Abstract
Glycidol (2,3‐epoxy‐1 ‐propanol), an industrial chemical, has been shown to be a repro‐ductive toxicant in short‐term studies and a carcinogen in rats and mice in oncogenicity studies. The reproductive toxicity of glycidol was believed to result from its conversion to α‐chlorohydrin by the action of HCI in the stomach. The comparative disposition of glycidol was investigated in rats following oral (po) or intravenous (iv) administration at doses of 37.5 and 75 mglkg. These were the doses used in the National Toxicology Program (NTP) oncogenicity study with glycidol. Approximately 87–92% of the dose was absorbed from the gastrointestinal tract of the rat. [14C]GIycidol equivalents were eliminated in urine (40–48% of dose in 72 h), feces (5–12%), and exhaled as CO2 (26–32%). At both doses, 9–12% and 7–8% (estimated) of the dose remained in tissues at 24 and 72 h following dosing, respectively. In general, the concentrations of glycidol equivalents in tissues were proportional to the dose. The highest concentrations of radioactivity were observed in blood cells, thyroid, liver, kidney, and spleen, and the lowest in adipose tissue, skeletal muscle, and plasma. The pattern of distribution of radioactivity in tissues was similar for both the iv and po routes. The total recovery of radioactivity ranged from 87 to 91% of dose. Urinary radioactivity was resolved by high‐performance liquid chromatography (HPLC) analysis into 15 metabolites. There were one major (14–21% of the dose) and four lesser metabolites (each representing 2–8%); the others were minor, each representing 1 % or less of the dose. In general, the urinary metabolic profile was similar following either iv or po administration at the two doses studied. Previous studies by other investigators suggested that α‐chlorohydrin, which was presumably formed from glycidol by the HCI in the stomach, was metabolized and excreted in urine as β‐chlorolactic acid. The results of the present study show that very little, if any, urinary radioactivity coeluted with authentic β‐chlorolactic acid following either iv or po administration. Therefore, it is concluded that the conversion of glycidol to α‐chlorohydrin is quantitatively insignificant. However, it may be significant with regard to glycidol reproductive toxicity. Also, the NTP oncogenicity study with glycidol was carried out within the dose range in which its disposition characteristics were linear.