Global modeling of narcotic chemicals: ciliate and fish toxicity

Abstract

This work explores the possibilities of generalizing a variety of narcotic global quantitative structure–activity relationships used in aquatic toxicological studies. The models developed herein are based on the static ciliate ( Tetrahymena pyriformis) population growth impairment (IGC 50 −1) data. Results are compared with models previously developed with the flow-through fish ( Pimephales promelas) mortality (LC 50 −1) data. The modeling approach is an extension of a recently developed expert system coupled with the response-surface concept. The expert system characterizes the molecular domain of non-specifically acting chemicals, both for neutral and amine narcotics. Toxicity surface(s) are defined using hydrophobicity quantified by the log 1-octanol/water partition coefficient (log K ow) and orbital electrophilicity quantified by the energy of the lowest unoccupied molecular orbital ( E LUMO) as global molecular descriptors. The ciliate response surface models: log(IGC 50 −1)=1.50+0.68 log K ow−0.13 E LUMO; n=411, R 2=0.890 and log(IGC 50 −1)=1.80+0.68 log K ow; n=51, R 2=0.854 for neutral and amine narcotics, respectively, compares favorably with the fish model. The fish and ciliates response-surfaces appear to be parallel as they significantly deviate only by their intercepts.