The absorption, distribution, and excretion of radiolabeled
ethyl oleate (EO) was studied in Sprague-Dawley rats after a single, peroral dose of 1.7 or 3.4 g/kg
body weight and was compared with a radiolabeled
triacylglycerol (TG) containing only
oleic acid as the
fatty acid (
triolein). Both test materials were well absorbed with approximately 70-90% of the EO dose absorbed and approximately 90-100% of the TG dose absorbed. At sacrifice (72 h post-dose), tissue distribution of EO-derived radioactivity and TG-derived radioactivity was similar. The tissue with the highest concentration of radioactivity in both groups was mesenteric fat. The other organs and tissues had very low concentrations of test material-derived radioactivity. Both test materials were rapidly and extensively excreted as CO(2) with no remarkable differences between their excretion profiles. Approximately 40-70% of the administered dose for both groups was excreted as CO(2) within the first 12 h (consistent with beta-oxidation of
fatty acids). Fecal elimination of EO appeared to be dose-dependent. At the dose of 1.7 g/kg, 7-8% of the administered dose was eliminated in the feces. At the dose of 3.4 g/kg, approximately 20% of the administered dose was excreted in the feces. Excretion of TG-derived radiolabel in the feces was approximately 2-4% for both doses. Overall, the results demonstrate that the absorption, distribution, and excretion of radiolabeled EO is similar to that of TG providing evidence that the
oleic acid moiety of EO is utilized in the body as a normal dietary TG-derived
fatty acid. To confirm the expected safety of EO in humans, a total of 235 subjects participated in a 12-week trial where two levels of
ethyl oleate in a milk-based beverage were investigated: 8 g/day in a single serving (approximately 0.1 g/kg) and 16 g/day taken in two divided servings (approximately 0.2 g/kg). Adverse events (AEs) were recorded throughout the 12-week trial. In addition, a brief physical exam (including vital signs and
body weight), ECGs, fasting serum chemistry profile, serum
lipid profile, and urinalysis were performed at baseline and after study completion. Results showed the incidence of reported AEs was similar between the EO groups and the control groups. Analysis of comprehensive laboratory data revealed no EO exposure-related, clinically significant adverse changes in laboratory parameters. These studies demonstrated that EO has a highly favorable safety profile and is well tolerated in the diet.