Registration Dossier

Toxicological information

Acute Toxicity: inhalation

Currently viewing:

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented report which meets basic scientific principles.

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1979
Report date:
1979
Reference Type:
publication
Title:
OECD SIDS Dimethylformamide
Author:
OECD
Year:
2004
Bibliographic source:
also cited in OECD SIDS Dimethylformamide, Final April 2004

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
no
Test type:
other: comparable with OECD 403 guideline
Limit test:
no

Test material

Constituent 1
Reference substance name:
Dimethylformamide
IUPAC Name:
Dimethylformamide
Constituent 2
Chemical structure
Reference substance name:
N,N-dimethylformamide
EC Number:
200-679-5
EC Name:
N,N-dimethylformamide
Cas Number:
68-12-2
Molecular formula:
C3H7NO
IUPAC Name:
N,N-dimethylformamide
Details on test material:
- Name of test material (as cited in study report): DMF=Dimethylformamid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: WIGA, Sulzfeld and MUS RATTUS, Brunnthal, Germany
- Weight at study initiation: male: 183 g (mean), female: 182 g (mean)
- Diet: Herilan MRH, ad libitum
- Water: tap water ad libitum

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
data not available
Analytical verification of test atmosphere concentrations:
yes
Remarks:
Gaschromatography
Duration of exposure:
4 h
Concentrations:
5.85, 5.10, 4.92, 2.23 mg/L
No. of animals per sex per dose:
10
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: daily
- Frequency of weighing: day 0, 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
no information given

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.85 mg/L air
Exp. duration:
4 h
Mortality:
5.85 mg/L: 3 males died within 3 days post exposure.
4.92 mg/L: 2 males and 1 female died within 3 days post exposure
Clinical signs:
other:
Body weight:
No significant alterations compared to controls were observed.
Gross pathology:
Animals that died:
Heart: acute dilation and congestive hyperaemia,
Lungs: filled with blood,
Thymus: widespread haemorrhage,
Stomach: haemorrhage,
Liver: dark red/brownish; grey/brownish marbled (haemorrhagic dystrophy);
Kidneys: pale cortex, yellowish papilla.
Pancreas: punctate haemorrhages.
Other findings:
no

Any other information on results incl. tables

Mortality:

 Dose (mg/L)  male  female
 5.85  3/10  0/10
 5.10  0/10  0/10
 4.92  2/10  1/10
 2.23  0/10  0/10

Animal supplier:

5.85, 4.92, 2.23 mg/L: WIGA;

5.10 mg/L: MUS RATTUS

Weight:

 Dose (mg/L)  day 0     day 7     day 14   
   male  female  male  female  male  female
 5.85  180  179  217  204 252  219
 5.10  183  179  214  190  266  208
 4.92  187  187 205   194  267  206
 2.23  188  186  211  192  257  208
 control  178  180  219  190  254  210
Toxic/Harmful if inhaled.

Applicant's summary and conclusion

Interpretation of results:
other:
Remarks:
EU GHS Criteria not met
Conclusions:
N,N-dimethylformamide is considered to be of low acute toxicity. Irregular or intermittent respiration were observed in the treated animals.
Executive summary:

Study design

This non-GLP study was performed similar to the OECD Test Guideline 403: Acute Inhalation Toxicity.

In the study 10 male and 10 female Sprague-Dawley rats per dose group were exposed by whole-body exposure to N,N-dimethylformamide (DMF) vapour for 4 hours at (analytical determined) concentrations of 2.23, 4.92, 5.10 and 5.85 mg/L. The concentration of 5.85 mL was the maximum technical attainable concentration. A concurrent control group of ten male and female animals run in parallel. After the 4-h DMF exposure, the animals were examined for 14 days. Body weight was determined before the beginning of the study, after 7 days during the study and at the end of the post observation period. The animals were daily observed for clinical signs and mortality. Animals that died during the study and the surviving animals sacrificed at the end of the post observation period were necropsied and macroscopically examined.

Results

At the analytical concentration of 2.23 mg/L all animals survived and did not show any clinical signs related to DMF exposure. In the other three treatment groups dyspnoea (irregular or intermittent respiration) and rough fur were observed as well in 3 females at 5.1 mg/L a minimal alopecia at the head. Deaths occurred 3 days after the start of the study: at 4.92 mg/L 2 of 10 males and 1 of 10 females died, at 5.1 mg/L all animals survived and at 5.85 mg/L 3 of 10 males and no female animal died.

Surviving animals recovered 6 -7 days after exposure. These animals did not show any gross lesions at necropsy, whereas the animals that died during the study had some organ findings, e.g. discoloration of the liver, haemorrhage in thymus and punctate haemorrhage in pancreas and in the gastric mucous membrane.

Conclusion

DMF is considered to be of low acute toxicity. Irregular or intermittent respiration were observed in the treated animals. LD50for both sexes was determined to be >5.85 mg/L air.