Carcinogenicity of "non-dioxinlike" polychlorinated biphenyls

Complex technical mixtures of polychlorinated biphenyls (PCBs) cause liver and thyroid neoplasms in rodents, whereas very few data are available on the carcinogenic potency of single non-dioxinlike (NDL) PCB congeners. In most genotoxicity assays technical PCB mixtures and individual congeners were inactive, suggesting that PCBs act as indirect, nongenotoxic carcinogens. Various mechanisms, including suppression of apoptosis in preneoplastic cells or inhibition of intercellular communication, have been suggested to be active in liver tumor promotion by PCBs. A decrease in thyroid hormone levels after PCB treatment has been suggested to play a role in the development of thyroid neoplasms in rats; however, other mechanisms may also be involved. Results from a chronic carcinogenicity study in rats indicate that not the dose of total PCBs but the total TCDD or toxic equivalents (TEQs) associated with "dioxinlike" (DL) constituents within a technical mixture are mainly if not exclusively responsible for the development of liver neoplasms in female rats. Quantitative comparison reveals almost identical dose-response curves for the total TEQs in various technical PCB mixtures and for TCDD as inducers of hepatic neoplasms in female rats. Tumor promotion experiments have shown, however, that, after initiation with a genotoxic carcinogen, technical PCB mixtures and individual DL-and NDL-PCBs act as liver tumor promoters in rodents. Based on these data, a weak carcinogenic potency of individual NDL-PCB congeners cannot be excluded. In epidemiological studies, increased mortality from cancers of the liver, gallbladder, biliary tract, gastrointestinal tract, and from brain cancer and malignant melanoma were observed in workers exposed to a series of technical PCB mixtures. A significant association between PCB concentrations in adipose tissue and non-Hodgkins lymphoma was found in another study. While in all human studies mixed exposure to DL-and NDL-PCBs occurred, no comprehensive data are available on the relative contribution of NDL-PCBs to the overall external and/or internal PCB exposure in those cohorts.