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1.  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
2.  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
3.  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
4.  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
5.  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
6.  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
7.  Breast Milk Dioxins in Hong Kong and Pearl River Delta 
Environmental Health Perspectives  2005;114(2):202-208.
There are no previous reports from South China on chemically determined polychlorinated dibenzo-para-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and dioxin-like poly-chlorinated biphenyls (PCBs) in human breast milk expressed as World Health Organization (WHO) toxic equivalents (TEQs). In a 2002–2003 WHO exposure study, 13 pools of breast milk comprising samples from 316 primiparous women in Hong Kong in 2002 were analyzed by gas chromatography/mass spectrometry for 29 PCDD/F and dioxin-like PCB congeners. Total WHO-TEQs ranged from 8.97 to 16.7 pg/g fat (weighted mean, 12.9 pg; weighted median, 13.4 pg). Variations in TEQs included positive associations with age (R2 = 0.73, p < 0.0005), higher consumption of dairy products and seafood, and lower TEQs in overseas mothers and ever-smokers. Congener profiles indicated geographic specificity of exposure in Hong Kong, mainland China, and overseas Asian countries, including higher proportions of PCB-TEQs (overseas) and PCDF-TEQs (mainland China). The median TEQs of PCDD/Fs (8.69 pg/g fat) and PCBs (4.73 pg/g fat) in Hong Kong were highest among the five Asian Pacific countries but lower than the levels for at least half of the European countries that participated in the WHO study. However, future international studies should incorporate mother’s age in the design of the pooling strategy to allow standardization by other exposure factors and valid comparisons among different countries. The findings allow support for the WHO breast-feeding advisory. Trends in human dioxin levels in the region cannot yet be determined, and rigorous controls are needed to reduce emissions of dioxins and human exposure in mainland China.
doi:10.1289/ehp.8116
PMCID: PMC1367832  PMID: 16451855
breast milk; China; dioxin-like polychlorinated biphenyls; Hong Kong; polychlorinated dibenzofurans; polychlorinated dibenzo-para-dioxins
8.  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
9.  Birth weight and sex of children and the correlation to the body burden of PCDDs/PCDFs and PCBs of the mother. 
Polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs) were analyzed in 167 random human milk samples from urban and rural areas in Finland. Dietary habits and background information on each mother and child were gathered by questionnaire. Body mass indexes (BMI) before pregnancy and delivery in the rural area were 5-10% higher than in the urban area, but fat content of mother's milk was about 10% higher in the urban area. The mean weights of children (+/- standard deviation) were similar in the rural and urban areas among primiparae, 3,500 +/- 597 g and 3,505 +/- 454 g, respectively, although dioxin international toxic equivalents (I-TEQs) were significantly higher in the urban area. The mother's level of education did not affect the weight of the child, but concentrations of PCDDs/PCDFs (I-TEQ, 2,3,4,7,8-Cl5 dibenzofuran,1,2, 3,7,8-Cl5 dibenzodioxin) and PCBs [sum of PCBs (sumPCB), PCB-TEQ, and most PCB congeners] increased with advanced education. This is considered to be due to differences in the mother's consumption of fish. The birth weight, especially of boys, slightly decreased with increasing concentrations of I-TEQ, 2,3,4,7,8-Cl5 dibenzofuran, 1,2,3, 7,8-Cl5 dibenzodioxin, and 2,3,7,8-Cl4 dibenzodioxin; however, when the analysis was restricted to primiparae, there was no statistically significant correlation between birth weight and the concentrations of PCDDs/PCDFs. No correlation was found between the weight of the child and PCBs, PCB-TEQs, or individual PCB congeners in the whole material or among primiparae, or among boys or girls. The concentrations of PCDDs/PCDFs and PCBs inhuman milk were modeled for primiparae by weighing fish consumption, age of mother, milk fat content, and BMI before pregnancy. The linear regression resulted in values of R = 0.67 and 0.30 for the modeled dioxin I-TEQs in the urban and rural areas, respectively, and the corresponding values for sumPCBs of R = 0.60 and 0.11. The increase of PCDD/PCDF body burden was calculated to be on average 0.58 pg I-TEQ/g milk fat/year in the urban area and 0.39 pg I-TEQ/g milk fat/year in the rural area.
