**2. Arsenic**

#### **2.1. Chemistry of arsenic**

Arsenic is a chemical element found in several oxidation states (+III, +V, 0, and \_ III) and various inorganic and organic forms. Arsenic rarely occurs as a pure element. The most common ores of arsenic are arsenopyrite (FeAsS) and arsenic sulfur compounds [orpiment (As2S3) and realgar (As4S4)]. The inorganic forms are considered to be of greater toxicity, and the ascending order of toxicity is elemental arsenic < arsenobetaine < methylated forms < arsenate < arsenite < arsine [4]. As(III) and As(V) are apparently of comparable bioavailability but differ in terms of their biochemistry. Preferentially, As(III) binds thiol groups, whereas As(V) does not. So, the oxidation state of arsenic can affect its toxicity [5, 6].

#### **2.2. Occurrence in the environment**

Arsenic compounds are used in glass and semiconductor production, as a preservative for wood, and as a feed additive to increase weight gain for poultry and swine [7]. Historically, arsenic compounds were used in agriculture as insecticides or herbicides. Due to its wide‐ spread use, it can contaminate the environment. Environmental pollution by arsenic occurs as a result of anthropogenic activities and natural phenomena such as volcanic eruptions and soil erosion [8].

Arsenic can be present as a contaminant in environmental compartments, such as water, soil, and plants, and ultimately can seriously affect the human health through exposures to these contaminated compartments. Inorganic arsenic species are the most important chemical forms of arsenic in natural waters [9].

#### **2.3. Dietary sources of arsenic**

Arsenic can be found in fish, shellfish, meat, poultry, dairy products, and cereals. Howev‐ er, in fish and shellfish, organic chemical species are found, and thus the arsenic is less toxic. Marine organisms tend to accumulate more arsenic than those living in freshwater or terrestrial environments, which typically have lower arsenic concentrations of around 0.25 mg kg−1 [10–12].

China has established the acceptable level of arsenic in rice as 200 ng g−1, while the Codex Alimentarius Committee on Contaminants in Food considers levels of 200 and 300 ng g−1 in polished and raw rice, respectively, to be safe [13]. The Joint FAO/WHO Expert Committee on Food Additives (JECFA) reports that the provisional tolerable daily intake (PTDI) of inorganic arsenic is 0.002 mg kg−1 body weight, equivalent to 0.12 mg day−1 for an adult of 60 kg [14]. However, if contamination with arsenic trioxide occurs, it should be noted that the minimum lethal dose of this compound is 70–180 mg in humans [15]. In general, high levels of arsenic are found in rice and the concentration can vary from 10 to 510 μg kg−1, when rice is irrigated with contaminated water, contributing to the daily intake of arsenic [16].

Due to the toxicity and the many diseases resulting from the ingestion of arsenic, the concen‐ trations of this metalloid and its species in different types of food need to be investigated. Numerous studies on arsenic levels in food have been conducted, and the results have been published in journals, newspapers, and other media. Figure 1 shows the number of publica‐ tions per year in the Web of Science on the contamination of food with arsenic, demonstrating the interest of the scientific community. occurs, it should be noted that the minimum lethal dose of this compound is 70–180 mg in humans [15]. In general, high levels of arsenic are found in rice and the concentration can vary from 10 to 510 μg kg−1, when rice is irrigated with contaminated water, contributing to the daily intake of arsenic [16]. Due to the toxicity and the many diseases resulting from the ingestion of arsenic, the concentrations of this metalloid and its species in different types of food need to be investigated. Numerous studies on arsenic levels in food have been conducted, and the results have been published in journals, newspapers, and other media. Figure 1 shows the number of publications per year in the Web of Science on the

contamination of food with arsenic, demonstrating the interest of the scientific community.

equivalent to 0.12 mg day−1 for an adult of 60 kg [14]. However, if contamination with arsenic trioxide

Figure 1. Publications on food contamination with arsenic. **Figure 1.** Publications on food contamination with arsenic.

The concentration of arsenic that is safe to human health is under discussion by organizations such as the World Health Organization (WHO), the Food and Agriculture Organization (FAO), the US Food and Drug Administration (FDA), the Food Standards Agency (FSA), and the European Food Safety Authority (EFSA) [17]. The Codex has adopted 0.2 mg kg−1 as the maximum level of arsenic in rice. This committee has the task of The concentration of arsenic that is safe to human health is under discussion by organizations such as the World Health Organization (WHO), the Food and Agriculture Organization (FAO), the US Food and Drug Administration (FDA), the Food Standards Agency (FSA), and the European Food Safety Authority (EFSA) [17].

establishing international food safety and quality standards for consumers worldwide, which are widely used as a basis for national legislation. To date, the European Union (EU) has not set maximum levels for arsenic in food. However, for water The Codex has adopted 0.2 mg kg−1 as the maximum level of arsenic in rice. This committee has the task of establishing international food safety and quality standards for consumers worldwide, which are widely used as a basis for national legislation.

intended for human consumption, the value is 10 mg L−1 for total arsenic, with no distinction between the various chemical species of arsenic [18, 19]. Thus, extensive research should be conducted, aimed at more in-depth studies and attaining greater consistency in the data for the creation of relevant legislation regarding arsenic in foods [20–23]. **2.4. Routes of entry into plants, animals, and humans**  To date, the European Union (EU) has not set maximum levels for arsenic in food. However, for water intended for human consumption, the value is 10 mg L−1 for total arsenic, with no distinction between the various chemical species of arsenic [18, 19]. Thus, extensive research should be conducted, aimed at more in-depth studies and attaining greater consistency in the data for the creation of relevant legislation regarding arsenic in foods [20–23].

