Air to Blood Distribution of Volatile Organic Compounds: A Linear Free Energy Analysis

Abstract

Partition coefficients, K_blood, for volatile organic compounds from air to blood have been collected for 155 compounds (air to human blood) and 127 compounds (air to rat blood). For 86 common compounds, the average error, AE, between the two sets of log K_blood values is 0.12 log units, somewhat smaller than our estimated interlaboratory average SD value of around 0.16 log units. We conclude that with regard to experimental errors, there is no significant difference between K_blood values in human blood and in rat blood. There are 196 compounds for which either or both K_blood (human) and K_blood (rat) are available. A training set of 98 compounds could be fitted with the Abraham solvation parameters with R² = 0.933 and SD = 0.34 log units. The training equation was then used to predict the test set of values with AE = 0.04 log units, SD = 0.33 log units, and an average absolute error, AAE, of 0.25 log units. A second training and test set yielded similar values: AE = 0.01, SD = 0.39, and AAE = 0.29 log units. It is concluded that it is possible to construct an equation capable of predicting further values of log K_blood to around 0.30 log units. Because the descriptors used in the correlation equations can be predicted from structure, it is now possible to predict log K_blood for any chemical structure.