Alteration of serotonin system by polychlorinated biphenyls exposure

Previous studies have suggested that exposure to polychlorinated biphenyls (PCBs) may alter thyroid function, but data on effects of PCB exposure on other endogenous hormones has been lacking. The current study is ancillary to a larger investigation of the effects of Great Lakes fish consumption on PCBs and reproductive function. In the current study we examine associations of PCBs, 1,1-bis (4-chlorophenyl)-2,2-dichloroethene (DDE), and fish consumption with thyroid and steroid hormones in 178 men and PCBs, DDE, and fish consumption with thyroid hormones in 51 women from the original study. Serum PCB level and consumption of Great Lakes fish are associated with significantly lower levels of thyroxine (T(4)) and free thyroxine index (FTI) in women and with significantly lower levels of T(4) in men. Fish consumption, but not PCB level, is significantly and inversely associated with triiodothyronine (T(3)) in men. Results for thyroid-stimulating hormone (TSH) are inconsistent. Among men, there are significant inverse associations of both PCB and fish consumption with sex hormone-binding globulin (SHBG)-bound testosterone, but no association with SHBG or free testosterone. There are no significant overall associations of PCB, DDE, or fish consumption with estrone sulfate, follicle-stimulating hormone, luteinizing hormone, or dehydroepiandrosterone sulfate. The results of this study are consistent with previous studies showing effects of fish consumption and PCB exposure on thyroid hormones and suggest that PCBs may also decrease steroid binding to SHBG. Elucidation of specific mechanisms must await future investigations.

Polychlorinated biphenyls (PCBs) were commercially manufactured in the United States from about 1930 until 1979, when their production was banned under the Toxic Substances Control Act (TSCA) because of concerns about their extreme environmental persistence, ability to bioaccumulate, and adverse human health effects. PCBs were used in numerous industrial and consumer applications, most notably as insulation fluids in electrical transformers and generators but also in products including fluorescent lamp ballasts, caulk, and carbonless copy paper. These now-discontinued manufactured chemicals have received a great deal of attention in terms of research and environmental remediation. But other, lesser-known PCBs continue to be generated and released into the environment, not from intentionally created commercial products but as unintentional by-products of manufacturing processes including, according to recent studies, those used to make certain pigments used in dyes, inks, and paints. PCBs do not occur naturally, and once in the environment they can last for decades. Until recently, PCBs that were being detected in the environment were thought to come entirely from “legacy” sources. Yet developments in analytical technology have given researchers a better understanding of PCB sources, of the patterns of individual PCBs (or congeners) that are being detected environmentally, and the fate of PCBs in the environment—how they move between soil, sediment, water, and air. These advances have also enabled the detection of individual congeners at very low levels and the identification of many new and ongoing sources of PCBs beyond those resulting from historical commercial mixtures. Unintentionally produced PCBs were known to be present in inks and dyes when the U.S. Environmental Protection Agency (EPA) announced the final rule barring commercial PCB production in 1979. A rule allowing exemptions for PCBs in controlled manufacturing processes and as unintentional contaminants was promulgated under TSCA a few years later. This rule allowed for PCB concentrations of up to 50 ppm in certain products as a result of manufacturing processes.1 Recently, manufacturing by-product PCBs have been identified in wastewater, sediments, and air in numerous locations. They have also been positively identified in testing of new products colored with such pigments, so it is clear these PCBs are not occurring as a result of legacy commercial mixtures. What is emerging is an increasingly complex picture of the prevalence of nonlegacy PCBs alongside the persisting environmental presence of legacy PCBs, and a concurrent and likewise complex picture of how PCBs can affect human health at very low levels of exposure.

