Adherence to the EAT-Lancet diet in relation to mortality and exposure to food contaminants in population-based cohorts of Swedish men and women.

BACKGROUND: The EAT-Lancet diet was created to support dietary transition towards sustainable diets. Current evidence indicates that adherence to the EAT-Lancet diet may reduce mortality risk, yet how adherence may impact dietary exposure to food contaminants remains unexplored. We aimed to estimate the association between adherence to the EAT-Lancet diet and i) all-cause, cardiovascular-, and cancer-mortality and ii) predicted dietary exposure to the following food contaminants: cadmium, methylmercury, polychlorinated biphenyls (PCBs), and pesticide residues. METHODS: We used self-reported dietary data from a 96-item food frequency questionnaire of two population-based cohorts - the Cohort of Swedish Men (n = 35,687) and the Swedish Mammography Cohort (n = 32,488). The EAT-Lancet Adherence Index (EAI) was created by scoring consumption of the 14 dietary components included in the EAT-Lancet diet (totalling 0-14 points). Cox proportional hazards regression models were applied to assess the association between EAI and mortality outcomes, presented as multivariable-adjusted hazard ratios (HR) and 95 % confidence intervals (CI). Descriptive statistics were used to characterise predicted exposure to food contaminants, and the correlations between EAI and food contaminants assessed using Spearman's rank correlation. RESULTS: Increased adherence to the EAT-Lancet diet was associated with a lower risk of all-cause mortality (per 3-point increase in EAI: HR = 0.93; CI:0.90,0.97 and HR = 0.91; CI:0.87,0.95 for men and women, respectively) and cardiovascular-mortality (corresponding HR = 0.94; CI:0.88,1.00 and HR = 0.93; CI:0.87,1.00). No clear association was found with cancer-mortality. Increasing EAI was correlated with increased predicted dietary exposure to cadmium, methylmercury, PCBs, and pesticide residues and their median predicted dietary exposures were greater in the high adherence group, compared to the low adherence group. CONCLUSION: High adherence to the EAT-Lancet diet is associated with a reduction in risk of all-cause and cardiovascular-mortality, but also increased dietary exposure to food contaminants.

Prenatal organochlorine pollutant exposure and risk of schizophrenia in a national birth cohort.

Non-genetic prenatal exposures have been associated with schizophrenia risk. However, the role of prenatal exposure to environmental neurotoxicants in offspring schizophrenia risk has been studied in only limited instances. Polychlorinated biphenyls (PCBs) and the pesticide metabolite p,p'-dichlorodiphenyl dichloroethylene (DDE) have been linked to neurodevelopmental outcomes, including impairments implicated in schizophrenia. To determine whether prenatal maternal levels of organochlorine pollutants including PCBs or DDE are associated with schizophrenia in the offspring, an investigation was conducted in the Finnish Prenatal Study of Schizophrenia (FIPS-S), a case-control study nested in a national birth cohort. Cases were born in 1987-1991 and had at least two diagnoses of schizophrenia (ICD-10 F20; ICD-9 295) or schizoaffective disorder (ICD-10 F25; ICD-9 295.7) recorded in the national Care Register for Health Care. Each case was individually matched to a control on sex, date of birth, and residence in Finland on the date of case diagnosis. In 500 case-control pairs, PCB congeners 74, 99, 118, 138, 153, 156, 170, 180, 183, 187, and some widespread organochlorine pesticides or their metabolites including DDE were measured in archived prenatal maternal sera using gas chromatography - high triple quadrupole mass spectrometry. Maternal total PCBs were quantified as the sum of concentrations of the measured congeners. Associations with schizophrenia were examined using conditional logistic regression. Maternal PCB or DDE levels greater than the 75th percentiles of the control distributions showed no evidence of association with offspring schizophrenia (PCBs: adjusted odds ratio (aOR) = 1.13, 95 % CI = 0.85-1.50), p = 0.41; DDE: aOR = 1.08, 95 % CI = 0.80-1.45; p = 0.63). Maternal levels of either pollutant dichotomized at the 90th percentile or considered as a continuous variable also did not show evidence for association with offspring schizophrenia. This study found a lack of evidence that prenatal maternal levels of the organochlorine pollutants DDE and PCBs are associated with offspring risk of schizophrenia.

