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1.  Neurodevelopmental toxicity of prenatal polychlorinated biphenyls (PCBs) by chemical structure and activity: a birth cohort study 
Environmental Health  2010;9:51.
Background
Polychlorinated biphenyls (PCBs) are ubiquitous environmental toxins. Although there is growing evidence to support an association between PCBs and deficits of neurodevelopment, the specific mechanisms are not well understood. The potentially different roles of specific PCB groups defined by chemical structures or hormonal activities e.g., dioxin-like, non-dioxin like, or anti-estrogenic PCBs, remain unclear. Our objective was to examine the association between prenatal exposure to defined subsets of PCBs and neurodevelopment in a cohort of infants in eastern Slovakia enrolled at birth in 2002-2004.
Methods
Maternal and cord serum samples were collected at delivery, and analyzed for PCBs using high-resolution gas chromatography. The Bayley Scales of Infant Development -II (BSID) were administered at 16 months of age to over 750 children who also had prenatal PCB measurements.
Results
Based on final multivariate-adjusted linear regression model, maternal mono-ortho-substituted PCBs were significantly associated with lower scores on both the psychomotor (PDI) and mental development indices (MDI). Also a significant association between cord mono-ortho-substituted PCBs and reduced PDI was observed, but the association with MDI was marginal (p = 0.05). Anti-estrogenic and di-ortho-substituted PCBs did not show any statistically significant association with cognitive scores, but a suggestive association between di-ortho-substituted PCBs measured in cord serum and poorer PDI was observed.
Conclusion
Children with higher prenatal mono-ortho-substituted PCB exposures performed more poorly on the Bayley Scales. Evidence from this and other studies suggests that prenatal dioxin-like PCB exposure, including mono-ortho congeners, may interfere with brain development in utero. Non-dioxin-like di-ortho-substituted PCBs require further investigation.
doi:10.1186/1476-069X-9-51
PMCID: PMC2939589  PMID: 20731829
2.  Immunologic effects of background exposure to polychlorinated biphenyls and dioxins in Dutch preschool children. 
Environmental Health Perspectives  2000;108(12):1203-1207.
Prenatal exposure to polychlorinated biphenyls (PCBs) and dioxins is associated with changes in the T-cell lymphocyte population in healthy Dutch infants. We investigated whether these changes persist into later childhood and whether background exposure to PCBs and dioxins is associated with the prevalence of infectious or allergic diseases and humoral immunity at preschool age. The total study group consisted of 207 healthy mother-infant pairs. We estimated prenatal exposure to PCBs and dioxins by the sum of PCBs 118, 138, 153, and 180 (sigmaPCB) in maternal and cord plasma and in breast-fed infants by the dioxin, planar, and mono-ortho PCB toxic equivalent (TEQ) levels in human milk. At 42 months of age, current body burden was estimated by the PCB in plasma. We assessed the prevalence of infectious and allergic diseases by parent questionnaire, and measured humoral immunity by antibody levels for mumps, measles, and rubella after primary vaccination. We performed immunologic marker analyses of lymphocytes in a subgroup of 85 children. Prenatal PCB exposure was associated with an increased number of lymphocytes, T-cells, and CD3CD8(+) (cytotoxic), CD4(+)CD45RO(+) (memory), T-cell receptor (TcR) [alpha]ss(+), and CD3(+)HLA-DR(+) (activated) T cells and lower antibody levels to mumps and measles at preschool age. Adjusted for confounders, prenatal PCB exposure was associated with less shortness of breath with wheeze, and current PCB body burden was associated with a higher prevalence of recurrent middle-ear infections and of chicken pox and a lower prevalence of allergic reactions. A higher dioxin TEQ was associated with a higher prevalence of coughing, chest congestion, and phlegm. We conclude that in Dutch preschool children the effects of perinatal background exposure to PCBs and dioxins persist into childhood and might be associated with a greater susceptibility to infectious diseases. Common infections acquired early in life may prevent the development of allergy, so PCB exposure might be associated with a lower prevalence of allergic diseases.
PMCID: PMC1240203  PMID: 11133402
3.  Prenatal Exposure to a Polychlorinated Biphenyl (PCB) Congener Influences Fixation Duration on Biological Motion at 4-Months-Old: A Preliminary Study 
PLoS ONE  2013;8(3):e59196.
Adverse effects of prenatal exposure to polychlorinated biphenyl (PCB) congeners on postnatal brain development have been reported in a number of previous studies. However, few studies have examined the effects of prenatal PCB exposure on early social development. The present study sought to increase understanding of the neurotoxicity of PCBs by examining the relationship between PCB congener concentrations in umbilical cord blood and fixation patterns when observing upright and inverted biological motion (BM) at four-months after birth. The development of the ability to recognize BM stimuli is considered a hallmark of socio-cognitive development. The results revealed a link between dioxin-like PCB #118 concentration and fixation pattern. Specifically, four-month-olds with a low-level of prenatal exposure to PCB #118 exhibited a preference for the upright BM over inverted BM, whereas those with a relatively high-level of exposure did not. This finding supports the proposal that prenatal PCB exposure impairs the development of social functioning, and indicates the importance of congener-specific analysis in the risk analysis of the adverse effects of PCB exposure on the brain development.
doi:10.1371/journal.pone.0059196
PMCID: PMC3610708  PMID: 23555630
4.  Predictors of serum dioxin levels among adolescent boys in Chapaevsk, Russia: A cross-sectional pilot study 
Background
Toxicological studies and limited human studies have demonstrated associations between exposure to polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and polychlorinated biphenyls (PCBs) and adverse developmental and reproductive health effects. Given that children may be particularly susceptible to reproductive and developmental effects of organochlorines, and the paucity of information available regarding childhood exposures to dioxins in particular, we undertook a pilot study to describe the distribution of, and identify potential predictors of exposure to, dioxin-like compounds and dioxins among adolescent boys in Chapaevsk, Russia. The pilot study was also designed to guide the development of a large prospective cohort study on the relationship of exposure to PCDDs, PCDFs, and PCBs with growth and pubertal development in peri-pubertal Chapaevsk boys.
