In vitro and in vivo evaluation of propylene glycol ethers metabolism in humans

Abstract

Propylene glycol ethers (PGEs) consist of a major α-isomer (secondary alcohol group) and a minor β-isomer (primary alcohol group). Animal studies have reported toxic effects of the β-isomer metabolites, but human metabolism of PGEs remains poorly understood. We aimed to characterize the metabolism of two common PGEs in humans. Nine participants were exposed under controlled conditions (4 h) to propylene glycol ethyl ether (PGEE) or propylene glycol propyl ether (PGPE) (<35 ppm). Blood and urine samples were collected, and the respective β-isomers metabolites; 2-ethoxypropanoic acid (2-EPA) and 2-propoxypropanoic acid (2-PPA) were quantified. The 2-PPA blood absorption rate was 0.0005 ± 0.0002 µg/mL/h*ppm followed by rapid urinary elimination (half-life: 2 h) and slower secondary elimination (half-life: 10 h). No dose-response was observed for 2-EPA; therefore, β-PGEE metabolism was investigated in vitro using human liver S9 fractions. We provide 2-EPA hepatic kinetic and enzyme kinetic parameters. We recommend using of 2-PPA as a biomarker for PGPE exposures.