Insights into Organochlorine Pesticides Exposure in the Development of Cardiovascular Diseases: A Systematic Review.

Many human diseases such as cancer, neurological diseases, autism and diabetes are associated with exposure to pesticides, especially organochlorine pesticides. However, pesticide exposure is also associated with cardiovascular disease (CVD) as the leading cause of death worldwide. In this systematic review, results on the link between organochlorine pesticide pollution and CVD were collected from databases (Medline (PubMed), Scopus and Science Direct) in May 2022 from studies published between 2010 and 2022. A total of 24 articles were selected for this systematic review. Sixteen articles were extracted by reviewers using a standardized form that included cross-sectional, cohort, and ecological studies that reported exposure to organochlorine pesticides in association with increased CVD risk. In addition, eight articles covering molecular mechanisms organochlorine pesticides and polychlorinated biphenyls (PCBs) on cardiovascular effects were retrieved for detailed evaluation. Based on the findings of the study, it seems elevated circulating levels of organochlorine pesticides and PCBs increase the risk of coronary heart disease, especially in early life exposure to these pesticides and especially in men. Changes in the regulatory function of peroxisome proliferator-activated γ receptor (PPARγ), reduction of paroxonase activity (PON1), epigenetic changes of histone through induction of reactive oxygen species, vascular endothelial inflammation with miR-expression 126 and miR-31, increased collagen synthesis enzymes in the extracellular matrix and left ventricular hypertrophy (LVH) and fibrosis are mechanisms by which PCBs increase the risk of CVD. According to this systematic review, organochlorine pesticide exposure is associated with increased risk of CVD and CVD mortality through the atherogenic and inflammatory molecular mechanism involving fatty acid and glucose metabolism.

Sex, menopause, and age differences in the associations of persistent organic pollutants with thyroid hormones, thyroxine-binding globulin, and peripheral deiodinase activity: A cross-sectional study of the general Korean adult population.

Persistent organic pollutants (POPs) can disrupt the thyroid hormone system in humans. We assessed the associations of several POPs with serum thyroid hormones (T3 and T4) and thyroid-stimulating hormone, and investigated the modulating effects of sex, menopausal status, and age on these associations, in a subgroup of the adult population (n = 1250) from the Korean National Environmental Health Survey. PCB105 and PCB118 were negatively associated with total T4 in premenopausal females and males aged <50, whereas the associations were insignificant in other groups. PCB180, p,p'-DDE, and p,p'-DDT showed positive associations with total T3 in postmenopausal females; however, among males aged ≥50, PCB118, PCB138, and p,p'-DDE showed negative associations with total T3. The effects of exposure to multiple POPs were examined in multi-factor analyses. Factor 2 comprised PCB52, hexachlorobenzene, and BDE-47 was associated with an increase in free T4 in premenopausal females (ß = 0.015, p = 0.024), while Factor 1, which contained most POPs, was associated with a change in total T3 in postmenopausal females (ß = 0.032, p = 0.040) and males aged ≥50 (ß = -0.039, p = 0.023). Changes in total T4 or total T3 could be explained by differences in thyroxine-binding globulin (TBG) and peripheral deiodinase activity (GD). Negative associations of TBG with PCB105 in premenopausal females and PCB153 in males aged <50 may mediate the effect of decreasing total T4. PCB180, p,p'-DDE, p,p'-DDT, and Factor 1 were positively associated with GD, which is consistent with an increased total T3 in postmenopausal females. PCB118 was negatively associated with GD and total T3 in males aged ≥50. BDE-47 and ß-hexachlorocyclohexane were associated with thyroid autoantibodies in premenopausal females and males aged <50. Our observations suggest that the thyroid-disrupting effects of POPs may differ by sex, sex hormonal status, and age, and may be mediated by TBG and GD.

