Registration Dossier

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:
other: Comparable to guideline study with acceptable restrictions (only 4 animals per group, occlusive wrapping, limited reporting)

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1962
Report Date:
1962

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
: only 4 animals per group, occlusive wrapping, limited reporting
Principles of method if other than guideline:
Pre-guideline test, but method similar to OECD TG 402
GLP compliance:
no
Remarks:
pre-GLP study
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 2-Methyl propionic acid
- Analytical purity: no data
- Impurities (identity and concentrations): no data
- Stability under test conditions: no data
- Storage condition of test material: no data

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: no data
- Age at study initiation: no data
- Weight at study initiation: 2.5 - 3.5 kg

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: part of the trunk
- % coverage: no data
- Type of wrap if used: impervious plastic film

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no data
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): graduate doses were applied, but individual doses are not specified
Duration of exposure:
24 hours
Doses:
no individual doses specified
No. of animals per sex per dose:
4
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: no data
- Necropsy of survivors performed: no data
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: no data
Statistics:
LD50 values were calculated by the method of Thompson (1947, Bacteriol. Rev. 11, 115) using the tables of Weil (1952, Biometrics 8, 249. The limits of ± 1.96 standard deviations are presented.

Results and discussion

Effect levels
Sex:
male
Dose descriptor:
LD50
Effect level:
0.5 mL/kg bw
Remarks on result:
other: corresponds to 474 mg/kg
Mortality:
no data

Any other information on results incl. tables

Fiducial range of LD50 value (presented as ± 1.96 S.D.) was from 0.37 - 0.67 mL/kg.

Values converted to mg/kg are (substance density = 0.949): 474 mg/kg (351 - 636 mg/kg).

There is no information on local effects reported.

Applicant's summary and conclusion

Interpretation of results:
Category 3 based on GHS criteria
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute dermal LD50 for isobutyric acid was 474 mg/kg bw in male rabbits requiring the classification as harmful according to EU legislation.
Executive summary:

The acute dermal toxicity of isobutyric acid was determined in groups of 4 male albino New Zealand rabbits receiving graduate single doses of test substance per group. Number and quantity of indivual doses are not specified. The exposure time was 24 hours followed by an observation period of 14 days. From mortality data, the LD50 and a range of ± 1.96 SD was calculated according to the method of Thomson (1947).

Overall the study was conducted similar to OECD test guideline 403 with some restrictions (only 4 animals per group, occlusive wrapping, limited reporting).

 

The acute dermal LD50 was 474 mg/kg bw in rabbits (Smyth, 1962).

 

Based on this LD50 value, isobutyric acid requires classification as harmful according to EU regulations.