Methods
221 boys age 14 to 17 participated in the pilot study. Each of the boys, with his mother, was asked to complete a nurse-administered detailed questionnaire on medical history, diet, and lifestyle. The diet questions were used to measure the current and lifetime consumption of locally grown or raised foods. Blood samples from 30 of these boys were sent to the Centers for Disease Control and Prevention (CDC) for analysis of dioxins, furans and PCBs.
Results
The median (25th, 75th percentile) concentrations for total PCDDs, PCDFs and coplanar PCBs were 95.8 pg/g lipids (40.9, 144), 33.9 pg/g lipids (20.4, 61.8), and 120 pg/g lipids (77.6, 157), respectively. For WHO-TEQs, the median (25th, 75th percentile) for total PCDDs, PCDFs, and coplanar PCBs were 0.29 (0.1, 9.14), 7.98 (5.27, 12.3), and 7.39 (4.51, 11.9), respectively. Although TCDD was largely non-detectable, two boys had high TCDD levels (17.9 and 21.7 pg/g lipid). Higher serum levels of sum of dioxin-like compounds and sum of dioxin TEQs were positively associated with increased age, consumption of fish, local meats other than chicken, PCB 118, and inversely with weeks of gestation.
Conclusion
The total TEQs among Chapaevsk adolescents were higher than most values previously reported in non-occupationally exposed populations of comparable or even older ages. Dietary consumption of local foods, as well as age and weeks of gestation, predicted dioxin exposure in this population.
doi:10.1186/1476-069X-4-8
PMCID: PMC1168904  PMID: 15918907
5.  Associations between Prenatal Exposure to Polychlorinated Biphenyls and Neonatal Thyroid-Stimulating Hormone Levels in a Mexican-American Population, Salinas Valley, California 
Environmental Health Perspectives  2007;115(10):1490-1496.
Background
Studies have reported that prenatal exposure to polychlorinated biphenyls (PCBs) may alter neurodevelopment in both humans and animals. Furthermore, prenatal exposure to some PCB congeners and commercial mixtures has been shown to decrease free and total thyroxine (T4) blood levels in animals. Because thyroid hormones (TH) are essential for normal neurologic development, it has been suggested that the deleterious neurodevelopmental effect of PCBs may occur through TH disruption. PCBs may in turn affect TH levels by inducing the microsomal enzyme uridinediphosphate glucuronosyltransferase (UDP-GT), which is involved in TH elimination.
Objectives
Our goals were to group PCB congeners based on their potential to induce microsomal enzymes in animals, and to examine the relationship between neonatal TSH levels and prenatal exposure to PCB congeners grouped according to their structure and potential mechanisms of action.
Methods
We measured the concentration of 34 PCB congeners in serum samples collected from 285 pregnant women and the thyroid-stimulating hormone (TSH) levels in their children’s blood collected shortly after birth.
Results
We found no association between the sum of PCB congeners, the toxic equivalents, or structure-based groupings (mono- or di-ortho substituted congeners), and TSH blood concentration. However, we found a positive association between the sum of congeners suspected to be UDP-GT inducers (more specifically cytochrome P450 2B inducers) in animals and neonatal TSH levels. In individual congener analyses, PCBs 99, 138, 153, 180, 183, 187, 194, and 199 were positively associated with neonatal TSH levels after adjustment for covariates. PCBs 194 and 199 remained significant after adjustment for multiple hypothesis testing.
Conclusions
Our results support grouping PCB congeners based on their potential mechanism of action of enzyme induction when investigating associations with TH. Findings also suggest that PCBs affect TH homeostasis even at the low background level of exposure found in the CHAMA-COS (Center for the Health Assessment of Mothers and Children of Salinas) population.
doi:10.1289/ehp.9843
PMCID: PMC2022659  PMID: 17938741
cytochrome P450; enzyme inducers; in utero; microsomal enzymes; neonatal; polychlorinated biphenyls; prenatal; thyroid hormone; TSH; UDP-glucuronosyltransferase
6.  Effects of perinatal exposure to PCBs and dioxins on play behavior in Dutch children at school age. 
Environmental Health Perspectives  2002;110(10):A593-A598.
Polychlorinated biphenyls (PCBs) and dioxins are known as neurotoxic compounds that may modulate sex steroid hormones. Steroid hormones play a mediating role in brain development and may influence behaviors that show sex differences, such as childhood play behavior. In this study we evaluated the effects of perinatal exposure to environmental levels of PCBs and dioxins on childhood play behavior and whether the effects showed sex differences. As part of the follow-up to the Dutch PCB/dioxin study at school age, we used the Pre-School Activity Inventory (PSAI) to assess play behavior in the Rotterdam cohort (n = 207). The PSAI assesses masculine or feminine play behavior scored on three subscales: masculine, feminine, and composite. Prenatal exposure to PCBs was defined as the sum of PCB 118, 138, 153, and 180 in maternal and cord plasma and breast milk. For breast milk we measured additional PCBs as well as 17 dioxins. Respondents returned 160 questionnaires (age 7.5 years +/- 0.4). Effects of prenatal exposure to PCBs, measured in maternal and cord plasma, on the masculine and composite scales were different for boys and girls (p <.05). In boys, higher prenatal PCB levels were related with less masculinized play, assessed by the masculine scale (p(maternal) =.042; p(cord) =.001) and composite scale (p(cord) =.011), whereas in girls higher PCB levels were associated with more masculinized play, assessed by the composite scale (p(PCBmilk) =.028). Higher prenatal dioxin levels were associated with more feminized play in boys as well as girls, assessed by the feminine scale (p =.048). These effects suggest prenatal steroid hormone imbalances caused by prenatal exposure to environmental levels of PCBs, dioxins, and other related organochlorine compounds.
