Abstract  HEEP COPYRIGHT: BIOL ABS. The dermatological, medical and laboratory findings of patients poisoned with PCB (polychlorinated biphenyl) and related compounds in Taiwan (Yusho poisoning). Together with their symptoms, skin lesions and hematological, immunological and other clinical features were explained. A grading of clinical severity was tried, and its possible association with PCB concentrations in the blood was examined but could not be demonstrated. Various treatments were applied but without success. A follow-up study of patients 1 yr later showed that ? 38% of patients were clinically improved, while 54% were not altered.

Abstract  For understanding the possible role of PCBs in breast cancer induction we have to 1. Unravel the mechanisms of PCB carcinogenesis, 2. Investigate whether these mechanisms occur in the breast. We found that: i. 4- chlorobiphenyl is an initiator in rat liver; ii. Human breast tissue is qualitatively able to metabolically activate PCBs similarly as the liver; iii. in mouse liver PCBs are activated to metabolites that bind to nuclear protein and DNA; the structure of the adduct still needs to be determined; iv. PCB quinone and hydroquinone metabolites bind to DNA in vitro, deplete intracellular glutathione and produce reactive oxygen species (ROS) in cells in culture; v. PCB treatment results in the activation of transcription factors, 8-OH-d and formation, and increase in lipid peroxidation derived endogenous polar DNA adducts in rat liver; vi. PCBs produce oxidative stress by redox reactions of the metabolites or/and by changes in the levels of anti-oxidant enzymes and cofactors; vii. Human breast tissue varies greatly in pro-/anti-oxidant enzyme activity. Oxidative stress could be the major factor in PCB carcinogenesis. Therefore we will analyze oxidative stress in breast tissue after PCB treatment, and try to identify enzymatic risk factors for PCB carcinogenesis in women.

Abstract  BACKGROUND: Polychlorinated biphenyls (PCBs) may interact with several thyroid functions. Severe environmental pollution by PCBs has been observed in Brescia, Italy, due to the presence of a factory that produced these compounds until 1984.

OBJECTIVES: We aimed to investigate the correlation between serum levels of total PCBs and PCB 153 and thyroid hormone serum levels in adults in a cross-sectional population-based study.

METHODS: A total of 527 subjects were enrolled; they were face-to-face interviewed about their history of thyroid disease and provided a blood sample under fasting conditions. The serum levels of free and total triiodothyronine (FT3 and TT3), thyroxine (FT4 and TT4) and thyroid-stimulating hormone (TSH), anti-thyroperoxidase (anti-TPO) and anti-thyroglobulin (anti-TGA), and lipid-adjusted total PCBs and PCB 153 were determined.

RESULTS: There was no statistically significant difference in total PCB and PCB 153 concentrations in subjects with and without thyroid disease. Inverse, weak, statistically significant correlations were found between total PCBs and FT3 (Spearman's r=-0.09) and between total PCBs and PCB 153 and TSH (Spearman's r=-0.16 and -0.12, respectively). However, multiple regression analysis with FT3 and TSH serum levels as dependent variables and total PCBs and PCB 153 serum levels as predictors, including age, gender and BMI, showed a positive, rather than negative, association of PCBs and PCB 153 with FT3 and no association with TSH.

CONCLUSIONS: This study does not support the hypothesis that relatively high PCB environmental exposure can determine substantial alterations in thyroid function among adult people.

Abstract  We examined plasma dichlorodiphenyldichloroethene (DDE) and total polychlorinated biphenyl (PCB) levels in relation to breast cancer in a population-based, case-control study of African-American women (292 cases and 270 controls) and white women (456 cases and 389 controls) in North Carolina. Adjusted odds ratios (ORs) for breast cancer comparing the highest to lowest third of DDE were 1.41 [95% confidence interval (CI), 0.87-2.29] in African-American women and 0.98 (95% CI, 0.67-1.43) in white women. ORs comparing the highest to lowest third of total PCBs were 1.74 (95% CI, 1.00-3.01) in African-American women and 1.03 (95% CI, 0.68-1.56) in white women. Among African-Americans, the OR for total PCBs was highest for obese women (body mass index 234.2; OR, 4.92; 95% CI, 1.63-14.83). In contrast, the OR for DDE was highest for the leanest African-American women (body mass index, <25; OR, 3.84; 95% CI, 0.98-15.08). ORs for DDE were not elevated among women who lived or worked on farms or elevated among farming women who reported exposure to pesticides. Our results suggest absence of a strong effect for DDE or total PCBs in breast cancer but lend support for associations among subgroups of women. In our study, factors such as income, parity, breastfeeding, race/ethnicity, and body mass index influenced the relationship of organochlorines and breast cancer. Differing distributions of such factors may explain some of the inconsistencies across previous studies.

