Eva C. Hartmann, M. Boettcher, H. Bolt
Jul 1, 2009
Citations
5
Influential Citations
33
Citations
Quality indicators
Journal
Archives of Toxicology
Abstract
The N-acetyl-S-(1-carbamoyl-2-hydroxy-ethyl)-l-cysteine (iso-GAMA) could be identified as a further human metabolite of acrylamide. In this study, we report the excretion of d3-iso-GAMA in human urine after single oral administration of deuterium labelled acrylamide (d3-AA). One healthy male volunteer ingested a dose of about 1 mg d3-AA which is equivalent to a dose of 13 μg/kg bodyweight. Over a period of 46 h the urine was collected and the d3-iso-GAMA levels analysed by LC-ESI-MS/MS. The excretion of iso-GAMA begins five hours after application. It rises to a maximum concentration (cmax) of 43 μg/l which was quantified in the urine excreted after 22 h (tmax). The excretion pattern is parallel to that of the major oxidative metabolite N-acetyl-S-(2-carbamoyl-2-hydroxy-ethyl)-l-cysteine (GAMA). Total recovery of iso-GAMA was about 1% of the applied dose. Together with N-acetyl-S-(2-carbamoylethyl)-l-cysteine (AAMA) and GAMA, 57% of the applied dose is eliminated as mercapturic acids. The elimination kinetics of the three mercapturic acids of AA are compared. We show that dietary doses of acrylamide (AA) cause an overload of detoxification via AAMA and lead to the formation of carcinogenic glycidamide (GA) in the human body.