Predicted toxicities of aryl alkanols and related compounds

The relative toxicity of selected aryl and/or alkyl alcohols was evaluated in the batch culture Tetrahymena pyriformis population-growth impairment assay. Chemicals evaluated included normal and branched primary alcohols with mono-, bi- or diaromatic substituents as well as aryl-substituted ethers. Log 1-octanol/water partition coefficients (log Kow) along with previously developed quantitative structure-activity relationships (QSARs) for both the non-polar narcosis and polar narcosis mechanism of action were used to predict relative toxicity. Observed and predicted toxicities measured as log IGC50(-1) were compared. All phenols and naphthyl-substituted compounds, as well as the biphenyl methanols, benzhydrols and 1,1-diphenylethanol, model more accurately as polar narcotics. Both monoaromatic- and diaromatic-substituted branched arylalkyl alcohols, as well as monoaromatic ethers, model best as non-polar narcotics. The C1-C6 straight-chain aryl alkanols, as well as 3-phenyl-1-butanol, model intermediately between non-polar and polar narcosis. The triaromatic-substituted alcohol was not toxic at saturation. These findings are consistent with the idea that narcosis, the reversible state of arrested bioactivity, is a series of mechanisms.