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A prospective toxicity evaluation (COMPACT) on 40 chemicals currently being tested by the National Toxicology Program. 1990

D F Lewis, and C Ioannides, and D V Parke
Department of Biochemistry, University of Surrey, Guildford, UK.

The computer-optimized molecular parametric analysis of chemical toxicity (COMPACT) procedure has been used to determine the molecular conformation and electronic structure of a series of 40 chemicals (out of a total of 44). The procedure can evaluate whether they interact with the active site of cytochrome P450 I or to the binding site of the Ah receptor, and hence to manifest carcinogenicity/toxicity. This is in response to the recent publication by Tennant et al. and their invitation to participate in a prospective identification of potential mutagenicity/carcinogenicity of these 44 chemicals. Correlation of COMPACT with potential genotoxicity was 25/40 (63%); COMPACT also predicted toxicity/carcinogenicity in 10 chemicals (25%) considered to be potentially non-genotoxic (naphthalene, promethazine, resorcinol, p-nitrophenol, tricresyl phosphate, bis(bromoethyl) propanediol, 3,4-dihydrocoumarin, theophylline, triamterene and chloramine), and predicted the absence of toxicity in four chemicals (10%) considered to be potentially genotoxic (methyl bromide, hydrazoic acid, 2,3-dibromo-1-propanol and 1,2,3-trichloropropane).

UI MeSH Term Description Entries
D008968 Molecular Conformation The characteristic three-dimensional shape of a molecule. Molecular Configuration,3D Molecular Structure,Configuration, Molecular,Molecular Structure, Three Dimensional,Three Dimensional Molecular Structure,3D Molecular Structures,Configurations, Molecular,Conformation, Molecular,Conformations, Molecular,Molecular Configurations,Molecular Conformations,Molecular Structure, 3D,Molecular Structures, 3D,Structure, 3D Molecular,Structures, 3D Molecular
D009152 Mutagenicity Tests Tests of chemical substances and physical agents for mutagenic potential. They include microbial, insect, mammalian cell, and whole animal tests. Genetic Toxicity Tests,Genotoxicity Tests,Mutagen Screening,Tests, Genetic Toxicity,Toxicity Tests, Genetic,Genetic Toxicity Test,Genotoxicity Test,Mutagen Screenings,Mutagenicity Test,Screening, Mutagen,Screenings, Mutagen,Test, Genotoxicity,Tests, Genotoxicity,Toxicity Test, Genetic
D011446 Prospective Studies Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group. Prospective Study,Studies, Prospective,Study, Prospective
D003201 Computers Programmable electronic devices designed to accept data, perform prescribed mathematical and logical operations at high speed, and display the results of these operations. Calculators, Programmable,Computer Hardware,Computers, Digital,Hardware, Computer,Calculator, Programmable,Computer,Computer, Digital,Digital Computer,Digital Computers,Programmable Calculator,Programmable Calculators
D003577 Cytochrome P-450 Enzyme System A superfamily of hundreds of closely related HEMEPROTEINS found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (MIXED FUNCTION OXYGENASES). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (BIOTRANSFORMATION). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism. Cytochrome P-450,Cytochrome P-450 Enzyme,Cytochrome P-450-Dependent Monooxygenase,P-450 Enzyme,P450 Enzyme,CYP450 Family,CYP450 Superfamily,Cytochrome P-450 Enzymes,Cytochrome P-450 Families,Cytochrome P-450 Monooxygenase,Cytochrome P-450 Oxygenase,Cytochrome P-450 Superfamily,Cytochrome P450,Cytochrome P450 Superfamily,Cytochrome p450 Families,P-450 Enzymes,P450 Enzymes,Cytochrome P 450,Cytochrome P 450 Dependent Monooxygenase,Cytochrome P 450 Enzyme,Cytochrome P 450 Enzyme System,Cytochrome P 450 Enzymes,Cytochrome P 450 Families,Cytochrome P 450 Monooxygenase,Cytochrome P 450 Oxygenase,Cytochrome P 450 Superfamily,Enzyme, Cytochrome P-450,Enzyme, P-450,Enzyme, P450,Enzymes, Cytochrome P-450,Enzymes, P-450,Enzymes, P450,Monooxygenase, Cytochrome P-450,Monooxygenase, Cytochrome P-450-Dependent,P 450 Enzyme,P 450 Enzymes,P-450 Enzyme, Cytochrome,P-450 Enzymes, Cytochrome,Superfamily, CYP450,Superfamily, Cytochrome P-450,Superfamily, Cytochrome P450
D001665 Binding Sites The parts of a macromolecule that directly participate in its specific combination with another molecule. Combining Site,Binding Site,Combining Sites,Site, Binding,Site, Combining,Sites, Binding,Sites, Combining
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
D016002 Discriminant Analysis A statistical analytic technique used with discrete dependent variables, concerned with separating sets of observed values and allocating new values. It is sometimes used instead of regression analysis. Analyses, Discriminant,Analysis, Discriminant,Discriminant Analyses

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