N,N-dimethylacetamide

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study is comparable to OECD Guideline 402 with acceptable restrictions (partly limited documentation, e.g. no details on test substance; no data about systemic clinical signs; 4 animals per dose used, 5 per dose recommended in the Guideline).

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1955

Report date:

1955

Reference 2

Reference Type:

publication

Title:

Range-finding toxicity data: List VI

Author:

Smyth HF, Carpenter CP, Weil CS, Pozzani UC, Striegel JA

Year:

1962

Bibliographic source:

Am Ind Hyg Assoc J 23: 95-107

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

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)
No details available.

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: ca. 2.5 kg
- Age at study initiation: 3-5 months old

No further details available.

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

The fur was closely clipped over the entire trunk; the dose was retained under an impervious plastic film; animals were immobilized during the exposure period.

Duration of exposure:

24 h

Doses:

1260, 2520, 5000 µL/kg bw (corresponding to 1180, 2370, 4700 mg/kg bw)

No. of animals per sex per dose:

4 rabbits

Control animals:

no

Details on study design:

Dosages greater than 20 mL/kg bw could not be retained in contact with the skin; after 24 h contact the impervious plastic film was removed.
Post exposure observation period: 14 days

Statistics:

The LD50 value and its fiducial range were estimated by the method of Thompson (Bact. Rev. 11 :115, 1947) using the tables of Weil (Biometrics 8 :249, 1952).

Results and discussion

Effect levels

Sex:

male

Dose descriptor:

LD50

Effect level:

2 240 other: µL/kg bw

95% CL:

>= 1 230 - <= 4 110

Remarks on result:

other: corresponding to 2100 mg/kg bw

Mortality:

5 mL/kg bw: 4/4 rabbits died. One rabbit died within 60 minutes, the other 3 animals died after 1-3 days.
2.5 mL/kg bw: 2/4 rabbits died 2 and 5 days after application.
1.26 mL/kg bw: 1/4 rabbits died after 3 days.

Clinical signs:

other: Local effects were found noted including erythema, necrosis and desquamation. There are no data about systemic effects.

Gross pathology:

Several rabbits that died had lung haemorrhage and speckled or pitted kidney surface; in one animal of the highest dose level, there was blood in the peritoneum.

Other findings:

No

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The dermal LD50 of DMAC was determined to be 2100 mg/kg bw in male rabbits.

Executive summary:

Groups of 4 male New Zealand rabbits were dermally exposed to doses of 1.26, 2.5, or 5 mL/kg bw. The post exposure observation period was 14 days. One out of 4, 2/4, or 4/4 rabbits died after exposure, respectively. Local effects like erythema, necrosis, desquamation were recorded (no data about systemic effects). Necropsy of dead animals revealed lung hemorrhage, speckled or pitted kidney surface and blood in peritoneum. The dermal LD50 in male rabbits was 2240 µL/kg bw corresponding to 2100 mg/kg bw.