**4.6 Lead**

In contrast to manganese or nickel, lead is not a trace element and is well known to be toxic [90]. In general, absorption by ingestion is the predominant route of exposure to lead. After ingestion, lead absorbed from the gastrointestinal tract enters the bloodstream by attaching to red blood cells, which transport it to various tissues or organs in the body [91]. This distribution of Pb in the body is independent of the route of absorption. As it cannot be destroyed in the body, lead accumulates in the bones. In fact, in adults, more than 90% of the lead present in the body is stored in the adult bones, compared with 70% in children. However, certain phenomena such as pregnancy, breastfeeding, menopause and osteoporosis increase the passage of lead from the bones to the blood [92, 93].

The mechanism of lead toxicity is manifested by the ability of this metal to replace cations such as Ca2+, Mg2+, Fe2+ Na + that have important functions in the cell [94, 95]. This disrupts the metabolism of the cell and leads to significant changes in various biological processes such as cell adhesion, intra- and intercellular signalling, protein folding, ion transport, enzyme regulation and neurotransmitter release. Furthermore, this substitution may also affect protein kinase C, which regulates neuronal excitation and memory storage [96]. These phenomena will therefore lead to adverse effects on human health regardless of the age group, even if infants and young children are more at risk [96, 97]. Organic forms are more toxic to humans than inorganic forms of lead. These reach humans through the food chain [93]. The pathologies resulting from lead poisoning are numerous and can be separated into two categories: physiological disorders and neurological disorders [53]. About physiological disorders [98], demonstrated that an average concentration of 29 μg.L−1 caused arterial hypertension in men. Studies have also shown that blood lead concentrations below 100 μg.L−1 are associated with kidney failure [98]. Moreover, according to Robert and et al., in 2004 [99] prolonged exposure to lead can cause sterility or serious problems for the fetus in the case of a pregnant woman. There are numerous studies demonstrating the existence of neurotoxic effects of lead in adults and children. According to Oscar and al, 2017 and Sanders and al, 2009 [53, 101], lead is believed to cause a decrease in intelligence quotient in children. Also, in their studies, Hsiang and Díaz in 2011, [102] showed that this metal was the basis of neurological dysfunctions and neurodegenerative effects. According to the same authors, these disorders generally follow chronic exposure to lead. In addition, other studies have shown disturbances in cognitive and behavioural functions, resulting from changes in the brain caused by lead poisoning [100]. According to these authors, children were more affected by these disorders than adults. Also, lead poisoning leads to lead

poisoning, which manifests itself by anaemia, digestive disorders and damage to the nervous system with memory loss and disturbances in cognitive and behavioural functions [103].

#### **4.7 Zinc**

The absorption of zinc after ingestion takes place in the central part of the small intestine (jejunum). Zinc is transported by metallothionein from the enterocytes to the blood. In the blood, zinc is bound to albumin which distributes it throughout the body [104]. As an essential element for living beings, it plays a major role in cellular metabolism. It is involved in enzymatic systems either as an integral part of the active site of numerous enzymes or as a cofactor regulating the activity of so-called "zinc-dependent" enzymes [32]. Zinc is therefore an essential micronutrient for human health [105]. This metal is involved in major metabolic pathways through its role in enzyme systems. It is also essential in the structure and function of a large number of macromolecules. It is implicated in gene expression and stabilises the structure of proteins [106]. Zinc also plays a role in cell signalling, hormone release and nerve transmission.

However, at high concentrations of zinc in the body, the concentration of metallothionein increases to regulate zinc. This leads to a decrease in the concentration of certain metals such as copper, whose homeostasis is ensured by metallothionein. This leads to a malfunction in the metabolism of copper, which can have several adverse effects. It is true that the acute toxicity of Zn is found in rare abnormal food conditions (poisoning). According to studies, several cases of gastrointestinal disturbances and diarrhea have been caused by high zinc ingestion [107, 108]. In a study by Samman and Roberts in 1989, and reported by the US Environmental Protection Agency [109] symptoms such as abdominal cramps, vomiting and nausea appeared in 26 of 47 healthy volunteers after six-week ingestion of zinc sulphate tablets, containing 150 mg.kg−1 of elemental zinc, for six weeks.

In addition, Gary in 1990 [110], stated that an ingestion of 1–2 g of zinc sulphate would have resulted in a concentration of nausea and vomiting, epigastric pain, abdominal cramps and diarrhoea (often bloody), while a young boy who ingested 12 g of elemental zinc over two days suffered only lethargy, dizziness, a slight shift in gait and difficulty in writing. These studies also show that the acute effects of zinc also depend on the form of zinc ingested.

In addition, chronic toxicity can manifest itself in bone marrow effects and polyneuropathy due to concomitant copper deficiency. It may also manifest itself as anaemia resulting from the malfunction of copper metabolism. Also, excessive zinc intake over a prolonged period of time increases the risk of prostate cancer and prostate cancer-related mortality [111].
