Correlations of nitrenium ion selectivities with quantitative mutagenicity and carcinogenicity of the corresponding...

There is a correlation (r(adj)(2) = 0.5491-0.6338) of quantitative mutagenicity, log m, for a series of heterocyclic (HCAs) and carbocyclic (AAs) aromatic amines in Salmonella typhimurium TA 98 (18 amines) and TA 100 (15 amines) vs log S, the log of the azide/solvent selectivity of the corresponding nitrenium ion. Monocyclic aromatic amines, MAAs, are less mutagenic than other amines of similar log S. Multiple variable linear regression analysis led to a two parameter regression model, significant at the 95% confidence level for both variables, that includes log S and a ring index variable, I(rings), that is 0 for MAAs and 1 for all other amines. These models have r(adj)(2) = 0.8448 for TA 98, and 0.8927 for TA 100. Inclusion of a third variable, Clog P, increases r(adj)(2) to 0.8913 for TA 98 and 0.9011 for TA 100. This model is significant at the 95% confidence level for all variables for TA 98, but only for two of the three variables for TA 100. The confidence level is 80% for Clog P in TA 100. Quantitative carcinogenicity data in mice and rats are more weakly correlated with log S (r(adj)(2) = 0.5357 for 12 amines in mice, r(adj)(2) = 0.4216 for 10 amines in rats). Several two parameter regression models, all containing Clog P and one containing log S, adequately correlate the mouse data.