**1. Introduction**

Acrylamide (ACR), a water-soluble vinyl monomer, is a by-product of foods rich in carbohydrates that are cooked at higher temperatures. It has been shown to evoke genotoxic, carcinogenic, and neurotoxic effects in various kinds of animal species [1]. When exposed to humans through lifestyle, diet, occupation, and various other environmental factors it can cause adverse neurotoxic effects like ataxia, peripheral neuropathy and may result in the pathogenesis of neurodegenerative diseases. ACR could be found as a result of the use of polyacrylamide (PAM) in the environment. It can be seen in ingredients that are eaten by humans daily, including biscuits, breakfast cereals, bread, and crackers [2]. They are also used in cosmetics and toiletries, paper and textile production, production of dyes and organic chemicals, sugar refining, etc. PAM depolymerizes when it is exposed to high temperatures or pH to form ACR causing contamination to the environment [3]. Some other ways of exposure to ACR are through oral, inhalation, and dermal routes. It is formed from the amino acid asparagine during high-temperature cooking like baking and frying. Studies have reported that ACR is obtained from reducing sugars and the amino acid asparagine through the Maillard reaction [2]. Asparagine has been considered to be a major precursor of ACR, and heating foods having high starch content such as potatoes can result in high levels of asparagine eventually resulting in high ACR formation [4]. Rats subjected to specific time and dose-dependent measures of ACR have shown decreased norepinephrine levels and density of noradrenergic axons in different parts of the brain showing morphological evidence. According to the US FDA, a survey of 2015 on ACR values in individual food product samples, 70 ppb of ACR level was found for bread and bakery products, 500 ppb for Nuts and Fruits, and 1030 ppb for French Fries and Other Potato Foods. The no-observed-adverse-effect limit (NOAEL) and lowest observed adverse effect level (LOAEL) for laboratory animals is 0.2–0.5 μg/kg/day and 2 μg/kg/day respectively whereas the mean dietary exposure estimated by the World Health Organisation (WHO) is 0.001 cmg/kg/day [5]. It is, therefore, crucial to identify the cause of and exposure to ACR, its ways of reduction, and the health risks that are involved to establish a safer environment. The European Food Safety Authority (EFSA) has estimated the Benchmark Dose Lower Confidence Limit (BMDL) for ACR. For tumours, experts chose a BMDL10 of 0.17 mg/kg bw/day and for other effects, neurological alterations were seen to be closely related with a BMDL10 of 0.43 mg/kg bw/day [6]. Currently, many mitigation strategies are being investigated for their therapeutic effects against ACR present in the environment. Due to the harmful effects of ACR, research focuses on human health risks, dietary exposure to ACR, and its limit in foods by modulating processing ACR [3, 4].

Although the exact mechanism of ACR toxicity is still under investigation, many studies have shown that an imbalance in the antioxidant system can be one of the major reasons [7]. However, the US FDA [8] suggests that the level of ACR used in laboratory studies is higher than what humans are exposed through food. Also, the study by [9] states that more investigation is required to establish occupational exposure levels of ACR.

This review chapter aims to throw light on ACR as a neurotoxin and hazardous waste by discussing various aspects like the occurrence of ACR as a hazardous waste, effects of ACR and its by-products, ACR induced neurotoxicity leading to neurodegenerative changes and the potential of different therapeutic strategies to mitigate the toxicity.

### **2. Occurrence of acrylamide as a hazardous waste**

ACR is a monomer and may be found in the environment because of the use of PAM polymers. ACR and its derivatives are used as sewage-flocculating agents and mainly occur in mineral extraction and chemical and food processing industries [10]. PAMs are agents also used in soil conditioning and strengthening in paper manufacturing [11]. ACR contaminates water through the use of PAM polymers in a range of industries such as agricultural, oil drilling, cement, herbicide, paper production, cosmetics, soap, chalk, adhesives, dyes, explosives, printing inks, and latex. All of these PAM applications, particularly flocculants and soil stabilisers, are potential sources of PAM contamination in drinking water supplies. Toxicity testing with some PAM-sensitive aquatic organisms revealed that oil-based PAM was harmful, whereas water-based PAM products were not. The cationic PAM has a lethal concentration (LC50a) of 0.3–10 mg/L, and it adheres to fish gills, obstructing the osmoregulation system. Several studies have found that anionic PAM products are safer to use

#### *Acrylamide: A Neurotoxin and a Hazardous Waste DOI: http://dx.doi.org/10.5772/intechopen.102607*

in environmental water than cationic and neutral PAM products. Rainbow trout, especially larger fish rather than fingerlings, have seen acute alterations in their gills at LC as a result of cationic PAM poisoning. Due to ACR exposure, goldfish developed acute tissue lesions in the pancreas and genotoxic damages in their erythrocytes, disrupting homeostasis and eventually having a carcinogenic effect. It is also noted that ACR is not accumulated in sludges produced by PAM flocculants [10]. At room temperature, ACR is a solid, however it is extremely soluble (2155 g L1 of water) and mobile in water [12]. The major source of ACR in drinking water is the residual monomer of PAM, which is released throughout the treatment process. PAMs can be a source of release to drinking water sources when used as a chemical grouting agent and soil stabiliser in the building of tunnels, sewers, wells, reservoirs, and dams. ACR is also released into water by plastic and dye industries. Because ACR does not participate in soil binding but is extremely soluble and mobile in water, it will travel quickly with seepage, increasing the risk of pollution of surface or groundwater [13]. The concentration of ACR in aquatic and terrestrial ecosystems around ACR or PAM using—industries was found to be 0.3 ppb to 5 ppm [14].

Individuals inhale ACR mostly through smoking [15]. The amount of haemoglobin adduct identified was precisely related to the amount of ACR inhaled from three cigarettes each day [16]. Continuous ACR exposure, particularly by blue-collar workers, has been linked to headaches, muscle weakness, increased sensitivity in their extremities, dyspnea, and in certain cases, balance impairment, paresthesia, discomfort, and truncal ataxia [13]. The average ACR level per cigarette is 679.3 ng, with a range of 455.0– 822.5 ng per cigarette. Adult smokers in Poland are predicted to be exposed to 0.17 g/ kg b.w. of ACR per day via tobacco smoke [17]. It has been stated that each cigarette contains an average of 1.2 μg of ACR. According to the study, smoking 20 cigarettes per day exposes the body to 0.5 μg/kg b.w. per day [18]. ACR poisoning causes rashes, peeling of the skin and hands, cramping, and sweating, among other symptoms. It's also a skin irritant that causes peeling contact dermatitis on the palms, which can lead to neurologic conditions. In humans, dermal exposure can cause an exfoliative reddish rash [13, 19, 20]. In a study including two grouting workers, it was observed that one has experienced skin peeling after 2 weeks of exposure to high concentration of ACR and systemic neuropathy in the next 6 months whereas the other worker showed cerebellar dysfunctions, including gait ataxia and slurred speech after 1-month exposure [19]. The use of ACR in cosmetics is a risk to the population. Due to ACR toxicity, the initial approved dose of 100 mg.kg−1 cosmetic product was reduced to 0.5 mg.kg−1 therefore the daily exposure due to cosmetics has lowered to 0.7 g.kg−1 b.w. per day.
