Risks of Nitrous Oxide

  • Kunal Gupta
  • Amit Sethi


Are there any risks associated with nitrous oxide? Is nitrous oxide a health hazard for dentists and their staff? Any such risk or hazard is related to the leakage of nitrous oxide from various sources in a dental office. Factors governing the concentration of nitrous oxide in ambient air of operatory have been enlisted along with a stepwise description on its measurement. This chapter talks about the recommended level of nitrous oxide in an operatory, in different countries, followed by the steps to minimize the level. “Safe practice controls” when working with nitrous oxide in order to curtail the exposure of team members are highlighted. Questions related to the safety of nitrous oxide around mothers or staff members who could be pregnant are answered. Pictorial explanation of biochemical basis of hazards related to nitrous oxide, has been done accompanied with the description of effects, if any, on the various systems of human body.


Nitrous oxide hazard Nitrous oxide diffusive sampling Occupational exposure limit Methionine synthase MTHFR deficiency 


  1. 1.
    Yagiela JA. Health hazards and nitrous oxide: a time for reappraisal. Anesth Prog. 1991;38(1):1–11.PubMedPubMedCentralGoogle Scholar
  2. 2.
    Vaisman AI. Working conditions in surgery and their effect on the health of anesthesiologists (in Russian). Eksp Khir Anesteziol. 1967;3:44–9.Google Scholar
  3. 3.
    Ericson HA, Killen AJB. Hospitalization for miscarriage and delivery outcome among Swedish nurses working in operating rooms 1973-1978. Anesth Analg. 1985;64:981–8.PubMedGoogle Scholar
  4. 4.
    Hemminki K, Kyyronen P, Lindbohm M-L. Spontaneous abortions and malformation in the offspring of nurses exposed to anaesthetic gases, cytostatic drugs, and other potential hazards in hospitals based on registered information of outcome. J Epidemiol Community Health. 1985;39:141–7.PubMedPubMedCentralGoogle Scholar
  5. 5.
    Mustafa O. Exposure of dental staff to nitrous oxide. Dent News (Lond). 2013;20(3):32–8.Google Scholar
  6. 6.
    Freilich MM, Alexander L, Sandor GKB, Judd P. Effectiveness of 2 scavenger mask systems for reducing exposure to nitrous oxide in a hospital-based pediatric dental clinic: a pilot study. JCDA. 2007;73(7):5.Google Scholar
  7. 7.
    Imbriani M, Ghittori S, Pezzagno G, Capodaglio E. Nitrous oxide (N2O) in urine as biological index of exposure in operating room personnel. Appl Ind Hyg. 1988;3:223–7.Google Scholar
  8. 8.
    Ontario Ministry of Labour. Occupational Health and Safety Act. Regulation 833, Control of exposure to biological or chemical agents. 2005. Accessed 15 Jan 2019.
  9. 9.
    Alert request for assistance in controlling exposure to Nitrous oxide during anesthesia administration. Cincinnati. US Dept of Health and Human Services. Public Health Service. Centre of Disease Control, National Institutes of Occupational Safety and Health. 1994; DHHS/NIOSH Publication number 94–100. Accessed 15 Jan 2019.Google Scholar
  10. 10.
    Primosch R, McLellan M, Jerrell G, Venezie R. Effect of scavenging on psychomotor and cognitive functions of subjects sedated with nitrous oxide and oxygen inhalation. Pediatr Dent. 1997;19(8):480–3.PubMedGoogle Scholar
  11. 11.
    McGlothlin JD, Jensen PA, Todd WF, Fischbach TJ. Study protocol: control of anesthetic gases in dental operatories. Cincinnati, OH: U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control, National Institute for Occupational Safety and Health, Division of Physical Sciences and Engineering; 1988. Accessed 15 Jan 2019.Google Scholar
  12. 12.
    McGlothlin JD, Jensen PA, Cooper TC, Fischbach TJ, Fairfield CL. In-depth survey report: control of anesthetic gases in dental operatories at University of California at San Francisco Oral Surgical Dental Clinic, San Francisco, CA. Cincinnati, OH: U.S. Department of Health and Human Services, Centers for Disease Control, National Institute for Occupational Safety and Health, Report No. ECTB 166B12b; 1990. Accessed 15 Jan 2019.Google Scholar
  13. 13.
