Abstract
A dose of 0.99 mg d3-acrylamide (d3-AA) (13.2 μg/kg body weight) was ingested by a healthy male volunteer. Urine samples were collected over a period of 46 h after the intake and analyzed for the hydrolysis product of glycidamide (GA), 2,3-dihydroxy-propionamide (OH-PA), a metabolite of the toxicologically relevant oxidative AA metabolism pathway; 5.4% of the administered d3-AA dose was eliminated as OH-PA within 46 h after ingestion. Therefore, OH-PA represents a major metabolite of the oxidative metabolism pathway. Elimination kinetics of OH-PA is similar to the oxidative metabolites N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-cysteine (GAMA) and N-acetyl-S-(1-carbamoyl-2-hydroxyethyl)-cysteine (iso-GAMA). The major excretion of d3-OH-PA took place between 8 and 22 h with the highest urinary d3-OH-PA concentration (c max) of 69.3 μg/L urine, 18 h (t max) postdose. OH-PA (5.4%), together with the other known urinary metabolites of the oxidative pathway GAMA (4.6%) and iso-GAMA (0.8%), represents 10.8% of the total AA dose. The share of the oxidative pathway metabolites is much smaller than the share of the reductive pathway metabolite N-acetyl-S-(2-carbamoylethyl)-cysteine (AAMA) that represents 51.7% of the ingested d3-AA dose. However, this new quantitative human data on OH-PA together with the previous data on the other oxidative pathway metabolites are of special importance when evaluating the carcinogenic potential of AA and when comparing human data with data from animal studies.
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We especially thank the DFG (German Research Foundation) for their financial support of the project (AN 107/17-1 and 17-2).
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Hartmann, E.C., Latzin, J.M., Schindler, B.K. et al. Excretion of 2,3-dihydroxy-propionamide (OH-PA), the hydrolysis product of glycidamide, in human urine after single oral dose of deuterium-labeled acrylamide. Arch Toxicol 85, 601–606 (2011). https://doi.org/10.1007/s00204-010-0605-x
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DOI: https://doi.org/10.1007/s00204-010-0605-x