Polybrominated Biphenyls Levels Research Articles

Exploring autism spectrum disorder (ASD) and attention deficit disorder (ADD/ADHD) in children exposed to polybrominated biphenyl.

Although the causes of attention-deficit/hyperactivity disorder (ADHD) and autism have not been identified, exposure to endocrine-disrupting chemicals, such as polybrominated biphenyl (PBB), during fetal development and early life has been suspected to impact neurological development. This study aims to investigate the association between prenatal and early life exposure to PBB and the development of ADHD and autism later in life. Data from the Michigan PBB Registry, a cohort of Michigan residents who had been exposed to PBB in a mass contamination event in 1973, was leveraged for this nested case-control analysis among two distinct samples: (1) Those who self-reported ADHD or autism diagnosis, and (2) mothers who reported their child's ADHD or autism diagnosis. PBB exposure was measured in participants of the PBB Registry, and the mother's PBB level was used in mother-reported analyses. Cases were matched with controls by sex and year of birth. Conditional logistic regression models were used to estimate the association between PBB level and case status. PBB levels were higher among those who were exposed in early life compared with those exposed in utero (geometric mean: 0.300 ng/ml vs. 0.016 ng/ml). Among women in this cohort, a higher than expected proportion of self-reported ADHD diagnosis (11.11%), compared with population estimates. PBB was not associated with ADHD or autism in either self-reported or mother-reported analyses. This study adds to the sparse literature about prenatal and early life exposure to PBB-153 and ADHD and autism. Future studies should examine potential effect modification by sex.

Birth outcomes associated with paternal polybrominated and polychlorinated biphenyl exposure

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.

Birth Outcomes Associated with Paternal Polybrominated and Polychlorinated Biphenyl Exposure

BACKGROUND AND AIM: In 1973, polybrominated biphenyl (PBB) flame retardant was shipped to Michigan 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 decreased DNA methylation in sperm regulatory elements controlling imprinted genes, which may lead to adverse birth outcomes in children whose fathers have increased levels of serum PBB or polychlorinated biphenyl (PCB), an analogue of PBB. To further understand the impact of paternal exposures on children, we analyzed paternal PBB and PCB levels and premature birth and low birthweight. METHODS: We investigated the outcomes of birthweight and gestational age of offspring whose fathers enrolled in the PBB Registry and provided serum to measure PBB and PCB concentrations. Birth outcomes were determined by linking paternal PBB records to the Michigan vital records. Birthweight and gestational age were dichotomized at the 25th percentile and 37 weeks respectively, and paternal PBB and PCB levels were divided into tertiles. Offspring birthweight and gestational age were modeled against paternal PBB and PCB serum concentrations using log-risk regression, adjusting for clustering, paternal health and lifestyle factors, and offspring sex. RESULTS:Elevated PBB and PCB levels are associated with an increased risk of low offspring birthweight, but not preterm birth. Fathers in the middle and upper PBB and PCB tertiles illustrated increased risk ratios (RR) for low offspring birthweight, RR=1.42 (CI=0.93-2.17) and RR=1.47 (CI=1.03-2.10) for PBB, and RR=1.73 (CI=1.12-2.67) and RR=1.42 (CI=0.84-2.41) for PCB respectively. Elevated PBB and PCB levels illustrated no significant increased risk for preterm birth in the middle and upper tertiles. CONCLUSIONS:These findings suggest increased paternal PBB and PCB levels may negatively impact offspring birthweight. KEYWORDS: Endocrine disrupting chemicals, Birth outcomes, Children's environmental health, Community outreach, Environmental epidemiology

Sex-specific DNA methylation differences in people exposed to polybrominated biphenyl.

Aim: 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. Materials and methods: DNA methylation in blood from 381 women and 277 men with PBB exposure was analyzed with the MethylationEPIC BeadChip. Results: 675CpGs wereassociated with PBBs levelsin males, while only 17 CpGs wereassociated 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. Conclusion: Exposure to PBBs may have sex-specific effects on the epigenome that may underlie sex-specific adverse health outcomes.

