Similar levels of exposure to PCBs that were not contaminated by PCDFs were associated with markedly less toxicity, thus implicating the PCDFs or other thermal breakdown products present in the contaminated cooking oil in the observed neurodevelopmental effects . Children in the Japanese rice oil poisoning were not formally tested but were reported to exhibit hypotony, hyperactivity, and altered latencies and amplitudes of auditory evoked potentials and were reported to have lower mean intelligence quotients . Table 14 summarizes the associations of neurodevelopmental outcomes in infants and children with the PCB exposure levels of their mothers.One of the difficulties is that different specimens were used for exposure assessment, and the results were expressed per wet-weight or per gram lipid of the respective tissues. Additionally, the earlier studies measured PCBs by the packed column gas chromatography method and did not quantitate individual congeners, whereas in more recent studies, various combinations of individual congeners were measured. Longnecker et al. used a variety of approaches to re-express the reported PCB concentrations as median PCB 153 levels in nanogram per gram of lipid in maternal serum for six of these cohorts as well as for four other cohorts for which data on neurological testing are not yet available. These calculated PCB 153 concentrations are included in Table 14. The use of PCB 153 for this purpose is appropriate because PCB 153 is highly correlated with total PCBs. Although substantial uncertainty arises from the assumptions that were made to convert packed-column into high-resolution results and milk into serum levels, the authors felt that the primary findings were not be substantially altered.
These primary findings demonstrated substantial overlap in the distribution of exposure in the majority of studies,drying marijuana but the median exposure in the Faroe Islands was fourfold higher than the overall median. As summarized in Table 14, the overall results of these studies indicate that prenatal PCB exposure is associated with subtle, but significant, delays in the neurodevelopment of infants and children. Despite the much greater transfer of OCs from the mother to the infant via breast milk, most studies have not revealed any significant associations between postnatal exposure via breastfeeding and neurodevelopmental outcomes . The exceptions are discussed here. The strongest and most persistent adverse effects were observed in the Michigan cohort, which included mothers who frequently consumed PCB-contaminated sports-caught fish from Lake Michigan . Notably, the early developmental findings in the Michigan cohort have essentially been replicated in the Oswego cohort, which also included mothers who had consumed substantial amounts of sport-caught fish from Lake Ontario . The only difference was that studies of the Michigan cohort indicated a weak, but statistically significant, association between maternal fish consumption and performance on the Fagan test , whereas such an association was not found in the Oswego cohort . However, the effect size in the Oswego cohort was considerably smaller than reported for the Lake Michigan cohort , which might be attributable to the lower levels of PCB and other contaminants in the Lake Ontario mothers compared with the Oswego mothers. However, note that the estimated PCB 153 concentrations in the Michigan cohort were similar to those observed in the Dutch cohort and were somewhat lower compared with the German cohort . In the German cohort, no effect of prenatal PCB exposure was found using either the Fagan test or Bayley Scales of Infant Development . However, early postnatal PCB exposure showed a significant negative association with the Bayley II mental, but not psychomotor, developmental index at age 7 mo .
Negative associations between the PCB concentration in milk and mental and motor development were only of borderline significance at age 7 and 18 mo but became highly significant in 30-mo-old children in that cohort . Mental development continued to be negatively affected by lactational PCB exposure at age 42 mo . In the Rotterdam cohort, postnatal PCB and dioxin exposure via breastfeeding was also negatively correlated with BSID scores at age 7 mo . Conversely to the German findings, this study also demonstrated an effect from prenatal exposure. In further contrast to the results from the German cohort, it was the psychomotor, but not the mental, development index that was significantly decreased, and the associations were no longer significant at age 18 mo. Lower full-scale and verbal IQ scores were still associated with a composite measure of prenatal PCB exposure in 11-yr-old children from the Lake Michigan cohort . No other cohort has been followed for such an extended period, but in another study, significant effects of prenatal PCB exposure were no longer apparent in children past age 3 yr . Others found that the children with the highest prenatal exposure caught up to the performance level of the least exposed children by age 54 mo or that in utero PCB and dioxin exposure continued to significantly affect cognitive and motor abilities past age 6 yr only in those with suboptimal home environments . The latter finding suggests that more optimal intellectual stimulation can counteract the effects of prenatal PCB exposure. Other investigations confirmed that the home environment had a positive influence on mental development that was greater overall than the negative effect of neonatal PCB exposure . There are also indications that breastfeeding has a positive influence on mental and psychomotor development and can counteract some of the negative effects of PCB exposure . Because the majority of studies indicated that prenatal rather than postnatal exposure was associated with neurodevelopmental parameters, a WHO working group did not find the evidence sufficient to change the WHO recommendation to support breastfeeding . In the Dutch cohort from Rotterdam and Groningen , exposure to both PCBs and dioxins was assessed .
