The first US National Toxicology Program exercise on the prediction of rodent carcinogenicity: definitive results. 1997

R Benigni
Istituto Superiore di Sanita, Laboratory of Comparative Toxicology and Ecotoxicology, Rome, Italy.

A few years ago, the US National Toxicology Program sponsored an exercise aimed at comparing different prediction approaches for carcinogenicity by challenging them on a common set of chemicals. The exercise was considered to be sufficiently completed when 40 (out of 44) chemicals were actually experimentally tested, and the experimental and estimated carcinogenicity were compared. More recently, the rodent results for the remaining 4 chemicals have been disclosed, making it possible to draw definitive conclusions on the comparative exercise. Having analyzed the first subset of results with multivariate statistical methods, we present here the analysis of the complete set of results. The present analysis also considers aspects (e.g., the complementarity of the different systems in identifying the carcinogens), which had not been investigated previously. The conclusion of this study were: (a) the expansion of the data base from 40 to 44 chemicals did not significantly change the results of the exercise; (b) the structure-activity approaches generated prediction profiles different from those generated by the prediction systems mainly relying on the use of experimental data (in vitro and in vivo); (c) the performance of the predictive systems was generally rather limited; (d) the prediction systems were affected by over sensitivity; they were generally capable of identifying the molecules containing the potentially alerting substructures, but were not so refined as to be able to discriminate between potential and actual carcinogenicity; (e) the combination of the systems into batteries did not permit a significant increase in the performance of the individual methods. The need for, and possible approaches to finely tuning the systems are discussed.

UI MeSH Term Description Entries
D008954 Models, Biological Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment. Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D002273 Carcinogens Substances that increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. Carcinogen,Oncogen,Oncogens,Tumor Initiator,Tumor Initiators,Tumor Promoter,Tumor Promoters,Initiator, Tumor,Initiators, Tumor,Promoter, Tumor,Promoters, Tumor
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012680 Sensitivity and Specificity Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Specificity is the probability of correctly determining the absence of a condition. (From Last, Dictionary of Epidemiology, 2d ed) Specificity,Sensitivity,Specificity and Sensitivity
D012984 Software Sequential operating programs and data which instruct the functioning of a digital computer. Computer Programs,Computer Software,Open Source Software,Software Engineering,Software Tools,Computer Applications Software,Computer Programs and Programming,Computer Software Applications,Application, Computer Software,Applications Software, Computer,Applications Softwares, Computer,Applications, Computer Software,Computer Applications Softwares,Computer Program,Computer Software Application,Engineering, Software,Open Source Softwares,Program, Computer,Programs, Computer,Software Application, Computer,Software Applications, Computer,Software Tool,Software, Computer,Software, Computer Applications,Software, Open Source,Softwares, Computer Applications,Softwares, Open Source,Source Software, Open,Source Softwares, Open,Tool, Software,Tools, Software
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D014116 Toxicology The science concerned with the detection, chemical composition, and biological action of toxic substances or poisons and the treatment and prevention of toxic manifestations. Toxinology,Evidence Based Toxicology,Evidence-Based Toxicology,Based Toxicologies, Evidence,Based Toxicology, Evidence,Evidence Based Toxicologies,Evidence-Based Toxicologies,Toxicologies, Evidence Based,Toxicologies, Evidence-Based,Toxicology, Evidence Based,Toxicology, Evidence-Based
D015197 Carcinogenicity Tests Tests to experimentally measure the tumor-producing/cancer cell-producing potency of an agent by administering the agent (e.g., benzanthracenes) and observing the quantity of tumors or the cell transformation developed over a given period of time. The carcinogenicity value is usually measured as milligrams of agent administered per tumor developed. Though this test differs from the DNA-repair and bacterial microsome MUTAGENICITY TESTS, researchers often attempt to correlate the finding of carcinogenicity values and mutagenicity values. Tumorigenicity Tests,Carcinogen Tests,Carcinogenesis Tests,Carcinogenic Activity Tests,Carcinogenic Potency Tests,Carcinogen Test,Carcinogenesis Test,Carcinogenic Activity Test,Carcinogenic Potency Test,Carcinogenicity Test,Potency Test, Carcinogenic,Potency Tests, Carcinogenic,Test, Carcinogen,Test, Carcinogenesis,Test, Carcinogenic Activity,Test, Carcinogenic Potency,Test, Carcinogenicity,Test, Tumorigenicity,Tests, Carcinogen,Tests, Carcinogenesis,Tests, Carcinogenic Activity,Tests, Carcinogenic Potency,Tests, Carcinogenicity,Tests, Tumorigenicity,Tumorigenicity Test
D015999 Multivariate Analysis A set of techniques used when variation in several variables are studied simultaneously. In statistics, multivariate analysis is interpreted as any analytic method that allows simultaneous study of two or more dependent variables. Analysis, Multivariate,Multivariate Analyses

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