Examining Reproductive Health Outcomes in Females Exposed to Polychlorinated Biphenyl and Polybrominated Biphenyl

In 1973, accidental contamination of Michigan livestock with polybrominated biphenyls (PBBs) led to the establishment of a registry of exposed individuals that have been followed for > 40 years. Besides being exposed to PBBs, this cohort has also been exposed to polychlorinated biphenyls (PCBs), a structurally similar class of environmental pollutants, at levels similar to average US exposure. In this study, we examined the association between current serum PCB and PBB levels and various female reproductive health outcomes to build upon previous work and inconsistencies. Participation in this cross-sectional study required a blood draw and completion of a detailed health questionnaire. Analysis included only female participants who had participated between 2012 and 2015 (N = 254). Multivariate linear and logistic regression models were used to identify associations between serum PCB and PBB levels with each gynecological and infertility outcome. Additionally, a generalized estimating equation (GEE) model was used to evaluate each pregnancy and birth outcome in order to account for multiple pregnancies per woman. We controlled for age, body mass index, and total lipid levels in all analyses. A p-value of <0.05 was used for statistical significance. Among the women who reported ever being pregnant, there was a significant negative association with higher total PCB levels associating with fewer lifetime pregnancies ( β = −0.11, 95% CI = −0.21 to −0.005, p = 0.04). There were no correlations between serum PCB levels and the self-reported gynecological outcomes (pelvic inflammatory disease, endometriosis, polycystic ovarian syndrome, or uterine fibroids). No associations were identified between serum PCB levels and the prevalence of female infertility in women reporting ever having sexual intercourse with a male partner. There were no associations identified between serum PCB levels and pregnancy outcomes (singleton live births or miscarriages) or birth outcomes (preterm birth, birth weight, birth defects, hypertensive disorders of pregnancy, or gestational diabetes). PBB was not associated with any outcome. Further research is needed to determine if and how PCB may reduce pregnancy number.

Polybrominated Biphenyl Exposure and Menstrual Cycle Function.

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. 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). 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. 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.

Environmental exposure to polybrominated biphenyl (PBB) associates with an increased rate of biological aging.

Advanced age increases risk for cancer, cardiovascular disease, and all-cause mortality. However, people do not age at the same rate, and biological age (frequently measured through DNA methylation) can be older than chronological age. Environmental factors have been associated with the rate of biological aging, but it is not known whether persistent endocrine-disrupting compounds (EDCs) like polybrominated biphenyl (PBB) would associate with age acceleration. Three different epigenetic age acceleration measures (intrinsic, extrinsic, and phenotypic) were calculated from existing epigenetic data in whole blood from a population highly exposed to PBB (N=658). Association between serum PBB concentration and these measures was tested, controlling for sex, lipid levels, and estimated cell type proportions. Higher PBB levels associated with increased age acceleration (intrinsic: β=0.24, 95%CI=0.01-0.46, p = 0.03; extrinsic: β=0.39, 95%CI=0.12-0.65, p = 0.004; and phenotypic: β=0.30, 95%CI=0.05-0.54, p = 0.01). Neither age when exposed to PBB nor sex statistically interacted with PBB to predict age acceleration, but, in stratified analyses, the association between PBB and age acceleration was only in people exposed before finishing puberty and in men. This suggests that EDCs can associate with the biological aging process, and further studies are warranted to investigate other environmental pollutants’ effect on aging.

OR23-2 Increased Exposure to Brominated Flame Retardant Associates with Differences in DNA Methylation Similar to Natural Estrogen

In 1973, approximately 6.5 million Michigan residents were exposed to an industrial mixture of polybrominated biphenyl (PBB), an endocrine-disrupting compound, when it was added to farm animal feed during a factory accident. Highly exposed individuals and their children have numerous endocrine-related health problems, including genitourinary conditions, spontaneous abortions, and early puberty, though the underlying mechanism behind these health problems remains unknown. Other endocrine-disrupting compounds have been linked to epigenetic differences, but no epigenetic studies have been done for PBB. In this study, DNA from the blood of individuals with PBB exposure was interrogated with the MethylationEPIC BeadChip (N = 658). Associations between each of the ~850,000 CpG sites and current, serum PBB levels were tested with a linear regression that controlled for age, sex, lipid levels, and cell type proportions. 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). In order to better understand the function of the enhancers that were enriched, PBB-associated CpGs were also interrogated for transcription factor binding sites, correlations with hormones, and links to gene expression. 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 associated with the expression of genes that were enriched for pathways related to endocrine-related autoimmune disease (FDR <0.05). Taken together, 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 endocrine-related autoimmune pathways.

