N,N-dimethylacetamide

Acute Toxicity: inhalation

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

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

Test material information

Constituent 1

Reference substance name:

N,N-dimethylacetamide

EC Number:

204-826-4

EC Name:

N,N-dimethylacetamide

Cas Number:

127-19-5

Molecular formula:

C4H9NO

IUPAC Name:

N,N-dimethylacetamide

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 or test system 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 levels

Effect levels 1

Sex:

female

Dose descriptor:

LC50

Effect level:

8.8 mg/L air

Exp. duration:

1 h

Remarks on result:

other: estimated LC50

Effect levels 2

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:

other: 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

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.