Biological effects of acrylamide after daily ingestion of various foods in comparison to water: A study in rats

Berger, Franz; Feld, Julia; Bertow, Daniel; Eisenbrand, Gerhard; Fricker, Gert; Gerhardt, Natalie; Merz, Karl‐Heinz; Richling, Elke; Baum, Matthias

doi:10.1002/mnfr.201000234

Cited by 29 publications

(38 citation statements)

References 55 publications

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“…The procedure has had widespread applications for monitoring environmental and occupational exposure to alkylating agents. GC-MS/MS procedures (Paulsson et al, 2003;Schettgen et al, 2004bSchettgen et al, , 2010Urban et al, 2006;Berger et al, 2011) and HPLC-MS/MS procedures have been developed for the analysis of Hb adducts with AA and GA. A typical HPLC-MS/MS procedure involves precipitation of globin from red blood cells, which is then reacted with pentafluorophenyl isothiocyanate, followed by addition of stable isotope-labelled analytes as internal standards, SPE purification and ESI HPLC-MS/MS Tareke et al, 2006;Bjellas et al, 2007c;Huang et al, 2012). In the procedure of Vesper et al (2006) the analytes were isolated using liquid-liquid extraction on diatomaceous earth.…”

Section: Methodsmentioning

confidence: 99%

“…Spiking, i.e. addition of AA to the food, may lead to loss of part of the added AA due to covalent binding to food constituents, suggesting an apparent reduced absorption (Berger et al, 2011).…”

Section: Effect Of Food Matrixmentioning

confidence: 99%

“…per day were fed for 1, 3, 5, 7, and 9 days (Berger et al, 2011). The AA levels were analytically determined.…”

Section: Effect Of Food Matrixmentioning

confidence: 99%

“…Analytical methods AAMA and GAMA are generally analysed by HPLC methods with detection by tandem mass spectrometry (MS/MS) using multiple reaction mode (MRM). The procedures involve addition of stable isotopically labelled standards (d 3 -AAMA, d 3 -GAMA) to a urine sample, and HPLC-MS/MS with either positive or negative ESI (Bjellas et al, 2005;Fennell et al, 2006;Kopp et al, 2008;Schettgen et al, 2008;Berger et al, 2011;Huang et al, 2011a,b;Chiang et al, 2015). In most procedures SPE column purification of the metabolite prior to MS analysis has been used, although column switching techniques with an on-line trap column have also been developed (Kellert et al, 2006;Kopp et al, 2008).…”

Section: Mercapturic Acidsmentioning

confidence: 99%

“…Studies on the excretion of mercapturic acids following administration of AA in food matrices by Bjellaas et al (2007a) and Berger et al (2011) are reported in Section 7.1.1.…”

Section: Experimental Animal Studiesmentioning

confidence: 99%

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Scientific Opinion on acrylamide in food

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2015

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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...

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Section: Methodsmentioning

confidence: 99%

Section: Effect Of Food Matrixmentioning

confidence: 99%

“…per day were fed for 1, 3, 5, 7, and 9 days (Berger et al, 2011). The AA levels were analytically determined.…”

Section: Effect Of Food Matrixmentioning

confidence: 99%

Section: Mercapturic Acidsmentioning

confidence: 99%

“…Studies on the excretion of mercapturic acids following administration of AA in food matrices by Bjellaas et al (2007a) and Berger et al (2011) are reported in Section 7.1.1.…”

Section: Experimental Animal Studiesmentioning

confidence: 99%

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Scientific Opinion on acrylamide in food

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2015

EFS2

331

170

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Profiling of mercapturic acids of acrolein and acrylamide in human urine after consumption of potato crisps*

Watzek

Scherbl

Feld

et al. 2012

Molecular Nutrition Food Res

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Toxicokinetics of acrylamide in primary rat hepatocytes: coupling to glutathione is faster than conversion to glycidamide

et al. 2013

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Acrylamide (AA), classified as class 2A carcinogen (probably carcinogenic to humans) by the International Agency for Research on Cancer (IARC), is formed during heating of food from reducing carbohydrates and asparagine by Maillard reaction chemistry. After dietary uptake, AA is in part metabolically converted into the proximate genotoxic phase I metabolite glycidamide (GA). GA reacts with nucleophilic base positions in DNA, primarily forming N7-(2-carbamoyl-2-hydroxyethyl)guanine (N7-GA-Gua) adducts. In a competing phase II biotransformation pathway AA, as well as its phase I metabolite GA, is coupled to glutathione (GSH). The GSH coupling products are further biotransformed and excreted via urine as mercapturic acids (MA), N-acetyl-S-(2-carbamoylethyl)cysteine (AAMA), and N-acetyl-S-(2-hydroxy-2-carbamoylethyl)cysteine (GAMA). In the present study, hepatic biotransformation pathways and DNA adduct formation were studied in primary rat hepatocytes, incubated with AA (0.2-2,000 μM) for up to 24 h. Contents of AA-GSH, GA, AAMA, and GAMA were measured in the cell culture medium after solid phase extraction (SPE). N7-GA-Gua adducts in DNA of hepatocytes were determined by HPLC-ESI-MS/MS after lysis of the cells and neutral thermal hydrolysis. Formation of AA-GSH was linear with AA concentration and incubation time and became detectable already at 0.2 μM (4 h). In contrast to AA, GA was not detected before 16 h incubation at 10-fold higher AA concentration (2 μM). In summary, the rate of AA-GSH formation was found to be about 1.5-3 times higher than that of GA formation. N7-GA-Gua adducts were found only at the highest AA concentration tested (2,000 μM).

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Biological effects of acrylamide after daily ingestion of various foods in comparison to water: A study in rats

Abstract: The results suggest AA at dietary intake levels, exceeding estimated human mean intake by a factor of at least 100 to become detoxified in Sprague-Dawley rats to a major extent through glutathione coupling.

Cited by 29 publications

References 55 publications

Scientific Opinion on acrylamide in food

Scientific Opinion on acrylamide in food

Profiling of mercapturic acids of acrolein and acrylamide in human urine after consumption of potato crisps*

Toxicokinetics of acrylamide in primary rat hepatocytes: coupling to glutathione is faster than conversion to glycidamide

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