Relationship between olive oil:air, saline:air, and rat brain:air partition coefficients of organic solvents in vitro.
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) = alpha(o)P(oil:air) + alpha(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 alpha(O'), 0.845 for alpha(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.
D000388:Air; D000818:Animals; D001921:Brain / Q000187:drug effects*; D046508:Culture Techniques; D004347:Drug Interactions; D008297:Male; D000069463:Olive Oil; D010938:Plant Oils / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012044:Regression Analysis; D012965:Sodium Chloride / Q000494:pharmacology*; D012997:Solvents / Q000737:chemistry / Q000494:pharmacology*
D000069463:Olive Oil; D010938:Plant Oils; D012997:Solvents; D012965:Sodium Chloride