Kinetics of metabolism of propene and covalent binding to macromolecules in the mouse

The rate of uptake of propene from air was studied by exposing CBA mice to various concentrations of the gas in a closed, recirculating all-glass chamber. The rate curves showed a saturable dependence on the propene concentration. The inhalational Km and Vmax were calculated to be 800 +/- 60 ppm and 8 +/- 0.5 mg (kg body wt)-1 hr-1, respectively, from a Lineweaver-Burk plot of the rate data. The homologous compound ethene is known to be metabolized in the mouse to ethene oxide. When a trace amount of 14C-labeled ethene was administered in combination with a high concentration of propene, the uptake of [14C]ethene was lower than in the absence of propene, suggesting a competitive interaction in their metabolic pathways. One group of animals were exposed at 20,000 ppm of propene 4 hr/day during 8 consecutive days. Hemoglobin was isolated from the treated group and a control group. After hydrolysis of the protein, two diastereomers of N tau-(2-hydroxypropyl)histidine were identified in the hydrolysate from treated animals, suggesting that propene, analogous to ethene, is metabolized to the corresponding epoxide and showing that the oxidation is not stereospecific. 2-Hydroxypropylated products were found in hemoglobin from mice treated with 14C-labeled propene. The amounts of alkylated products in DNA were below the detection limit.