title: Species differences in toxicokinetic parameters of glycidol after a single dose of glycidol or glycidol linoleate in rats and monkeys.
abstract: Glycidol fatty acid esters (GEs) have been identified as contaminants in refined edible oils. Although the possible release of glycidol (G) from GEs is a concern, little is known about the conversion of GEs to G in the human body. This study addressed the toxicokinetics of glycidol linoleate (GL) and G in male Crl:CD(SD) rats and cynomolgus monkeys. Equimolar amounts of GL (341 mg/kg) or G (75 mg/kg) were administered by gavage to each animal. G was found in both species after the G and GL administration, while plasma GL concentrations were below the lower limit of quantification (5 ng/ml) in both species. In rats, the administration of GL or G produced similar concentration-time profiles for G. In monkeys, the C(max) and AUC values after GL administration were significantly lower than those after G administration. The oral bioavailability of G in monkeys (34.3%) was remarkably lower than that in rats (68.8%) at 75 mg/kg G administration. In addition, plasma G concentrations after oral administration at three lower doses of GL or G were measured in both species. In monkeys, G was detected only at the highest dose of G. In contrast, the rats exhibited similar plasma G concentration-time profiles after GL or G administration with significantly higher G levels than those in monkeys. In conclusion, these results indicate that there are remarkable species differences in the toxicokinetics of GEs and G between rodents and primates, findings that should be considered when assessing the human risk of GEs.
authors.affiliation: Safety Science Research Laboratories, Kao Corporation, Tochigi, Japan.
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Wakabayashi
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Kurata
authors.forename: Tomoo
authors.initials: T
authors.lastname: Harada
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Tamaki
authors.forename: Naohiro
authors.initials: N
authors.lastname: Nishiyama
authors.forename: Toshio
authors.initials: T
authors.lastname: Kasamatsu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D004075:Diglycerides / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004852:Epoxy Compounds / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity*; D019787:Linoleic Acid / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity*; D008041:Linoleic Acids / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity*; D008252:Macaca fascicularis; D008297:Male; D020005:Propanols / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity
chemical_list: D004075:Diglycerides; D004852:Epoxy Compounds; D008041:Linoleic Acids; D020005:Propanols; C576812:glycidol linoleate; D019787:Linoleic Acid; C004312:glycidol