Abstract  OBJECTIVE: The aim of this study was to examine associations between endocrine disorders, fish consumption habits, and biomarkers of contaminants and nutrients

METHODS: : Male anglers aged at least 50 years living in Wisconsin (n = 154) completed a questionnaire and provided biological samples. Adjusted logistic regression models were used to evaluate risk factors for endocrine outcomes.

RESULTS: Nineteen percent of anglers reported either pre-diabetes or diabetes, while 4.6% reported thyroid disease. There were few associations between endocrine disease and fish consumption, fish meal source, or species, aside from a notable increase in diabetes risk with lake trout consumption. Docosahexaenoic acid, certain polychlorinated biphenyls (PCBs), and perfluorinated compounds were associated with an increased risk of diabetes or pre-diabetes. PCBs were associated with a decreased risk of thyroid disease.

CONCLUSION: Fish consumption patterns may affect risk for endocrine outcomes, but direction and magnitude of association may depend on the balance of the contaminants and nutrients in the individual diet.

Abstract  BACKGROUND: The biopersistent organochlorine pollutants dichlorodiphenyldichloroethylene (p,p'-DDE), hexachlorobenzene (HCB) and polychlorinated biphenyls (PCBs) can be detected in humans worldwide. The chemicals can cross the placenta and may interfere with endogenous hormonal homeostasis.

OBJECTIVES: To investigate effects on female reproduction following intrauterine exposure to selected biopersistent organochlorines.

METHODS: We used data from a Danish pregnancy cohort with follow-up on 436 eligible daughters at approximately 20years of age. Information on age of menarche (n=335), menstrual cycle length (n=230) and serum concentrations of reproductive hormones (n=243) was obtained. Number of antral follicles was counted by vaginal ultrasound (n=147). Of 244 daughters who attended clinical examination, 170 used hormonal contraceptives and 74 were non-users. Concentrations of p,p'-DDE, HCB and six PCB congeners were analysed in maternal serum samples obtained in pregnancy week 30.

RESULTS: Age of menarche and menstrual cycle length were found not to be statistically significant associated with prenatal organochlorine exposure. Among non-users of hormonal contraceptives with information on antral follicle number (n=43), daughters exposed to the highest tertile of p,p'-DDE had 28% (95% confidence interval (95% CI): 5; 46%) lower follicle number compared to the low-level exposed reference group. Those exposed to medium and higher levels of HCB had 30% (95% CI: 5; 48%) and 28% (95% CI: 7; 44%) lower follicle number compared to the reference group. Furthermore, maternal serum HCB concentrations were inversely associated with free androgen index among non-users of hormonal contraceptives (n=73). These associations were not found in users of hormonal contraceptives.

CONCLUSIONS: Among non-users of hormonal contraceptives, we found indications of adverse long-term effects on female reproduction following prenatal exposure to biopersistent organochlorines. These findings may have wide implications for public health as intrauterine exposure occurs worldwide.

Abstract  BACKGROUND: A subset of obese individuals does not exhibit metabolically unfavorable features; this group is referred to as metabolically healthy obese (MHO). Serum concentrations of polychlorinated biphenyls (PCBs), which are chemicals with endocrine-disrupting properties, have been shown to be lower in MHO than in metabolically unhealthy obese (MUO).

OBJECTIVE: We studied PCB serum concentrations during and after weight loss and their relation with metabolic health.

DESIGN: We determined metabolic health features (weight, blood pressure, lipids, inflammation, and glucose metabolism) and serum PCB concentrations of 27 PCBs in a cohort of 184 overweight and obese subjects. Metabolic health was evaluated with the use of the criteria of the metabolic syndrome (MetS) [metabolic syndrome according to Adult Treatment Panel III criteria present (MetS+) or metabolic syndrome according to Adult Treatment Panel III criteria absent (MetS-)] or with extended criteria with inflammation and insulin resistance taken into account (MUO compared with MHO). Participants were treated with lifestyle counseling or bariatric surgery. A metabolic and toxicological re-evaluation was performed after 6 and 12 mo.

RESULTS: At baseline, serum ΣPCB concentrations were significantly higher in MUO than in MHO (ΣPCBs: 138 ±105 compared with 365 ± 481 ng/g lipid weight; P = 0.01) but not in MetS+ compared with MetS- subjects. No difference was detected in the percentage increase in PCB serum concentrations in MetS+ compared with MetS- subjects (median: 58% compared with 43% and 31% compared with 69% at 6 and 12 mo, respectively). The comparison of persistent with resolved MetS and MUO did not reveal any difference in ΣPCB concentration increments (median: 49% compared with 58% at 12 mo for MUO; P > 0.05). In a regression model with age, smoking, and body mass index corrected for, PCB serum concentrations at baseline were not predictive of the persistence or resolution of a metabolically unfavorable state.