Dietary intakes of dioxins and polychlorobiphenyls (PCBs) and breast cancer risk in 9 European countries.

BACKGROUND: Dioxins and polychlorobiphenyls (PCBs) are persistent organic pollutants that have demonstrated endocrine disrupting properties. Several of these chemicals are carcinogenic and positive associations have been suggested with breast cancer risk. In general population, diet represents the main source of exposure. METHODS: Associations between dietary intake of 17 dioxins and 35 PCBs and breast cancer were evaluated in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort from nine European countries using multivariable Cox regressions. The present study included 318,607 women (mean ± SD age: 50.7 ± 9.7) with 13,241 incident invasive breast cancers and a median follow-up of 14.9 years (IQR = 13.5-16.4). Dietary intake of dioxins and PCBs was assessed combining EPIC food consumption data with food contamination data provided by the European Food Safety Authority. RESULTS: Exposure to dioxins, dioxins + Dioxin-Like-PCBs, Dioxin-Like-PCBs (DL-PCBs), and Non-Dioxin-Like-PCBs (NDL-PCBs) estimated from reported dietary intakes were not associated with breast cancer incidence, with the following hazard ratios (HRs) and 95% confidence intervals for an increment of 1 SD: HRdioxins = 1.00 (0.98 to 1.02), HRdioxins+DL-PCB = 1.01 (0.98 to 1.03), HRDL-PCB = 1.01 (0.98 to 1.03), and HRNDL-PCB = 1.01 (0.99 to 1.03). Results remained unchanged when analyzing intakes as quintile groups, as well as when analyses were run separately per country, or separating breast cancer cases based on estrogen receptor status or after further adjustments on main contributing food groups to PCBs and dioxins intake and nutritional factors. CONCLUSIONS: This large European prospective study does not support the hypothesis of an association between dietary intake of dioxins and PCBs and breast cancer risk.

Firefighting and melanoma, epidemiological and toxicological associations: a case report.

The International Agency for Research on Cancer (IARC) classifies firefighting as possibly carcinogenic to humans, and polychlorinated biphenyls (PCBs) as carcinogens with sufficient evidence for development of melanoma in humans. We present a case report of a firefighter with melanoma and history of 33 years of occupational exposure. Based on the available epidemiological and toxicological evidence of association between being a firefighter and developing melanoma, melanoma was recognized by the Norwegian Labour and Welfare Service as an occupational disease in our patient. In 2017, melanoma was acknowledged as an occupational disease in only 8 out of 28 surveyed European countries. Melanoma should be considered as a possible occupational disease among firefighters with a history of relevant exposure. Further recognition of the occupational exposures leading to increased risk of melanoma is still needed for preventive purposes.

Prenatal exposure to persistent organic pollutants and childhood obesity: A systematic review and meta-analysis of human studies.

We conducted a systematic review and meta-analysis of the associations between prenatal exposure to persistent organic pollutants (POPs) and childhood obesity. We focused on organochlorines (dichlorodiphenyltrichloroethane [DDT], dichlorodiphenyldichloroethylene [DDE], hexachlorobenzene [HCB], and polychlorinated biphenyls [PCBs]), perfluoroalkyl and polyfluoroalkyl substances (PFAS), and polybrominated diphenyl ethers (PBDEs) that are the POPs more widely studied in environmental birth cohorts so far. We search two databases (PubMed and Embase) through July/09/2021 and identified 33 studies reporting associations with prenatal organochlorine exposure, 21 studies reporting associations with prenatal PFAS, and five studies reporting associations with prenatal PBDEs. We conducted a qualitative review. Additionally, we performed random-effects meta-analyses of POP exposures, with data estimates from at least three prospective studies, and BMI-z. Prenatal DDE and HCB levels were associated with higher BMI z-score in childhood (beta: 0.12, 95% CI: 0.03, 0.21; I2 : 28.1% per study-specific log increase of DDE and beta: 0.31, 95% CI: 0.09, 0.53; I2 : 31.9% per study-specific log increase of HCB). No significant associations between PCB-153, PFOA, PFOS, or pentaPBDEs with childhood BMI were found in meta-analyses. In individual studies, there was inconclusive evidence that POP levels were positively associated with other obesity indicators (e.g., waist circumference).

