Identification of research needs to resolve the carcinogenicity of high-priority IARC Carcinogens. Views and expert opinions of an IARC/NORA expert group meeting, Lyon, France, 30 June - 2 July 2009. Lyon, France: International Agency for Research on Cancer, IARC Technical Publication No. 42. 2010 Jul; 42:166-183
1. Gaps in understanding related to PCB sources and exposures: a. Mechanisms for human exposure to Aroclor and non-Aroclor PCBs. Recently non- Aroclor PCBs have been identified in air. PCB11, for example, appears to be associated with paint (Hu et al., 2008). There is a need to identify sources, including volatilization from paint. Mechanisms that deserve study include inhalation, child consumption of paint chips and other building materials, accumulation in food, accumulation in fish, occupational exposures, for example, during building demolition. b. Distribution of airborne PCB sources in cities. c. Storage of Aroclors, particularly in cities. There is a great need for reasonably accurate inventories of stored PCBs. Some countries do a much better job of tracking their old transformers than others. d. Human exposure to PCB degradation products and metabolites (these compounds are not well studied but are found in human tissues and in the environment). 2. Research needs related to mechanisms of action/toxicity: a. There is an overwhelming need to investigate the metabolic fate of lower chlorinated PCBs found in buildings, in cities, near waste sites, and in schools. What are the reaction products? Are they mutagenic? Are any of these accessible/stable such that they may serve as biomarkers of exposure/effect? Can we prevent or abrogate the negative impacts of exposure? The fate of these residues, whether excreted without causing harm, or converted to metabolites that are toxic, or if bound covalently to tissues, is unknown. b. The roles of metabolism of OHPCBs (e.g., further oxidation, sulfation, and other metabolic reactions) in the disposition and toxicity represent a significant gap in our knowledge about mechanisms for carcinogenesis and other toxic responses to PCBs. c. Many mechanisms of genotoxicity/carcinogenicity for PCBs appear to involve issue of reactive oxygen species/oxidative stress, including the appearance of oxidative DNA damage. The recent identification of M1dG DNA adducts after chronic exposure to PCBs 126/153 (Jeong et al., 2008), and the recent report by Spencer and colleagues (Spencer et al., 2009) demonstrate a role for oxidative DNA damage in the carcinogenic action of PCBs in rodent liver. In general these increases are associated with the higher exposures, which are also where the increases in liver tumors occur. More research is needed with this mode of action and with cell proliferation, as the two could drive the induction of mutations and subsequent carcinogenicity. Specific attention needs to focus on dose-response. More PCB congeners need to be studied!! 3. Airborne PCB profiles are distinctly different from those of commercial PCB mixtures like Aroclor 1254, and enzyme induction in the liver is most likely a completely inappropriate endpoint of toxicity for inhalation exposure. There is a great need to identify appropriate biomarkers for exposure /effect/susceptibility for airborne PCB exposure. Issues of dietary/nutritional deficiencies, in utero exposures, and developmental impacts are all unknown. 4. The existing epidemiologic literature, most of it produced since the last review of PCBs in 1987, may suffice for a re-evaluation of the carcinogenicity by an IARC working group. Possible studies include cancer incidence of the large (>26,000 workers) NIOSH cohort, which is under way. Nested case-control studies within this cohort and/or those in Sweden and Italy, evaluating current PCB blood levels in cases and controls, might be informative. A large population of individuals living in Aniston, Alabama, around the former PCB manufacturing facility received high levels of exposure through various routes. This group may be a useful study population.
Cancer; Carcinogens; Carcinogenesis; Carcinogenicity; Air-contamination; Airborne-particles; Vapors; Inhalants; Inhalation-studies; Children; Paints; Construction-materials; Food-contaminants; Construction; Construction-industry; Construction-materials; Fishing-industry; Occupational-exposure; Storage-facilities; Storage-containers; Metabolites; Toxic-effects; Toxic-vapors; Genotoxicity; Oxygen-toxicity; Biomarkers
Identification of research needs to resolve the carcinogenicity of high-priority IARC Carcinogens. Views and expert opinions of an IARC/NORA expert group meeting, Lyon, France, 30 June - 2 July 2009