PMCID: PMC1241045  PMID: 12361940
7.  Associations between congenital cryptorchidism in newborn boys and levels of dioxins and PCBs in placenta 
In animal studies, exposure to dioxins has been associated with disrupted development of the male reproductive system, including testicular maldescent. Some polychlorinated biphenyls (PCBs) have also dioxin-like effects. In addition, one previous case–control study has reported an association between congenital cryptorchidism and colostrum PCB levels. We performed a case–control study to evaluate whether congenital cryptorchidism in boys was associated with increased levels of dioxins or PCBs in placenta reflecting foetal exposure. In addition, associations between placenta levels of these chemicals and reproductive hormone levels in boys at 3 months were studied. Placentas were collected in a Danish–Finnish joint prospective cohort study on cryptorchidism (1997–2001). The boys were examined for cryptorchidism at birth and at 3 months. Altogether, 280 placentas [112 Finnish (56 cases, 56 controls) and 168 Danish (39 cases, 129 controls)] were analysed for 17 toxic polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and 37 PCBs (including 12 dioxin-like PCBs). Infant serum samples taken at 3 months were analysed for reproductive hormones. No significant differences between cases and controls were observed in either country in dioxin WHO-TEq levels (median 9.78 vs. 8.47 pg/g fat, respectively, in Finland, and 11.75 vs. 10.88 pg/g fat in Denmark) or PCB WHO-TEq levels (median 2.12 vs. 2.15 pg/g fat in Finland, 2.34 vs. 2.10 pg/g fat in Denmark) or total-TEq levels (median 11.66 vs. 10.58 pg/g fat in Finland, 13.94 vs. 13.00 pg/g fat in Denmark). Placenta WHO-TEq levels of dioxins were not associated with infant reproductive hormone levels at 3 months. In Finland, PCB WHO-TEq levels in placenta associated positively with infant LH levels. WHO-TEq levels of dioxins and PCBs and total-TEq levels were higher in Danish than Finnish samples. In conclusion, no association between placenta levels of dioxins or PCBs and congenital cryptorchidism was found. Significant country differences in chemical levels were observed.
doi:10.1111/j.1365-2605.2011.01233.x
PMCID: PMC3417377  PMID: 22150420
cryptorchidism; dioxins; PCBs; placenta; testis
8.  Domain-Specific Effects of Prenatal Exposure to PCBs, Mercury, and Lead on Infant Cognition: Results from the Environmental Contaminants and Child Development Study in Nunavik 
Environmental Health Perspectives  2014;122(3):310-316.
Background: Polychlorinated biphenyls (PCBs), methylmercury (MeHg), and lead (Pb) are environmental contaminants known for their adverse effects on cognitive development.
Objectives: In this study we examined the effects of prenatal exposure to PCBs, MeHg, and Pb on cognitive development in a sample of Inuit infants from Arctic Québec.
Methods: Mothers were recruited at local prenatal clinics. PCBs, mercury (Hg), Pb, and two seafood nutrients—docosahexaenoic acid (DHA) and selenium (Se)—were measured in umbilical cord blood. Infants (n = 94) were assessed at 6.5 and 11 months of age on the Fagan Test of Infant Intelligence (FTII), A-not-B test, and Bayley Scales of Infant Development–2nd Edition (BSID-II).
Results: Multiple regression analyses revealed that higher prenatal PCB exposure was associated with decreased FTII novelty preference, indicating impaired visual recognition memory. Prenatal Hg was associated with poorer performance on A-not-B, which depends on working memory and is believed to be a precursor of executive function. Prenatal Pb was related to longer FTII fixation durations, indicating slower speed of information processing.
Conclusions: PCBs, MeHg, and Pb each showed specific and distinct patterns of adverse associations with the outcomes measured during infancy. By contrast, none of these exposures was associated with performance on the BSID-II, a global developmental measure. The more focused, narrow band measures of cognitive function that appeared to be sensitive to these exposures also provide early indications of long-term impairment in specific domains that would otherwise not likely be evident until school age.
Citation: Boucher O, Muckle G, Jacobson JL, Carter RC, Kaplan-Estrin M, Ayotte P, Dewailly É, Jacobson SW. 2014. Domain-specific effects of prenatal exposure to PCBs, mercury, and lead on infant cognition: results from the Environmental Contaminants and Child Development Study in Nunavik. Environ Health Perspect 122:310–316; http://dx.doi.org/10.1289/ehp.1206323
doi:10.1289/ehp.1206323
PMCID: PMC3948023  PMID: 24441767
9.  Effects of maternal dioxin exposure on newborn size at birth among Japanese mother–infant pairs 
Objective
Maternal exposure to dioxins [polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (DFs)] during pregnancy is known to affect infant growth and neurodevelopment in humans and animals. The aim of this study was to investigate the relationship between newborn size and the concentration of dioxin isomers in breast milk and to subsequently evaluate the potential toxicity of each dioxin isomer among mothers living in sea coast areas who are at a high risk of contamination due to a high consumption of fish.
Methods
A total of 75 milk samples were obtained within 1 month of delivery from Japanese mothers living in the coastal areas of the Japan Sea. The relationships between the levels of seven dioxins and ten furan isomers in maternal breast milk, measured by high-resolution-gas chromatography/mass spectrometry, and the birth size of newborns, which is related to fetal growth, were investigated after adjustment for confounding factors.
Results
The concentrations of 1,2,3,6,7,8-HxCDD (hexachlorodibenzo-p-dioxin), 2,3,4,7,8-PeCDF (pentachlorodibenzofuran), 2,3,4,6,7,8-HxCDF, and three dioxin toxic equivalent (TEQ) levels (PCDDs-TEQ, PCDFs-TEQ, and total-TEQ) in maternal breast milk were inversely correlated to newborn length even after adjustment for gestational weeks, infant sex, and maternal age and height. These isomers were abundant among the 17 isomers tested and reflected the TEQ levels. Only 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD), the most toxic isomer, was negatively correlated with newborn head circumference, even after adjustment for gestational weeks, infant birth weight, and other confounding factors.
