Abstract  When reporting circulating levels of persistent organic pollutants (POPs), usually lipid-normalized values are given. However, animal experiments and some human data indicate that exposure to POPs may change lipid values. The aim of the present study is to investigate if POP levels can predict future changes in levels of circulating lipids. In the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study, lipids were measured at age 70 and at age 75 in 598 subjects without lipid-lowering medication. Twenty-three different POPs, including 16 polychlorinated biphenyls (PCBs), five organochlorine pesticides, one dioxin (OCDD) and one flame retardant brominated compound (BDE47) were analyzed by high-resolution chromatography coupled to high-resolution mass spectrometry (HRGC/HRMS) at age 70. Strong relationships were seen among the baseline levels of the non-dioxin-like PCBs 194, 206 and 209 and the degree of increase in total serum cholesterol and LDL-cholesterol during the 5 year follow-up. These relationships were generally stronger when lipid-normalized levels were used compared to wet-weight based levels. On the contrary, for two of the pesticides, hexachlorobenzene and trans-nonachlordane, levels were inversely related to the change in LDL-cholesterol, with strongest associations found using wet-weight based levels. PCBs 194, 206 and 209 were inversely related to the change in HDL-cholesterol, in particular for wet-weight based levels. However, these relationships were only significant for wet-weight PCB 194 following adjustment for multiple testing. None of the POPs was related to the change in serum triglycerides. When investigating the association between the change in total serum cholesterol and LDL-cholesterol across different categories of change in BMI, we noted robust results especially in the group with stable BMI, suggesting that the observed relationships were not due to fluctuations in BMI over time. In conclusion, POPs are related to the change in lipids over time, especially LDL-cholesterol. This may explain why POP exposure previously has been linked to atherosclerosis and cardiovascular disease.

Abstract  Background: Persistent organic pollutants may affect the immune and respiratory systems, but available evidence is based on small study populations. We studied the association between prenatal exposure to dichlorodiphenyldichloroethylene (DDE) and polychlorinated biphenyl 153 (PCB 153) and children’s respiratory health in European birth cohorts. Methods: We included 4608 mothers and children enrolled in 10 birth cohort studies from 7 European countries. Outcomes were parent-reported bronchitis and wheeze in the first 4 years of life. For each cohort, we performed Poisson regression analyses, modeling occurrences of the outcomes on the estimates of cord-serum concentrations of PCB 153 and DDE as continuous variables (per doubling exposure) and as cohort-specific tertiles. Summary estimates were obtained through random-effects meta-analyses. Results: The risk of bronchitis or wheeze (combined variable) assessed before 18 months of age increased with increasing DDE exposure (relative risk [RR] per doubling exposure = 1.03 [95% confidence interval = 1.00–1.07]). When these outcomes were analyzed separately, associations appeared stronger for bronchitis. We also found an association between increasing PCB 153 exposure and bronchitis in this period (RR per doubling exposure = 1.06 [1.01–1.12]) but not between PCB 153 and wheeze. No associations were found between either DDE or PCB 153 and ever-wheeze assessed after 18 months. Inclusion of both compounds in the models attenuated risk estimates for PCB 153 tertiles of exposure, whereas DDE associations were more robust. Conclusion: This large meta-analysis suggests that prenatal DDE exposure may be associated with respiratory health symptoms in young children (below 18 months), whereas prenatal PCB 153 levels were not associated with such symptoms.

Abstract  Persistent organic pollutants (POPs), xenobiotics that accumulate in fat tissue, may impair bone metabolism. We studied (1) the association of bone mineral density (BMD) with POPs and (2) whether associations of fat mass (FM) or lean mass (LM), two components of body composition, with BMD differed depending on levels of POPs. Participants aged ≥ 20 in the National Health and Nutrition Examination Survey 1999-2004 were included (n=2769). Eight POPs with detection rate ≥ 80% and three skeletal subregions (left arm, pelvis, and right leg) were selected. All analyses were stratified by gender and age (cutpoint 50 years or more). POPs at background concentrations were mostly unassociated with BMD. However, the associations of FM and LM with BMD depended on POPs concentrations, in particular with BMD of the left arm (usually not weight-bearing) in postmenopausal women. When POPs concentrations were low, FM showed inverse associations with BMD while LM showed positive associations. However, when POPs levels were high, FM showed positive associations with BMD while the positive associations between LM and BMD weakened. POPs may biologically modify the associations of FM and LM with BMD, especially among postmenopausal women, possibly explaining inconsistent associations between FM and BMD in previous epidemiological studies.

