Explore the vast range of titles available.

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.

Background This study is a long-term follow-up of individuals exposed to polybrominated biphenyls (PBBs). Widespread contamination of PBBs began in 1973 in Michigan when PBBs entered the food chain. PBBs are synthetic chemicals that were once used in industrial products. Their production in the United States ended following this incident. PBBs and other brominated flame retardants belong to a class of persistent organic pollutants that have been shown to affect human health. We conducted this study to investigate whether PBB exposure was associated with all-cause or cause-specific mortality risk. Methods We included cohort data from 1976 (when the study began) and linked to National Death Index data obtained through the early release of 2021. Serum PBB concentrations were measured at enrollment in the study. We used survival analysis to estimate sex-specific hazard ratios (HR) and 95% confidence intervals (CI), adjusting for age and other important risk factors. The mortality study included 3,954 individuals. Results In age-stratified analyses, higher PBB exposure was not associated with all-cause mortality risk in males or females. In cause-specific analyses conducted in the 16 or older group, we found no association between PBB exposure and circulatory system disease mortality. For all-cancer mortality, we found higher PBB exposure associated with increased risk of mortality in females (HR: 1.50, 95% CI: 1.02–2.22), which was inversed in males (HR: 0.68, 95% CI: 0.46–1.01). BMI appeared to modify the association between PBB exposure and all-cause mortality risk in males and all-cancer mortality risk in males and females. Conclusions This comprehensive study found that the association between PBB exposure and cancer mortality risk varied by sex. Further research is needed to understand these sex-specific differences.

In 1973, the Velsicol Chemical Company, which manufactured FireMaster, a brominated flame retardant, and NutriMaster, a nutritional supplement, mistakenly shipped hundreds of pounds of FireMaster to grain mills around Michigan where it was incorporated into animal feed and then into the food chain across the state. An estimated 6.5 million Michigan residents consumed polybrominated biphenyl (PBB)-laced animal products leading to one of the largest agricultural accidents in U.S. history. To date, there have been no studies investigating the effects of PBB on epigenetic regulation in sperm, which could explain some of the endocrine-related health effects observed among children of PBB-exposed parents. Fusing epidemiological approaches with a novel in vitro model of human spermatogenesis, we demonstrate that exposure to PBB153, the primary component of FireMaster, alters the epigenome in human spermatogenic cells. Using our novel stem cell-based spermatogenesis model, we show that PBB153 exposure decreases DNA methylation at regulatory elements controlling imprinted genes. Furthermore, PBB153 affects DNA methylation by reducing de novo DNA methyltransferase activity at increasing PBB153 concentrations as well as reducing maintenance DNA methyltransferase activity at the lowest tested PBB153 concentration. Additionally, PBB153 exposure alters the expression of genes critical to proper human development. Taken together, these results suggest that PBB153 exposure alters the epigenome by disrupting methyltransferase activity leading to defects in imprint establishment causing altered gene expression, which could contribute to health concerns in the children of men exposed to PBB153. While this chemical is toxic to those directly exposed, the results from this study indicate that the epigenetic repercussions may be detrimental to future generations. Above all, this model may be expanded to model a multitude of environmental exposures to elucidate the effect of various chemicals on germline epigenetics and how paternal exposure may impact the health of future generations.

