Exploring the role of octanol-water partition coefficient and Henry's law constant in predicting the lipid-water partition coefficients of organic chemicals

Partition coefficients for storage lipid-water (logK(lw)) and phospholipid-water (logK(pw)) phases are key parameters to understand the bioaccumulation and toxicity of organic contaminants. However, the published experimental databases of these properties are dwarfs and current estimation approaches are cumbersome. Here, we present partition models that exploit the correlations of logK(lw), and of logK(pw) with the linear combinations of the octanol-water partition coefficient (logK(ow)) and the dimensionless Henry's law constant (air-water partition coefficient, logK(aw)). The calibrated partition models successfully describe the variations in logK(lw) data (n = 305, R-2 = 0.971, root-mean-square-error (rmse) = 0.375), and in logK(pw) data (n = 131, R-2 = 0.953, rmse = 0.413). With the inputs of logK(ow) and logK(aw) estimated from the U.S. EPA's EPI Suite, our models of logK(lw) and logK(pw) have exhibited rmse = 0.52 with respect to experimental values indicating suitability of these models for inclusion in the EPI Suite. Our models perform similar to or better than the previously reported models such as one parameter partition models, Abraham solvation models, and models based on quantum-chemical calculations. Taken together, our models are robust, easy-to-use, and provide insight into variations of logK(lw) and logK(pw) in terms of hydrophobicity and volatility trait of chemicals.

Automated summary

Partition models based on linear combinations of octanol-water partition coefficient and dimensionless Henry's law constant are proposed and successfully described the variations in storage lipid-water and phospholipid-water partition coefficients. The models exhibit good performance when compared to experimental values and are suitable for inclusion in the EPI Suite.