Abstract  BACKGROUND: Animal studies and laboratory experiments have demonstrated that exposure to dioxins may be involved in the pathophysiology of endometriosis. However, recent epidemiological investigations have shown conflicting results. Although peritoneal fluid is a specific microenvironment playing a pivotal role in the development of endometriosis, to our knowledge, there is no published study evaluating the concentrations of dioxins in serum and peritoneal fluid simultaneously. The present study explores the possible correlation between the local peritoneal fluid levels of dioxins and concurrent endometriosis.

METHODS: There were 17 infertile women enrolled in the present study. After the diagnostic laparoscopic examination, the women were divided into two groups: endometriosis (n = 10) and controls (n = 7). We measured 29 dioxins simultaneously in serum and peritoneal fluid samples: 7 polychlorinated dibenzo-p-dioxins (PCDDs), 10 polychlorinated dibenzofurans (PCDFs), and 12 polychlorinated biphenyls (dioxin-like PCBs). A dioxin toxic equivalency (TEQ) system was utilized to calculate the dioxin concentration in each sample.

RESULTS: Serum concentrations of itemized components of 29 dioxins were similar in the endometriosis patients compared with the controls. Higher concentrations of PCDFs and dioxin-like PCBs were observed in peritoneal fluid than in serum, whereas the reverse was shown for PCDDs. Statistical analysis showed that higher levels of dioxin TEQ (PCDDs and PCDFs) in peritoneal fluid were significantly associated with an increased risk of endometriosis (OR: 2.5; 95% CI: 1.17-5.34; P = 0.035).

CONCLUSIONS: This is the first report suggesting that higher concentrations of dioxins (PCDDs and PCDFs) in peritoneal fluid are linked to endometriosis. More detail and epidemiological research is warranted to further explore this link.

Abstract  BACKGROUND: Persistent organochlorine pollutants (POP) may affect both the female and male reproductive system in animals as well as in humans.

METHODS: Blood samples were collected from pregnant women and their partners from Greenland, Warsaw and Kharkiv, and from a cohort of Swedish fishermen's wives. Blood samples were analysed for 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p'-DDE). Information on the participants' fertility, measured as time to pregnancy (TTP), was collected. In total, 778 men and 1505 women were included in the analyses.

RESULTS: The data from Warsaw, Kharkiv and the Swedish fishermen's wives indicated no effect of either male or female exposure to POP on TTP. However, among men and women from Greenland, there seemed to be an association between serum concentrations of CB-153 and p,p'-DDE and prolonged TTP. Due to the strong intra-individual correlation between CB-153 and p,p'-DDE in the Greenlandic population, it was not possible to determine whether the risk was associated with CB-153 or p, p'-DDE or was an interaction between the two compounds.

CONCLUSIONS: The overall results of the present study create a somewhat ambiguous pattern, but give some support to the idea that dietary POP exposure might be harmful for couple fertility.

Abstract  Polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and dioxin-like polychlorinated biphenyls (dioxin-like PCBs) are highly-toxic environmental pollutants that are still ubiquitous. About 40 years ago, a mass food poisoning, termed "Yusho", occurred in western Japan, and the causal agent of Yusho was thought to be PCDFs. The preserved umbilical cords of babies who were born to mothers with Yusho 2-5 years after the outbreak of Yusho and diagnosed with fetal Yusho were recently obtained, and the concentrations of PCDDs, PCDFs, dioxin-like PCBs and polychlorinated biphenyls (PCBs) in these preserved umbilical cords were determined. Among babies with fetal Yusho, the pollutant concentrations in umbilical cords were compared between "black babies", a term that describes the dermatologic abnormality that is classically seen in fetal Yusho, and "non-black babies". There was almost no difference in the concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) toxic equivalents (TEQ) concentrations of PCDDs, PCDFs and dioxin-like PCBs found in these two groups of babies. Therefore, the Yusho infants with the dark brown skin pigmentation seemed to have a hypersensitive genetic predisposition to the production of melanin pigment in the skin after the exposure to these toxic compounds. The concentrations of PCDDs, PCDFs, dioxin-like PCBs and PCBs in the preserved umbilical cords of infants diagnosed with fetal Yusho and of healthy babies were also determined and compared. PCDDs, dioxin-like PCBs and PCBs were detected in both groups. PCDFs, however, were found at high concentration only in the babies with fetal Yusho. In 2,3,7,8-TCDD TEQ concentrations, 90% of the total TEQ concentrations were attributable to PCDFs after taking into account the baseline concentrations found in healthy babies. This evidence shows that fetal Yusho is caused by PCDF intoxication.

