Strategies and testing methods for identifying mutagenic risks

The evolution of testing strategies and methods for identification of mutag enic agents is discussed, beginning with the concern over potential health and population effects of chemical mutagens in the late 1940s that led to t he development of regulatory guidelines for mutagenicity testing in the 197 0s and 1980s. Efforts to achieve international harmonization of mutagenicit y testing guidelines are summarized, and current issues and needs in the fi eld are discussed, including the need for quantitative methods of mutagenic risk assessment, dose-response thresholds, indirect mechanisms of mutageni city, and the predictivity of mutagenicity assays for carcinogenicity in vi vo. Speculation is offered about the future of mutagenicity testing, includ ing possible near-term changes in standard test batteries and the longer-te rm roles of expression profiling of damage-response genes, in vivo mutageni city testing methods, and models that better account for differences in met abolism between humans and laboratory model systems. Published by Elsevier Science B.V.