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: 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 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  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  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  OBJECTIVE: Several studies have shown that some organochlorine compounds (OCs) can interfere with the thyroid system. As thyroid hormones (THs) are essential for normal brain development, it is important to study the association between THs and OCs during pregnancy and childhood. We have evaluated the relationship between thyroid function and OCs in preschool children. METHODS: Children from a general population birth cohort in Menorca (n = 259), Spain were assessed at the age of 4 years. Concentrations of THs (free T4 and total T3), thyrotropin (TSH) and a range of OCs were measured in peripheral blood. RESULTS: Blood levels of dichlorodiphenyl trichloroethane (p,p'-DDT), beta-hexachlorocylcohexane (beta-HCH), polychlorinated biphenyls (congeners PCB-138, PCB-153 and PCB-118) were related to lower total T3 levels (p<0.05). In addition, free T4 was inversely associated with PCB-118, while no relationship was found between TSH and any of the measured OCs. CONCLUSIONS: This study suggests that even at background levels of exposure, OCs may affect the thyroid system, particularly total T3 levels.

Abstract  During the recent two decades, a remarkable drop in fertility rates has been noticed almost all over the world. A series of studies have showed that environmental factors had the primary role causing the observed adverse trends in the male reproductive health problems. Especially chlorinated hydrocarbons, for instance polychlorinated biphenyls (PCB) and pesticides, could mimic or antagonize the effects of steroid hormones, like estrogens and androgens and possibly interfering with male reproductive capacity. Organochlorine pesticides (OCPs) (i.e. p.p'-DDT, endosulfan...) and PCBs are widespread used chemicals in agriculture and industry for different purposes all over the world. Although direct evidence is lacking, theoretical considerations and epidemiological evidence implicate these compounds as potential hazards to human and wildlife reproductive health. For this purpose, in this study adipose tissue samples have provided from healthy males which were diagnosed as infertile men living in Ankara, Turkey at least for 5 years. Residual levels of OCPs (alpha-BHC, beta-BHC, gamma-BHC, HCB, Endosulfan I, II, p,p'-DDE, and p,p'-DDT) and seven major persistent PCB congeners (PCB 28, 52, 101, 118, 138, 153, and 180) were measured in 25 infertile men and 21 healthy men's adipose tissue samples by GC-ECD. Levels of OCPs and PCBs in adipose tissue of infertile men compared with those provided from controls. When the concentrations of each of the OCP were compared between the fertile and infertile groups, no statistical significance was obtained. Concentrations of each of the PCB congeners were compared between the fertile and infertile groups, no statistical significance was obtained (p > 0.05), except for 2,2',5,5'-Tetrachlorobiphenyl (PCB 52) (p = 0.032) and 2,2',3,4,4',5,5'-heptachlorobiphenyl (PCB 180) (p = 0.017).

Abstract  BACKGROUND: Polychlorinated biphenyls (PCBs) are industrial chemicals that were used widely for approximately 50 years. Now banned, they are still ubiquitous because of their persistence in the environment, the food chain, and human fatty tissue. High in utero exposures cause developmental deficits accompanied by growth retardation. Studies examining intrauterine growth at lower exposures have been inconsistent, with most such investigations having relied on surrogate exposure indicators such as consumption of fish from contaminated bodies of water. METHODS: In the 1960s, serum specimens were collected from pregnant women participating in the Child Health and Development Study in the San Francisco Bay Area. The women were interviewed and their serum samples stored at -20 degrees C. At 5 years of age, detailed anthropometric measurements were made on children born in the years 1964-1967. We measured PCBs in specimens from 399 mothers using gas chromatography/electron capture detection. We conducted multiple linear regression to examine the relationship between these organochlorine concentrations and both intrauterine and 5-year growth, with adjustment for medical, lifestyle, sociodemographic, and specimen characteristics. RESULTS: In male infants, higher total in utero PCB exposure was associated with reduced birth weight, head circumference, and weight-for-gestational age. An increase from the 10th to 90th percentile in total PCBs was related to 290 g lower birth weight, a 0.7-cm decrease in head circumference, and for weight for gestational age, a reduction in z-score of 0.6. In girls, smaller head circumference and shorter gestations were observed. In contrast, prenatal PCBs were associated with greater growth in 5-year-old girls, with no apparent effect in 5-year-old boys. CONCLUSIONS: Maternally mediated exposure to PCBs may be detrimental to fetal growth, particularly in boys. These effects apparently are not persistent. Interpretation of greater childhood growth of girls is unclear.

