Co-ordinator’s Report: In vivo Assays Used in the Second UKEMS Collaborative Study

Abstract

When this study commenced it was known that the four test agents (BZD, DAT, DAB and CDA) were genotoxic in some in vitro assays. It was therefore expected that a large proportion of the additional in vitro studies conducted within the study would also prove positive. The beginning of a rationalisation for the occasionally divergent in vitro assay results for these agents is made in the Study Overview which follows this chapter. Far less certain at the start, and probably more intriguing, was how short-term rodent assays conducted in vivo would respond to these agents. It was apparent at the start of the study that an adequate representation of the rodent bone marrow cytogenetic assays would be provided, but both of the established carcinogens in the study (BZD and DAB) were already known to be only weakly clastogenic in this tissue (de Serres and Ashby, 1980). The danger therefore existed that short-term in vivo assays would be judged collectively by the performance of the bone marrow assays. This was considered inappropriate at this critical stage in the development of in vivo assays, especially as a major in vivo study organised by the IPCS was running in parallel with this one (Ashby et al., 1983). An effort was therefore made to incorporate additional rodent assays in the study, in particular, those associated with the rodent liver, bladder, foetus and urine. This grouping remained incomplete at the end of the study, but when considered within the context of the carcinogenicity bioassay data for DAT and the extensive disposition and metabolism data generated, a useful database was formed. The present chapter considers the acute rodent assay data available and how they relate to the available carcinogenic data on these four in vitro genotoxins.