Explore the vast range of titles available.

Polybrominated diphenyl ethers (PBDEs) are used in large quantities as flame-retardant additives in a number of commercial products. Biomonitoring data show that, in recent years, PBDE concentrations have increased rapidly in the bodies of wildlife and humans. Usually, PBDE levels in North America have been reported to be higher than those in Europe and Asia. Moreover, body burden of PBDEs is three- to ninefold higher in infants and toddlers than in adults, showing these last two age groups the highest levels of these compounds, due to exposure via maternal milk and through dust. Tetra-, Penta-, and Hexa-BDEs are the isomers most commonly found in humans. Based on studies on experimental animals, the toxicological endpoints of exposure to PBDEs are likely to be thyroid homeostasis disruption, neurodevelopmental deficits, reproductive changes, and even cancer. Experimental studies in animals and epidemiological observations in humans suggest that PBDEs may be developmental neurotoxicants. Pre- and/or postnatal exposure to PBDEs may cause long-lasting behavioral abnormalities, particularly on motor activity and cognition. This paper is focused on reviewing the current status of PBDEs in the environment, as well as the critical adverse health effects based on the recent studies on the toxic effects of PBDEs.

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.

Tetrabromobisphenol A (TBBPA) is a known endocrine disruptor employed in a range of consumer products and has been predominantly found in different environments through industrial processes and in human samples. In this review, we aimed to summarize published scientific evidence on human biomonitoring, toxic effects and mode of action of TBBPA in humans. Interestingly, an overview of various pretreatment methods, emerging detection methods, and treatment methods was elucidated. Studies on exposure routes in humans, a combination of detection methods, adsorbent-based treatments and degradation of TBBPA are in the preliminary phase and have several limitations. Therefore, in-depth studies on these subjects should be considered to enhance the accurate body load of non-invasive matrix, external exposure levels, optimal design of combined detection techniques, and degrading technology of TBBPA. Overall, this review will improve the scientific comprehension of TBBPA in humans as well as the environment, and the breakthrough for treating waste products containing TBBPA.

Polybrominated biphenyls (PBBs) are commonly used flame retardants that pose severe risks to humans. However, there is a lack of systematic research on the transformation process and biological toxicities of PBBs in the environment, which is not conducive to the prevention and control of pollution risks of PBBs. Therefore, the transformation pathways (i.e., photodegradation, microbial degradation, combustion oxidation, and in vivo metabolism) of PBBs and previously designed PBB substitutes were deduced first. Then the potential rodent carcinogenicity, rodent toxicity, mutagenicity, developmental toxicity, skin and eye irritation, skin sensitization, and aquatic toxicity of the transformation products were evaluated using the toxicokinetics (TOPKAT) model. Finally, 3D quantitative structure activity relationship (3D-QSAR) models were constructed to assess the human toxicity (i.e., carcinogenicity, developmental toxicity, hepatotoxicity, epigenetic toxicity, neurotoxicity, and immunotoxicity) of PBBs, PBBs substitutes, and their transformation products. Results showed that the transformation products of PBBs and their substitutes exhibit high toxicity risks (i.e., potential carcinogenicity, mutagenicity, and developmental toxicity) to organisms. The D3-A1 molecule had the highest carcinogenic risk probability at 0.826. The dihydroxy metabolite 2,2′-OH-PBB-80 of the PBB-80 molecule presented the highest potential developmental toxicity risk (toxicity probability 0.713). Polybrominated dibenzofuran (PBDF) showed the strongest skin irritation (probability 0.995). The combustion oxidation products of PBBs exhibited higher potential ecological and human health risks than other transformation products. Among potential toxicity risks to humans, the developmental toxicity of the transformation products of PBBs and their substitutes was theoretically significant, with characterization values ranging from 70.53 to 100.87. This is the first study to comprehensively evaluate the ecological and human health risks of PBBs and their transformation products by combining the inference of transformation pathways with the prediction of transformation product toxicities, providing theoretical support for the design of environmentally friendly PBB substitutes in future studies.