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

ABSTRACTIn 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.

Polybrominated and polychlorinated biphenyls and thyroid function in a cohort of Michigan women.

Introduction: In 1973-74, Michigan residents were exposed to polybrominated biphenyls (PBBs) through an accidental contamination of the food supply. This cohort of exposed individuals and their children has been followed for over 40 years and the population remains highly exposed. There is evidence that exposure to halogenated compounds such as PBBs and polychlorinated biphenyls (PCBs) may interfere with thyroid function. Methods: Between 2004-2014, serum PBB and PCB congeners were measured in 466 women (ages 18-86) who completed questionnaires on health conditions including physician-diagnosed thyroid disease; behaviors; and demographics. Thyroid hormones are also being measured in a subset of women not on thyroid-disrupting medication (N=391). Logistic regression was used to estimate the associations between serum levels of PBB and PCB congeners, considered both individually and grouped according to chemical structure, and thyroid disease. Results: PBB-153 was detected in the serum of 93% of women (median=0.23 ng/mL, interquartile range (IQR)=0.06-0.48), whereas PBB-77, 101 and 180 were detected in &lt;5%. PCB-153, 138, 118 and 180 were detected in &gt;99% of samples and were summed (∑PCB; median=0.71 ng/mL, IQR=0.30-1.20). Ninety-six women (20.6%) reported a physician-diagnosed thyroid condition after the contamination event, and 44 specified a diagnosis of hypothyroidism. PCB congeners and ∑PCB were not associated with any thyroid conditions, but an IQR increase in PBB-153 was associated with increased odds of hypothyroidism, although the estimate for any thyroid condition was closer to the null (adjusted odds ratio (aOR)=1.50, 95% confidence interval (CI): 1.0, 2.3 and aOR=1.13, 95% CI: 0.8, 1.6, respectively). Ongoing measurement of thyroid hormones in this cohort will allow for the assessment of possible subclinical thyroid dysfunction, and results will be reported. Conclusions: These results suggest that PBB-153 exposure may influence thyroid function in women.

Air is still contaminated 40 years after the Michigan Chemical plant disaster in St. Louis, Michigan.

The Michigan Chemical (also known as Velsicol Chemical) plant located in St. Louis, Michigan operated from 1936-1978. During this time, the plant manufactured polybrominated biphenyls (PBBs), hexabromobenzene (HBB), 1,1,1-trichloro-2,2-bis(4-chlorophenyl) ethane (DDT), and tris(2,3-dibromopropyl) phosphate (TDBPP), among other products. Due to widespread PBB contamination of Michigan, the plant eventually became a Superfund site, and despite years of cleanup activities, many of the compounds can still be found in the local ecosystem. To investigate the current atmospheric levels and to determine their spatial distributions, we collected tree bark samples from around Michigan and measured the concentrations of these pollutants. For comparison, other organic pollutants, such as polybrominated diphenyl ethers (PBDEs) and organophosphate esters (OPEs), which were not manufactured at the Michigan Chemical plant, were also measured in the same tree bark samples. Our results show levels of PBBs, DDT, and HBB in tree bark collected within 10 km of the Velsicol Superfund site (43, 477, and 108 ng/g lipid wgt., respectively) are 1-2 orders of magnitude higher than at sites located more than 10 km from the site (0.36, 28, and 0.36 ng/g lipid wgt., respectively). Levels of PBDEs and OPEs did not depend on distance from St. Louis. This is the first study on the atmospheric distribution of these chemicals around the Superfund site.

