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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
fertility, other
Remarks:
based on test type (migrated information)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non-GLP, no TG followed. One-generation exposure

Data source

Reference
Reference Type:
publication
Title:
The effects of intermittent chronic exposure of nitrous oxide on rat fertility and pregnancy
Author:
Webman, S.
Year:
1980
Bibliographic source:
Pediatric Dentistry, 2(3); p 208-216

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The effects of intermittent chronic exposure of nitrous oxide on rat fertility and pregnancy over one-generation exposure
GLP compliance:
no
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Dinitrogen oxide
EC Number:
233-032-0
EC Name:
Dinitrogen oxide
Cas Number:
10024-97-2
Molecular formula:
N2O
IUPAC Name:
nitrogen oxide
Test material form:
gas under pressure: liquefied gas

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female

Administration / exposure

Route of administration:
inhalation: gas
Type of inhalation exposure (if applicable):
whole body
Vehicle:
air
Details on mating procedure:
After 30 d of exposure rats were mated as follows: a) 7 pairs from N2O exposed M and F; b) 6 pairs from N2O exposed M and O2 exposed females, c) 6 pairs from O2 exposed M and N2O exposed F, d) 6 pairs from O2 exposed M and F, e) 5 pairs from unexposed M & F.
Analytical verification of doses or concentrations:
yes
Duration of treatment / exposure:
30 d prior to mating and then over one generation
Frequency of treatment:
2h/d
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 70%
Basis:
nominal conc.
No. of animals per sex per dose:
12/gp
Control animals:
yes, concurrent no treatment

Results and discussion

Results: P0 (first parental generation)

Effect levels (P0)

Dose descriptor:
NOAEC
Effect level:
> 700 000 ppm
Sex:
male/female
Basis for effect level:
other: No effects on fertility

Results: F1 generation

Effect levels (F1)

Dose descriptor:
NOAEC
Generation:
F1
Effect level:
> 700 000 ppm
Sex:
male/female
Basis for effect level:
other: No effect on litter size or pups

Overall reproductive toxicity

Reproductive effects observed:
not specified

Any other information on results incl. tables

A total of 22 litters were born to 30 dams, distributed almost evenly amongst the pairings. No gross developmental deformities were noted in either the treated or control group animals. Chi-square analysis shows no significant difference in the no. of litters produced by exposed and unexposed pairings.

 

Histological examination of the ovaries and testes showed no demonstrable difference between experimental and control animals, no focal or generalised destruction was observed in the testes or ovaries of treated animals even when exposure to N2O was for 30 d.

 

Dams were allowed to deliver pups. Pups were weighed, measured and examined for abnormalities. No effects on fertility, litter size or pups were found in this study.

Applicant's summary and conclusion

Conclusions:
Dams were allowed to deliver pups. Pups were weighed, measured and examined for abnormalities. No effects on fertility, litter size or pups were found in this study.
 
As animals were exposed to a single dose concentration of N2O, the objective therefore of the study was not to establish a NOAEC. It however could be concluded that the NOAEC was >70% as no effects on fertility were observed.
Executive summary:

Groups of 22 rats were exposed via whole body inhalation to 70% N2O / 30% O2 for 2 h/for 30 consecutive days. A group of 12 rats of each sex exposed to O2 only over the same schedule. There was a further unexposed control group of 5 rats/sex. Two rats of each sex exposed to N2O were killed at 5, 01, 20 or 30 d of treatment and the gonads removed and fixed in formalin. One rat of each sex from the same group was killed before the start of exposure to provide a histological baseline. After 30 d of exposure rats were mated as follows: a) 7 pairs from N2O exposed M and F; b) 6 pairs from N2O exposed M and O2 exposed females, c) 6 pairs from O2 exposed M and N2O exposed F, d) 6 pairs from O2 exposed M and F, e) 5 pairs from unexposed M & F.

 

Dams were allowed to give birth to their litters and pups were weighed measured for abnormalities.

 

A total of 22 litters were born to 30 dams, distributed almost evenly amongst the pairings. No gross developmental deformities were noted in either the treated or control group animals. Chi-square analysis shows no significant difference in the no. of litters produced by exposed and unexposed pairings.

 

Histological examination of the ovaries and testes showed no demonstrable difference between experimental and control animals, no focal or generalised destruction was observed in the testes or ovaries of treated animals even when exposure to N2O was for 30 d.

 

Dams were allowed to deliver pups. Pups were weighed, measured and examined for abnormalities. No effects on fertility, litter size or pups were found in this study.

 

As animals were exposed to a single dose concentration of N2O, the objective therefore of the study was not to establish a NOAEC. It however could be concluded that the NOAEC was >70% as no effects on fertility were observed.