survey periods decreased in concentration, except BDE153, for which concentrations increased by 12.0% (95% CI 7.1-16.4) and 8.4% (95% CI 2.9-14.1) for the age groups 40-59 and ≥60 years, respectively; no significant change was observed in younger age groups. Excluding BDE153, we observed larger percentage decreases by a 2-year survey period for the age groups 12-19, 20-39, and ≥60 years compared with the age group 40-59 years. The percentage decrease by a two-year survey period ranged between -19.6% (BDE99, 20-39 years old) and -4.5% (BDE100, 40-59 years old). Although five polybrominated diphenyl ether (PDBE) congeners and BB153 are still frequently detected in the U.S. general population, PBDE concentrations have decreased since 2005-2006, likely, because of changes in manufacturing practices that started in the mid-2000s.
Topics: Biphenyl Compounds; Halogenated Diphenyl Ethers; Nutrition Surveys; Polybrominated Biphenyls; United States
PubMed: 31002243
DOI: 10.1021/acs.est.9b00471 -
Epigenetics Jan 2019In 1973, Michigan residents were exposed to polybrominated biphenyl (PBB) when it was accidentally added to farm animal feed. Highly exposed individuals and their...
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). PBB-associated 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.
Topics: Adult; Aged; Blood Cells; CpG Islands; DNA Methylation; Endocrine Disruptors; Epigenesis, Genetic; Female; Humans; Male; Middle Aged; Polybrominated Biphenyls; Regulatory Sequences, Nucleic Acid
PubMed: 30676242
DOI: 10.1080/15592294.2019.1565590 -
Ecotoxicology and Environmental Safety Jun 2022Polybrominated biphenyls (PBBs) can bioaccumulate in nature and are toxic to humans. Long-time exposure to PBBs in pregnant women can lead to the birth of an infant with...
Polybrominated biphenyls (PBBs) can bioaccumulate in nature and are toxic to humans. Long-time exposure to PBBs in pregnant women can lead to the birth of an infant with abnormal conditions. Hence, in this study, we used molecular docking, molecular dynamics, Taguchi experimental design, and fractional factorial experimental design to identify the developmental toxicity characteristics of 10 typical developmental toxic pollutants such as PBBs to which humans are frequently exposed. Furthermore, the correlation and sensitivity analyses of molecular developmental toxicity and structural parameters were performed. The molecular key structural parameters of the pollutants affecting human development were screened. Moreover, the supplementary food factors that could alleviate the developmental toxicity of pollutants were screened to develop supplementary food schemes to prevent or alleviate human developmental toxicity in the special population (e.g., pregnant women, infants) exposed to the pollutants. The results showed that the developmental toxicity was controlled by the main effects of the 10 pollutants. Among the 10 pollutants with developmental toxicity, the most significant pollutant with the main effects was PBB-153 (37.06%). In addition, the correlation and sensitivity analyses of the molecular developmental toxicity of the pollutants and structural parameters showed that the total energy value and infrared C-H vibration frequency of the pollutants were significantly correlated with human developmental toxicity. Accordingly, 15 supplementary food cofactors were selected for the Taguchi experiment design, among which the top seven cofactors were designed by fractional factorial analysis. The most significant cofactor that alleviated the developmental toxicity of PBB-153 exposure was the combination of carotene and docosahexaenoic acid (DHA), with an improvement of 17.28%. The combination of carotene and DHA significantly alleviated the effects of toxicity caused by most of the other pollutants, indicating that the selected supplementary food has certain universality. In this study, we developed a method to identify the characteristics of the developmental toxicity of pollutant exposure and developmental toxicity alleviation. Our study provided theoretical support for the regulation strategy of developmental toxicity caused by pollutants such as PBBs.
Topics: Carotenoids; Environmental Pollutants; Female; Humans; Infant; Molecular Docking Simulation; Polybrominated Biphenyls; Pregnancy
PubMed: 35487171
DOI: 10.1016/j.ecoenv.2022.113543 -
Environmental Research Jan 2022The 32-mile Detroit River and surrounding tributaries have been designated as a Great Lakes Area of Concern due to pollution from decades of municipal and industrial...
