Dinitrogen oxide

Toxicity to reproduction

Administrative data

Endpoint:

fertility, other

Remarks:

spermatogenesis

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Testicular reaction to prolonged exposure to nitrous oxide

Author:

Kripke BJ, Kelman AD, Shah NK, Balogh K, Handler AH

Year:

1976

Bibliographic source:

Anesthesiology 44: 104–113 cited in 'Nitrous oxide [MAK Value Documentation, 1993]'

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Male rats were exposed to 200 000 ppm nitrous oxide for a maximum of 35 days and the testicular reaction was investigated.

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:

nitrogen oxide

Test material form:

gas

Test animals

Species:

rat

Strain:

other: LEW/f Mai

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:

35 days at a maximum

Frequency of treatment:

8 h/d

Details on study schedule:

Four to six rats were sacrificed by cardiac puncture and exsanguination after 1, 2, 3, 4, 5, 7, 10, 14, 21, 28, 32 and 35 days of exposure.

Doses / concentrations

Dose / conc.:

200 000 ppm

Remarks:

(20%)

No. of animals per sex per dose:

In sum 135 animals were treated with nitrous oxide.

Control animals:

yes, concurrent vehicle

Examinations

Parental animals: Observations and examinations:

HORMONE MEASUREMENTS:
Blood, removed by cardiac puncture at the time of exsanguination, had its serum separated for measurement of testosterone level.

Sperm parameters (parental animals):

Parameters examined in male animals:
testis weight, microscopic appearance of testis

Postmortem examinations (parental animals):

SACRIFICE
- Male animals: All surviving animals
GROSS NECROPSY
- Gross necropsy consisted of external and internal examinations including the cervical, thoracic, and abdominal viscera.
HISTOPATHOLOGY / ORGAN WEIGHTS
Testis were prepared for microscopic examination and weighed, respectively.

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Endocrine findings:

no effects observed

Description (incidence and severity):

There was no significant difference in serum testosterone levels between the control and the experimental group.

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Description (incidence and severity):

Injury of spermatogenic cells in the seminiferous tubules was observed. Cells, that had divided to become spermatocytes, spermatids, and spermatozoa by mitosis and meiosis, respectively, were subject to damage or destruction. A reduction in the number of spermatogenic cells with some disorganization of the normal architecture could also be observed. Cells in active division could be seen within seminiferous tubules that contained fewer spermatides and mature spermatozoa.

Effect levels (P0)

Key result

Dose descriptor:

LOAEC

Effect level:

200 000 ppm

Based on:

test mat.

Sex:

male

Basis for effect level:

reproductive function (sperm measures)

Target system / organ toxicity (P0)

Key result

Critical effects observed:

yes

Lowest effective dose / conc.:

200 000 ppm

System:

male reproductive system

Organ:

testes

Treatment related:

yes