Abstract
We investigated the human metabolism of AA to the mercapturic acids N-acetyl-S-(2-carbamoylethyl)-l-cysteine (AAMA) and N-(R/S)-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-l-cysteine (GAMA) which are derived from AA itself and from its oxidative genotoxic metabolite glycidamide (GA), respectively. A healthy male volunteer received a single dose of about 1 mg deuterium-labelled acrylamide (d3-AA), representing 13 μg/kg body weight, in drinking water. Urine samples before dosing and within 46 h after the dose were analysed for d3-AAMA and d3-GAMA by LC-ESI-MS/MS. A first phase of increase in urinary concentration was found to last 18 h with a broad plateau between 8 and 18 h for AAMA, and 22 h for GAMA. Elimination half-lives of both AAMA and GAMA were estimated to be approximately 3.5 h for the first phase and more than 10 h up to few days for the second phase. Total recovery in urine after 24 h was about 51% as the sum of AAMA and GAMA and hereby well in accordance with former studies in rats. After 2 days AAMA, accounting for altogether 52% of the total AA dose, was the major metabolite of AA in humans. GAMA, accounting for 5%, appeared as a minor metabolite of AA. In humans we found a urinary ratio of 0.1 for GAMA/AAMA compared to previously reported values of 0.2 for rats and 0.5 for mice. Therefore, the metabolic fate of AA in humans was more similar to that in rats than in mice as already demonstrated in terms of the haemoglobin adducts. Consequently a genotoxic potency of AA mediated by GA could be supposed to be comparable in rats and humans.
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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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Boettcher, M.I., Bolt, H.M., Drexler, H. et al. Excretion of mercapturic acids of acrylamide and glycidamide in human urine after single oral administration of deuterium-labelled acrylamide. Arch Toxicol 80, 55–61 (2006). https://doi.org/10.1007/s00204-005-0011-y
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DOI: https://doi.org/10.1007/s00204-005-0011-y