ACUTE TOXICITY ESTIMATION BY CALCULATION-TUBIFEX ASSAY AND QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIPS

摘要

A quantitative structure-activity relationship (QSAR) model dependent on log P(n - octanol/water), or log P_(OW), was developed with acute toxicity index EC50, the median effective concentration measured as inhibition of movement of the oligochaeta Tubifex tubifex with 3 min exposure, EC50(Tt) (mol/L): log EC50(Tt) = -0.809 (±0.035) log P_(OW) - 0.495 (±0.060), n = 82, r - 0.931, r~2 = 0.867, residual standard deviation of the estimate = 0.315. A learning series for the QSAR model with the oligochaete contained alkanols, alkenols, and alkynols; saturated and unsaturated aldehydes; aniline and chlorinated anilines; phenol and chlorinated phenols; and esters. Three cross-validation procedures proved the robustness and stability of QSAR models with respect to the chemical structure of compounds tested within a series of compounds used in the learning series. Predictive ability was described by q~2 = 0.801 (cross-validated r~2; predicted variation estimated with cross-validation) in LSO (leave-a structurally series-out) cross-validation.