    Hillman KM, Saloojee Y, Brett I, Cole PV. Nitrous oxide concentrations in the dental surgery. Anaesthesia. 1981;36:257.PubMedGoogle Scholar
  14. 14.
    Dames BL, MC Glothlin JD. National Institute for occupational safety and health. Controlling exposure to nitrous oxide during anesthetic administration. DHHS (NIOSH) Publication Number 94–100; 1994. Accessed 7 Feb 2019.
  15. 15.
    Gilchrist F, Whitters CJ, Cairns MA, Simpson M, Hosey MT. Exposure to nitrous oxide in a pediatric dental unit. Int J Pediatr Dent. 2007;17:116–22.Google Scholar
  16. 16.
    Policy on minimizing health hazards associated with nitrous oxide. Am Assoc Pediatr Dent. 2013;39:102–3.Google Scholar
  17. 17.
    Sittig M. Handbook of toxic and hazardous chemicals. 3rd ed. Park Ridge, NJ: Noyes Publications; 1991.Google Scholar
  18. 18.
    Bruce DL, Bach MJ, Arbit J. Trace anesthetic effects on perceptual, cognitive, and motor skills. Anesthesiology. 1974;40:453–8.PubMedGoogle Scholar
  19. 19.
    Bruce DL, Bach MJ. Trace effects of anesthetic gases on behavioral performance of operating room personnel, HEW Publication No. (NIOSH) 76-169. Cincinnati, OH: US Department of Health, Education and Welfare; 1976. Accessed 15 Jan 2019.Google Scholar
  20. 20.
    Cook TL, Smith M, Starkweather JA, Winter PM, Eger EI II. Behavioral effects of trace and subanesthetic halothane and nitrous oxide in man. Anesthesiology. 1978;49:419–24.PubMedGoogle Scholar
  21. 21.
    Sweeney B, Bingham RM, Amos RJ, Petty AC, Cole PV. Toxicity of bone marrow in dentists exposed to nitrous oxide. Br Med J (Clin Res Ed). 1985;291(6495):567–9.Google Scholar
  22. 22.
    Chanarin I. The effects of nitrous oxide on cobalamins, folates, and on related events. Crit Rev Toxicol. 1982;10(3):179–213.PubMedGoogle Scholar
  23. 23.
    Deacon R, Lumb M, Perry J, Chanarin I, Minty B, Halsey MJ, Nunn JF. Selective inactivation of vitamin B,, in rats by nitrous oxide. Lancet. 1978;2:1023.PubMedGoogle Scholar
  24. 24.
    Koblin DD, Waskell L, Watson JE, Stokstad ELR, Eger EI n. Nitrous oxide inactivates methionine synthetase in human liver. Anesth Anal. 1982;62:7.Google Scholar
  25. 25.
    Nunn JF. Clinical aspects of the interaction between nitrous oxide and vitamin B12. Br J Anaesth. 1987;59(1):3–13.PubMedGoogle Scholar
  26. 26.
    Cohen EN, Brown BW, Wu ML, Whitcher CE, Brodsky JB, Gift HC, Greenfield W, Jones TW, Driscoll EJ. Occupational disease in dentistry and chronic exposure to trace anesthetic gases. JADA. 1980;101:21–31.PubMedGoogle Scholar
  27. 27.
    Middendorf PJ, Jacobs DE, Smith KA, Mastro DM. Occupational exposure to nitrous oxide in dental operatories. Anesth Prog. 1986;33(2):91–7.PubMedPubMedCentralGoogle Scholar
  28. 28.
    Sanders DR, Weimann J, Maze M. Biological effects of nitrous oxide. Anesthesiology. 2008;109:707–22.PubMedGoogle Scholar
  29. 29.
    Nitrous Oxide Monitoring Certificate for Dental Hygienists and Dental Assistants.
  30. 30.
    Rowland AS, Baird DD, Weinberg CR, Shore DL, Shy CM, Wilcox AJ. Reduced fertility among women employed as dental assistants exposed to high levels of nitrous oxide. N Engl J Med. 1992;327(14):993–7.PubMedGoogle Scholar
  31. 31.
