Dinitrogen oxide

Toxicity to reproduction: other studies

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

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:

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.