Systematic review of the potential respiratory carcinogenicity of metallic nickel in humans

Crit Rev Toxicol. 2020 Aug;50(7):605-639. doi: 10.1080/10408444.2020.1803792.


The inhalation of dust containing certain nickel compounds has been associated with an increased risk of lung and nasal cancers in occupational studies of workers who process or refine sulfidic nickel ores and are exposed to relatively high levels of mixtures of water-soluble, sulfidic, oxidic, and/or metallic forms of nickel. We conducted a systematic review of the potential carcinogenicity of metallic nickel, focusing on cancers of the respiratory tract. We evaluated the quality and risk of bias (RoB) of the relevant epidemiology, experimental animal, and in vitro mechanistic studies using the National Toxicology Program's Office of Health Assessment and Translation (OHAT) RoB Rating Tool. We then used a systematic review protocol based on the OHAT approach to critically assess whether metallic nickel should be considered a human respiratory carcinogen. Our evaluation of the epidemiology studies indicates that there is no substantive evidence of increased respiratory cancer risk in workers exposed predominantly to metallic nickel. Animal evidence indicates that metallic nickel does not increase the incidence of respiratory tumors in rodents exposed by inhalation. The in vitro studies are limited in value, as they bypass normal clearance mechanisms. Nevertheless, the mechanistic evidence indicates that metallic nickel is not mutagenic but can induce DNA strand breaks under certain conditions. Based on a standard framework for assessing causality, we conclude that the evidence does not support a causal relationship between metallic nickel exposure and respiratory cancer in humans.

Keywords: Nickel; cancer bioassay; causal framework; epidemiology; metal; mutagenicity; respiratory cancer; risk assessment; risk of bias; study quality; systematic review; weight of evidence.

Publication types

  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Air Pollutants, Occupational / analysis*
  • Carcinogens / toxicity*
  • Humans
  • Inhalation Exposure / statistics & numerical data*
  • Nickel / toxicity*
  • Occupational Exposure / statistics & numerical data*


  • Air Pollutants, Occupational
  • Carcinogens
  • Nickel