The 32-mile Detroit River and surrounding tributaries have been designated as a Great Lakes Area of Concern due to pollution from decades of municipal and industrial discharges, sewer overflows and urban development. The Agency for Toxic Substances and Disease Registry and the Michigan Department of Health and Human Services conducted a biomonitoring study to assess exposures to persistent toxic substances in Detroit urban shoreline anglers who may be at high exposure risk due to consumption of locally caught fish. Using a modified venue-based sampling approach, 287 adult shoreline anglers along the Detroit River were recruited and participated in the program. Study participants provided blood and urine specimens and completed a questionnaire interview. In this report, we examine percentile estimates for blood lead, blood manganese, urine arsenic, urine mercury, urine cadmium, organochlorine pesticides in serum (mirex, hexachlorobenzene, chlordane), and serum polybrominated biphenyl 153 (PBB 153) concentrations among study participants. Multiple linear regression was used to identify predictors of contaminant concentrations. The Detroit urban anglers' blood lead concentrations were 2 times higher than the general adult U.S. population (median (95% CI): 2.9 μg/dL (1.8-2.3) vs. 0.94 μg/dL (0.90-0.98)). PBB 153 levels were 1.8 times higher than the general adult U.S. population at the 95th percentile (95th percentile, 95% CI: 62.7 ng/g of lipid, 53.2-75.2 vs. 34.6 ng/g of lipid, 12.8-66.8). Percentile estimates of the other study pollutants were similar to background levels found in the general U.S. population. Eating more locally caught fish was not associated with increased body burdens for any of the contaminants examined in this report. Higher blood lead was associated with increased age, male sex, current smoking, residing in a home built before 1960, an annual income less than $25,000, and a work history of lead paint removal. Evidence of PBB exposure in our study cohort likely reflects the continued effect of a widespread contamination of livestock feed in 1973 among Michigan's lower peninsula population. These study results help determine if the pollutants examined warrant further consideration in subsequent population-based biomonitoring of frequent consumers of fish from the Detroit River and surrounding waterways. The biomonitoring data from this study also served to inform public health officials regarding the potential need for environmental public health actions to reduce harmful exposures.
Topics: Adult; Animals; Biological Monitoring; Fishes; Humans; Male; Mercury; Michigan; Pesticides; Polybrominated Biphenyls
PubMed: 34384752
DOI: 10.1016/j.envres.2021.111851 -
Toxicology and Applied Pharmacology Jan 1981
Comparative Study
Topics: Animals; Beta-Globulins; Biphenyl Compounds; Female; Hematocrit; Liver; Male; Mice; Microscopy, Electron; Organ Size; Polybrominated Biphenyls; Rats; Rats, Inbred F344; Thymus Gland; gamma-Glutamyltransferase
PubMed: 6163229
DOI: 10.1016/0041-008x(81)90029-6 -
Chemosphere Aug 2017It has been previously been shown by our lab and others that persistent organic pollutants, such as polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers...
It has been previously been shown by our lab and others that persistent organic pollutants, such as polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs), are contaminants in milk produced for human consumption. To further this research we determined the concentration of 21 PCB and 14 PBDE congeners in livestock serum, mainly bovine, across California. Congeners were extracted from serum using solid phase extraction (SPE), cleaned up by silica cartridge and quantified using gas chromatography-triple quadruple mass spectrometry. We detected significant differences among species and the production class of cattle (beef or dairy). The sum of all 21 PCB congeners (ΣPCBs) in caprine and ovine sera had a mean value of 9.26 and 9.13 ng/mL, respectively, compared to 3.98 ng/mL in bovine sera. The mean value for the sum of all 14 PBDE congeners (ΣPBDEs) in caprine and ovine sera was 2.82 and 2.39 ng/mL, respectively, compared to 0.91 ng/mL in bovine sera. Mean ΣPCBs in dairy cattle was 5.92 ng/mL compared to 2.70 ng/mL in beef cattle. Mean ΣPBDEs in dairy cattle was 1.33 ng/mL compared to 0.70 ng/mL in beef cattle. There were no regional differences in the ΣPCBs or ΣPBDEs in cattle distributed across California. These results highlight the fact that livestock are still being exposed to these pollutants yet little is known about where this exposure may be coming from.
Topics: Animals; California; Cattle; Environmental Pollutants; Gas Chromatography-Mass Spectrometry; Goats; Halogenated Diphenyl Ethers; Humans; Milk; Polybrominated Biphenyls; Polychlorinated Biphenyls; Sheep; Solid Phase Extraction
PubMed: 28426942
DOI: 10.1016/j.chemosphere.2017.04.059