Evolution of testing strategies for genetic toxicity.
Shortly following the inception of genetic toxicology as a distinct discipline within toxicology, questions arose regarding the type and number of tests needed to classify a chemical as a mutagenic hazard or as a potential carcinogen. To some degree the discipline separated into two sub-specialties, (1) genetic risk assessment and (2) cancer prediction since data from experimental oncology also supports the existence of a genotoxic step in tumor initiation. The issue of which and how many tests continued to be debated, but is now focused more tightly around two independent phenomena. Tier or sequential testing was initially proposed as a logical and cost-effective method, but was discarded on the basis that the lower tier tests appeared to have too many false responses to force or exclude further testing of the test agent. Matrix (battery) testing was proposed for screening on the hypothesis that combinations of endpoints and multiple phylogenetic target organisms were needed to achieve satisfactory predictability. As the results from short-term test 'validation' studies for carcinogen prediction and evaluations of EPA's Gene-Tox data accumulated, it became obvious that qualitative differences remained between predictive and definitive tests and by assembling different combinations of short-term assays investigators did not appear to resolve the lack of concordance. Recent trends in genetic toxicology testing have focused on mathematical models for test selection, and standardized systems for multi-test data assessment.
Brusick
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Department of Genetics, Hazleton Laboratories America, Inc., Kensington, MD 20895.
D000818:Animals; D002273:Carcinogens; D004249:DNA Damage; D049673:History, 20th Century; D066298:In Vitro Techniques; D009152:Mutagenicity Tests / Q000266:history / Q000379:methods*; D009153:Mutagens
D002273:Carcinogens; D009153:Mutagens