2,6-di-tert-butyl-α-dimethylamino-p-cresol

Acute Toxicity: dermal

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

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

Test material information

Constituent 1

Reference substance name:

2,6-di-tert-butyl-α-dimethylamino-p-cresol

EC Number:

201-816-1

EC Name:

2,6-di-tert-butyl-α-dimethylamino-p-cresol

Cas Number:

88-27-7

Molecular formula:

C17H29NO

IUPAC Name:

2,6-di-tert-butyl-4-[(dimethylamino)methyl]phenol

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 or test system 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

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.