Abstract  A national survey of polychlorinated dibenzo-p-dioxins (PCDD) and dibenzofurans (PCDF) in emission gases from the municipal waste incinerators in 1997 revealed that the Nose Bika Center was heavily contaminated by PCDF. Ninety-four workers underwent a physical examination, and blood biochemistry, lymphocyte marker, and NK activity studies were carried out, along with blood dioxin measurements. Information on working history, life-style, and dietary habits was obtained by questionnaire and interview. The blood dioxin levels were as follows. The median TEQ of dioxins was 39.7 pg I-TEQ/g lipid, and the range was 13.3 to 805.8. The median 2,3,7,8-TCDD concentration was 3.9 pg TEQ/g lipid, and the range was <1 pg TEQ/g lipid (one case) to 13.4 pg TEQ/g lipid. The median TEQ of coplanar PCB was 10.8 pg I-TEQ/g lipid, and the range was 3.1 to 54.2 pg TEQ/g lipid. The congener-specific distribution was quite similar to that in soil around incinerator and waste in the factory. The relationship between dioxin concentrations and work history in the factory showed that the fluidized incinerator and fly ash treatment areas were high-risk work areas. Correlation analyses between body burden, PCDD/PCDF TEQ, Co-PCB TEQ and various laboratory data showed significant positive correlations between dioxin levels and GGT, total protein, uric acid and calcium, and a negative correlation with Fe. However, these correlations disappeared as a result of multivariate analysis adjusted for age, smoking status, and alcohol drinking. Increased NK activity and lower response to PHA stimulation remained significant even after adjusting for age. History of hyperlipidemia and allergy had significantly increased odds ratios. A study on the risk to other workers in the same type of incinerators is under way. Health effects of chronic exposure mainly to PCDF will be clarified by follow-up.

Abstract  Experimental studies show that hormonal and nonhormonal activities of polychlorinated biphenyls (PCBs) are structure dependent, suggesting that the breast cancer risk associated with PCBs may vary according to specific PCB congeners. In 1994-1997, the authors conducted a case-control study of Connecticut women to investigate whether breast cancer risk is associated with body burden of PCBs and varies by PCB congeners. A total of 304 breast cancer cases and 186 controls aged 40-79 years were recruited into the study. Fresh breast adipose tissue was analyzed for PCBs. The age- and lipid-adjusted geometric mean tissue levels of total PCBs were not significantly different (p = 0.46) for the cases (478.6 parts per billion) and controls (494.1 parts per billion). The covariate-adjusted odds ratio was 0.7 (95% confidence interval: 0.4, 1.1) for all study participants when the third tertile was compared with the lowest tertile. No individual congeners or groups of congeners were associated with a significantly increased risk of breast cancer. Further stratification by type of breast disease; menopausal, parity, and lactation status; and body size also showed no significant association with body levels of PCBs. These results suggest that environmental exposure to PCBs may not substantially affect breast cancer risk.

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  Background and objective: Yusho occurred in western Japan in 1968 and was caused by ingestion of rice bran oil that was contaminated with polychlorinated biphenyls (PCBs) and dioxins such as polychlorinated dibenzofurans (PCDFs). At that time, the skin symptoms presented by patients with Yusho were at their most prominent and worst severity. Analysis of blood to determine the concentration of dioxins started in 2001 in Fukuoka prefecture, and in 2002 the examination was performed throughout Japan. There have been no reports on the relationship between blood concentration of dioxins and skin symptoms in Yusho. This is the first report to examine the relationship between blood concentration of dioxins and skin symptoms in Yusho, using statistical analyses. Methods: Using the global skin severity grade, we analyzed the change in skin symptoms, which were examined at the annual medical check-up of patients with Yusho. We also investigated the relationship between the items of the annual dermatological examination and blood concentrations of total PCDFs; and total PCBs. Results: The severity of skin symptoms improved significantly in the first 20 years; nowadays, however, further improvement can hardly be observed. Using three-way analysis of variance (ANOVA), we found that of the 21 items of the dermatological examination, nine were significantly related to total PCDFs, and five were related to total PCBs. Only one item was significantly related both to total PCDFs and total PCBs. Conclusion: More than 36 years have passed since the Yusho incident, and about 60% of the patients currently present with no skin symptoms. In contrast, in about 40% of the patients, characteristic skin symptoms of Yusho, such as pigmentation of skin, black comedones and acneform eruptions, could stilt be observed. Our analysis of the relationship between skin symptoms and blood concentrations of total PCDFs and total PCBs proves that not only PCBs but also PCDFs have an important role in the skin symptoms of Yusho. (C) 2004 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

