Toxicological Sciences 71, 164-175 (2003)
Copyright © 2003 by the Society of Toxicology
BIOTRANSFORMATION AND TOXICOKINETIC |
Comparison of the Hemoglobin Adducts Formed by Administration of N-Methylolacrylamide and Acrylamide to Rats
* CIIT Centers for Health Research, P.O. Box 12137, Research Triangle Park, North Carolina 27709
Acrylamide (AM) and N-methylolacrylamide (NMA) are used in the formulation of grouting materials. AM undergoes metabolism to a reactive epoxide, glycidamide (GA). Both AM and GA react with hemoglobin to form adducts that can be related to exposure to AM. The objective of this study was to evaluate the extent to which NMA could form the same adducts as AM. N-(2-carbamoylethyl)valine (AAVal derived from AM) and N-(2-carbamoyl-2-hydroxyethyl)valine (GAVal derived from GA) were measured following a single oral dose of AM (50 mg/kg) or NMA (71 mg/kg) in male F344 rats. AAVal and GAVal were measured by a modified Edman degradation to produce phenylthiohydantoin derivatives and liquid chromatography/tandem mass spectrometry. In AM-treated rats, AAVal was 21 ± 1.7-pmol/mg globin (mean ± SD, n = 4), and GAVal was 7.9 ± 0.8 pmol/mg. In NMA-treated rats, AAVal was 41 ± 4.9 pmol/mg, and GAVal was 1.4 ± 0.1 pmol/mg. Whether AAVal was derived from reaction of NMA with globin followed by loss of the hydroxymethyl group, or loss of the hydroxymethyl group to form AM prior to reaction with globin, is not known. However, the higher ratio of AAVal:GAVal in NMA-treated rats (29 vs. 2.6 in AM-treated rats) suggests that reaction of NMA with globin is the predominant route to AAVal in NMA-treated rats. The detection of GAVal in NMA-treated rats indicates oxidation of NMA, either directly or following conversion to AM. The lower levels of GAVal on NMA administration suggest that a much lower level of epoxide was formed than compared with AM treatment.
Key Words: acrylamide; glycidamide; N-methylolacrylamide; hemoglobin; adduct.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  H. W. Vesper, J. T. Bernert, M. Ospina, T. Meyers, L. Ingham, A. Smith, and G. L. Myers Assessment of the Relation between Biomarkers for Smoking and Biomarkers for Acrylamide Exposure in Humans Cancer Epidemiol. Biomarkers Prev., November 1, 2007; 16(11): 2471 - 2478. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Bjellaas, P. T. Olesen, H. Frandsen, M. Haugen, L. H. Stolen, J. E. Paulsen, J. Alexander, E. Lundanes, and G. Becher Comparison of Estimated Dietary Intake of Acrylamide with Hemoglobin Adducts of Acrylamide and Glycidamide Toxicol. Sci., July 1, 2007; 98(1): 110 - 117. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. I. Ghanayem, L. P. McDaniel, M. I. Churchwell, N. C. Twaddle, R. Snyder, T. R. Fennell, and D. R. Doerge Role of CYP2E1 in the Epoxidation of Acrylamide to Glycidamide and Formation of DNA and Hemoglobin Adducts Toxicol. Sci., December 1, 2005; 88(2): 311 - 318. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. R. Fennell, S. C.J. Sumner, R. W. Snyder, J. Burgess, R. Spicer, W. E. Bridson, and M. A. Friedman Metabolism and Hemoglobin Adduct Formation of Acrylamide in Humans Toxicol. Sci., May 1, 2005; 85(1): 447 - 459. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. A. Wetmore and B. A. Merrick Invited Review: Toxicoproteomics: Proteomics Applied to Toxicology and Pathology Toxicol Pathol, October 1, 2004; 32(6): 619 - 642. [Abstract] [PDF]
|
|
|
|
|
|
S. C. J. Sumner, C. C. Williams, R. W. Snyder, W. L. Krol, B. Asgharian, and T. R. Fennell Acrylamide: A Comparison of Metabolism and Hemoglobin Adducts in Rodents following Dermal, Intraperitoneal, Oral, or Inhalation Exposure Toxicol. Sci., October 1, 2003; 75(2): 260 - 270. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Dybing and T. Sanner Risk Assessment of Acrylamide in Foods Toxicol. Sci., September 1, 2003; 75(1): 7 - 15. [Abstract] [Full Text] [PDF]
|
|