Abstract  INTRODUCTION: Several epidemiological studies have reported that some organochlorine compounds (OCs), such as polychlorobiphenyls (PCBs) and 1,1-dichloro-2,2-bis(4-chlorophenyl)ethylene (4,4'-DDE), may alter thyroid function. OBJECTIVE: The aim of the present study was to investigate the association of maternal serum OC concentrations of 4,4'-DDE and the sum of seven PCB congeners (PCB 28, 52, 101, 118, 138, 153, and 180) with thyroid hormone (TH) status. METHODS: We measured OC concentrations in 157 maternal serum samples at 12 weeks of pregnancy in a cohort from Valencia (Spain). Thyroid-stimulating hormone (TSH), total triiodothyronine (TT3), and free thyroxine (FT4) were measured as biomarkers of thyroid function in the same samples. Linear and logistic regression analyses were performed between OCs and TH levels, and variables were log transformed. RESULTS: Mothers with higher levels of 4,4'-DDE had higher odds of having TSH levels >2.5 mIU/L (OR=2.53; 95% CI=1.36; 4.73; p=0.004), and we found a significant negative association between serum 4,4'-DDE concentrations and FT4 levels (beta=-0.03; 95% CI=-0.05; 0.00; p=0.050) after adjustment for covariates and total lipids. No association was found between sum of PCBs and TH levels. CONCLUSION: Serum concentrations of 4,4'-DDE were associated with increased TSH and reduced FT4 but not TT3 levels. Our results suggest that some environmental chemicals may interfere with the thyroid system of pregnant women. The major role that maternal THs may play in fetal neurodevelopment makes these findings especially relevant.

Abstract  Perinatal exposure to PCBs and dioxins is associated with immune changes in healthy Dutch preschool children. To examine whether such effects persist into later childhood, we here report on the immunological effects of perinatal exposure to PCBs and dioxins in 167 Dutch children at school age. A higher postnatal PCB exposure was associated with a higher prevalence of recurrent middle ear infections and a higher prenatal PCB exposure with less shortness of breath with wheeze, as assessed by parent questionnaire. Our data indicate that, at environmental levels of these man made chemicals, subtle health effects may occur.

Abstract  Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants. In utero exposure to background levels of PCBs has been associated with intellectual impairment among children in most, but not all, studies. The authors evaluated prenatal PCB exposure in relation to cognitive test (intelligence quotient (IQ)) scores on the Wechsler Intelligence Scale for Children at age 7 years. Pregnant women were recruited from 12 US study centers from 1959 to 1965, and their children were followed until age 7 years (the Collaborative Perinatal Project). Third trimester serum was analyzed for PCBs in 1997-1999 for 732 women selected at random and for an additional 162 women whose children had either a low or a high IQ score. The PCB-IQ association was examined in multivariate models. Among those in the lowest exposure category (<1.25 microg of PCB/liter of serum), the fully adjusted mean IQ score was 93.6 (standard error: 1.8); among those in the highest category (> or =5 microg of PCB/liter), the mean IQ was 97.6 (standard error: 1.2); and overall the increase in IQ per unit increase in PCB level (microg/liter) was 0.22 (95% confidence interval: -0.28, 0.71). In these data, in utero exposure to background levels of PCBs was not associated with lower IQ at age 7 years.

Abstract  Prenatal exposure to polychlorinated biphenyls (PCBs) and polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) can affect neurobehavioral development of infants and children. This effect may be mediated through disruption of thyroid hormone homeostasis. However, epidemiological studies reveal no consistent influence of PCDD/Fs and PCBs on thyroid status and neurodevelopment at environmental background levels. The effects may resolve with time of further decreasing exposure to these compounds. The aim of this study was to find out if there are still effects related to prenatal PCDD/F and PCB observable at the meanwhile decreased levels of exposure by using the same methods which have been applied in similar studies during the last 10 years in Europe. The birth cohort study was initiated in the year 2000 in the industrialized city of Duisburg, Germany. 232 healthy mother-infant pairs were recruited between 2000 and 2002. Dioxins, dioxin-like PCBs and six indicator PCBs were analyzed in maternal blood during pregnancy and in maternal milk following extraction and sample clean-up by HRGC/HRMS. Thyroid stimulating hormone (TSH), total thyroxine (T4), total triiodothyronine (T3), free thyroxine (FT4) and free triiodothyronine (FT3) were measured in serum samples of the pregnant women and in cord serum samples by chemiluminescent immunometric assay. Neurological examinations were performed at ages 2 weeks and 18 months using the neurological optimality score (NOS), mental and motor development were assessed using the Bayley Scales of Infant Development (BSID) at ages 12 and 24 months. Multiple linear regression analysis was used to describe the association of PCDD/F and PCB in maternal blood or milk with the outcome measurements after adjustment for confounding. Blood levels (n=182) of WHO 2005 toxic equivalents (TEQ) (PCDD/F+PCB) were in the range of 3.8-58.4 pg/glipid base (median: 19.3 pg/glipid base). The corresponding data for human milk (n=149) were 2.6-52.4 pg/glipid base (median: 19.7 pg/glipid base). Multiple regression analysis showed no decrease of thyroid hormones related to WHO 2005 TEQ in blood and milk of mothers and their newborns. Furthermore, no associations between exposure and neurological and developmental measures were observed. This study supports the view that the current decreased exposure to PCDD/Fs and PCBs does not impair thyroid function of newborns and neurodevelopment of infants until the age of 24 months.