Polybrominated biphenyls (PBB) and polychlorinated biphenyls (PCB) are persistent organic pollutants with potential endocrine-disrupting effects linked to adverse health outcomes. In this study, we utilize high-resolution metabolomics (HRM) to identify internal exposure and biological responses underlying PCB and multigenerational PBB exposure for participants enrolled in the Michigan PBB Registry. HRM profiling was conducted on plasma samples collected from 2013 to 2014 from a subset of participants enrolled in the Michigan PBB Registry, including 369 directly exposed individuals (F0) who were alive when PBB mixtures were accidentally introduced into the food chain and 129 participants exposed to PBB or through breastfeeding, if applicable (F1). Metabolome-wide association studies were performed for PBB-153 separately for each generation and (PCB-118, PCB-138, PCB-153, and PCB-180) in the two generations combined, as both had direct PCB exposure. Metabolite and metabolic pathway alterations were evaluated following a well-established untargeted HRM workflow. Mean levels were [standard deviation (SD): 13.9] for PBB-153 and (SD: 0.788) for . Sixty-two and 26 metabolic features were significantly associated with PBB-153 in F0 and F1 [false discovery rate (FDR) ], respectively. There were 2,861 features associated with (FDR ). Metabolic pathway enrichment analysis using a bioinformatics tool revealed perturbations associated with in numerous oxidative stress and inflammation pathways (e.g., carnitine shuttle, glycosphingolipid, and vitamin B9 metabolism). Metabolic perturbations associated with PBB-153 in F0 were related to oxidative stress (e.g., pentose phosphate and vitamin C metabolism) and in F1 were related to energy production (e.g., pyrimidine, amino sugars, and lysine metabolism). Using authentic chemical standards, we confirmed the chemical identity of 29 metabolites associated with levels (level 1 evidence). Our results demonstrate that serum PBB-153 is associated with alterations in inflammation and oxidative stress-related pathways, which differed when stratified by generation. We also found that was associated with the downregulation of important neurotransmitters, serotonin, and 4-aminobutanoate. These findings provide novel insights for future investigations of molecular mechanisms underlying PBB and PCB exposure on health. https://doi.org/10.1289/EHP12657.

Tetrabromobisphenol A (TBBPA) mono-ether structural analogs, identified as the by-products or transformation products of commercial TBBPA bis-ether derivatives, have been identified as emerging widespread pollutants. However, there is very little information regarding their toxicological effects. We aimed to explore the potential thyroid hormone (TH) system-disrupting effect of TBBPA mono-ether structural analogs. The binding potencies of chemicals toward human TH transport proteins [transthyretin (TTR) and thyroxine-binding globulin (TBG)] and receptors [ ligand-binding domain (LBD) and ] were determined by fluorescence competitive binding assays. Molecular docking was used to simulate the binding modes of the chemicals with the proteins. The cellular TR-disrupting potencies of chemicals were assessed by a GH3 cell proliferation assay. The intracellular concentrations of the chemicals were measured by high-performance liquid chromatography and mass spectrometry. TBBPA mono-ether structural analogs bound to TTR with half maximal inhibitory concentrations ranging from to but did not bind to TBG. They also bound to both subtypes of TR-LBDs with 20% maximal inhibitory concentrations ranging from to . The docking results showed that the analogs fit into the ligand-binding pockets of TTR and TR-LBDs with binding modes similar to that of TBBPA. These compounds likely induced GH3 cell proliferation via TR [with the lowest effective concentrations (LOECs) ranging from to ] and further enhanced TH-induced GH3 cell proliferation (with LOECs ranging from to ). Compared with TBBPA, TBBPA-mono(2,3-dibromopropyl ether) showed a 4.18-fold higher GH3 cell proliferation effect and 105-fold higher cell membrane transportation ability. This study provided a possible mechanism underlying the difference in TTR or TR binding by novel TBBPA structural analogs. These compounds might exert TH system-disrupting effects by disrupting TH transport in circulation and TR activity in TH-responsive cells. https://doi.org/10.1289/EHP6498.

The Michigan Polybrominated Biphenyl (PBB) Registry, followed since 1976, was created after a 1973 chemical manufacturing mistake. The flame retardant PBB was accidentally mixed into animal feed and distributed to Michigan farms for nearly a year, exposing farm residents and animal product consumers. We synthesized knowledge to date on health effects of PBB exposure within the Michigan PBB Registry and describe research findings in the context of literature on other persistent organic pollutants (POPs) and endocrine-disrupting chemicals (EDCs). We reviewed literature published from 1973 to 2025 on human health effects of PBB following the Michigan contamination, using PubMed and Thompson Reuters (ISI) Web of Science databases. We excluded studies not in English; studies on exposures besides PBB; animal studies; reviews, abstracts, or letters to the editor; studies without a health outcome; and studies outside of Michigan or unrelated to the 1973 contamination. For each article, two researchers performed title and abstract screening, full article review, and data extraction. We included 79 publications out of 601 identified and screened. Early studies did not find many health outcomes associated with PBB, possibly because of methodological limitations. More recent studies on long-term and multigenerational impacts found an increased breast cancer risk, accelerated pubertal development and earlier menarche for girls exposed , urogenital problems and slower pubertal development in boys exposed , lower estrone 3-glucuronide and follicle-stimulating hormone among women exposed in childhood, and increased miscarriage risk among daughters of exposed women. Epigenetic and metabolomic research reported altered pathways related to estrogenic effects and immune function as well as the epigenetic alterations of spermatogenic cells. This unique community-academic partnership has produced insights into multigenerational consequences of EDC/POP exposures across the life course. The findings from this cohort underscore the broader relevance of critical windows of vulnerability, particularly during fetal development and childhood. https://doi.org/10.1289/EHP15012.

