Prediction of in vivo metabolic clearance of 25 different petroleum hydrocarbons by a rat liver head-space technique

In vitro rates of metabolism and Michaelis-Menten constants were determined for 25 different C6 to C10 hydrocarbons using rat liver slices in a vial h ead-space equilibration system. The rates of metabolism were compared with steady-state levels obtained in vivo in the same strains of rats after inha lation. Aromates were metabolized at a higher rate than naphthenes n-alkane s, isoalkanes and 1-alkenes. The aromates showed, in contrast to the other hydrocarbons investigated, increased metabolism with increasing number of c arbon atoms up to C8 (o-xylene, the most extensively metabolized compound). The in vivo steady-state concentrations of the aromates in blood were inve rsely related to the in vitro efficiency of their metabolism. This explains the pattern of blood levels observed for the C6 to C10 aromates in the rat after inhalation, with o-xylene demonstrating the lowest concentration. In general, the extent of tissue metabolism of the investigated hydrocarbons might be of greater importance for their body distribution than their Lipop hilicity, especially for the highly metabolized compounds. The high in vitr o intrinsic liver clearances found for the aromates indicate a flow-depende nt metabolism of these hydrocarbons in vivo. The head-space liver slice equ ilibration system seems to work adequately for metabolic studies of hydroca rbons with different volatility and water solubility.