Review on Chronic Exposure of Acrylamide Causes a Neurotoxicity Risk


The exposure and inhalation of acrylamide (ACR) are not safe to the human health leading to the potential neurotoxicity. ACR is widely used in biochemical techniques and highly occurs in processing foods such as potato chips prepared at high temperatures. ACR is formed from reducing sugars and asparagine through the Maillard reaction. It exerts various harmful and toxic effects such as neurotoxicity both in humans and animal studies. The extensive damage of synaptic proteins, the formation of ACR-DNA adducts, degeneration of motor neurons, neurofilament reduction, are the most common neurological symptoms. The main metabolite of ACR metabolism is glycidamide, and it causes harmful effects as same as ACR. The main purpose of this study is to analyze the neurotoxic effects of ACR on various regions of the brain and its different mechanistic pathways that are involved in ACR neurotoxicity. The consumption of ACR-containing foods and its exposure are reduced by the human, leading to the reduction of toxic effects associated with ACR.


Nguyen, V,; Cooper, L,; Lowndes, J,; Melanson, K,; Angelopoulos, T.J,; Rippe, J.M,; Reimers, K., Popcorn is more satiating than potato chips in normal-weight adults. Nutr J 2012, 14, 71.

El-Sayyad, H.I,; Sakr, Sa,; Badawy, G.M,; Afify, H.S., Hazardous effects of potato chips on the development of retina in albino rats. Asian Pac J Trop Biomed 2011, 1(4), 253-260.

Friedman, M., Chemistry, biochemistry, and safety of acrylamide. A review. J Agric Food Chem 2003, 51(16), 4504-4526.

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), 3843-3854.

Koklamaz, E,; Palazoglu, T.K,; Kocadagli, T,; Gokmen, V., Effsct of combining conventional frying with radiofrequency post drying on acrylamide level and quality attributes of potato chips. J Sci Food Agric 2014, 94 (10), 2002-2008.

Williams, J.S.E., Influence of variety and processing conditions on acrylamide levels in fried potato crisps. Food Chem 2005, 52, 875-881.

Amrein, T.M,; Bachmann, S,; Noti, A,; Biedermann, M,; Barbosa, M.F,; Biedermann-Brem, S,; Grob, K,; Keiser, A,; Realini, P,; Escher, F,; Amado, R., Potential of acrylamide formation, sugars, and free asparagine in potatoes: a comparison of cultivars and farming systems. J Agric Food Chem 2003, 51, 5556-5560.

Swedish National Food Administration. Acrylamide in food 2002.

Wilson, K.M,; Rimm, E.B,, Thompson, K.M,; Mucci, L.A., Dietary Acrylamide and Cancer Risk in Humans: A Review. J Verbr Lebensm 2006, 1, 19-27.

Faria, M,; Ziy, T,; Gomez-Canela, C,; Ben-Lulu, S,; Prats, E,; Novoa-Luna, K.A,; Admon, A,; Pina, B,; Tauler, R,; Gomez-Olivan, L.M,; Raldua, D., Acrylamide acute neurotoxicity in adult zebra fish. Sci Rep 2018, 8 (1) 7918.

He, F.S,; Zhang, S.L,; Wang, H.L,; Li, G,; Zhang, Z.M,; Li, F.L,; Dong, X.M,; Hu, F.R., Neurological and electro neuromyographic assessment of the adverse effects of acrylamide on occupationally exposed workers. Scand J Work Environ Health 1989, 15 (2), 125-129.

Aras, D,; Cakar, Z,; Ozkavukcu, S,; Can, A,; Cinar, O., Invivo acrylamide exposure may cause severe toxicity to mouse oocytes through its metabolite glycidamide. PLoS One 2017, 12 (2), e0172026.

Hsu, H.T,; Chen, M.J,; Tseng, T.P,; Cheng, L.H,; Huang, L.J,; Yeh, T.S., Kinetics for the distribution of acrylamide in french fries, fried oil and vapour during frying of potatoes. Food Chemistry 2016, 211, 669-678.

Mojska, H,; Gielecinska, I,; Cendrowski, A., Acrylamide content in cigarette mainstream smoke and estimation of exposure to acrylamide tobacco smoke in Poland. Ann Agric Environ Med 2016, 23 (3), 456-461.

International Agency for Research on Cancer (IARC): Acrylamide, IARC monographs on the evaluation of carcinogenic risks to humans, some industrials chemicals. International Agency for Research on Cancer: Lyon, France1994, 60, 389-433.

Kopp, E.K,; Dekant, W., Toxicokinetics of acrylamide in rats and humans following single oral administration of low doses. Toxicol Appl Pharmacol 2009, 235 (2), 135-142.

