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. IARC Technical Publication No. 42. Lyon, France: International Agency for Research on Cancer, 2010 Jul; 42:61-72
Epidemiology: Currently there is a single study of UK carbon black production workers providing strong (though novel) evidence that carbon black is a late stage human lung carcinogen. This hypothesis has been given no support whatsoever from the German study of carbon black production workers, although it would be worthwhile for an IARC Working Group to evaluate these recent studies. Ideally, at least one further test of the hypothesis that carbon black is a late stage lung carcinogen is also required. The most obvious candidate is the United States study of carbon black production workers. Attempts should be made to a) locate the 76 unascertained death certificates for this study, b) review plant-specific frequency distributions by year of hire and year of leaving employment to make sure that expected numbers of deaths are not being increased artifactually by including periods of follow-up when no deaths could have occurred, c) collect work history details and derive estimates of cumulative exposure, and d) carry out analyses of lung cancer risks in relation to "lugged" (recent) exposures. Examination of 1) possible relationships between lung cancer risks and other exposure metrics and 2) possible effects of age at exposure need to be carried out for all three published cohorts of carbon black production workers. The cancer experience of workers at many other carbon black production factories remains unexamined, including workers at Columbian (Hannover, Germany), Hanan (Germany), Columbian (Trecate, Italy), Cabot (Ravenna, Italy), Degussa (Ravenna, Italy), Cabot (France), Cabot (Berre L'etang, France), Carbon Black Nederland (Botlek, Netherlands), Cabot (Rozenburg, Netherlands), Carbesa (Cadiz, Spain), Columbian (Santander, Spain), Cabot (Santurce, Spain), and Nordisk (Malmo, Sweden). The outcome variable could be cancer incidence, mortality, but preference would be to use an effect biomarker such as 8- OHdG with the exposure biomarkers. Toxicology: Experimental studies are needed that improve our understanding of the mechanisms of particle-elicited lung cancer. A study examining the relationship between occupational exposure to carbon black and validated biomarkers of oxidative stress may provide information on the early biological responses relevant to particle-induced lung cancer mechanisms. These exposure-response relationships should be quantitatively compared in humans and rodents, and the role of particle size should also be examined. Given the recent findings of an association between the production of microRNA and immune and inflammation processes (Hussain and Harris 2007), it may be useful to investigate the production of microRNA in vitro and in vivo in experimental systems with conditions equivalent to those in which inflammation and tumors were observed in rats (e.g., Elder et al., 2005; Heinrich et al., 1995; Nikula et al., 1995). Investigation of microRNA in other rodent species (mice and hamsters) could provide data on whether the microRNA responses are associated with the chronic inflammation and lung tumor responses. However, investigating a role of microRNA in particle-induced lung responses in humans may not be feasible without the availability of noninvasive or minimally invasive procedures. Studies elucidating the role of particle size in the biological mechanism of particle-elicited carcinogenesis would be useful. Currently, there is uncertainty of whether nanoparticles can interact directly with DNA, in addition to the secondary genotoxic mechanism involving inflammation, oxidative stress, and oxidative DNA damage (Schins and Knaapen 2007).
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, IARC Technical Publication No. 42