THE PARALLELOGRAM APPROACH IN STUDIES OF GENOTOXIC EFFECTS

Over the past two decades mutagenicity tests have been used for the id entification of potential human mutagens and have had an ancillary rol e, as supportive evidence in the assessment of human carcinogens. The demonstration of human germinal mutagens has been beyond the main scop e of short-term testing strategies. However, just as mutagenicity test s have been useful in detecting potential carcinogens so should carcin ogenicity tests assist the identification of presumptive germ cell mut agens. Cancer is an easily observable phenotype of mutation for genoto xic carcinogens and multi-site carcinogens or gonadal carcinogens logi cally could be germ cell mutagens. Thus carcinogenicity and mutagenici ty data for a given genotoxic chemical should be considered together i n the identification of putative germinal mutagens. Clearly, most clas sified human carcinogens are genotoxic thus helping to build the case for human germ cell mutagenicity. This paper describes the issues invo lved in such thinking and suggests an enhanced parallelogram approach incorporating the cancer endpoint. The enhanced parallelogram is explo red using 1,3-butadiene and ethylene oxide as examples. The obvious la ck of data for extrapolations using the parallelogram method suggests the need for targeted studies specifically designed for use in this ap proach.