QUANTUM-CHEMICAL DESCRIPTORS FOR ESTIMATING THE ACUTE TOXICITY OF SUBSTITUTED BENZENES TO THE GUPPY (POECILIA-RETICULATA) AND FATHEAD MINNOW (PIMEPHALES-PROMELAS)

Benzene derivatives elicit variable modes of toxic action to fish and, as a result, their toxic potency does not depend exclusively on bioac cumulation. In an attempt to develop quantitative structure-activity r elationships (QSARs) for acute toxicity across a relatively large and well-defined chemical domain, a series of benzenes extracted from exis ting collections of toxicity data for guppies (Poecilia reticulata) an d fathead minnows (Pimephales promelas) were studied. The selection of compounds was based on ''prohibited'' substructural screens that repr esent inherently reactive electrophilic groups or other chemical funct ions known to induce particular toxic effects. The resultant correlati on samples were comprised of 64 and 122 substituted benzenes tested on the guppy and fathead minnow, respectively. The QSAR analysis showed that, for both samples, the toxicodynamic component of the toxic poten cy is mainly related to the electrophilicity of the aromatic ring in t erms of the maximal acceptor superdelocalizability, A(max). By inclusi on of A(max) as an additional variable into the generic log LC(50)-log K-ow linear regression, the explained variance increased from 51% to 73% and from 67% to 83% for the guppy and fathead minnow data sets, re spectively. The significance of A(max) is interpreted by the fact that it provides a crude differention between benzenes acting through diff erent modes of toxic action. For the guppy sample, a significant three -variable QSAR (R(2) = 0.855) was derived, which employed both maximal acceptor and donor superdelocalizabilities as electronic descriptors and provided a more definite quantitative separation for the benzene d erivatives.