Serum concentrations of p, p'-DDE, HCB, PCBs and reproductive hormones among men of reproductive age

Exposure to polychlorinated biphenyls (PCBs) has been associated with changes in reproductive hormone levels, however most groups studied have been highly exposed. We investigated the association of PCBs, hexachlorobenzene (HCB) and p, p'-DDE with serum sex hormones in 341 adult men from a US infertility clinic with exposure levels consistent with those observed in the general population. In crude regression models we observed several negative associations of PCBs and HCB with steroid hormone-binding globulin (SHBG) and total and free testosterone. After adjustment for lipids, age and BMI, nearly all significant associations were attenuated. A negative relationship remained between PCB 118 and SHBG (p<0.01), and relationships of dioxin-like PCBs with SHBG and total testosterone, and between PCB 118 and total testosterone, were suggestive. These results suggest a minimal relationship between PCB exposures at low background levels similar to those observed in the general population of the US and circulating reproductive hormones.     

Associations between intrauterine exposure to polychlorinated biphenyls on neonatal ano-genital distance

Polychlorinated Biphenyls (PCBs) are widespread environmental contaminants. PCBs have endocrine disrupting properties which raises concerns regarding their effect on the developing fetus.This study aimed to examine the association between prenatal exposure to PCBs and anogenital distance (AGD) in newborns.Serum concentrations of PCB congeners -118, -138, -153 and -180 were measured in 175 pregnant women presenting to the delivery room. AGD was measured in their newborns. Regression models were used to estimate associations between maternal PCB exposure and infant anogenital measurements, controlling for possible confounding variables.Mean maternal serum concentrations were 2.95 ± 2.18 ng/g, 4.62 ± 3.54 ng/g, 7.67 ± 6.42 ng/g and 5.10 ± 3.91 ng/g for congeners -118, -138, -153 and -180, respectively. Higher maternal concentrations of PCBs were associated with reduced AGD measures in male infants. Higher maternal concentrations of PCB-138 and PCB-153 were associated with reduced ano-scrotal distances and higher maternal concentrations of all four PCB congeners were associated with reduced ano-penile distances. No significant associations were found between any PCB congener and any AGD measure in female newborns.This study demonstrates that intrauterine exposure to PCBs may be associated with reduced AGD in male newborns. More research is needed to reveal the implications for adult reproductive health.     

Issues in the interpretation of associations of PCBs and IQ

The literature concerning the relationship between polychlorinated biphenyl (PCB) exposure and Intelligence (IQ) is not entirely consistent. Two studies showed inverse associations between PCBs and IQ in cohorts of children whose mothers consumed Great Lakes fish contaminated with PCBs and other organochlorines (Jacobson & Jacobson 1996; Stewart et al. 2008). Another study from the general US population, where women were exposed to background levels of PCBs, showed no association between PCBs and IQ (Gray et al. 2005). The current report examines two potential sources of inconsistency across studies: 1) confounding with non-PCB organochlorines [Hexachlorobenzene (HCB), dichlorodiphenyldichloroethylene (DDE), and Mirex]; and 2) the presence of negative confounding (i.e., suppressor variables). The former could confound PCBs and lead to spurious associations (Type I errors), while the latter could suppress PCB associations and obscure true associations (Type II errors). These issues were explored through the analysis of associations between placental levels of organochlorines and IQ in children at 9 and 11 years of age in the Oswego study. Neither DDE nor mirex was related to lower IQ at either age; PCBs predicted lower IQ at both ages; and hexachlorobenzene (HCB) appeared as a significant predictor of IQ at the 11-year assessment. However, analysis of the IQ data set as a whole showed that both PCBs and HCB predicted lower IQ in a generally independent fashion. There was, however, overlap in the variance in some cases, and the pattern of findings between the two was remarkably similar. These results may provide some evidence for the potential involvement of non-PCB organochlorines in the Oswego study. To explore negative confounding, we analyzed the relationships between PCB exposure and demographic variables as well as the unadjusted and adjusted relationships between PCB and IQ. Results revealed that placental PCB levels were associated with older mothers who were more educated and came from higher socioeconomic strata. Due to this fact, unadjusted relationships between PCBs and IQ appeared null or slightly positive. After control for confounders, several significant negative associations between PCBs and IQ were revealed. These data might suggest that inadequate control for confounders in PCB studies, where negative confounding is present, may bias results toward the null (Type II error) rather than spurious associations (Type I error). This pattern of confounding with PCB exposure in the Oswego study also has implications for the assessment of risk. The most highly exposed children came from families with somewhat higher socioeconomic status, and tended to score in the average to above-average range, well above IQ scores that are considered “at risk.” Further, such children were exposed prenatally to PCBs through maternal consumption of PCB-contaminated Great Lakes fish in the early 1990s, when PCB levels were higher than today.     