Abstract  The effects of exposure to polychlorinated biphenyls (PCBs) on dental caries of first permanent molars in children in the Faroe Islands, where the population is exposed to PCBs in their traditional diet, were evaluated. This study was part of a cohort study aimed at determining developmental risks resulting from the consumption of contaminated seafood. One hundred and fourteen children from a birth cohort of 182 motherchild pairs, aged 910 years, were examined. Caries scoring was performed according to WHO criteria; cavitated and noncavitated lesions were included. Exposure assessment was based on the PCB concentrations in maternal milk samples. Data from the project data set provided information on various confounding factors. Mean maternal milk PCB concentration was 2205 (range 7011,150) ng/g lipids. The number of carious surfaces of first permanent molars correlated with milk PCB concentration (r = 0.26, p = 0.01). In multivariate linear regression analysis, PCB exposure was significantly related to caries susceptibility. The findings support an association between children's PCB exposure and caries prevalence.

Abstract  An increased prevalence of thyroid antibodies was seen in employees of a factory that formerly produced polychlorinated biphenyls (PCBs). In this study, the authors expand the evaluation of possible long-term PCB effects by comparing the prevalence of glutamic acid decarboxylase (anti-GAD) antibodies with the development of diabetes mellitus. The sera of 240 factory employees and 704 control subjects were analyzed. Anti-GAD antibody values exceeded 1.20 U/ml in all employees (40.4%), was 4 times higher (p < .001) than in all controls (10.5%), and were 5 times higher in employees aged 51-60 yr (53.2%) than in age-matched controls (10.5%) (p < .001). Although the prevalence of diabetes could not be determined from this retrospective study, this is the first report of a possible relationship between xenobiotics and the prevalence of anti-GAD antibodies, and it supports the concept of an immunomodulatory effect of PCBs. However, such antibodies may be present decades before the development of clinical diabetes, and not all anti-GAD antibody-positive individuals become diabetic. Presently, it is unknown whether there is an increased prevalence of diabetes among the former factory employees.

Abstract  This study aimed to investigate the association of Parkinson's disease (PD) with dietary exposure to polychlorinated biphenyls (PCBs) and methylmercury (MeHg) in a community with increased exposure levels. A total of 79 clinically verified idiopathic PD cases and 154 controls matched by sex and age were examined in this case-control study in the Faroe Islands. Blood and hair samples were collected and a questionnaire recorded lifetime information on residence, dietary habits, smoking history, and occupational exposure to solvents, pesticides, and metals. Both unconditional and conditional logistic regression analyses were used to estimate the odds ratio (OR) and 95% confidence interval (CI) in regard to relevant exposure variables. Increased ORs for dietary intakes of whale meat and blubber during adult life were statistically significant. The ORs for occupational exposure to solvents, pesticides and metals also suggested an increased risk for PD. Current serum concentrations of summation operator PCB and related contaminants suggested slightly increased ORs, although only beta-hexachlorocyclohexane (beta-HCH) was statistically significant. Increased intake of whale meat and blubber in adult life was significantly associated with PD, thus suggesting a positive association between previous exposure to marine food contaminants and development of PD.

Abstract  Endometriosis is a gynaecological disorder characterized by the presence and growth of endometrial tissue in ectopic sites. In this study we examined the immunological functions of patients with endometriosis and serum level of PCBs and p,p'-DDE to verify the impact of these environmental contaminants on the dysregulation of immune functions. We found that proliferative responses and immunoglobulin production were not dysregulated in patients with endometriosis while NK cell activity was significantly down-regulated in these patients. Moreover, a significant down-regulation of IL-1beta and IL-12 production was found in patients with respect to controls. Serum levels of PCBs and p,p'-DDE were found to be significantly higher in women with endometriosis than in the control group, with respect to the sum of the congeners most prominent in human tissues. In particular, total PCBs concentration in patients with endometriosis and controls was respectively 330 and 160 ng/g fat with respect to the most abundant congeners, while p,p'-DDE concentration was of 770 and 310 ng/g fat. Moreover, we found that normal human PBMC pulsed with PCBs, p,p'-DDE and their combination showed a significant down-regulation of NK cell cytotoxic activity and IL-1beta and IL-12 production. These findings suggest that changes in specific immune parameters correlate with elevated serum PCBs and DDE levels and endometriosis.

