Aspects of database construction and interrogation of relevance to the accurate prediction of rodent carcinogenicity and mutagenicity.
Attempts to reconcile qualitative carcinogenicity databases with qualitative mutagenicity database continue to indicate that there is no useful relationship between mutagenicity/genotoxicity and rodent carcinogenicity. It is suggested that recognition of two classes of carcinogen, genotoxic and nongenotoxic, is the first step in finding meaningful correlations between the above parameters. This then leads to purposeful intervention into the databases, including rejecting low quality data, abandoning some assays from the database, and clustering certain end points as repetitive rather that independent of each other. Seeking specific correlations within a focused database may yield knowledge from the current wealth of information. The effort required to build databases, particularly quantitative ones, has so far prevented the equally arduous task of their correct interrogation. Preliminary indications are the mutagenicity is closely correlated with genotoxic carcinogenesis and completely independent of nongenotoxic carcinogenesis.
Ashby
J
J
ICI Central Toxicology Laboratory, Alderley Park, Cheshire, UK.
D000818:Animals; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000145:classification* / Q000633:toxicity; D016208:Databases, Factual; D004305:Dose-Response Relationship, Drug; D007390:International Agencies; D051379:Mice; D016296:Mutagenesis; D009152:Mutagenicity Tests; D051381:Rats; D013045:Species Specificity; D013329:Structure-Activity Relationship; D014116:Toxicology; D014481:United States; D014484:United States Environmental Protection Agency
D002273:Carcinogens