Increased lung cancer risks are similar whether arsenic is ingested or inhaled

J Expo Sci Environ Epidemiol. 2009 May;19(4):343-8. doi: 10.1038/jes.2008.73. Epub 2009 Feb 4.


In 1980, the International Agency for Research on Cancer (IARC) determined there was sufficient evidence to support that inorganic arsenic was a human lung carcinogen based on studies involving exposure through inhalation. In 2004, IARC listed arsenic in drinking water as a cause of lung cancer, making arsenic the first substance established to cause human cancer through two unrelated pathways of exposure. It may initially seem counterintuitive that arsenic in drinking water would cause human lung cancer, and even if it did, one might expect risks to be orders of magnitude lower than those from direct inhalation into the lungs. In this paper, we consider lung cancer dose-response relationships for inhalation and ingestion of arsenic by focusing on two key studies, a cohort mortality study in the United States involving Tacoma smelter workers inhaling arsenic, and a lung cancer case-control study involving ingestion of arsenic in drinking water in northern Chile. When exposure was assessed based on the absorbed dose identified by concentrations of arsenic in urine, there was very little difference in the dose-response findings for lung cancer relative risks between inhalation and ingestion. The lung cancer mortality rate ratio estimate was 8.0 (95% CI 3.2-16.5, P<0.001) for an average urine concentration of 1179 microg/l after inhalation, and the odds ratio estimate of the lung cancer incidence rate ratio was 7.1 (95% CI 3.4-14.8, P<0.001) for an estimated average urine concentration of 825 microg/l following ingestion. The slopes of the linear dose-response relationships between excess relative risk (RR-1) for lung cancer and urinary arsenic concentration were similar for the two routes of exposure. We conclude that lung cancer risks probably depend on absorbed dose, and not on whether inorganic arsenic is ingested or inhaled.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Oral
  • Arsenic / administration & dosage
  • Arsenic / toxicity*
  • Carcinogens / administration & dosage
  • Carcinogens / toxicity*
  • Case-Control Studies
  • Cohort Studies
  • Dose-Response Relationship, Drug
  • Humans
  • Inhalation Exposure
  • Lung Neoplasms / chemically induced*
  • Risk Assessment


  • Carcinogens
  • Arsenic