Images
PMCID: PMC1533022  PMID: 9432971
10.  Behavioral Sexual Dimorphism in School-Age Children and Early Developmental Exposure to Dioxins and PCBs: A Follow-Up Study of the Duisburg Cohort 
Environmental Health Perspectives  2013;122(3):292-298.
Background: Polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and polychlorinated biphenyls (PCBs) are persistent organic pollutants that have been characterized as endocrine-disrupting chemicals (EDCs).
Objectives: Within the Duisburg birth cohort study, we studied associations of prenatal exposure to PCDD/Fs and PCBs with parent-reported sexually dimorphic behavior in children.
Methods: We measured lipid-based and WHO2005-TEQ (toxic equivalents established in 2005 by the World Health Organization)–standardized PCDD/Fs and PCBs in maternal blood samples and in early breast milk using gas chromatography/high-resolution mass spectrometry. At the child’s age of 6–8 years, parents (mostly mothers) reported sex-typical characteristics, preferred toys, and play activities using the Pre-School Activities Inventory (PSAI), which was used to derive feminine, masculine, and difference (feminine – masculine) scores. We estimated exposure–outcome associations using multivariate linear regression. A total of 91–109 children were included in this follow-up.
Results: Mean blood levels of summed WHO2005-TEQ–standardized dioxins (ΣPCDD/Fs) were 14.5 ± 6.4 pg/g blood lipids, and ΣPCBs were 6.9 ± 3.8 pg/g blood lipids, with similar values for milk lipids. Regression analyses revealed some highly significant interactions between sex and exposure—such as for ΣPCBs in milk, pronounced positive (boys: β = 3.24; CI = 1.35, 5.14) or negative (girls: β = –3.59; CI = –1.10, –6.08) associations with reported femininity. Less pronounced and mostly insignificant but consistent associations were found for the masculinity score, positive for boys and negative for girls.
Conclusions: Given our results and the findings of previous studies, we conclude that there is sufficient evidence that these EDCs modify behavioral sexual dimorphism in children, presumably by interacting with the hypothalamic–pituitary–gonadal axis.
Citation: Winneke G, Ranft U, Wittsiepe J, Kasper-Sonnenberg M, Fürst P, Krämer U, Seitner G, Wilhelm M. 2014. Behavioral sexual dimorphism in school-age children and early developmental exposure to dioxins and PCBs: a follow-up study of the Duisburg Cohort. Environ Health Perspect 122:292–298; http://dx.doi.org/10.1289/ehp.1306533
doi:10.1289/ehp.1306533
PMCID: PMC3948031  PMID: 24273228
11.  Prevalence of Metabolic Syndrome Associated with Body Burden Levels of Dioxin and Related Compounds among Japan’s General Population 
Environmental Health Perspectives  2008;117(4):568-573.
Background
Environmental exposure to some persistent organic pollutants has been reported to be associated with a metabolic syndrome in the U.S. population.
Objectives
We evaluated the associations of body burden levels of dioxins and related compounds with the prevalence of metabolic syndrome among the general population in Japan.
Methods
We conducted a cross-sectional study with 1,374 participants not occupationally exposed to these pollutants, living throughout Japan during 2002–2006. In fasting blood samples, we measured biochemical factors and determined lipid-adjusted concentrations of 10 polychlorinated dibenzo-p-dioxins (PCDDs), 7 polychlorinated dibenzofurans (PCDFs), and 12 dioxin-like poly-chlorinated biphenyls (DL-PCBs) all of which have toxic equivalency factors. We also performed a questionnaire survey.
