title: Structure-toxicity relationships for benzenes evaluated with Tetrahymena pyriformis.
abstract: Toxicity data for 200 substituted benzenes tested in the two-day Tetrahymena pyriformis population growth impairment assay representing the neutral narcosis, polar narcosis, respiratory uncoupling, and weak and strong electrophilic mechanisms of toxic action were evaluated. A quantitative structure-toxicity model correlating toxic potency [log(IGC(50)(-)(1))] with hydrophobicity quantified by the 1-octanol/water partition coefficient (log K(ow)) and electrophilic reactivity quantified by the molecular orbital parameter, maximum superdelocalizability (S(max)), was developed. This model [log(IGC(50)(-)(1)) = 0.50(log K(ow)) + 9.85(S(max)) - 3.47; n = 197, r(2) = 0.816, s = 0.34, F = 429, Pr > F = 0.0001] allows for the prediction of acute potency without the a priori identification of the mechanism of action. The examination of residuals reveals that neutral narcotics with high volatility (e.g., methyl- and chloro-substituted benzenes) and highly reactive fluoro- and nitro-containing derivatives are fitted poorly. A comparison of observed (obs) and predicted (pred) toxicities on the additional set of derivatives [log(obs IGC(50)(-)(1)) = 1.05[log(pred IGC(50)(-)(1))] + 0.02; n = 20, r(2) = 0.979, s = 0.13, F = 825, Pr > F = 0.0001] validated the model as a good predictor of toxicity regardless of the mechanism of toxic action.
authors.affiliation: College of Veterinary Medicine, The University of Tennessee, P.O. Box 1071, Knoxville, Tennessee 37901-1071, USA. tschultz@utkux.utcc.utk.edu
authors.forename: T W
authors.initials: TW
authors.lastname: Schultz
mesh_terms: D000818:Animals; D001555:Benzene Derivatives / Q000737:chemistry / Q000633:toxicity*; D008954:Models, Biological; D000442:Octanols / Q000737:chemistry; D013329:Structure-Activity Relationship; D013769:Tetrahymena pyriformis / Q000187:drug effects* / Q000254:growth & development; D018675:Toxicity Tests; D014867:Water / Q000737:chemistry
chemical_list: D001555:Benzene Derivatives; D000442:Octanols; D014867:Water