Abstract  Environmental pollutants can act as endocrine modulators. In this study, we examined whether weight loss-induced changes in plasma organochlorine compounds (OC) were associated with those in plasma insulin levels. Fasting insulin and the area under the curve (AUC) of insulin after a 75-g oral glucose load, plasma levels of 1 commercial polychlorinated biphenyl (PCB) mixture (Aroclor 1260), 1 PCB congener (PCB 153), and 3 pesticides (2,2'-bis(4-chlorophenyl)-1,1-dichloroethylene (p,p'-DDE), beta-hexachlorocyclohexane (beta-HCH), and hexachlorobenzene (HCB)) were measured before and after a 15-week weight loss program induced by a caloric restriction in a sample of obese men and women. Both genders showed a similar reduction in body weight (approximately 11 kg) in response to treatment, although men lost significantly more fat mass than women (mean +/- SD 9.4 +/- 4.1 v 5.9 +/- 5 kg, respectively, P <.05). Fasting insulin and AUC of insulin significantly decreased in men and women after the treatment. In response to weight loss, a significant increase in OC was observed in both genders, and this effect was more pronounced in men. The greater the increase in plasma OC levels, the greater the reduction in fasting insulin was in response to weight loss in men (-.49 < r < -.59, P <.05), but not in women (-.22 < r <.01, not significant [NS]). In both genders, no relationship was observed between changes in plasma OC levels and changes in AUC of insulin (-.41 < r < -.08, NS). In men, relationships between changes in plasma HCB, Aroclor 1260, and PCB-153 concentrations and those in fasting insulin levels in response to weight loss remained significantly correlated after correction for fat mass loss (-.46 < partial r < -.51, P values ranging from.05 to.07). These results suggest that weight loss-induced increase in plasma pollutant levels tends to be independently associated with the reduction of fasting insulin levels in men, but not in women. Further studies are needed to verify whether these findings are causally related.

Abstract  The purpose of this study was to investigate possible associations between concentrations of hydroxylated PCBs (OH-PCBs) and PCBs in the serum of women in the first trimester of pregnancy and thyroid hormone levels and body size of newborn infants in 79 mother-neonate pairs. We measured 16 OH-PCB isomers and 29 PCB isomers in the serum of Japanese women sampled at 11.1±1.9 weeks of gestation. The concentrations of free thyroxine (fT4) and thyroid stimulating hormone (TSH) were measured in whole blood spots on filter papers sampled from the neonates. Dietary and lifestyle information of the mothers were obtained by self-administered questionnaires. Geometric mean (GM) concentrations of the sum of 16 OH-PCB isomers and of 29 PCB isomers were 1.2×10(2)pg/g wet wt. and 69ng/g lipid wt., respectively, in maternal serum. The GM concentrations of neonatal fT4 and TSH were 2.21ng/dL and 1.37μIU/mL, respectively. Multiple regression analysis was performed using measures of neonatal thyroid hormones as dependent variable and serum levels of OH-PCBs/PCBs and other potential covariates (age, pre-pregnancy weight, smoking status, etc.) as independent variables. The results demonstrated a significant positive association between the concentrations of some OH-PCB isomers and that of neonatal TSH. There were no significant associations between levels of PCBs and neonatal fT4, or between OH-PCBs/PCBs and body size of neonates. We conclude that exposure to/body burden of OH-PCBs, but not PCBs, at environmental levels during the first trimester of pregnancy can affect neonatal thyroid hormone status.

