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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:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1950
Report date:
1950
Reference Type:
publication
Title:
Unnamed
Year:
1951
Reference Type:
review article or handbook
Title:
Industrial Hygiene and Toxicology
Author:
Sutton W.L.
Year:
1962
Bibliographic source:
cited in: Patty's Ind.Hyg. and Toxicol. 2, p. 2044

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
other: Draize (one day cuff method)
Principles of method if other than guideline:
- Principle of test:
Penetration of rabbit skin was estimated by a technique closely to the one-day cuff method of Draize and associates, using groups of 5 male albino rabbits weighing 2 to 3 kg. The fur was removed from the entire trunk by clipping, and the dose was retained beneath an impervious plastic film. The animals are immobilized during the 24 hour contact period, after which the film was removed and the rabbits are caged for the subsequent 14 day observation period.
GLP compliance:
no
Remarks:
predating GLP
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: 3-5 month
- Weight at study initiation: 2- 3 kg
- Diet (e.g. ad libitum): Rockland rabbit diet

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Duration of exposure:
24 h
Doses:
0.252, 0.5, 1.0, 2.0 mL/kg bw = 179, 355, 710 and 1420 mg/kg bw (conversion in mg/kg bw is based on the density d: 0.71 g/cm3)
No. of animals per sex per dose:
5 (males only)
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: daily
- Frequency of weighing: day 0, 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology

Results and discussion

Effect levels
Sex:
male
Dose descriptor:
LD50
Effect level:
582 mg/kg bw
95% CL:
376 - 895
Remarks on result:
other: original value 0.82 mL/kg
Mortality:
1420 mg/kg bw: 5/5, days to death: 1, 1, 1, 1, 1
710 mg/kg bw: 3/5, days to death: 6, 1, 1
355 mg/kg bw: 1/5, days to death: 1
179 mg/kg bw: 0/5
Clinical signs:
Local effects: the substance caused hemorrhage and necrosis of the skin and underlaying muscular layers
Body weight:
The survivors of the 355 and 710 mg/kg bw dose group lost weight
Gross pathology:
Animals that died: pale or mottled livers, pale, mottled or roughened surfaces of the kidneys, and congested or hemorrhagic intestines. Spleens were darkened to the point of being called black, pancreas congested and testes hemorrhagic.

Applicant's summary and conclusion

Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
The mean lethal dose of the test substance after single dermal application for 24 hours was found to be 582 mg/kg bw in rabbits.
Executive summary:

Penetration of rabbit skin was estimated by a technique closely to the one-day cuff method of Draize and associates, using groups of 5 male albino rabbits weighing 2 to 3 kg. The fur was removed from the entire trunk by clipping. The different substance concentrations (0.252, 0.5, 1.0, 2.0 mL/kg bw) were retained beneath an impervious plastic film. The animals were immobilized during the 24 hour contact period, after which the film was removed and the rabbits were caged for the subsequent 14-day observation period. Based on the available mortality data a LD50 of 0.82 mg/L (equivalent to 582 mg/kg bw) was derived. The substance provoked local effects (hemorrhage and necrosis of the skin and underlaying muscular layers). Moreover, gross pathology analysis revealed effects on the liver, kidneys, intestines, spleens, pancreas and testes.