Urinary Metabolites from F344 Rats and B6C3F1 Mice Coadministered Acrylamide and Acrylonitrile for 1 or 5 Days

Abstract

The purpose of this study was to examine the feasibility of using 13C NMR spectroscopy to analyze urinary metabolites produced following coadministration of two structurally similar carbon-13-labeled compounds to rodents. Acrylonitrile (AN) and acrylamide (AM) are used in the chemical industry to manufacture plastics and polymers. These compounds are known to produce carcinogenic, reproductive, or neurotoxic effects in laboratory animals. The potential for human exposure to AN and AM occurs in manufacturing facilities and environmentally. Male F344 rats and B6C3F1 mice were coadministered po [1,2,3-13C]AN (16-17 mg/kg) and [1,2,3-13C]AM (21-22 mg/kg) after 0 or 4 days of administration of unlabeled AN or AM. Urine was collected for 24 h following administration of the 13C-labeled compounds and analyzed by 13C NMR spectroscopy. Rats and mice excreted metabolites derived from glutathione (GSH) conjugation with AM or AN or derived from GSH conjugation with the epoxides cyanoethylene oxide (CEO) or glycidamide (GA). GA and its hydrolysis product were also detected in the urine of rats and mice. For mice, an increased urinary excretion of total AN- and total AM-derived metabolites (p < 0.05) on repeated coadministration suggested a possible increase in metabolism via oxidation. In addition, mice had an increased (p < 0.05) percentage of dose excreted as metabolites derived from GSH conjugation with AM, AN, CEO, or GA after five exposures as compared with one exposure that may be related to a significant increase in the synthesis of GSH or an increase in glutathione transferase activity. The only significant (p < 0.05) increase between one and five exposures for the rat was in the percentage of metabolites produced following conversion of AM to GA. The use of 13C NMR spectroscopy has provided a powerful methodology for elucidation of the metabolism of two 13C-labeled chemicals administered simultaneously.

Differences in hemoglobin adduct levels of acrylamide in the general population with respect to dietary intake, smoking habits and gender

“…AA is mainly detoxified by conjugation with glutathione (GSH), but is also transformed to GA by P450 (CYP2E1) [48,49]. In vitro studies indicate no influence of GSH transferase (GST) in the detoxification of AA, which then would mean that polymorphism in GST has no influence on the variation of the level of Hb adducts from AA, i.e.…”

Scientific Opinion on acrylamide in food

“…In rats, small amounts of the non-acetylated precursor of AAMA, i.e. S-(2-carbamoylethyl)-L-cysteine, have been found (Sumner et al, 1997). The mercapturic acids GAMA and iso-GAMA exist as diastereomers due to their chiral C-atom carrying the hydroxyl group ( Figure 9).…”

Toxicity of acrylamide and evaluation of its exposure in baby foods

“…Data suggest that mice are more vulnerable to acrylamide tumorigenicity. The metabolic activation of acrylamide is more efficient and the detoxification process is poorer in mice than rats, since mice have higher levels of glycidamide and lower levels of GSH -glycidamide conjugates (27) . Acrylamide causes induction of the following genotoxic effects (28,29) (e) cell transformation in mouse cell lines; (f) somatic mutation in the spot test in vivo; (g) heritable translocation and specific locus mutations in mice and dominant lethal mutations in both mice and rats; (h) unscheduled DNA synthesis in rat spermatocytes in vivo; but not in rat hepatocytes.…”