Dimyristoyl Phosphatidylcholine/water Partitioning-dependent Modeling of Narcotic Toxicity toTetrahymena pyriformis

Regression-type structure-toxicity relationships have been developed between Tetrahymena pyriformis population growth impairment toxicity data (log 1/IGC50) and the dimyristoyl phosphatidylcholine/water partition coefficient (log KDMPC) or the 1-octanol/water partition coefficient (log Kow). A statistically robust model [log(1/ IGC50)= 0.73 log (KDMPC)−1.62; n=23, r2=0.926, s=0.24, F=263, Pr/gt F=0.0001] was found for non-polar narcotics, polar narcotics, as well as esters with the DMPC partition coefficient. The above model was statistically better than the model [log(1/IGC50) = 0.71 (log Kow) − 1.60; n = 23, r2 = 0.828, s = 0.39, F = 101, Pr> F = 0.0001] developed for the same compounds with 1-octanol/water partitioning as the independent variable. The former equation does not explain the difference in the acute mechanisms of toxic action known to exist in fish for non-polar and polar narcotics. However, log KDMPC appears to correct for differences in the concentration of toxicant reaching the site of toxic action between narcotic mechanisms. Outliers to the log KDMPC model were primary aliphatic amines.