Sex specific associations between in utero exposure to persistent organic pollutants and allergy-related outcomes in childhood: The Rhea Mother-Child Cohort (Crete, Greece).

Accumulating evidence suggests that in utero exposures can influence the development of the immune system. Few studies have investigated whether prenatal exposure to persistent organic pollutants (POPs) is associated with allergy-related phenotypes in childhood, nor explored sex differences. We examined the association between prenatal exposure to POPs and offspring allergic outcomes in early and mid-childhood. We included 682 mother-child pairs from the prospective birth cohort Rhea. We measured dichlorodiphenyldichloroethylene (DDE), hexachlorobenzene (HCB) and 6 polychlorinated biphenyl (PCB) congeners in maternal first trimester serum. Parents completed the questionnaires adapted from the International Study on Asthma and Allergy in Childhood (ISAAC) for allergy-related phenotypes when their children were 4 and 6 years old. We used Poisson regression models to estimate Risk Ratios. Prenatal HCB was associated with increased risk for rhinoconjunctivitis at 6 years (RR (95% CI): 2.5; (1.3, 4.8) for a doubling in the exposure). Among girls, prenatal DDE was associated with increased risk for current wheeze, current asthma and current rhinoconjunctivitis at 4 years (RR (95%CI): 1.4 (0.8, 2.6), 1.6 (1.1, 2.4) and 1.8 (1.0, 3.3) and p-interaction = 0.035, 0.027 and 0.059, respectively), with increased risk for current rhinoconjunctivitis at 6 years (RR (95%CI): 1.7 (0.7, 3.8) and p-interaction = 0.028) and total PCBs were associated with increased risk for current eczema at 4 years (RR (95%CI): 2.1 (1.1, 4.2) and p-interaction = 0.028). In boys, prenatal DDE was associated with decreased risk for current wheeze and current asthma at 4 years. Our findings suggest that even low levels of exposure to POPs prenatally may affect the development of childhood allergy-related outcomes in a sex and age-specific manner.

Persistent organic pollutants in pregnant women potentially affect child development and thyroid hormone status.

BACKGROUND: Potentially harmful effects of persistent organic pollutants (POPs) such as polychlorinated biphenyls (PCBs) and dichlorodiphenyltrichloroethane (DDT) on prenatal development and the endocrine system have been controversially discussed. METHODS: Working with a German cohort of 324 pregnant women, we assessed POP levels and used robust linear regression models to determine potential associations between maternal POP concentrations and pre- and postnatal development in the children, as well as the thyroid hormone status of the mother and child. RESULTS: Maternal p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) and most measured PCBs positively correlated with postnatal weight gain. We detected no correlation between newborn birth weight and head circumference, respectively, and maternal PCB and p,p'-DDE serum levels, while body length at birth was negatively associated with the maternal serum concentration of PCB 183. Maternal p,p'-DDE and nearly all PCB serum levels showed a negative correlation with maternal free triiodothyronine (FT3). p,p'-DDE and PCB 74 and 118 were negatively associated with maternal thyroid-stimulating hormone levels. In addition, we identified significant associations between maternal POP levels and thyroid hormone parameters of the child. CONCLUSIONS: These results indicate that POP exposure likely affects different aspects of pre- and postnatal development and impacts the thyroid hormone status of both mother and child. IMPACT: Pregnant women in a German cohort display a substantial accumulation of POPs. Body mass index and age influence maternal serum POP levels. Maternal POP levels show correlations with the child's length at birth and weight gain, and FT3 levels in the mother and child. Our data provide additional evidence for the potentially harmful influence of POPs. Our data indicate that POPs influence pre- and postnatal development.