PHAHs in 14 principal river sediments from Hai River basin, China

This study was undertaken to investigate the current contamination status of polyhalogenated aromatic hydrocarbons (PHAHs) in sediments from 14 principal rivers of the Hai River basin. The concentrations of 22 polybrominated biphenyl (PBB) congeners, 27 polybrominated diphenyl ether (PBDE) congeners, and 27 polychlorinated biphenyl (PCB) congeners in sediments were measured using GC–MS/MS technique. The highest PBB levels were detected in sediments from River Daqing: PBB3, 10, 4, 15, 26, 31, and 49 were observed in the sediments. The highest concentrations of PBDEs were in River Tuhe (G.M.=2.10ngg−1 dw), and PBDE15 was the most predominant congener in the sediments from all of the rivers of this study, except for River Tuhe, which accounted for >13.5% of the total PBDEs in sediments. PBDE209 was detected in sediments from the Beijingpaiwu, Nanyun, Majia and Tuhe rivers, with observed values ranging from 0.06 to 0.13ngg−1 dw. PCBs had the highest concentrations in sediment samples collected from River Luan and River Daqing, with levels of 18.13 and 25.62ngg−1 dw, respectively. The most predominant PCB congener in these samples was PCB138, which accounted for about 24% of the sum of the seven indicator PCB congeners (PCB28, 52, 101, 118, 138, 153, and 180) measured in the two rivers. The measured levels of PHAHs were compared with recent results, reported in the literature, and the respective sediment quality guidelines recommended by USEPA. The levels of PHAHs in the present study were generally lower than respective threshold-effect levels, or were comparable to those reported in relatively uncontaminated freshwaters from other regions. This suggests that, in these rivers, toxic biological effects on aquatic biota—due to PHAH contamination of sediments—can be expected to be negligible. Thus, in terms of PHAHs, the sediments can be regarded as relatively uncontaminated.

Maternal exposure to a brominated flame retardant and genitourinary conditions in male offspring.

BackgroundThe upward trend in industrial nations in the incidence of male genitourinary (GU) conditions may be attributed to increased exposure to endocrine disruptors. Polybrominated biphenyl (PBB), a brominated flame retardant, is one such suspected endocrine disruptor.ObjectiveWe investigated the relationship between maternal serum levels of PBBs and GU conditions among male offspring exposed in utero.MethodsIn this cohort study of sons born to women accidentally exposed to PBBs during 1973–1974, we examined self-reported data on GU conditions among male offspring in relation to maternal serum PBB levels. We used generalized estimating equations to calculate odds ratios (ORs), controlling for gestational age at birth.ResultsOf 464 sons, 33 reported any GU condition (13 hernias, 10 hydroceles, 9 cryptorchidism, 5 hypospadias, and 1 varicocele). Four reported both hernia and hydrocele, and one both hernia and cryptorchidism. After adjustment for gestational age at birth, sons of highly exposed women (> 5 ppb) were twice as likely to report any GU condition compared with sons of the least exposed women [≤1 ppb; OR = 2.0; 95% confidence interval (CI), 0.8–5.1]. This risk was increased when we excluded sons born after the exposure but before the mother’s serum PBB measurement (OR = 3.1; 95% CI, 1.0–9.1). We found evidence of a 3-fold increase in reported hernia or hydrocele among sons with higher PBB exposure (test of trend p-value = 0.04). Neither hypospadias nor cryptorchidism was individually associated with PBB exposure.ConclusionsAlthough cryptorchidism and hypospadias were not associated with in utero PBB exposure, this study suggests that other GU conditions may be associated with exposure to endocrine-disrupting chemicals during development.

Maternal exposure to polybrominated and polychlorinated biphenyls: Infant birth weight and gestational age

Understanding the influence of maternal exposures on gestational age and birth weight is essential given that pre-term and/or low birth weight infants are at risk for increased mortality and morbidity. We performed a retrospective analysis of a cohort exposed to polybrominated biphenyls (PBB) through accidental contamination of cattle feed and polychlorinated biphenyls (PCB) through residual contamination in the geographic region. Our study population consisted of 444 mothers and their 899 infants born between 1975 and 1997. Using restricted maximum likelihood estimation, no significant association was found between estimated maternal serum PBB at conception or enrollment PCB levels and gestational age or infant birth weight in unadjusted models or in models that adjusted for maternal age, smoking, parity, infant gender, and decade of birth. For enrollment maternal serum PBB, no association was observed for gestational age. However, a negative association with high levels of enrollment maternal serum PBB and birth weight was suggested. We also examined the birth weight and gestational age among offspring of women with the highest (10%) PBB or PCB exposure, and observed no significant association. Because brominated compounds are currently used in consumer products and therefore, are increasingly prevalent in the environment, additional research is needed to better understand the potential relationship between in utero exposure to brominated compounds and adverse health outcomes.

