A BIOLOGICALLY-BASED ALGORITHM FOR PREDICTING HUMAN TISSUE - BLOOD PARTITION COEFFICIENTS OF ORGANIC CHEMICALS

A biologically-based algorithm for predicting the tissue: blood partit ion coefficients (PCs) of organic chemicals has been developed. The ap proach 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) calcu lating the tissue: blood PCs by assuming that the solubility of a chem ical in n-octanol corresponds to its solubility in neutral lipids, the solubility in water corresponds to the solubility in tissue/blood wat er fraction, and the solubility in phospholipids is a function of solu bility in water and n-octanol. The adequacy of this approach was verif ied by comparing the predicted values with previously published experi mental data on human tissue (liver, lung, muscle, kidney, brain, adipo se 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 lit erature. The predicted brain: and kidney: blood PCs were greater than the experimental PCs in most cases by approximately a factor of two. W hereas the adipose tissue: blood PCs of relatively less hydrophilic ch emicals were adequately predicted, the predicted PCs for relatively mo re hydrophilic chemicals were much greater than the experimentally-det ermined values. There was a good agreement between the predicted and e xperimentally-determined blood solubility of the 23 chemicals chosen f or this study, indicating that the over-estimation of tissue: blood PC s by the present method is not due to under-estimation of blood solubi lity of chemicals. Rather, it might be due to the lower tissue solubil ity of chemicals observed experimentally due to the complexity of the tissue matrices. This novel approach of describing tissues in terms of the type of lipid and water content should enable the prediction of t he tissue: blood PCs of organic chemicals with information on their so lubility in water and n-octanol, for developing physiologically-based toxicokinetic models.