Abstract  Maternal diet not only provides essential nutrients to the developing fetus but is also a source of prenatal exposure to environmental contaminants. We investigated the association between dietary intake of dioxins and PCBs during pregnancy and birth size. The study included 50,651 women from the Norwegian Mother and Child Cohort Study (MoBa). Dietary information was collected by FFQs and intake estimates were calculated by combining food consumption and food concentration of dioxins, dioxin-like PCBs and non-dioxin-like PCBs. We used multivariable regression models to estimate the association between dietary intake of dioxins and PCBs and fetal growth. The contribution of fish and seafood intake during pregnancy was 41% for dietary dioxins and dioxin-like PCBs and 49% for dietary non-dioxin-like PCBs. Further stratified analysis by quartiles of seafood intake during pregnancy was conducted. We found an inverse dose-response association between dietary intake of dioxins and PCBs and fetal growth after adjustment for confounders. Newborns of mothers in the upper quartile of dioxin and dioxin-like PCBs intake had 62g lower birth weight (95% CI: -73, -50), 0.26cm shorter birth length (95% CI: -0.31, -0.20) and 0.10cm shorter head circumference (95% CI: -0.14, -0.06) than newborns of mothers in the lowest quartile of intake. Similar negative associations for intake of dioxins and dioxin-like PCBs were found after excluding women with intakes above the tolerable weekly intake (TWI=14pg TEQ/kg bw/week). The negative association of dietary dioxins and PCBs with fetal growth was weaker as seafood intake was increasing. No association was found between dietary dioxin and PCB intake and the risk for small-for-gestational age neonate. In conclusion, dietary intakes of dioxins and PCBs during pregnancy were negatively associated with fetal growth, even at intakes below the TWI.

Abstract  Persistent organic pollutants such as polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and organochlorine pesticides (OCPs) are of global concern because of their widespread contamination and adverse health effects. Potential endocrine disruption, especially of thyroid status by PCBs has been repeatedly suggested in both experimental and epidemiological studies. However the associations with PBDEs or OCPs have been arguable especially in human populations. We investigated the associations between major groups of POPs and thyroid hormone balances among pregnant women. One hundred five pregnant women at delivery were recruited from four cities of Korea in 2011 and were investigated. Blood samples were collected within a day before delivery. Serum was then analyzed for 19 PCBs, 19 PBDEs, and 19 OCPs, along with five thyroid hormones (free and total T3 and T4, and TSH). Several PCBs such as PCB28, 52, and 118 showed negative associations with T3 or T4. BDE47 and total PBDEs showed significant associations with T3 or T4. For OCPs, dichlorodiphenyltrichloroethanes (DDTs) and hexachlorobenzene (HCB) were generally associated with reduction of T3 or T4. The thyroid hormone levels of all subjects were within the reference range, however exposure to several target POPs were clearly related with potential for disrupting thyroid hormone balance among pregnant women, at the current level of exposure. Although subtle, the changes in thyroid hormones should be seen with caution because even minor changes within pregnant women may have significant consequences especially on sensitive population like fetus.

Abstract  BACKGROUND: Polychlorinated biphenyls (PCBs) are ubiquitous environmental pollutants that are potentially toxic to the developing brain. Hydroxylated metabolites of PCBs (OH-PCBs) are suggested to be even more toxic. Little is known about their short-term effects on human health.

OBJECTIVES: To determine whether prenatal background exposure to PCBs and OH-PCBs was associated with the motor development of three-month-old infants.

METHODS: Ninety-seven mother-infant pairs participated in this Dutch, observational cohort study. We determined the concentrations of PCBs and OH-PCBs in cord blood samples. When the infants were three months old we evaluated their motor development by assessing the presence and performance of spontaneous movement patterns from video recordings. We calculated a Motor Optimality Score (MOS). The score could range from low (5) to high (28) optimality. We explored the correlations between PCB and OH-PCB levels and MOS. Subsequently, we tested whether the levels differed between infants with a low (<26) or high (≥26) MOS and whether the levels associated with detailed aspects of their motor repertoires.