Brominated flame retardants (BFRs) have been using to reduce the flammability of plastics contained in many products, such as household articles, furniture, mattresses, textiles or insulation. Considering the fact that these compounds may be released into the environment leading to the exposure of living organisms, it is necessary to study their possible effects and mechanisms of action. Proteins play a crucial role in all biological processes. For this reason, a simple model of human serum albumin (HSA) was chosen to study the mechanism of BFRs’ effect on proteins. The study determined interactions between selected BFRs, i.e., tetrabromobisphenol A (TBBPA), tetrabromobisphenol S (TBBPS), 2,4-dibromophenol (2,4-DBP), 2,4,6-tribromophenol (2,4,6-TBP) and pentabromophenol (PBP), and HSA by measurement of fluorescence of intrinsic tryptophan and absorbance of circular dichroism (CD). In addition, in order to understand the possible effect of these compounds in their native environment, the effect of BFRs on membrane proteins of human erythrocytes (red blood cells, RBCs) was also assessed. Among bromophenols, PBP had the strongest oxidative effect on RBC membrane, and 2,4-DBP demonstrated the weakest fluorescence-quenching effect of both membrane tryptophan and HSA. By contrast to PBP, 2,4-DBP and 2,4,6-TBP caused spatial changes of HSA. We have observed that among all analyzed BFRs, TBBPA caused the strongest oxidation of RBC membrane proteins and the model HSA protein, causing reduction of fluorescence of tryptophan contained in them. TBBPA also changed albumin conformation properties, leading to impairment of the α-helix structure. However, TBBPS had the weakest oxidative effect on proteins among studied BFRs and did not affect the secondary structure of HSA.

In this updated follow-up, we investigated the breast cancer experience among women in Michigan exposed to brominated flame retardants, some 30 years following exposure. Michigan residents were enrolled in a study cohort after exposure to polybrominated biphenyls (PBBs) through the consumption of contaminated food products. PBB concentrations were measured in serum at the time of enrolment. Cancer experience was determined by linkage to the Michigan Cancer Registry. We conducted a nested case–control study that included 51 women diagnosed with breast cancer during 1974–2004 and 202 age-matched controls. While the data suggest an increase in breast cancer risk with higher PBB exposure, this did not reach statistical significance. The OR of having breast cancer among women with PBB concentrations ≥10 ng/mL compared to women with PBB concentrations at or below the limit of detection of 1 ng/mL was 2.60, 95% CI 0.93 to 7.27, (p=0.07), when adjusted for age and family history of cancer in a first-degree female relative. It remains important to examine exposure to brominated chemicals and possible health effects, and to continue following the cancer experience of participants in this study.

Although tetrabromobisphenol A (TBBPA) has been well proven to disturb TH signaling in both in vitro and in vivo assays, it is still unclear whether TBBPA can affect brain development due to TH signaling disruption. Here, we employed the T3-induced Xenopus metamorphosis assay (TIXMA) and the spontaneous metamorphosis assay to address this issue. In the TIXMA, 5–500 nmol/L TBBPA affected T3-induced TH-response gene expression and T3-induced brain development (brain morphological changes, cell proliferation, and neurodifferentiation) at premetamorphic stages in a complicated biphasic concentration-response manner. Notably, 500 nmol/L TBBPA treatment alone exerted a stimulatory effect on tadpole growth and brain development at these stages, in parallel with a lack of TH signaling activation, suggesting the involvement of other signaling pathways. As expected, at the metamorphic climax, we observed inhibitory effects of 50–500 nmol/L TBBPA on metamorphic development and brain development, which was in agreement with the antagonistic effects of higher concentrations on T3-induced brain development at premetamorphic stages. Taken together, all results demonstrate that TBBPA can disturb TH signaling and subsequently interfere with TH-dependent brain development in Xenopus; meanwhile, other signaling pathways besides TH signaling could be involved in this process. Our study improves the understanding of the effects of TBBPA on vertebrate brain development.

Flame retardants (FRs) are used in a variety of common items from furniture to carpet to electronics to reduce flammability and combustion, but the potential toxicity of these compounds is raising health concerns globally. Organophosphate FRs (OPFRs) are becoming more prevalent as older, brominated FRs are phased out, but the toxicity of these compounds, and the FR mixtures that contain them, is poorly understood. Work in a variety of in vitro model systems has suggested that FRs may induce metabolic reprogramming such that bone density is compromised at the expense of increasing adiposity. To address this hypothesis, the present studies maternally exposed Wistar rat dams orally across gestation and lactation to 1000 µg daily of the FR mixture Firemaster 550 (FM 550) which contains a mixture of brominated FRs and OPFRs. At six months of age, the offspring of both sexes were examined for evidence of compromised bone composition. Bone density, composition, and marrow were all significantly affected, but only in males. The fact that the phenotype was observed months after exposure suggests that FM 550 altered some fundamental aspect of mesenchymal stem cell reprogramming. The severity of the phenotype and the human-relevance of the dose employed, affirm this is an adverse outcome meriting further exploration.

