title: Risk assessment of carcinogenic chemicals in The Netherlands. Health Council of The Netherlands: Committee on the Evaluation of the Carcinogenicity of Chemical Substances.
abstract: The Health Council of The Netherlands advises the Dutch government on scientific issues concerning health and environmental protection. In 1978 a committee of the Council established mechanistic criteria for quantitative risk assessment of carcinogenic substances. For this purpose it adopted the multistage model of carcinogenesis. Based on this model two categories of carcinogens were distinguished. The first category includes complete carcinogens and tumor initiators; these agents induce irreversible modification of DNA and act by a stochastic mechanism. The second category includes promoters and other substances acting as cocarcinogens; these agents act by nonstochastic mechanisms. Stochastic action implies that there is no threshold for the contribution to the carcinogenic effect, whereas nonstochastic action implies a threshold dose. Recently, reevaluation of the method for carcinogenic risk assessment was considered due because of remarkable scientific progress since 1978, such as the identification of cellular oncogenes and tumor suppressor genes, and the partial clarification of mechanisms at the cellular and/or molecular level by which tumor promoters stimulate tumor development. The present paper discusses the Dutch method for carcinogenic risk assessment in the light of the recent scientific developments. It concludes that this method for risk assessment is still a valid and appropriate one.
mesh_terms: D000818:Animals; D015197:Carcinogenicity Tests / Q000592:standards*; D004247:DNA / Q000187:drug effects; D006801:Humans; D008954:Models, Biological; D015233:Models, Statistical; D009153:Mutagens / Q000633:toxicity; D009426:Netherlands; D012307:Risk Factors; D013329:Structure-Activity Relationship
chemical_list: D009153:Mutagens; D004247:DNA