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Toxicological information

Carcinogenicity

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Description of key information

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no study available

Carcinogenicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
carcinogenicity: inhalation
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
GLP compliance:
no
Species:
mouse
Strain:
Swiss Webster
Sex:
male/female
Route of administration:
inhalation: gas
Type of inhalation exposure (if applicable):
whole body
Vehicle:
air
Analytical verification of doses or concentrations:
yes
Duration of treatment / exposure:
78 wks
Frequency of treatment:
mice were exposed 4h/d, 5d/wk
Post exposure period:
78 wks
Remarks:
Doses / Concentrations:
0, 10, 40%
Basis:
nominal conc.
No. of animals per sex per dose:
75-77 animals/sex/treatment gp
88-91 animals/sex/treatment gp
Control animals:
yes, concurrent no treatment
Dose descriptor:
NOAEC
Effect level:
> 400 000 ppm
Remarks on result:
other: Effect type: carcinogenicity (migrated information)

More than 40 tissues were examined and fixed. Liver, spleen, kidneys and testes were weighed. Haematology was limited to bone marrow and blood smears (the latter for RBC, differential white blood cell, reticulocyte and platelets counts).

No treatment related significant decrease in body weights. Gross and microscopic examination of tissues revealed a variety of non-neoplastic lesions including ovarian cyst, cholecystitis, bladder stones and testicular atrophy. Their presence was unrelated to treatment. In general, there was no microscopic evidence of cellular damage and in particular a detailed examination of blood smears and bone marrow sections showed no evidence of megaloblastic changes or bone marrow depression.

 

The first neoplastic lesion appeared 26 weeks after the start of treatment and numerous other tumours appeared throughout the study. Most of the tumours in both the control and test animals were either lung adenomas or alveolar cell origin or liver tumours of the basophilic hepatocellular adenoma type. There were no statistical differences among the groups either in the total number of tumours or in the number of tumours of a particular cell type.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEC
400 000 mg/m³
Study duration:
chronic
Species:
mouse

Justification for classification or non-classification

In accordance with the REACh endpoint specific guidance: -

 

For substances which there is no concern for mutagenic activity, and no other toxicological indicators of carcinogenicity (i.e. for the substance itself or for structurally-related substances), there is no need for further consideration of its carcinogenic potential.”N2O is confirmed to be devoid of mutagenic potential, with the repeat dose toxicity studies showing no evidence of pre-cancerous lesions. Furthermore, human epidemiological data confirms no convincing evidence that N2O poses a carcinogenic hazard to humans. Therefore no classification is required.

Additional information

The incidence of tumours in male and female Swiss Webster mice treated with N2O at concentrations of 0, 10% (100000mg/m3) or 40% (400000 mg/m3), 4h/d, 5d/wk for 78 wks was not increased. In the high dose group body weights were reduced by 5%. Other studies examining the carcinogenic effect of N2O also produced negative results, however the exposure period was either too short (Eger et al., 1978) or the concentration used was too low with N2O co-administered with halothane (Coate et al., 1979). These studies therefore have not been included in the evaluation of carcinogenicity.

 

References:

- Coate, W.B., Ulland, B.M. & Lewis , T.R. (1979). Chronic exposure to low concentrations of halothane-nitrous oxide: lack of carcinogenic effect in the rat. Anesthesiology, 50; pp 310-318.

- Eger II, E.I., White, A.E., Brown, C.L., Biava, C.G., Corbett, T.H. & Stevens, W.C. (1978). A test of the carcinogenicity of enflurane, isoflurane, halothane, methoxyflurane and nitrous oxide in mice. Anesth Analg, 57; pp 678-694