**3.6 Toxicity of chromium (Cr)**

Chromium exists in environment in oxidation states and from Cr+2 to Cr+6 [1, 3, 5, 22, 63]. It does not exist in elementary state (Cr0 ) [3, 22]. Trivalent oxidation state of Cr is considered more stable, followed by Cr+4. The most commonly forms are Cr+3 and Cr+6, both oxidation states being toxic to animals, humans and plants [5, 63].

Cr+3 is immobile and insoluble in water, while Cr+6 is mobile and highly soluble in water [1, 13]. The solubility of chromium depends on its pH, Cr+3 is soluble only in acidic pH, while in neutral and alkaline pH, Cr+3 gets precipitated [23].

Environmental contamination with it, occurs by oil burning, catalyst, pigments production, chromium steel, tannery facilities, but also fertilizers and sewage, because is extensively used in several industries, like metallurgy, refractory, tannins, production of paints and pigments, pulp and paper production, wood preservation [1, 9, 22]. Chromium released by the anthropogenic activities in the environment occurs mainly in the hexavalent form [22].

Human exposure occurs through ingestion of food and water which contain, inhalation, especially in case of occupational workers or by dermal contact [5, 64]. Through their bioaccumulation in the body, a variety of affections can appear, such as, dermal, renal, neurological and gastrointestinal diseases, but also development of several types of cancer, on lung, larynx, kidney, testicles, bones, bladder, thyroid [5, 65]. Chromium can affect the reproductive function in men, due to sperm count decline [19]. Ingestion of drinking water containing high level of chromium may cause tumor in stomach [3]. The target organs are lungs, but significant chromium exposure can take place through skin [3, 22].

Occupational exposure to chromium increases the risk of cancer of lung, liver, gastrointestinal tract and central nervous system, while in female workers cause abortion [3, 13, 38]. Excess of chromium can produce thyroid cancer through reduction of requirement level of thyroid hormone in the body, disrupting hormones synthesis and secretion, interfering in its metabolism or interaction with their receptors [3, 66].

Some humans are sensitive to Cr3+ and after exposure allergic reactions, including redness and swelling of the skin, can appear. This oxidation state is poorly absorbed by any way, the toxicity being attributable to Cr+6 oxidation form [22].

Ingestion of Cr+4 can cause irritation and ulcer of stomach and small intestine, anemia, disfunctions of male reproductive system and at high dose produces sever problems on nervous, respiratory and cardiovascular systems, digestive organs, excretory function [3]. Researcher studies demonstrated that high levels in water were associated with cancers of liver, lung and genitourinary system [5, 67].

Cr+6 can produce adverse effects on excretory system, reproductive system, asthma, allergy, irritation and ulcers in the stomach and small intestine, anemia, increased mortality due the development of cancer of lung, larynx, kidney, testicular, thyroid, bones [3, 5, 22, 68], and in case of excess inhalation appear irritation and ulcer of nose [3, 22]. Also, it can reduce the DNA replication, damage DNA transcription, chromosome aberrations and affection of RNA [3, 5, 69]. Inside the cell, Cr+6 is converted into Cr+5, as intermediate, and then in Cr+3, which can form complexes with proteins and DNA [1, 3]. Cr+5 and other intermediate compounds, including reactive species of carbon and oxygen, that form during the reduction of Cr+6 to Cr+3, can react with DNA [3]. When hexavalent cation reacts with cellular reductants, Cr+4 and Cr+3 can also be obtained. Cr+6 was classified as group I occupational carcinogen [5, 70].

In cell, mechanism of chromium toxicity generates reactive oxygen species (ROS), which bring cell apoptosis, damage of DNA, genomic instability [3, 5, 71], suppression of DNA synthesis and genes expression [3], but also induces hyperexpression of some antioxidant enzymes, such as, peroxidase, catalase, superoxide dismutase [23].

Their carcinogenicity and toxicity depend of concentration, time of exposure, tissue and cell type [5, 72], route of exposure (ingestion, inhalation or dermal) [10], generation of free radicals [5, 73], oxidation state and its reactivity [5, 10, 22],