The influence of age at exposure to PBBs on birth outcomes

The determination of critical windows of susceptibility to environmental chemical exposures and health has become a major public health focus. This study examined the association between early age at exposure to polybrominated biphenyls (PBBs) and subsequent birth weight and gestational length in offspring among females. The study population consisted of 1111 births that occurred among 560 women enrolled in the Michigan PBB Cohort from 1975 to 1994. Maternal age at exposure was categorized into three groups:<10 years ( n=64), 11–16 years ( n=149), and 17–42 years ( n=347). Overall serum PBB levels ranged from 0 to 1490 ppb, with a median of 2, 3, and 2 ppb in the three age groups, respectively. Separate mixed-effects linear regression models were used to evaluate the effect of age at exposure (years) and initial PBB level (ppb) on birth weight (grams) and gestational age (weeks), controlling for gestational age (weeks) (in the model examining effects on birth weight), BMI (kg/m 2) and serum PCB level at enrollment (ppb), maternal age and paternal education at delivery, parity, infant gender, interval between the initial serum test and date of delivery (years), and the trimester in which prenatal care was initiated. Relative to the oldest age group, age<10 years at exposure was the most important predictor of increased birth weight (estimated regression coefficient=225 g, P=0.012). Infant birth weight increased approximately 16 g for every 10 ppb increase in serum PBBs ( P=0.004). There was no association between initial PBB levels and gestational age, nor were initial serum PCB levels associated with either infant birth weight or gestational length. These results provide support for the hypothesis that early age at exposure may be an important determinant in subsequent health effects due to environmental chemical exposures.

Polybrominated Biphenyls, Polychlorinated Biphenyls, Body Weight, and Incidence of Adult-Onset Diabetes Mellitus

Prior studies have reported an increased risk of diabetes related to polychlorinated biphenyl (PCB) exposure. No study has yet investigated whether polybrominated biphenyls (PBBs), which are similar in chemical structure, increase the incidence of diabetes. The Michigan PBB cohort was established in 1976 and surveyed again in 1991-1993 and in 2001. PBB and PCB serum levels were measured from blood collected at enrollment. To determine the incidence of adult-onset diabetes, we analyzed cohort members without diabetes at enrollment, ages 20 years and older, with known PBB and PCB levels, who participated in at least 1 follow-up survey (n = 1384). Using Poisson regression, we determined the incidence density ratio (IDR) of diabetes for different serum levels of PBB and PCB, controlling for age, body mass index, smoking, and alcohol consumption at enrollment. Analyzing 25 years of follow-up data, we did not find that higher PBB serum levels were a risk factor for the incidence of diabetes mellitus. However, in women, but not in men, higher PCB serum levels were associated with increased incidence of diabetes (IDR = 2.33; 95% confidence interval = 1.25-4.34 in the highest PCB group compared with the lowest). In both men and women, overweight and obesity increased the diabetes incidence. We found no association between PBB serum levels and diabetes incidence. In women, there was a positive linear association of diabetes incidence with PCB serum levels at enrollment. This finding is in agreement with 2 prior studies indicating a higher relative risk of diabetes in PCB-exposed women.

Pharmacokinetic Variability and the Miracle of Modern Analytical Chemistry

Background: Prior studies have reported an increased risk of diabetes related to polychlorinated biphenyl (PCB) exposure. No study has yet investigated whether polybrominated biphenyls (PBBs), which are similar in chemical structure, increase the incidence of diabetes. Methods: The Michigan PBB cohort was established in 1976 and surveyed again in 1991-1993 and in 2001. PBB and PCB serum levels were measured from blood collected at enrollment. To determine the incidence of adult-onset diabetes, we analyzed cohort members without diabetes at enrollment, ages 20 years and older, with known PBB and PCB levels, who participated in at least 1 follow-up survey (n = 1384). Using Poisson regression, we determined the incidence density ratio (IDR) of diabetes for different serum levels of PBB and PCB, controlling for age, body mass index, smoking, and alcohol consumption at enrollment. Results: Analyzing 25 years of follow-up data, we did not find that higher PBB serum levels were a risk factor for the incidence of diabetes mellitus. However, in women, but not in men, higher PCB serum levels were associated with increased incidence of diabetes (IDR = 2.33; 95% confidence interval = 1.25-4.34 in the highest PCB group compared with the lowest). In both men and women, overweight and obesity increased the diabetes incidence. Conclusions: We found no association between PBB serum levels and diabetes incidence. In women, there was a positive linear association of diabetes incidence with PCB serum levels at enrollment. This finding is in agreement with 2 prior studies indicating a higher relative risk of diabetes in PCB-exposed women.

