QUANTITATIVE STRUCTURE-TOXICITY RELATIONSHIPS AND VOLUME FRACTION ANALYSES FOR SELECTED ESTERS

The acute toxicity of aliphatic and aromatic mono and diesters in two eucaryotic organisms was compared. The test systems were the static 2- d Tetrahymena pyriformis 50% population growth impairment (IGC(50)(-1) ) assay, and the flow-through 4-d Pimephales promelas 50% mortality (L C(50)(-1)) assay. In ciliates, esters act via the nonpolar narcosis me chanism of toxic action. This was indicated by: the high quality 1-oct anol/water partition coefficient (log K-ow) dependent quantitative str ucture-activity relationship (QSAR), log IGC(50)(-1) = 0.79 (log K-ow) - 1.93, n = 15, r(2) = 0.945, s = 0.22, f = 222.37 Pr > f = 0.0001); volume fraction (V-f) (0.8e-02); and ''a'' coefficient (0.3) which are not different from other nonpolar narcotics. In vivo hydrolysis in Te trahymena appears to be insignificant. However, in fish, presumably be cause of more active esterases, in vivo hydrolysis is significant and leads to greater toxicity of esters than observed for nonpolar narcoti cs. Moreover, it leads to a unique high quality QSAR, log LC(50)(-1) = 0.64 (log K-ow) - 0.64, n = 14, r(2) = 0.945, s = 0.22, f = 207.08, P r > f = 0.0001). Due to in vivo hydrolysis, a nonreducing concentratio n gradient is formed between water and fish. Therefore, the fish take up more toxicant as compared to a situation that leads to thermodynami c equilibrium. Additional information about the mechanism of ester tox icity in fish was gained by applying corrections for hydrolysis in vol ume fraction analyses. The corrected V-f (0.6e-02) is very close to th e one found for nonpolar narcotics (0.7e-02). These analyses suggest t hat esters which hydrolyze to an acid and aliphatic alcohol act as non polar narcotics. Moreover, the mechanism of toxic action of esters tha t yield a phenol upon hydrolysis is mixed and represents polar and non polar narcoses.