In the last decade advances in the analytic methods for quantification of polychlorinated biphenyls (PCBs) have resulted in widespread availability of congener-specific analysis procedures, and large amounts of data on PCB congener profiles in soil, air, water, sediments, foodstuffs, and human tissues have become available. These data have revealed that the PCB residues in environmental media and human tissues may not closely resemble any of the commercial PCB mixtures, depending on source of exposure, bioaccumulation through the food chain, and weathering of PCBs in the environment. At the same time, toxicological research has led to a growing awareness that different classes of PCB congeners have different profiles of toxicity. These advances in analytic techniques and toxicological knowledge are beginning to influence the risk assessment process. As the data from ongoing PCB studies assessing the mediators of neurobehavioral outcomes in children are published, the weight of evidence for PCB effects on neurodevelopment is growing. Studies in Taiwan, Michigan (USA), New York (USA), Holland, Germany, and the Faroe Islands have all reported negative associations between prenatal PCB exposure and measures of cognitive functioning in infancy or childhood. The German study also reported a negative association between postnatal PCB exposure and cognitive function in early childhood--a result that had not been found in previous studies. Only one published study in North Carolina (USA) has failed to find an association between PCB exposure and cognitive outcomes. Despite the fact that several more recent studies have used congener-specific analytic techniques, there have been only limited attempts to assess the role of specific PCB congeners or classes of congeners in mediating neurodevelopmental outcomes. From a statistical standpoint, attempts to determine the role of individual congeners in mediating outcomes are hampered by the fact that concentrations of most individual congeners are highly correlated with each other and with total PCBs. From a toxicological standpoint, these efforts are hampered by the fact that many of the PCB congeners present in human tissues have never been studied in the laboratory, and their relative potency to produce nervous system effects is unknown. More complete information on the health effects of various congeners or congener classes would allow more informed scientific and risk assessment decisions.

Effects of PCB exposure on serum thyroid hormone levels in dogs and cats

Assessing the effects of polychlorinated biphenyls (Aroclor 1254) on a scleractinian coral ( Stylophora pistillata) at organism, physiological, and molecular levels

BackgroundAnimal studies have shown that exposure to common, low-level environmental contaminants [e.g., polychlorinated biphenyls (PCBs), lead] causes excessive and inappropriate responding on intermittent reinforcement schedules. The Differential Reinforcement of Low Rates task (DRL) has been shown to be especially sensitive to low-level PCB exposure in monkeys.ObjectivesWe investigated the relationships between prenatal PCB and postnatal Pb exposure performance on a DRL schedule in children. We predicted that a) prenatal PCB exposure would reduce interresponse times (IRTs) and reinforcements earned, and b) postnatal Pb exposure would reduce IRTs and reinforcements earned.MethodsWe tested 167 children on a DRL20 (20 sec) reinforcement schedule, and recorded IRTs and the number of reinforced responses across the session. We measured prenatal PCB exposure (cord blood), methylmercury (MeHg) (maternal hair), and postnatal Pb exposure (venous blood), and > 50 potentially confounding variables.ResultsResults indicated impaired performance in children exposed to PCBs, MeHg, and Pb. Children prenatally exposed to PCBs responded excessively, with significantly lower IRTs and fewer reinforcers earned across the session. In addition, exposure to either MeHg or Pb predicted statistically significant impairments of a similar magnitude to those for PCBs, and the associated impairments of all three contaminants (PCB, MeHg, and Pb) were statistically independent of one another.ConclusionsThese results, taken with animal literature, argue the high sensitivity of DRL performance to low-level PCB, MeHg, and Pb exposure. Future research should employ behavioral tasks in children, such as DRL, that have been demonstrably sensitive to low-level PCB, MeHg, and Pb exposure in animals.

Changes in the quality of eggs of birds exposed to polychlorinated biphenyls (PCBs) have been described, but have never been directly attributed to PCBs. Polychlorinated biphenyl residues in eggs have been associated with reduced reproductive success and embryonic deformities in wild birds. Egg size and composition, specifically the amount of albumen, yolk, and water in an egg, also influence the growth and viability of embryos and hatchlings, and consequently the reproductive success of birds. To deter mine whether PCB exposure of adult birds affected the size and composition of their eggs, 25 pairs of captive American kestrels (Falco sparverius) were fed a mixture of PCB-spiked (1248:1254:1260) food to give an approximate exposure of 7 mg/kg body weight/d, beginning 1 mo prior to pairing, and continuing throughout the courtship, egg-laying, and incubation periods. This dietary level in the adult female kestrels resulted in mean total PCB residues in the eggs of 34.1 µg/g wet weight (geometric mean), which is environmentally relevant. PCB residues in eggs increased with the time of female exposure to the contaminated diet and laying date. Variation in egg size within PCB clutches was significantly greater than within control clutches, although absolute egg mass and volume did not differ markedly by treatment. Only infertile eggs and only one egg per clutch were used for egg composition analysis. Yolks in the PCB-contaminated eggs were heavier, with less wet and dry albumen relative to control eggs. Water content and eggshell thickness were not significantly affected by PCB exposure. These results suggest that eggs from the PCB treatment have relatively more lipid and less protein available for embryonic development. Changes in egg composition were not associated with egg size, lay date, ambient temperature, humidity, or precipitation, which are factors known to affect these variables in bird eggs. The PCB-induced changes in egg composition described here provide insight into possible mechanisms contributing to reduced reproductive performance in wild birds exposed to PCBs.

