Toxicokinetics of acrylamide and glycidamide in Fischer 344 rats

Doerge, Daniel R.; Young, John F.; McDaniel, L. Patrice; Twaddle, Nathan C.; Churchwell, Mona I.

doi:10.1016/j.taap.2005.03.003

Cited by 95 publications

(71 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…ROC curve for acrylamide adducts, glycidamide adducts, and the ratio of glycidamide-to-acrylamide adducts describing the sensitivity and specificity of these markers for identifying individuals with cotinine values z10 ng/mL having higher acrylamide adduct values than individuals with PC values of <10 ng/mL. We observed gender differences in the glycidamideto-acrylamide adduct ratio, with women having higher ratios than men, which is consistent with previous findings from animal studies (36). Acrylamide is metabolized to glycidamide mainly through the action of CYP2E1 (37)(38)(39), which is affected by genetic factors (40)(41)(42) and other exposures such as ethanol and smoking (43,44).…”

Section: Discussionsupporting

confidence: 90%

Assessment of the Relation between Biomarkers for Smoking and Biomarkers for Acrylamide Exposure in Humans

Vesper

Bernert

Ospina

et al. 2007

Cancer Epidemiology, Biomarkers &Amp; Prevention

View full text Add to dashboard Cite

Smoking is an important source of acrylamide exposure in the general population. We assessed the relationship between hemoglobin adducts of acrylamide (HbAA) and glycidamide (HbGA) as biomarkers of acrylamide exposure and plasma cotinine (PC) as biomarkers of tobacco smoke exposure in 94 men and 67 women. The median (5th-95th percentile) biomarker concentrations (pmol/g Hb) in the group of individuals with PC concentrations of V10 ng/mL were 51 (29-155) and 34 (16-117) for HbAA and HbGA, respectively. They were significantly lower than those in the group of individuals with PC concentrations of >10 ng/mL [194 (87-403) and 107 (41-215) for HbAA and HbGA, respectively]. In individuals with PC concentrations of <1 ng/mL, HbAA and HbGA were similar to those observed in the group with PC values of V10 ng/mL. The intersubject variability was profoundly smaller in the group with PC values of V10 ng/mL compared with the group with PC values of >10 ng/mL. Although HbAA and HbGA could be categorized into distinguishable groups using PC concentration ranges commonly used to categorize presumed smokers and nonsmokers, no significant relationship was observed between these two biomarkers and PC within each group. The different exposure periods reflected by these biomarkers and the resulting different susceptibility to short-term variations in exposure patterns may in part explain these observations. The findings suggest that tobacco smoke exposure in individuals with PC values of <1 ng/mL has only a minimal effect

show abstract

Section: Discussionsupporting

confidence: 90%

Assessment of the Relation between Biomarkers for Smoking and Biomarkers for Acrylamide Exposure in Humans

Vesper

Bernert

Ospina

et al. 2007

Cancer Epidemiology, Biomarkers &Amp; Prevention

View full text Add to dashboard Cite

show abstract

“…administration was roughly 100% when given in aqueous solution and had reached f40% when given with the diet (26). In a very similar study in Fischer 344 rats, the calculated values of the absorbed fraction of a 0.09 to 0.14 mg/ kg dose were in the range of 80% to >100% when given as a solution, and the absorbed fraction was reduced to f60% to 80% when given with the food (27). These values, however, are derived from experiments with three mice or three to seven rats per group and/or data points, and show pronounced variability, and therefore, provide only a very preliminary estimate.…”

Section: Discussionmentioning

confidence: 85%

“…In mice, the glycidamide/acrylamide area under the curve ratios were (mean of male and female animals) 0.76, 2.7, and 2.2 following i.v. administration, oral gavage as a solution, or administration with food, respectively (26), whereas the corresponding values in rats were 0.14, 0.77, and 1.0 (27). These data show clearly that (a) lower doses do not result in a decreased formation of glycidamide (and probably are related to an increased glycidamide formation), (b) conversion of acrylamide to glycidamide is more extensive in rats compared with mice, and (c) conversion of acrylamide to glycidamide is more extensive on oral administration than on i.v.…”

Section: Discussionmentioning

confidence: 97%

“…There are only two studies in which a relatively low defined dose has been given to laboratory animals to assess toxicokinetic data. The (26,27), whereas typical doses tested were in the 1 to 50 mg/kg range (6). Despite these higher relative doses in the animals, the 60.3% mean fraction of the dose recovered in the urine in this study was similar to that reported in rodents.…”

Section: Discussionmentioning

confidence: 99%

“…This dose dependency has been explained by a saturable formation of glycidamide at higher doses in rodents (30). Plasma concentrations were measured by Doerge et al (26,27) following administration of a low 0.1 mg/kg dose of acrylamide or glycidamide to rats and mice. In mice, the glycidamide/acrylamide area under the curve ratios were (mean of male and female animals) 0.76, 2.7, and 2.2 following i.v.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Toxicokinetics of Acrylamide in Humans after Ingestion of a Defined Dose in a Test Meal to Improve Risk Assessment for Acrylamide Carcinogenicity

Fuhr

Boettcher

Kinzig‐Schippers

et al. 2006

Cancer Epidemiology, Biomarkers &Amp; Prevention

151

105

View full text Add to dashboard Cite

High amounts of acrylamide in some foods result in an estimated daily mean intake of 50 Mg for a western style diet. Animal studies have shown the carcinogenicity of acrylamide upon oral exposure. However, only sparse human toxicokinetic data is available for acrylamide, which is needed for the extrapolation of human cancer risk from animal data. We evaluated the toxicokinetics of acrylamide in six young healthy volunteers after the consumption of a meal containing 0.94 mg of acrylamide. Urine was collected up to 72 hours thereafter. Unchanged acrylamide, its mercapturic acid metabolite N-acetyl-S-(2-carbamoylethyl)-cysteine (AAMA), its epoxy derivative glycidamide, and the respective metabolite of glycidamide, N-acetyl-S-(2-hydroxy-2-carbamoylethyl)cysteine (GAMA), were quantified in the urine by liquid chromatography-mass spectrometry. Toxicokinetic variables were obtained by noncompartmental methods. Overall, 60.3 F 11.2% of the dose was recovered in the urine. Although no glycidamide was found, unchanged acrylamide, AAMA, and GAMA accounted for urinary excretion of (mean F SD) 4.4 F 1.5%, 50.0 F 9.4%, and 5.9 F 1.2% of the dose, respectively. Apparent terminal elimination half-lives for the substances were 2.4 F 0.4, 17.4 F 3.9, and 25.1 F 6.4 hours. The ratio of GAMA/AAMA amounts excreted was 0.12 F 0.02. In conclusion, most of the acrylamide ingested with food is absorbed in humans. Conjugation with glutathione exceeds the formation of the reactive metabolite glycidamide. The data suggests an at least 2-fold and 4-fold lower relative internal exposure for glycidamide from dietary acrylamide in humans compared with rats or mice, respectively. This should be considered for quantitative cancer risk assessment. (Cancer Epidemiol Biomarkers Prev 2006;15(2):266 -71)

show abstract