N,N-dimethylformamide

Acute Toxicity: inhalation

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

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1979

Report date:

1979

Reference 2

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

Test material information

Constituent 1

Reference substance name:

Dimethylformamide

IUPAC Name:

Dimethylformamide

Constituent 2

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.