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  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  BACKGROUND: Pregnant women are exposed to a mixture of endocrine disrupting chemicals (EDCs). Gestational EDC exposures may be associated with changes in fetal growth that elevates the risk for poor health later in life, but few studies have examined the health effects of simultaneous exposure to multiple chemicals. This study aimed to examine the association of gestational exposure to five chemical classes of potential EDCs: phthalates and bisphenol A, perfluoroalkyl substances (PFAS), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and organochlorine pesticides (OCPs) with infant birth weight.

METHODS: Using data from the Health Outcomes and Measures of Environment (HOME) Study, we examined 272 pregnant women enrolled between 2003-2006. EDC concentrations were quantified in blood and urine samples collected at 16 and 26 weeks gestation. We used Bayesian Hierarchical Linear Models (BHLM) to examine the associations between newborn birth weight and 53 EDCs, 2 organochlorine pesticides (OPPs) and 2 heavy metals.

RESULTS: For a 10-fold increase in chemical concentration, the mean differences in birth weights (95% credible intervals (CI)) were 1 g (-20, 23) for phthalates, -11 g (-52, 34) for PFAS, 0.2 g (-9, 10) for PCBs, -4 g (-30, 22) for PBDEs, and 7 g (-25, 40) for OCPs.

CONCLUSION: Gestational exposure to phthalates, PFAS, PCBs, PBDEs, OCPs or OPPs had null or small associations with birth weight. Gestational OPP, Pb, and PFAS exposures were most strongly associated with lower birth weight.

Abstract  BACKGROUND: In 1973-1974, Michigan residents were exposed to polybrominated biphenyls (PBBs) through an accidental contamination of the food supply. Residents were enrolled in a registry assembled after the incident, and they and their children participated in follow-up studies to assess subsequent health outcomes.

OBJECTIVES: We evaluated associations between serum PBBs and polychlorinated biphenyls (PCBs) and markers of thyroid function among Michigan adults.

METHODS: Serum concentrations of four PBB and four PCB congeners were measured at least once in 753 adults, including 79 women who participated in a 2004-2006 study and 683 women and men with follow-up during 2012-2015. Participants completed questionnaires on health conditions (including physician-diagnosed thyroid disease), behaviors, and demographics. Thyroid hormones were measured in a subset without thyroid disease (n=551). In multivariable linear regression models, PBB and PCB congener concentrations, on both the volume (nanogram/milliliter) and lipid (nanogram/gram lipid) basis, were assessed in relation to thyroid hormones. Logistic regression models were used to estimate associations between serum PBBs and PCBs and thyroid disease.

RESULTS: Thyroid disease was common (18% overall; 25% among women). Among women, all odds ratios (ORs) for PBB-153 and thyroid disease were positive for quintiles above the reference level, but estimates were imprecise and were without a monotonic increase. For an interquartile range (IQR) increase in PBB-153 (0.43 ng/mL), the OR (any thyroid disease)=1.12; (95% CI: 0.83, 1.52) (n=105 cases); for hypothyroidism, OR=1.35 (95% CI: 0.86, 2.13) (n=49 cases). There were 21 cases of thyroid disease in men [OR=0.69 (95% CI: 0.33); 1.44 for an IQR increase (0.75 ng/mL) in serum PBB-153]. PCB congeners were statistically significantly associated with greater total and free thyroxine and total triiodothyronine among women and with total and free triiodothyronine among men in lipid-standardized models.

CONCLUSIONS: We found some evidence to support associations of PBBs and PCBs with thyroid disease and thyroid hormone levels. https://doi.org/10.1289/EHP1302.