Menstrual function among women exposed to polybrominated biphenyls: A follow-up prevalence study

BackgroundAlteration in menstrual cycle function is suggested among rhesus monkeys and humans exposed to polybrominated biphenyls (PBBs) and structurally similar polychlorinated biphenyls (PCBs). The feedback system for menstrual cycle function potentially allows multiple pathways for disruption directly through the hypothalamic-pituitary-ovarian axis and indirectly through alternative neuroendocrine axes.MethodsThe Michigan Female Health Study was conducted during 1997–1998 among women in a cohort exposed to PBBs in 1973. This study included 337 women with self-reported menstrual cycles of 20–35 days (age range: 24–56 years). Current PBB levels were estimated by exponential decay modeling of serum PBB levels collected from 1976–1987 during enrollment in the Michigan PBB cohort. Linear regression models for menstrual cycle length and the logarithm of bleed length used estimated current PBB exposure or enrollment PBB exposure categorized in tertiles, and for the upper decile. All models were adjusted for serum PCB levels, age, body mass index, history of at least 10% weight loss in the past year, physical activity, smoking, education, and household income.ResultsHigher levels of physical activity were associated with shorter bleed length, and increasing age was associated with shorter cycle length. Although no overall association was found between PBB exposure and menstrual cycle characteristics, a significant interaction between PBB exposures with past year weight loss was found. Longer bleed length and shorter cycle length were associated with higher PBB exposure among women with past year weight loss.ConclusionThis study suggests that PBB exposure may impact ovarian function as indicated by menstrual cycle length and bleed length. However, these associations were found among the small number of women with recent weight loss suggesting either a chance finding or that mobilization of PBBs from lipid stores may be important. These results should be replicated with larger numbers of women exposed to similar lipophilic compounds.

MENSTRUAL CYCLE FUNCTION AMONG WOMEN WITH POLYBROMINATED BIPHENYL EXPOSURE

ISEE-274 Introduction: The Michigan Female Health Study was conducted in 1997-1998 among women in a cohort exposed to polybrominated biphenyls (PBBs) in 1973. We investigated whether menstrual cycle function was altered among these women. Methods: A total of 337 women, aged 24 to 56, with self-reported menstrual cycles between 20 and 35 days, were eligible for analyses. We estimated PBB levels at the time of interview by modeling the exponential decay of serum PBB levels that had been measured from 1975 to 1987 when the women were enrolled in the Michigan PBB Cohort. Linear regression models related menstrual cycle length and bleed length to estimated current PBB exposure. Results: Higher levels of physical activity were associated with shorter bleed length, and increasing age was associated with shorter cycle length. The association of age with bleed length was J-shaped. Although no overall association was found between PBB exposure and menstrual cycle characteristics, significant interactions of PBB exposure with age and weight loss were found. Among women with weight loss, PBB exposure was associated with longer bleed length and shorter cycle length. Discussion: These observations generate hypotheses for specific mechanisms of endocrine disruption by organohalogen compounds.

Retrospective Time-Trend Study of Polybrominated Diphenyl Ether and Polybrominated and Polychlorinated Biphenyl Levels in Human Serum from the United States

Six polybrominated diphenyl ethers (PBDEs), one hexabromobiphenyl [polybrominated biphenyl (PBB)], and one hexachlorobiphenyl [polychlorinated biphenyl (PCB)] were measured in 40 human serum pools collected in the southeastern United States during 1985 through 2002 and in Seattle, Washington, for 1999 through 2002. The concentrations of most of the PBDEs, which are commercially used as flame retardants in common household and commercial applications, had significant positive correlations with time of sample collection, showing that the concentrations of these compounds are increasing in serum collected in the United States. In contrast, PCB and PBB levels were negatively correlated with sample collection year, indicating that the levels of these compounds have been decreasing since their phaseout in the 1970s.