    Contemporary issues surrounding nitrous oxide. Chapter 17. In: Malamed SF, editor. Sedation—a guide to patient management, 6th edn. p. 253–63.Google Scholar
  32. 32.
    Kugel G, Letelier C, Zive MA, King JC. Nitrous oxide and infertility. Anesth Prog. 1990;37:176–80.PubMedPubMedCentralGoogle Scholar
  33. 33.
    Keeling PA, Rocke DA, Nunn JF, Monk SJ, Lumb MJ, Halsey MJ. Folinic acid protection against nitrous oxide teratogenicity in the rat. Br J Anaesth. 1986;58:528.PubMedGoogle Scholar
  34. 34.
    Lumb M, Deacon R, Perry J, Chanarin I. The effect of nitrous oxide inactivation of vitamin B12 on rat hepatic folate. Implications for the methylfolate-trap hypothesis. Biochem J. 1980;186:933.Google Scholar
  35. 35.
    Hewlett AM, Lewis JD, Lumb M, Nunn JF, Chanarin I. Studies on the haemopoietic toxicity of nitrous oxide in man. Br J Haematol. 1983;53:189.PubMedGoogle Scholar
  36. 36.
    Snider SM, Webster GM. Maternal and fetal hazards of surgery during pregnancy. Am J Obstet Gynecol. 1965;92:891.Google Scholar
  37. 37.
    Duncan PG, Pope WDB, Cohen MM, Greer N. Fetal risk of anesthesia and surgery during pregnancy. Anesthesiology. 1986;64:790.PubMedGoogle Scholar
  38. 38.
    Konieczko KM, Chappie JC, Nunn JF. Fetotoxic potential of general anaesthesia in relation to pregnancy. Br J Anaesth. 1987;59(4):449–54.PubMedGoogle Scholar
  39. 39.
    Brodsky JN, Cohen EN, Brown BW, Wu ML, Whitcher CE. Exposure to nitrous oxide and neurological disease among dental professionals. Anaesth Analg. 1981;60:297–301.Google Scholar
  40. 40.
    William E, Steinberg E, Rose J. Vitamin B12 deficiency induced neuropathy secondary to prolonged recreational use of nitrous oxide. Am J Emerg Med. 2018;36:1717.e1–2.Google Scholar
  41. 41.
    Pugliese RS, Slagle EJ, Oettinger GR, Neuburger KJ, Ambrose TM. Subacute combined degeneration of the spinal cord in a patient abusing nitrous oxide and self-medicating with cyanocobalamin. Am J Health Syst Pharm. 2015;72(11):952–7.PubMedGoogle Scholar
  42. 42.
    Safari A, Emadi F, Jamali E, Borhani-Haghighi A. Clinical and MRI manifestations of nitrous oxide induced vitamin B12 deficiency: a case report. Iran J Neurol. 2013;12(3):111–3.PubMedPubMedCentralGoogle Scholar
  43. 43.
    Green R, Kinsella LJ. Current concepts in the diagnosis of cobalamin deficiency. Neurology. 1995;45(8):1435–40.PubMedGoogle Scholar
  44. 44.
    Senol MG, Sonmez G, Ozdag F, Saracoglu M. Reversible myelopathy with vitamin B12 deficiency. Singap Med J. 2008;49(11):e330–2.Google Scholar
  45. 45.
    Blanco G, Peters HA. Myeloneuropathy and macrocytosis associated with nitrous oxide abuse. Arch Neurol. 1983;40(7):416–8.PubMedGoogle Scholar
  46. 46.
  47. 47.
    Nagele P, Tallchief D, Blood J, Sharma A, Kharasch ED. Nitrous oxide anesthesia and plasma homocysteine in adolescents. Anesth Analg. 2011;113:843–8.PubMedPubMedCentralGoogle Scholar
  48. 48.
    Nagele P. Notorious oxide. Anesthesiology. 2012;117:3–5.PubMedPubMedCentralGoogle Scholar
  49. 49.