Prenatal PCB exposure and neonatal behavioral assessment scale (NBAS) performance

We examined the relationship between prenatal (cord blood) polychlorinated biphenyls (PCBs) and Neonatal Behavioral Assessment Scale (NBAS) performance in babies born to women who consumed contaminated Lake Ontario fish. Cord blood PCBs, DDE, HCB, Mirex, lead, and hair mercury levels were determined for 152 women who reported never consuming Lake Ontario fish and 141 women who reported consuming at least 40 PCB-equivalent lbs. of Lake Ontario fish over their lifetime. Earlier work demonstrated that the newborns of fish eaters are exposed to a more heavily chlorinated distribution of PCB congeners, and that highly chlorinated PCBs (hepta-, octa-, and nonachlorinated biphenyls) are most strongly correlated with breast milk levels, perhaps providing the best index of PCB exposure in the Oswego cohort. Given the above, one would predict that these PCBs would be related to impaired performance on those NBAS clusters associated with fish consumption: namely Habituation, Autonomic, and Reflex clusters of the NBAS. Excepting the Relex cluster, these predictions were confirmed. Results revealed significant linear relationships between the most heavily chlorinated PCBs and performance impairments on the Habituation and Autonomic clusters of the NBAS at 25-48 h after birth. Additionally, higher prenatal PCB exposure was associated with a nonspecific performance impairment on the NBAS as evidenced by a significantly greater proportion of NBAS scales in which poor performance was exhibited (more than 1 standard deviation below the mean) in the most highly exposed neonates. Moreover, PCBs of lighter chlorination were unrelated to NBAS performance, as were DDE, Mirex, HCB, lead, and mercury. These results corroborate our earlier findings linking Lake Ontario fish consumption to the most heavily chlorinated PCB congeners, and suggest that the chlorination and persistence of PCBs may be an important factor both for exposure assessment and for determining relationships with neurobehavioral functions.     

Exposure to polychlorinated biphenyls and hearing impairment in children

The objective of this cross-sectional epidemiological study was to assess if long-term exposure to polychlorinated biphenyls (PCBs) is associated with hearing impairment. Four hundred and thirty-three children aged 8-9 years residing in an area polluted by PCBs in Eastern Slovakia were examined otoscopically, tympanometrically and by pure tone audiometry. PCB levels in their serum were determined by gas chromatography. Transient otoacoustic emissions (TEOAE) were measured in a subgroup of 161 children. The mean of the sum of PCB concentrations in serum was 528.2ng/g serum lipids (median 321ng/g serum lipids). Serum PCB concentrations were associated with an increase of hearing threshold at low frequencies and a negative correlation between serum PCBs and the amplitude of TEOAE response was observed in the uppermost tertile of children grouped with regard to serum PCBs, not related to thyroid hormone levels. It was concluded that long-term environmental exposure to PCBs is associated with subclinical but diagnosable hearing deficits.     

Effects of acute exposure to PCBs 126 and 153 on anterior pituitary and thyroid hormones and FSH isoforms in adult Sprague Dawley male rats.

