**3. Chromium**

#### **3.1. Chemistry of chromium**

Cr is a naturally occurring element present in the earth's crust and is found in two oxidation states, namely hexavalent chromium (Cr(VI)) and trivalent chromium (Cr(III)). Hexavalent chromium (Cr(VI)) compounds are, in general, more toxic than Cr(III) compounds. Cr rarely occurs as a pure element. The most common ore of Cr is ferrochromite [44, 45].

#### **3.2. Occurrence in the environment**

Cr is an element available in the environment, found mostly in minerals, rocks, plants, soil, water, dust, and volcanic gases. Cr can be present as a contaminant in the environment from various natural and anthropogenic sources [46]. Cr released into the environment as anthro‐ pogenic activity occurs mainly from metallurgical and chemical industries such as tannery facilities, chromate production, stainless steel welding, and ferrochrome and chrome pigment production.

The health hazard associated with exposure to Cr depends on its oxidation state, ranging from the low toxicity of the Cr(III) form to the high toxicity of the Cr(VI) form [47]. Cr(III) is an essential trace mineral present in trace amounts in some foods, such as meat, whole grains, oleaginous plants, and legumes.

#### **3.3. Dietary sources of chromium**

Cr(III) is considered to be essential to mammals for the maintenance of glucose, protein, and lipid metabolism, whereas Cr(VI) is detrimental to human health even at relatively low concentration levels, because it can be involved in the pathogenesis of some diseases such as liver, kidney, lung, and gastrointestinal cancers [48–50]. Cr(III) is a stable and biologically active state of Cr, and it is found in many types of foods, including egg yolk, whole grains, cereals, coffee, nuts, green beans, broccoli, meat, beer yeast, and drinks produced from grapes. Cr is also available in many dietary supplements and is responsible for the proper functioning of the metabolism of carbohydrates and lipids. Table 1 shows the amounts of Cr that can be found in some foods.


a Adapted source by NHI [51].

b Adapted source by Oliveira and Machine [52].

c Adapted source by Cabrera-Vique *et al*. [53].

**Table 1.** Quantity of chromium in some foods.

#### **3.4. Routes of entry into plants, animals, and humans**

Cr-containing compounds have been a major concern because of Cr release into the environ‐ ment and the high risk of Cr-induced diseases in industrial workers occupationally exposed to Cr(VI) [54]. The route of human exposure to Cr is through skin and mainly through inhalation, and the lung is the target organ [55–57]. Non-occupational exposure occurs through ingestion of Cr- containing food and water. Cr content in foods varies greatly and depends on the processing and preparation of foods.

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

The main path for Cr(III) to get into the organism is through the digestive system. The mechanism of Cr intestinal absorption is not yet fully known, but it is known that Cr(VI) compounds are absorbed better than Cr(III) compounds. Absorbed Cr circulates in blood bound to the β-globulin plasma fraction and is transported to tissues bound to transferrin or other complexes at the physiological concentration [58]. Cr from blood is relatively quickly absorbed by bones, accumulating also in the spleen, liver, and kidneys. Cr is excreted especially by the urinary system.

#### **3.6. Biological functions**

Cr plays an important role in carbohydrate, lipid, and glucose metabolism [58–60]. Studies show evidence that Cr acts as a cofactor for insulin, and therefore, Cr activity in the organism is parallel to insulin functions. It is assumed that the activity of Cr is mediated by the anabolic action of insulin. Cr supplementation intensifies amino acid uptake by tissues such as these the binding of Cr to nucleic acids is stronger than in other metal ions [60]. Cr(III) seems to be involved in the structure and expression of genetic information in animals. Also, Cr protects RNA from heat denaturation and, among other functions, promotes the growth of the animals.

#### **3.7. Mechanisms of toxicity of chromium**

The toxicity of Cr compounds depends on its oxidation state and solubility [61–63]. Cr(VI) compounds are more toxic than Cr(III) compounds most likely due to the ease with which Cr(VI) can pass through cell membranes and its subsequent intracellular reduction to reactive intermediates [64–66]. As Cr(III) is poorly absorbed by any route, the reduction of Cr(VI) is considered as being a detoxification process. If Cr(VI) is reduced to Cr(III) extracellularlly, then Cr(III) is not readily transported into cells, and so toxicity is not observed. Under physiological conditions, Cr(VI) can be reduced Cr(III) by hydrogen peroxide (H2O2), glutathione (GSH) reductase, ascorbic acid, and GSH [66, 67].

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

Cr is of particular interest because its toxicity is highly dependent upon its chemical forms and concentration. Cr(VI) shows high toxicity and is related to clinical cases such as nasal irritation and ulceration, hypersensitivity reactions, and dermatitis through contact. The lethal dose is between 50 and 100 mg kg−1, which is much lower than that of Cr(III), with a lethal dose between 1900 and 3300 mg kg−1 (both cases tested by oral ingestion in rats). Furthermore, Cr(VI) is classified as carcinogenic because it penetrates the cell membranes of living organisms [59]. Exposure to Cr(VI) can occur mostly through inhalation, skin contact, and ingestion. Cr(VI) inhalation, for example, besides causing severe irritation of the respiration system, is also carcinogenic. Although the WHO has established a limit for human consumption of 0.005 mg kg−1 body weight per day, no scientific studies have proved that Cr ingestion can cause disease. The potential effects of Cr(VI) vary mainly with the species, the amount absorbed into the bloodstream, and the route and duration of exposure [68–70]. Thus, Cr(VI) is found in most lists of high-toxicity elements for which strict control procedures apply. The difficulty in establishing a recommended dietary allowance (RDA) for Cr is mainly due to the limitations related to estimating the ingestion levels of this mineral, which range from the absence of data on the amount of Cr present in foods, due to analytical difficulties given the trace concentra‐ tions, to environmental contamination problems [70].

The ingestion of Cr(VI) is detrimental to human health even at relatively low concentration levels because it may be involved in the pathogenesis of some diseases, such as liver, kidney, lung, and gastrointestinal cancers. Following studies, many authors have suggested that chromium picolinate can cause DNA damage [60, 61], but there is no confirmation of carcino‐ genesis in animals [62]. There are reports of toxicity after supplementation, but the results of other investigations did not indicate hepatic alterations [64–70]. Based on this impasse, the US Agency of Toxic Substance and Disease Registration concluded that there is no conclusive evidence that supplementation causes liver damage, although it does have proven deleterious effects on the kidneys [67].

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

The determination of Cr can be carried out through sensitive techniques that are able to quantify a few micrograms of this element. One of these techniques is graphite furnace–atomic absorption (GF-AAS), consolidated after 1981, and is able to detect Cr concentrations of around 0.2 μg kg−1 in food. More sensitive techniques developed later, such as ICP-MS and ICP-OES [71], are used for the determination of Cr. These techniques quantify only total Cr without promoting speciation, and separation techniques, such as chromatography, are required.

The official method for the analysis of Cr in food samples is ICP-OES using nitric acid and hydrogen peroxide to oxidize organic materials in food samples [71]. This technique has high sensitivity (of the order of 1 ng L−1). However, this equipment is sophisticated and expen‐ sive with high operational costs. An option that combines higher sensitivity and lower cost is GF-AAS technique. This technique has important advantages such as a reduced amount of sample and high sensitivity, and the analysis can be carried out with minimal or no sample preparation [71].
