Registration Dossier

Administrative data

Endpoint:
toxicity to reproduction: other studies
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
no details about the test substance, details of results not tabulated; no positive control

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1980
Report Date:
1980

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Sperm abnormalities in male mice were assessed after repeated inhalation exposure to the test substance.
GLP compliance:
not specified
Type of method:
in vivo

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material: dimethylacetamide (DMAC)
Specific details on test material used for the study:
- Name of test material: dimethylacetamide (DMAC)
No details available.

Test animals

Species:
mouse
Strain:
B6C3F1
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Food and water: ad libitum (but not during exposure)

No further details available.

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure (if applicable):
whole body
Vehicle:
other: nitrogen and air
Details on exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION / EXPOSURE
Whole body exposure; generation of exposure atmosphere by bubbling nitrogen through DMAC contained in a glass gas washing bottle (50 °C); the vapour mixture was diluted with filtered compressed air; atmospheres in the exposure chambers were dynamic (continuously generated for a single pass through the animal holding zone); concentrations within the exposure chambers were maintained by regulating the flow of nitrogen and diluting air into the mixing vessels.
Continuously monitoring was conducted in the breathing zone by infra-red gas analysers; calibrations were performed daily.
Chamber relative humidity and temperature were measured every hour.
After exposure, rats were observed for clinical signs, ear numbers checked, body weights recorded and the animals returned to their cages.
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Monitoring was perfomred continuously via infrared-spectroscopy.
Duration of treatment / exposure:
7 h/day for 5 days
Frequency of treatment:
Once daily
Duration of test:
5 days
Doses / concentrationsopen allclose all
Dose / conc.:
20 ppm (nominal)
Remarks:
equivalent to 70 mg/m³
Dose / conc.:
700 ppm (nominal)
Remarks:
equivalent to 2500 mg/m³
No. of animals per sex per dose:
No details
Control animals:
yes, concurrent vehicle
Details on study design:
5 weeks after the last exposure mice were sacrificed and sperm smears prepared for light microscopy.
Scoring:
(1) separated tails and heads
(2) clumps of sperm
(3) sperm orientated so that the hook could not be seen
(4) sperm partially masked by any remaining stain droplets

Otherwise, sperm was scored and placed in one of the following categories: I Normal or II Abnormal
A) hook upturned or elongated
B) banana-shaped head
C) amorphous head
D) abnormal tail (sharp, 180° angle or tight coiling only)
E) miscellaneous
Statistics:
Data were transformed using the Freeman-Tukey transformation.
Student's t-test

Results and discussion

Effect levels

Dose descriptor:
NOAEC
Effect level:
2 500 mg/m³ air (nominal)
Based on:
test mat.
Sex:
male
Basis for effect level:
other: no sperm abnormalities

Observed effects

Abnormal sperm was observed in one mouse of the high dose group, but normal sperm in the other animals of this group.
This isolated finding was not considered to be treatment related.
No clinical signs were detected (but toxic effects are expected; see Section 7.5.3).

Applicant's summary and conclusion

Conclusions:
There were no sperm abnormalities in male B6C3F1 mice after repeated exposure to 700 ppm (2500 mg/m³).
Executive summary:

Sperm abnormality tests were performed in male B6C3F1 mice after in vivo exposure to 20 or 700 ppm of the test substance for 7 hours/day for 5 days (non-guideline, GLP not specified). Mice were exposed via whole body exposure. Mice were killed five weeks after the last day of dosing. Sperm was placed in the categories "normal" and "abnormal" whereas for abnormal the subcategories "hook upturned or elongated", "banana-shaped" or "amorphous" head, "abnormal tail", and "miscellaneous" were chosen. There were no increases in the frequencies of abnormal sperm in any of the categories examined. There were no sperm abnormalities in male B6C3F1 mice after repeated exposure to 700 ppm (2500 mg/m³).