Results
The toxic equivalents (TEQs) of PCDDs, PCDFs, and DL-PCBs and total TEQs had significant adjusted associations with metabolic syndrome, whether or not we excluded diabetic subjects. By analyzing each component of metabolic syndrome separately, the DL-PCB TEQs and total TEQs were associated with all components, and the odds ratios (ORs) in the highest quartile of DL-PCB TEQs in four of the five components were higher than those for PCDDs or PCDFs. We also found congener-specific associations with metabolic syndrome; in particular, the highest quartiles of PCB-126 and PCB-105 had adjusted ORs of 9.1 and 7.3, respectively.
Conclusions
These results suggest that body burden levels of dioxins and related compounds, particularly those of DL-PCBs, are associated with metabolic syndrome. Of the components, high blood pressure, elevated triglycerides, and glucose intolerance were most closely associated with these pollutants.
doi:10.1289/ehp.0800012
PMCID: PMC2679600  PMID: 19440495
cross-sectional study; metabolic syndrome; dioxins; PCBs; PCDDs; PCDFs; poly-chlorinated biphenyls; polychlorinated dibenzofurans; polychlorinated dibenzo-p-dioxins
12.  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
13.  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
14.  Polychlorinated biphenyl levels in the tissues of exposed and nonexposed humans. 
Environmental Health Perspectives  1994;102(Suppl 1):149-158.
Polychlorinated biphenyls (PCBs) are synthetic chemicals, manufactured in volume from about 1929 to the 1970s. Environmental contamination by PCBs has been documented in various substances, including human tissue. PCBs have been measured in human tissue by a variety of analytical methods. PCB levels have been reported as an approximation of total PCB content expressed in terms of a commercial mixture, by identification and quantification of chromatographic peaks, or by qualitative and quantitative characterization of specific congeners. Until recently, the coplanar mono-ortho- and di-ortho substituted PCBs, which are especially toxic and present in significant concentration in humans from industrial countries, had not been measured in human tissues. Examples of various types of commonly used analyses are presented in general population subjects and in persons who experienced special exposure. In this paper, the usefulness of PCB blood determinations following potential exposure is demonstrated, and their application in health studies is illustrated from a number of case studies. Coplanar PCB, mono-ortho-substituted and di-ortho-substituted PCB levels in human blood are presented and compared with polychlorinated dioxin (PCDD) and polychlorinated dibenzofuran (PCDF) levels in the U.S. population. Dioxin toxic equivalents for the two groups of chemicals are calculated and compared. It is found that mono-ortho-substituted and, to a lesser extent, coplanar PCBs, contribute substantially to dioxin toxic equivalents (TEq) in blood from U.S. adults. Because of substantial PCB contribution to dioxin toxic equivalents, total dioxinlike toxicity can only be determined if dioxins, dibenzofurans, and dioxinlike PCBs are measured.(ABSTRACT TRUNCATED AT 400 WORDS)
PMCID: PMC1566903  PMID: 8187704
15.  PCDD and PCDF exposure and levels in humans in Germany. 
Environmental Health Perspectives  1994;102(Suppl 1):173-185.
For nonoccupationally exposed persons, the daily intake via food consumption has been calculated to be 0.35 pg/kg body weight per day for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and 2.3 pg/kg body weight per day for TCDD equivalents (TEqs). As compared to food, other sources and pathways are of minor importance. Food of animal origin contributes most, although human exposure begins with atmospheric emissions depositing these compounds on plant surfaces. In the meantime, a possible additional body burden from cardboard containers for cow's milk and coffee filters has been practically excluded. Of the 210 existing PCDDs and PCDFs, only 15 2,3,7,8-substituted isomers with a characteristic congener pattern can be found in samples of human origin. In adipose tissue and milk samples, mean levels for 2,3,7,8-TCDD of 7.2 and 3.6 pg/g fat, respectively, and of 56 (range 18-122) and 30 (range 10-72) pg TEqs/g fat, respectively, were determined. Human data revealed a dependency of polychlorinated dibenzo-p-dioxins/polychlorinated dibenzofurans (PCDD/PCDF) levels on age. In human milk, levels became reduced with the number of children born to mothers and duration of breast-feeding period. The average daily intake for a breast-fed child has been calculated to be 17 pg 2,3,7,8-TCDD/kg body weight per day and 142 pg TEqs/kg body weight per day, respectively. Levels in adipose tissue of infants, even if breast fed, were distinctly lower compared to human milk. In human milk, adipose tissue, and whole blood, PCDD/PCDF concentrations have been found to be equal on a fat-weight basis. Liver fat accumulated PCDD/PCDF with an alteration in the congener distribution pattern, whereas brain, even on a fat-weight basis, showed the lowest concentrations. Elevated or even high levels were found in occupationally exposed persons working in special chemical plants or involved in specific processes. There are limited data suggesting slightly elevated PCDD/PCDF levels are due to long-term consumption of a large share of food produced near point sources with a heavy emission or ingestion of soil or dust from such areas.
