**4. Toxicological profile of metallic trace elements through dietary intake**

#### **4.1 Cadmium**

Food is one of the main sources of cadmium exposure [29]. After absorption from the gastrointestinal tract, cadmium is transported into the blood plasma, initially bound to albumin [33, 34]. Albumin-bound cadmium is preferentially absorbed by the liver.

In the liver, cadmium induces the synthesis of metallothionein and a few days after exposure, cadmium bound to metallothionein appears in the blood plasma. Due to the low molecular weight of metallothionein, this protein transports cadmium to the tubules via the glomerulus of the kidney. Cadmium then accumulates in the human kidney throughout life [35–37]. The accumulation of cadmium in the kidneys leads to the most serious chronic effect of oral cadmium exposure, which is renal toxicity. This critical effect is characterised by tubular proteinuria resulting from renal tubular dysfunction [38]. In addition, the fixation of cadmium to albumin can lead to the disruption of calcium, zinc and iron homeostasis [39]. This lack of stability of calcium, zinc and iron concentration is capable of causing liver damage.

In addition, the disruption of calcium homeostasis due to the decrease in serum parathyroid hormone (PTH) concentration induces the release of calcium from bone tissue [40, 41]. This leads to loss of strength and bone fracture. Also, having the same oxidation states as zinc, cadmium can replace the zinc present in metallothionein (MT), thus preventing this protein from acting as a free radical scavenger in the cell [42].

According to Andujar, et al., 2010 [43], cadmium also has cardiovascular, hematological and hepatic effects. Inaba et al., 2005 [44], showed that cadmium was responsible for Itaï-Itaï disease, which occurred after long exposure to a concentration of up to 1 ppm. All these health effects have led to a very low tolerable daily intake of

0.36 μg.kg−1 is proposed by the National Agency for Food, Environmental and Health Safety [45]. Note that acute cadmium toxicity is very rare and requires very high concentrations.
