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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:
supporting study
Study period:
1973
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Remarks:
Only 2 animals/sex used, diluted substance (50%), Occlusive patch instead of semi-acclusive. The study was not considered sufficient in its own for acute dermal toxicity endpoint and was therefore used in a weight of evidence assessment.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1973
Report Date:
1973

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
basic data given; no details on environmental conditions of animal room; occlusive dressing and 2 animals/sex/dose used
Principles of method if other than guideline:
The test substance was applied to skin of albino rabbits with occlusive patch for 24 h at dose of 2000 mg/kg bw. The animals were observed for mortality, clinical signs and body weight for 14 days and then necropsied for macroscopic observations.
GLP compliance:
no
Remarks:
pre-GLP
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Test material form:
not specified
Details on test material:
- Physical state: not reported
- Storage condition of test material: not reported
- Source: Firmenich Incorporated

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Housing: Animals were housed individually in suspended wire-bottomed cages.
- Diet: Food (standard laboratory ration), ad libitum
- Water, ad libitum
- Acclimation period: 7 days

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
PRETREATMENT
- Twenty-four hours prior to the dermal applications, the backs of the rabbits were shaved free of hair with electric clippers. The shaved area on each animal constituted about 30% of the total body surface area. The animals were then returned to their cages to await testing on the following day. The 24 h waiting period allowed recovery of the stratum corneum from the disturbance which accompanied the close- clipping procedure and permitted healing of any microscopic abrasions possibly produced during the process.

TEST SITE
- Area of exposure: Backs of rabbits
- % coverage: 30% of the total body surface area
- Type of wrap if used: Test site was covered by wrapping the trunk of the animal with impervious plastic sheeting which was securely taped in place. This plastic wrap insured close contact of the epidermis and test material. To prevent oral ingestion of the test material, each animal was fitted with a light-weight, flexible plastic collar which was worn throughout the observation period.

REMOVAL OF TEST SUBSTANCE
- Washing: At the end of exposure (24 h), the plastic sheeting and all residual test material were removed.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Concentration: Test material was applied undiluted
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
2
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Test sites were examined for local skin reactions and the animals were returned to their cages. Observations for mortality, local skin reactions, and behavioural abnormalities were continued for a total of 14 days following the skin applications. Initial and final body weights were recorded.
- Necropsy of survivors performed: Yes, at the end of observation, necropsy was conducted on all animals.
Statistics:
None

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks:
50%
Remarks on result:
other: 100% test substance: > 1000 mg/kg bw
Mortality:
No mortality was observed during the study.
Clinical signs:
No untoward behavioral reactions were noted.
Body weight:
Two animals (1 male and 1 female) showed weight gain, but weight loss was observed in remaining two animals (1 male and 1 female).
Gross pathology:
Necropsy of all animals did not reveal any gross pathologic alterations other than the dermal alterations.
Other findings:
Skin reactions observed at 24 h were pale red to red, well-defined erythema and barely perceptible edema. Severe desquamation was observed at 7and 14 days.

Any other information on results incl. tables

None

Applicant's summary and conclusion

Interpretation of results:
study cannot be used for classification
Conclusions:
This study cannot be used for classification since the test substance was not tested up to limit doses which are relevant for classification according to the annex VI of the Regulation EC No. 1272/2008 (CLP) and to the GHS.
Executive summary:

In an acute dermal toxicity study (limit test), a group of New Zealand Albino rabbits (2/sex) were given a single dermal application of test substance at 2000 mg/kg bw. The test substance ( 50% N-1505 573507 GEL) was applied topically to the shaved skin area of the animals and covered with occlusive binding for 24 h. Animals were observed for toxicity, clinical signs and body weight for 14 days and then necropsied for macroscopic observations.

 

No mortality or clinical signs were observed. Skin reactions observed at 24 h were pale red to red, well-defined erythema and barely perceptible edema. Severe desquamation was observed at 7and 14 days. No other gross pathologic alterations were observed.

 

Dermal median LD50 rabbit (50%) > 2000 mg/kg bw, thus dermal median LD50 rabbit (100%) > 1000 mg/kg bw

                                                                     

This study cannot be used for classification since the test substance was not tested up to limit doses which are relevant for classification according to the annex VI of the Regulation EC No. 1272/2008 (CLP) and to the GHS.

The study was not considered sufficient in its own for acute dermal toxicity endpoint.