A quantitative property-property relationship (QPPR) approach to estimate in vitro tissue-blood partition coefficients of organic chemicals in rats and humans

• Published in: Archives of toxicology Vol. 72; no. 1; pp. 17 - 25
• Main Authors: DEJONG, J, VERHAAR, H. J. M, HERMENS, J. L. M
• Format: Journal Article
• Language: English
• Published: Berlin Springer 1997
• Subjects: 1-Octanol - chemistry; Adipose Tissue - chemistry; Algorithms; Animals; Biological and medical sciences; Brain Chemistry; General aspects. Methods; Humans; Hydrocarbons - blood; Hydrocarbons - chemistry; Liver - chemistry; Medical sciences; Models, Biological; Muscles - chemistry; Rats; Toxicology; Water - chemistry; Xenobiotics - blood; Xenobiotics - chemistry; Water; Human; Rat; Chemical compound; Rodentia; Lipids; Partition coefficient; Volatile organic compound; Physicochemical properties activity relationship; Blood; Toxicokinetics; Tissue; Vertebrata; Mammalia; Animal; Distribution; Physiologically based pharmacokinetic model; Pharmacokinetics
• ISSN: 0340-5761; 1432-0738
• DOI: 10.1007/s002040050463

The present study describes quantitative property-property relationships (QPPRs) for the partitioning of organic chemicals between blood and tissue homogenates from both rats and humans. The n-octanol/water partition coefficient (K[ow]) is used as a non-biological descriptor. QPPRs for human tissue-blood partition coefficients (PCs) were derived from a dataset of 24 volatile organic compounds in blood, liver, muscle, fat, kidney and brain tissue homogenates. QPPRs were also derived for the PCs of rat tissues, using a dataset of 42 volatile organic compounds in blood, liver, muscle and fat tissue homogenates. These QPPRs were evaluated using a test set of 10 compounds for human tissues and a test set of 14 compounds for rat tissues. For both human and rat test sets, it was generally observed that most estimated PCs were within a range of 50-200% of their experimental values. The present approach is concluded to offer a rapid means for the estimation of tissue-blood PCs of compounds on the basis of K(ow) values. In addition, indications for a possible role of tissue components other than lipid and water in the tissue-blood partitioning process of compounds were observed from the calibration results of the model.