CONCLUSION: Our study indicates that the increment in serum concentrations of PCBs does not differ according to metabolic health and does not seem to influence the beneficial metabolic health effects of weight loss. This study was registered at clinicaltrials.gov at NCT01778868.

Abstract  BACKGROUND: Atopic allergy is much more common in Finnish compared with Russian Karelia, although these areas are geographically and genetically close. To explore the role of environmental chemicals on the atopy difference a random sample of 200 individuals, 25 atopic and 25 non-atopic school-aged children and their mothers, were studied. Atopy was defined as having at least one positive skin prick test response to 14 common inhalant and food allergens tested. Concentrations of 11 common environmental pollutants were measured in blood samples.

RESULTS: Overall, the chemical levels were much higher in Russia than in Finland, except for 2,2',4,4'-tetra-bromodiphenyl ether (BDE47). In Finland but not in Russia, the atopic children had higher concentrations of polychlorinated biphenyls and 1,1-Dichloro-2,2-bis-(p-chlorophenyl)-ethylene (DDE) than the non-atopic children. In Russia but not in Finland, the atopic mothers had higher DDE concentrations than the non-atopic mothers.

CONCLUSIONS: Higher concentrations of common environmental chemicals were measured in Russian compared with Finnish Karelian children and mothers. The chemicals did not explain the higher prevalence of atopy on the Finnish side.

Abstract  BACKGROUND: Many previous studies have dealt with the effect of polychlorinated biphenyls (PCBs) on the thyroid gland, but their findings are inconsistent. One problem of these studies has been their use of cross-sectional designs.

OBJECTIVES: The aim of the current study is to investigate longitudinal effects of PCBs on the thyroid gland, focusing on: morphological changes in thyroid tissue (i.e. thyroid volume), changes in thyroid hormones and in thyroid antibodies.

METHODS: A total of 122 individuals (Mage=44.7) were examined over a period of four years (t(1) until t(4)). Medical history was collected via interviews, an ultrasound examination was performed and blood samples were taken to determine plasma PCB levels, thyroid stimulating hormone (TSH), free triiodthyronine (fT3), free thyroxine (fT4), thyroid peroxidase antibodies (TPOab), thyreoglobulin antibodies (TGab) and thyroid-stimulating hormone receptor antibodies (TSHRab). Rank correlation coefficients and mixed effect models were performed controlling for age and total lipids.

RESULTS: There were negative correlations between higher chlorinated biphenyls and fT3, cross-sectionally as well as longitudinally. We also found an interaction effect of higher-chlorinated PCBs over time for fT4 as well as TSHRab. In case of high exposure, a decrease in fT4 and an increase in TSHRab level were found over time. In regards to the other variables, our findings yielded no clear results in the examined time period.

CONCLUSION: This is the first study to shows a PCB-related effect on fT3, fT4 and TSHRab over a four year period. The data also suggest that morphological and antibody findings remain inconsistent and do not allow for unambiguous interpretation.

Abstract  The effects of occupational exposure to low concentrations of polychlorobiphenyls (PCBs) on the urinary excretion of corticosteroid hormones were evaluated, taking into account the influence of cigarette smoking. The study included 26 males working as electrical maintenance staff in a steel factory, previously exposed to a mixture of PCBs (exposed workers), and 30 male workers with no occupational exposure to PCBs (controls). Serum PCBs (33 congeners), urinary 17-hydroxycorticosteroids, 17-ketosteroids (KS) and pregnanes, and their respective glucuronidated and sulfonated compounds, were determined for each subject. PCBs were significantly higher in the exposed workers than controls, and were correlated with age. Both the urinary concentrations of the total 17-KS and pregnanes, and those of some single steroids and their glucuronidated compounds, were significantly lower in the exposed workers than controls, but higher in smokers than the non-smokers + ex-smokers. Two-way analysis of variance showed a negative association between serum PCBs and both total glucuronidated 17-KS and total and glucuronidated pregnanes, and a positive association between cigarette smoking and both total and glucuronidated 17-KS. PCBs seem to act as endocrine disruptors by reducing the urinary excretion of corticosteroid hormones, particularly of the glucuronidated fraction. Cigarette smoking could boost these effects of PCBs in smokers.

