Acrylamide

The industrial and laboratory use of acrylamide mainly concerns the production of polyacrylamides, which are used primarily as flocculants, mainly for clarifying drinking water and treating wastewater. Acrylamide and polyacrylamides are also used in the production of dyes, organic chemicals, permanent-press fabrics, textiles, pulp and paper products.
In the oil industry, acrylamide is used as a flow control agent to enhance oil production from wells. Beyond the chemical industry use, acrylamide is used in building and construction (e.g. as grouting agent and soil stabilizer for the construction of tunnels, sewers, wells, and reservoirs), health service, and scientific research (10). Moreover, in 2002 it was observed to be generated during food processing at temperatures above 120 degrees Celsius under low moisture conditions. It is formed predominantly by food containing asparagine and reducing sugars via Maillard reaction when processed at high temperature such as frying, roasting and baking (not boiling).
The main food sources of acrylamide are coffee (and solid coffee substitute), potatoes fried products (including potatoes and vegetables crisps), biscuits, cereals and other products such as roasted nuts, olives in brine, prunes and dates and baby food. Protein-based foods (such as meats) probably contain low amounts of acrylamide (11). Acrylamide is also present in tobacco smoke.

Acrylamide (also named 2-propenamide, acrylic amide, ethylene carboxamide, structural formula: CH₂=CH-CO-NH₂) is a low molecular weight, highly water soluble, organic compound produced for different uses in chemical industry. The concern about hazardous exposure arose in 2002 when acrylamide was discovered to be formed in certain high carbohydrate food at high temperature.
From experimental animal studies, acrylamide has been shown to have neurotoxic, carcinogenic, genotoxic and mutagenic effects (category 1B, CLP classification) and also possible/suspected immunotoxic and developmental toxic (category 2 CLP classification) effects as well as adverse effects on the reproductive function in particular in males (1-4). In humans, occupational exposure to acrylamide has been shown to cause neurotoxicity in the peripheral nervous system through prolonged or repeated exposure. Other toxic effects of acrylamide in humans are still under investigation.
Although epidemiological studies have not consistently observed an increasing risk of common cancers in relation to dietary acrylamide, there is a concern about its possible carcinogenic effects in humans (IARC classification 2A: probably carcinogenic to humans; SVHC: substance of very high concern). Glycidamide, its main metabolite, is considered to represent the main metabolite, from which the genotoxicity and carcinogenicity of acrylamide originate. A recent study found glycidamide mutational signature in a full one-third of approximately 1600 tumor genomes corresponding to 19 human tumor types from 14 different organs (5). Evidence from a limited number of epidemiological studies suggests that acrylamide may also negatively affect fetal growth (5, 6). It may also cause allergic reactions if in contact with the skin (7).
There is no consistent evidence in humans that acrylamide may act as endocrine disruptor. A possible adverse effect of mixtures of acrylamide and other chemical compounds, particularly other carcinogens in food should be taken in consideration for the risk assessment and needs to be further investigated (8, 9).

Please see the link to the scoping document on Acrylamide at the top of the page for this information.

Humans are exposed through inhalation, ingestion and dermal uptake.

Oral uptake through the ingestion of food, cigarette smoke and water is the predominant exposure route for the general population. For occupational exposure, inhalation and dermal contact at the workplace where acrylamide is used or produced is another important route of acrylamide exposure. Moreover, transplacental exposure should also be taken in consideration for the risk assessment, although more investigation is needed (6, 12, 13).

Acrylamide is extensively metabolised, mostly by conjugation with glutathione but also by epoxidation to glycidamide. Both acrylamide and glycidamide might be measured in serum. Serum concentration of acrylamide and glycidamide have both been shown to be highly correlated to acrylamide exposure but they have a short half-life.

Other biomarkers include the urinary metabolites of acrylamide, mercapturic acids of acrylamide and glycidamide (AAMA and GAMA, respectively), and the hemoglobin adducts of acrylamide and glycidamide (AAVal and GAVal). Urinary metabolites are stable compounds and can be quantified with high specificity and sensitivity. They are measures of metabolic deactivation of AA and GA but are not directly related to critical target tissue doses.

The hemoglobin adducts have a lifetime of about 110 days and have been shown to have high correlation with acrylamide exposure (21). Analytical methods for the determination of the aforementioned biomarkers are available and are characterised by the use of liquid- or gaschromatography (HPLC or GC, respectively) with detection by tandem mass spectrometry (MS/MS) using multiple reaction monitoring (MRM).

Following on the Advisory Board’s advice to strengthen the science-policy interface, HBM4EU developed a strategic and systematic approach to outreach and align science and policy. A legislative mapping exercise was done by RPA Consultants, providing relevant public policy processes that may benefit from the knowledge generated under HBM4EU. The documents are available for consultation here, with the tables presented here.

