Urinary acrylamide metabolites as biomarkers for short-term dietary exposure to acrylamide

Bjellaas, Thomas; Stølen, Linn Helene; Haugen, Margaretha; Paulsen, Jan Erik; Alexander, Jan; Lundanes, Elsa; Becher, Georg

doi:10.1016/j.fct.2006.12.007

Cited by 56 publications

(61 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In a study of 47 non-smoking individuals the estimated AA intake did not correlate with urinary biomarkers (Bjellaas et al, 2007b). The median (range) total excretion of AA as mercapturic acid metabolites in urine during 24 hours was 16 (7-47) µg for non-smokers.…”

Section: Human Studiesmentioning

confidence: 90%

Scientific Opinion on acrylamide in food

Publication¹

2015

EFS2

342

170

View full text Add to dashboard Cite

EFSA was asked to deliver a scientific opinion on acrylamide (AA) in food. AA has widespread uses as an industrial chemical. It is also formed when certain foods are prepared at temperatures above 120 °C and low moisture, especially in foods containing asparagine and reducing sugars. The CONTAM Panel evaluated 43 419 analytical results from food commodities. AA was found at the highest levels in solid coffee substitutes and coffee, and in potato fried products. Mean and 95th percentile dietary AA exposures across surveys and age groups were estimated at 0.4 to 1.9 µg/kg body weight (b.w.) per day and 0.6 to 3.4 µg/kg b.w. per day, respectively. The main contributor to total dietary exposure was generally the category 'Potato fried products (except potato crisps and snacks)'. Preferences in home-cooking can have a substantial impact on human dietary AA exposure. Upon oral intake, AA is absorbed from the gastrointestinal tract and distributed to all organs. AA is extensively metabolised, mostly by conjugation with glutathione but also by epoxidation to glycidamide (GA). Formation of GA is considered to represent the route underlying the genotoxicity and carcinogenicity of AA. Neurotoxicity, adverse effects on male reproduction, developmental toxicity and carcinogenicity were identified as possible critical endpoints for AA toxicity from experimental animal studies. The data from human studies were inadequate for dose-response assessment. The CONTAM Panel selected BMDL 10 values of 0.43 mg/kg b.w. per day for peripheral neuropathy in rats and of 0.17 mg/kg b.w. per day for neoplastic effects in mice. The Panel concluded that the current levels of dietary exposure to AA are not of concern with respect to non-neoplastic effects. However, although the epidemiological associations have not demonstrated AA to be a human carcinogen, the margins of exposure (MOEs) indicate a concern for neoplastic effects based on animal evidence. © European Food SUMMARYFollowing a request from the European Commission, the Panel on Contaminants in the Food Chain (CONTAM Panel) was asked to deliver a scientific opinion on acrylamide (AA) in food. The Panel developed the draft scientific opinion which underwent a public consultation from 1 July 2014 to 15 September 2014. The comments received and how they were taken into account when finalising the scientific opinion were published in an EFSA Technical Report (EFSA, 2015).AA is a low molecular weight, highly water soluble, organic compound. It is used inter alia as an industrial chemical and in the production of polyacrylamides. Heightened concerns about exposure to AA arose in 2002 when it was discovered that it forms when certain foods are prepared at temperatures usually above 120 °C and low moisture. It forms, at least in part, due to a Maillard reaction between certain amino acids, such as asparagine, and reducing sugars. However, several other pathways and precursors have also been proposed to contribute to AA formation. AA forms in numerous baked or fried carbohydrate-rich f...

show abstract

Section: Human Studiesmentioning

confidence: 90%

Scientific Opinion on acrylamide in food

Publication¹

2015

EFS2

342

170

View full text Add to dashboard Cite

show abstract

“…This prompts the speculation that additional undetected, probably small-molecule metabolites beyond glycidamide (including secondary glycidamide metabolites such as glycidamide diol) are formed (10,23) by the enzymes inhibited by disulfiram (assumed to be CYP2E1). It is also possible that in the absence of disulfiram, a major fraction of acrylamide is metabolized to glycidamide, which then is bound rapidly to macromolecules and therefore is not available for excretion as GAMA.…”

