The major metabolites of PCBs are methyl sulfones and polychlorobiphenylols

TDI or acceptable daily intake values indicate the amount of a chemical a person can be exposed to on a daily basis over his or her lifetime without suffering deleterious effects. There are numerous indications from studies of adipose, serum, and breast milk levels showing that exposure to OCs has been generally declining in North America and Europe since their peak production in the late 1960s and early 1970s . The most consistent decline is observed in the concentrations of DDT and its metabolites, whereas the temporal development of PCB and PCDD/F levels is somewhat more erratic. In Europe, concentrations of PCDD/Fs and PCBs have been decreasing in many food stuffs, and there are indications that changes in consumer dietary patterns— particularly reduced fat consumption—have also contributed to a decrease in OC intake . Note that DDT is still utilized for vector control, and the use of many OC compounds continued for much longer periods in many other countries around the world than in the United States and Europe. Therefore, the body burden of certain OCs is still very high in numerous populations . Additionally, major contamination incidents continue to occur because of inappropriate waste disposal, and these add considerably to the body burden of the affected populations in countries where OC levels are generally declining . Although levels of OCs in breast milk have been decreasing since the earliest measurements in the 1980s , they still frequently result in infant exposures that are up to two orders of magnitude higher than TDI values. Such values are based on lifetime intakes and are not intended to apply to the relatively short nursing period. On the other hand,cannabis drying as previously discussed, infants are likely to be considerably more susceptible to the various toxic effects of environmental pollutants, including OC compounds. It has been estimated that nursing contributes 6 to 12% of cumulative TEQ intake until the age of 25 yr.

For children and adolescents up to age 17 yr, duration of breast feeding alone or in combination with PCB concentrations in breast milk or maternal plasma lipids predicted serum PCB concentrations . Inclusion of an index of body fat mass was found to further improve the predictive ability of this model . For almost 2000 participants of NHANES III, serum concentrations were determined for 25 PCB congeners . For all congeners, including some of the most commonly detected, the 50th percentile was lower than the limit of detection . For a surprising number of congeners, even the 95th percentile was lower than the LOD. For PCBs 118, 138, 153, and 180, the 75th percentile values were 13.1, lower than LOD, lower than LOD, and 37.4 ng/g of lipid, respectively. Similar data from other studies are not directly comparable because they were not population-based, were obtained by different analytical methods, and were not always on blood lipid base. Nonetheless, it is striking that some of these studies detected PCBs 138 and 153 in a high percentage of subjects. For example, despite similar detection limits as those reported in the Centers for Disease Control study, PCBs 138 and 153 were detected in 93 and 97%, respectively, of umbilical cord plasma samples obtained from neonates born to Canadian women living in southern Québec and exposed to background levels of PCB . The geometric mean values were 12.7 and 16.9 ng/g of plasma lipids, respectively. In blood samples from German schoolchildren obtained between 1996 and 2003, all 5th percentile values for PCBs 138, 153, and 180 were above the detection limit . Median concentrations in the most recent samples were 0.01, 0.03, and 0.01 µg/L for PCBs 138, 153, and 180, respectively. Significant correlations between maternal and cord serum concentrations of PCBs and other OC compounds suggest the occurrence of transplacental transfer , and neonatal levels of PCBs have been found to increase with length of gestation in full-term neonates born after 38 to 42 wk of gestation . The detection of OCs in amniotic fluid and meconium samples has also been reported , further confirming that OC exposure starts in utero.The limited human data available indicate almost complete absorption of lower chlorinated PCB and PCDD/F congeners and somewhat lesser, but still substantial, absorption of the higher chlorinated congeners . There is still uncertainty about the extent of dermal absorption, which appears to depend not only on the degree of chlorination but also on the matrix in which PCBs are applied and on the method used to estimate absorption .

One of the most common methods, fecal and/or urinary excretion of label, may considerably underestimate dermal absorption, as indicated by the finding that when tissue distribution was accounted for in a mass balance study in pigs, absolute dermal absorption of a single PCB congener was found to be 22%, whereas the urinary and fecal excretion methods would have indicated absorption of only 8 to 10% . After initial distribution to highly perfused tissues such as liver and muscle, PCBs are then redistributed to adipose tissue and skin, which serve as long-term storage sites . The primary sites to which more than 95% of the body burden of PCDD/Fs distributes are the liver and adipose tissues, including blood lipids and the adipose tissue of muscles and skin .Although the hydroxylation of lipophilic substances renders them more hydrophilic and generally facilitates their excretion, there are indications that some OH-PCBs are selectively retained, mainly by binding to plasma proteins such as albumin and the thyroid hormone transport protein, transthyretin . In vitro, the affinity of certain OH-PCBs for transthyretin has been shown to be up to four times stronger than that of thyroxine . Although at least 38 OH-PCBs have been identified in human blood plasma , five hydroxylated metabolites constitute the vast majority of OH-PCBs in plasma . The ratio of total OH-PCBs to total PCBs is generally in the range of 0.1 to 0.3, with declining ratios at higher total PCB concentrations . Estimated half-lives range from a few years to 30 yr or more for the more persistent PCBs , from 7 to 8 yr for TCDD , from 3 to more than 15 yr for other PCDDs, and from 3 to almost 20 yr for PCDFs ; half-lives are approx 7 yr for DDT and approx 10 yr for DDE . Notably, elimination rates for TCDD appear to depend on age and body fat and are believed to slow with decreasing body burden . OCs are primarily excreted in the bile . Lactation can also represent a major route of excretion. The high levels of OCs found in breast milk indicate that OCs are mobilized from adipose tissue during lactation,grow trays and significant decreases in the maternal body burden of PCDD/Fs and PCBs with simultaneous accumulation in their infants has been observed, particularly following the first delivery .