Nutritional status and prey energy density govern reproductive success in a small cetacean.

A variety of mammals suppress reproduction when they experience poor physical condition or environmental harshness. In many marine mammal species, reproductive impairment has been correlated to polychlorinated biphenyls (PCBs), the most frequently measured chemical pollutants, while the relative importance of other factors remains understudied. We investigate whether reproductively active females abandon investment in their foetus when conditions are poor, exemplified using an extensively studied cetacean species; the harbour porpoise (Phocoena phocoena). Data on disease, fat and muscle mass and diet obtained from necropsies in The Netherlands were used as proxies of health and nutritional status and related to pregnancy and foetal growth. This was combined with published life history parameters for 16 other areas to correlate to parameters reflecting environmental condition: mean energy density of prey constituting diets (MEDD), cumulative human impact and PCB contamination. Maternal nutritional status had significant effects on foetal size and females in poor health had lower probabilities of being pregnant and generally did not sustain pregnancy throughout gestation. Pregnancy rates across the Northern Hemisphere were best explained by MEDD. We demonstrate the importance of having undisturbed access to prey with high energy densities in determining reproductive success and ultimately population size for small cetaceans.

Developmental exposure to non-dioxin-like polychlorinated biphenyls promotes sensory deficits and disrupts dopaminergic and GABAergic signaling in zebrafish.

The most abundant polychlorinated biphenyl (PCB) congeners found in the environment and in humans are neurotoxic. This is of particular concern for early life stages because the exposure of the more vulnerable developing nervous system to neurotoxic chemicals can result in neurobehavioral disorders. In this study, we uncover currently unknown links between PCB target mechanisms and neurobehavioral deficits using zebrafish as a vertebrate model. We investigated the effects of the abundant non-dioxin-like (NDL) congener PCB153 on neuronal morphology and synaptic transmission linked to the proper execution of a sensorimotor response. Zebrafish that were exposed during development to concentrations similar to those found in human cord blood and PCB contaminated sites showed a delay in startle response. Morphological and biochemical data demonstrate that even though PCB153-induced swelling of afferent sensory neurons, the disruption of dopaminergic and GABAergic signaling appears to contribute to PCB-induced motor deficits. A similar delay was observed for other NDL congeners but not for the potent dioxin-like congener PCB126. The effects on important and broadly conserved signaling mechanisms in vertebrates suggest that NDL PCBs may contribute to neurodevelopmental abnormalities in humans and increased selection pressures in vertebrate wildlife.

Maternal exposure to airborne polychlorinated biphenyls (PCBs) and risk of adverse birth outcomes.

Human health effects of airborne lower-chlorinated polychlorinated biphenyls (LC-PCBs) are largely unexplored. Since PCBs may cross the placenta, maternal exposure could potentially have negative consequences for fetal development. We aimed to determine if exposure to airborne PCB during pregnancy was associated with adverse birth outcomes. In this cohort study, exposed women had lived in PCB contaminated apartments at least one year during the 3.6 years before conception or the entire first trimester of pregnancy. The women and their children were followed for birth outcomes in Danish health registers. Logistic regression was performed to estimate odds ratios (OR) for changes in secondary sex ratio, preterm birth, major congenital malformations, cryptorchidism, and being born small for gestational age. We performed linear regression to estimate difference in birth weight among children of exposed and unexposed mothers. All models were adjusted for maternal age, educational level, ethnicity, and calendar time. We identified 885 exposed pregnancies and 3327 unexposed pregnancies. Relative to unexposed women, exposed women had OR 0.97 (95% CI 0.82, 1.15) for secondary sex ratio, OR 1.13 (95% CI 0.76, 1.67) for preterm birth, OR 1.28 (95% CI 0.81, 2.01) for having a child with major malformations, OR 1.73 (95% CI 1.01, 2.95) for cryptorchidism and OR 1.23 (95% CI 0.88, 1.72) for giving birth to a child born small for gestational age. The difference in birth weight for children of exposed compared to unexposed women was - 32 g (95% CI-79, 14). We observed an increased risk of cryptorchidism among boys after maternal airborne LC-PCB exposure, but due to the proxy measure of exposure, inability to perform dose-response analyses, and the lack of comparable literature, larger cohort studies with direct measures of exposure are needed to investigate the safety of airborne LC-PCB exposure during pregnancy.

