Air to fat and blood to fat distribution of volatile organic compounds and drugs: Linear free energy analyses

Partition coefficients, Kfat, from air to human fat and to rat fat have been collected for 129 volatile organic compounds, VOCs. A linear free energy relationship, LFER, correlates the 129 values of log Kfat with R2 = 0.958 and a standard deviation, S.D., of 0.194 log units. Use of training and test sets gives a predictive assessment of around 0.20 log units. Combination of log Kfat with our previously listed values of log Kblood enables blood/plasma to fat partition coefficients, as log Pfat, to be obtained for 126 VOCs. These values can be correlated with R2 = 0.847, S.D. = 0.304 log units; the latter is also our assessment of the predictive capability of the LFER. Values of log Pfat have been collected for 46 drugs, and can be fitted to an LFER with R2 = 0.811 and S.D. = 0.355 log units. Unlike partition into brain or muscle, the data for VOCs and drugs cannot be combined. There are marked discrepancies for PCBs for which partition from blood/plasma into fat is very much less than that calculated from the data on VOCs or from the data on drugs.

Figure optionsDownload as PowerPoint slide