BackgroundPrenatal exposure to persistent organic pollutants, e.g. polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) has been suggested to negatively affect birth weight although epidemiological evidence is still inconclusive. We investigated if prenatal exposure to PCBs and PBDEs is related to birth weight in a Swedish population with background exposure.MethodsBreast milk was sampled during the third week after delivery from first-time mothers in Uppsala county, Sweden 1996–2010 (POPUP cohort) (N = 413). Samples were analysed for di-ortho PCBs (CB-138, 153, 180) and tetra- to hexa- brominated PBDEs (BDE-47, 99, 100, 153). Simple and multiple linear regression models were used to investigate associations between lipid-adjusted, ln-transformed PCB and PBDE concentrations, and birth weight. Covariates included in the multivariate regression model were PCB and PBDE exposure, maternal age, pre-pregnancy BMI, weight gain during pregnancy, education, smoking, gender of the infant and gestational length. The effect of including fish consumption was also investigated.ResultsIn the multivariate model, prenatal exposure to di-ortho PCBs was significantly associated with increased birth weight (β = 137; p = 0.02). The result did not change when gestational length was added to the model. An inverse association between PBDE(4) (sum of BDE-47, -99, -100 and −153) and birth weight was observed in the multivariate model including gestational length (β = −106; p = 0.04). Maternal pre-pregnancy BMI and weight gain during pregnancy were important confounders of the association between di-ortho PCBs and birth weight. The associations were not alleviated after adjustment for fish consumption, a major source of PCB and PBDE exposure. The observed associations were stronger for boys than for girls.ConclusionsOur results indicate that prenatal exposure to di-ortho PCBs and PBDE(4) may influence birth weight in different directions, i.e. PCB exposure was associated with higher birth weight and PBDE exposure with lower birth weight. Maternal pre-pregnancy BMI and weight gain during pregnancy were important confounders that may hide positive association between di-ortho PCB exposure and birth weight if they are not included in the statistical model. We speculate that even small PCB- and PBDE-induced shifts in the distribution of birth weight may influence future public health in populations with background exposure.

Prenatal exposure to polychlorinated biphenyls (PCBs) impairs cognitive development in infants and children, according to numerous studies of these ubiquitous environmental pollutants. Studies of PCB damage have considered many different end points, but the results of these different studies have never been coordinated to pinpoint the neuropsychologic functions most likely to be damaged by prenatal exposure to PCBs. However, a review of longitudinal birth cohort studies in the medical literature reveals that impairment of executive functions—high-order brain processes responsible for planning, flexible thinking, abstract reasoning, problem solving, and inhibition of inappropriate actions—most consistently reflects prenatal PCB exposure [EHP 117:7–16; Boucher et al.]. The review authors selected nine longitudinal birth cohort studies performed between 1959 to 2008 in North America, Europe, and Japan. Consumption of fish, whale blubber, and dairy products by pregnant women was the main source of prenatal PCB exposure as reflected by maternal serum concentrations that ranged from 23 to 450 ng/g of fat. All combined, about 4,000 children were monitored at different ages, from as early as 3 months to as late as 11 years, depending on the study. The types of tests conducted in the various studies included assessments of mental and psychomotor development of infants, IQ tests, and specific measures of verbal skills, visual–spatial ability, memory, attention, and executive functions. No one study measured all these neuropsychologic skills. Such a comprehensive evaluation would require a battery of complicated and expensive procedures. The overall analysis found that executive functions are especially sensitive to PCB exposure. Three studies involving about 1,000 children specifically documented executive functions, and they all found that poor response inhibition was consistently related to prenatal PCB exposure. In one of these studies, children were exposed to some of the lowest doses of PCBs among the reviewed cohorts. Some of the studies reported that processes similar to executive functions—such as task planning, speed of information processing, verbal abilities, and visual recognition memory—were negatively impacted by prenatal exposure to PCBs as well. The authors conclude that executive functions in particular should be assessed in future cohort studies of the neurotoxic effects of PCBs and other organochlorine compounds.

