Structure-toxicity relationships for aminoalkanols : a comparison with alkanols and alkanamines

The relative toxicity (log IGC₅₀^-1) of 35 selected alkanamines and aminoalkanols was evaluated in the static Tetrahymena pyriformis population growth assay. Excess toxicity, indicated by potency greater than predicted for alkanols, was associated with both classes of chemicals. Moreover, the aminoalkanols were found to be more toxic than corresponding alkanamines. A high quality 1-octanol/water partition coefficient (log Kq^) dependent quantitative structure-activity relationship (QSAR), log IGCsub>50^-1 = 0.72 (log Kqw) - 1 -32; r² = 0.939, was developed for alkanamines. This QSAR represented the amine narcosis mechanism of toxic action. Several structure-toxicity features were observed for the aminoalkanols. These included 2-amino-l-hydroxy derivatives being more toxic than corresponding derivatives where the amino and hydroxy moieties were separated by methylene groups, and hydrocarbon branching next to the amino moiety resulting in decreased toxicity. Regression analysis of log Kqw versus the log IGCsub>50^-1 for selected aminoalkanols yielded the model, log IGCsub>50^-1 =0.17 (log K_ow) - 0.70; r² =0.833.