Abstract  AbstractBackground lorinated dibenzo-p-dioxins/dibenzofurans (dioxins) and polychlorinated biphenyls (PCBs) are persistent organic pollutants (POPs) with potentially adverse impact on child neurodevelopment. Whether the potential detrimental effects of dioxins and PCBs on neurodevelopment are of specific or unspecific character is not clear. ives rpose of the current study was to examine the influence of maternal dietary exposure to dioxins and PCBs on ADHD symptoms and cognitive functioning in preschoolers. We aimed to investigate a range of functions, in particular IQ, expressive language, and executive functions. al and methods tudy includes n = 1024 children enrolled in a longitudinal prospective study of ADHD (the ADHD Study), with participants recruited from The Norwegian Mother and Child Cohort Study (MoBa). Boys and girls aged 3.5 years participated in extensive clinical assessments using well-validated tools; The Preschool Age Psychiatric Assessment interview (PAPA), Stanford-Binet 5th revision (SB-5), Child Development Inventory (CDI), and Behavior Rating Inventory of Executive Function, Preschool version (BRIEF-P). Maternal dietary exposure to dioxins and PCBs was estimated based on a validated food frequency questionnaire (FFQ) answered mid-pregnancy and a database of dioxin and PCB concentrations in Norwegian foods. Exposure to dioxins and dioxin-like PCBs (dl-compounds) was expressed in total toxic equivalents (TEQ), and PCB-153 was used as marker for non-dioxin-like PCBs (ndl-PCBs). Generalized linear and additive models adjusted for confounders were used to examine exposure-outcome associations. s re to PCB-153 or dl-compound was not significantly associated with any of the outcome measures when analyses were performed for boys and girls together. After stratifying by sex, adjusted analyses indicated a small inverse association with language in girls. An increase in the exposure variables of 1 SD was associated with a reduction in language score of − 0.2 [CI − 0.4, − 0.1] for PCB-153 and − 0.2 [CI − 0.5, − 0.1] for dl-compounds in girls. For boys, exposure to PCB-153 or dl-compounds was not associated with language skills. The difference between sex-specific associations was not statistically significant (p-value = 0.13). No sex-specific effects were observed for ADHD-symptoms, IQ scores, or executive functions. sions nd no indications that variation in current low-level exposure to PCB-153 or dl-compounds in Norway is associated with variation ADHD-symptoms, verbal/non-verbal IQ, or executive functions including working memory in preschoolers. However, our findings indicated that maternal dietary exposure to PCB-153 or dl-compounds during pregnancy was significantly associated with poorer expressive language skills in preschool girls, although the sex-specific associations were not significantly different.

Abstract  The study aim was to identify the timing of sensitive windows for ototoxicity related to perinatal exposure to PCBs. A total of 351 and 214 children from a birth cohort in eastern Slovakia underwent otoacoustic testing at 45 and 72 months, respectively, and distortion product otoacoustic emissions (DPOAEs) at 11 frequencies were recorded. Cord and child 6-, 16-, 45-, and 72- month blood samples were analyzed for PCB 153 concentration. The PCB 153 concentration-time profiles were approximated with a system model to calculate area under the PCB*time curves (AUCs) for specific time intervals (3 and 6 months for 45 and 72 months data, respectively). DPOAE amplitudes were correlated (Spearman) with cord serum PCB and AUCs, markers of prenatal and postnatal exposure, respectively. Two exposure critical windows were identified in infants, the first related to prenatal and early postnatal and the second to postnatal exposure to PCBs. Our data have shown tonotopicity, sexual dimorphism, and asymmetry in ototoxicity of PCBs.

Abstract  Type 2 diabetes is a chronic metabolic disease that is of increasing concern in Inuit communities. Behavioural factors such as physical inactivity and poor diet are well-known risk factors. Exposure to persistent organic pollutants (POPs) has emerged as an additional factor in the pathogenesis of diabetes. In this study, association between polychlorinated biphenyls (PCBs) and p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) with diabetes in Canadian Inuit was examined. Data from the Adult Inuit Health Survey (2007-2008) of Inuit participants from the Canadian Arctic were analyzed. Self-reported diabetes (excluding gestational diabetes) and clinical measurement of fasting glucose were examined as outcomes. Association with individual PCB congeners, sum of dioxin-like PCBs (∑DL-PCB), non-dioxin-like PCBs (∑NDL-PCB), total PCBs (∑PCB), and p,p'-DDE were investigated using multiple regression models adjusted for confounding factors. Using different methods to incorporate serum lipids, highest vs. lowest quartile exposures to PCB-105, PCB-118, PCB-153, PCB-156, PCB-170, PCB-180, PCB-183, ∑PCB, and p,p'-DDE were associated with increased risk of diabetes. For these PCBs, odds ratios (ORs) ranged from 1.9-3.5 (lower 95% CI: 0.8-1.4, upper 95% CI: 4.4-9.0) and for p,p'-DDE the OR was 2.5 (lower 95% CI: 1.1-1.2, upper 95% CI: 5.9-6.0). The highest vs. lowest quartile exposure to most PCBs and p,p'-DDE were associated with an increase of fasting glucose by 3-7%. PCBs and p,p'-DDE were associated with increased risk of diabetes and higher fasting glucose level in a cross-sectional survey of Canadian Inuit. Cause-effect relationships of PCBs and p,p'-DDE with diabetes and diabetes-related outcomes need to be further investigated in a cohort study.