Section: Discussionmentioning

confidence: 99%

“…Acrylamide and glycidamide are conjugated to glutathione, which is the main pathway of acrylamide metabolism in both rodents and humans (10)(11)(12)(22)(23)(24). As products of this conjugation, the following mercapturic acid metabolites have been observed: N-acetyl-S-(2-carbamoylethyl)-cysteine (AAMA); N-acetyl-S-(2-carbamoylethyl)-cysteine-S -oxide; N -(R,S )-acetyl-S -(2-hydroxy-2-carbamoylethyl)-cysteine (GAMA); and Nacetyl-S -(1-carbamoyl-2-hydroxyethyl)-cysteine.…”

Section: Introductionmentioning

confidence: 99%

“…In humans, the urinary concentration ratio of AAMA and GAMA, which is considered as a metric to describe the extent of conversion of acrylamide to glycidamide (9) and thus reflects internal exposure, varies considerably between subjects (22,23). It is unclear to which extent the activity and expression of metabolizing enzymes influences acrylamide metabolism and, therefore, contributes to differences in acrylamide disposition and carcinogenicity among species and between individuals (20,33).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

In vivo Role of Cytochrome P450 2E1 and Glutathione-S-Transferase Activity for Acrylamide Toxicokinetics in Humans

Doroshyenko

Fuhr

Kunz

et al. 2009

Cancer Epidemiology, Biomarkers &Amp; Prevention

View full text Add to dashboard Cite

Acrylamide, a potential food carcinogen in humans, is biotransformed to the epoxide glycidamide in vivo. Both acrylamide and glycidamide are conjugated with glutathione, possibly via glutathione-S-transferases (GST), and bind covalently to proteins and nucleic acids. We investigated acrylamide toxicokinetics in 16 healthy volunteers in a four-period change-over trial and evaluated the respective role of cytochrome P450 2E1 (CYP2E1) and GSTs. Participants ingested selfprepared potato chips containing acrylamide (1 mg) without comedication, after CYP2E1 inhibition (500 mg disulfiram, single dose) or induction (48 g/d ethanol for 1 week), and were phenotyped for CYP2E1 with chlorzoxazone (250 mg, single dose). Unchanged acrylamide and the mercapturic acids N -acetyl-S-(2-carbamoylethyl)-cysteine (AAMA) and N-acetyl-S -(2-hydroxy-2-carbamoylethyl)-cysteine (GAMA) accounted for urinary excretion [geometric mean (percent coefficient of variation)] of 2.9% (42), 65% (23), and 1.7% (65) of the acrylamide dose in the reference period.Hemoglobin adducts increased clearly following the acrylamide test-meal. The cumulative amounts of acrylamide, AAMA, and GAMA excreted and increases in AA adducts changed significantly during CYP2E1 blockade [point estimate (90% confidence interval)] to the 1.34-fold (1.14-1.58), 1.18-fold (1.02-1.36), 0.44-fold (0.31-0.61), and 1.08-fold (1.02-1.15) of the reference period, respectively, but were not changed significantly during moderate CYP2E1 induction. Individual baseline CYP2E1 activity, CYP2E1*6, GSTP1 313A>G and 341T>C single nucleotide polymorphisms, and GSTM1-and GSTT1-null genotypes had no major effect on acrylamide disposition. The changes in acrylamide toxicokinetics upon CYP2E1 blockade provide evidence that CYP2E1 is a major but not the only enzyme mediating acrylamide epoxidation in vivo to glycidamide in humans. No obvious genetic risks or protective factors in xenobiotic-metabolizing enzymes could be determined for exposed subjects. (Cancer Epidemiol

show abstract

“…The half-lives of AAMA, GAMA2, and GAMA3 were reported to be 11, 19, and 19 h, respectively (Hartmann et al 2009). Urinary AAMA and GAMA3 were proposed as biomarkers for AA exposure in general populations exposed to AA via tobacco smoke or foods processed at high temperatures (Bjellaas et al 2005(Bjellaas et al , 2007Boettcher et al 2005;Li et al 2005;Fennell et al 2006;Urban et al 2006;Huang et al 2007). The relationship between GAMA3 and AAMA is also important indicator of AA metabolized to GA, the ultimate carcinogenic AA metabolite (Besaratinia and Pfeifer 2005).…”

Section: Introductionmentioning

confidence: 99%