International Commission for Protection Against Environmental Mutagens and Carcinogens. Two million rodent carcinogens? The role of SAR and QSAR in their detection.
The accurate prediction of chemical carcinogenicity can only be achieved by a balanced consideration of the following factors: the chemistry and metabolism of the test agent, the interaction between toxicity and genetic toxicity, the possibility of non-genotoxic events that trigger subsequent non-targeted mutagenesis, the difference between activities observed in vitro and in vivo, and the possible inadequacy and/or partiality of all datasets and observations. Extrapolation of activities within a series of congeners is usually possible, but predictions across different chemical classes/mechanisms of carcinogenicity are difficult. Artificial intelligence systems can be used to predict one or more of the above parameters given adequate learning sets, but the hope for a single, coherent and self-contained method of predicting all instances of carcinogenicity is unreal. The future of carcinogen/mutagen prediction lies with data-rich artificial intelligence systems based on known mechanistic principles used selectively within the context of chemical and biological human insight. The major current obstacle to progress is the assumption that mutagenicity and carcinogenicity are unitary phenomena that can be learned and predicted by artificial intelligence systems operating in isolation.
Ashby
J
J
Zeneca Central Toxicology Laboratory, Macclesfield, Ches., UK.
D000477:Alkylating Agents / Q000737:chemistry; D000818:Animals; D001711:Biotransformation; D002273:Carcinogens / Q000737:chemistry* / Q000145:classification / Q000633:toxicity*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D016208:Databases, Factual; D004583:Electrons; D005103:Expert Systems; D005544:Forecasting / Q000379:methods; D008433:Mathematics; D008830:Microbodies / Q000187:drug effects; D008956:Models, Chemical; D015394:Molecular Structure; D009153:Mutagens / Q000737:chemistry / Q000145:classification / Q000633:toxicity; D012377:Rodentia; D013329:Structure-Activity Relationship
D000477:Alkylating Agents; D002273:Carcinogens; D009153:Mutagens