The quantitative effects of nonpolar narcotics on Tetrahymena pyriformis and Escherichia coli

Nonpolar narcosis, the most basic toxicity mechanism, is thought to be nonspecific interaction with a cellular membrane, due to the accumulation in the hydrophobic phases of the cell or organism. This mechanism is described by QSARs using hydrophobicity, measured by log K_ow (the 1-octanol/water partition coefficient). In this manuscript, QSARs for multiple endpoints from the no effect concentration to 100% lethality using hydrophobicity have been developed for a protozoan and bacteria population, Tetrahymena pyriformis and Escherichia coli, respectively. For Tetrahymena, both acute and chronic data were generated and compared using the acute to chronic ratio. A bacterial toxicity assay was developed using Escherichia coli that mimics the protozoan growth inhibition assay. These two species show good correlation in toxicity with hydrophobicity for the selected nonpolar narcotics. The potency to one species could be used to determine the potency of the other. In addition, it is possible to predict toxicity of endpoints based on other endpoints within a species. Using a population kinetics assay, the generation times of Tetrahymena affected by nonpolar narcotics with varying hydrophobicity and molecular structure were observed. Using chemicals with low, intermediate, and high log K_ow, the response of Tetrahymena varied. Under the influence of the low log Kow chemicals, there was a direct relationship between toxicant concentration and growth rate. For the high log K_ow chemicals, the lag phase in growth increased with toxicant concentration. Additionally, the generation times were identical to control growth with the high log K_ow chemicals. A median response was seen for the intermediate chemicals. It is hypothesized that the variation in population growth kinetics seen in this study may be due to different placement of the toxicant within the cellular membrane.