Toxicokinetics of acrylamide in rats and humans following single oral administration of low doses

• Published in: Toxicology and applied pharmacology Vol. 235; no. 2; pp. 135 - 142
• Main Authors: Kopp, Eva Katharina, Dekant, Wolfgang
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.03.2009; Elsevier
• Subjects: 60 APPLIED LIFE SCIENCES; ACRYLAMIDE; Acrylamide - pharmacokinetics; Acrylamide - toxicity; Administration, Oral; Adult; Animals; Area Under Curve; Biological and medical sciences; Biotransformation; Calibration; Carcinogenesis, carcinogens and anticarcinogens; CARCINOGENS; Chemical agents; Chromatography, High Pressure Liquid; CYSTEINE; Diet; DRINKING WATER; EPOXIDES; Female; Glycidamide; Human urine; Humans; LIQUID COLUMN CHROMATOGRAPHY; Male; Mass spectrometry; MASS SPECTROSCOPY; Medical sciences; METABOLITES; ORAL ADMINISTRATION; RATS; Rats, Inbred F344; Spectrometry, Mass, Electrospray Ionization; STARCH; Sulfoxide; SULFOXIDES; Toxicokinetics; Toxicology; Tumors; URINE; Young Adult; Toxicokinetics; Sulfoxide; Acrylamide; Mass spectrometry; Human urine; Glycidamide; Human; Urine; Biological fluid; Rat; Low dose; Rodentia; Single dose; Oral administration; Carcinogen; Vertebrata; Mammalia; Animal
• ISSN: 0041-008X; 1096-0333; 1096-0333
• DOI: 10.1016/j.taap.2008.12.001

The rodent carcinogen acrylamide (AA) is formed during preparation of starch-containing foods. AA is partly metabolized to the genotoxic epoxide glycidamide (GA). After metabolic processing, the mercapturic acids N-acetyl- S-(2-carbamoylethyl)- L-cysteine (AAMA), rac- N-acetyl- S-(2-carbamoyl-2-hydroxyethyl)- L-cysteine (GAMA) and rac- N-acetyl- S-(1-carbamoyl-moyl-2-hydroxyethyl)- L-cysteine (iso-GAMA) are excreted with urine. In humans, AAMA can be sulfoxidized to AAMA-sulfoxide. The aim of this study was to assess potential species-differences in AA-toxicokinetics in rats and humans after single oral administration of doses similar to the daily human dietary exposure. Male Fischer 344 rats ( n = 5/dose group) were administered 20 and 100 μg/kg b.w. 13C 3-AA in deionized water via oral gavage. Human subjects ( n = 3/gender) were orally administered 0.5 and 20 μg/kg b.w. 13C 3-AA with drinking water. Urine samples were collected in intervals for 96 and 94 h, respectively. Urinary concentrations of 13C 3-AAMA, 13C 3-GAMA and 13C 3-AAMA-sulfoxide were monitored by liquid chromatography-tandem mass spectrometry. The recovered urinary metabolites accounted for 66.3% and 70.5% of the 20 and 100 μg/kg b.w. doses in rats and for 71.3% and 70.0% of the 0.5 and 20 μg/kg b.w. doses in humans. In rats, 13C 3-AAMA accounted for 33.6% and 38.8% of dose and 32.7% and 31.7% of dose was recovered as 13C 3-GAMA; 13C 3-AAMA-sulfoxide was not detected in rat urine. In humans, 13C 3-AAMA, 13C 3-GAMA and 13C 3-AAMA-sulfoxide accounted for 51.7% and 49.2%, 6.3% and 6.4% and 13.2% and 14.5% of the applied dose, respectively. The obtained results suggest that the extent of AA bioactivation to GA in humans is lower than in rodents.