    Amos RJ, Amess JA, Nancekievill DG, Rees GM. Prevention of nitrous oxide-induced megaloblastic changes in bone marrow using folinic acid. Br J Anaesth. 1984;56:103–7.PubMedGoogle Scholar
  50. 50.
    Lassen HCA, Henriksen E, Neukirch F. Treatment of tetanus. Severe bone marrow depression after prolonged nitrous oxide anaesthesia. Lancet. 1956;270(6922):527–30.PubMedGoogle Scholar
  51. 51.
    Nunn JF, Sharer NM, Gorchein A. Megaloblastic haemopoiesis after multiple short term exposure to nitrous oxide. Lancet. 1982;1(8286):1379–81.PubMedGoogle Scholar
  52. 52.
    Amess JAL, Burman JF, Rees GM, Nancekievill DG, Mollin DL. Megaloblastic haemopoiesis in patients receiving nitrous oxide. Lancet. 1978;2:339.PubMedGoogle Scholar
  53. 53.
    Skacel PO, Chanarin I, Hewlett A, Nunn JF. Failure to correct nitrous oxide toxicity with folinic acid. Anesthesiology. 1982;57(6):557–8.PubMedGoogle Scholar
  54. 54.
    Nunn JF, O'Morain C. Nitrous oxide decreases motility of human neutrophils in vitro. Anesthesiology. 1982;456:45–8.Google Scholar
  55. 55.
    Sullivan H, Jennings F, Ward K, McCann S, Scott JM, Weir DG. Human bone marrow biochemical function and megaloblastic hematopoiesis after nitrous oxide anesthesia. Anesthesiology. 1981;55:645–9.Google Scholar
  56. 56.
    Garakani A, Jaffe RJ, Savla D, Welch AK, Protin CA, Bryson EO, et al. Neurologic, psychiatric, and other medical manifestations of nitrous oxide abuse: a systematic review of the case literature: toxic effects of nitrous oxide abuse. Am J Addict. 2016;25(5):358–69.PubMedGoogle Scholar
  57. 57.
    Rasmussen SA, et al. Vitamin B12 deficiency in children and adolescents. J Pediatr. 2001;138(1):10–7.PubMedGoogle Scholar
  58. 58.
    Jessika T. Toxicology of nitrous oxide. Best Pract Res Clin Anesthesiol. 2001;15:349–62.Google Scholar
  59. 59.
    Selzer RR, Rosenblatt DS, Laxova R, Hogan K. Adverse effects of nitrous oxide in a child with 5,10 methylenetetrahydrofolate reductase deficiency. N Engl J Med. 2003;349:45–50.PubMedGoogle Scholar
  60. 60.
    Duma A, Cartmill C, Blood J, Sharma A, Kharasch E, Nagele P. The hematological effects of nitrous oxide anesthesia in pediatric patients. Anesth Analg. 2015;120(6):1325–30.PubMedPubMedCentralGoogle Scholar
  61. 61.
    Skacel PO, Hewlett AM, Lewis JD, Lumb M, Nunn JF, Chanarin I. Studies on the haemopoietic toxicity of nitrous oxide in man. Br J Haematol. 1983;53:189–200.PubMedGoogle Scholar
  62. 62.
    Cohen EN, et al. A survey of anesthetic health hazards among dentists. JADA. 1975;90:1291–6.PubMedGoogle Scholar
  63. 63.
    Bennett CR. Nitrous oxide hallucinations. J Am Dent Assoc. 1980;101(4):595.. 597PubMedGoogle Scholar
  64. 64.
    Jastak JT, Malamed SF. Nitrous oxide sedation and sexual phenomena. J Am Dent Assoc. 1980;101(1):38–40.PubMedGoogle Scholar
  65. 65.
    Lambert C. Sexual phenomena hypnosis and nitrous oxide sedation. J Am Dent Assoc. 1982;105(6):990–1.PubMedGoogle Scholar

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© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Kunal Gupta
    • 1
  • Amit Sethi
    • 2
  1. 1.Children’s Dental CenterGurugramIndia
  2. 2.Department of Oral and Maxillofacial SurgeryHenry Goldman School of Dental Medicine, Boston UniversityBostonUSA

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