Abstract  Objective: To investigate the possible association between the body burden of dioxin-like compounds and endometriotic disease. Design: Case-control study. Setting: Gynecology ward in a university hospital. Patient(s): Seventy-one women with peritoneal endometriosis (n = 25) or deep endometriotic (adenomyotic) nodules (n = 25) and controls (n = 21). Intervention(s): Collection of 200 mL of blood (fasted) and face-to-face interview. Main Outcome Measure(s): Assessment of dioxin (PCDD), furan (PCDF), and dioxin-like PCB serum concentrations (picograms toxic equivalent [TEQ]/g lipids). Result(s): Age and body mass index were traced by linear multiple regression as determinants of total TEQ levels. After standardization for these variables (30 years and 22.5 kg/m2), the mean TEQ levels were 24.21 (controls), 30.62 (peritoneal endometriosis), and 37.60 (deep endometriotic [adenomyotic] nodules) pg TEQ/g lipids. Logistic regression analysis indicated a significantly increased risk of deep endometriotic (adenomyotic) nodules (odds ratio [OR], 3.3; 95% confidence interval [CI], 1.4–7.6) for an increment of 10 pg in total TEQ levels/g lipids. An increased risk was also found for peritoneal endometriosis (OR, 1.9; 95% CI, 0.9–3.8) for total TEQ levels and for dioxins alone (OR, 3.2; 95% CI, 1.0–9.9). Conclusion(s): The results provide the first epidemiological evidence of an association between increased PCDD/PCDF and PCB body burden and endometriosis.

Abstract  Background: Production of polychlorinated biphenyls (PCBs) ended in the United States in the 1970s, but PCBs persist in the environment and are detectable in the blood of approximately 80% of Americans over age 50. PCBs decrease dopamine levels in rats and monkeys. Loss of dopamine is the hallmark of Parkinson disease, a neurodegenerative disease. There are no epidemiologic studies of PCBs and neurodegenerative disease. Methods: We conducted a retrospective mortality study of 17,321 PCB-exposed workers to determine whether mortality from Parkinson disease, dementia, and amyotrophic lateral sclerosis was elevated compared with the U.S. population. All workers had a least 90 days employment in 1 of 3 electrical capacitor plants using PCBs from the 1940s to the 1970s. PCB serum levels from a sample of these workers in the 1970s were approximately 10 times the level of community controls. Results: We found no overall excess of Parkinson disease, amyotrophic lateral sclerosis, or dementia in the PCB-exposed cohort (standardized mortality ratios [SMRs]-1.40, 1.11, and 1.26, respectively, and number of deaths-14, 10, and 28 respectively). However, sex-specific analyses revealed that women had an excess of amyotrophic lateral sclerosis (SMR-2.26; 95% confidence interval [CI] = 1.08-4.15; 10 deaths). Furthermore, among highly exposed women (defined by a job-exposure matrix), we found an excess of Parkinson disease (SMR-2.95; 95% CI = 1.08-6.42; 6 deaths) and dementia (SMR-2.04; 95% CI = 1.12-3.43; 14 deaths). Conclusions: Our data are limited due to small numbers and reliance on mortality rather than incidence data, but are suggestive of an effect of PCBs on neurodegenerative disease for women. The literature does not offer an explanation for why women would be more affected than men by PCB exposure for these outcomes.

Abstract  The aim of this study was to examine the effects of prenatal and postnatal chronic exposure to mercury (Hg), polychlorinated biphenyls (PCBs) and lead (Pb) on the neuromotor development of preschool children. The study population consisted of 110 preschool Inuit children from Nunavik (Canada). Blood Hg, PCBs and Pb concentrations were measured at birth (cord blood) and at the time of testing. Gross motor functions were evaluated and a neurological examination was performed. Fine neuromotor performance was assessed using quantitative measures of postural hand tremor, reaction time, sway oscillations, as well as alternating and pointing movements. Potential covariates were documented including demographic and familial characteristics, other prenatal neurotoxicants (alcohol, tobacco) and nutrients (selenium (Se), Omega-3 polyunsaturated fatty acids (n-3 PUFA)). Hierarchical multivariate regression analyses were performed, controlling for significant covariates. Gross motor development was not linked to prenatal exposures. However, significant associations were observed between blood Pb concentration at testing time and changes in reaction time, sway oscillations, alternating arm movements and action tremor. For some of these outcomes, neuromotor effects of Pb exposure are observed at blood concentrations below 10 μg/dl. Negative effects of PCBs on neuromotor development were not clearly observed, neither were the potential beneficial effects of n-3 PUFA and selenium. Tremor amplitude was related to blood Hg concentrations at testing time, which corroborate an effect already reported among adults.

