Practical aspects of mutagenicity testing strategy: an industrial perspective

Genetic toxicology studies play a central role in the development and marke ting of new chemicals for pharmaceutical, agricultural, industrial, and con sumer use. During the discovery phase of product development, rapid screeni ng tests that require minimal amounts of test materials are used to assist in the design and prioritization of new molecules. At this stage, a modifie d Salmonella reverse mutation assay and an in vitro micronucleus test with mammalian cell culture are frequently used for screening. Regulatory geneti c toxicology studies are conducted with a short list of compounds using pro tocols that conform to various international guidelines. A set of four assa ys usually constitutes the minimum test battery that satisfies global requi rements. This set includes a bacterial reverse mutation assay, an in vitro cytogenetic test with mammalian cell culture, an in vitro gene mutation ass ay in mammalian cell cultures, and an in vivo rodent bone marrow micronucle us test. Supplementary studies are conducted in certain instances either as a follow-up to the findings from this initial testing battery and/or to sa tisfy a regulatory requirement. Currently available genetic toxicology assa ys have helped the scientific and industrial community over the past severa l decades in evaluating the mutagenic potential of chemical agents. The eme rging field of toxicogenomics has the potential to redefine our ability to study the response of cells to genetic damage and hence our ability to stud y threshold phenomenon. (C) 2000 Elsevier Science B.V. All rights reserved.