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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:
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

Referenceopen allclose all

Reference Type:
publication
Title:
Unnamed
Year:
1980
Report Date:
1980
Reference Type:
secondary source
Title:
N,N-Dimethylacetamide: Criteria Document for an occupational exposure limit
Author:
Fairhurst S, Gregg N, Cocker J, Brown R, South D, and Garrod A
Year:
1992
Bibliographic source:
published by HMSO C20, London

Materials and methods

Principles of method if other than guideline:
Sperm abnormality test in male mice: Expoure to atmospheres containing 20 ppm or 700 ppm N,N-dimethylacetamide for 7 h per day for 5 consecutive days. Analysis of test atmospheres was by continuous infrared absorption monitoring at a wavelength of 9.9 μm. Mice were killed 5 weeks from the last day of dosing by neck dislocation. Sperm from the cauda epididymides was spread on slides, stained in 1% eosin and examined microscopically.
GLP compliance:
not specified

Test material

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

Test animals

Species:
mouse
Strain:
not specified
Sex:
male

Administration / exposure

Route of administration:
inhalation
Details on exposure:
GENERATION OF TEST ATMOSPHERE
The test atmospheres were produced by bubbling dry, oxygen-free nitrogen (BOC Limited) through a liquid reservoir of N,N-dimethylacetamide contained in a glass gas washing, or Drechsel bottle immersed in a temperature controlled water bath at 50°C. The nitrogen/N,N-dimethylacetamide vapour mixture so generated was ducted through 7/16", ID stainless steel piping to a glass mixing vessel and diluted with filtered, compressed air. The resultinq mixture of N,N-dimethylacetamide/air was ducted through 3/1" stainless steel piping to the top of the exposure chamber. The atmospheres in the exposure chambers were dynamic in that they were continuously generated for a single pass through the animal holding zone, before being extracted from the bottom and ducted away for 'scrubbing'. The required atmospheric concentrations within the exposure chambers were maintained by finely regulating the flow of nitrogen and diluting air into the mixing vessels, by means of adjustable flow meters.

HOMOGENEITY DATA
Before starting the animal expsures, chamber concentrations at both the high and low levels were determined by continuous monitoring for periods of up to 6 h. In addition, samples were measured from different areas (at least 9) of the animal holding zone to confirm uniformity of N,N-dimethylacetamide concentration. The maximum deviations encountered were +/-2.3% at the 20 ppm target concentration and +/- 2.4% at the 700 ppm target concentration.

MEASUREMENT OF CHAMBER CONCENTRATIONS
Continous monitoring during the 7 h exposure period from the breathing zone of the animals. Stainless steel sampling lines, fitted with a particulate filter (Whatman Mini-Filter, Grade 80) and positioned on a central reference point in each exposure chamber, were connected to the infra-red gas analysers. The sampling flow rate was approximately 4 l/min.
Calibration ranges adopted were 9.4-47.0 ppm (20 ppm target concentration) and 188-940 ppm (700 ppm target concentration).

TEST COMPOUND UTILISATION
The DMAC reservoir was replenished daily with test compound. Utilisation of test material was calculated on a daily basis by weighing the bottle before vapour generation began and deducting the weight of the bottle and remaining test compound on completion of the exposure period.

EXPOSURE PROCEDURE
Exposures were conducted during the 7 h of between approximately 09 .00 h and 16 .00 h on each exposure day. Animals were examined for any signs of ill health before and after exposure. They were not allowed access to food or water during the exposure period. Animal positions within the exposure chambers were rotated on a daily basis to minimise any possible exposure location variations. The chamber temperature and relative humidity were recorded at hourly intervals throughout the exposure period. The animals were also observed at regular intervals for the appearance of clinical signs or adverse reactions to treatment.

POSITIVE CONTROL
Dosing solutions were prepared daily 5 min before administration to the animals was started. The desired amount of ethyl methanesulphonate was weighed into a volumetric flask and diluted with distilled water to obtain the correct concentration. Positive control animals were not allowed access to food or water whilst the remaining test groups were being exposed. 200 mg/kg ethyl methanesulphonate was administered orally by gavage to the mice at a constant dose volume of 10 ml/kg at around 16.00 h for 5 consecutive days.
Details on mating procedure:
no mating
Duration of treatment / exposure:
Exposure period: 5 days
Premating exposure period (males): no mating
Premating exposure period (females): no mating
Duration of test: 6 weeks
Frequency of treatment:
7 h/d
Details on study schedule:
Expoure to atmospheres containing 20 ppm or 700 ppm N,N-dimethylacetamide for 7 h per day for 5 consecutive days. Mice were killed 5 weeks from the last day of dosing by neck dislocation. Sperm from the cauda epididymides was spread on slides, stained in 1% eosin and examined microscopically.
Doses / concentrationsopen allclose all
Dose / conc.:
0.07 other: mg/L
Remarks:
20 ppm
Dose / conc.:
2.53 other: mg/L
Remarks:
700 ppm
Control animals:
yes, concurrent no treatment
Positive control:
yes

Results and discussion

Results: P0 (first parental animals)

General toxicity (P0)

Clinical signs:
no effects observed
Description (incidence and severity):
No clinical signs of toxicity considered to be due to exposure to DMAC were observed in mice.
Body weight and weight changes:
no effects observed
Description (incidence and severity):
Body weight values of the B6C3F1 mice taken at the time of dosing showed no effects upon mouse weight gain. EMS treated mice showed adversely affected body weights to some extent.

Reproductive function / performance (P0)

Reproductive function: sperm measures:
no effects observed
Description (incidence and severity):
SPERM ABNORMALITY TEST
There were no increases in the frequencies of abnormal sperm in any of the categories examined. The categories C and D, amorphous head and folded tail respectively, showed significantly higher frequencies in the EMS treated groups than in the air control group.
Reproductive performance:
not examined

Overall reproductive toxicity

Reproductive effects observed:
not specified

Any other information on results incl. tables

In a sperm abnormality test, groups of 10 male mice were exposed to the test substance for 5 consecutive days. No clinical signs of toxicity and no effects on body weight gain were observed. Sperm was  examined 5 weeks after the end of exposure. No significant differences in frequency of abnormal sperm between the exposed groups and controls were observed.

Applicant's summary and conclusion