3,3'4,4',5-Pentachlorobiphenyl (PCB 126) and 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153) were administered to adult male rats in order to identify sensitive indicators of endocrine disruption. We tested the hypothesis that PCB exposure modifies follicle-stimulating hormone (FSH) pituitary isoforms, as well as the pituitary and serum concentrations of FSH, luteinizing hormone (LH), growth hormone, prolactin, and thyroid-stimulating hormone (TSH). Effects on serum levels of thyroxine (T4) and testosterone (T), and prostate androgen receptor content, were also tested. In one experiment, 5 groups of 8 rats each received two i.p. injections, one day apart, of either corn oil or 6.25, 25, 100 or 400 micrograms/kg/day of PCB 126. Decreases (p < 0.05) in the serum concentrations of T4 and LH started at doses of 25 and 100 micrograms/kg/day, respectively. Serum FSH concentrations were reduced (p = 0.07) in the highest dose group. In contrast, pituitary content of FSH and LH increased with PCB-126 doses (p = 0.004, p = 0.002, respectively). Despite changes in reproductive hormones, PCB-126 had no effect on the androgen receptor content of the prostate. The effect of PCB-126 was tested in the hemicastrated rat, and suggested adverse effects on testosterone secretion. To test the effects of PCB exposure on FSH pituitary isoforms, 4 groups of 10 male rats received two i.p. injections, one day apart, of either corn oil, PCB 153 (25 mg/kg/day), estradiol-17 beta (E2; 20 micrograms/kg/day), or PCB 126 (0.1 mg/kg/day). Serum T4 levels were higher (p < 0.01) in the E2 and PCB 153 groups, and slightly reduced in the PCB 126-treated groups, compared to controls. Simultaneous purification of pituitary FSH and TSH isoforms was performed by HPLC, using two chromatofocusing columns in series. In contrast to TSH isoforms, the distribution of FSH isoforms over the chromatography run differed slightly between treatment groups; the amounts of FSH isoform eluted during the pH gradient were lower (p < 0.05) in E2 and PCB 153-treated rats than in control or PCB 126-treated rats. The similarity between the effects of E2 and PCB 153 on T4 and FSH isoforms supports the contention that PCB 153 possesses estrogenic properties. Serum LH and T4 concentrations were the most sensitive and practical endocrine indicators of PCBs 126 and 153 exposure in male rats.     

Neurobehavioral deficits at age 7years associated with prenatal exposure to toxicants from maternal seafood diet

To determine the possible neurotoxic impact of prenatal exposure to polychlorinated biphenyls (PCBs), we analyzed banked cord blood from a Faroese birth cohort for PCBs. The subjects were born in 1986-1987, and 917 cohort members had completed a series of neuropsychological tests at age 7 years. Major PCB congeners (118, 138, 153, and 180), the calculated total PCB concentration, and the PCB exposure estimated in a structural equation model showed weak associations with test deficits, with statistically significant negative associations only with the Boston Naming test. Likewise, neither hexachlorobenzene nor p,p'-dichlorodiphenyldichloroethylene showed clear links to neurobehavioral deficits. Thus, these associations were much weaker than those associated with the cord-blood mercury concentration, and adjustment for mercury substantially attenuated the regression coefficients for PCB exposure. When the outcomes were joined into motor and verbally mediated functions in a structural equation model, the PCB effects remained weak and virtually disappeared after adjustment for methylmercury exposure, while mercury remained statistically significant. Thus, in the presence of elevated methylmercury exposure, PCB neurotoxicity may be difficult to detect, and PCB exposure does not explain the methylmercury neurotoxicity previously reported in this cohort.     

