STRUCTURAL IMPLICATIONS OF THE ICPEMC METHOD FOR QUANTIFYING GENOTOXICITY DATA

Committee 1 of ICPEMC (International Commission for Protection against Environmental Mutagens and Carcinogens) devised a weight-of-evidence scheme for ranking chemicals with respect to their probability of inducing genetic effects. The score is based upon a hierarchical scheme which combines the results of many assays and assigns relative levels of relevance depending upon the phylogenic level of the assay, the nature of the genetic endpoint and the dose of chemical required. Analysis of the ICPEMC data base of quantitative genotoxicity scores by CASE and MULTICASE, two structure-activity relational expert systems, revealed that the ICPEMC quantitative classification ''made sense'' structurally, i.e. there was internal consistency with respect to the structural determinants associated with the qualitative as well as the quantitative classifications. Analysis of subsets of in vitro and in vivo genotoxicity results revealed that there was almost a complete overlap among the structural determinants associated with the qualitative classifications [i.e. likelihood of having a positive or negative score] of chemicals but that there were significant differences among the determinants related to the quantitative in vitro and in vivo scores (i.e. potency). Overall, the analyses suggest that there is a continuum in the structural bases of genetic effects which span phyla.