QSARs for aquatic toxicity: celebrating, extending and displaying the pioneering contributions of Ferguson, Konemann and Veith

Abstract

Significant advances were made in the development of quantitative structure-activity relationships (QSARs) relating molecular structure to aquatic toxicity by three studies over 30 years ago by Ferguson in 1939, Konemann in 1981, and Veith and colleagues in 1983. We revisit the original concepts and data from these studies and review these contributions from the bases of current perspectives on the hypothesized mechanism of baseline narcotic toxicity and the underlying thermodynamic and kinetic aspects. The relationships between LC50, octanol-water partition coefficient, aqueous solubility, chemical activity and chemical volume fraction in lipid phases are outlined including kinetic influences on measured toxicities. These relationships provide a compelling and plausible explanation of the success of these and other QSARs for aquatic toxicity. Suggestions are made for further advances in these QSARs to improve assessments of toxicity by baseline narcotic toxicity and selective modes of action, especially using emerging quantum chemical computational capabilities.

Keywords: QSAR; aquatic toxicity; chemical activity; mode of action; narcosis; partition coefficients.