Relationship between Olive Oil:Air, Saline:Air, and Rat Brain:Air Partition Coefficients of Organic Solvents In Vitro

Abstract

Partition coefficients of 28 volatile organic solvents (13 alkylbenzenes, 10 chlorinated hydrocarbons, and 5 ketones) in olive oil, saline, and rat brain tissue homogenates were measured by equilibration in a closed vial and subsequent gas-chromatographic analysis of headspace air. The values of oil and saline partition coefficients correlate well with previously reported data. Brain partition coefficients were fit to a bilinear equation of the form P brain:air = f o P oil:air + f s P saline:air + c. The regression coefficients accurately predicted previously reported rat brain partition coefficients of 19 solvents with distinct physicochemical properties within a factor of 2.5. The combined data set of presently determined and previously reported brain partition coefficients (n = 46) yields tissue-specific regression coefficients for solvent partitioning in rat brain of 0.028 for f O' , 0.845 for f S' , and 0.90 for the intercept, with coefficients of variation amounting to 11%, 4%, and 463%, respectively. The generalized empirical relationship predicts the brain partition coefficients within a factor of 2.5 accurately for 95% of the compounds. The ratios of rat brain concentrations calculated from predicted and measured P brain:air and P blood:air values were within a factor of 4 for 95% of the compounds. It was concluded that the enlargement of the empirical data set leads to more reliable predictions of rat brain partition coefficients, particularly for the lipophilic volatile organic compounds.