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Toxicological information

Acute Toxicity: dermal

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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

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1955
Report Date:
1955
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:
OECD Guideline 402 (Acute Dermal Toxicity)
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)
No details available.

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male
Details on test animals 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:
Local effects were found noted including erythema, necrosis and desquamation.
There are no data about systemic effects.
Body weight:
Increased body weight was observed in most survivors except 2 rabbits of the low dose group.
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.