Abstract  BACKGROUND: Organohalogen compounds (OHCs), i.e. polychlorinated biphenyls (PCBs, are wide-spread environmental pollutants known to be neurotoxic for the developing brain. The hydroxylated metabolites of PCBs, OH-PCBs, might be even more toxic due to their structure and interference with thyroid hormone metabolism. We found that prenatal exposure to OH-PCBs was associated with thyroid hormone metabolism at toddler age. Little, however, is known about the neurotoxicity of OH-PCBs in humans.

OBJECTIVES: To determine whether prenatal background exposure to OHCs has an effect on mental and motor development in children at the age of 18 and 30 months.

METHODS: One hundred and eighty-one healthy mother-infant pairs were included in this observational study performed in the Netherlands. We measured maternal pregnancy levels of PCB-153 and three OH-PCBs. In one part of the cohort we measured another nine PCBs and three OH-PCBs and in the other part we measured five brominated diphenyl ethers (BDEs), dichloro-diphenyldichloroethylene (p,p'-DDE), pentachlorophenol (PCP), and hexabromocyclododecane (HBCDD). We used the mental development index (MDI) and the motor development index (PDI) of the Bayley Scales of Infant Development II (BSID-II) to assess children's mental and motor development (mean = 100; delayed score <85).

RESULTS: Higher prenatal PCB-153 levels were associated with a delayed MDI score at 18 months. None of the other compounds were associated with a delayed score, but several associations were found between OHC levels and BSID-II scores. The sum of all six OH-PCBs and three individual OH-PCBs, 4-OH-PCB-107, 3-OH-PCB-153, and 4'-OH-PCB-172, correlated positively with MDI at 30 months. The compound 3'-OH-PCB-138 showed a similar trend. A higher 4-OH-PCB-187 was associated with a lower MDI at 18 months. We found a similar trend for higher BDE-99. Higher BDE levels were associated with higher PDI at 18 months. The levels of p,p'-DDE-, PCP, and HBCDD were not associated with BSID-II scores at 18 months.

CONCLUSIONS: Higher prenatal levels of PCB-153 were associated with a delayed MDI score at 18 months. None of the other compounds were associated with a delayed score, but several associations were found between OHC levels and BSID-II scores. Prenatal OH-PCBs were positively associated with mental development at 30 months, whereas one OH-PCB was negatively associated at 18 months. BDE levels were positively associated with psychomotor development. Prenatal p,p'-DDE, PCP, and HBCDD levels were not associated with neurodevelopment at 18 months.

Abstract  OBJECTIVES: Exposome-wide association studies (EWAS) are a systematic and unbiased way to investigate multiple environmental factors associated with phenotype. We applied EWAS to study semen quality and queried the sample size requirements to detect modest associations in a reproductive cohort.

STUDY DESIGN AND SETTING: We conducted 1) a multivariate EWAS of 128 endocrine disrupting chemicals (EDCs) from 15 chemical classes measured in urine/serum relative to 7 semen quality endpoints in a prospective cohort study comprising 473 men and 2) estimated the sample size requirements for EWAS etiologic investigations.

RESULTS: None of the EDCs were associated with semen quality endpoints after adjusting for multiple tests. However, several EDCs (e.g., polychlorinated biphenyl congeners 99, 105, 114, and 167) were associated with raw p < 0.05. In a post hoc statistical power analysis with the observed effect sizes, we determined that EWAS research in male fertility will require a mean sample size of 2696 men (1795-3625) to attain a power of 0.8. The average size of four published studies is 201 men.

CONCLUSION: Existing cohort studies with hundreds of participants are underpowered (<0.8) for EWAS-related investigations. Merging cohorts to ensure a sufficient sample size can facilitate the use of EWAS methods for assessing EDC mixtures that impact semen quality.

Abstract  To improve the applicability of the toxic equivalents principle for human health risk assessment, systemic relative effect potencies (REPs) for dioxin-like compounds (DLCs) deriving from human in vivo data are required. A prospective nested case-control study was performed to determine REPs from the human serum concentration of DLCs using gestational diabetes mellitus (GDM) and fasting blood glucose (FBG) as the end points of concern. Serum concentration of 29 DLCs from 77 cases and 154 controls were measured. Logistic and linear regression were used to estimate the effects of individual congeners on GDM and FBG, respectively. The REPs based on GDM and FBG were calculated from the ratios of regression coefficients, βi (DLCs)/βTCDD. Two sets of consistent human serum-based REPs, that is, GDM-REP and FBG-REP, were established and largely agree with REPs from other human studies. These human-serum REPs show much smaller variation compared to the 4 to 5 orders of magnitude span in REPs database for the present WHO-TEF determination. Moreover, the established REPs fitted well with WHO-TEFs, especially for polychlorinated dibenzo- p-dioxins, furans. These REPs reflecting real human exposure scenarios exhibited validity and could be used to improve health risk assessment of human body burden of DLCs.