RESULTS: We found several associations between PCB and OH-PCB levels and MOS, including detailed aspects of the early motor development. High 4-OH-PCB-107 levels were associated with a low MOS (P=.013). High PCB-187 levels were associated with reduced midline arm and leg movements (P=.047 and P=.043, respectively). High 4'-OH-PCB-172 levels were associated with more manipulation (P=.033).

CONCLUSIONS: Prenatal exposure to high background levels of most PCBs and 4-OH-PCB-107 seems to impair early motor development, whereas only 4'-OH-PCB-172 showed the opposite.

Abstract  Animal studies showed that the developing brain is particularly sensitive to chemical exposure. Human studies carried out in areas with high exposures have proven neurodevelopmental disorders in relation to e.g. lead and PCBs. Whether these chemicals are associated with behavioural problems in childhood at current environmental levels is not well known. Therefore, we assessed the association between prenatal exposure to lead, cadmium, PCBs, dioxin-like compounds, HCB and p,p'-DDE and behavioural problems in 7-8year old children. Prenatal exposure data were obtained from the Flemish mother-new-born cohort. Lead, cadmium, PCBs, dioxin-like compounds, HCB and p,p'-DDE were analysed in cord blood. When the child reached 7-8years, 270 mothers completed the Strengths and Difficulties Questionnaire assessing their children's behavioural health. We found that doubling the prenatal lead exposure (cord blood lead levels) was associated with a 3.43 times higher risk for hyperactivity in both boys and girls. In addition, total difficulties were 5.08 times more likely in the highest tertile for prenatal lead exposure compared to the lowest tertile. In girls, total difficulties were 4.92 more likely when doubling cord blood p,p'-DDE, whereas no significant association was found in boys. Further, we noted in boys a 1.53 times higher risk for emotional problems when doubling cord blood cadmium, whereas no significant association was found in girls. These results indicate that the presence of environmental contaminants influences the mental health of the next generation.

Abstract  Persistent organic pollutants (POPs) are suggested to contribute to lower vitamin D levels; however, studies in humans are scarce and have never focused on pregnancy, a susceptibility period for vitamin D deficiency. We investigated whether serum levels of POPs were associated with circulating 25-hydroxyvitamin D3 [25(OH)D3] concentration in pregnancy. Cross-sectional associations of serum concentrations of eight POPs with plasma 25(OH)D3 concentration were analyzed in 2031 pregnant women participating in the Spanish population-based cohort INfancia y Medio Ambiente (INMA) Project. Serum concentrations of POPs were measured by gas chromatography and plasma 25(OH)D3 concentration was measured by high-performance liquid chromatography in pregnancy (mean 13.3±1.5weeks of gestation). Multivariable regression models were performed to assess the relationship between blood concentrations of POPs and 25(OH)D3. An inverse linear relationship was found between serum concentration of PCB180 and circulating 25(OH)D3. Multivariate linear regression models showed higher PCB180 levels to be associated with lower 25(OH)D3 concentration: quartile Q4 vs. quartile Q1, coefficient=-1.59, 95% CI -3.27, 0.08, p trend=0.060. A non-monotonic inverse relationship was found between the sum of predominant PCB congeners (PCB 180, 153 and 138) and 25(OH)D3 concentration: coefficient (95% CI) for quartile Q2 vs. Q1 [-0.50 (-1.94, 0.94)], quartile Q3 vs. Q1 [-1.56 (-3.11, -0.02)] and quartile Q4 vs. Q1 [-1.21 (-2.80, 0.38)], p trend=0.081. No significant associations were found between circulating 25(OH)D3 and serum levels of p,p'-DDE, p,p'-DDT, HCB, and ß-HCH. Our results suggest that the background exposure to PCBs may result in lower 25(OH)D3 concentration in pregnant women.

Abstract  OBJECTIVE: To determine the relationships between tibial bone lead and serum polychlorinated biphenyl (PCB) concentrations and neurocognitive function.

METHODS: The study population consisted of men and women former capacitor workers had been employed by the General Electric Corporation between 1946 and 1977. Regression analyses evaluated the association between neurocognitive function and lipid-adjusted serum PCB and tibia lead concentrations.

RESULTS: Tibia lead, but not serum PCBs, was significantly correlated with deficits in neurocognitive function. Women showed more associations between tibia lead and neurocognitive function than men, especially regarding executive function.