Polychlorinated biphenyls (PCBs) are ubiquitously detected and have been linked to metabolic diseases. Gut microbiome is recognized as a critical regulator of disease susceptibility; however, little is known how PCBs and gut microbiome interact to modulate hepatic xenobiotic and intermediary metabolism. We hypothesized the gut microbiome regulates PCB-mediated changes in the metabolic fingerprints and hepatic transcriptome. Ninety-day-old female conventional and germ-free mice were orally exposed to the Fox River Mixture (synthetic PCB mixture, 6 or 30 mg/kg) or corn oil (vehicle control, 10 ml/kg), once daily for 3 consecutive days. RNA-seq was conducted in liver, and endogenous metabolites were measured in liver and serum by LC-MS. Prototypical target genes of aryl hydrocarbon receptor, pregnane X receptor, and constitutive androstane receptor were more readily upregulated by PCBs in conventional conditions, indicating PCBs, to the hepatic transcriptome, act partly through the gut microbiome. In a gut microbiome-dependent manner, xenobiotic, and steroid metabolism pathways were upregulated, whereas response to misfolded proteins-related pathways was downregulated by PCBs. At the high PCB dose, NADP, and arginine appear to interact with drug-metabolizing enzymes (ie, Cyp1-3 family), which are highly correlated with Ruminiclostridium and Roseburia, providing a novel explanation of gut-liver interaction from PCB-exposure. Utilizing the Library of Integrated Network-based Cellular Signatures L1000 database, therapeutics targeting anti-inflammatory and endoplasmic reticulum stress pathways are predicted to be remedies that can mitigate PCB toxicity. Our findings demonstrate that habitation of the gut microbiota drives PCB-mediated hepatic responses. Our study adds knowledge of physiological response differences from PCB exposure and considerations for further investigations for gut microbiome-dependent therapeutics.

Lower birth weight and growth retardation has been found in studies with laboratory animals, in children born of mothers exposed to accidental high levels of polychlorinated biphenyls (PCBs) and related compounds, and in children born of mothers who consumed PCB-contaminated fish. The effect of background exposure to PCBs and dioxins on birth size and growth in human newborns, however, is still unknown. This study examined birth size and postnatal growth of term newborns in relation to their background PCB and dioxin exposure. Birth weight and weight, length, and head circumference were measured at 10 d and 3, 7, 18, and 42 mo of age in 207 children, of whom 105 were breast-fed and 102 were formula-fed during infancy. The effect of in utero exposure to PCBs on birth size, assessed by cord and maternal plasma PCB levels, was investigated in the whole group. The effect of prenatal PCB exposure on postnatal growth was studied in the formula-fed group, whereas the effect of prenatal as well as lactational exposure to PCBs and dioxins on postnatal growth was studied in the breast-fed group. After adjustment for covariates, cord and maternal plasma PCB levels where both negatively associated with birth weight. Infants with high cord plasma PCB levels (P90 = 0.80 microL) weighed 165 g less compared with infants with low cord plasma PCB levels (P10 = 0.20 microg/L). Cord and maternal plasma PCB levels where both significantly associated with lower growth rate, defined as change in SD score (SDS) of weight, length, and head circumference from birth to 3 mo in the formula-fed group (all p values <0.05). No negative effects of prenatal PCB exposure on growth rate were found from 3 to 42 months of age. Postnatal PCB and dioxin exposure was not negatively associated with growth rate in the breast-fed group. In utero exposure to environmental levels of PCBs is negatively associated with birth weight and postnatal growth until 3 mo of age. Although this growth delay was described in healthy term born infants, intrauterine and postnatal growth retardation are potentially harmful to the developing human and should be avoided by reducing maternal PCB and dioxin body burden, and consequently fetal exposure to these pollutants.

BackgroundBeyond its nutritional benefits, seafood is a source of toxicant exposure including polychlorinated biphenyls (PCB). The association of PCB exposure from seafood intake during pregnancy and/or lactation (PL) and child growth outcomes is uncertain. ObjectiveThis systematic review investigated the evidence and quantified the association between PCB exposure during PL from seafood intake and child growth outcomes. MethodsEmbase, PubMed, and CENTRAL databases were searched from their inception for peer-reviewed English articles. Records were screened independently by two researchers at title and abstract, and then full text levels. Studies were included if they: i) were conducted in a country with high Human Development Index, ii) measured maternal PCB exposure directly, iii) assessed the relationship between PCB and seafood exposures or PCB or seafood associations with a child growth outcome, iv) were randomized or non-randomized interventions, cohort, or nested case-control studies. Pooled partial correlations (rp) were calculated using random effects models for studies with sufficient data and narratively for the remaining studies. Cochrane ROBINS-E and GRADE tools were used to assess risk of bias and certainty of evidence, respectively. Child growth outcomes included birthweight, birth length, head and chest circumference at birth, and small for gestational age (SGA). ResultsSeven studies were included. PCB exposure during PL was weakly but significantly associated with lower birthweight (rp =−0.07; 95%CI: −0.12, −0.02; n=5), but showed no association with birth length (rp=−0.04; 95%CI: −0.09, 0.02; n=4) and head circumference (rp=−0.03, 95%CI: −0.09, 0.03; n=3). Studies on SGA and chest circumference yielded inconclusive results. The certainty of evidence was low or very low due to risk of bias from confounding, missing data, and exposure misclassification. ConclusionsThe evidence suggests minimal to no link between PCB exposure from seafood during PL on child growth outcomes but with low to very low certainty.Registry and registry number for systematic reviews or meta-analyses. This systematic review protocol was registered in PROSPERO (CRD42023493302).