Abstract  Background. Children are commonly exposed at background levels to several ubiquitous environmental pollutants, such as lead and persistent organic pollutants, that have been linked to neurologic and endocrine effects. These effects have prompted concern about alterations in human reproductive development. Few studies have examined the effects of these toxicants on human sexual maturation at levels commonly found in the general population, and none has been able to examine multiple toxicant exposures. The aim of the current investigation was to examine the relationship between attainment of menarche and levels of 6 environmental pollutants to which children are commonly exposed at low levels, ie, dichlorodiphenyldichloroethylene (p,p′-DDE), hexachlorobenzene (HCB), polychlorinated biphenyls (PCBs), mirex, lead, and mercury. Methods. This study was conducted with residents of the Akwesasne Mohawk Nation, a sovereign territory that spans the St Lawrence River and the boundaries of New York State and Ontario and Quebec, Canada. Since the 1950s, the St Lawrence River has been a site of substantial industrial development, and the Nation is currently adjacent to a US National Priority Superfund site. PCB, p,p′-DDE, HCB, and mirex levels exceeding the US Food and Drug Administration recommended tolerance limits for human consumption have been found in local animal species. The present analysis included 138 Akwesasne Mohawk Nation girls 10 to 16.9 years of age. Blood samples and sociodemographic data were collected by Akwesasne community members, without prior knowledge of participants' exposure status. Attainment of menses (menarche) was assessed as present or absent at the time of the interview. Congener-specific PCB analysis was available, and all 16 PCB congeners detected in >50% of the sample were included in analyses (International Union of Pure and Applied Chemistry numbers 52, 70, 74, 84, 87, 95, 99, 101 [+90], 105, 110, 118, 138 [+163 and 164], 149 [+123], 153, 180, and 187). Probit analysis was used to determine the median age at menarche for the sample. Binary logistic regression analysis was used to determine predictors of menarcheal status. Six toxicants (p,p′-DDE, HCB, PCBs, mirex, lead, and mercury) were entered into the logistic regression model. Age, socioeconomic status (SES), and BMI were tested as potential cofounders and were included in the model at P < .05. Interactions among toxicants were also evaluated. Results. Toxicant levels were measured in blood for this sample and were consistent with long-term exposure to a variety of toxicants in multiple media. Mercury levels were at or below background levels, all lead levels were well below the Centers for Disease Control and Prevention action limit of 10 μg/dL, and PCB levels were consistent with a cumulative, continuing exposure pattern. The median age at menarche for the total sample was 12.2 years. The predicted age at menarche for girls with lead levels above the median (1.2 μg/dL) was 10.5 months later than that for girls with lead levels below the median. In the logistic regression analysis, age was the strongest predictor of menarcheal status and SES was also a significant predictor but BMI was not. The logistic regression analysis that corrected for age, SES, and other pollutants (p,p′-DDE, HCB, mirex, and mercury) indicated that, at their respective geometric means, lead (geometric mean: 0.49 μg/dL) was associated with a significantly lower probability of having reached menarche (β = −1.29) and a group of 4 potentially estrogenic PCB congeners (E-PCB) (geometric mean: 0.12 ppb; International Union of Pure and Applied Chemistry numbers 52, 70, 101 [+90], and 187) was associated with a significantly greater probability of having reached menarche (β = 2.13). Predicted probabilities at different levels of lead and PCBs were calculated on the basis of the logistic regression model. At the respective means of all toxicants and SES, 69% of 12-year-old girls were predicted to have reached menarche. However, at the 75th percentile of lead levels, only 10% of 12-year-old Mohawk girls were predicted to have reached menarche; at the 75th percentile of E-PCB levels, 86% of 12-year-old Mohawk girls were predicted to have reached menarche. No association was observed between mirex, p,p′-DDE, or HCB and menarcheal status. Although BMI was not a significant predictor, we tested BMI in the logistic regression model; it had little effect on the relationships between menarcheal status and either lead or E-PCB. In models testing toxicant interactions, age, SES, lead levels, and PCB levels continued to be significant predictors of menarcheal status. When each toxicant was tested in a logistic regression model correcting only for age and SES, we observed little change in the effects of lead or E-PCB on menarcheal status. Conclusions. The analysis of multichemical exposure among Akwesasne Mohawk Nation adolescent girls suggests that the attainment of menarche may be sensitive to relatively low levels of lead and certain PCB congeners. This study is distinguished by the ability to test many toxicants simultaneously and thus to exclude effects from unmeasured but coexisting exposures. By testing several PCB congener groupings, we were able to determine that specifically a group of potentially estrogenic PCB congeners affected the odds of reaching menarche. The lead and PCB findings are consistent with the literature and are biologically plausible. The sample size, cross-sectional study design, and possible occurrence of confounders beyond those tested suggest that results should be interpreted cautiously. Additional investigation to determine whether such low toxicant levels may affect reproduction and disorders of the reproductive system is warranted.