Sub-Chronic Effects of Slight PAH- and PCB-Contaminated Mesocosms in Paracentrotus lividus Lmk: A Multi-Endpoint Approach and De Novo Transcriptomic.

Sediment pollution is a major issue in coastal areas, potentially endangering human health and the marine environments. We investigated the short-term sublethal effects of sediments contaminated with polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) on the sea urchin Paracentrotus lividus for two months. Spiking occurred at concentrations below threshold limit values permitted by the law (TLVPAHs = 900 µg/L, TLVPCBs = 8 µg/L, Legislative Italian Decree 173/2016). A multi-endpoint approach was adopted, considering both adults (mortality, bioaccumulation and gonadal index) and embryos (embryotoxicity, genotoxicity and de novo transcriptome assembly). The slight concentrations of PAHs and PCBs added to the mesocosms were observed to readily compartmentalize in adults, resulting below the detection limits just one week after their addition. Reconstructed sediment and seawater, as negative controls, did not affect sea urchins. PAH- and PCB-spiked mesocosms were observed to impair P. lividus at various endpoints, including bioaccumulation and embryo development (mainly PAHs) and genotoxicity (PAHs and PCBs). In particular, genotoxicity tests revealed that PAHs and PCBs affected the development of P. lividus embryos deriving from exposed adults. Negative effects were also detected by generating a de novo transcriptome assembly and its annotation, as well as by real-time qPCR performed to identify genes differentially expressed in adults exposed to the two contaminants. The effects on sea urchins (both adults and embryos) at background concentrations of PAHs and PCBs below TLV suggest a need for further investigations on the impact of slight concentrations of such contaminants on marine biota.

Association Between Gestational Exposure to Toxicants and Autistic Behaviors Using Bayesian Quantile Regression.

Autism spectrum disorder, which is characterized by impaired social communication and stereotypic behaviors, affects 1%-2% of children. Although prenatal exposure to toxicants has been associated with autistic behaviors, most studies have been focused on shifts in mean behavior scores. We used Bayesian quantile regression to assess the associations between log2-transformed toxicant concentrations and autistic behaviors across the distribution of behaviors. We used data from the Maternal-Infant Research on Environmental Chemicals study, a pan-Canadian cohort (2008-2011). We measured metal, pesticide, polychlorinated biphenyl, phthalate, bisphenol-A, and triclosan concentrations in blood or urine samples collected during the first trimester of pregnancy. Using the Social Responsiveness Scale (SRS), in which higher scores denote more autistic-like behaviors, autistic behaviors were assessed in 478 children aged 3-4 years old. Lead, cadmium, and most phthalate metabolites were associated with mild increases in SRS scores at the 90th percentile of the SRS distribution. Manganese and some pesticides were associated with mild decreases in SRS scores at the 90th percentile of the SRS distribution. We identified several monotonic trends in which associations increased in magnitude from the bottom to the top of the SRS distribution. These results suggest that quantile regression can reveal nuanced relationships and, thus, should be more widely used by epidemiologists.

Adverse health effects of PCBs on fine motor performance - Analysis of a neurophysiological pathway in the HELPcB surveillance program.