Regulatory measures have been taken at the EU level. Acrylamide is registered under REACH and included in the candidate list of substances of very high concern (SVHC) due to its possible carcinogenic and mutagenic effect. Based on the inclusion in the registration list Annex XVII of REACH, after 5 November 2012 acrylamide should not be placed on the market or used as a substance or constituent of mixture in a concentration equal or greater than 0.1% by weight for grouting applications. Acrylamide has also a harmonised classification under the Classification Labelling & Packaging (CLP) Regulation. The European Drinking Water Directive 98/83/EC has set a parametric value of acrylamide in water for human consumption of 0.10 µg/L. The parametric value for acrylamide refers to the residual monomer concentration in the water as calculated according to specifications of the maximum release from the corresponding polymer in contact with the water.
Acrylamide is also listed in the Annex II as substance prohibited in cosmetic products. Precautions for this substance have been recommended by industries under REACH. Moreover, since 2007 acrylamide levels in food are monitored according to a EU Recommendation (further extended Commission Recommendation 2013/647/EU and 2010/307/EU). Use of acrylamide is banned in plastic material and articles intended to come in contact with food (Commission Regulation (EU) No 10/2011 of 14 January 2011). Recently, the EU established mitigation measures and benchmark levels for reducing levels of acrylamide in food (Commission Regulation (EU) 2017/2158).
The societal concern is mainly related to the discovery that acrylamide is produced in processed foods rich in carbohydrates making acrylamide a widespread exposure. From the public perspective, different actions have been taking by several organisations. Chemsec, an independent organisation aiming to solicit legislators to speed-up in the decision-making process, has included acrylamide in the Sin List (Substitute it Now!) of the chemical compounds that can cause cancer, alter DNA or damage the reproductive system (CMR, class I&II).

Acrylamide has also been included in the Trade Union Priority List with priority number 3, score 43. Non-governmental organisations (Safe Food Advocacy Law, and Changing Market and SumOfUs) call for mandatory EU limits of acrylamide in food after the “public scandal” related to the finding that acrylamide levels were clearly above the new benchmark level set by the European legislation in 2017, according to results from analyses of samples of potatoe crisps available on the market; in seven out of eighteen samples the acrylamide level exceeded the benchmark level.

1. What is the current exposure of the EU population to acrylamide?
2. Are the exposure levels a concern for health? Is the exposure to acrylamide associated to cancer, neurological alterations and fetal growth in humans? Is the health risk dependent on long term or intermittent exposure to low quantity of acrylamide?
3. Does the exposure to acrylamide differ significantly between countries and population groups? Are the main reasons for these differences related to different dietary habits or to other factors?
4. Are the health risks dependent on age and gender?
5. Which population groups are more at risk? Are there other sources of exposure of acrylamide that need to be discovered (e.g. smoking habits or other food sources)?
6. Is there a possible mixture of effect between acrylamide and other carcinogens (particularly dietary carcigonogens e.g.benzopyrene) ?
7. Is there an impact from the mitigation for the production in food processing and manufacturing and REACH restrictions on the distribution of acrylamide exposure? Do we need to implement other restrictions to decrease the level of exposure of acrylamide?

Please find answers to the updated (2020) Policy-related questions on Acrylamide here

In the interest of transparency and accountability, HBM4EU invites interested stakeholders to submit comments on the scoping document on acrylamide.
All submitted comments will be made available for download on this webpage and will be taken into consideration by the HBM4EU consortium, where possible.
Please click here to submit your comments.

Please click here to access the Substance Report.