Auld, R.B,; Bedwell, S.F., Peripheral neuropathy with sympathetic overactivity from industrial contact with acrylamide. Can Med Assoc J 1967, 96, 652-654.

Abou-Donia, M.B,; Ibrahim, S.M,; Corcoran, J.J,; Lack, L,; Friedman, M.A,; Lapadula, D.M., Neurotoxicity of glycidamide, an acrylamide metabolite, following intraperitoneal injections in rats. J Toxicol Environ Health 1993, 39 (4) 447-464.

Collins, J.J,; Swaen, G.M,; Marsh, G.M,; Utidjian, H.M,; Caporossi, J.C,; Lucas, L.J., Mortality patterns among workers exposed to acrylamide. J Occup Med 1989, 31, 614-617.

LoPachin, R.M,; Lehning, E.J., Acrylamide-induced distal axon degeneration: a proposed mechanism of action. Neurotoxicology 1994, 15 (2), 247-259.

Boyes, W.K,; Cooper, G.P., Acrylamide neurotoxicity: effects on far-field somatosensory evoked potentials in rats. Neurobehav Toxicol Teratol 1981, 3 (4), 487-490.

Johnson, K.A,; Gorzinski, S.J,; Bodner, K.M,; Campbell, R.A,; Wolf, C.H,; Friedman, M.A,; Mast, R.W., Chronic toxicity and oncogenicity study on acrylamide incorporated in the drinking water of Fischer 344 rats. Toxicol Appl Pharmacol 1986, 85 (2), 154-168.

Myers, J.E,; Macun, I., Acrylamide neuropathy in a South African factory: an epidemiologic investigation. Am J Ind Med 1991, 19 (4), 487-493

Smith, E.A,; Oehme, F.W., Acrylamide and polyacrylamide: A review of production, use, environmental fate and neurotoxicity. Rev Environ Health 1991, 9, 215-228.

Costa, L.G,; Deng, H,; Gregotti, C,; Manzo, L,; Faustman, E.M,; Bergmark, E,; Calleman, C.J., Comparative studies on the neuro- and reproductive toxicity of acrylamide and its epoxide metabolite glycidamide in the rat. Neurotoxicology 1992, 13 (1), 219-224.

Deng, H,; He, F,; Zhang, S,; Calleman, C.J,; Costa, L.G., Quantitative measurements of vibration threshold in healthy adults and acrylamide workers. Int Arch Occup Environ Health 1993, 65 (1), 53-56.

Calleman, C.J,; Wu, Y,; He, F,; Tian, G,; Bergmark, E,; Zhang, S,; Deng, H,; Wang, Y,; Crofton, K.M,; Fennell, T,; et al., Relationships between biomarkers of exposure and neurological effects in a group of workers exposed to acrylamide. Toxicol Appl Pharmacol 1994, 126 (2), 361-371.

Specer, P.S,; Schaumburg, H.H., A review of acrylamide neurotoxicity. In Part II Experimental animal neurotoxicity and pathologic mechanisms. Can J Neurol Sci 1974, 1, 152-169.

Ali, S.F,; Hong, J.S,; Wilson, W.E,; Uphouse, L.L,; Bondy, S.C., Effect of acrylamide on neurotransmitter metabolism and neuropeptide levels in several brain regions and upon circulating hormones. Arch Toxicol 1983, 52 (1) 35-43.

Hogervorst, J.G,; Schouten, L.J,; Konings, E.J,; Goldbohm, R.A,; van den Brandt, P.A., Dietary acrylamide intake and the risk of renal cell, bladder, and prostate cancer. American Journal of Clinical Nutrition 2008, 87 (5), 1428-1438.

Edwards, P.M,; Sporel-Ozakat, R.E,; Gispenm W.H., Peripheral pain fiber function is relatively insensitive to the neurotoxic actions of acrylamide in the rat. Toxicol Appl Pharmacol 1991, 111 (1), 43-48.

Lopachin, R.M., The changing view of acrylamide neurotoxicity. Neurotoxicology 2004; 25 (4), 617-630.

Endo, H,; Kittur, S,; Sabri, M.I., Acrylamide alters neurofilament protein gene expression in rat brain. Neurochem Res 1994, 19, 815-820.

Deng, H,; Jiao, X,; He, F., A study on neurotoxicity of acrylamide and glycidamide. Zhonghua Yu Fang Yi Xue Za Zhi 1997, 31 (4), 202-205.

Al Deeb, S,; Al Moutaery, K,; Arshaduddin, M,; Biary, N,; Tariq, M., Attenuation of acrylamide-induced neurotoxicity in diabetic rats. Neurotoxicol Teratol 2000, 22 (2), 247-253.