PMCID: PMC1566882  PMID: 8187706
16.  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
17.  Persistent organic pollutants in Finnish reindeer (Rangifer tarandus tarandus L.) and moose (Alces alces) 
Acta Veterinaria Scandinavica  2012;54(Suppl 1):S11.
Summary
Background
The aim of this study was to determine 17 Polychlorinated Dibenzo-p-dioxin and Dibenzofuran (PCDD/F) and 12 Dioxin-like Polychlorinated Biphenyl (DL-PCB) concentrations in the tissues of Finnish terrestrial herbivore species, semi-domesticated reindeer (Rangifer tarandus tarandus L.), and wild moose (Alces alces), investigate transfer and accumulation of PCDD/Fs and DL-PCBs in milk of the lactating reindeer hinds, and explore contaminant concentrations in stillborn reindeer calves exposed via placental transfer to PCDD/Fs and DL-PCBs.
Methods
Reindeer and moose tissue sampling was focused in Finnish reindeer herding region. Reindeer milk samples were sampled in summer and autumn from reindeer hinds in experimental reindeer station in northern Finland. PCDD/Fs and DL-PCBs were analyzed using HRGC/HRMS method. The results are reported here as WHO-TEQ upper bound concentrations and congener-specific lower bound concentrations.
Results
WHO-PCDD/F- and PCB-TEQs in reindeer muscle and liver were generally higher in the calves than in adults. Concentrations in moose calves were lower than in reindeer calves, while in adult reindeer and moose the levels were equal. General PCDD/F congeners in reindeer muscle and liver were 23478-PeCDF, 123678-HxCDD and OCDD. In reindeer milk, the highest PCDD/F detected was OCDD, and it was common also in the moose muscle samples. A strong contribution of non-ortho-PCBs to WHO-TEQ was detected in all studied samples. The most dominating non-ortho-DL-PCB congener was PCB-126 in reindeer muscle, liver and milk. In moose muscle samples PCB-77 was the most abundant congener. Species-, individual- and tissue-specific accumulation of PCDD/Fs and DL-PCBs may be the result from varying extent and quality of exposure, and to some extent from different metabolic potential.
Conclusions
PCDD/Fs showed partly similar profiles in reindeer and moose muscle, reindeer liver and milk samples - indicating equal mode of bioaccumulation. A strong contribution of non-ortho-PCBs to WHO-TEQ was detected, although there were some differences in frequency of particular congeners in these species. Due to the harmonized sampling method the study offers the way to determine and compare the levels of PCDD/Fs and DL-PCBs in reindeer and moose tissues and examine the transfer and dynamics of dioxins and dioxin-like compounds in northern terrestrial food web.
doi:10.1186/1751-0147-54-S1-S11
PMCID: PMC3305487
18.  Polychlorinated dibenzo-p-dioxins, dibenzofurans, and biphenyls in fishermen in Finland. 
Environmental Health Perspectives  2002;110(4):355-361.