Much of the knowledge of the health effects of OCs comes from highly exposed occupational cohorts and from Air Force personnel involved in the spraying of Agent Orange in Vietnam. Additionally, there are three cohorts that experienced high levels of environmental exposure. Because of an industrial accident in Seveso, Italy, the air and soil from surrounding areas were contaminated mostly with TCDD. Two industrial accidents in Japan and Taiwan resulted in the contamination of cooking oil, primarily with PCBs and PCDFs. The resulting symptoms were referred to as Yusho in Japan and Yu-Cheng in Taiwan . Table 13 provides brief descriptions of these cohorts. There should be a note of caution in interpreting epidemiological studies that analyze associations between exposures to OC compounds and various health effects. Generally, either PCBs or PCDD/Fs, but not both groups of compounds, have been measured in these studies. However, humans are invariably exposed to mixtures of these and other OC compounds, and the contributions of the individual components of the mixture to the effect under investigation are unknown. Additionally, several studies of OC tissue levels in North America and Europe found modest-to-strong correlations not only between total PCBs and PCDD/Fs but also among and between individual PCBs and PCDD/Fs . Together, these factors can result in not only considerable confounding but in misclassifications of the observed effects . This is most clearly illustrated by the fact that some PCB congeners are dioxin-like and, similar to dioxins, exert most of their effects through the Ah receptor, whereas others act as Ah receptor antagonists. Developmental neurotoxicities represent an example of an effect to which both Ah receptor-mediated mechanisms and mechanisms that are not Ah receptor-mediated are likely to contribute. On the other hand, the strong correlation between some individual PCB congeners, such as PCB 153 or PCB 138, and total PCBs allows use of only a few PCB congeners as a measure of total PCB exposure. In many recent epidemiological studies, PCBs 138, 153, 180, and, frequently, PCB 118 were used to estimate total PCB burden . In 1997, the IARC classified TCDD as a group 1 human carcinogen but considered other PCDDs and PCDFs as not classifiable regarding their carcinogenicity in humans . DDE and certain PCBs have estrogenic activity in vitro and in vivo, and an association between higher blood levels of DDE and PCBs and breast cancer has been suggested in some case–control studies, but this has not been confirmed in most of the recent studies . There is increasing, although not entirely consistent, evidence from occupationally and otherwise highly exposed cohorts that TCDD and possibly other PCDD/Fs are associated with increased mortality from ischemic heart disease.

Even at background levels of exposure, TCDD was found to increase the risk of type 2 diabetes , and this increase was not associated with the TCDD elimination rate . Again, the data are not entirely consistent . An association has also been suggested between PCB exposure and diabetes .In women who gave birth between 1959 and 1966, the OR of preterm birth was significantly increased, with increasing concentrations of DDE in maternal serum . A less consistent, but significant, increase in the OR of being small for gestational age was also observed . The reduction in birth weight of children born to mothers who frequently consumed more Great Lakes sport-caught fish compared to children of mothers who rarely consumed contaminated fish was also associated with higher maternal serum DDE levels but not PCB levels . However, such effects of DDE have not been observed in studies of more recent cohorts, suggesting that they may no longer occur at current exposure levels . There were signs of intrauterine growth retardation in children of Yusho and Yu-Cheng mothers , but it is unclear whether this resulted from the PCBs, PCDFs, and/or the thermal degradation products of PCBs. An association between exposure to background levels of PCBs and birth weight or gestational age hasnot been seen consistently . There is also no strong evidence for a negative effect of PCDDs and PCDFs on birth outcomes . In the Seveso cohort, the sex ratio in the children born after the accident became lower with increasing paternal exposure to TCDD, as assessed in serum samples collected in 1976 and 1977 . This was particularly obvious in fathers exposed before the age of 19 yr . The exposure levels of the mothers were not associated with any changes in sex ratio. Almost identical results were recently reported in workers from a Russian pesticide-producing plant exposed to high levels of dioxin . Conversely, no significant differences in the sex ratio were observed in the Yusho and Yu-Cheng incidents in Japan and Taiwan or in children born to veterans of Operation Ranch Hand who were exposed to Agent Orange .The possible neurodevelopmental toxicities of PCBs and PCDD/Fs are one of the major concerns regarding environmental background exposure to OCs and are the focus of much ongoing research. Gestational exposure of rodents and monkeys to PCBs is consistently found to have negative effects on learning as well as locomotor activity and function . In the Taiwanese Yu-Cheng incident, exposed mothers reported a delay in 32 of 33 developmental milestones in their children who were born up to 7 yr following the poisoning . The exposed children also scored consistently lower than controls on several formal cognitive and behavioral tests, with the exception of the verbal IQ on the Wechsler Intelligence Scale for Children .