Abstract  Wildlife studies suggest that consumption of contaminated fish from the Great Lakes may expose humans to polychlorinated biphenyls and persistent chlorinated pesticides. To assess whether time to pregnancy or fecundability is affected, we conducted a telephone survey in 1993 with female members of the New York State Angler Cohort Study who were considering pregnancy between 1991 and 1994 (N = 2,445). Among the 1,234 (50%) women who became pregnant, 895 (73%) had a known time to pregnancy. Upon enrollment into the cohort in 1991, both partners reported duration and frequency of Lake Ontario sport fish consumption. We estimated lifetime exposure to polychlorinated biphenyls from recent consumption and used a discrete-time analog of Cox proportional hazards analysis to estimate conditional fecundability ratios and 95% confidence intervals (CIs) for fish consumption among couples with complete exposure data who discontinued birth control to become pregnant (N = 575). Maternal consumption of fish for 3-6 years was associated with reduced fecundability (fecundability ratio = 0.75; 95% CI = 0.59-0.91), as was more than a monthly fish meal in 1991 (fecundability ratio = 0.73; 95% CI = 0.54-0.98). Our findings suggest that maternal but not paternal consumption of contaminated fish may reduce fecundability among couples attempting pregnancy.

Abstract  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.

Abstract  The effect of organochlorine compounds (OCs) on thyroid function, as well as the potential confounding effect of iodine intake, was studied in a large sample of pregnant women from two population-based cohort studies in Sabadell (n = 520) and Gipuzkoa (n = 570), Spain. Thyroid hormones (free T4 and total T3), thyrotropin, and polychlorinated biphenyls (PCB congeners 118, 138, 153, and 180), hexachlorobenzene (HCB), beta-hexachlorocyclohexane (beta-HCH), dichlorodiphenyl dichloroethylene (p'p'-DDE) and dichlorodiphenyl richloroethane (p'p-DDT) were measured in serum samples collected at first trimester of pregnancy. Urinary iodine concentration (UIC) was measured and iodine intake from diet, iodized salt, and supplements were estimated from a food frequency questionnaire. Levels of HCB and PCBs congeners 180, 153, and 138 were related to lowe rtotal T3 levels (adjusted coefficient (SE): -4.0(1.1), -6.1(1.6), -5.5(1.6), and 3.8(1.4), respectively) and higher free T4 levels (adjusted coefficient (SE): 0.013(0.05), 0.017(0.007), 0.016(0.007), and 0.007(0.006), respectively). These associations were homogeneous in both cohorts, especially for PCBs and total T3 (p-value forthe interaction between cohorts >0.8). Iodine intake and UIC did not affect the association between OCs and thyroid hormones. Our results indicate that exposure to OCs during pregnancy can alter TH levels.

Abstract  BACKGROUND: We expanded an existing cohort of workers (n = 2,588) considered highly exposed to polychlorinated biphenyls (PCBs) at two capacitor manufacturing plants to include all workers with at least 90 days of potential PCB exposure during 1939-1977 (n = 14,458). Causes of death of a priori interest included liver and rectal cancers, previously reported for the original cohort, and non-Hodgkin lymphoma (NHL), melanoma, and breast, brain, intestine, stomach, and prostate cancers, based on other studies. METHODS: We ascertained vital status of the workers through 1998, and cumulative PCB exposure was estimated using a new job exposure matrix. Analyses employed standardized mortality ratios (SMRs; U.S., state, and county referents) and Poisson regression modeling. RESULTS: Mortality from NHL, melanoma, and rectal, breast, and brain cancers were neither in excess nor associated with cumulative exposure. Mortality was not elevated for liver cancer [21 deaths; SMR 0.89; 95% confidence interval (CI), 0.55-1.36], but increased with cumulative exposure (trend p-value = 0.071). Among men, stomach cancer mortality was elevated (24 deaths; SMR 1.53; 95% CI, 0.98-2.28) and increased with cumulative exposure (trend p-value = 0.039). Among women, intestinal cancer mortality was elevated (67 deaths; SMR 1.31; 95% CI, 1.02-1.66), especially in higher cumulative exposure categories, but without a clear trend. Prostate cancer mortality, which was not elevated (34 deaths; SMR 1.04; 95% CI, 0.72-1.45), increased with cumulative exposure (trend p-value = 0.0001). CONCLUSIONS: This study corroborates previous studies showing increased liver cancer mortality, but we cannot clearly associate rectal, stomach, and intestinal cancers with PCB exposure. This is the first PCB cohort showing a strong exposure-response relationship for prostate cancer mortality.

