Design of the Study ‘Scientific Rationale and Chemical Selection’

Abstract

The first UKEMS study represented a unique and adventurous collaboration between scientists concerned with the identification of possible human carcinogens and mutagens (UKEMS, 1982). 4-Chloromethyl-biphenyl (4CMB), a bacterial mutagen containing an overtly DNA-reactive substituent on an optimal aromatic nucleus (Ashby et al., 1982a,) was adopted for study in assays ranging from bacteria to mammals and encompassing endpoints as diverse as point mutation, transformation, dominant lethality and carcinogenicity. The central purpose of that study was to determine if the potential mammalian carcinogenicity and mutagenicity of 4CMB, as defined in bacteria exposed to it in vitro, would be realised in mammals exposed to it in vivo. A subsidiary objective was to compare and contrast the activity of a single chemical in a range of assays with different genetic endpoints, or with the same endpoint represented in different phyla. Both of these objectives were of prime relevance to the science of environmental mutagenesis and carcinogenesis: the extrapolation to mammals of genotoxity data generated in experimental systems, in particular, to man (Ashby, 1983).