Conclusions
Based on our results, fetal growth may be influenced by maternal total exposure to dioxins, but only exposure to 2,3,7,8-TCDD would appear to possibly affect fetal head size during pregnancy.
doi:10.1007/s12199-008-0061-x
PMCID: PMC2684781  PMID: 19568852
Birth size; Breast milk; Dioxins; Newborn; 2,3,7,8-Tetrachlorodibenzo-p-dioxin
10.  Predictors of Serum Dioxins and PCBs among Peripubertal Russian Boys 
Environmental Health Perspectives  2009;117(10):1593-1599.
Background
Although sources and routes of exposure to dioxins and polychlorinated biphenyls (PCBs) have been studied, information regarding exposure among children is limited. Breast-feeding and diet are two important contributors to early life exposure. To further understand other significant contributors to childhood exposure, we studied a cohort of children from a city with high environmental dioxin levels.
Objectives
We investigated predictors of serum concentrations of polychlorinated dibenzo-p-dioxins (PCDDs)/polychlorinated dibenzofurans (PCDFs)/co-planar PCBs (C-PCBs), toxic equivalents (TEQs), and PCBs among 8- to 9-year-old boys in Chapaevsk, Russia.
Methods
We used general linear regression models to explore associations of log10-transformed serum concentrations of PCDDs/PCDFs/C-PCBs, TEQs, and PCBs at study entry with anthropometric, demographic, geographic, and dietary factors in 482 boys in Chapaevsk, Russia.
Results
The median (25th, 75th percentile) concentration for total 2005 TEQs was 21.1 pg/g lipid (14.4, 33.2). Boys who were older, consumed local foods, were breast-fed longer, and whose mothers were employed at the Khimprom chemical plant (where chlorinated chemicals were produced) or gardened locally had significantly higher serum dioxins and PCBs, whereas boys with higher body mass index or more educated parents had significantly lower serum dioxins and PCBs. Boys who lived < 2 km from Khimprom had higher total TEQs (picograms per gram lipid) [adjusted mean = 30.6; 95% confidence interval (CI), 26.8–35.0] than boys who lived > 5 km away (adjusted mean = 18.8; 95% CI, 17.2–20.6).
Conclusions
Our findings suggest that there are specific local sources of dioxin and PCB exposure among children in Chapaevsk including maternal gardening, consumption of locally grown food, and residential proximity to the Khimprom plant.
doi:10.1289/ehp.0800223
PMCID: PMC2790515  PMID: 20019911
children; diet; environment; epidemiology; polychlorinated biphenyls; polychlorinated dibenzodioxins; polychlorinated dibenzofurans
11.  Maternal and early postnatal polychlorinated biphenyl exposure in relation to total serum immunoglobulin concentrations in 6-month-old infants 
Journal of immunotoxicology  2011;8(1):95-100.
Animal data indicate that developmental tetrachlorodibenzo-p-dioxin exposure alters immune function; however, the potential immunotoxicity of dioxin-like and non-dioxin-like polychlorinated biphenyls (PCBs) in the developing infant is an understudied area. The aim of the current study is to examine the association between maternal and early postnatal PCB concentrations in relation to total infant serum immunoglobulin concentrations determined at 6-months-of-age. We selected 384 mother-infant pairs participating in a birth cohort study in Eastern Slovakia. PCB concentrations of several congeners were determined in maternal and cord serum samples and in infant serum samples collected at 6-months-of-age using gas chromatography with electron capture detection. Total immunoglobulin (Ig) G, A, and M concentrations were determined by nephelometry, and IgE concentrations were determined by enzyme-linked immunoassay. Linear regression models with adjustment for potential confounding factors were used to estimate the associations between maternal, cord, and 6-month infant PCB concentrations and total serum immunoglobulins. The median maternal serum concentration of PCB-153 was 140 ng/g lipid, ≈10-fold higher than concentrations in childbearing-age women in the United States during the same period. Maternal, cord, or 6-month infant PCB concentrations were not associated with total serum immunoglobulin levels at 6 months, regardless of the timing of PCB exposure, PCB congener, or specific immunoglobulin. In this population, which has high PCB concentrations relative to most populations in the world today, we did not observe any association between maternal and early postnatal PCB concentrations and total immunoglobulin measures of IgG, IgA, IgM, or IgE.
doi:10.3109/1547691X.2010.549096
PMCID: PMC3086069  PMID: 21299357
Epidemiology; cohort; DAG; roma
12.  Body Burdens of Polychlorinated Dibenzo-p-dioxins, Dibenzofurans, and Biphenyls and Their Relations to Estrogen Metabolism in Pregnant Women 
Environmental Health Perspectives  2006;114(5):740-745.
Polychlorinated dibenzo-p-dioxins (PCDDs, dioxins), polychlorinated dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs) are environmental endocrine disruptors that have half-lives of 7–10 years in the human body and have toxicities that probably include carcinogenesis. A high ratio of 4-hydroxyl estradiol (4-OH-E2) to 2-hydroxyl estradiol (2-OH-E2) has been suggested as a potential biomarker for estrogen-dependent neoplasms. In this cohort study of maternal–fetal pairs, we examined the relationship of PCDD/PCDF and PCB exposure to levels of estrogen metabolites in the sera of 50 pregnant women 25–34 years of age from central Taiwan. Maternal blood was collected during the third trimester, and the placenta was collected at delivery. We measured 17 dioxin congeners, 12 dioxin-like PCBs, and 6 indicator PCBs in placenta using gas chromatography coupled with high-resolution mass spectrometry. Estrogen metabolites in maternal serum were analyzed by liquid chromatography tandem mass spectrometry. The ratio of 4-OH-E2:2-OH-E2 decreased with increasing exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (β = −0.124, p = 0.004 by the general linear regression model, R = 0.4). Meanwhile, serum levels of 4-OH-E2 increased with increasing concentrations of high-chlorinated PCDFs (i.e., 1,2,3,4,6,7,8-hepta-CDF: β = 0.454, p = 0.03, R = 0.30). Altered estrogen catabolism might be associated with body burdens of PCDDs/PCDFs. Our study suggests that exposure to PCDDs/PCDFs significantly affects estrogen metabolism. Therefore, PCDD/PCDF exposure must be considered when using the OH-E2 ratio as a breast cancer marker.
doi:10.1289/ehp.8809
PMCID: PMC1459929  PMID: 16675430
breast neoplasm; carcinogenic marker; estrogen catabolism; estrogen metabolism; polychlorinated biphenyls; polychlorinated dibenzodioxins; polychlorinated dibenzofurans
13.  Dietary exposure to polychlorinated biphenyls and dioxins from infancy until adulthood: A comparison between breast-feeding, toddler, and long-term exposure. 
