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ToxSci Advance Access published online on July 26, 2006
Toxicological Sciences, doi:10.1093/toxsci/kfl069
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© The Author 2006. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received February 23, 2006
Accepted July 24, 2006

Biotransformation and Toxicokinetics

Kinetics of Elimination of Urinary Metabolites of Acrylamide in Humans

Timothy R. Fennell 1 *, Susan C.J. Sumner 1, Rodney W. Snyder 1, Jason Burgess 1, and Marvin A. Friedman 2

1 RTI International, Research Triangle Park, NC
2 UMDNJ, Newark, NJ

* To whom correspondence should be addressed.
Timothy R. Fennell, E-mail: Fennell{at}RTI.org


  Abstract

Acrylamide (AM), used in the manufacture of polyacrylamide and grouting agents, is produced during the cooking of foods. Workplace exposure to AM can occur through the dermal and inhalation routes. The objective of this study was to define the kinetics of elimination of AM and its metabolites following oral and dermal administration. This is the second part of a study in which metabolites and hemoglobin adducts of AM were determined in people (Fennell et al., Toxicol. Sci. 2005, 447-459). (1,2,3-13C3)AM was administered in an aqueous solution orally (single dose of 0.5, 1.0, or 3.0 mg/kg) or dermally (3 daily doses of 3.0 mg/kg) to sterile male volunteers. Urine samples were collected at 0-2, 2-4, 4-8, 8-16 and 16-24 h following administration orally, or at 0-2, 2-4, 4-8, 8-16 and 16-24 h following each of 3 daily dermal doses. 13C3-AM and its metabolites in urine, 13C3-glycidamide, 13C3-N-acetyl-S-(3-amino-3-oxopropyl)cysteine and its S-oxide, and 13C3-N-acetyl-S-(3-amino-2-hydroxy-3-oxopropyl)cysteine were quantitated using LC-MS/MS. The recovered urinary metabolites accounted for 45.6, 49.9, and 39.9 % of a 0.5, 1.0, and 3.0 mg/kg oral dose (0-24 h), respectively, and for 4.5 % of the dose after 3 mg/kg administered daily for 3 days dermally (0-4 days). These results indicate that after oral administration AM is rapidly absorbed and eliminated. The half life estimated for elimination of AM in urine was 3.1-3.5 h. After dermal administration, AM uptake is slow. This study indicated that skin provides a barrier that slows the absorption of AM, and results in limited systemic availability following dermal exposure to AM.


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