• Wang H, Huang P, Lie T, Li J, Hutz RJ, Li K, et al. Reproductive toxicity of acrylamide-treated male rats. Reprod Toxicol. 2010;29(2):225-30.
• Wei Q, Li J, Li X, Zhang L, Shi F. Reproductive toxicity in acrylamide-treated female mice. Reprod Toxicol. 2014;46:121-8.
• Prats E, Gomez-Canela C, Ben-Lulu S, Ziv T, Padros F, Tornero D, et al. Modelling acrylamide acute neurotoxicity in zebrafish larvae. Sci Rep. 2017;7(1):13952.
• Zhao M, Lewis Wang FS, Hu X, Chen F, Chan HM. Acrylamide-induced neurotoxicity in primary astrocytes and microglia: Roles of the Nrf2-ARE and NF-kappaB pathways. Food Chem Toxicol. 2017;106(Pt A):25-35.
• Duarte-Salles T, von Stedingk H, Granum B, Gutzkow KB, Rydberg P, Tornqvist M, et al. Dietary acrylamide intake during pregnancy and fetal growth-results from the Norwegian mother and child cohort study (MoBa). Environ Health Perspect. 2013;121(3):374-9.
• Pedersen M, von Stedingk H, Botsivali M, Agramunt S, Alexander J, Brunborg G, et al. Birth weight, head circumference, and prenatal exposure to acrylamide from maternal diet: the European prospective mother-child study (NewGeneris). Environ Health Perspect. 2012;120(12):1739-45.
• Dotson GS, Chen CP, Gadagbui B, Maier A, Ahlers HW, Lentz TJ. The evolution of skin notations for occupational risk assessment: a new NIOSH strategy. Regul Toxicol Pharmacol. 2011;61(1):53-62.
• Kassotis CD, Klemp KC, Vu DC, Lin CH, Meng CX, Besch-Williford CL, et al. Endocrine-Disrupting Activity of Hydraulic Fracturing Chemicals and Adverse Health Outcomes After Prenatal Exposure in Male Mice. Endocrinology. 2015;156(12):4458-73.
• David RM, Gooderham NJ. Dose-dependent synergistic and antagonistic mutation responses of binary mixtures of the environmental carcinogen benzo[a]pyrene with food-derived carcinogens. Arch Toxicol. 2018;92(12):3459-69.
• ECHA. Brief profile on acrylamide. https://echa.europa.eu/sv/brief-profile/-/briefprofile/100.001.067 [
• (CONTAM). EPoCitFC. Scientific Opinion on Acrylamide in Food. EFSA Journal 2015;13(6):4104. 2015.
• Annola K, Karttunen V, Keski-Rahkonen P, Myllynen P, Segerback D, Heinonen S, et al. Transplacental transfer of acrylamide and glycidamide are comparable to that of antipyrine in perfused human placenta. Toxicol Lett. 2008;182(1-3):50-6.
• Schettgen T, Kutting B, Hornig M, Beckmann MW, Weiss T, Drexler H, et al. Trans-placental exposure of neonates to acrylamide–a pilot study. Int Arch Occup Environ Health. 2004;77(3):213-6.
• Pennisi M, Malaguarnera G, Puglisi V, Vinciguerra L, Vacante M, Malaguarnera M. Neurotoxicity of acrylamide in exposed workers. Int J Environ Res Public Health. 2013;10(9):3843-54.
• Hagmar L, Tornqvist M, Nordander C, Rosen I, Bruze M, Kautiainen A, et al. Health effects of occupational exposure to acrylamide using hemoglobin adducts as biomarkers of internal dose. Scand J Work Environ Health. 2001;27(4):219-26.
• Kjuus H, Goffeng LO, Heier MS, Sjoholm H, Ovrebo S, Skaug V, et al. Effects on the peripheral nervous system of tunnel workers exposed to acrylamide and N-methylolacrylamide. Scand J Work Environ Health. 2004;30(1):21-9.
• Olesen PT, Olsen A, Frandsen H, Frederiksen K, Overvad K, Tjonneland A. Acrylamide exposure and incidence of breast cancer among postmenopausal women in the Danish Diet, Cancer and Health Study. Int J Cancer. 2008;122(9):2094-100.
• Olsen A, Christensen J, Outzen M, Olesen PT, Frandsen H, Overvad K, et al. Pre-diagnostic acrylamide exposure and survival after breast cancer among postmenopausal Danish women. Toxicology. 2012;296(1-3):67-72.
• Wilson KM, Balter K, Adami HO, Gronberg H, Vikstrom AC, Paulsson B, et al. Acrylamide exposure measured by food frequency questionnaire and hemoglobin adduct levels and prostate cancer risk in the Cancer of the Prostate in Sweden Study. Int J Cancer. 2009;124(10):2384-90.
• Kutting B, Schettgen T, Schwegler U, Fromme H, Uter W, Angerer J, et al. Acrylamide as environmental noxious agent: a health risk assessment for the general population based on the internal acrylamide burden. Int J Hyg Environ Health. 2009;212(5):470-80.
• Hays SM, Aylward LL. Biomonitoring Equivalents (BE) dossier for acrylamide (AA) (CAS No. 79-06-1). Regul Toxicol Pharmacol. 2008;51(3 Suppl):S57-67.
• Kutting B, Schettgen T, Schwegler U, Fromme H, Uter W, Angerer J, et al. Acrylamide as environmental noxious agent: a health risk assessment for the general population based on the internal acrylamide burden. Int J Hyg Environ Health. 2009;212(5):470-80.
• Hays SM, Aylward LL. Biomonitoring Equivalents (BE) dossier for acrylamide (AA) (CAS No. 79-06-1). Regul Toxicol Pharmacol. 2008;51(3 Suppl):S5