Methoxylated polybrominated diphenyl ethers (MeO-PBDEs) have been found bioaccumulated in the tissues of a variety of aquatic animals and at concentrations comparable to those of anthropogenic halogenated organic compounds, including polychlorinated biphenyls (PCBs). The origin of the MeO-PBDEs has been uncertain; circumstantial evidence supports a natural and/or an industrial source. By analyzing the natural abundance radiocarbon content of two MeO-PBDEs isolated from a True's beaked whale (Mesoplodon mirus), we show that these compounds were naturally produced.

Background: Polybrominated diphenyl ethers (PBDEs) are persistent, bioaccumulative, and endocrine-disrupting chemicals. Objectives: We used handwipes to estimate exposure to PBDEs in house dust among toddlers and examined sex, age, breast-feeding, race, and parents' education as predictors of serum PBDEs. Methods: Eighty-three children from 12 to 36 months of age were enrolled in North Carolina between May 2009 and November 2010. Blood, handwipe, and house dust samples were collected and analyzed for PBDEs. A questionnaire was administered to collect demographic data. Results: PBDEs were detected in all serum samples (geometric mean for ΣpentaBDE in serum was 43.3 ng/g lipid), 98% of the handwipe samples, and 100% of the dust samples. Serum ΣpentaBDEs were significantly correlated with both handwipe and house dust ΣpentaBDE levels, but were more strongly associated with handwipe levels (r = 0.57; p < 0.001 vs. r = 0.35; p < 0.01). Multivariate model estimates revealed that handwipe levels, child's sex, child's age, and father's education accounted for 39% of the variation in serum ΣBDE₃ levels (sum of BDEs 47, 99, and 100). In contrast, age, handwipe levels, and breast-feeding duration explained 39% of the variation in serum BDE 153. Conclusions: Our study suggests that hand-to-mouth activity may be a significant source of exposure to PBDEs. Furthermore, age, socioeconomic status, and breast-feeding were significant predictors of exposure, but associations varied by congener. Specifically, serum ΣBDE₃ was inversely associated with socioeconomic status, whereas serum BDE-153 was positively associated with duration of breast-feeding and mother's education.

In 1973-1974, Michigan residents were exposed to polybrominated biphenyls (PBBs) through an accidental contamination of the food supply. Residents were enrolled in a registry assembled after the incident, and they and their children participated in follow-up studies to assess subsequent health outcomes. We evaluated associations between serum PBBs and polychlorinated biphenyls (PCBs) and markers of thyroid function among Michigan adults. Serum concentrations of four PBB and four PCB congeners were measured at least once in 753 adults, including 79 women who participated in a 2004-2006 study and 683 women and men with follow-up during 2012-2015. Participants completed questionnaires on health conditions (including physician-diagnosed thyroid disease), behaviors, and demographics. Thyroid hormones were measured in a subset without thyroid disease (n=551). In multivariable linear regression models, PBB and PCB congener concentrations, on both the volume (nanogram/milliliter) and lipid (nanogram/gram lipid) basis, were assessed in relation to thyroid hormones. Logistic regression models were used to estimate associations between serum PBBs and PCBs and thyroid disease. Thyroid disease was common (18% overall; 25% among women). Among women, all odds ratios (ORs) for PBB-153 and thyroid disease were positive for quintiles above the reference level, but estimates were imprecise and were without a monotonic increase. For an interquartile range (IQR) increase in PBB-153 (0.43 ng/mL), the OR (any thyroid disease)=1.12; (95% CI: 0.83, 1.52) (n=105 cases); for hypothyroidism, OR=1.35 (95% CI: 0.86, 2.13) (n=49 cases). There were 21 cases of thyroid disease in men [OR=0.69 (95% CI: 0.33); 1.44 for an IQR increase (0.75 ng/mL) in serum PBB-153]. PCB congeners were statistically significantly associated with greater total and free thyroxine and total triiodothyronine among women and with total and free triiodothyronine among men in lipid-standardized models. We found some evidence to support associations of PBBs and PCBs with thyroid disease and thyroid hormone levels. https://doi.org/10.1289/EHP1302.