Julian Wilbourn

Human Carcinogens So Far Identified

The massive exploitation of natural resources, of which tobacco and asbestos are two conspicuous, though very different examples, and the synthesis of industrial chemicals have generated new hazards and new carcinogens which have been added to older ones. The majority of the over 50 agents that have been firmly identified so far as being human carcinogens belong to the relatively new hazards, that is environmental chemicals or chemical mixtures to which humans have been exposed only during the last century and a half. They are of more importance for cancer occurring in men than in women, and there is no evidence so far that they are related to cancers occurring at some of the most common target sites in either sex. It would be mistaken to believe that complete cancer prevention could be achieved solely by controlling these new, or relatively new, carcinogenic agents, but it would be similarly wrong to deny the importance of trying to control them and of continuing to do so. The experimental approach for the identification of carcinogens has an irreplaceable role to play in preventing the dispersal into our environment of new hazards and in identifying among the chemicals already in use, those that are carcinogenic. That a closer integration between the epidemiological and the experimental approaches may succeed in substantially reducing the size of the unknown region within the spectrum of cancer‐causing factors, is todays hope that awaits confirmation. At the same time, advances in the understanding of the mechanisms underlying the different steps of the process leading to the clinical manifestation of cancer may help in the uncovering of agents and risk factors that the approaches used, at least in the way they have been used until now, may not have been apt to identify.

Evaluation of the carcinogenic risks to humans associated with surgical implants and other foreign bodies — a report of an IARC Monographs Programme Meeting

A meeting was held within the International Agency for Research on Cancer (IARC) Programme on the Evaluation of Carcinogenic Risks to Humans of surgical implants and other foreign bodies. This meeting report summarises the types of materials considered, their wear and degradation, their cancer epidemiology in both humans and other animals, the published experimental carcinogenicity data and selected data on their toxic, including genotoxic, effects. Evaluations resulting in a classification of Group 2B (possibly carcinogenic to humans) were reached for: (1) polymeric implants prepared as thin smooth films [with the exception of poly(glycolic acid)]; (2) metallic implants prepared as thin smooth films; and (3) implanted foreign bodies consisting of metallic cobalt, metallic nickel and a particular alloy powder consisting of 66-67% nickel, 13-16% chromium and 7% iron. Group 3 classifications (not classifiable as to their carcinogenicity to humans) were made for: (1) organic polymeric materials as a group; (2) orthopaedic implants of complex composition and cardiac pacemakers; (3) silicone breast implants; (4) dental materials; and (5) ceramic implants.

Tumors of the Nervous System in Carcinogenic Hazard Identification

In the absence of adequate data on humans, it is biologically plausible and prudent to regard agents and mixtures for which there is sufficient evidence of carcinogenicity in experimental animals, usually rats and mice, as if they presented a carcinogenic risk to humans. Prediction of cancer sites in humans from bioassay data in rodents is much less certain, however, regardless of organ or tissue. For tumors of the nervous system, there is practically no basis for judging the validity of such predictions, as only ionizing radiation is known to cause tumors of the central nervous system (CNS) in humans. Brain tumors are relatively uncommon findings in bioassays and are rare in untreated rodents, even in rats, which appear to be the most susceptible species. However, CNS tumors have been readily induced in rodents by systemic exposures to some chemicals, notably N-nitrosoalkylureas and other alkylating agents and certain alkyl hydrazine derivatives. CNS tumors in rodents have played a significant role in carcinogenic hazard evaluations of several other chemicals, including acrylonitrile, ethylene oxide, and acrylamide, and have been implicated as part of the tumor spectrum induced by vinyl chloride and certain inorganic lead compounds. In some of these evaluations, it is not certain that all tumors diagnosed as primary brain tumors were correctly identified. Diagnostic difficulties have been presented by undifferentiated small-cell tumors that may invade the brain, including carcinomas of the nasal cavity and undifferentiated schwannomas arising in cranial nerve ganglia, and by the difficulty of reliably distinguishing between focal reactive gliosis and early glial neoplasms. The most striking experimental finding regarding the induction by chemicals of tumors of the nervous system is the dramatically greater susceptibility of the fetal and neonatal nervous system to some carcinogens, as compared with the susceptibility of the nervous system in adults of the same species.

Identification of Chemicals Carcinogenic to Man

Although both the epidemiologic and experimental studies have led to the identification of chemical carcinogens, the limitations in epidemiologic approaches and the need for primary prevention of cancer require a greater reliance on experimental studies. Long-term carcinogenicity studies in experimental animals have been instrumental in identifying chemicals with carcinogenic activity, and, in some cases, the experimental evidence has preceded the epidemiologic evidence (for 4-aminobiphenyl, aflatoxin B1, diethylstilbestrol, melphalan, mustard gas, and vinyl chloride). A better understanding of the multistage process of carcinogenesis and the findings from various short-term tests available more recently may provide a more solid basis for extrapolating experimental findings to man.