Nickel

In 1990, the International Agency for Cancer Research (IARC) concluded that nickel compounds were human carcinogens, and in 2009 affirmed the Group 1 carcinogenicity of both soluble and insoluble nickel in 2009 (IARC, 2012). Studies of the underlying molecular and epigenetic pathways reviewed in this chapter show that nickel compounds are both genotoxic and epigenotoxic, especially when cells are chronically exposed for long durations of up to several weeks to allow sufficient nickel uptake, with some persistent effects remaining even after withdrawal of the nickel exposure. This chapter offers a fresh review of the most recent information on global nickel production and use, biological uptake across all species, metabolism, environmental and occupational exposures and exposure limits, and human disease epidemiology, focusing on some of the newest literature in the areas of environmental exposures, nickel-induced allergies, reproductive effects, nanoparticles, and e-cigarette exposures. Updated information on the epigenetic mechanisms of nickel's action and carcinogenic actions are summarized here, and further reading of recent literature reviews on nickel can supplement this chapter (Chen and Costa, 2017; Buxton et al., 2019; Chen et al., 2020). Additional knowledge can also be gained from Chapter 11, Volume I, Selected Molecular Mechanisms of Metal Toxicity and Carcinogenicity. Furthermore, additional details on the carcinogenicity and mechanisms of carcinogenesis related to nickel exposure can be gleaned from Chapter 23, Volume I of this handbook, Carcinogenicity of Metal Compounds.