Student Abstracts: Medical and Health Sciences at PNNL

The In Vitro Metabolism of Propyl Acetate in Blood and S-9 fractions of Male Sprague Dawley Rats. ALLISON CARTMELL (Gonzaga University, Spokane, WA 99352) TORKA POET (Pacific Northwest National Laboratory, Richland, WA 99352).

Propyl acetate (1-propyl acetate, CAS 109-60-4) is a solvent that can cause headaches, dizziness, drowsiness, and coughing at high vapour concentrations. To avoid typical solvent exposure symptoms, the current conservative exposure limit of 200 ppm has been established. However, little is known about the pharmacokinetics of propyl acetate. The purpose of this study was to determine the metabolic rate constants (Km and Vmax) for the metabolism of propyl acetate to its major metabolites, propanol (1-propanol, CAS 71-23-8) and propionic acid (CAS 79-09-4) respectively, in blood and S-9 fractions prepared from male Sprague-Dawley rats. Michaelis-Menten metabolic rate constants were obtained by quantifying the amount of the major metabolites produced from an initial propyl acetate concentration of 60 µM or 600 µM after an incubation time period of up to 20 minutes. The different Michaelis-Menten constant (Km) for blood and S-9 fractions suggest that a different esterase is involved in the metabolism of propyl acetate to propanol in the blood and S-9 fractions. Although these esterases produce the same metabolites, the metabolic rate (Vmax) is also very different. In S-9 fractions, propyl acetate is metabolized at 59.48 ± 8.246 nmol/min/mg to propanol, which is three times higher than the Vmax in blood. The Vmax for the metabolism of propanol to propionic acid is substantially lower than the Vmax for the previous metabolic step. Propanol is much more slowly metabolized to propionic acid than the metabolism of propyl acetate to propanol. The blood and S-9 fractions having equivalent Km metabolic rate constants, 17.98 ± 0.7384 µM, for propanol to propionic acid metabolism suggest that the same esterase in blood and S-9 fractions is responsible for this second metabolic step. These metabolic rate constants will be applied to develop a physiologically based pharmacokinetic (PBPK) model in an attempt to assess the human health risks pertaining to propyl acetate.