CONCLUSIONS: These results demonstrate that low levels of tibia lead, but not serum PCBs, are associated with neurocognitive deficits and that postmenopausal women show a greater number of deficits in executive function than men.

Abstract  Recent research emphasizes the contribution of environmental as well as genetic factors to the etiology of autism but studies testing associations between chemical exposures and autism have been limited. Prenatal exposure to persistent organic pollutants (POPs) has previously been associated with decrements in cognitive and developmental performance. We conducted a pilot study in the Finnish Prenatal Study of Autism (FiPS-A). Seventy-five cases with autism and 75 controls matched on sex, birth year, urbanization and maternal age were sampled from first-born children in the Finnish Maternity Cohort, which includes over 1million births. The study sample included births occurring from 1991 to 2000. Subjects were followed up for autism through 2007. DDT, DDE, PCB-118, PCB-138, PCB-153, PCB-156, PCB-170, PCB-180, hexachlorobenzene, and BDE-47 were measured in archived maternal serum samples taken during pregnancy using gas chromatography-high resolution mass spectrometry. Correlations between pollutant measures were assessed and mechanistically-related weighting schemes for summarizing PCB levels were compared. Case and control differences were assessed using graphical and statistical methods. All analytes, with the exception of DDT and BDE-47, were detected above the limit of quantification in all samples. The correlation between levels of individual PCB congeners and weighted summary measures was high (0.71-1.00). Paired t-tests revealed no significant differences between cases and controls for log-transformed mean values of any analyte; however, in an adjusted model the odds ratios for autism were 1.91 (p=0.29) and 1.79 (p=0.36) respectively, for subjects with total PCBs and DDE above the 90th percentile of control values. Levels of prenatal PCB exposure in FIPS-A were similar to the levels which previously correlated with poorer neurodevelopmental measures in other populations. Further study in a larger sample will be required to fully determine whether exposure to high POP levels is associated with autism diagnosis in the population.

Abstract  Background: Because of their lipophilic nature, polychlorinated biphenyls (PCBs) bioaccumulate in the food chain and their residues have been detected in foods. Consequently, they accumulate readily in the human body. Reports suggest that PCB blood Levels remain constant or increase. Little, however, is known about the Longterm hazardous effects of PCBs and dioxins on human health. Yusho is a type of food poisoning caused by PCBs and dioxins that contaminated rice bran oil. We analyzed blood samples of the Yusho patients from 1986 to 2002, and studied changes in blood cell counts, blood chemistry and tumor markers. Participants and methods: A population of 1041 patients was divided into patient and control groups based on the diagnostic criteria established for Yusho and participant's blood polychlorinated quarterphenyl (PCQ) levels. In total, 1666 blood and 1652 urine samples from 374 patients in the patient group (PCQ levels = 0.1 ppb), and 373 blood and 302 urine samples from 151 people in the control group (PCQ levels < 0.02 ppb) were analyzed. Blood Levels of PCBs, PCQs, polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) were determined, and we analyzed their correlation with the data of complete blood cell counts, blood chemistry and urinalysis. Results and conclusion: Blood analyses, blood chemistry and urine values in Yusho patients were not significantly different from those in the control group 34 years after the Yusho incident. PCBs, PCQs or PCDFs may, however, affect hematogenesis, serum potassium, serum phosphorus, protein metabolism and creatine kinase metabolism because these parameters had slight but significant correlations with the levels of PCBs, PCQs or PCDFs. Exposure to PCBs and the related organochlorine compounds should be avoided. (C) 2004 Published by Elsevier Ireland Ltd on behalf of Japanese Society for Investigative Dermatology.

Abstract  BACKGROUND: Prenatal exposure to environmental levels of organochlorines (OCs) has been demonstrated to have immunotoxic effects in humans. We investigated the relationship between prenatal exposure to OCs and the occurrence of otitis media (OM) among Inuit children in Greenland.

METHODS: We estimated the concentration of 14 PCB congeners and 11 pesticides in maternal and cord blood samples and in breast milk in a population-based cohort of 400 mother-child pairs. At follow-up, we examined the children's ears and used their medical records to assess the OM occurrence and severity. Multivariate regression analyses were used with adjustments for passive smoking, crowding, dietary habits, parent's educational level, breast feeding and the use of child-care.