Food is the major source for polychlorinated biphenyl (PCB) and dioxin accumulation in the human body. Therefore, investigating food habits from early ages until reproductive age (25 years) is important in order to assess exposure risk for the next generation. The objective of this study was to assess the PCB/dioxin exposure and the relative contribution of different foods to total exposure during preschool age. Particularly, the importance of lactational PCB/dioxin exposure vs. dietary exposure until adulthood was investigated. A cohort of 207 children was studied from birth until preschool age. Based on 3 planar PCBs and 17 2,3,7,8-substituted dibenzo-para-dioxins (PCDDs) and dibenzofurans (PCDFs) measured in breast milk, a model was developed to calculate the cumulative toxic equivalent (TEQ) intake during breast-feeding (0-1 year). In 3. 5-year-old children, daily dietary intake of planar PCB-TEQ and dioxin-TEQ was measured with a validated food questionnaire. Cumulative TEQ intake from 1 to 5 years was estimated using the PCB- and dioxin-TEQ intake measured with the food questionnaire. Cumulative TEQ intake from 6 to 25 years was estimated using national food consumption and contamination data of PCB- and dioxin-TEQ intake. In toddlers, dairy products contributed 43% to PCB-TEQ and 50% to dioxin-TEQ intake. Meat and meat products contributed 14% and 19%, respectively, and processed foods 23% and 15%, respectively. Breast-feeding for 6 months contributed to the cumulative PCB/dioxin TEQ intake until 25 years of age, 12% in boys and 14% in girls. The daily TEQ intake per kilogram body weight is 50 times higher in breast-fed infants and three times higher in toddlers than in adults. Long-term dietary exposure to PCBs and dioxins in men and women is partly due to breast-feeding (12 and 14%, respectively). After weaning, dairy products, processed foods, and meat are major contributors of PCB and dioxin accumulation until reproductive age. Instead of discouraging breast-feeding, maternal transfer of PCBs and dioxins to the next generation must be avoided by enforcement of strict regulations for PCB and dioxin discharge and by reducing consumption of animal products and processed foods in all ages.
Images
PMCID: PMC1566290  PMID: 9872716
14.  Lactational Exposure to Polychlorinated Biphenyls, Dichlorodiphenyltrichloroethane, and Dichlorodiphenyldichloroethylene and Infant Neurodevelopment: An Analysis of the Pregnancy, Infection, and Nutrition Babies Study 
Environmental Health Perspectives  2008;117(3):488-494.
Background
Polychlorinated biphenyls (PCBs) and dichlorodiphenyltrichloroethane (DDT) are persistent, bioaccumulative, and toxic pollutants that were broadly used in the United States until the 1970s. Common exposure to PCBs, DDT, and dichlorodiphenyldichloroethylene (DDE), the most stable metabolite of DDT, may influence children’s neurodevelopment, but study results are not consistent.
Objectives
We examined the associations between lactational exposure to PCBs, DDT, and DDE and infant development at 12 months, using data from the Pregnancy, Infection, and Nutrition Babies Study, 2004–2006.
Methods
We measured PCBs, DDT, and DDE in breast milk at the third month postpartum. Lactational exposure of these chemicals was estimated by the product of chemical concentrations and the duration of breast-feeding. Infant development at 12 months of age was measured by the Mullen Scales of Early Learning (n = 231) and the Short Form: Level I (infant) of the MacArthur–Bates Communicative Development Indices (n = 218).
Results
No consistent associations were observed between lactational exposure to PCBs, DDT, and DDE through the first 12 months and the measures of infant development. However, DDE was associated with scoring below average on the gross motor scale of the Mullen among males only (adjusted odds ratio = 1.9; 95% confidence interval, 1.1–3.3).
Conclusion
Infant neurodevelopment at 12 months of age was not impaired by PCBs, DDT, and DDE at the concentrations measured here, in combination with benefits from long duration of breast-feeding in this population.
doi:10.1289/ehp.0800063
PMCID: PMC2661922  PMID: 19337527
breast milk; DDE; DDT; lactation; MacArthur-Bates Communicative Development Indices; Mullen Scales of Early Learning; PCBs
15.  Impact of Perinatal Dioxin Exposure on Infant Growth: A Cross-Sectional and Longitudinal Studies in Dioxin-Contaminated Areas in Vietnam 
PLoS ONE  2012;7(7):e40273.
Dioxin exposure levels remain elevated in residents living around former US Air Force bases in Vietnam, indicating potential adverse impacts on infant growth. In this study, 210 mother–infant pairs in dioxin-contaminated areas in Vietnam were recruited at the infants’ birth and followed up for 4 months. Perinatal dioxin exposure levels were estimated by measurement of polychlorinated dibenzo-p-dioxins/furans toxic equivalent (PCDDs/Fs-TEQ) in breast milk. The infants’ size was measured at birth and 1 and 4 months after birth, and neurodevelopment was evaluated using the Bayley Scales III at 4 months of age. Among 4 dioxin groups (<25, 25–50, 50–75, ≥75 percentile of PCDDs/Fs-TEQ), cross-sectional comparisons of body size and neurodevelopment scales and comparisons of longitudinally assessed body size were performed respectively. At birth, head circumference of girls in the ≥75 percentile group was significantly larger than those in the <25 and 50–75 percentile groups. At 4 months of age, the weight and body mass index (BMI) of boys in the ≥75 percentile group were significantly lower than those in the other groups. Increase in weight was significantly lower in the ≥75 percentile group in both sexes from birth to 1 month but only in boys at 1–4 months of age. Estimated marginal mean values in a mixed model of weight and BMI during the first 4 months of life were significantly lower in the ≥75 percentile group in boys. In girls, marginal mean values for head circumference were increased with increase in dioxin levels. Only in boys, cognitive, language, and fine motor scores in the ≥75 percentile group were significantly lower than those in the other groups. These results suggested a considerable impact of perinatal dioxin exposure on infant growth, particularly in boys exposed to dioxins at high level of PCDDs/Fs-TEQ.
doi:10.1371/journal.pone.0040273
PMCID: PMC3398034  PMID: 22815734
16.  Exposure to Hydroxylated Polychlorinated Biphenyls (OH-PCBs) in the Prenatal Period and Subsequent Neurodevelopment in Eastern Slovakia 
Environmental Health Perspectives  2009;117(10):1600-1606.