The effect of prenatal and postnatal exposure to polychlorinated biphenyls and child neurodevelopment at age twenty four months

We examined the association between prenatal and postnatal exposure to PCBs and development at age 24 months as measured by the Bayley Scales of Infant Development II. 44 (85%) of 52 children had information available. When prenatal and postnatal exposure were modeled together, we found no association between total PCB exposure and the mental development index (MDI) or the physical development index (PDI). In examining PCB 153, we found no association between PCB 153 and MDI, while higher levels of postnatal exposure was associated with a decrease in PDI after adjustment [β for highest tertile=-24.9; 95% CI (-44.3, -5.5)]. Higher levels of prenatal PCB 153 exposure were associated with a statistically significant increased odds of screening positive for a motor delay. In sum, when prenatal and postnatal exposures were considered together, breast milk exposure to PCB 153 appears to be associated with decrements in motor development; however, we cannot rule out that the finding was due to chance.     

The hypothalamo-pituitary-thyroid (HPT) axis: a target of nonpersistent ortho-substituted PCB congeners.

Coplanar polychlorinated biphenyls (PCBs) cause adverse effects in developing and adult animals. Less is known about the effects of nonplanar ortho-substituted PCBs. We investigated the effects of 2 nonplanar PCB congeners, 95 (2,3,6-2',5'-penta CB) or 101 (2,4,5-2',5'-penta CB), and estradiol on selected endocrine parameters. In Study 1, weanling female Sprague-Dawley (S-D) rats were given a single dose of PCB 95 ip at 4, 8, 16, and 32 mg/kg/day for 2 consecutive days and killed 24 h after the last dose. PCB 95 exposure caused a dose-dependent (p < 0.001) decrease in serum thyroxine (T4) levels. Serum thyroid stimulating hormone (TSH) concentrations did not change, but prolactin (PRL) levels increased in a nonlinear (with dose) manner. No significant changes were seen in thyroid gland morphology and pituitary lactotroph number. In Study 2, progression or regression of effects was assessed by lengthening the time and a second congener was tested. Weanling female S-D rats received a single dose of PCB 95 or PCB 101 ip at 16 and 32 mg/kg/day for 2 days and were killed 48 h after the last dose. PCB 95 and PCB 101 both decreased serum T4 (p < 0.001) and hypothalamic dopamine (DA; p < 0.05) levels. No changes were seen in serum triiodothyronine (T3), TSH, and PRL concentrations. Morphological analysis of the thyroid gland showed a decrease (p < 0.05) in colloid area in rats treated with PCB 95 or 101. However, the epithelial cell height increased only in PCB 95 treated rats. Thyroid epithelial cell proliferation increased (p < 0.05) following exposure to estradiol and PCB 95. The results suggest that the HPT axis appears to be a target of ortho-substituted PCBs. PCB 95 was more effective than PCB 101 in causing these changes.     

PCB Concentrations and Dioxin‐like Activity in Blood Samples from Danish School Children and Their Mothers living in Urban and Rural Areas

Human exposure to persistent organic pollutants (POPs) is of major concern due to a diversity of adverse effects from prolonged exposure and bioaccumulation. Manufacturing of polychlorinated biphenyls (PCBs), a subgroup of POPs, has been prohibited for many decades; however, human exposure still occurs due to the persistent nature of the chemicals. The concentrations of the dioxin‐like PCB congeners 105, 118 and 156 and the non‐dioxin‐like PCB congeners 28, 52, 101, 138, 153 and 180, p,p′‐DDE, p,p′‐DDT, o,p′‐DDE, o,p′‐DDT, HCB and β‐HCH as well as the dioxin‐like activity using the AhR transactivity assay were analysed in blood samples from Danish schoolchildren and their mothers in the European framework of the DEMOCOPHES/COPHES projects. The participants were selected from an urban and a rural area, respectively. The PCB concentrations and the AhR‐TEQ (TCDD toxic equivalent) were significantly higher in schoolchildren living in the urban area compared with the rural, and for AhR‐TEQ, a strong correlation between the mothers and children was observed. We found a significant negative correlation between BMI and PCB concentrations in the children. Finally, in the mothers, there was a positive association between age and PCB concentration. These results show that both PCBs and dioxin‐like activity can be measured as biomarkers of exposure and effects in blood samples from children and women. The results indicate that people living in urban areas may be exposed to higher concentrations of PCBs, dioxins and dioxin‐like chemicals, which may lead to a greater risk of adverse effects for urban populations.     

