Toxicokinetics of acrylamide and glycidamide in Fischer 344 rats

Journal Article · Tue Nov 01 04:00:00 EST 2005 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2005.03.003· OSTI ID:20722021

Doerge, Daniel R ^[1]; Young, John F ^[1]; McDaniel, L Patrice ^[1]; Twaddle, Nathan C ^[1]; Churchwell, Mona I ^[1]

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1. National Center for Toxicological Research, Jefferson, AR 72079 (United States)

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.

• OSTI ID: 20722021
• Journal Information: Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 3 Vol. 208; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ACRYLAMIDE
ACUTE EXPOSURE
BIOLOGICAL AVAILABILITY
DIET
DNA
DNA ADDUCTS
EPOXIDES
FOOD
GERM CELLS
LIVER
METABOLISM
MICE
ORAL ADMINISTRATION
RATS