QSARs for monosubstituted anilines eliciting the polar narcosis mechanism of action. 1991

T W Schultz, and D T Lin, and L M Arnold
College of Veterinary Medicine, University of Tennessee, Knoxville 37901-1071.

The relative toxicities (log IGC50(-1] of a fairly heterogeneous series of 66 anilines that were monosubstituted in the 2-, 3-, and 4-positions have been evaluated in the 48 h static Tetrahymena population growth impairment system. Quantitative structure-activity relationships (QSARs) were examined using the 1-octanol/water partition coefficient (log KOW) and the summation of the Hammett sigma electronic substituent constant (sigma sigma) as orthogonal independent predictors. Four chemicals, 4-decylaniline, 4-dodecylaniline, 4-tritylaniline and 4-aminophenethyl alcohol, did not elicit the measured response at saturation. Five chemicals, 2-aminophenol, 2-phenylenediamine, 4-aminophenol, 4-phenylenediamine and 4-nitroaniline, had an altered HPLC spectrum with time. As previously reported, the parent compound, aniline, as well as the 4-position halogen derivatives have been shown to be aberrantly more toxic than expected. None of these chemicals were included in QSAR development which employed linear regression analysis. Log IGC50(-1) = 0.599(log KOW) - 0.905 (n = 52, r2 = 0.885, s = 0.265, f = 383.65, Pr greater than f = 0.0001) was found to be a good predictor of relative toxicity of these monosubstituted anilines. The addition of sigma sigma as a second predictor did not improve the predictability of this QSAR. Abiotic loss over the duration of the assay varied markedly with derivative; however, chemical persistence was not considered to be a factor with this model. The above equation was strikingly similar to log IGC50(-1) = 0.595(log KOW) - 0.996 (n = 67, r2 = 0.866, s = 0.254, f = 421.64, Pr greater than f = 0.0001), a previously developed QSAR from data on a heterogeneous set of monosubstituted phenols. The data for these two equations were combined and subsequent regression analysis resulted in log IGC50(-1) = 0.588(log KOW) - 0.939 (n = 119, r2 = 0.873, s = 0.261, f = 806.49, Pr greater than f = 0.0001). The authors feel that this represents the log KOW-dependent QSAR in the Tetrahymena population growth assay for the polar narcosis mechanism of toxic action.

UI MeSH Term Description Entries
D012044 Regression Analysis Procedures for finding the mathematical function which best describes the relationship between a dependent variable and one or more independent variables. In linear regression (see LINEAR MODELS) the relationship is constrained to be a straight line and LEAST-SQUARES ANALYSIS is used to determine the best fit. In logistic regression (see LOGISTIC MODELS) the dependent variable is qualitative rather than continuously variable and LIKELIHOOD FUNCTIONS are used to find the best relationship. In multiple regression, the dependent variable is considered to depend on more than a single independent variable. Regression Diagnostics,Statistical Regression,Analysis, Regression,Analyses, Regression,Diagnostics, Regression,Regression Analyses,Regression, Statistical,Regressions, Statistical,Statistical Regressions
D000814 Aniline Compounds Compounds that include the aminobenzene structure. Phenylamine,Phenylamines,Anilines,Compounds, Aniline
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D013769 Tetrahymena pyriformis A species of ciliate protozoa used extensively in genetic research. Tetrahymena pyriformi,pyriformi, Tetrahymena

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