Js. Jaworska et al., QUANTITATIVE STRUCTURE-TOXICITY RELATIONSHIPS AND VOLUME FRACTION ANALYSES FOR SELECTED ESTERS, Archives of environmental contamination and toxicology, 29(1), 1995, pp. 86-93
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.