Registration Dossier

Toxicological information

Acute Toxicity: inhalation

Currently viewing:

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The study is comparable to Guideline study with acceptable restrictions (partly limited documentation, e.g. no details about the test substance; recommended limit concentration reached but exposure duration 1 h; conspicuous variations in dose levels; exclusive exposure to vapour not clear).

Data source

Reference
Reference Type:
publication
Title:
Acute and subchronic toxicity of dimethylformamide and dimethylacetamide following various routes of administration
Author:
Kennedy GL & Sherman H
Year:
1986
Bibliographic source:
Drug Chem Toxicol 9: 147-170

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
(1 h exposure)
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

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)
- Batch No.: Haskell No. 12,346
No further details available.

Test animals

Species:
rat
Strain:
other: ChR-CD
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 235-265 g in males, 180-220 g in females
- Fasting period before study: no data, but no water and no diet were provided during exposure
- Housing: two rats per cage
- Diet and water ad libitum
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
No details available.

Administration / exposure

Route of administration:
other: Vapour, but aerosol generation not excluded
Type of inhalation exposure:
whole body
Vehicle:
other: houseline air
Details on inhalation exposure:
The test substance was syringe-driven into a spraying system nebulizer; standards and samples were prepared in absolute ethanol; a Beckman Model 25 Spectrophotometer was used for analysing concentration; sampling was performed every 10 minutes; comparison with standard curve.
Authors stated that 8.8 mg/L was the max. vapour concentration at room temperature (25 °C), no higher concentrations available at this temperature.
4 rats of each sex were exposed in a stainless steel exposure chamber.
Analytical verification of test atmosphere concentrations:
yes
Remarks:
(results are presented below, see concentrations)
Duration of exposure:
1 h
Concentrations:
Time weighted average: 3.4 (measured range 2.4-4.8), 5.8 (3.8-22.9), or 8.8 (6.6-13.0) mg/L
No. of animals per sex per dose:
8 rats
Control animals:
no
Details on study design:
- Post exposure observation period: 14 days
- Frequency of observations and weighing: yes, but no details
- Necropsy of survivors performed: no
- Other examinations performed: no
Statistics:
No data

Results and discussion

Effect levelsopen allclose all
Sex:
female
Dose descriptor:
LC50
Effect level:
8.8 mg/L air
Exp. duration:
1 h
Remarks on result:
other: estimated LC50
Sex:
male
Dose descriptor:
LC0
Effect level:
8.8 mg/L air
Exp. duration:
1 h
Remarks on result:
other: max. available vapour concentration
Mortality:
Females were more susceptible than males, 4/8 females treated at 8.8 mg/L died within 2 days postexposure. There was no mortality in any other group.
Clinical signs:
No clinical signs were noted in males; females were more susceptible than males: at the low and mid dose level (3.4 and 5.8 mg/mL) hyperactivity was observed the first week post exposure; there was no hyperactivity at the high dose level of 8.8 mg/mL (no further signs were reported).
Body weight:
Males
There were no effects at the low dose of 3.4 mg/L;
at 5.8 mg/L, there was initial body weight loss (5-10 %) within 48 h and thereafter body weight gain;
at 8.8. mg/L, there was initial body weight loss (20 %) and thereafter body weight gain.

Females
At 3.4 and 5.8 mg/L, there was no relevant effect on body weight;
at 8.8 mg/L, there was body weight loss (15 %) in survivors within 48 h.
Gross pathology:
No data

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The LC50(1 hour) of DMAC was determined to be 8.8 mg/L in female rats. Female rats were more susceptible than males.
Executive summary:

Groups of 8 male and 8 female ChR-CD rats were exposed for 1 h to time weighted concentrations of: 3.4 (measured range 2.4-4.8), 5.8 (3.8-22.9), or 8.8 (6.6-13.0) mg/L. The test substance was syringe-driven into a spraying system nebulizer. The post exposure observation period was 14 days. No mortality was found in males at any exposure concentration. Females were more susceptible than males. At 8.8 mg/L 4 out of 8 females died within 48 h but no deaths were seen at the low and mid dose level. No clinical signs were recorded except hyperactivity in females on day 3-7 after exposure. Initial reduction in body weight was detected in males at >= 5.8 mg/L and in females at 8.8 mg/L. Conclusion: The LC50 (1 h) in female rats was estimated to be 8.8 mg/L; no mortality was seen in male rats at the time weighted average of 8.8 mg/L. The LC50(1 hour) of DMAC was determined to be 8.8 mg/L in female rats. Female rats were more susceptible than males. However, in this study conspicuous variations in dose levels were obvious and exclusive exposure to vapour (as mentioned by the authors) was not clear.