Introduction: Fish consumption may promote cardiovascular health. The role of major food contaminants present in fish, such as polychlorinated biphenyls (PCBs) is, however, largely unexplored. Experimental studies indicate that PCBs cause endothelial cell dysfunction, hyperlipidemia and hypertension and cross-sectional associations have been observed between PCB-biomarkers and several intermediate risk factors for cardiovascular disease. PCBs accumulate and magnify in the food chain and fatty fish is a dominating source of exposure in populations with a relatively high fish intake. We assessed the hypothesis that dietary PCB exposure is associated with increased risk of myocardial infarction (MI) and that the exposure may mask a protective association with marine omega-3 fish fatty acids intake. Methods: Validated food frequency questionnaire-based estimates of dietary PCB exposure was obtained at baseline (1997) in 36,759 men from the population-based Cohort of Swedish Men, free of cancer, cardiovascular disease and diabetes. The estimated dietary PCB exposure was based on the food concentrations of PCB congener 153 at the time of baseline. PCB-153 is the most abundant congener in food and an excellent indicator for total PCB in food and in blood. The long-term dietary PCB exposure assessments showed acceptable validity against six PCB congeners in serum (correlation coefficients 0.30 to 0.58). Cases of MI were ascertained via register-linkage through 2010. Relative risks (RR) and 95% confidence intervals (CI) were adjusted for known cardiovascular risk factors. : Results During 12 years of follow-up (433,243 person-years), we ascertained 3,005 incident cases of MI. The major dietary sources of PCB exposure was fish, dairy products and meat. Compared with the lowest quintile of dietary PCB exposure (median 113 ng/day), men in the highest quintile (median 436 ng/day) had multivariable-adjusted RR of 1.22 (95% CI, 1.05-1.41) for MI, without adjusting for the intake of marine omega-3 fish fatty acids. In a separate model, we observed no association between the intake of marine omega-3 fish fatty acids and MI (RR, 1.07; 95% CI, 0.93-1.24). In mutually-adjusted models, dietary PCB exposure was associated with RR 1.72 (95% CI 1.28-2.30), and the intake of marine omega-3 fish fatty acids with RR, 0.67 (95% CI, 0.50-0.90), comparing highest quintiles with lowest. Conclusions: Exposure to an integrated measure of total PCBs from food was associated with increased risk of MI in men. The results may provide important information regarding the risk-benefit analysis of fish consumption. To increase the net benefits of fish consumption, PCB contamination should be reduced to a minimum: Future studies are needed to clarify the concentrations of PCBs that may offset the beneficial effects of fish consumption.

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Polychlorinated biphenyls (PCBs) are widely distributed environmental toxicants, whose biological toxicity is magnified step by step through the transmission of the food chain. However, there is little research about the effect of PCBs on intestinal epithelial barrier function. In this experiment, the effects of PCB exposure on the intestines of zebrafish were evaluated. Animals were exposed to Aroclor 1254 (5 μg/L, 10 μg/L, 15 μg/L). After 21 days, the changes in histology, enzyme biomarkers, intestinal microorganisms, and metabolomics were detected. The inflammation and oxidative stress in the intestines of zebrafish were observed. Additionally, there were significant changes in intestinal microbiota and tissue metabolism, most of which were associated with oxidative stress, inflammation, and lipid metabolism. The results showed that PCBs exposure resulted in intestinal inflammation and oxidative stress in zebrafish.Moreover, intestinal metabolites and intestinal microflora of zebrafish were also disturbed. This study verified that exposure can lead to intestinal damage and changes in intestinal metabolic capacity and microorganisms, enlightening the consequences of PCB exposure.