A biologically-based algorithm for predicting human tissue: blood partition coefficients of organic chemicals

A biologically-based algorithm for predicting the tissue: blood partition coefficients (PCs) of organic chemicals has been developed. The approach consisted of (i) describing tissues and blood in terms of their neutral lipid, phospholipid, and water contents, (ii) obtaining data on the solubility of chemicals in n-octanol and water, and (iii) calculating the tissue: blood PCs by assuming that the solubility of a chemical in n-octanol corresponds to its solubility in neutral lipids, the solubility in water corresponds to the solubility in tissue/blood water fraction, and the solubility in phospholipids is a function of solubility in water and n-octanol. The adequacy of this approach was verified by comparing the predicted values with previously published experimental data on human tissue (liver, lung, muscle, kidney, brain, adipose tissue): blood PCs for 23 organic chemicals. In the case of liver, lung, and muscle, the predicted PC values were in close agreement with the higher-end of the range of experimental PC values found in the literature. The predicted brain: and kidney: blood PCs were greater than the experimental PCs in most cases by approximately a factor of two. Whereas the adipose tissue: blood PCs of relatively less hydrophilic chemicals were adequately predicted, the predicted PCs for relatively more hydrophilic chemicals were much greater than the experimentally-determined values. There was a good agreement between the predicted and experimentally-determined blood solubility of the 23 chemicals chosen for this study, indicating that the over-estimation of tissue:blood PCs by the present method is not due to under-estimation of blood solubility of chemicals.(ABSTRACT TRUNCATED AT 250 WORDS)