Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1976
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented publication/study carried out according to national standards

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1976
Report Date:
1976

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
other: US-Federal Hazardous Substance Act (FHSA) Guideline 16.CFR 1500.40
Deviations:
no
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Hedione
- Substance type: pure active substance
- Analytical purity: > 95 %
- isomers composition: ca. 10 % cis- and 90 % trans- isomers

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
not specified
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Not provided in study report
- Age at study initiation: Not provided in study report
- Weight at study initiation: Not provided in study report
- Fasting period before study: Not provided in study report
- Housing: Not provided in study report
- Diet (e.g. ad libitum): Not provided in study report
- Water (e.g. ad libitum): Not provided in study report
- Acclimation period: Not provided in study report


ENVIRONMENTAL CONDITIONS
- Temperature (°C): Not provided in study report
- Humidity (%): Not provided in study report
- Air changes (per hr): Not provided in study report
- Photoperiod (hrs dark / hrs light): Not provided in study report

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: area ca. 12 cm wide covering the entire circumference of the rabbit. Skin was abraded
- % coverage: > 10% body surface area
- Type of wrap if used: animals were wrapped with binders of rubber dam, gauze and adhesive tape


REMOVAL OF TEST SUBSTANCE
- Washing (if done): not performed


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 5 g/kg
Duration of exposure:
24 hours
Doses:
5 g/kg (limit test)
No. of animals per sex per dose:
10 (sex not specified)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animal were wighted before and after treatment and were observed 24 hours after application and for a period of 14 days.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, skin irritation
Statistics:
Not applicable (limit test)

Results and discussion

Preliminary study:
Not performed/Not Applicable
Effect levels
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no 95% CL provided
Mortality:
One rat died after 3 days
Clinical signs:
Diarrhea was observed in 4 rabbits on day 1 (reversible)
Body weight:
No significant bodyweight changes observed
Gross pathology:
No abnormalities were noted
Other findings:
Skin irritation, type of irritation observed and number of rats reacting:
- Slight redness: 3, Moderate redness: 7
- Slight edema: 6, Moderate edema: 3

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: other: Federal Hazardous Substance Act - FHSA 16 CFR 1500.40
Executive summary:

Introduction. Acute dermal toxicity of the test material was determined according to the Federal Substance Hazardous Act (FHSA) test guideline 16 CFR 1500.40 on acute dermal toxicity.

Methods. Pure test material was tested at a unique dose level of 5 g/kg in occlusive conditions for 24 hours on abraded skin in a group of ten New Zealand white albino rabbits. Animals were observed for 14 days for mortality, clinical signs and bodyweight changes. A necropsy was performed on all animals at the end of the study.

Results and conclusions. Diarrhea was observed in four animals on day 1 and one animal died on day 3. The harsh skin test conditions used in that test (48h exposure on abraded skin, occlusive conditions) lead to local skin irritation in some animals. No clinical signs were otherwise observed, expected bodyweight gains were monitored at the end of the study and no abnormalities were noted during the necropsy.

The LD50 was therefore determined to greater than 5000 mg/kg and the test material is classified as non toxic according to FHSA criteria for acute dermal toxicity.