Abstract  Persistent organic pollutants, such as polychlorinated biphenyls (PCBs), hexachlorobenzene (HCB), and p,p'-dichlorophenyldichloroethylene (DDE), have been found to elicit a broad spectrum of biologic, metabolic, and immunologic responses. The potential of these pollutants to impair immune responses and trigger autoimmune disease is of growing concern, given their structural similarity to thyroid hormones and their potential to modulate the mechanisms and interfere with the binding of these hormones. We examine the relationship of different groupings of PCBs, according to chlorination and structure, and of p,p'-DDE and HCB to anti-thyroid peroxidase antibody, a useful tool in the evaluation of thyroid dysfunction, among 115 young adults of the Akwesasne Mohawk Nation. Overall, 18 participants (15.4%) had anti-thyroid peroxidase antibodies (TPOAb) levels above the normal laboratory reference range (23% of females, 9% of males). Among participants who were breast fed (n=47), those with an elevated TPOAb level had significantly higher levels of all PCB groupings, with the exception of levels of non-persistent PCBs which did not differ significantly. Levels of p,p'-DDE were also significantly elevated, while HCB and mirex were not higher among those with elevated TPOAb. Also, after stratifying by breast-feeding status, participants who were breast fed showed significant, positive relationships between TPOAb levels and all PCB groupings, except groups comprised of non-persistent PCBs, and with p,p'-DDE, HCB, and mirex. No effects were evident among non-breast-fed young adults. Further studies are necessary to elucidate the site and mechanism of action of these persistent organic pollutants (POPs) and to establish thresholds for these effects, especially among populations with background levels of toxicant exposure.

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: 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  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  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  BACKGROUND: Prior studies have reported an increased risk of diabetes related to polychlorinated biphenyl (PCB) exposure. No study has yet investigated whether polybrominated biphenyls (PBBs), which are similar in chemical structure, increase the incidence of diabetes. METHODS: The Michigan PBB cohort was established in 1976 and surveyed again in 1991-1993 and in 2001. PBB and PCB serum levels were measured from blood collected at enrollment. To determine the incidence of adult-onset diabetes, we analyzed cohort members without diabetes at enrollment, ages 20 years and older, with known PBB and PCB levels, who participated in at least 1 follow-up survey (n = 1384). Using Poisson regression, we determined the incidence density ratio (IDR) of diabetes for different serum levels of PBB and PCB, controlling for age, body mass index, smoking, and alcohol consumption at enrollment. RESULTS: Analyzing 25 years of follow-up data, we did not find that higher PBB serum levels were a risk factor for the incidence of diabetes mellitus. However, in women, but not in men, higher PCB serum levels were associated with increased incidence of diabetes (IDR = 2.33; 95% confidence interval = 1.25-4.34 in the highest PCB group compared with the lowest). In both men and women, overweight and obesity increased the diabetes incidence. CONCLUSIONS: We found no association between PBB serum levels and diabetes incidence. In women, there was a positive linear association of diabetes incidence with PCB serum levels at enrollment. This finding is in agreement with 2 prior studies indicating a higher relative risk of diabetes in PCB-exposed women.

Abstract  Although lead (Pb) exposure has been identified as an important risk factor in child behavioral development, less is known regarding the relation between child behavior and exposure to polychlorinated biphenyls (PCBs) and mercury (Hg). Inuit children are particularly exposed to these chemicals and the aim of this study was to investigate the association between prenatal and postnatal exposure to Pb, PCBs, Hg and several aspects of behavioral function in Inuit preschoolers. The sample consisted of one hundred and ten 5-year-old Inuit children from Arctic Quebec. An umbilical cord blood sample was used to document prenatal exposure to Pb, PCBs and Hg. Child blood samples were collected at age 5 and the same contaminants were measured. A modified version of the Infant Behavior Rating Scale from the Bayley Scales of Infant Development-II was used to assess child behavior through examiners' ratings. Furthermore, attention, activity and emotional outcomes were assessed through behavioral coding of video recordings taken during fine motor testing. Pb exposure during childhood was associated with examiners ratings of greater impulsivity, irritability and with coding of observed inattention. Prenatal exposure to PCB 153 correlated with the examiners ratings of increased state of unhappiness and anxiety during the testing session, which was corroborated from video coding since cord PCB 153 was related to fewer manifestations of positive affects. No association was found with Hg exposure. These data corroborated those from previous Pb cohort studies and revealed an association between prenatal PCBs exposure and emotional outcomes in preschoolers.