Abstract  In a sample of 442 births from the Child Health and Development Studies cohort, we examined associations between maternal prenatal exposure to hydroxylated polychlorinated biphenyl metabolites (OH-PCBs) and pregnancy outcomes, and whether associations were mediated by maternal thyroid hormone levels and/or modified by maternal smoking. Compared to nonsmokers, smokers had twice the mean concentration of 4-OH-CB107 (p<0.001) and lower levels of its parent compound, PCB118 (p=0.001). Among mothers who smoked, the birth weight of newborns with maternal concentrations of 4-OH-CB107 in the upper quartile was 316g lighter (95% confidence interval (CI) 566, 65) compared to those with maternal concentrations in the lowest quartile, after control for PCB118 and other potential confounders. This association was not observed for non-smoking mothers and was not mediated by maternal thyroid hormone levels. Maternal prenatal 4-OH-CB107 levels appear to be influenced by maternal smoking and contribute to lower birth weight among smokers.

Abstract  Methylmercury, polychlorinated biphenyls (PCBs), and perfluorinated compounds (PFCs) are ubiquitous and persistent environmental chemicals with known or suspected toxic effects on the nervous system and the immune system. Animal studies have shown that tissue damage can elicit production of autoantibodies. However, it is not known if autoantibodies similarly will be generated and detectable in humans following toxicant exposures. Therefore, we conducted a pilot study to investigate if autoantibodies specific for neural and non-neural antigens could be detected in children at age 7 years who have been exposed to environmental chemicals. Both prenatal and age-7 exposures to mercury, PCBs, and PFCs were measured in 38 children in the Faroe Islands who were exposed to widely different levels of these chemicals due to their seafood-based diet. Concentrations of IgM and IgG autoantibodies specific to both neural (neurofilaments, cholineacetyltransferase, astrocyte glial fibrillary acidic protein, and myelin basic protein) and non-neural (actin, desmin, and keratin) antigens were measured and the associations of these autoantibody concentrations with chemical exposures were assessed using linear regression. Age-7 blood-mercury concentrations were positively associated with titers of multiple neural- and non-neural-specific antibodies, mostly of the IgM isotype. Additionally, prenatal blood-mercury and -PCBs were negatively associated with anti-keratin IgG and prenatal PFOS was negatively associated with anti-actin IgG. These exploratory findings demonstrate that autoantibodies can be detected in the peripheral blood following exposure to environmental chemicals. The unexpected association of exposures with antibodies specific for non-neural antigens suggests that these chemicals may have toxicities that have not yet been recognized.

Abstract  BACKGROUND: Some legacy and emerging environmental contaminants are suspected risk factors for intrauterine growth restriction. However, the evidence is equivocal, in part due to difficulties in disentangling the effects of mixtures.

OBJECTIVES: We assessed associations between multiple correlated biomarkers of environmental exposure and birth weight.

METHODS: We evaluated a cohort of 1250 term (≥37 weeks' gestation) singleton infants, born to 513 mothers from Greenland, 180 from Poland, and 557 from Ukraine, who were recruited during antenatal care visits in 2002‒2004. Secondary metabolites of diethylhexyl and diisononyl phthalates (DEHP, DiNP), eight perfluoroalkyl acids, and organochlorines (PCB-153 and p,p'-DDE) were quantifiable in 72‒100% of maternal serum samples. We assessed associations between exposures and term birth weight, adjusting for co-exposures and covariates, including pre-pregnancy body mass index. To identify independent associations, we applied the elastic net penalty to linear regression models.