Since research literature indicates neurotoxic health effects of polychlorinated biphenyls (PCBs), it is necessary to identify by which mechanism PCBs might affect the human central nervous system and human behavior. In the present study, a neurophysiological pathway is assumed to explain the negative association of PCB exposure and performance in fine motor tasks mediated by the level of the dopamine (DA) metabolite homovanillic acid (HVA). A total of 113 occupationally PCB exposed workers and their relatives from an occupational health monitoring program were examined (89.4 % men). PCBs were analyzed in plasma via human biomonitoring and HVA was assessed in urine. The motor performance series was used to measure two dimensions of fine motor skills with 5 subgroups (accuracy: steadiness, line tracking accuracy; speed: line tracking speed, aiming, tapping). The direct effects of PCBs on fine motor performance and the indirect effects of PCBs on fine motor performance via DA metabolite HVA were tested with multiple regressions. We found significant effects for the accuracy dimension, namely a negative direct effect of PCBs on line tracking accuracy mediated by HVA. Further, an indirect effect could be found for PCBs with steadiness accuracy through HVA. There were no significant effects related to fine motor performances in the speed dimension. These results provide first indications for an underlying neurochemical pathomechanism involving the dopamine system of PCB-related deterioration of fine motor performance regarding accuracy.

Chloracne: a case series on cutaneous expression of CYP1A1 as diagnostic biomarker.

Chloracne, also known as metabolizing acquired dioxin-induced skin hamartomas (MADISH), is a rare disfiguring disease related to dioxin exposure. There is a paucity of literature on the clinical manifestations and pathogenesis of chloracne/MADISH. The aim of this study was to assess the clinical features of this very unusual acneiform eruption and to explore the pathogenesis of the disease. This was a retrospective, observational report study was conducted on five patients belonging to the same nuclear family (father, mother and three children) and a relative (father's brother) living in the same house. Histopathological, immunohistochemical, laboratory and toxicological analyses were performed for all patients. The results suggest that CYP1A1 in human skin is a diagnostic biomarker in chloracne, and was positive for all the patients in our sample. Tetrachlorodibenzo-p-dioxin is the most investigated dioxin responsible for chloracne; however, several other agonists, whether dioxin-like or not, can activate the aryl hydrocarbon receptor. To our knowledge, this Italian case series is the first study to suggest polychlorinated biphenyls as a possible cause of an overstimulation of aryl hydrocarbons causing the consequent acneiform eruption.

Prenatal environmental exposures and associations with teen births.

BACKGROUND: Children's prenatal exposure to multiple environmental chemicals may contribute to subsequent deficits in impulse control, predisposing them to risk-taking. OBJECTIVE: Our goal was to investigate associations between prenatal exposure mixtures and risk of teen birth, a manifestation of high-risk sexual activity, among 5865 girls (1st generation) born in southeast Massachusetts from 1992-1998. METHODS: Exposures included prenatal modeled polychlorinated biphenyls (PCBs), ρ,ρ'-dichlorodiphenyl dichloroethylene (DDE), hexachlorobenzene (HCB), lead (Pb), and mercury (Hg). We fit adjusted generalized additive models with multivariable smooths of exposure mixtures, 1st generation infant's birth year, and maternal age at 1st generation birth. Predicted odds ratios (ORs) for teen birth were mapped as a function of joint exposures. We also conducted sensitivity analyses among 1st generation girls with measured exposure biomarkers (n = 371). RESULTS: The highest teen birth risk was associated with a mixture of high prenatal HCB, Hg, Pb, and PCB, but low DDE exposure, with similar associations in sensitivity analyses. The highest OR predicted for girls born in 1995 to mothers of median age (26 years) was at the 95th percentile of the HCB and PCB exposure distributions (OR = 3.09; 95% confidence interval: 0.29, 32.4). Additionally, girls born earlier in the study period or to teen mothers were at increased risk of teen birth. SIGNIFICANCE: Prenatal environmental chemical exposures and sociodemographic characteristics may interact to substantially increase risk of teen births.

Environmental chemicals and metabolic disruption in primary and secondary human parathyroid tumors.

