Toxicity of nitrous oxide

Best Pract Res Clin Anaesthesiol. 2003 Mar;17(1):47-61. doi: 10.1053/bean.2002.0264.


Nitrous oxide interacts with vitamin B12 resulting in selective inhibition of methionine synthase, a key enzyme in methionine and folate metabolism. Thus, nitrous oxide may alter one-carbon and methyl-group transfer most important for DNA, purine and thymidylate synthesis. Long-term exposure to high concentrations of nitrous oxide may cause megaloblastic bone-marrow depression and neurological symptoms. Exposure to higher doses for less than 6 hours, as in clinical anaesthesia, are considered harmless. Recent studies seem to suggest a correlation between nitrous oxide anaesthesia and hyperhomocysteinaemia which is accepted to be an independent risk factor for coronary artery disease. As for today, available data do not support the notion that exposure to trace amounts of nitrous oxide is associated with impaired fertility or an increased risk of developing cancer. Emission of nitrous oxide from medical use is estimated to contribute less than 0.05% to total annual greenhouse gas emission.

Publication types

  • Review

MeSH terms

  • Animals
  • Bone Marrow / drug effects
  • Folic Acid Deficiency / chemically induced
  • Humans
  • Methionine / metabolism
  • Nervous System Diseases / chemically induced
  • Nitrous Oxide / adverse effects*
  • Occupational Exposure / adverse effects
  • Vitamin B 12 / physiology
  • Vitamin B 12 Deficiency / chemically induced


  • Methionine
  • Nitrous Oxide
  • Vitamin B 12