RESULTS: Two phthalate metabolites (MEHHP, MOiNP), perfluorooctanoate (PFOA), and p,p'-DDE were most consistently predictive of term birth weight based on elastic net penalty regression. In an adjusted, unpenalized regression model of the four exposures, 2-SD increases in natural log-transformed MEHHP, PFOA, and p,p'-DDE were associated with lower birth weight: -87 g (95% CI: -137, -340 per 1.70 ng/mL), -43 g (95% CI: -108, 23; per 1.18 ng/mL), and -135 g (95% CI: -192, -78 per 1.82 ng/g lipid), respectively; while MOiNP was associated with higher birth weight (46 g; 95% CI: -5, 97 per 2.22 ng/mL).

CONCLUSIONS: This study suggests that several of the environmental contaminants, belonging to three chemical classes, may be independently associated with impaired fetal growth. These results warrant follow-up in other cohorts.

Abstract  Outcome-dependent sampling (ODS) scheme is a cost-effective sampling scheme where one observes the exposure with a probability that depends on the outcome. The well-known such design is the case-control design for binary response, the case-cohort design for the failure time data, and the general ODS design for a continuous response. While substantial work has been carried out for the univariate response case, statistical inference and design for the ODS with multivariate cases remain under-developed. Motivated by the need in biological studies for taking the advantage of the available responses for subjects in a cluster, we propose a multivariate outcome-dependent sampling (multivariate-ODS) design that is based on a general selection of the continuous responses within a cluster. The proposed inference procedure for the multivariate-ODS design is semiparametric where all the underlying distributions of covariates are modeled nonparametrically using the empirical likelihood methods. We show that the proposed estimator is consistent and developed the asymptotically normality properties. Simulation studies show that the proposed estimator is more efficient than the estimator obtained using only the simple-random-sample portion of the multivariate-ODS or the estimator from a simple random sample with the same sample size. The multivariate-ODS design together with the proposed estimator provides an approach to further improve study efficiency for a given fixed study budget. We illustrate the proposed design and estimator with an analysis of association of polychlorinated biphenyl exposure to hearing loss in children born to the Collaborative Perinatal Study. Copyright © 2016 John Wiley & Sons, Ltd.

Abstract  BACKGROUND: Several studies have shown effects of polychlorinated biphenyls (PCBs) on serum thyroid hormone levels in pregnant woman and their infants, while other studies did not find such effects. How PCBs might affect thyroid hormone metabolism, is still unclear. Potential mechanisms are direct influence on the thyroid gland, binding to thyroid binding proteins, increased excretion or metabolism of thyroid hormones by deiodinases or sulfatases. It is also not well known whether the effect on thyroid hormone levels is caused by PCBs themselves, or by their hydroxylated metabolites (OH-PCBs).

OBJECTIVE: To determine the effects of perinatal exposure to PCBs and OH-PCBs on thyroid hormone levels in cord blood and in serum of newborn infants.

METHODS: In a Dutch cohort of 100 mother-infant pairs, exposed to background PCB levels, correlations were assessed between 10 PCBs and 6 OH-PCBs in maternal blood during pregnancy and serum thyroxine (T4), T4 sulfate (T4S), triiodothyronine (T3), reverse T3 (rT3), thyroid-stimulating hormone (TSH) and thyroxine-binding globulin (TBG) levels in cord blood and in serum of three- and 18-month-old infants. We corrected for age of the mother, gestational age, gender and type of feeding.

RESULTS: After correction, prenatal levels of three of 10 measured PCBs showed a positive correlation with cord serum T3, and four PCBs showed a negative correlation with cord serum rT3. After correction, two PCBs and the sum of the 10 measured PCBs were positively correlated with the cord serum T3/rT3 ratio, an indicator of deiodinase 3 activity. No correlations were found between PCBs and T4, TSH and TBG in cord blood. 4-OH-PCB-107 was correlated with T4 at 3months and T4, T4S and T3 at 18months.

CONCLUSION: Our results suggest that PCBs have a negative effect on deiodinase type 3 activity, as reflected by a positive correlation with the T3/rT3 ratio. We identified a potential mechanism by which PCBs may affect thyroid hormone metabolism during human development.

