A prospective toxicity evaluation (COMPACT) on 40 chemicals currently being tested by the National Toxicology Program.
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).
Lewis
D F
DF
Department of Biochemistry, University of Surrey, Guildford, UK.
Ioannides
C
C
Parke
D V
DV
D001665:Binding Sites; D015197:Carcinogenicity Tests; D003201:Computers; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D016002:Discriminant Analysis; D008968:Molecular Conformation; D009152:Mutagenicity Tests; D011446:Prospective Studies
D003577:Cytochrome P-450 Enzyme System