Dinitrogen oxide

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Nitrous oxide was not mutagenic in a reverse mutation assay in Salmonella typhimurium in the absence and presence of S9-mix (Baden et al., 1979).

Nitrous oxide did not induce sister chromatid exchanges in CHO cells with and without metabolic activation (White et al., 1979).

Nitrous oxide was not mutagenic in a mammalian cell gene mutation assay in V79 cells without S9-mix (Sturrock, 1977).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Description of key information

There are no in vivo studies available which have been performed according to currently accepted OECD TG methods.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

The summary of the available studies is derived from the MAK value documentation (1993).

In vitro

The in vitro genotoxicity studies described below were carried out in closed systems with nitrous oxide concentrations of 750 000 to 810 000 ppm.  After 24 hours exposure, a SCE test with CHO cells (a cell line from Chinese hamster ovary) (White et al. 1979) and an HPRT (hypoxanthine guanine phosphoribosyl transferase) test with V79 cells but without a positive control (Sturrock 1977) yielded negative results.

After 8 hours exposure under pressure in the Salmonella mutagenicity test, nitrous oxide was not mutagenic in the strains TA98, TA100 and TA1535 with or without added S9 mix (Baden et al. 1979, Baden and Monk, 1981).

In V79 cells exposed for 24 hours, no abnormal nuclei were observed. The clastogenic effect of halothane, however, was increased if the cells were incubated simultaneously with halothane and nitrous oxide (Sturrock and Nunn 1976).

In vivo

A 1-hour exposure to nitrous oxide concentrations of 400 000 and 800 000 ppm did not increase the incidence of sex-linked recessive lethal mutations in Drosophila (Kundomal and Baden 1984, 1985a). Dose-dependent chromosomal aberrations in the bone marrow cells and spermatogonia were observed after exposure of rats to a mixture of halothane and nitrous oxide (1 ppm and 50 ppm or 10 ppm and 500 ppm, 7 hours/day, 5 days/week for 12 weeks followed after 3 weeks pause by the same exposure pattern for a further 40 weeks) (Coate et al. 1979a). Halothane, both alone and in combination with nitrous oxide, has been shown to have clastogenic effects in vitro so that it is not clear whether or not nitrous oxide has a clastogenic effect in vivo (Sturrock and Nunn 1976).

In conclusion, nitrous oxide does not induce gene mutation in vitro. There are no in vivo studies available which have been performed according to currently accepted OECD TG methods.

 

General remark

1 mL/m³ (ppm) = 1.83 mg/m³

 

References

- Baden JM, Monk SJ (1981) Mutagenicity and toxicity studies with high pressure nitrous oxide. Toxicol Lett 7: 259–262

- Coate WB, Kapp RW, Lewis TR (1979) Chronic exposure to low concentrations of halothanenitrous oxide: reproductive and cytogenetic effects in the rat. Anesthesiology 50: 310–318

- Kundomal YR, Baden JM (1984) Anesthetic mutagenicity in Drosophila. Environm Mutagen 6: A417

- Kundomal YR, Baden JM (1985a) Mutagenicity of inhaled anesthetics in Drosophila melanogaster. Anesthesiology 62: 305–309

- Sturrock JE, Nunn JF (1976) Synergism between halothane and nitrous oxide in the production of nuclear abnormalities in the dividing fibroblast. Anesthesiology 44: 461–471

Justification for classification or non-classification

Classification, Labeling, and Packaging Regulation (EC) No 1272/2008

The criteria for classification for genotoxicity according to Regulation (EC) No 1272/2008, as amended for fifteenth time in Regulation (EU) No 2020/1182, are not met.