Abstract  Background: The effects of prenatal exposures to polychlorinated biphenyls (PCBs), methylmercury, and lead on birth weight remain disputable. The aim of this study was to investigate whether these chemicals affect birth weight of Japanese newborns, with special emphasis on determining whether these effects differ between males and females. Methods: The subjects from Tohoku Study of Child Development, which was designed to examine the developmental effects of prenatal exposures to such hazardous chemicals, were 489 mother-newborn pairs with complete data including smoking habit during pregnancy. Results: The mean birth weight of all newborns was 3083 (range, 2412-4240) g. The median values of biomarkers in cord blood were 46.0 (5th and 95th percentiles, 18.6-13.8) ng/g lipid for total PCBs, 10.1 (4.3-22.4) ng/g for total mercury (THg), and 1.0 (0.6-1.7) mu g/dL for lead. The birth weight was significantly heavier in the 252 male newborns than in the 237 female ones. A negative association between total PCBs and birth weight was observed in both male and female newborns, even after adjusting for possible confounders. However, a negative association of THg with birth weight was found only in the male newborns. There was no significant relationship between lead and birth weight in both groups. Conclusion: Birth weight appears to be affected by prenatal PCB exposure in Japanese male and female newborns, and the effect of methylmercury exposure on male fetal growth may be stronger than that for females. This implication is that the effects on fetal growth should be assessed in males and females separately.

Abstract  Factors underlying metabolic phenotypes, such as the metabolically healthy but obese phenotype, remain unclear. Differences in metabolic phenotypes-particularly, among individuals with a similar body mass index-could be related to concentrations of persistent organic pollutants (POPs). To our knowledge, no studies have analyzed POPs and metabolic phenotypes in normal-weight persons. We investigated the relationships between serum concentrations of POPs and metabolic phenotypes in 860 normal-weight, overweight, and obese participants in the 2002 Catalan Health Interview Survey (Spain). POP concentrations were significantly higher in metabolically unhealthy than in metabolically healthy individuals. In models adjusting for body mass index and other confounders, hexachlorobenzene, β-hexachlorocyclohexane, and polychlorinated biphenyls were associated with the unhealthy metabolic phenotype and metabolic syndrome. Among normal-weight individuals, the adjusted prevalence ratio of having an unhealthy phenotype for the upper category of the sum of orders of the 6 mentioned POPs (all individually associated with metabolic phenotypes) was 4.1 (95% confidence interval: 1.7, 10.0). Among overweight and obese individuals, the corresponding prevalence ratio for the sum of polychlorinated biphenyls was 1.4 (95% confidence interval: 1.0, 1.8). Our results supported the hypothesis that POP concentrations are associated with unhealthy metabolic phenotypes, not only in obese and overweight individuals but also (and probably more strongly) in normal-weight individuals.

Abstract  Polychlorinated biphenyls (PCB) are well known persistent and toxic environmental pollutants. Our aim was to identify effects of moderate-high exposure to dioxin-like (dl) and non-dioxin-like (ndl)-PCBs on the skin in order to provide more insight in the pathophysiological effects of these compounds. We performed a dermatological examination on 92 former workers from a transformer recycling company with known elevated serum PCB and/or dioxin (polychlorinated dibenzo-p-dioxin/polychlorinated dibenzo-p-furan (PCDD/F)) levels. In addition, we performed a skin cancer screening over a period of seven years (2010-2016) on resp. 268, 271, 210, 149, 92, 129 and 79 participants. We found a higher incidence of acne and malignancies of the skin (malignant melanoma, basal cell carcinoma and mycosis fungoides) in the workers compared to normal population. The probability of having hyperpigmentation on the skin was statistically significantly higher in workers with higher sumPCBs- (OR:1.09(1.12-2.17)), dioxin-like (dl)-PCBs- (OR:1.56(1.12-2.17)) and dioxin (PCDD/Fs) (OR:1.09(1.02-1.16)) levels. Age was a confounding factor in this model. Formation of hyperpigmentation could be an indicator for (moderate-high) exposure to toxic compounds like PCBs. The higher incidence of cutaneous malignancies found in the workers might be associated with PCB- and dioxin exposure, warranting further investigation on larger cohorts.

Abstract  Background: Non-Hodgkin lymphoma (NHL) is the most common hematologic malignancy in the world. Involvement of organochlorines has been proposed in disease etiology. No study has investigated organochlorine exposure in relation to survival after a NHL diagnosis.Methods: In a survivor cohort consisting of 232 NHL cases from the Danish Diet, Cancer and Health cohort, we examined the association between adipose tissue organochlorine concentrations [polychlorinated biphenyls (PCBs) and pesticides] and subsequent survival, using Cox proportional hazards models.Results: We found no statistically significant association between organochlorine concentrations and subsequent survival. If anything, there was a nonsignificant tendency toward an inverse association with PCBs, but not pesticides.Conclusions: In conclusion, the current study does not support an increased risk of death among NHL patients with high tissue concentrations of organochlorines.Impact: This is the first study to investigate adipose organochlorine concentrations and survival after a NHL diagnosis. Cancer Epidemiol Biomarkers Prev; 27(2); 224-6. ©2017 AACR.

