Module 3: Toxicology - Section 13: Occupational Carcinogenesis

TOX 13.13: Carcinogen Exposure Assessment

INTERNATIONAL AGENCY FOR RESEARCH ON CANCER (IARC) CLASSIFICATION OF CARCINOGENS:

The IARC has a monographs programme in which agents, mixtures and exposure circumstances are evaluated if there is evidence of human exposure,  and human or animal data on carcinogenicity.Evaluation of evidence of carcinogenicity in the IARC Monographs programme

1. The evidence for the induction of cancer in humans, which obviously plays an important role in the identification of human carcinogens is considered. Three types of epidemiological studies contribute to an assessment of carcinogenicity in humans: cohort studies, case-control studies and correlation (or ecological) studies. Case reports of cancer in humans may also be reviewed. The evidence relevant to carcinogenicity from studies in humans is classified into one of the following categories:

• Sufficient evidence of carcinogenicity. A causal relationship has been established between exposure to the agent, mixture or exposure circumstance and human cancer. That is, a positive relationship has been observed between the exposure and cancer in studies in which chance, bias and confounding could be ruled out with reasonable confidence.
• Limited evidence of carcinogenicity. A positive association has been observed between exposure to the agent, mixture or exposure circumstance and cancer for which a causal interpretation is considered to be credible, but chance, bias or confounding could not be ruled out with reasonable confidence.
• Inadequate evidence of carcinogenicity. The available studies are of insufficient quality, consistency or statistical power to permit a conclusion regarding the presence or absence of a causal association, or no data on cancer in humans are available.
• Evidence suggesting lack of carcinogenicity. There are several adequate studies covering the full range of levels of exposure that human beings are known to encounter, which are mutually consistent in not showing a positive association between exposure to the agent and the studied cancer at any observed level of exposure.

2. Studies in which experimental animals (mainly rodents) are exposed chronically to potential carcinogens and examined for evidence of cancer are reviewed and the degree of evidence of carcinogenicity is then classified into categories similar to those used for human data.

3. Data on biological effects in humans and experimental animals that are of particular relevance are reviewed. These may include toxicological, kinetic and metabolic considerations and evidence of DNA binding, persistence of DNA lesions or genetic damage in exposed humans. Toxicological information, such as that on cytotoxicity and regeneration, receptor binding and hormonal and immunological effects, and data on structure-activity relationship are used when considered relevant to the possible mechanism of the carcinogenic action of the agent.

4. The body of evidence is considered as a whole, in order to reach an overall evaluation of the carcinogenicity to humans of an agent, mixture or circumstance of exposure and translated to the classification system below:

Postgraduate Diploma in Occupational Health (DOH) - Modules 3: Occupational Medicine & Toxicology (Basic) by Profs Mohamed Jeebhay and Rodney Ehrlich, Health Sciences UCT is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 2.5 South Africa License. Major contributors: Mohamed Jeebhay, Rodney Ehrlich, Jonny Myers, Leslie London, Sophie Kisting, Rajen Naidoo, Saloshni Naidoo. Source available from here. For any updates to the material, or more permissions beyond the scope of this license, please email healthoer@uct.ac.za or visit www.healthedu.uct.ac.za. Last updated Jan 2007.
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