Because of the requirement for rather large sample volumes, PCDD/Fs could not be measured in cord blood, but they were determined in a 24-h breast milk sample obtained during the second week after birth. Their concentrations were not associated with any measure of neurological condition up to age 42 mo . In another brief publication on this cohort, it was reported that the mean sum of all TEQs from dioxins and dioxin-like PCBs was actually higher in neurologically normal newborns compared with the 24 children classified as neurologically slightly or definitely abnormal . However, at age 3 mo, total PCB–dioxin TEQs tended to be associated with a reduction in the psychomotor developmental index . Additionally, postnatal total PCB–dioxin TEQ exposure was associated with significantly lower psychomotor developmental index scores in 7-mo-old infants . Studies on a small sample of infants from the Netherlands focused exclusively on developmental outcomes associated with perinatal PCDD/F exposure, as determined by measuring 7 PCDD and 10 PCDF congeners in breast milk samples obtained within 3 wk after birth . At age 5 to 7 d and 26 wk, the Prechtl neurological optimality score did not show an association with exposure level nor did the BSID scores show an association at age 2 yr . The Hempel test of neuromotor functioning revealed significantly enhanced maturation in the high-exposure group, as evidenced by significantly fewer sub-optimal scores. The authors hypothesized that dioxins may have acted as thyroxine agonists because they found that thyroid function in this cohort was rather elevated in the high-exposure group in the first 11 wk after birth . Together,pruning cannabis these data indicate that prenatal or perinatal exposure to PCBs and possibly PCDD/Fs adversely affects neurodevelopment. However, we emphasize that the various neurodevelopmental parameters were in the normal range, even at the highest exposure levels. It is highly unfortunate that differences in study design, in the reporting of quantitative exposure data and the outcomes associated with them, and in the number and types of confounders considered in the statistical analyses, as well as inconsistencies in some of the results, seriously hamper comparison of the results. Additionally, the differences in the reported outcomes make an evaluation of the effect size difficult. Ultimately, however, the fact that there is any effect at all is of paramount concern.In vitro and animal studies have shown that PCBs and their hydroxylated metabolites can induce various enzymes involved in the metabolism of thyroid hormones and can displace thyroid hormones from their binding proteins . Both of these mechanisms are likely to contribute to the decreased plasma levels and reduced availability of T4 and T3 observed in experimental animals. Reductions in brain T4 concentrations have also been reported, but brain T3 levels are frequently unaffected, suggesting the existence of effective compensatory mechanisms. In utero exposure to single PCB congeners was associated with reduced plasma T4 levels in rat pups, and reduced T4 levels were also observed in wildlife species. Results of thyroid-stimulating hormone levels are inconsistent. Learning and behavioral deficits as well as reductions in auditory evoked potentials have been observed in rodents and monkeys perinatally exposed to PCBs.
These manifestations resemblethose induced by fetal hypothyroidism, but a causal link between the neurodevelopmental and the thyroid effects of PCB exposure cannot be established using the available data. High levels of environmental exposure to OCs have also been reported to affect neonatal thyroid hormone status. In a comparison of various populations in the Québec province, concentrations of total PCBs and total OH-PCBs in cord blood both showed significant negative correlations with TSH concentrations but were not associated with levels of T3 or free T4 . Notably, in those cord plasma samples, the major chlorinated phenolic compound was pentachlorophenol, and it was negatively correlated with T3, free T4, and thyroxine-binding globulin. In the Faroese birth cohort, more frequent maternal fish consumption during pregnancy was significantly associated with decreased TSH concentration, but not T4 levels, in neonatal blood samples obtained 4 to 7 d after birth . A slight tendency for TSH and T4 to decrease with increasing PCB concentrations in umbilical cord tissue was no longer evident after adjustment for the frequency of maternal fish consumption during pregnancy. When stored cord-blood samples form 160 of the children from the North Carolina cohort were assayed for free and total T4 and TSH, their levels were not found to be associated with the originally measured average PCB concentrations in mother’s milk and serum that had been scaled to be comparable with the level in milk at birth . In the Dutch cohort, higher values for the sum of all TEQs from dioxins or planar or nonplanar PCBs in a 24-h representative breast milk sample obtained during the second week after delivery were significantly correlated with decreased maternal plasma levels of total T3 and T4 . The TEQ sum of dioxins , dioxins and dioxin-like PCBs , and PCBs were all positively correlated with plasma TSH levels in the infants at ages 2 wk and 3 mo. Infants exposed to dioxin levels greater than the median exhibited significantly decreased mean plasma total T4 and increased plasma TSH levels in the second week after birth, whereas only TSH levels were increased in umbilical cord plasma and plasma obtained 3 mo after birth. In marked contrast, in 38 Dutch neonates, T4 concentrations were increased at birth and at ages 1 and 11 wk in the group in which mothers’ breast milk contained high levels of dioxin compared with the group with low exposure . Thyroxine-binding globulin was not significantly different at birth and at age 1 wk but was significantly higher in the group with high exposure at age 11 wk. Notably, the more highly exposed children in this cohort had significantly fewer sub-optimal scores on the Hempel test of neuromotor functioning, suggesting enhanced maturation . The authors hypothesized that this could result from the thyroxine agonist activity of dioxins. Elevated serum T3 and T4 concentrations, but normal TSH levels, have been reported in Yusho patients compared with unexposed controls; however, they do not correlate with PCB levels, suggesting that the effect is mediated by PCDFs or other thermal breakdown products of PCB .PM consists of a complex mixture of organic and inorganic liquids and solids in the form of particles of different sizes and structures. The precise mixture varies by region and season. For example, PM in the northeastern United States has a high sulfate content , whereas nitrates and organic compounds comprise approx 30% of the mass of PM in parts of the western United States .Within a given area, there can be substantial differences between winter and summer particulate air pollution concentrations; some areas show peak levels in the summer because of photochemical reactions, whereas other areas are more polluted in the winter because of increased emissions resulting from heating, and yet others show little seasonal variation .