Dinitrogen oxide

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

sub-chronic toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: limited pathology and blood work undertaken

Data source

Reference

Reference Type:

publication

Title:

Effects of subchronic intermittent exposure to nitrous oxide in Swiss Webster mice

Author:

Rice, S.A., Mazze, R.I. & Baden, J.M.

Year:

1983

Bibliographic source:

Journal of Environmental Pathology, Toxicology & Pathology, 6(2), pp 271-282

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 413 (Subchronic Inhalation Toxicity: 90-Day Study)

Deviations:

yes

Remarks:

limited pathology and blood work undertaken

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Dinitrogen oxide

EC Number:

233-032-0

EC Name:

Dinitrogen oxide

Cas Number:

10024-97-2

Molecular formula:

N2O

IUPAC Name:

Dinitrogen Oxide

Test material form:

gas under pressure: liquefied gas

Test animals

Species:

mouse

Strain:

Swiss

Sex:

male/female

Administration / exposure

Route of administration:

inhalation: gas

Type of inhalation exposure:

whole body

Vehicle:

air

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

14 wks

Frequency of treatment:

4h/d, 5d/wk

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 0.5, 5, 50%
Basis:
nominal conc.

No. of animals per sex per dose:

15/sex/gp

Control animals:

yes, concurrent vehicle

Results and discussion

Effect levels

Dose descriptor:

NOAEC

Effect level:

ca. 50 000 ppm

Sex:

male/female

Basis for effect level:

other: statistically significant reductions in body weight gains

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

OBSERVATIONS:

Clinical signs of toxicity:

All animals survived to the scheduled necropsy.

 

Bodyweight and bodyweight gain:

Treatment related decreases in body weight were observed in high dose group animals, with a depression of 77 and 63% in body weight gain in males and females respectively. This depression in weight gain was statistically significant (p<0.025 and p<0.01, respectively).

 

Haematology & clinical chemistry:

No treatment related changes were observed in any of the parameter measured.

 

Urinalysis:

None undertaken

 

Sacrifice and Gross Pathology:

No treatment related changes were observed in any of the parameter measured.

 

Organ weights: 

No discussion of organ weight data.

Applicant's summary and conclusion

Conclusions:

The objective of the study was to demonstrate the maximum tolerated concentration of N2O, which was deemed to be 50% (500000 ppm). In terms of establishing a NOAEL, based on the results of this study and the data presented, 50000 ppm (5%) was deemed to be the NOAEL, based on statistically significant reductions in body weight gains observed at the LOAEL (500000 ppm [50%]).

Executive summary:

Swiss Webster mice (15/sex/gp) were exposed to N2Oviawhole body inhalation at concentrations of 0, 5000, 50000 or 500000 ppm [0, 0.5, 5, 50%] for 4/h/d, 5d/wk over 14 wks. At necropsy limited histopathology and haematology / biochemistry parameters were measured. 

 

All animals survived to the scheduled necropsy. The study failed to demonstrate exposure related haematopoietic changes. There was no change in the white blood cell count nor was granulocytopenia or thrombocytopenia observed. The lack of effect suggests that either the strain of mouse was insensitive to N2O, or more likely that continuous exposure is necessary to induce leucocytopenia, as previous demonstrated following continuous exposure to N2O at high concentrations (20-80%). Furthermore, no treatment related changes in organ weights, biochemical or histopathological parameters were observed. 

 

Treatment related decreases in body weight were observed in high dose group animals, with a depression of 77 and 63% in body weight gain in males and females respectively. This depression in weight gain was statistically significant (p<0.025 and p<0.01, respectively).

 

The objective of the study was to demonstrate the maximum tolerated concentration of N2O, which was deemed to be 50% (500000 ppm). In terms of establishing a NOAEL, based on the results of this study and the data presented, 50000 ppm (5%) was deemed to be the NOAEL, based on statistically significant reductions in body weight gains observed at the LOAEL (500000 ppm [50%]).