The qualitative relationship between carcinogenicity and mutagenicity (DNA-damaging activity), based on chemicals which are known to be or suspected of being carcinogenic to man and/or to experimental animals, is analyzed using 532 chemicals evaluated in Volumes 1-25 of the IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. About 40 compounds (industrial processes) were found to be either definitely or probably carcinogenic to man, and 130 chemicals have been adequately tested in rodents and most of them also in various short-term assays. For a comparison between the carcinogenicity of a chemical and its behavior in short-term tests, systems were selected that have a value for predicting carcinogenicity. These were divided into mutagenicity in (A) the S. typhimurium/microsome assay, (B) other submammalian systems and (C) cultured mammalian cells; (D) chromosomal abnormalities in mammalian cells; (E) DNA damage and repair; (F) cell transformation (or altered growth properties) in vitro.The following conclusions can be drawn. In the absence of studies in man, long-term animal tests are still today the only ones capable of providing evidence of the carcinogenic effect of a chemical. The development and application of an appropriate combination of short-term tests (despite current limitations) can significantly contribute to the prediction/confirmation of the carcinogenic effects of chemicals in animals/man. Confidence in positive tests results is increased when they are confirmed in multiple short-term tests using nonrepetitive end points and different activation systems. Assays to detect carcinogens which do not act via electrophiles (promoters) need to be developed. The results of a given short-term test should be interpreted in the context of other toxicological data. Increasing demand for quantitative carcinogenicity data requires further examination of whether or not there is a quantitative relationship between the potency of a carcinogen in experimental animals/man, and its genotoxic activity in short-term tests. At present, such a relationship is not sufficiently established for it to be used for the prediction of the carcinogenic potency of new compounds.There is increasing evidence to suggest that DNA damage (expressed mainly as mutations) is involved in the induction of many cancers; however, the relevance of the various biological end points used in short-term assays to mechanisms of tumor induction is not known precisely. All test procedures must therefore be validated before they can be used to predict the carcinogenicity of chemicals. Ideally, such validations would be based on correlations between responses in short-term tests and data from epidemiological studies in humans.

The various adverse biological effects of vinyl chloride appear to be dependent upon the metabolic conversion of this compound into chemically reactive metabolites. The metabolism of vinyl chloride in mammals and in man, including the formation of monochloroacetic acid and some identified sulfur conjugates is reviewed. Hepatic microsomal mixed function oxidases from rats, mice, and humans were equally effective in transforming vinyl chloride into alkylating agents in vitro. Two of the enzyme reaction products, i.e., chloroethylene oxide and 2-chloroacetaldehyde, showed potent genetic activity in microorganisms and Chinese hamster V79 cells. The role of liver microsomal enzymes in the generation of electrophilic mutagenic vinyl chloride metabolites is discussed.Chlorinated hydrocarbons, such as vinyl chloride (VCM) or vinylidene chloride, are widely used in the production of plastic resins and are present in the environment (1, 2). It is now recognized that VCM is responsible for various adverse biological effects which induce neoplastic and nonneoplastic diseases in man as well as in animals (2) and that these effects seem to be attributable not to VCM itself but to reactive metabolites formed by microsomal mixed-function oxidases. Many chemical carcinogens have been shown to exert a carcinogenic effect following their metabolic activation into elctrophilic metabolites which react readily with cellular macromolecules (3). This paper is a review of results obtained in our laboratory and by others concerning the mutagenicity of VCM and related compounds and the metabolism of some of these compounds. MutagenicityThe mutagenicity of VCM has been examined in various strains of S. typhimurium in which

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