Abstract  BACKGROUND: Endocrine disrupting chemicals (EDCs) present in the environment may disrupt thyroid hormones, which in early life are essential for brain development. Observational studies regarding this topic are still limited, however as the presence of chemicals in the environment is ubiquitous, further research is warranted. The objective of the current study was to assess the association between exposure markers of various EDCs and thyroxine (T4) levels in newborns in a mother-child cohort in the Netherlands.

METHODS: Exposure to dichlorodiphenyldichloroethylene (DDE), three di-2-ethylhexyl phthalate (DEHP) metabolites, hexachlorobenzene (HCB), polychlorinated biphenyl (PCB)-153, perfluorooctanesulfonic acid (PFOS), and perfluorooctanoic acid (PFOA) was determined in cord plasma or breast milk, and information on T4 levels in heel prick blood spots was obtained through the neonatal screening programme in the Netherlands. Linear regression models were composed to determine associations between each of the compounds and T4, which were stratified for gender and adjusted for a priori defined covariates.

RESULTS: Mean T4 level was 86.9 nmol/L (n = 83). Girls in the highest quartile of DDE and PFOA exposure showed an increased T4 level compared to the lowest quartile with both crude and fully adjusted models (DDE > 107.50 ng/L, +24.8 nmol/L, 95% CI 0.79, 48.75; PFOA > 1200 ng/L, +38.6 nmol/L, 95% CI 13.34, 63.83). In boys a lower T4 level was seen in the second quartile of exposure for both PFOS and PFOA, however after fully adjusting the models these associations were attenuated. No effects were observed for the other compounds.

CONCLUSION: DDE and perfluorinated alkyl acids may be associated with T4 in a sex-specific manner. These results should however be interpreted with caution, due to the relatively small study population. More research is warranted, as studies on the role of environmental contaminants in this area are still limited.

Abstract  Primitive electronic-waste recycling resulted in serious pollution of polychlorinated biphenyls (PCBs) in the environment of Guiyu, China. We aimed to assess body burdens of PCBs and potential health risks for neonates. Umbilical cord blood (UCB) samples were collected from Guiyu, and the control area of Chaonan, China. PCBs in UCB were determined by gas chromatography coupled with mass spectrometry. The median ∑PCBs concentration was 338.56 ng g⁻¹ lipid in UCB samples from Guiyu, vs. 140.16 ng g⁻¹ lipid in samples from Chaonan. Mothers' involvement in electronic-waste recycling activities and house used as family workshop were the significant factors that contributed to ∑PCBs level. Some individual PCB congeners were found to correlate with reduced neonatal height, weight, Apgar scores, gestational age, and body mass index (BMI). Difference of ∑PCBs level was found between normal birth and adverse birth outcomes. Neonates from Guiyu are exposed to high levels of PCBs; prenatal exposure to PCBs appears to influence neonatal health, but still needs further confirmation.

Abstract  Correlations of blood polychlorinated biphenyl (PCB) levels or PCB patterns and blood pressures were studied in 59 patients with yusho (PCB poisoning) above 40 years old. In spite of the passage of 13 years from the onset, 52.5% of these patients still have PCB levels higher than the range found in the general population. The frequency of hypertension in the patients was 16.9%, a value similar to that expected on the basis of the rate for a population of the same age and sex compositions. As an independent variable, the blood pressure of patients was not associated with blood PCB levels and PCB patterns. No PCB blood pressure association was confirmed in 20 patients with PCB levels persistently higher than 5 ppb for 9 years. On the other hand, age, obesity and habitual alcohol intake, known influencing factors for hypertension, tended to be positively associated with elevated blood pressure in these yusho patients.

Abstract  BACKGROUND: Polychlorinated biphenyls (PCBs) have been hypothesized to increase the risk of non-Hodgkin lymphoma (NHL), although conclusive evidence is still lacking. High levels of PCBs were found in soil in some areas close to a PCB-producing factory in Brescia, North Italy. We conducted a population-based case-control study among residents of the town to investigate the possible association between PCB pollution and NHL in this area.

METHODS: We included both incident and deceased NHL cases, and a random sample of the town residents as controls, frequency matched to cases as regards age and gender. Exposure to PCBs was estimated on the basis of the lifetime residential history of cases and controls in four different areas of the town-A, B and C (polluted areas) and D (control area).