Polybrominated diphenyl ethers (PBDEs) are widely used flame retardants; currently, they are identified as ubiquitous environmental contaminants. Several studies indicate that PBDEs might affect male fertility. We present the results of a pilot study on the relationship between human serum PBDEs and sperm quality. The PBDE levels in Japan are comparable to those found in European countries. Strong inverse correlations were observed between the serum concentration of 2,2',4,4',5,5'-hexabromodiphenyl ether and sperm concentration (r = -0.841, p = 0.002) and testis size (r = -0.764, p = 0.01). Extensive studies on the relationship between PBDEs and sperm quality are required.

Brominated flame retardants (BFR), including tetrabromobisphenol A (TBBPA) represents 25% of the global market of flame retardants. Among them, TBBPA is used on the largest scale (approx. 60%) because of its firebreak properties and widespread occurrence in every day products such as furniture, upholstery, adhesives and electronic equipment. A broad application of TBBPA can contribute to environmental pollution. Tetrabromobisphenol A has been determined in soil, water, river sediments and the atmosphere. Tetrabromobisphenol A is characterized by a high value of coefficient n-octanol/water (log P = 4.5), low acidity, and it may exist in undissociated or dissociated form. Due to the high hydrophobicity, TBBPA may accumulate in living organisms, including humans at different food chain levels. The occurrence of TBBPA in humans, e.g., in blood, fat tissue and mother milk, has been reported. Tetrabromobisphenol A is classified as hazard statements (H) H400/H410, which means that it is toxic to aquatic biota, causing long-term changes in these organisms. Up to now, only a few studies have been conducted to assess potential toxicity of high doses of TBBPA to mammals. Although many people are occupationally exposed to TBBPA during production or processing of this substance in their workplaces, there are only a few studies that have assessed the real hazard associated with TBPPA exposure. The aim of the study was to discuss the latest literature (mainly from the years 2010-2016) referring to the presence of TBBPA in the environment and its effects to living organisms. Data concerning occupational exposure to TBBPA were also presented. Med Pr 2017;68(1):121-134.

Data on Polybrominated diphenylether (PBDE) concentrations in individual U.S. women were compiled. PBDE levels in adipose tissue, serum, and breast milk from individual U.S. women were found to follow similar lognormal distributions, which exhibited a high degree of variability. The distribution of lipid-normalized PBDE concentrations for all media combined had a median of 47.9 ng/g and a 95th percentile estimate of 302 ng/g. Estimates of congener-specific kinetic parameters were used to calculate the total daily intake of the PBDEs (sum of 5 PBDE prominent congeners, PBDE-47, -99, -100, -153, and -154) that would be required to achieve the measured body burdens. PBDE intake estimates from all routes of exposure were 8.5 ng/kg/d (median) and 54 ng/kg/d (95th percentile). The potential health risks posed by the PBDEs were examined by comparing 95th percentile tissue concentrations in humans (Chuman) to modeled and measured tissue concentrations in rodents that caused no developmental neurotoxicity and reproductive effects (Crodent). The ratio of rodent-to-human PBDE concentrations (Crodent:Chuman) was <1 for alterations of male and female reproductive organs in rats, <10 for neurodevelopmental effects in mice, and <100 for neurodevelopmental effects in rats. If humans are as sensitive as animals to PBDE-induced developmental toxicity, the current margin of safety appears low for a fraction of the population.