We measured plasma concentrations of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), and polychlorinated biphenyls (PCBs) in fishermen from the Finnish Baltic Sea area and fishermen fishing in inland lakes. The concentrations clearly correlated with the frequency of fish meals and consumption of Baltic fatty fish. The body burden of PCDD/Fs reached the median level of 170 pg/g toxic equivalents (I-TEq) in fat for Baltic Sea fishermen, with the maximum being 420 pg/g. Results for 2,3,7,8-tetrachlorodibenzo-p-dioxin (range = 4.9-110 pg/g fat) showed that lifetime exposure in a population consuming much Baltic fatty fish can reach the levels of exposures seen in Seveso, Italy, in 1976. After we summed the PCB-TEqs, the total median exposure of Baltic Sea fishermen increased to 290 pg/g TEq in fat, and the highest concentration was 880 pg/g. There was a noted individual variation in fishermen's PCDD/F congener patterns, and it was possible to associate this variation with congener patterns of PCDD/Fs in the fish species that the fisherman reported they had consumed. Linear regression models for ln WHO(PCDD/F)-TEq, ln WHO(PCB)-TEq, and ln total WHO-TEq, from the World Health Organization, explained 48%, 60%, and 53% of the variability, respectively. Age was the only significant predictor of ln WHO(PCDD/F)-TEq, whereas age, amount of fish eaten, and place of residence were significant predictors of ln WHO(PCB)-TEq, and ln total WHO-TEq.
PMCID: PMC1240798  PMID: 11940453
19.  Exposure of remote maritime populations to coplanar PCBs. 
Environmental Health Perspectives  1994;102(Suppl 1):205-209.
Two remote maritime populations were evaluated for their biological exposure to organochlorines in 1989-1990. Because of their high intake of seafood, these two populations have high biological levels. One hundred nine breast milk samples from Inuit women from Arctic Québec were analyzed to determine levels of polychlorodibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and coplanar polychlorinated biphenyls (PCBs) including non-ortho, mono-ortho, and di-ortho congeners. Total 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents (TEqs) for PCBs were 3.5 times higher in Inuit milk samples than in 96 Caucasian milk samples. Among the 185 fishermen from the Lower North Shore of the Gulf of the St. Lawrence River, we evaluated 10 highly exposed fishermen for their coplanar PCB blood levels. Total TEqs were 900 ng/kg for highly exposed individuals with 36 ng/kg for controls. In these two nonoccupationally exposed populations, coplanar PCBs make a larger contribution to the TEq than PCDDs and PCDFs. However, the mono-ortho penta CB No. 118 is the major contributor for the total toxicity.
PMCID: PMC1566874  PMID: 8187710
20.  PCDDs, PCDFs, and PCBs in human blood in relation to consumption of crabs from a contaminated Fjord area in Norway. 
Environmental Health Perspectives  1996;104(7):756-764.
Consumption of fish and shellfish from contaminated areas may be an important source of human exposure to persistent organohalogen compounds such as polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins (PCDDs), and polychlorinated dibenzofurans (PCDFs). We determined concentrations of 2,3,7,8-substituted PCDDs and PCDFs and 19 PCB congeners in whole blood samples from three groups of men, 40-54 years of age, with different consumption levels of crabs from a fjord area in southern Norway polluted with organochlorine compounds from a magnesium production plant. A significant increase of many PCDD/PCDF congeners was found in the blood when comparing the referents, moderate-, and high-intake groups. The greatest difference was observed for several of the PCDFs that are characteristic for the contamination of the marine biota of the fjord. PCBs, in general, play a minor role in the contamination of the fjord by the magnesium production process, except for the highly chlorinated congeners such as PCB-209. Nevertheless, almost all PCBs increased from the referents to the high-intake group. However, the relative concentrations of several highly chlorinated PCBs (particularly PCB-209) in blood are unexpectedly low compared to their abundance in crabs, indicating low uptake of these congeners. The exposure to PCDDs/PCDFs from crab consumption calculated from individual body burdens of these compounds were in good agreement with the intake estimated from previously measured concentrations in crabs, reported fishing sites, and consumption. Almost all subjects in the high-intake group exceeded the tolerable weekly intake of 35 pg TEQ/kg body weight/week proposed by a Nordic Expert Group.
