Quantitative Structure–Activity Relationships and Volume Fraction Analysis for Nonpolar Narcotic Chemicals to the Australian Cladoceran Ceriodaphnia cf. dubia

Abstract.

The toxicity of eleven nonpolar narcotic chemicals to the cladoceran Ceriodaphnia cf. dubia was determined. C. cf. dubia was found to be approximately four times more sensitive to these narcotic chemicals than Daphnia magna tested under virtually identical conditions. The toxicity data were also used to develop and validate quantitative structure–activity relationships (QSARs) using a range of physicochemical properties of the chemicals. The three best QSARs, based on octanol–water partition coefficients and two lipid–water partition coefficients, were able to explain 98% of the variation in toxicity. The mean absolute percentage errors between the predicted and experimental EC50 values for these three QSARs were 17.3%, 20.6%, 24.6%. Neither the critical concentration (CC) nor the critical volume (CV) hypotheses validly modeled the toxicity data when octanol–water and triolein–water partition coefficients were used although the CV hypothesis was the better of the two. When a phospholipid–water partition coefficient was used the CV hypothesis was valid. The mean toxic membrane volume fraction of 0.48 × 10⁻² m³/m³ derived in this study agreed with published values for nonpolar narcotics and supports the use of this property to determine the mode of action of chemicals.