Effects of exposure to PCBs and related compounds on growth and activity in children

Two hundred thirty-six children from two established cohorts at risk for exposure to polychlorinated biphenyls (PCBs) and related contaminants were evaluated at age 4 years. Prenatal exposure (assessed by cord serum PCB level) was associated with lower weight, an effect consistent with reports of growth retardation in laboratory rats and in children exposed at high levels in Taiwan and at general population levels in Japan. The highest exposed children weighed 1.8 kg less on the average than the least exposed. Contemporary body burden (assessed by 4-year serum PCB level) was associated with reduced activity based on composite ratings provided by the child's mother and two independent examiners. This effect, attributable to lactation exposure, was strongest among the offspring of women with above average milk PCB levels who breast fed for at least 1 year. While the weight deficit is consistent with previous data linking developmental effects of low-dose human PCB exposures specifically to the prenatal period, activity is the first domain found to be affected by lactation at contemporary levels of exposure.     

Thyroid dysfunction in sea bass (Dicentrarchus labrax): underlying mechanisms and effects of polychlorinated biphenyls on thyroid hormone physiology and metabolism

The current study examines the effect of subchronic exposure to a mixture of Aroclor standards on thyroid hormone physiology and metabolism in juvenile sea bass. The contaminant mixture was formulated to reflect the persistent organic pollution to which the European sea bass population could conceivably be exposed (0.3, 0.6 and 1.0 μg Σ7PCBs per g food pellets) and higher (10 μg Σ7PCBs per g food pellets). After 120 days of exposure, histomorphometry of thyroid tissue, muscular thyroid hormone concentration and activity of enzymes involved in metabolism of thyroid hormones were assessed. Mean concentrations of 8, 86, 142, 214 and 2279 ng g(-1)ww (Σ7 ICES PCB congeners) were determined after 120 days exposure. The results show that the effects of PCB exposures on the thyroid system are dose-dependent. Exposure to environmentally relevant doses of PCB (0.3-1.0 μg Σ7PCBs per g food pellets) induced a larger variability of the follicle diameter and stimulated hepatic T(4) outer ring deiodinase. Muscular thyroid hormone levels were preserved thanks to the PCB induced changes in T(4) dynamics. At 10 times higher concentrations (10 μg Σ7PCBs per g food pellets) an important depression of T(3) and T(4) levels could be observed which are apparently caused by degenerative histological changes in the thyroid tissue.     

Relative concentrations of organochlorines in adipose tissue and serum among reproductive age women

Much of the available literature focusing on organochlorine exposure and human health effects has relied upon serum for quantifying exposure despite adipose tissue being the purported "gold standard". The accuracy of exposure status is dependent upon serum being a valid and reliable proxy for adipose tissue regardless of compound under study and served as the impetus for study. Serum and omentum fat concentrations for 62 polychlorinated biphenyls (PCBs) and 7 organochlorine pesticides (OCPs) were determined using gas chromatography with electron capture and compared to assess their relative abundance and correlation among 15 women aged 18-40 years undergoing laparoscopy. The relation between concentration in serum and fat was determined by linear regression. Of the 20 organochlorines (OCs) (29%) present in both serum and fat samples, moderate linear correlations (r > 0.6) were observed between lipid-adjusted serum and fat concentrations for PCBs #138, 153, 180, 188, 194, 206, and DDE. Forty-nine OCs were present in adipose samples but measured below the LOD in serum samples. Our findings underscore the potential for discrepant human health results associated with OC exposure on the basis of medium used for quantification purposes, especially for less ubiquitous compounds or when study samples include individuals with relatively low exposures. These data support earlier findings and argue for concerted methodological work aimed at developing standardized laboratory methods for epidemiologic studies.     