Abstract  An Indiana capacitor-manufacturing cohort (n=3,569) was exposed to polychlorinated biphenyls (PCBs) from 1957 to 1977. The original study of mortality through 1984 found excess melanoma and brain cancer; other studies of PCB-exposed individuals have found excess non-Hodgkin lymphoma and rectal, liver, biliary tract, and gallbladder cancer. Mortality was updated through 1998. Analyses have included standardized mortality ratios (SMRs) and 95% confidence intervals (CIs) using rates for Indiana and the United States, standardized rate ratios (SRRs), and Poisson regression rate ratios (RRs). Estimated cumulative exposure calculations used a new job-exposure matrix. Mortality overall was reduced (547 deaths; SMR, 0.81; 95% CI, 0.7-0.9). Non-Hodgkin lymphoma mortality was elevated (9 deaths; SMR, 1.23; 95% CI, 0.6-2.3). Melanoma remained in excess (9 deaths; SMR, 2.43; 95% CI, 1.1-4.6), especially in the lowest tertile of estimated cumulative exposure (5 deaths; SMR, 3.72; 95% CI, 1.2-8.7). Seven of the 12 brain cancer deaths (SMR, 1.91; 95% CI, 1.0-3.3) occurred after the original study. Brain cancer mortality increased with exposure (in the highest tertile, 5 deaths; SMR, 2.71; 95% CI, 0.9-6.3); the SRR dose-response trend was significant (p=0.016). Among those working >or= 90 days, both melanoma (8 deaths; SMR, 2.66; 95% CI, 1.1-5.2) and brain cancer (11 deaths; SMR, 2.12; 95% CI, 1.1-3.8) were elevated, especially for women: melanoma, 3 deaths (SMR, 5.99; 95% CI, 1.2-17.5); brain cancer, 3 deaths (SMR, 2.87; 95% CI, 0.6-8.4). These findings of excess melanoma and brain cancer mortality confirm results of the original study. Melanoma mortality was not associated with estimated cumulative exposure. Brain cancer mortality did not demonstrate a clear dose-response relationship with estimated cumulative exposure.

Abstract  Objective: To determine whether exposure to polychlorinated biphenyls (PCBs) or dichlorodiphenyl dichloroethene (DDE), either transplacentally or through breast feeding, affected scores on the Bayley Scales of Infant Development at 6 or 12 months of age. Design: Cohort followed from birth to 1 year of age. Setting: General community. Participants: Volunteer sample of 858 infants, of whom 802 had Bayley scores available at either 6 months or 12 months or both. Interventions: None. Measurements and main results: Bayley scales and chemical measurements were done independently. Higher transplacental exposure to PCBs was associated with lower psychomotor scores at both 6 and 12 months of age; the difference between the mean scores in the lowest and highest PCB groups was 7 points at 6 months and 8 points at 12 months. Higher transplacental exposure to DDE was associated with higher mental scores at 6 months of age (the difference between the mean scores in the lowest and highest DDE groups was 6 points), but no relationship was seen at 12 months. Exposure to either chemical through breast feeding was apparently unrelated to Bayley scores. Conclusions: Transplacental exposure to PCBs was associated with lower psychomotor scores. No deleterious effects were associated with breast feeding.

Abstract  Objective: Determining whether early developmental effects of perinatal exposure to polychlorinated biphenyls (PCBs) or dichlorodiphenyl dichloroethene (DDE) persist. Design: Cohort followed from birth; ages now 5 1/2 to 10 1/2 years. Setting: General community. Participants: Volunteer sample of 859 children, of whom 712 had been examinedwith the McCarthy Scales of Children's Abilities at 3, 4, or 5 years; 506 sent report cards. Interventions: None. Measurements and results: Neither transplacental nor breast-feeding exposure to PCBs or DDE affected McCarthy scores at 3, 4, or 5 years. There was no statistically significant relationship between poorer grades and PCB or DDE exposure by either route. Conclusions: The deficits seen in these children on the Bayley Scales of infantDevelopment through 2 years of age are no longer apparent.

Abstract  Spirometric findings (forced vital capacity [FVC], forced expiratory volume at one second [FEV1], FEV1/FVC) in a population of capacitor workers with occupational exposure to polychlorinated biphenyls (PCBs) are described during active PCB use (1976) and following the PCB ban (1979 and 1983). The initial finding of restrictive impairment (16%) in 1976 was not supported by chest roentgenogram findings, nor confirmed in 1979 and 1983, and was interpreted as artifactual due to test operator inexperience and inadequate expiratory efforts. Obstructive impairment was consistently found in 15% of the total population in 1976 and 1979. A history of respiratory illness and/or symptomatology and reduced FEV1/FVC was correlated with PCB exposure and serum PCB levels (lower homologs) in females in 1976, but not in males. Smoking was correlated with reduced FEV1 values. No correlation of spirometric variables with past exposure or serum PCB levels was found for either sex in 1979.

