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Toxicity to reproduction: other studies

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Administrative data

Endpoint:
toxicity to reproduction: other studies
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non-GLP, no TG available

Data source

Reference
Reference Type:
publication
Title:
Testicular reaction to prolonged exposure to nitrous oxide
Author:
Kripke, B.J., Kelman, A.d., Shah, N.K., Balogh, K. & Handler, A.H.
Year:
1976
Bibliographic source:
Anesthesiology, 44(2); pp 104-113

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Mechanistic study examining the effects of N2O on testicular function
GLP compliance:
no
Type of method:
in vivo

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

Administration / exposure

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:
Either 8 h/d or 24 h/d
Frequency of treatment:
Either 8 h/d or 24 h/d for 1, 2, 3, 4, 5, 7, 10, 14, 21, 28, 32 or 35 d
Duration of test:
up to 35 d
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 20%
Basis:
nominal conc.
No. of animals per sex per dose:
4-6/gp

Results and discussion

Effect levels

Dose descriptor:
NOAEC
Remarks on result:
not determinable
Remarks:
no NOAEC identified

Observed effects

Whilst results were not presented in relation to a time course of changes, histological examination of the testis was detailed.

Following continuous exposure over 35 d resulted in tubules almost empty of spermatids and spermatozoa. Intermittent exposure had milder effects typified by a reduction in the number of spermatogenic cells. Following 6 d without exposure there was clear evidence of recovery of spermatogenesis but in some animals the recovery took longer. There was no effect on testosterone level which was consistent with the lack of any histological changes in interstitial cells.

Applicant's summary and conclusion

Conclusions:
In conclusion, continual exposure to N2O resulted in depletion of spermatids and spermatozoa, which was reversible upon cessation of exposure. No histopathological changes were present in interstitial cells, with testosterone levels remaining unaffected.
Executive summary:

Groups of approximately 45 M rats were exposed to 20%N2 for either 8 h/d or 24 h/d for 1, 2, 3, 4, 5, 7, 10, 14, 21, 28, 32 or 35 d. Groups of 4-6 rats were killed immediately after exposure and examined for macroscopic abnormalities. Tissues were preserved for histological examination and blood samples were taken to determine testosterone levels. One group of rats following 32 d of exposure were removed from exposure and allowed to recover for 6 d prior to sacrifice. 

 

Following continuous exposure over 35 d resulted in tubules almost empty of spermatids and spermatozoa. Intermittent exposure had milder effects typified by a reduction in the number of spermatogenic cells. Following 6 d without exposure there was clear evidence of recovery of spermatogenesis but in some animals the recovery took longer. There was no effect on testosterone level which was consistent with the lack of any histological changes in interstitial cells.

 

In conclusion, continual exposure to N2O resulted in depletion of spermatids and spermatozoa, which was reversible upon cessation of exposure. No histopathological changes were present in interstitial cells, with testosterone levels remaining unaffected.