Hypertrophic Foci of Pancreatic Acinar Cells in Rats

Abstract

Polychlorinated biphenyls (PCBs) are a mixture of 209 different chlorinated biphenyl congeners (forms) of which 36 are environmentally relevant. PCBs are lipid (fat)-soluble, stable compounds. PCBs may be contaminated with more highly toxic polychlorinated dibenzofurans (PCDFs). Some PCDFs were primarily responsible for the two poisoning outbreaks — Yusho and Yu-Cheng.

Based on the reports on workers and the general population, no clear and convincing evidence that PCB exposures were casually associated with adverse health effects was advanced; this included cancer for a wide range of body burdens and exposures for serum PCB concentrations >1000 ppb (µ.g/1) and adipose PCB levels >400 ppm (mg/kg). No meaningful reproductive problems have been identified in female capacitor workers. In the opinion of the review author, the available evidence for cancer and for reproductive effects is inconclusive.

Adverse neurobehavioral effects in infants and young children have been reported in a study of women in the general population and a study of fish eaters and their offspring. The adverse effects observed in the two studies were not the same; the exposure assessments in both studies are not well defined and have many uncertainties.

Subhuman primates appear to be more sensitive to reproductive and other adverse effects of PCBs than humans. Obvious external clinical signs are observed in the offspring of subhuman primates at dosage levels below those experienced by female capacitor workers and members of the general population prior to the control of PCBs.     

Reduced levels of 1,25-dihydroxyvitamin D(3) in rat dams and offspring after exposure to a reconstituted PCB mixture.

Previous studies revealed effects of polychlorinated biphenyls (PCBs) and other polyhalogenated hydrocarbons on steroid hormone levels and hormone-dependent functions including behavior. In the present study serum concentrations of the vitamin D(3) metabolites 25-hydroxycholecalciferol (25-D) and 1,25-dihydroxycholecalciferol (1,25-D) were determined in rat dams and offspring after exposure to a PCB mixture that was reconstituted according to the congener pattern found in human breast milk. Unmated females were exposed to diets adulterated with 0; 5; 20; or 40 mg PCBs/kg diet. Exposure started 50 days prior to mating and was terminated at birth. Gestational exposure reduced serum concentrations of 1,25-D in dams in a dose-dependent manner. Concentration of 25-D was also decreased at the time of delivery, but not at weaning. Determination of 1,25-D in offspring at weaning revealed reductions in both high-exposure groups. Levels of 25-D were diminished only at the highest exposure level. Internal PCB concentrations in adipose tissue and brains exhibited a linear relation to dosages in diet. Concentrations of PCBs in brains were similar in dams and offspring at birth, but decreased at the end of lactation in dams. In offspring, values increased during this period because of continued exposure via the milk. In the adipose tissue, PCB levels were much lower in offspring than in dams. To our knowledge, this is the first report of PCB-induced effects on vitamin D(3) metabolites. In dams, reductions were seen even at the lowest exposure level used. Further studies are needed to evaluate the biological significance of these reductions in pregnant dams and possible consequences for the developing offspring.     

Purkinje cell and cerebellar effects following developmental exposure to PCBs and/or MeHg

