Allometric species comparison of toluene and n-hexane metabolism: prediction of hepatic clearance in man from experiments with rodent liver S9 in a head space vial equilibration system.

摘要

The liver S9 head space vial equilibration technique is an in vitro alternative that holds promises for a satisfactory in vivo extrapolation of liver metabolism of volatile organic chemicals. The aim of this study was to investigate the suitability of this methodology for the extrapolation of in vitro metabolic data from rodent to man by allometry with the two highly metabolized organic solvents toluene and n-hexane as model substances. The calculated hepatic clearance of toluene in man from rodent liver S9 in this study was equal to the reported total body clearance of toluene in man, suggesting insignificant extrahepatic clearance of toluene in humans. The calculated hepatic clearance of n-hexane was less than the reported values of total body clearance of n-hexane in man, indicating an about 80% extrahepatic clearance of n-hexane in humans. Both results are in line with our present knowledge of the metabolism of the two organic solvents in man. Allometric scaling from rodent liver S9 head space incubations to in vivo metabolism of toluene and n-hexane in man thus seems promising and could be a method of choice for scaling of organic solvent metabolism in general.