skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Toxicokinetics of acrylamide and glycidamide in Fischer 344 rats

Abstract

Acrylamide (AA) is a widely studied industrial chemical that is neurotoxic, mutagenic to somatic and germ cells, and carcinogenic in rodents. The recent discovery of AA at ppm levels in a wide variety of commonly consumed foods has energized research efforts worldwide to define toxic mechanisms, particularly toxicokinetics and bioavailability. This study compares the toxicokinetics of AA and its epoxide metabolite, glycidamide (GA), in serum and tissues of male and female F344 rats following acute exposure by intravenous, gavage, and dietary routes at 0.1 mg/kg AA or intravenous and gavage routes with an equimolar amount of GA. AA was rapidly absorbed after oral dosing, was widely distributed to tissues, was efficiently converted to GA, and produced increased levels of GA-DNA adducts in liver. GA was also rapidly absorbed, widely distributed to tissues, and produced increased liver DNA adduct levels. AA bioavailability after aqueous gavage was 60-98% and from the diet was 32-44%; however, first-pass metabolism or other kinetic change resulted in much higher internal exposures to GA (2- to 7-fold) when compared to the intravenous route. A similar effect on metabolism to GA following oral administration was previously observed under an identical exposure paradigm in mice. Furthermore, DNA adduct formationmore » in rat liver showed the same proportionality with the respective GA AUC value as did mice in the previous study. These findings suggest that as the AA content in food is reduced, species-differences in GA formation and subsequent DNA adduct formation may be minimized. These findings provide additional information needed to assess genotoxic risks from the low levels of AA that are pervasive in the food supply.« less

Authors:
 [1];  [2];  [2];  [2];  [2]
  1. National Center for Toxicological Research, Jefferson, AR 72079 (United States). E-mail: ddoerge@nctr.fda.gov
  2. National Center for Toxicological Research, Jefferson, AR 72079 (United States)
Publication Date:
OSTI Identifier:
20722021
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 208; Journal Issue: 3; Other Information: DOI: 10.1016/j.taap.2005.03.003; PII: S0041-008X(05)00128-6; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ACRYLAMIDE; ACUTE EXPOSURE; BIOLOGICAL AVAILABILITY; DIET; DNA; DNA ADDUCTS; EPOXIDES; FOOD; GERM CELLS; LIVER; METABOLISM; MICE; ORAL ADMINISTRATION; RATS

Citation Formats

Doerge, Daniel R., Young, John F., McDaniel, L. Patrice, Twaddle, Nathan C., and Churchwell, Mona I. Toxicokinetics of acrylamide and glycidamide in Fischer 344 rats. United States: N. p., 2005. Web. doi:10.1016/j.taap.2005.03.003.
Doerge, Daniel R., Young, John F., McDaniel, L. Patrice, Twaddle, Nathan C., & Churchwell, Mona I. Toxicokinetics of acrylamide and glycidamide in Fischer 344 rats. United States. doi:10.1016/j.taap.2005.03.003.
Doerge, Daniel R., Young, John F., McDaniel, L. Patrice, Twaddle, Nathan C., and Churchwell, Mona I. Tue . "Toxicokinetics of acrylamide and glycidamide in Fischer 344 rats". United States. doi:10.1016/j.taap.2005.03.003.
@article{osti_20722021,
title = {Toxicokinetics of acrylamide and glycidamide in Fischer 344 rats},
author = {Doerge, Daniel R. and Young, John F. and McDaniel, L. Patrice and Twaddle, Nathan C. and Churchwell, Mona I.},
abstractNote = {Acrylamide (AA) is a widely studied industrial chemical that is neurotoxic, mutagenic to somatic and germ cells, and carcinogenic in rodents. The recent discovery of AA at ppm levels in a wide variety of commonly consumed foods has energized research efforts worldwide to define toxic mechanisms, particularly toxicokinetics and bioavailability. This study compares the toxicokinetics of AA and its epoxide metabolite, glycidamide (GA), in serum and tissues of male and female F344 rats following acute exposure by intravenous, gavage, and dietary routes at 0.1 mg/kg AA or intravenous and gavage routes with an equimolar amount of GA. AA was rapidly absorbed after oral dosing, was widely distributed to tissues, was efficiently converted to GA, and produced increased levels of GA-DNA adducts in liver. GA was also rapidly absorbed, widely distributed to tissues, and produced increased liver DNA adduct levels. AA bioavailability after aqueous gavage was 60-98% and from the diet was 32-44%; however, first-pass metabolism or other kinetic change resulted in much higher internal exposures to GA (2- to 7-fold) when compared to the intravenous route. A similar effect on metabolism to GA following oral administration was previously observed under an identical exposure paradigm in mice. Furthermore, DNA adduct formation in rat liver showed the same proportionality with the respective GA AUC value as did mice in the previous study. These findings suggest that as the AA content in food is reduced, species-differences in GA formation and subsequent DNA adduct formation may be minimized. These findings provide additional information needed to assess genotoxic risks from the low levels of AA that are pervasive in the food supply.},
doi = {10.1016/j.taap.2005.03.003},
journal = {Toxicology and Applied Pharmacology},
number = 3,
volume = 208,
place = {United States},
year = {Tue Nov 01 00:00:00 EST 2005},
month = {Tue Nov 01 00:00:00 EST 2005}
}