We recently reported that rats exposed to PCBs and MeHg during development were impaired on the rotating rod, a test of balance and coordination that is often indicative of cerebellar damage. In addition, developmental PCB exposure is known to dramatically reduce circulating thyroid hormone concentrations, which may have a negative impact on cerebellar development. Therefore, we investigated the effects of combined PCB and MeHg exposure on Purkinje cells and the cerebellum. The serum and brains from littermates of the animals tested on the rotating rod were collected at weaning, and we also collected brains from the adult animals at the end of motor testing. Four groups were studied: 1) vehicle controls, 2) PCBs only (Aroclor 1254, 6 mg/kg/d, oral), 3) MeHg only (0.5 ppm, in dams' drinking water), and 4) PCB+MeHg (at the same doses as in individual toxicant exposures). Female Long-Evans rats were exposed beginning 4 weeks prior to breeding with an unexposed male and continuing until postnatal day (PND) 16. There was a significant reduction in serum T4 and T3 concentrations in the PCB and PCB+MeHg pups on PND21. Golgi-impregnated Purkinje cells were examined in PND21 brains, but there were no significant exposure-related effects on primary dendrite length, branching area, or structural abnormalities. However, all three male exposure groups had a marginally significant increase in Purkinje cell height, which may suggest a subtle thyromimetic effect in the cerebellum. Cresyl-violet stained sections from the adult brains showed no exposure-related effects within paramedian lobule in Purkinje cell number, total lobule volume or layer volumes (molecular, granule cell and white matter layers). Evidence is provided for the dysregulation of expression of cerebellar ryanodine receptor (RyR) isoforms in PCB-exposed brains, and this could contribute to the rotating rod deficit by changing critical aspects of intracellular calcium signaling within the cerebellum.     

Comparative metabolism of polychlorinated biphenyls and tissue distribution of persistent metabolites in rats, hamsters, and Guinea pigs.

The present study was performed to compare the metabolite profiles of polychlorinated biphenyls (PCBs) in the liver and serum of rats, hamsters, and guinea pigs after exposure to a PCB mixture, Kanechlor 500 (100 mg/kg, i.p.). The percentage of contribution of major PCB residues in the liver 5 days after exposure indicated that nonplanar PCBs with 2,4- or 2,3,4-chlorine substitution were more abundant in the liver in the order rats (43% of total PCBs) > hamsters (20%) > guinea pigs (11%), whereas coplanar PCBs with 4-, 3,4-, or 3,4,5-chlorine substitution were predominant in guinea pigs (61%), followed by hamsters and rats (both 26%). The hepatic concentrations of methylsulfonyl metabolites (MeSO(2)-CBs) were higher in the order guinea pigs > rats > hamsters. Whereas hamsters formed minute amounts of MeSO(2)-CBs from 2,5-dichloro-substituted PCBs, guinea pigs formed higher levels of meta-MeSO(2)-CBs derived from 2,3,6-trichloro-substituted PCBs. In contrast, the serum concentrations of phenolic PCBs were higher in the order hamsters > rats > guinea pigs. Metabolites were predominated by 4-OH-2,3,5,3',4'-pentaCB (89% contribution) for rats, 3-OH-2,4,5,2',4'-pentaCB (56%) for guinea pigs, and dihydroxylated metabolites (39%) for hamsters. The reduced elimination of coplanar PCBs and the specific distribution of MeSO(2)- and phenolic PCBs may have implications for the differences in sensitivity to PCB toxicity among rats, guinea pigs, and hamsters.     

Polychlorinated biphenyl (PCB) induction of CYP3A4 enzyme activity in healthy Faroese adults

The CYP3A4 enzyme is, along with other cytochrome P450 enzymes, involved in the metabolism of environmental pollutants and is highly inducible by these substances. A commercial polychlorinated biphenyl (PCB) mixture, 1,1,1,-trichloro-2-(o-chlorophenyl), 2-(p'-chlorophenyl)ethane (o,p'-DDT) and 1,1,-dichloro-2,2-bis (p-chlorophenyl)ethene (p,p'-DDE) are known to induce CYP3A4 activity through activation of nuclear receptors, such as the pregnane X receptor. However, this induction of CYP3A4 has not yet been investigated in humans. Thus, the aim of the study was to determine the variability of the CYP3A4 phenotype in regard to increased concentrations of PCBs and other persistent organohalogen pollutants (POPs) in healthy Faroese adults. In 310 randomly selected Faroese residents aged 18-60 years, the CYP3A4 activity was determined based on the urinary 6beta-hydroxycortisol/cortisol (6beta-OHC/FC) ratio. POP exposures were assessed by measuring their concentrations in serum lipid. The results showed a unimodal distribution of the 6beta-OHC/FC ratio with values ranging from 0.58 to 27.38. Women had a slightly higher 6beta-OHC/FC ratio than men (p=0.07). Confounder-adjusted multiple regression analysis showed significant associations between 6beta-OHC/FC ratios and summation PCB, PCB-TEQ and p,p'-DDE, o,p'-DDT and HCB, respectively, but the associations were statistically significant for men only.     

