Development and evaluation of two-parameter linear free energy models for the prediction of human skin permeability coefficient of neutral organic chemicals

Abstract The experimental values of skin permeability coefficients, required for dermal exposure assessment, are not readily available many chemicals. existing estimation approaches either less accurate or require parameters that available. Furthermore, current methods easy to apply complex environmental mixtures. We present two models estimate the coefficients neutral organic first model, referred here as 2-parameter partitioning model (PPM), exploits a linear free energy relationship (LFER) coefficient with combination partition octanol–water and air–water systems. second is based on retention time information nonpolar analytes comprehensive two-dimensional gas chromatography (GC × GC). PPM successfully explained variability in data ( n = 175) R 2 0.82 root mean square error RMSE ) 0.47 log unit. In comparison, US-EPA’s DERMWIN™ exhibited an 0.78 Zhang model—a 5-parameter LFER equation Abraham solute descriptors (ASDs)—performed slightly better value 0.44 However, limited by scarcity ASDs. GC variance chemicals 79) 0.90 0.23 can easily be implemented Estimation Program Interface Suite (EPI Suite™). applied mixtures