Images
PMCID: PMC1469397  PMID: 8841762
21.  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
22.  AhR transcriptional activity in serum of Inuits across Greenlandic districts 
Environmental Health  2007;6:32.
Background
Human exposure to lipophilic persistent organic pollutants (POPs) including polychlorinated dibenzo-p-dioxins/furans (PCDDs/PCDFs), polychlorinated biphenyls (PCBs) and organochlorine pesticide is ubiquitous. The individual is exposed to a complex mixture of POPs being life-long beginning during critical developmental windows. Exposure to POPs elicits a number of species- and tissue-specific toxic responses, many of which involve the aryl hydrocarbon receptor (AhR). The aim of this study was to compare the actual level of integrated AhR transcriptional activity in the lipophilic serum fraction containing the actual POP mixture among Inuits from different districts in Greenland, and to evaluate whether the AhR transactivity is correlated to the bio-accumulated POPs and/or lifestyle factors.
Methods
The study included 357 serum samples from the Greenlandic districts: Nuuk and Sisimiut (South West Coast), Qaanaaq (North Coast) and Tasiilaq (East Coast). The bio-accumulated serum POPs were extracted by ethanol: hexane and clean-up on Florisil columns. Effects of the serum extract on the AhR transactivity was determined using the Hepa 1.12cR mouse hepatoma cell line carrying an AhR-luciferase reporter gene, and the data was evaluated for possible association to the serum levels of 14 PCB congeners, 10 organochlorine pesticide residues and/or lifestyle factors.
Results
In total 85% of the Inuit samples elicited agonistic AhR transactivity in a district dependent pattern. The median level of the AhR-TCDD equivalent (AhR-TEQ) of the separate genders was similar in the different districts. For the combined data the order of the median AhR-TEQ was Tasiilaq > Nuuk ≥ Sisimiut > Qaanaaq possibly being related to the different composition of POPs. In overall, the AhR transactivity was inversely correlated to the levels of sum POPs, age and/or intake of marine food.
Conclusion
i) We observed that the proportion of dioxin like (DL) compounds in the POP mixture was the dominating factor affecting the level of serum AhR transcriptional activity even at very high level of non DL-PCBs; ii) The inverse association between the integrated serum AhR transactivity and sum of POPs might be explained by the higher level of compounds antagonizing the AhR function probably due to selective POP bioaccumulation in the food chain.
doi:10.1186/1476-069X-6-32
PMCID: PMC2173889  PMID: 17956617
23.  Reduced Antibody Responses to Vaccinations in Children Exposed to Polychlorinated Biphenyls 
PLoS Medicine  2006;3(8):e311.
Background
Developmental exposure to polychlorinated biphenyls (PCBs) has been implicated as a possible cause of deficient immune function in children. This study was designed to assess whether prenatal and postnatal exposure to PCBs impacts on antibody response to childhood immunizations.
Methods and Findings
Two birth cohorts were formed in the Faroe Islands, where exposures vary widely, because traditional diets may include whale blubber contaminated with PCBs. Prenatal exposure was determined from maternal concentrations of PCBs in pregnancy serum and milk. Following routine childhood vaccinations against tetanus and diphtheria, 119 children were examined at 18 mo and 129 children at 7 y of age, and their serum samples were analyzed for tetanus and diphtheria toxoid antibodies and for PCBs. The antibody response to diphtheria toxoid decreased at age 18 mo by 24.4% (95% confidence interval [CI], 1.63–41.9; p = 0.04) for each doubling of the cumulative PCB exposure at the time of examination. The diphtheria response was lower at age 7 y and was not associated with the exposure. However, the tetanus toxoid antibody response was affected mainly at age 7 y, decreasing by 16.5% (95% CI, 1.51–29.3; p = 0.03) for each doubling of the prenatal exposure. Structural equation analysis showed that the early postnatal exposure was the most important predictor of a decreased vaccination response.