Background
Hydroxylated polychlorinated biphenyls (OH-PCBs), unlike PCBs, are in general readily excreted yet are still detected in humans and animals. Active transport of OH-PCBs across the placenta and hydroxylation of PCBs by the fetus suggest the potential for greater impact on the fetus compared with the parent PCB compounds, but little is known about their health effects, particularly in humans.
Objectives
The objective of this study was to evaluate the associations between prenatal OH-PCB exposure and neurodevelopment in children at 16 months of age in eastern Slovakia.
Methods
A birth cohort (n = 1,134) was enrolled during 2002–2004. We analyzed six OH-PCB metabolites (4-OH-CB-107, 3-OH-CB-153, 4-OH-CB-146, 3′-OH-CB-138, 4-OH-CB-187, and 4′-OH-CB-172) in a subset of the cohort. The Bayley Scales of Infant Development were administered to the children at the 16-month follow-up visit. We developed multiple linear regression models predicting standardized scores for the Mental Development Index (MDI) and Psychomotor Development Index (PDI) from maternal (n = 147) and cord (n = 80) serum OH-PCB concentrations, adjusting for sex of child, district, HOME (Home Observation for Measurement of the Environment) score, and maternal score on Raven’s Progressive Matrices.
Results
Cord 4-OH-CB-107 was significantly associated with lower MDI (β = −2.27; p = 0.01) and PDI (β = −4.50; p = 0.004). Also, maternal 4-OH-CB-107 was significantly associated with lower MDI (β = −1.76; p = 0.03) but not PDI. No other OH-PCB metabolites were associated with decreased PDI or MDI.
Conclusions
Our findings showed a significant association of 4-OH-CB-107 with decreased MDI, which can possibly be mediated by endocrine disruption, altered neurotransmitter functions, or reduced thyroid hormone concentrations in brain.
doi:10.1289/ehp.0900611
PMCID: PMC2790516  PMID: 20019912
Bayley Scales of Infant Development; hydroxylated PCBs; Slovakia
17.  Polychlorinated biphenyls (PCBs) and neurological development in children: a systematic review 
BACKGROUND—Polychlorinated biphenyls (PCBs) are complex mixtures of persistent contaminants that are widespread in the environment. Newborns are exposed across the placenta and through breast feeding. Experimental animal studies have indicated that PCBs are neurotoxic. The neurological effects of these compounds on children are not clear. Methods—A systematic review of literature on the relation between neurological development in children and exposure to polychlorinated biphenyls.
RESULTS—Seven follow up studies evaluated the effect of prenatal exposure to PCBs. Two of these studies evaluated highly exposed children. In newborns, an increase of the abnormal reflexes was observed in all four studies evaluating it. During the first months of life, a decrease in motor skills was observed in four of the five studies that investigated psychomotor development; deficits in the acquisition of cognitive skills were observed only in one study assessing non-highly exposed populations. At 4 years of age, an effect on the cognitive areas was observed in four of the five studies that evaluated it. Postnatal exposure to PCBs through breast feeding was not clearly related to any effect on neurological development.
CONCLUSIONS—These studies suggest a subtle adverse effect of prenatal PCBs exposure on child neurodevelopment. Differences in study design, inconsistency in some of the results, and the lack of adequate quantitative exposure data, do not allow the derivation of the degree of risk associated with neurodevelopmental effects at current levels of exposure.


Keywords: polychlorinated biphenyls; neurological development; systematic review
doi:10.1136/jech.55.8.537
PMCID: PMC1731955  PMID: 11449010
18.  PCB 126 and Other Dioxin-Like PCBs Specifically Suppress Hepatic PEPCK Expression via the Aryl Hydrocarbon Receptor 
PLoS ONE  2012;7(5):e37103.
Dioxins and dioxin-like compounds encompass a group of structurally related heterocyclic compounds that bind to and activate the aryl hydrocarbon receptor (AhR). The prototypical dioxin is 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a highly toxic industrial byproduct that incites numerous adverse physiological effects. Global commercial production of the structurally similar polychlorinated biphenyls (PCBs), however, commenced early in the 20th century and continued for decades; dioxin-like PCBs therefore contribute significantly to total dioxin-associated toxicity. In this study, PCB 126, the most potent dioxin-like PCB, was evaluated with respect to its direct effects on hepatic glucose metabolism using primary mouse hepatocytes. Overnight treatment with PCB 126 reduced hepatic glycogen stores in a dose-dependent manner. Additionally, PCB 126 suppressed forskolin-stimulated gluconeogenesis from lactate. These effects were independent of acute toxicity, as PCB 126 did not increase lactate dehydrogenase release nor affect lipid metabolism or total intracellular ATP. Interestingly, provision of cells with glycerol instead of lactate as the carbon source completely restored hepatic glucose production, indicating specific impairment in the distal arm of gluconeogenesis. In concordance with this finding, PCB 126 blunted the forskolin-stimulated increase in phosphoenolpyruvate carboxykinase (PEPCK) mRNA levels without affecting glucose-6-phosphatase expression. Myricetin, a putative competitive AhR antagonist, reversed the suppression of PEPCK induction by PCB 126. Furthermore, other dioxin-like PCBs demonstrated similar effects on PEPCK expression in parallel with their ability to activate AhR. It therefore appears that AhR activation mediates the suppression of PEPCK expression by dioxin-like PCBs, suggesting a role for these pollutants as disruptors of energy metabolism.
doi:10.1371/journal.pone.0037103
PMCID: PMC3353882  PMID: 22615911
19.  Patient fat biopsies for chemical analysis and liver biopsies for ultrastructural characterization after exposure to polychlorinated dioxins, furans and PCBs. 
