**4.3 Copper**

Copper is an essential element for good health and the proper functioning of certain biological processes [55]. Copper in food can be in monovalent Cu (I) or divalent (Cu (II)) form [56]. The predominantly active copper uptake involves the copper transporter 1 (Ctr1) which is specific for the transport of monovalent copper (CuI) into cells (including gastrointestinal cells). Copper absorption occurs mainly in the small intestine and is likely to be inhibited by transition metals such as iron or zinc [57–59]. Copper absorbed by the small intestine is transported in the blood by binding mainly to albumin, but also transcuprein [60]. Copper is transported to the liver and can be stored in hepatocytes. Copper present in hepatocytes is mainly linked to metallothionein or transcuprein [61].

Once absorbed into the body, plays a particularly important role in seed production, disease resistance and water regulation in plants [62, 63]. As a result, it participates in various metabolic processes and maintains the functions of organisms. However, the transition of copper from its oxidised to its reduced form can lead to the production of superoxide and hydroxyl radicals which cause damage to the body [60]. Indeed, Myers and al, 1993; Sokol and al 1933 [64, 65] have shown in studies on rats that at high concentrations of copper, these radicals can attack the cell's membrane lipids. As a result, copper disrupts the total antioxidant capacity of the body [63, 66]. Free radicals from copper reduction also tend to be responsible for amyotrophic lateral sclerosis, which results in progressive muscle paralysis [67].

According to Ellingsen and al, 2015 [68], nausea is the most frequently observed symptom of acute copper toxicity. These authors showed that the minimum concentration that can cause nausea is 4 mg.L−1. In addition, Araya and al, 2007 [69], have shown that acute effects from a single, short-term exposure to copper result in gastrointestinal manifestations.

#### **4.4 Manganese**

After ingestion manganese is absorbed in the gastrointestinal (GI) tract by passive diffusion or by active transport by divalent metal transporter 1 (DMT1), which transports other metals such as iron, copper, zinc and calcium [70]. Manganese is then distributed through the bloodstream to the liver, pancreas, bones, kidneys, brain, colon, urinary system and erythrocytes [71]. The amount of manganese absorbed from the gastrointestinal tract in humans is variable, but generally averages around 3–5% [72].

As an essential nutrient, absorbed manganese plays many physiological roles. Manganese is required for the formation of cartilage and healthy bones and for the urea cycle, and also plays a key role in wound healing [73, 74].

However, once absorbed at high concentrations, manganese can exhibit various toxic effects, of which neurotoxicity is a prominent one. Mn neurotoxicity may be associated with the interaction with other essential trace elements, including iron [75–77]. Indeed, according to the work of Olanow [78], when neurons are exposed to a high concentration of manganese, the cellular regulation of iron by the divalent metal transporter 1 (DMT1) decreases, in favour of that of manganese. This leads to an accumulation of iron in neurons and can consequently produce cellular oxidative stress that leads to neuronal damage [77, 79]. In addition, in studies on rats, Mohammad [80] found a delay in the development of the skeleton and fetal organs in pups born to pregnant rats exposed to manganese by gavage at a dose of 33 mg.kg−1. d−1. Also, Bouabid et al. in 2016 [81], showed that during ingestion of high concentrations of manganese, a decrease in neurological activity was observed in rats.

### **4.5 Nickel**

Once absorbed into the bloodstream, nickel is bound to albumin. It can therefore go to all organs, such as the thyroid and adrenal glands, brain, kidneys, heart, liver, spleen and pancreas [82, 83]. This mobility confers beneficial effects on the body. In humans, nickel is involved in the metabolism of methionine, an amino acid involved in protein synthesis [84].

Although, easily eliminated from the body in faeces and urine, nickel can also have adverse health effects. Indeed, at high concentrations, much of the toxicity of nickel may be associated with its interference with the physiological processes of zinc, calcium and magnesium [85]. Nickel can thus replace magnesium in certain stages of complement activation. For example, replacing nickel with magnesium can increase the formation of the C3b enzyme by 40-fold, which amplifies the activation of the complement pathway [86]. Therefore, various disease states such as myocardial infarction and stroke are associated with altered transport and serum concentrations of nickel [86].

Aleksandra and Urszula in 2011 [87], reported that an accidental ingestion of 570 mg of nickel had caused cardiovascular effects and the death of a child who had 2 years old. It should be noted that the acute toxicity of nickel after oral exposure

#### *The Toxicity of Environmental Pollutants DOI: http://dx.doi.org/10.5772/intechopen.104088*

depends on the chemical form of nickel. For example, a death due to nickel-induced adult respiratory distress syndrome was reported in a worker spraying nickel using a thermal arc process [88]. The death occurred 13 days after a 90-minute exposure to an estimated nickel concentration of 382.1 mg/m3; the total nickel intake was estimated to be nearly one gram. Furthermore, Das et al. in 2002 [89], in a study on rats, demonstrated a decrease in body weight in rats after daily intakes of 8.6 mg.kg−1.d−1 for 91 days. According to some authors [85, 89], gastrointestinal disorders consisting of nausea, abdominal cramps, diarrhoea, and vomiting have been reported in workers who consumed water contaminated with nickel sulphate. To our knowledge, no study has demonstrated a carcinogenic effect of nickel, nor chronic toxicity of nickel on human health.