Abstract  Environmental chemicals are thought to adversely affect human reproductive function, however there are no studies that have explored the association between failed fertilization and exposure of both partners to environmental contaminants. Therefore, we collected blood and follicular fluid from the female partner and seminal plasma from the male partner of 21 couples attending an in vitro fertilization (IVF) program, in order to determine the extent of the existence of environmental chemicals in these fluids. Any relationship to the outcome of IVF was also considered. Sera and fluids were analysed for a variety of contaminants, including polychlorinated biphenyls, pesticides, cotinine, and the steroids progesterone and estradiol. Of the couples examined, 18 had fertilizations, three of whom became pregnant. There were no fertilizations in three other couples. The contaminants most frequently found in follicular fluid, more than 50% of the samples tested, were p,p'-DDE, mirex, hexachloroethane, 1,2,4-trichlorobenzene, PCB 49, PCB 153, and PCB 180. Cadmium was detected in eight of 21 (38.1%) samples of follicular fluid whereas cotinine was detected in 18 (85.7%). Residue levels of p,p'-DDE, endosulfan I, PCB 99, PCB 138, PCB 153, PCB 180 were quantified in more than 50% of the sera samples examined. Seminal plasma was relatively free of pollutants with mirex being the most frequently detected contaminant found in seven of 21 (33.3%) samples. Mirex could not be detected in the seminal plasma of the husbands whose partner's oocytes failed to fertilize whereas significant levels of mirex were found in the seminal plasma of all couples who had a pregnancy. Cadmium was also found in the follicular fluid of these pregnant subjects. No relationship was found between follicular fluid cotinine in pregnant and non-pregnant subjects. Where identical contaminants were found in both sera and follicular fluids, the levels were about twofold higher in serum and were positively correlated in both fluids. Fertilization was negatively correlated with serum and follicular fluid p,p'-DDE whereas pregnancy was positively correlated with follicular fluid PCB 49. These data reveal that more than 50% of the population of women attending a fertility program have had exposure to environmental chemicals sufficient to produce detectable concentrations in their serum and ovarian follicular fluid. Of the chemical contaminants detected in the serum and follicular fluid of these women, p,p'-DDE was the most frequently detected, had the highest residue levels, and was associated with failed fertilization.

Abstract  The present study reports the association between prenatal exposure to polychlorinated biphenyls (PCBs), the corpus callosum, and response inhibition in children who are 4.5 years old. Children (n = 189) enrolled in the Oswego study were tested using a continuous performance test. We measured (square millimeters) the splenium of the corpus callosum, a pathway implicated in the regulation of response inhibition, using magnetic resonance imaging. Results indicated a dose-dependent association between cord blood PCBs and errors of commission. Splenium size but not other brain areas predicted errors of commission (r(2) = 0.20), with smaller size associated with more errors of commission. There was an interaction between splenium size and PCB exposure. The smaller the splenium, the larger the association between PCBs and errors of commission. If the association between PCBs and response inhibition is indeed causal, then children with suboptimal development of the splenium are particularly vulnerable to these effects. These data await replication.

Abstract  To determine whether prenatal exposure to polychlorinated biphenyls (PCBs) with possible hormone-disrupting effects is capable of affecting sexual differentiation in boys at the age of puberty.

Following analysis for PCB in their umbilical cords, 196 boys from a Faroese birth cohort were examined for the development of puberty at 14 years of age.

Physical examination included determination of Tanner stages and testicular size. A morning urine sample was centrifuged and examined for the presence of sperm. Serum was analyzed for sex hormones.

twenty boys (10.2%) had abnormalities in testicular development, mainly cryptorchidism. only three of them had a positive spermaturia test, but the level of exposure to pcbs in this group had not been increased. occurrence of spermaturia in 58 of the remaining 176 boys was also not associated with pcb exposure but showed highly significant associations with tanner stages and testicular size. serum concentrations of testosterone, fsh and lh were higher in boys with spermaturia, while sex hormone-binding globulin was lower and no difference occurred in inhibin b. serum hormone parameters showed only weak associations with the level of prenatal pcb exposure.

These findings support the validity of spermaturia as a useful indicator of puberty, although a substantial rate of false negatives must be taken into account. Despite the wide range of exposure to PCB, the findings did not reveal any definite associations with the development of puberty. However, because of the limited size of the cohort, small effects cannot be excluded.

