Carcinogenicity Working Group

L4RC Working Group on the Evaluation of Carcinogenic Risk of Chemicals to Humans, Some N-Nitroso Compounds, lARC Monograph No. 17, International Agency for Research on Cancer, Lyon, France, 1978. 

The evaluations of carcinogenic risk are made by international working groups of independent scientists and are qualitative in nature. No recommendation is given for regulation or legislation. 

The objective of the programme is to prepare, with the help of international working groups of experts, and to publish in the form of monographs, critical reviews and evaluations of evidence on the carcinogenicity of a wide range of human exposures. The Monographs may also indicate where additional research efforts are needed. 

In coming to an overall evaluation of carcinogenicity in humans (see pp. 25-27), the Working Group also considers related data. The nature of the information selected for the summary depends on the agent being considered. 

Sufficient evidence of carcinogenicity. The Working Group considers that 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. 

Sufficient evidence of carcinogenicity The Working Group considers that a causal relationship has been established between the agent or mixture and an increased incidence of malignant neoplasms or of an appropriate combination of benign and malignant neoplasms in (a) two or more species of animals or (b) in two or more independent studies in one species carried out at different times or in different laboratories or under different protocols. 

For complex exposures, including occupational and industrial exposures, the chemical composition and the potential contribution of carcinogens known to be present are considered by the Working Group in its overall evaluation of human carcinogenicity. The Working Group also determines the extent to which the materials tested in experimental systems are related to those to which humans are exposed. 

In making its overall evaluation of the carcinogenicity to humans of di(2-ethyl-hexyl) phthalate, the Working Group took into consideration that (a) di(2-ethylhexyl) phthalate produces liver tumours in rats and mice by a non-DNA-reactive mechanism involving peroxisome proliferation h) peroxisome proliferation and hepatocellular proliferation have been demonstrated under the conditions of the carcinogenicity studies of di(2-ethylhexyl) phthalate in rats and mice and (c) peroxisome proliferation has not been documented in human hepatocyte cultures exposed to di(2-ethylhexyl) phthalate nor in the liver of exposed non-human primates. Therefore, the mechanism by which di(2-ethylhexyl) phthalate increases the incidence of hepatocellular tumours in rats and mice is not relevant to humans. 

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