RESULTS: A total of 495 cases (287 incident cases) and 1467 controls were enrolled. Positive associations were found between NHL and having resided for at least 10 years in the area A, the most polluted area (odds ratio, OR=1.8; p=0.02) and for having resided in any of the polluted areas considered together (A+B+C) (OR=1.4; p=0.08). However, no associations were evident for having resided 20 years or longer in the polluted areas or when analyzing the association with each subject's main residence in his/her lifetime.

CONCLUSION: This study provides some evidence for an association between PCB exposure and NHL, though results should be considered with caution in the absence of individual biological measures of exposure.

Abstract  Prenatal exposure to endocrine disrupting chemicals may affect fetal development through disruption of hormonal actions and epigenetic modifications, potentially predisposing individuals to later on-set health risks, such as obesity. The objective of this study was to determine associations between biological exposure markers of various endocrine disrupting chemicals and birth weight in a newly established, prospective mother-child cohort in the Netherlands. Birth weight (n = 91) was obtained from birth records, and exposure to dichlorodiphenyldichloroethylene (DDE), three di-2-ethylhexyl phthalate (DEHP) metabolites, polychlorinated biphenyl-153, perfluorooctanesulfonic acid (PFOS), and perfluorooctanoic acid (PFOA) was determined in cord plasma. For DDE, exposure was also measured in breast milk. Linear regression analysis was used to determine associations between compounds and birth weight, which were stratified for gender and adjusted for a priori defined covariates. Increased exposure to DDE was associated with lower birth weight in boys (>95.89 ng L(-1), -325.9 g, 95% CI -634.26 to -17.56), whereas in girls a tendency towards a higher birth weight was observed. Lower birth weights for boys were also observed for high exposure to MECPP, and to a certain extent also for PFOA. MEHHP and PFOS exposure on the other hand were associated with higher birth weights in boys. In girls no effects were observed for these compounds. It can be concluded that prenatal exposure to DDE, perfluorinated alkyl acids, and phthalates was associated with changes in birth weight in this population. Associations were gender specific, and appeared to be non-linear. Since the population was relatively small, results should be interpreted with caution.

Abstract  In utero co-exposure to endocrine disrupting compounds can perturb fetal development. However, the effect of co-exposure on pivotal regulatory genes has seldom been investigated. We explored the effects of in utero co-exposure to cadmium (Cd), bisphenol A (BPA) and polychlorinated biphenyls (PCBs) on master regulator genes. We recruited 284 healthy pregnant women, of whom 262 provided both cord blood and placenta samples, and 200 had all measurements taken. Placental Cd, cord blood BPA and total PCBs in the exposed group were higher than a reference group. KISS1 expression level in placental tissue was threefold higher in the exposed group than in the reference, and was positively associated with all toxicants. Leptin and leptin receptor expression were also significantly higher, but were only associated with BPA. From our findings, we conclude that lower birth weight is correlated with Cd and PCBs, and may result from the increased KISS1 mRNA expression.

Abstract  BACKGROUND: Although prenatal methylmercury exposure has been linked to poorer intellectual function in several studies, data from two major prospective, longitudinal studies yielded contradictory results. Associations with cognitive deficits were reported in a Faroe Islands cohort, but few were found in a study in the Seychelles Islands. It has been suggested that co-exposure to another contaminant, polychlorinated biphenyls (PCBs), may be responsible for the positive findings in the former study and that co-exposure to nutrients in methylmercury-contaminated fish may have obscured and/or protected against adverse effects in the latter.

OBJECTIVES: We aimed to determine the degree to which co-exposure to PCBs may account for the adverse effects of methylmercury and the degree to which co-exposure to docosahexaenoic acid (DHA) may obscure these effects in a sample of Inuit children in Arctic Québec.

METHODS: IQ was estimated in 282 school-age children from whom umbilical cord blood samples had been obtained and analyzed for mercury and other environmental exposures.

RESULTS: Prenatal mercury exposure was related to poorer estimated IQ after adjustment for potential confounding variables. The entry of DHA into the model significantly strengthened the association with mercury, supporting the hypothesis that beneficial effects from DHA intake can obscure adverse effects of mercury exposure. Children with cord mercury ≥ 7.5 μg/L were four times as likely to have an IQ score < 80, the clinical cut-off for borderline intellectual disability. Co-exposure to PCBs did not alter the association of mercury with IQ.

CONCLUSIONS: To our knowledge, this is the first study to document an association of prenatal mercury exposure with poorer performance on a school-age assessment of IQ, a measure whose relevance for occupational success in adulthood is well established. This association was seen at levels in the range within which many U.S. children of Asian-American background are exposed.