Carcinogenic hazards from inhaled carbon black, titanium dioxide, and talc not containing asbestos or asbestiform fibers:: Recent evaluations by an IARC Monographs working group

In February 2006, an IARC Monographs Working Group reevaluated the carcinogenic hazards to humans of carbon black, titanium dioxide, and talc, which belong to the group of poorly soluble, low-toxicity particles. The review of the relevant literature and the evaluations by the Working Group will be published in Volume 93 of the IARC Monographs series. This article summarizes the Working Group's conclusions. Epidemiological studies among workers in carbon black production and in the rubber industry provided inadequate evidence of carcinogenicity. The overall data from cancer studies in rodents exposed to carbon black provided sufficient evidence of carcinogenicity. The Working Group evaluated carbon black as possibly carcinogenic to humans, Group 2B. Reviewing the epidemiological studies in the titanium dioxide production industry, the Working Group concluded that there is inadequate evidence of carcinogenicity. Overall, the results from rodent cancer studies with titanium dioxide were considered to provide sufficient evidence. Titanium dioxide was evaluated as possibly carcinogenic to humans, Group 2B. Epidemiological studies on talc miners and millers provided inadequate evidence of carcinogenicity of inhaled talc not containing asbestos or asbestiform fibers. The evidence from rodent cancer studies was considered limited. The Working Group evaluated inhaled talc not containing asbestos or asbestiform fibers as not classifiable as to its carcinogenicity to humans, Group 3. The Working Group noted that prolonged exposure to inhaled particles at sufficiently high concentrations in experimental animals may lead to impairment of normal clearance mechanisms in the alveolar region of the lung, resulting in a continued buildup of particles that eventually leads to excessive lung burdens accompanied by chronic alveolar inflammation. The inflammatory response may give rise to increased generation of reactive oxygen species, cell injury, cell proliferation, fibrosis, induction of mutations, and, ultimately, cancer. Since many of these steps also occur in workers in dusty jobs, such as coal miners, data on cancer in animals obtained under conditions of impaired lung clearance were considered relevant to humans. In addition, impaired lung clearance in rodents exposed to ultrafine particles occurs at much lower mass concentrations than with fine particles, which adds to the human relevance.