#### The most important route of exposure to arsenic is the ingestion of foods and beverages, which in most cases are contaminated from the use of irrigation water with a high concentration of the element. In **2.4. Routes of entry into plants, animals, and humans**

general, the water is contaminated by dissolved minerals and contains different forms of arsenic [24]. Exposure to arsenic occurs via the oral route (ingestion), inhalation, dermal contact, and the parenteral route [25–27]. The most important route of exposure to arsenic is the ingestion of foods and beverages, which in most cases are contaminated from the use of irrigation water with a high concentration of the element. In general, the water is contaminated by dissolved minerals and contains different

> Arsenic occurs in both inorganic and organic forms, which exhibit large differences in their metabolism and toxicity. The high toxicity of arsenic is well known because arsenic compounds are readily absorbed

forms of arsenic [24]. Exposure to arsenic occurs via the oral route (ingestion), inhalation, dermal contact, and the parenteral route [25–27].

Arsenic occurs in both inorganic and organic forms, which exhibit large differences in their metabolism and toxicity. The high toxicity of arsenic is well known because arsenic compounds are readily absorbed by either inhalation or ingestion, the extent of absorption being dependent upon the solubility of the compound.

#### **2.5. Metabolism or transformation in the living system**

There is evidence that arsenic has a physiological role related to methionine metabolism [28]. However, the site of action of arsenic remains unknown. Studies with rats fed adequate amino acid–based diets have shown that arsenic deprivation had little effect on growth in rats. However, in rats fed suboptimal methionine, arsenic deprivation resulted in a significant reduction in body weight. It was shown that arsenic deprivation reduces the hepatic concen‐ tration of *S*-adenosylmethionine, indicating that arsenic maintains the metabolic pool of *S*adenosylmethionine [28].

In addition, arsenic status affects DNA methylation in animal and cell culture models, resulting in an apparent hypomethylation of DNA [29]. This process is associated with an increased incidence of cancer. So, there is an amount of dietary arsenic that is harmful or beneficial to humans [30, 31].

#### **2.6. Biological functions**

In body, arsenic is present as arsenite and arsenate. Arsenic species interact strongly with sulfhydryl groups of organic molecules. It affects several enzymes, causing damage in several cell systems. Because of their similar properties, arsenate can substitute for phosphate and other phosphate intermediates in several biochemical reactions. At the cellular level, arsenate depletes adenosine triphosphate (ATP) in human erythrocytes, interrupting the production of energy [31, 32].

Although some research has indicated that arsenic is an essential nutrient for rats, chickens, and pigs, however, no studies have been published in the literature to determine the nutritional importance of arsenic in humans [32].

#### **2.7. Mechanisms of toxicity of arsenic**

The toxicity of arsenic is highly influenced by its oxidation state and solubility, as well as many other factors [33]. As(III) binds to thiol or sulfhydryl groups on proteins and can inactivate over 200 enzymes. As(V) can replace phosphate, which is involved in many biochemical pathways [34].

Mechanism by which arsenic exerts its toxic effect is due its ability to interact with sulfhydryl groups of proteins and enzymes and to substitute phosphorous in various biochemical reactions [34].

In humans, As(III) is methylated to two major metabolites via a non-enzymatic process to monomethylarsonic acid (MMA), which is further methylated enzymatically to dimethyl arsenic acid (DMA) before excretion in the urine [34].

Various hypotheses have been proposed to explain the carcinogenicity of inorganic arsenic. Nevertheless, the molecular mechanisms by which this arsenic induces cancer are still poorly understood [35, 36].

#### **2.8. Incidence of (acute and chronic) toxicity**

Arsenic can cause numerous human health effects. Several epidemiological studies have reported a strong association between arsenic exposure and increased risks of both carcino‐ genic and systemic health effects [25]. The severity of adverse health effects is related to the chemical form of arsenic and is also time and dose dependent [26, 37, 38]. Among the notable effects and diseases are skin lesions, neurotoxicity, cardiovascular diseases, abnormal glucose metabolism, diabetes, peripheral vascular diseases, coronary heart diseases, myocardial infarction, stroke, gangrene, kidney failure and liver failure, cancer of the internal organs, particularly the bladder and lung, skin pigmentation, keratoses, and skin cancer [24, 26, 34–37].

#### **2.9. Comparative analysis of analytical techniques**

Several techniques have been used for the detection of arsenic in foods. Among the combined techniques are the use of chromatography or inductively coupled plasma coupled with mass spectrometry (MS) [39], mass spectrometry–desorption electrospray ionization (MS-DESI) spectrometry, inductively coupled plasma–optical emission spectrometry (ICP-OES), and hydride generation–atomic absorption spectrometry (HG-AAS) [39, 40], which generally allow the chemical speciation of arsenic and other techniques such as capillary electrophoresis coupled to inductively coupled plasma and mass spectrometry (CE-ICP-MS) [41]. However, these techniques are expensive. In this regard, an interesting approach to determining arsenic species with detection by electrothermal atomic absorption spectrometry after cloud point extraction (ETAAS/CPE) was developed by Baig *et al.* [42] and Costa *et al.* [43].
