# The Double Face of Metals: The Intriguing Case of Chromium
## 6 Toxicity of Chromium(VI)  
Hexavalent chromium (Cr(VI)) toxicity relies on its strong oxidizing ability and easy absorption by the cells through nonspecific anion carrier proteins [38; 39; 42]. After entering cells, hexavalent chromium may be quickly converted into the trivalent form, leading to the generation of reactive chromium intermediates and oxygen species that can alter normal cellular function and promote apoptosis [86; 87]. Cr(VI) is both mutagenic and carcinogenic to humans [38]. The first report of cancer in workers exposed to chromium is dated to about 130 years ago; after that, Cr(VI) compounds appeared in the inventory of potential chemical hazards to human health. Cr(VI) has been classified as a human carcinogen by the International Agency for Research on Cancer [24]. Cr(VI) concentrations in the general population vary depending on the territories and areas considered [88; 89; 90; 91]. Rural or suburban air generally contains lower concentrations of chromium than urban air (\(<\)10 ng/m\({}^{3}\) in rural areas; 0-30 ng/m\({}^{3}\) in urban areas). As a result of smoking, indoor air contaminated with Cr(VI) can be 10\(-\)400 times greater than outdoor air concentrations [88]. A plausible route of exposure to Cr(VI) may be via tap water at concentrations well in excess of the U.S. Environmental Protection Agency (USEPA) maximum contaminant level of 100 microg/L (ppb) [92]. Recently, [PERSON] et al. reported EU legislation with respect to the discharge limits into the aquatic environment for Cr(III) and Cr(VI) in comparison to the limits in other parts of the World [93]. In recent years, high concentrations of chromium in various natural systems such as atmosphere, pedosphere, hydrosphere, and biosphere have become a global issue, leading to severe deteriorating effects on different microorganisms, plants, and animals [94]. Chromium is absorbed by plants through carriers of essential ions such as sulfate. Symptoms of chromium toxicity in plants comprise decreased germination, reduction of growth, inhibition of enzymatic activities, impairment of photosynthesis and oxidative imbalances [95]. Chromium and its particulates are also released into the oceanic medium in effluent released from ventures like tanneries, materials, mining, coloring, printing, photographic and medicinal industries [96]. Chromium destabilizes the marine ecosystem due to its toxic impact on biota and bioaccumulation in certain organisms. Occurrence of chromium varies in fishes, depending on their age, development as well as other physiological variables. It induces cytotoxicity and detrimental impact on the behavior of fish, such as hypertrophy and paraplegia at gill epithelium, uneven swimming and suspended feeding [97]. Recently, it has been demonstrated that chromate ions may be adsorbed by schwertmannite, a Fe(III)-oxyhydroxysulfate mineral, precipitated over the pH range of 2.8-4.5 in acid mine drainage and acid rock drainage. Extremely high levels of chromium (812 mg/kg) were enriched in acid mine drainage sediments where schwertmannite formed [98,99]. The main mechanisms related to cellular damage caused by Cr(VI) include high oxidative stress, chromosome breaks, and DNA adduct production. Cr(VI) is a known irritant and skin sensitizer and can easily penetrate the skin, thus causing inflammation and contact dermatitis [76]. Cr(VI) is reduced by proteins or intracellular antioxidants to Cr(III), which, being a hapten, intercalates into DNA or proteins, leading to toxicity as a result. [PERSON] et al. (2010) demonstrated Mr(VI) may enhance the generation of ROS inside the cells and stimulate the NF-\(\kappa\)B, Akt and MAPK signaling cascades, resulting in higher formation of TNF-\(\alpha\) and IL-1\(\alpha\) in keratinocyte in vitro and in a guinea pig in vivo [100]. In 2018, the same authors documented that pterostilbene, a natural compound known for its antioxidant properties, mitigated Cr(VI)-induced skin inflammation by inhibiting TNF-\(\alpha\) and NLRP3-inflammatory (IL-1\(\beta\)) in mice [101].