Dorman, D.C., An integrative approach to neurotoxicology. Toxicol Pathol 2000, 28 (1), 37-42.

Barber, D,; Hunt, J.R,; Ehrich, M,; Lehning, E.J,; LoPachin, R.M., Metabolism, toxicokinetics and hemoglobin adduct formation in rats following subacute and subchronic acrylamide dosing. NeuroToxicology 2001, 22, 341-353.

Ho, W.H,; Wang, S.M,; Yin, H.S., Acrylamide disturbs the subcellular distribution of GABAA receptor in brain neurons. J Cell Biochem 2002, 85 (3), 561-571.

Nordin-Andersson, M,; Walum, E,; Kjellstrand, P,; Forsby, A., Acrylamide-induced effects on general and neurospecific cellular functions during exposure and recovery. Cell Biol Toxicol 2003, 19 (1), 43-51.

LoPachin, R.M,; Balaban, C.D,; Ross, J.F., Acrylamide axonopathy revisited. Toxicol Appl Pharmacol 2003, 188 (3), 135-153.

Barber, D.S,; LoPachin, R.M., Proteomic analysis of acrylamide-protein adduct formation in rat brain synaptosomes. Toxicol Appl Pharmacol 2004, 201 (2), 120-136.

Uttara, B,; Singh, A.V,; Zamboni, P,; Mahajan, R.T., Oxidative Stress and Neurodegenerative Diseases: A Review of Upstream and Downstream Antioxidant Therapeutic Options. Curr Neuropharmacol 2009, 7 (1), 65-74.

LoPachin, R.M,; Barber, D.S., Synaptic cysteine sulfhydryl groups as targets of electrophilic neurotoxicants. Toxicol Sci 2006, 94 (2), 240-55.

Lopachin, R.M,; Barber, D.S,; He, D,; Das, S., Acrylamide inhibits dopamine uptake in rat striatal synaptic vesicles. Toxicol Sci 2006, 89 (1), 224-234.

Exon, J.H., A review of the toxicology of acrylamide. J Toxicol Environ Health B Crit Rev 2006, 9 (5), 397-412.

Barber, D.S,; Stevens, S,; LoPachin, R.M., Proteomic analysis of rat striatal synaptosomes during acrylamide intoxication at a low dose rate. Toxicol Sci 2007, 100 (1), 156-167.

Zhu, Y.J,; Zeng, T,; Zhu, Y.B,; Yu, S.F,; Wang, Q.S,; Zhang, L.P,; Guo, X,; Xie, K.Q., Effects of acrylamide on the nervous tissue antioxidant system and sciatic nerve electrophysiology in the rat. Neurochem. Res 2008, 33, 2310-2317.

Bowyer, J.F,; Latendresse, J.R,; Delongchamp, R.R,; Warbritton, A.R,; Thomas, M,; Divine, B,; Doerge, D.R., The mRNA expression and histological integrity in rat forebrain motor and sensory regions are minimally affected by acrylamide exposure through drinking water. Toxicol Appl Pharmacol 2009, 240 (3), 401-411.

Mojska, H,; Gielecinska, I,; Szponar, L,; Ołtarzewski, M., Estimation of the dietary acrylamide exposure of the Polish population. Food Chem Toxicol 2010, 48, 2090-2096.

Lee, H.R,; Cho, S.J,; Park, H.J,; Kim, K.H,; Rhee, D.K,; Pyo, S., The inhibitory effect of acrylamide on NCAM expression in human neuroblastoma cells: involvement of CK2/Ikaros signaling pathway. Toxicol In Vitro 2010, 24 (7), 1946-1952.

Allam, A,; El-Ghareeb, A.A,; Abdul-Hamid, M,; Baikry, A,; Sabri, M.I., Prenatal and perinatal acrylamide disrupts the development of cerebellum in rat: Biochemical and morphological studies. Toxicol Ind Health 2011, 27 (4), 291-306.

Seale, S.M,; Feng, Q,; Agarwal, A.K,; El-Alfy, A.T., Neurobehavioral and transcriptional effects of acrylamide in juvenile rats. Pharmacol Biochem Behav 2012, 101 (1), 77-84.

LoPachin, R.M,; Gavin, T., Molecular mechanism of acrylamide neurotoxicity: lessons learned from organic chemistry. Environ Health Perspect 2012, 120 (12), 1650-1657.

Erkekoglu, P,; Baydar, T., Acrylamide neurotoxicity. Nutr Neurosci 2014, 17 (2), 49-57.