Abstract  BACKGROUND: Some evidence in humans suggests that persistent organic pollutants (POPs), including organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs), may alter the blood lipid composition. This study analyzed associations between serum POPs concentrations in young adulthood with blood lipid levels up to 23 years later.

METHODS: Serum POPs were measured in year 2 of follow-up (n = 180 men and women, ages: 20-32y), and plasma lipids in follow-up years 2, 7, 10, 15, 20 and 25. 32 POPs were detectable in ≥75% of participants (23 PCBs, 8 OCPs and PBB-153). We created summary scores for PCBs and OCPs for both wet-weight, and lipid standardized (LP) concentrations. We used repeated measures regression adjusting for demographic factors, BMI, smoking, diabetes status, among others.

RESULTS: We observed positive associations of the 23 LP-PCB score with total cholesterol (βper SD increase [95%CI]: 5.0 mg/dL [0.7, 9.2]), triglycerides (7.8 mg/dL [-0.9, 16.5]), LDL (4.2 mg/dL [0.2, 8.2]), oxidized LDL 3.4 U/L (-0.05, 6.8), and cholesterol/HDL ratio (0.2 [0.02, 0.3]). The associations for triglycerides (14.7 mg/dL [0.4, 20.1]), cholesterol/HDL (0.33 [0.09, 0.56]) and, to some extent, LDL (4.7 md/dL [-1.6, 10.9]) were only observed among participants in the upper 50th percentile of BMI. Non-dioxin-like PCBs had stronger associations that dioxin-like PCBs. OCPs and PBB-s had positive associations with most outcomes.

CONCLUSIONS: PCBs and PBB-153 measured in young adulthood were positively associated with prospective alterations in most blood lipid components, with evidence of effect modification by BMI. Further longitudinal studies with multiple measures of POPs overtime are needed.

Abstract  INTRODUCTION AND OBJECTIVE: Polychlorinated biphenyls (PCBs) have been used commercially since 1929 as dielectric and insulating non-flammable substances, additives for paints, etc. In Slovakia, 60 chemical production workers highly exposed to PCBs (mainly to Delor 103) were studied with duration of exposure ranging from 3 months to 19 years.

MATERIAL AND METHODS: Clinical examinations of skin, skin histology and laboratory tests concerning lipid metabolism, iron metabolism and levels of copper provided comparisons with a control group of healthy individuals and/or the upper limits of normal values.

RESULTS: Skin changes were found in 47 % of individuals. In most cases, milia-like efflorescences (57.14 %) occurred, as well as comedones (55.35 %); other symptoms occurred in a smaller number of workers. Hyperkeratosis, acanthosis of the epidermis (particularly in hair follicles), and a cellular infiltration of the corium were all found through histology. The intensity of cutaneous affections was associated with the changes in laboratory tests. Elevated triglycerides, cholesterol, and phospholipids were found in exposed workers. After a further two years, a significant increase in triglycerides was found in exposed individuals when compared with the control group. In addition, a significant increase in serum levels of copper, and total and unsaturated iron-binding capacity was detected.

CONCLUSIONS: Anamnesis showed that some people directly exposed to PCBs may develop skin changes after three months of occupational exposure. The results represent a unique snapshot of worker exposure at a given location, representing the basis for comparison with the population who grew up in the area and still live there today.