A subset of workers was followed after exposure to polychlorinated biphenyls (PCBs), dioxins, and furans in an occupational medicine clinic setting. Patterns of PCBs found in adipose tissue resembled the pattern seen when soot from the incident or Aroclor 1254 was examined by GC-MS. Adipose tissue also revealed levels of hepta- and octachlorinated furans and dioxins as high as 8400 ppt in one repeatedly exposed worker. Control fat from patients with no known exposure to furans or dioxins was usually in the several hundred parts per trillion range for these isomers, but slightly over 2000 ppt in one sample. Electron microscopic analysis of liver biopsies from three patients who developed mild elevations of hepatic enzymes in their serum revealed morphologic alterations in some ways similar to those seen in animals after feeding experiments with PCBs, dioxins or the Binghamton State Office Building soot. These include pleomorphic mitochondria, giant mitochondria, prominent dense mitochondrial granules, cristae parallel to the long axis of the mitochondria and crystalline structure within same mitochondria as well as lipid droplets in liver cells and slightly dilated smooth endoplasmic reticulum.
Images
PMCID: PMC1568539  PMID: 3928350
20.  Endometriosis and Organochlorinated Environmental Pollutants: A Case–Control Study on Italian Women of Reproductive Age 
Environmental Health Perspectives  2009;117(7):1070-1075.
Background
Endometriosis is a common gynecologic disease characterized by the ectopic growth of endometrial tissue. In industrialized countries, it affects approximately 10% of women of reproductive age. Its etiology is unclear, but a multifactorial origin is considered to be most plausible. Environmental organochlorinated persistent pollutants, in particular dioxins and polychlorinated biphenyls (PCBs), have been hypothesized to play a role in the disease etiopathogenesis. However, results of studies carried out on humans are conflicting.
Objective
We evaluated the exposure to organochlorinated persistent pollutants as a risk factor for endometriosis.
Methods
We conducted a case–control study in Rome on 158 women comprising 80 cases and 78 controls. In all women, serum concentrations of selected non-dioxin-like PCBs (NDL-PCBs) and dioxin-like PCBs (DL-PCBs), 1,1-dichloro-2,2,-bis(4-chlorophenyl)-ethene (p,p′-DDE), and hexachlorobenzene (HCB) were determined by ion-trap mass spectrometry. DR-CALUX bioassay was employed to assess the 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity equivalent (TEQ) concentrations of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and DL-PCBs.
Results
We found an increased risk of endometriosis for DL-PCB-118 [odds ratio (OR) = 3.79; 95% confidence interval (CI), 1.61–8.91], NDL-PCB-138 (OR = 3.78; 95% CI, 1.60–8.94), NDL-PCB-153 (OR = 4.88; 95% CI, 2.01–11.0), NDL-PCB-170 (OR = 3.52; 95% CI, 1.41–8.79), and the sum of DL-PCBs and NDL-PCBs (OR = 5.63; 95% CI, 2.25–14.10). No significant associations were observed with respect to HCB or to the sum of PCDDs, PCDFs, and DL-PCBs given as total TEQs.
Conclusions
The results of this study show that an association exists between increased PCB and p,p′-DDE serum concentrations and the risk of endometriosis.
doi:10.1289/ehp.0800273
PMCID: PMC2717132  PMID: 19654915
biomonitoring; case-control study; dioxins; endometriosis; PCBs
21.  Assessment of pre- and postnatal exposure to polychlorinated biphenyls: lessons from the Inuit Cohort Study. 
Environmental Health Perspectives  2003;111(9):1253-1258.
Polychlorinated biphenyls (PCBs) are food-chain contaminants that have been shown to induce adverse developmental effects in humans. In the course of an epidemiologic study established to investigate neurodevelopmental deficits induced by environmental PCB exposure in the Inuit population of northern Québec (Nunavik, Canada), we compared three biomarkers of prenatal exposure and models to predict PCB plasma concentration at 6 months postpartum. Concentrations of 14 PCB congeners were measured by high-resolution gas chromatography with electron capture detection in lipids extracted from maternal plasma, cord plasma, breast milk (collected at approximately 1 month postpartum), and 6-month-old infant plasma samples. Similar congener profiles were observed in all biologic samples, and PCB-153, the most abundant and persistent PCB congener, was strongly correlated with other frequently detected PCB congeners in all biologic media. When expressed on a lipid basis, maternal plasma, cord plasma, and milk concentrations of this congener were strongly intercorrelated, indicating that PCB concentration in any of these biologic media is a good indicator of prenatal exposure to PCBs. A multivariate model that included maternal PCB-153 plasma lipid concentration, breast-feeding duration, and the sum of two skin-fold thicknesses (an index of infant body fat mass) explained 72% of PCB-153 plasma concentration variance at 6 months postpartum (p < 0.001). By contrast, based on the product of breast-feeding duration times the concentration of PCBs in plasma lipids, which was used as an index of postnatal PCB exposure in several studies, only 36% of infant plasma concentration was explained.
PMCID: PMC1241583  PMID: 12842782
22.  Neurodevelopmental Effects of Low-level Prenatal Mercury Exposure From Maternal Fish Consumption in a Mediterranean Cohort: Study Rationale and Design 
Journal of Epidemiology  2013;23(2):146-152.
Background
Mercury is a neurotoxic environmental pollutant. However, the literature on the neurodevelopmental effect of low-level prenatal mercury exposure from maternal fish intake is inconsistent. We assessed the association between prenatal mercury exposure and infant neurodevelopment in coastal areas of 4 Mediterranean countries.