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  Pentachlorophenol (PCP), hexachlorocyclohexane-[alpha], -beta, and -[gamma] (HCH-[alpha], -beta, and -[gamma]), polychlorinated biphenyls (PCBs), and hexachlorobenzene (HCB) are widely distributed industrial chemicals. They are suspected to induce immunologic impairments in exposed individuals. We examined dose-response relationships of blood levels of these chemicals with cellular (numbers of lymphocyte subpopulations, in vitro lymphocyte response) or humoral (plasma cytokine levels, immunoglobulin autoantibodies) immunologic dysfunctions. We studied 146 patients who had been occupationally exposed primarily to PCBs for more than 6 months. Lymphocyte subpopulations, in vitro responses to mitogens and allogeneic stimulator cells, plasma neopterin, cytokines, soluble cytokine receptors, soluble adhesion molecules, anti-Ig autoantibodies, and liver transaminases were determined. Blood levels of the different compounds were strongly correlated with one another. There were only weak dose-response relationships between blood levels of PCBs with cellular immune parameters, and of HCHs and HCB with humoral immune parameters. An exception was the statistically significant negative association of HCB with interferon-[gamma] (IFN-[gamma]), indicating that HCB has a significant impact on Th1 lymphocytes. Patients with HCB blood levels above the mean of 1,109 ng/L more often had undetectable IFN-[gamma] blood levels than patients below the mean. Patients with increased PCB 138 (> 710 ng/L) had more frequently undetectable interleukin-4 blood levels than patients with PCB 138 below the mean, and patients with increased PCB 101 (> 31 ng/L) more often had low DR+ cell counts in the blood (< 190/microL) than patients with PCB 101 below the mean. To assess possible cumulative effects, we compared patients who had blood levels of all compounds below background with patients who had blood levels of all compounds above background. Patients with low or absent blood levels of the compounds studied had higher IFN-[gamma] plasma levels, providing some evidence for a cumulative effect of several weakly active compounds. In conclusion, exposure to PCBs, HCB, or HCHs is associated with weak immunologic abnormalities. These results contrast with those obtained in earlier studies of blood levels of PCP, which showed a strong dose-dependent relationship with immunologic impairments. Our data suggest that long-term exposure of patients to HCB suppresses IFN-[gamma] production.

Abstract  OBJECTIVE: We sought to study the concentrations of certain persistent organic pollutants with endocrine-disrupting properties in cases with prostate cancer and controls with benign prostate hyperplasia. METHODS: Adipose tissue was obtained from 58 cases and 20 controls. RESULTS: The median concentration among controls was used as cut-off in the statistical analysis. In the total material, a greater-than median concentration of PCB congener 153 yielded an odds ratio (OR) of 3.15 and 95% confidence interval (CI) of 1.04-9.54 and one chlordane type, trans-chlordane, yielded OR 3.49 (95% CI = 1.08-11.2). In the group of case subjects with PSA levels greater than the median level of 16.5 ng/mL, PCB 153 was OR 30.3 (95% CI = 3.24-284), hexachlorobenzene OR = 9.84 (95% CI = 1.99-48.5), trans-chlordane OR = 11.0 (95% CI = 1.87-64.9), and the chlordane-type MC6 OR = 7.58 (95% CI = 1.65-34.9). The grouping of PCBs according to structural and biological activity was found to produce significantly increased risks for enzyme and phenobarbital-inducing PCBs and lower chlorinated PCBs in the case group with PSA levels greater than 16.5 ng/mL. CONCLUSIONS: These chemicals might be of etiologic significance but need to be further investigated. The biological relevance of the arbitrary cut-off point of PSA is unclear.