Abstract  Most epidemiological studies of the association between breast cancer risk and exposure to organochlorine pesticides or polychlorinated biphenyls (PCBs), which are suspected endocrine disrupters and potential risk factors for human breast cancer, have been conducted in western countries, and the majority of results have been null and the rest inconsistent. Here, we examined these associations in Japanese women in the largest study in Asian women to date.

The study was a matched case-control study of breast cancer with 403 eligible matched pairs from May 2001 to September 2005 at four hospitals in Nagano Prefecture, Japan.

Serum samples were measured for PCBs and nine pesticide-related organochlorines, including dichlorodiphenyltrichloroethane (DDT). Odds ratios of breast cancer or its hormone-receptor-defined subtypes according to serum organochlorines were calculated.

No increase in the risk of breast cancer was seen among women with higher serum concentrations of any organochlorine: o,p'-DDT, p,p'-DDT, p,p'-dichlorodiphenyldichloroethylene, hexachlorobenzene, beta-hexachlorocyclohexane, trans-nonachlor, cis-nonachlor, oxychlordane, mirex, or PCBs. Rather, higher serum levels of cis-nonachlor, mirex, or total PCBs were associated with a decreased risk of breast cancer

Overall, these results suggest that breast cancer risk in Japan, a low-incidence country, is similar to that in western countries in terms of organochlorine exposure.

Abstract  Prenatal and postnatal polychlorinated biphenyl (PCBs) exposure has been associated with decrements in fetal and infant growth and development, although exposures during the preconception window have not been examined despite recent evidence suggesting that this window may correspond with the highest serum concentrations.

We assessed maternal serum PCB concentrations at two sensitive developmental windows in relation to birth weight.

Serum samples were collected from 99 women as they began trying to become pregnant (preconception) and after a positive pregnancy test (prenatal); 52 (53%) women gave birth and represent the study cohort. Using daily diaries, women recorded sexual intercourse, menstruation, and home pregnancy test results until pregnant or up to 12 menstrual cycles with intercourse during the estimated fertile window. With gas chromatography with electron capture, 76 PCB congeners were quantified (nanograms per gram serum) and subsequently categorized by purported biologic activity. Serum PCBs were log-transformed and entered both as continuous and categorized exposures along with birth weight (grams) and covariates [smoking (yes/no), height (inches), and infant sex (male/female)] into linear regression.

A substantial reduction in birth weight (grams) was observed for women in the highest versus the lowest tertile of preconception antiestrogenic PCB concentration (beta; = 429.3 g, p = 0.038) even after adjusting for covariates (beta; = 470.8, p = 0.04).

These data reflect the potential developmental toxicity of antiestrogenic PCBs, particularly during the sensitive preconception critical window among women with environmentally relevant chemical exposures, and underscore the importance of PCB congener-specific investigation.

Abstract  Background: Human exposure to polychlorinated biphenyls (PCBs) remains widespread. PCBs have been associated with adverse reproductive health outcomes including reduced fecundability and increased risk of pregnancy loss, although the human data remain largely inconclusive.Objective: Our goal was to explore the relationship between serum PCB concentrations and early pregnancy loss among a large cohort of women undergoing in vitro fertilization (IVF) between 1994 and 2003.Methods: Concentrations of 57 PCB congeners were measured in serum samples collected during 827 IVF/intracytoplasmic sperm injection cycles from 765 women. Joint statistical models that accommodate multiple outcomes and multiple cycles per woman were used to assess the relationship between serum PCB quartiles and implantation failure, chemical pregnancies (human chorionic gonadotropin level > 5.0 mIU/mL) that did not result in clinical pregnancy, or spontaneous abortion, while also adjusting for confounders.Results: PCB-153 was the congener present in the highest concentration (median, 46.2 ng/g lipid). Increasing quartiles of PCB-153 and the sum of all measured PCB congeners (ΣPCBs) were associated with significantly elevated dose-dependent odds of failed implantation. Adjusted odds ratios (95% confidence interval) for highest versus lowest quartile were 2.0 (1.2-3.4) for PCB-153 and 1.7 (1.0-2.9) for ΣPCBs. There were suggestive trends for increased odds of implantation failure for PCB-118 and cytochrome P450-inducing congeners (p-values for trend = 0.06). No statistically significant associations between PCBs and chemical pregnancy or spontaneous abortion were found.Conclusions: Serum PCB concentrations at levels similar to the U.S. general population were associated with failed implantation among women undergoing IVF. These findings may help explain previous reports of reduced fecundability among women exposed to PCBs.

Abstract  Polychlorinated biphenyls (PCB)/polychlorinated dibenzofurans (PCDF) are known to affect central nervous functioning. In recent studies, elderly patients who have been exposed to these have been noted to have psychological deficits. There is little known about which test is sensitive to neurotoxins in cognitive evaluation. The objective of the present study was to compare the significance between selective psychological tests in cognitive assessment in PCB-laden elderly.

