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: Similar to OECD guideline 402. Non-GLP study.

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:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
(Limit test requires five animals/sex. However, in the study five abraded rabbits and five intact rabbits were used)
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): Antioxidant 703
- Substance type: pale yellow powder
- Physical state: solid
- Lot/batch No.: 964-76

Test animals

Species:
rabbit
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: no data reported
- Age at study initiation: no data reported
- Weight at study initiation: 2.937 +/- 0.332 kg
- Housing: no data reported
- Diet (e.g. ad libitum): no data reported
- Water (e.g. ad libitum): no data reported

ENVIRONMENTAL CONDITIONS: no data reported

Administration / exposure

Type of coverage:
occlusive
Vehicle:
not specified
Details on dermal exposure:
TEST SITE
- Area of exposure: Upper back
- % coverage: Not reported
- Type of wrap if used: rabbits were wrapped with an impervious band

REMOVAL OF TEST SUBSTANCE
- Washing: After removal of the wrapping, the compound residue was gently flushed off.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 4000 mg/kg
Duration of exposure:
24 hours
Doses:
4000 mg/kg
No. of animals per sex per dose:
10 rabbits
- 5 rabbits Abraded
- 5 rabbits Intact
Control animals:
yes
Details on study design:
- Duration of observation period following administration: At 24 hours after removal of the wrapping and daily for 14 days
- Necropsy of survivors performed: yes - A macroscopic examination of the viscera was conducted on all rabbits survival at day 14.
- Other examinations performed: Body weights were recorded at Day 0, 3, 7, 10 and 14

Results and discussion

Preliminary study:
Range finding study:
Six rabbits were prepared for dosing by clipping the fur from the upper back and dermally applying equivalent doses of 1000 mg, 2000 mg or 4000 mg/kg body weight , two rabbits per dose . The rabbits were wrapped with an impervious band which was left in place for 24 hours. Observations for mortality were made for 72 hours
Effect levels
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 4 000 mg/kg bw
Based on:
test mat.
Mortality:
> 50% of the animals tested survived
Body weight:
Body weight gain over the 14-day observation period was acceptable for all survivors.
Gross pathology:
Macroscopic examination of the viscera revealed no treatment related observations.
Other findings:
Daily observation:
- Three of the 10 rabbits died during the first 48 hours. All of these animals were treated on abraded skin. A fourth rabbit died on day 9. This was the only death observed in an animal with intact skin.
- Three rabbits showed slight erythema at the treatment site at 24 hours. No other dermal or behavioral reactions were noted.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Rabbits were exposed during 24 hours to the test item according to test procedure in accordance with generally accepted scientific standards. The test substance was applied to 5 test animals with abraded skin and 5 test animals with intact skin. 3 of the animals with abraded skin died within the first 48 h indicating that test substance absorption was higher and faster when the skin was damaged. One animal with intact skin died on day 9. As the overall mortality was 40%, the LC50 is considered to be higher than 4000 mg/kg bw. Therefore, a classification for acute dermal toxicity according to Regulation 1272/2008/EC and amendments and Directive 67/548/EEC and amendments is not warranted following the study results.
Executive summary:

Ten rabbits were exposed to a limit dose of 4000 mg/kg bw to the test item under occlusive conditions for 24 h. The dose was chosen after a preliminary dose range finding study. In 5 animals the skin was abraded. The observation period was 14 days. Four of 10 animals died during the study (3 with abraded skin and one with intact skin). The LD50 was therefore > 4000 mg/kg bw. No signs of systemic toxicity and only slight erythema in three animals after 24h only. The results of this study show that the substance should not be classified for acute dermal toxicity following Regulation 1272/2008/EC and amendments and Directive 67/548/EEC and amendments.