Kopanska, M,; Czech, J,; Zagata, P,; Dobrek, L,; Thor, P,; Formicki, G., Effect of the different doses of acrylamide on acetylocholinoestease activity, thiol groups, malondialdehyde concentrations in hypothalamus and selected muscles of mice. J Physiol Pharmacol 2017, 68 (4), 565-571.

Adewale, O.O,; Brimson, J.M,; Odunola, O.A,; Gbadegesin, M.A,; Owumi, S.E,; Isidoro, C,; Tencomnao, T.,.The Potential for Plant Derivatives against Acrylamide Neurotoxicity. Phytother Res 2015, 29 (7), 978-985.

Tian, S.M,; Ma, Y.X,; Shi, J,; Lou, T.Y,; Liu, S.S,; Li, G.Y., Acrylamide neurotoxicity on the cerebrum of weaning rats. Neural Regen Res 2015, 10 (6), 938-943.

Santhanasabapathy, R,; Vasudevan, S,; Anupriya, K,; Pabitha, R,; Sudhandiran, G., Farnesol quells oxidative stress, reactive gliosis and inflammation during acrylamide-induced neurotoxicity: Behavioral and biochemical evidence. Neuroscience 2015, 308, 212-27.

Alemzadeh, I., Biotechnological method for decreasing hazardous compound (acrylamide) formation during phyto food product processing. Journal of Biotechnology and Phytochemistry 2017, 1.

Al-Gholam, M.A,; Nooh, H.Z,; El-Mehi, A.E,; El-Barbary, Ael, M,; Fokar, A.Z., Protective effect of rosemary on acrylamide motor neurotoxicity in spinal cord of rat offspring: postnatal follow-up study. Anat Cell Biol 2016, 49 (1), 34-49.

Chen, J.H,; Chou, C.C., Acrylamide inhibits cellular differentiation of human neuroblastoma and glioblastoma cells. Food Chem Toxicol 2015, 82, 27-35.

Ehsan, Z,; Mohammad, S,; Marjan, F,; Fatemeh, S., A review of acrylamide toxicity and its mechanism. Pharm Biomed Res 2017, 3 (1), 1-7.

Komoike, Y,; Matsuoka, M., Endoplasmic reticulum stress-mediated neuronal apoptosis by acrylamide exposure. Toxicol Appl Pharmacol 2016, 310, 68-77.

Mansour, S.Z,; Moawed, F.S.M,; Elmarkaby, S.M., Protective effect of 5, 7-dihydroxyflavone on brain of rats exposed to acrylamide or γ-radiation. J Photochem Photobiol B 2017, 175, 149-155.

Semla, M,; Goc, Z,; Martiniaková, M,; Omelka, R,; Formicki, G., Acrylamide: a common food toxin related to physiological functions and health. Physiol Res 2017, 66 (2), 205-217.

Kowalska, M,; Zbikowska, A,; Onacik-Gur, S,; Kowalska, D., Acrylamide in food products eating habits and consumer awareness among Medical School students. Ann Agric Environ Med 2017, 24 (4), 570-574.

Fuhr, U,; Boettcher, M.I,; Kinzig-Schippers, M,; Weyer, A,; Jetter, A,; Lazar, A,; Taubert, D,; Tomalik-Scharte, D,; Pournara, P,; Jakob, V,; Harlfinger, S,; Klaassen, T,; Berkessel, A,; Angerer, J,; Sorgel, F,; Schomig, E., Toxicokinetics of acrylamide in humans after ingestion of a defined dose in a test meal to improve risk assessment for acrylamide carcinogenicity. Cancer Epidemiology Biomarkers and Prevention 2006, 15 (2), 266-271.

Zhang, B,; Shao, H,; Wang, X.H,; Chen, X,; Li, Z.S,; Cao, P,; Zhu, D,; Yang, Y.G,; Xiao, J.W,; Li, B., Acrylamideinduced Subacute Neurotoxic Effects onthe Cerebral Cortex and Cerebellum at the Synapse Level in Rats. Biomed Environ Sci. 2017; 30(6):432-443.

Prats, E,; Gomez-Canela, C,; Ben-Lulu, S,; Ziv, T,; Padros, F,; Tornero, D,; Garcia-Reyero, N,; Tauler, R,; Admon, A,; Raldua, D., Modelling acrylamide acute neurotoxicity in zebrafish larvae. Sci Rep 2017, 7 (1), 139-152.

Erdemli, M.E,; Arif Aladag, M,; Altinoz, E,; Demirtas, S,; Turkoz, Y,; Yigitcan, B,; Bag, H.G., Acrylamide applied during pregnancy causes the neurotoxic effect by lowering BDNF levels in the fetal brain. Neurotoxicol Teratol 2018, 67, 37-43.

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