Methods
This was a prospective cohort study that planned to enroll approximately 1700 mother–infant pairs. Pregnant women and their newborn children were recruited in selected hospitals of the study areas. Biological samples, including maternal hair and cord blood, were collected from mothers and children, and the concentrations of mercury and other elements were measured. Exposures to lifestyle, environmental, and social factors were assessed through questionnaires. The main outcome was child neurodevelopment at 18 months, as measured by the Bayley Scales of Infant and Toddler Development, Third Edition.
Conclusions
This cohort has a number of strengths. First, mercury concentration was measured in several biological samples, which allows for a better understanding of mercury kinetics and is useful for sensitivity analyses. Therefore, we expect to be able to adjust for the potential confounding effects of lifestyle and social factors and for the effects of other elements that were measured in the biological samples. Finally, this is a multinational study and thus permits assessment of the relation between mercury and child neurodevelopment in different populations.
doi:10.2188/jea.JE20120030
PMCID: PMC3700240  PMID: 23269124
cohort study; mercury; polyunsaturated fatty acids; nervous system development; fish
23.  Predictors of Serum Dioxin, Furan and PCB Concentrations among Women from Chapaevsk, Russia 
Environmental science & technology  2010;44(14):5633-5640.
INTRODUCTION
Dioxins, furans and polychlorinated biphenyls (PCBs) are persistent and bioaccumulative toxic chemicals that are ubiquitous in the environment. We assessed predictors of their serum concentrations among women living in a Russian town contaminated by past industrial activity.
METHODS
Blood samples from 446 mothers aged 23–52 years were collected between 2003–2005 as part of the Russian Children’s Study. Serum dioxin, furan and PCB concentrations were quantified using high-resolution gas chromatography-mass spectrometry. Potential determinants of exposure were collected through interviews. Multivariate linear regression models were used to identify predictors of serum concentrations and toxic equivalencies (TEQs).
RESULTS AND DISCUSSION
The median total PCB concentrations and total TEQs were 260 ng/g lipid and 25 pg TEQ/g lipid, respectively. In multivariate analyses, both total PCB concentrations and total TEQs increased significantly with age, residential proximity to a local chemical plant, duration of local farming, and consumption of local beef. Both decreased with longer breastfeeding, recent increases in body mass index, and later blood draw date. These demographic and lifestyle predictors showed generally similar associations with the various measures of serum dioxins, furans, and PCBs.
doi:10.1021/es100976j
PMCID: PMC3128795  PMID: 20578718
24.  Thyroid Hormone Levels of Pregnant Inuit Women and Their Infants Exposed to Environmental Contaminants 
Environmental Health Perspectives  2009;117(6):1014-1020.
Background
An increasing number of studies have shown that several ubiquitous environmental contaminants possess thyroid hormone–disrupting capacities. Prenatal exposure to some of them, such as polychlorinated biphenyls (PCBs), has also been associated with adverse neurodevelopmental effects in infants.
Objectives
In this study we examined the relationship between exposure to potential thyroid hormone–disrupting toxicants and thyroid hormone status in pregnant Inuit women from Nunavik and their infants within the first year of life.
Methods
We measured thyroid hormone parameters [thyroid stimulating hormone (TSH), free thyroxine (fT4), total triiodothyronine (T3), thyroxine-binding globulin (TBG)] and concentrations of several contaminants [PCB-153, hydroxylated metabolites of PCBs (HO-PCBs), pentachlorophenol (PCP) and hexachlorobenzene (HCB)] in maternal plasma at delivery (n = 120), in umbilical cord plasma (n = 95), and in infant plasma at 7 months postpartum (n = 130).
Results
In pregnant women, we found a positive association between HO-PCBs and T3 concentrations (β = 0.57, p = 0.02). In umbilical cord blood, PCB-153 concentrations were negatively associated with TBG levels (β = −0.26, p = 0.01). In a subsample analysis, a negative relationship was also found between maternal PCP levels and cord fT4 concentrations in neonates (β = −0.59, p = 0.02). No association was observed between contaminants and thyroid hormones at 7 months of age.
Conclusion
Overall, there is little evidence that the environmental contaminants analyzed in this study affect thyroid hormone status in Inuit mothers and their infants. The possibility that PCP may decrease thyroxine levels in neonates requires further investigation.
doi:10.1289/ehp.0800219
PMCID: PMC2702396  PMID: 19590699
cohort; cord blood; Inuit; metabolites; organochlorines; pentachlorophenol; polychlorinated biphenyls; pregnant women; prenatal exposure; thyroid hormones
25.  PCBs contamination in seafood species at the Eastern Coast of Thailand 
Chemosphere  2009;76(2):239-249.
Polychlorinated biphenyls (PCBs) are a large group of persistent organic substances spread throughout the world. The most toxic PCBs are those that are dioxin-like (dl-PCBs). Environmental studies on PCBs in Thailand are limited, especially with regards to dl-PCBs. This study is one of the first in this country that demonstrates contamination of seafood with PCBs and determines the levels of PCBs and total dioxin like activity in mussels, oysters and shrimp, from the Eastern Coast of Thailand. Sixty pooled samples of mussels and twenty-seven pooled samples of oysters were collected from cultivation farms and twenty-one pooled samples of shrimp were collected from fisherman piers. Qualitative and quantitative measurements of 49 PCB congeners was obtained by HRGC-ECD analysis and total dioxin-like activity using the CAFLUX bioassay. Total PCB concentrations varied between three species, ranging between 19 and 1100 ng g−1 lipid adjusted weight, and the levels of PCBs in shrimp was three time higher than that in mussels and oysters. With respected to the pattern of PCB congeners, it implied that the source of PCBs exposure in this area could be from the regional contamination. The calculated CAFLUX bioanalytical equivalents (BEQs) values ranged between 0.8 and 18 pg BEQ g−1 lipid adjusted weight, and showed a good relationship with the chemical-derived TEQs. Therefore, the CAFLUX bioassay can be used for effective screening of dioxin-like activity in marine species effectively.
doi:10.1016/j.chemosphere.2009.03.018
PMCID: PMC2855220  PMID: 19375780
Dioxin; CAFLUX; BEQ; Mussels; Oysters; Shrimp

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