BACKGROUND: The incidence of primary hyperparathyroidism has increased 300% in the United States in the past 30 years, and secondary hyperparathyroidism is almost universal in patients with end-stage renal disease. We assessed the presence of environmental chemicals in human hyperplastic parathyroid tumors as possible contributing factors to this increase. METHODS: Cryopreserved hyperplastic parathyroid tumors and normal human parathyroids were analyzed by gas chromatography and liquid chromatography coupled to ultra-high-resolution mass spectrometry, bioinformatics, and biostatistics. RESULTS: Detected environmental chemicals included polychlorinated biphenyls, polybrominated diphenyl ethers, dichloro-diphenyl-trichloroethane derivatives, and other insecticides. A total of 99% had p,p'-dichlorodiphenyldichloroethylene. More than 50% contained other environmental chemicals, and many classified as endocrine disruptors. Polychlorinated biphenyl-28 and polychlorinated biphenyl-49 levels correlated positively with parathyroid tumor mass. Polybrominated diphenyl ether-47 concentrations in tumors were inversely correlated with patients' serum calcium levels. Cellular metabolites in pathways of purine and pyrimidine synthesis and mitochondrial energy production were associated with tumor growth and with p,p'-dichlorodiphenyldichloroethylene in primary hyperparathyroidism tumors. In normal parathyroids, p,p'-dichlorodiphenyldichloroethylene , polychlorinated biphenyl-28, polychlorinated biphenyl-74, and polychlorinated biphenyl-153, but not p,p'-dichlorodiphenyldichloroethylene or polychlorinated biphenyl-49, were detected. CONCLUSION: Environmental chemicals are present in human parathyroid tumors and warrant detailed epidemiologic and mechanistic studies to test for causal links to the growth of human parathyroid tumors.

Co-exposure to PCB126 and PFOS increases biomarkers associated with cardiovascular disease risk and liver injury in mice.

Polychlorinated biphenyl (PCB)126 and perfluorooctane sulfonic acid (PFOS) are halogenated organic pollutants of high concern. Exposure to these chemicals is ubiquitous, and can lead to potential synergistic adverse effects in individuals exposed to both classes of chemicals. The present study was designed to identify interactions between PCB126 and PFOS that might promote acute changes in inflammatory pathways associated with cardiovascular disease and liver injury. Male C57BL/6 mice were exposed to vehicle, PCB126, PFOS, or a mixture of both pollutants. Plasma and liver samples were collected at 48 h after exposure. Changes in the expression of hepatic genes involved in oxidative stress, inflammation, and atherosclerosis were investigated. Plasma and liver samples was analyzed using untargeted lipidomic method. Hepatic mRNA levels for Nqo1, Icam1, and PAI1 were significantly increased in the mixture-exposed mice. Plasma levels of PAI1, a marker of fibrosis and thrombosis, were also significantly elevated in the mixture-exposed group. Liver injury was observed only in the mixture-exposed mice. Lipidomic analysis revealed that co-exposure to the mixture enhanced hepatic lipid accumulation and elevated oxidized phospholipids levels. In summary, this study shows that acute co-exposure to PCB126 and PFOS in mice results in liver injury and increased cardiovascular disease risk.

Plasma levels of polychlorinated biphenyl, genetic polymorphisms, and the risk of advanced stage endometriosis.

Both environmental and genetic factors interact and play a critical role in the pathogenesis of endometriosis. We analyzed the plasma levels of 12 polychlorinated biphenyl (PCB) congeners with genetic polymorphisms of glutathione-S-transferase M1 (GSTM1), glutathione-S-transferase T1 (GSTT1), and aryl hydrocarbon receptor repressor (AhRR) codon 185. Total sum of the 12 congeners was significantly higher in the controls compared with endometriosis group. Women without C/C genotype in AhRR codon 185 had a significantly increased risk of endometriosis compared with those with C/C genotype. Total sum of the 12 congeners was significantly higher in women without C/C genotype compared with those with C/C genotype. Adjusting for age and AhRR codon 185 genotype, there was no significant association between exposure to PCBs and the risk of endometriosis. These findings suggest a possible presence of gene-environment interaction, however, we could not see any clear association between exposure to PCBs and the risk of endometriosis.