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(83-16) QSAR modelling of baseline narcotic chemicals: analyses of 430 compounds in Tetrahymena. Schultz, Terry1, Cronin, Mark2, Netzeva, Tatiana*,2, 1 College of Veterinary Medicine, Knoxville, TN2 School of Pharmacy and Chemistry, Liverpool, England ABSTRACT- Toxicity data for a large and structurally diverse set of industrial organic chemicals tested in the 2-d Tetrahymena pyriformis population growth impairment assay were evaluated. Chemicals were selected to represent baseline or minimal toxicity as defined by the neutral narcosis mechanisms of toxic action. A quantitative structure- toxicity model correlating toxic potency (log (IGC50-1)) with hydrophobicity quantified by the 1-octanol/water partition coefficient (log Kow) was developed. This model [log (IGC50-1) = 0.75 log Kow - 1.83; n = 430; r2 = 0.947, s = 0.25, F = 7576, Pr > F = 0.0001] allows for the accurate prediction of potency from an easily estimated parameter. With few exceptions the application of this QSAR can be extended to chemicals eliciting other mechanisms of toxic action (e.g., polar narcosis, soft electrophilicity) if the log Kow value is greater than 3.5 but less than 5.5. [This work was supported in part by the European Union IMAGETOX Research Training Network (HPRN-CT- 1999-00015)]. Key words: QSAR, non-polar narcosis, Tetrahymena pyriformis |
