Comparison of acrylamide metabolism in humans and rodents.
Acrylamide is metabolized by direct conjugation with glutathione or oxidation to glycidamide, which undergo further metabolism and are excreted in urine. In rats administered 3 mg/kg 1,2,3-13C3 acrylamide, 59% of the metabolites excreted in urine was from acrylamide-glutathione conjugation, whereas 25% and 16% were from two glycidamide-derived mercapturic acids. Glycidamide and dihydroxypropionamide were not detected at this dose level. The metabolism of acrylamide in humans was investigated in a controlled study with IRB approval, in which sterile male volunteers were administered 3 mg/kg 1,2,3-13C3 acrylamide orally. Urine was collected for 24 h after administration, and metabolites were analyzed by 13C NMR spectroscopy. At 24 h, urine contained 34% of the administered dose, and 75% of the metabolites were derived from direct conjugation of acrylamide with glautathione. Gycidamide, dihydroxypropionamide and one unidentified metabolite were also detected in urine. This study indicated differences in the metabolism of acrylamide between humans and rodents.
Fennell
Timothy R
TR
RTI International, Research Triangle Park, North Carolina, USA. Fennell@rti.org
Friedman
Marvin A
MA
D020106:Acrylamide / Q000378:metabolism* / Q000633:toxicity; D000818:Animals; D017666:Deuterium Oxide; D004305:Dose-Response Relationship, Drug; D004852:Epoxy Compounds / Q000737:chemistry; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008956:Models, Chemical; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D013045:Species Specificity; D013997:Time Factors
D004852:Epoxy Compounds; D020106:Acrylamide; C071834:glycidamide; D005978:Glutathione; D017666:Deuterium Oxide; D010100:Oxygen