Cognitive development in preschool children prenatally exposed to PCBs and MeHg

A number of epidemiological studies have shown predictive relationships between prenatal exposure to polychlorinated biphenyls (PCBs) and subtle deficits in cognitive development in infancy through the preschool years [Child Dev. 56 (1985) 853; J. Pediatr. 116 (1990) 38; J. Pediatr. 134 (1999) 33; Toxicol. Lett. 102-103 (1998) 423; Neurotox. 21 (6) (2000) 1029-1038]. However, since not all studies have demonstrated these relationships (J. Pediatr. 119 (1991) 58-63), debate regarding the role of prenatal PCB exposure in cognitive development continues. The current study was designed to provide additional data to assist in resolving this question. Two hundred twelve children enrolled in the Oswego Newborn and Infant Development Project were assessed using the McCarthy Scales of Children's Abilities at 38 months of age, followed by a reassessment at 54 months of age. The relationship between prenatal exposure to PCBs (cord blood PCBs) and McCarthy performance was assessed at both ages after first controlling for a wide range of important predictors of cognitive development, including socioeconomic status (SES), maternal IQ, maternal education, home environment, cigarette smoking, and many others. Cord blood PCBs were statistically significant predictors of small but measurable deficits in McCarthy performance at 38 months of age. Moreover, a significant interaction between cord blood PCBs and maternal hair mercury (MeHg) was found, such that negative associations between prenatal MeHg exposure and McCarthy performance were found in subjects with higher levels of prenatal PCB exposure. No relationship between PCBs and/or MeHg and McCarthy performance was observed when the children were reassessed almost 1.5 years later (54 months of age). Inspection of the age-related trajectory of McCarthy performance revealed that the more highly exposed children caught up with the least exposed children by 54 months. Although the current data partially replicate the findings of Jacobson et al., Patandin et al., and Walkowiak et al. [J. Pediatr. 116 (1990) 38; J. Pediatr. 134 (1999) 33; Lancet 358 (2001) 1602], results reported here suggest that functional recovery may occur. Moreover, the interaction between PCB and MeHg cannot be considered conclusive until it has been replicated in subsequent investigations.     

Endocrine disruption induced by organochlorines (OCs): field studies and experimental models

Long-range transport of persistent organic compounds by air and ocean currents from industrialized areas resulted in high levels of these pollutants in food webs in the Svalbard area. With the aim to test if organochlorine (OC) exposure in free-living polar bears from Svalbard affected their plasma steroid hormone concentrations, it was found that polychlorinated biphenyls (PCBs) were associated with increased progesterone levels in females. The sum of pesticides (sigma pesticides) and sigma PCBs contributed significantly negative to the variation of the plasma testosterone in males, and the overall contribution of the OCs to the plasma cortisol variation was negative. A second objective was to study the effects of selected OCs (i.e., PCB 153 and PCB 126) on animal health as a consequence of effects on endocrine-regulated functions such as reproduction and immunity in a goat model focusing on long-term and low-level exposure during the periods of fetal development and in the neonatal period. Additionally, acute exposure was studied in adult mice. The results indicated that exposure to low doses of PCB 153 in utero and in the suckling period influenced reproductive functions and both PCB 153 and PCB 126 exerted immunomodulatory effects on the offspring, whereas acute exposure of adult mice had minor effects on male reproductive function.