RESULTS: The children were 4-10 years of age at follow-up and 223 (85%) participated. We found no association between prenatal OC exposure and the development of OM. Factors associated with the child's hazard of OM during the first 4 years of life were: mother's history of OM (HR 1.70, 95% CI 1.11-2.59, p=0.01); mother's smoking habits: current (HR 2.47, 95% CI 1.45-4.21, p<0.01) and previous (HR 2.00, 95% CI 1.19-3.36, p<0.01); number of smokers in the home (HR 1.17, 95% CI 1.05-1.31, p<0.01). After adjustment mothers' smoking habits remained significant.

CONCLUSION: We found no relationship between high levels of prenatal exposure of OCs and occurrence of OM. Passive smoking was found as the strongest environmental risk factor for the development of OM. Interventions to reduce passive smoke in children's environment are needed.

Abstract  BACKGROUND: People in developed countries are widely exposed to low levels of organochlorine pesticides, polychlorinated biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs). Seafood is a major contributor to PCB exposure. Toxicity of those various pollutants to reproductive and endocrine functions raises questions about possible effects on fertility. We explored whether serum levels of these pollutants and seafood consumption were associated with the fertility of couples enrolled in a French birth cohort (PELAGIE).

METHODS: Time-to-pregnancy was investigated in 3,421 pregnant women by asking how many months they had taken to conceive. Levels of 14 organochlorine pesticides, 12 PCBs, and 10 PBDE compounds were measured in cord blood serum from a random subcohort (n = 394). Mercury concentrations measured in maternal hair were considered as a potential coexposure. Fecundability odds ratios (ORs) were estimated from multivariate discrete-time Cox proportional hazard models.

RESULTS: Shellfish consumption was associated with longer time-to-pregnancy (fecundability OR ≥twice/week vs. <twice/month = 0.71 [95% confidence interval = 0.60-0.83]), but fish consumption was not. Time-to-pregnancy increased with increasing serum levels for most of the compounds studied (for total PCBs >0.410 µg/L vs. <0.266 µg/L, fecundability OR = 0.46 [0.32-0.66]). In multiple sensitivity analyses, reduced fecundability was most consistently associated with shellfish consumption, p,p'-DDE, total PCBs, PCB153, and PCB187. Models that simultaneously included multiple coexposure factors led to similar conclusions.

CONCLUSIONS: Our findings were robust in sensitivity analyses, including analysis restricted to primiparous women. These results suggest that PCBs, p,p'-DDE, and other shellfish contaminants may impair human fertility.

Abstract  OBJECTIVES: The purpose of this study was to investigate the associations between serum concentrations of hydroxylated PCBs (OH-PCBs) and PCBs and measures of thyroid hormone status of Japanese pregnant women.

METHODS: The concentrations of free thyroxine (fT4), thyroid stimulating hormone (TSH), and thyroxine binding globulin (TBG) as well as 16 OH-PCB isomers and 29 PCB isomers were analyzed in the serum of 129 women sampled in the first trimester of gestation. Dietary and lifestyle information of the subjects was obtained by self-administered questionnaire. Multiple regression analysis was performed using measures of thyroid hormones as the dependent variable and serum levels of OH-PCBs/PCBs, urinary iodine concentration, and other potential covariates (age, BMI, smoking, etc.) as independent variables.

RESULTS: Geometric mean (GM) concentration of the sum of 16 isomers of OH-PCBs was 120 pg/g wet wt. and that of 29 isomers of PCBs was 68 ng/g lipid wt., respectively, in the serum of the subjects. Iodine nutrition was considered adequate to high from urinary iodine level (GM, 370 μg/g creatinine). The mean concentration of TSH, fT4 and TBG was 1.34 ± 1.37 μIU/mL, 1.22 ± 0.16 ng/dL and 33.0 ± 6.4 μg/mL, respectively, with a small number of subjects who were outside the reference range. Multiple regression analysis revealed that serum concentrations of OH-PCBs/PCBs were not significantly associated with any of the measures of thyroid hormone status.