Conclusions
Increased perinatal exposure to PCBs may adversely impact on immune responses to childhood vaccinations. The clinical implications of insufficient antibody production emphasize the need for prevention of immunotoxicant exposures.
A study of two birth cohorts in the Faroe Islands, where diets may include whale blubber contaminated with polychlorinated biphenyls (PCBs), suggests exposure to PCBs may reduce immune response to childhood vaccinations.
Editors' Summary
Background.
These days, mothers are as likely to worry about potential side-effects of childhood vaccinations as about whether they completely protect their child against infections. But healthy children vary in how well vaccinations “take.” After tetanus and diphtheria vaccination, for example, some children produce large quantities of antibodies that protect them against these serious bacterial diseases; others make a weaker, sometimes inadequate, immune response. What causes this variation is unclear, but one possibility is that the developing immune system is damaged in some babies by exposure both before birth and after birth through breast milk to “immunotoxicants” such as polychlorinated biphenyls (PCBs). These stable, man-made chemicals, which were widely used last century as insulators in electrical equipment and as fire retardants, accumulate and persist in the environment where they affect animal and human health. PCB-exposed babies often have a small thymus (the gland where immune system cells mature), make decreased amounts of antibodies, and have more childhood infections.
Why Was This Study Done?
Given these observations, could exposure to PCBs be partly responsible for the variable immunological responses of children to vaccination? If it is, and if environmental PCB levels remain high, it might be necessary to adapt more intensive vaccination programs so that all children are adequately protected against infectious diseases. In this study, the researchers examined whether prenatal and postnatal exposure to PCBs affects antibody responses to childhood vaccinations
What Did the Researchers Do and Find?
The researchers enrolled two groups of children—one group born in 1994–1995, the other in 1999–2001—living on the Faroe Islands in the North Atlantic. Here, people are exposed to high levels of PCBs through eating contaminated whale blubber. All the children received routine vaccinations against diphtheria and tetanus. The bacteria that cause these illnesses do so by producing a “toxoid,” so a harmless quantity of these toxic proteins is injected to stimulate a protective antibody response. For the older group, a blood sample was taken when they were seven and half years old to test for antibodies against diphtheria and tetanus toxoids; for the younger group, a sample was taken at 18 months. The exposure of the children to PCBs was assessed by measuring PCBs in their mothers' blood during pregnancy, in their mothers' milk soon after birth, and in their own blood when their antibodies were tested. The researchers found that the antibody response to diphtheria toxoid in the younger group of children was reduced by nearly a quarter for every doubling in their total exposure to PCBs. The tetanus toxoid response in the older children was reduced by a similar amount by prenatal exposure to PCBs. Although most of the children made enough antibodies to both toxoids to provide protection, about a fifth of the older children—mainly those with the highest exposures to PCBs—had worryingly low levels of diphtheria toxoid antibodies.
What Do These Findings Mean?
These results reveal an association between exposure to PCBs, particularly soon after birth, and a reduction in immunoprotection after childhood vaccinations. It is not clear, however, exactly how big this effect may be. This is uncertain for two reasons. First, the estimates of how much antibody responses are reduced by doubling PCB exposure are imprecise—for the younger children this change in exposure might actually have very little effect on their response to diphtheria vaccination or it could halve their response. Second, the estimates of PCB exposures are based on only three samples of body fluids so provide only a crude indication of exposure. Nevertheless, these results in children exposed to high levels of PCBs indicate that the immune function of children might also be adversely affected by the lower levels of PCBs found elsewhere in the world. Although the changes in immune function are subtle, they could be clinically important, write the researchers, and might affect both the general health of children and the degree of protection against infectious diseases that vaccination provides. Finally, these findings suggest that efforts must be stepped up to reduce PCB exposure levels to protect the sensitive immune systems of young children from these potent immunotoxicants.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0030311.
