Acute toxicity of nonpolar versus polar narcosis: Is there a difference?

Narcosis I and II chemicals exhibit different lethal body burdens (LBBs) and acute toxicities (median lethal concentrations [LC50's]) in fish, when compared with their log n‐octanol‐water partition coefficient (Kow). The higher toxicity of polar narcosis chemicals has often been suggested to be related to the polar group in these molecules. Recently we showed that membrane (L‐α‐dimyristoyl phosphatidyl‐choline [DMPC])–water partition coefficients (log KDMPC) are higher than log Kow for narcosis II chemicals. Using log KDMPC to model the acute toxicities to fish (log LC50) of the two classes of chemicals together, gives one high‐quality quantitative structure‐activity relationship (R2 = 0.98, Q2 = 0.97). In addition, assuming that the apolar fat‐water partition coefficient behaves like the n‐octanol–water partition coefficient, differences in LBB can also be explained. Thus, using log KDMPCs, all earlier reported quantitative differences between narcosis I and II chemicals can be explained.