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.
Schultz
T W
TW
College of Veterinary Medicine, University of Tennessee, Knoxville 37901-1071.
Lin
D T
DT
Culberson
R W
RW
D000438:Alcohols / Q000633:toxicity*; D000818:Animals; D008954:Models, Biological; D009281:Naphthalenes / Q000633:toxicity; D009294:Narcotics / Q000633:toxicity; D010636:Phenols / Q000633:toxicity; D013329:Structure-Activity Relationship; D013769:Tetrahymena pyriformis / Q000187:drug effects / Q000254:growth & development
D000438:Alcohols; D009281:Naphthalenes; D009294:Narcotics; D010636:Phenols