Tox Town, a Web site available from the US National Institutes of Health, provides an introduction to toxic chemicals and environmental health risks
US Agency for Toxic Substances and Disease Registry fact sheet on PCBs
US Environmental Protection Agency information on PCBs
MedlinePlus encyclopedia entries on immunization tetanus vaccine, and diphtheria vaccine
Wikipedia pages on PCBs and vaccines (note: Wikipedia is a free online encyclopedia that anyone can edit)
doi:10.1371/journal.pmed.0030311
PMCID: PMC1551916  PMID: 16942395
24.  PCDD/PCDF indoor exposure in day-care centers and PCDD/PCDF blood concentrations of female employees. 
Environmental Health Perspectives  1998;106(Suppl 2):707-714.
We determined blood concentrations of polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) in 41 female employees with previous exposure to pentachlorophenol-based wood preservatives from 10 day-care centers in the Hamburg, Germany, area. We compared the blood concentrations with estimated age-dependent reference values and analyzed the correlation between PCDD/PCDF indoor air exposure and blood concentrations. The analyses based on the PCDD congeners 1,2,3,4,7,8-, 1,2,3,6,7,8-, and 1,2,3,7,8,9-hexaCDD (hexaCDD), 1,2,3,4,6,7,8-heptaCDD (heptaCDD), octaCDD, and the 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity equivalents calculated according to the international NATO-CCMS model (I-TEQ). In comparison to the estimated reference values, the blood concentrations of hexaCDD and I-TEQ spread around the mean estimate. Data for octaCDD scattered in some cases distinctly above the upper confidence limit. Reference values for heptaCDD could not be estimated. The correlation between PCDD/PCDF indoor air exposure and PCDD/PCDF blood concentrations was examined by linear multiple regression analysis considering different exposure variables and taking confounders into account. Analyses were carried out with the total study group and with a restricted subgroup. Associations were shown between the PCDD/PCDF indoor air concentrations and blood concentrations for heptaCDD and for the I-TEQ, whereas hexaCDD showed no association. OctaCDD showed a negative association in the total study group and no association in the subgroup analysis. In summary, the analyses showed no clear association between PCDD/PCDF indoor air exposure in day-care centers and PCDD/PCDF blood levels of female employees previously exposed to wood preservatives. By contrast, the results consistently indicated a positive association between PCDD/PCDF blood concentrations and exposure to wood preservatives in private homes.
PMCID: PMC1533422  PMID: 9599721
25.  Case Report: Human Exposure to Dioxins from Clay 
Environmental Health Perspectives  2007;116(2):238-242.
Context
For the general population, the dominant source of exposure to dioxin-like compounds is food. As part of the University of Michigan Dioxin Exposure Study (UMDES), we measured selected polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and dioxin-like polychlorinated biphenyls (PCBs) in serum of 946 subjects who were a representative sample of the general population in five Michigan counties.
Case presentation
The total toxic equivalency (TEQ; based on 2005 World Health Organization toxic equivalency factors) of serum from the index case was 211 ppt on a lipid-adjusted basis, which was the highest value observed in the UMDES study population. This subject had no apparent opportunity for exposure to dioxins, except that she had lived on property with soil contaminated with dioxins for almost 30 years, and had been a ceramics hobbyist for > 30 years. Soil from her property and clay that she used for ceramics were both contaminated with dioxins, but the congener patterns differed.
Discussion
The congener patterns in this subject’s serum, soil, and ceramic clay suggest strongly that the dioxin contamination in clay and not soil was the dominant source of dioxin contamination in her serum.
Relevance to public health practice: It appears that ceramic clay, in particular the process of firing clay with unvented kilns, can be a significant nonfood and nonindustrial source of human exposure to dioxins among ceramics hobbyists. The extent of human exposure from ceramic clay is unclear, but it may be widespread. Further work is needed to more precisely characterize the routes of exposure.
doi:10.1289/ehp.10594
PMCID: PMC2235223  PMID: 18288324
ball clay; clay; dioxins; furans; human exposure; polychlorinated biphenyls

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