Abstract  Introduction Exposure to mixtures of environmental chemicals are prevalent among pregnant women and may be associated with altered fetal growth and gestational age. To date, most research regarding environmental chemicals and neonatal outcomes has focused on the effect of individual agents. Methods In a prospective cohort of 380 pregnant women from Cincinnati, OH (enrolled 2003–2006), we used biomarkers to estimate exposure to 43 phenols, phthalates, metals, organophosphate/pyrethroid/organochlorine pesticides, polychlorinated biphenyls, polybrominated diphenyl ethers, perfluoroalkyl substances (PFAS), and environmental tobacco smoke. Using three approaches, we estimated covariate-adjusted associations of chemical mixtures or individual chemicals with gestational-age-specific birth weight z-scores, birth length, head circumference, and gestational age: k-means clustering, principal components (PC), and one-chemical-at-a-time regression. Results We identified three chemical mixture profiles using k-means clustering. Women in cluster 1 had higher concentrations of most phenols, three phthalate metabolites, several metals, organophosphate/organochlorine pesticides, polychlorinated biphenyls, and several PFAS than women in clusters 2 and 3. On average, infants born to women in clusters 1 (-1.2?cm; 95% CI: -1.9, -0.5) and 2 (-0.5?cm; 95% CI: -1.1, 0.1) had lower birth length than infants in cluster 3. Six PCs explained 50% of the variance in biomarker concentrations and biomarkers with similar chemical structures or from shared commercial/industrial settings loaded onto commons PCs. Each standard deviation increase in PC 1 (organochlorine pesticides, some phenols) and PC 6 (cadmium, bisphenol A) was associated with 0.2?cm (95% CI: -0.4, 0.0) and 0.1?cm (95% CI: -0.4, 0.1) lower birth length, respectively. Organochlorine compounds, parabens, and cadmium were inversely associated with birth length in the one-chemical-at-a-time analysis. Cluster membership, PC scores, and individual chemicals were not associated with other birth outcomes. Conclusion All three methods of characterizing multiple chemical exposures in this cohort identified inverse associations of select organochlorine compounds, phenols, and cadmium with birth length, but not other neonatal outcomes.

Abstract  Background: Environmental exposures in early life influence the development of behavioral outcomes in children, but research has not considered multiple exposures. We therefore aimed to investigate the impact of a broad spectrum of pre- and postnatal environmental exposures on child behavior. Methods and findings: We used data from the HELIX (Human Early Life Exposome) project, which was based on six longitudinal population-based birth cohorts in Europe. At 6-11 years, children underwent a follow-up to characterize their exposures and assess behavioral problems. We measured 88 prenatal and 123 childhood environmental factors, including outdoor, indoor, chemical, lifestyle and social exposures. Parent-reported behavioral problems included (1) internalizing, (2) externalizing scores, using the child behavior checklist (CBCL), and (3) the Conner's Attention Deficit Hyperactivity Disorder (ADHD) index, all outcomes being discrete raw counts. We applied LASSO penalized negative binomial regression models to identify which exposures were associated with the outcomes, while adjusting for co-exposures. In the 1287 children (mean age 8.0 years), 7.3% had a neuropsychiatric medical diagnosis according to parent's reports. During pregnancy, smoking and car traffic showing the strongest associations (e.g. smoking with ADHD index, aMR:1.31 [1.09; 1.59]) among the 13 exposures selected by LASSO, for at least one of the outcomes. During childhood, longer sleep duration, healthy diet and higher family social capital were associated with reduced scores whereas higher exposure to lead, copper, indoor air pollution, unhealthy diet were associated with increased scores. Unexpected decreases in behavioral scores were found with polychlorinated biphenyls (PCBs) and organophosphate (OP) pesticides. Conclusions: Our systematic exposome approach identified several environmental contaminants and healthy lifestyle habits that may influence behavioral problems in children. Modifying environmental exposures early in life may limit lifetime mental health risk.

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  Polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) are common persistent organic pollutants (POPs) that may be associated with childhood asthma. The concentrations of PBDEs, PCBs and OCPs were analyzed in pooled serum samples from both asthmatic and non-asthmatic children. The differences in the internal exposure levels between the case and control groups were tested (p value <0.0012). The associations between the internal exposure concentrations of the POPs and childhood asthma were estimated based on the odds ratios (ORs) calculated using logistic regression models. There were significant differences in three PBDEs, 26 PCBs and seven OCPs between the two groups, with significantly higher levels in the cases. The multiple logistic regression models demonstrated that the internal exposure concentrations of a number of the POPs (23 PCBs, p,p'-DDE and α-HCH) were positively associated with childhood asthma. Some synergistic effects were observed when the children were co-exposed to the chemicals. BDE-209 was positively associated with asthma aggravation. This study indicates the potential relationships between the internal exposure concentrations of particular POPs and the development of childhood asthma.