A retrospective PCB/PCDF exposed cohort was observed. Exposed elderly aged ≥ 60 years and registered in Central Health Administration were enrolled, and similar age- and sex-matched subjects served as non-exposed controls. The Mini-Mental State Examination (MMSE) and Attention and Digit Span (ADS) were tested in both groups. Student's t-test, χ(2) -test and linear regression models were used for statistical analysis.

 A total of 165 exposed patients and 151 controls were analyzed. The exposed group included 49% men, a mean age of 69.3 ± 6.4 years and an education level of 4.0 ± 3.9 years. The controls included 52% men, a mean age of 69.9 ± 5.5 years and an education level of 4.5 ± 3.2 years. There was no statistical difference in MMSE before and after adjusting for the confounding variables of age, sex and education (P= 0.16 vs P= 0.12). However, ADS-forward and ADS-total scores showed a significant decline in the exposed subjects (P= 0.0001 vs P= 0.001). Using a linear regression among stratified PCB and cognitive functioning (≤30 ppb; 31-89; ≥90), a dose effect was found at the medium (31-89 ppb) and high exposure (≧90 ppb) levels.

Our observations showed attention and short-term memory were impaired in PCB-laden elderly patients. Higher exposure level showed lower cognitive functioning in ADS. The MMSE was insensitive to neurotoxins. The present study shows that the selective test has a decisive role in toxic-related cognitive assessments.

Abstract  Though commercial production of polychlorinated biphenyls was banned in the United States in 1977, exposure continues due to their environmental persistence. Several studies have examined the association between environmental polychlorinated biphenyl exposure and modulations of the secondary sex ratio, with conflicting results.

Our objective was to evaluate the association between maternal preconceptional occupational polychlorinated biphenyl exposure and the secondary sex ratio.

We examined primipara singleton births of 2595 women, who worked in three capacitor plants at least one year during the period polychlorinated biphenyls were used. Cumulative estimated maternal occupational polychlorinated biphenyl exposure at the time of the infant's conception was calculated from plant-specific job-exposure matrices. A logistic regression analysis was used to evaluate the association between maternal polychlorinated biphenyl exposure and male sex at birth (yes/no).

Maternal body mass index at age 20, smoking status, and race did not vary between those occupationally exposed and those unexposed before the child's conception. Polychlorinated biphenyl-exposed mothers were, however, more likely to have used oral contraceptives and to have been older at the birth of their first child than non-occupationally exposed women. Among 1506 infants liveborn to polychlorinated biphenyl-exposed primiparous women, 49.8% were male; compared to 49.9% among those not exposed (n = 1089). Multivariate analyses controlling for mother's age and year of birth found no significant association between the odds of a male birth and mother's cumulative estimated polychlorinated biphenyl exposure to time of conception.

Based on these data, we find no evidence of altered sex ratio among children born to primiparous polychlorinated biphenyl-exposed female workers.

Abstract  There is emerging evidence that background exposure to persistent organic pollutants (POPs) are important in the development of conditions predisposing to diabetes as well as of type 2 diabetes itself. We recently reported that low dose POPs predicted incident type 2 diabetes in a nested case-control study. The current study examined if low dose POPs predicted future adiposity, dyslipidemia, and insulin resistance among controls without diabetes in that study.

The 90 controls were diabetes-free during 20 years follow-up. They were a stratified random sample, enriched with overweight and obese persons. POPs measured in 1987-88 (year 2) sera included 8 organochlorine (OC) pesticides, 22 polychlorinated biphenyls (PCBs), and 1 polybrominated biphenyl (PBB). Body mass index (BMI), triglycerides, HDL-cholesterol, LDL-cholesterol, and homeostasis model assessment value for insulin resistance (HOMA-IR) were study outcomes at 2005-06 (year 20). The evolution of study outcomes during 18 years by categories of serum concentrations of POPs at year 2 was evaluated by adjusting for the baseline values of outcomes plus potential confounders. Parallel to prediction of type 2 diabetes, many statistically significant associations of POPs with dysmetabolic conditions appeared at low dose, forming inverted U-shaped dose-response relations. Among OC pesticides, p,p'-DDE most consistently predicted higher BMI, triglycerides, and HOMA-IR and lower HDL-cholesterol at year 20 after adjusting for baseline values. Oxychlordane, trans-nonachlor, and hexachlorobenzene also significantly predicted higher triglycerides. Persistent PCBs with ≥7 chlorides predicted higher BMI, triglycerides, and HOMA-IR and lower HDL-cholesterol at year 20 with similar dose-response curves.

Simultaneous exposure to various POPs in the general population may contribute to development of obesity, dyslipidemia, and insulin resistance, common precursors of type 2 diabetes and cardiovascular diseases. Although obesity is a primary cause of these metabolic abnormalities, POPs exposure may contribute to excess adiposity and other features of dysmetabolism.