pH-dependence and QSAR analysis of the toxicity of phenols and anilines toDaphnia magna

The toxicity of 13 anilines and 11 phenols to Daphnia magna has been assess ed at pH values of 6.0, 7.8, and 9.0. Toxicity of anilines decreases with d ecreasing pH, whereas the toxicity of phenols decreases with increasing pH. These variations in toxicity, are clearly brought about by the effect of i onization, especially for the phenols. Toxicity decreased with an increasin g proportion of ionized molecules. The relative contribution of the ionized and unionized molecules was assessed. it is believed that, at least for th e phenols, the ionized form of the compounds does contribute to the toxicit y of the molecules. However, the decreased overall toxicity suggests that a tower relative toxicity is attributable to the ionized form. Attempts were also made to develop quantitative structure-activity relationship (QSAR) m odels for these toxicity data. Reasonable QSARs were produced for the anili nes and phenols, acting as polar narcotics, considered together; these QSAR s included a measure of hydrophobicity, pK(a), and hydrogen bonding. When t he phenols and anilines were considered separately, better, hydrophobicity- based, QSARs were obtained. Most compounds, with the exception of 2,4-dinit rophenol, resorcinol, and pentachlorophenol, were thought to be acting by a polar narcosis mechanism of toxic action. There was some evidence that 2,4 -dichlorophenol and 2,4,6-trichlorophenol may be acting as weak acid respir atory uncouplers, despite earlier suggestions that they act as polar narcot ics. (C) 2000 by John Wiley & Sons, Inc.