CONCLUSIONS: Exposure/body burden of OH-PCBs and PCBs at environmental levels does not have a measurable effect on thyroid hormones.

Abstract  EIS: Epidemiology Information System

Abstract  During the last ten years, interest has been focussed on occupational exposure in thermoelectric power plants (i.e., coal dust, polycyclic aromatic hydrocarbons, dioxin, dielectric liquids, PCB's, asbestos, etc.), although available evidence on its effects on the health status of the occupational population are far from being definitive. A retrospective cohort study was carried out to investigate the association between exposure to risk factors and mortality for cancer in three thermoelectric power plants located in the north-east of Italy. The three plants studied started with oil and coal but since 1968 they utilized mostly coal as fuel. In spite of the different fuel used at the beginning, the production process has been fairly constant since the main conversion from oil to coal with a substantial increase in power production. A total of 1,772 male workers were included in the total study cohort and followed-up from 1968 to 1987, with a total of 22,090 person-years of exposure. Eighty percent of the cohort began to work in the plant before 30 years of age, and had a mean period of employment of 9.5 years. The cohort was completely traced to the end of the follow-up period by using an original computer system based on personal fiscal codes. Causes of death were ascertained in the municipalities where the deaths occurred and coded according to the International Classification of Disease, IX Revision. During the study period 68 deaths were observed with an SMR for all causes of death equal to 0.79.

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

Abstract  It has been shown by others that offspring of mothers who had been exposed to dioxins and polychlorinated biphenyls (PCBs) during pregnancy have elevated plasma levels of thyroid-stimulating hormone (TSH) for at least 3 months after birth and reduced plasma levels of free and total thyroxine during the second week after birth. As elevated levels of dioxins and PCB s can thus alter thyroid hormone status, the relation between the levels of some polychlorinated organic compounds in the blood lipids and growth and thyroid hormone status was studied in 12 hospitalized schoolchildren from the Aral Sea region known to have high exposure to such compounds. Their level of PCBs was two to four times higher than in healthy Stockholm children. Their height was found to be lower than in healthy Swedish children of the same age mean (SDS -0.52) and the body mass index (BMI) was inversely correlated to the total concentrations of PCBs and dichlorodiphenyltrichloroethane (DDT) and its metabolite dichlorophenyldichloroethylene (DDE) in the blood lipids. As the levels of insulin-like growth factor- were reduced to the same extent as the BMI it seems likely that PCBs and DDT cause malnutrition as a result of malabsorption. None of the children had any impairment of thyroid function, as revealed by the plasma levels of TSH and thyroxine. Although the concentrations of beta-hexachlorocyclohexane (beta-HCH) and DDE were extremely high in some of the children there was no relation between thyroid hormone status and the blood lipid levels of PCBs, hexachlorocyclohexane and DDT. However, the concentration of dioxins was not analysed.

Abstract  Environmental exposures, timing and duration of exposure, and one's genetic susceptibility all contribute to breast carcinoma and its progression. The purpose of this article was to identify known and suspected environmental causes of breast carcinoma, identify some environmental risk factors that may represent significant risk factors for certain groups, and describe current studies, supported by the National Institutes of Health/National Institute of Environmental Health Sciences, that clarify how environmental factors contribute to the development of breast carcinoma. Known and suspected environmental risk factors include organochlorine pesticides and other synthetic chemicals, hormonal factors (including exogenous endocrine disrupters), diet, tobacco and alcohol use, radiation, and magnetic fields. In at least 50% of breast carcinoma cases, none of the known risk factors apply. It is likely that an environmental component accounts for much of the unknown 50% of risk. Knowing the environmental factors for breast carcinoma development is an area that should be investigated intensely because it offers our best hope for prevention. Understanding why African-American women have a more aggressive form of breast carcinoma, whether they receive adequate follow-up treatment, and how these factors contribute to increased mortality rates requires further exploration. Data that demonstrate the lower incidence rate of breast carcinoma in Asian women, the relation to low fat diets and diets high in phytoestrogens, and how this might serve as a model for all women should be investigated. Finally, differences in behavioral and cultural attitudes, ethnicity, economic status, and life-style influences among different groups of women require further study to determine how these factors contribute to enhancing or reducing breast carcinoma risk.