reaction mass of isomers of: C7-9-alkyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Study period:

between 17 January 2000 and 31 January 2000.

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Details on test material:

- Name of test material (as cited in study report): OS 144267
- Molecular formula (if other than submission substance): C21H34O3
- Molecular weight (if other than submission substance): 334.491
- Smiles notation (if other than submission substance): Oc1c(C(C)(C)C)cc(cc1C(C)(C)C)CCC(=O)OCCCC
- InChl (if other than submission substance): 1S/C21H34O3/c1-8-9-12-24-18(22)11-10-15-13-16(20(2,3)4)19(23)17(14-15)21(5,6)7/h13-14,23H,8-12H2,1-7H3
- Structural formula attached as image file (if other than submission substance): see Fig.1
- Substance type: alkylated phenol
- Physical state: yellow crystalline solid block
- Analytical purity: Data relating to the identity, purity and stability of the test material are the responsibility of the Sponsor
- Storage condition of test material: room temperature in the dark
- Other: For the purpose of the study the test material was warmed in a water bath set at 60°C to produce a liquid and allowed to cool at room temperature.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd, Margate, Kent
- Age at study initiation: eight to twelve weeks old
- Weight at study initiation: the males weighed 206 to 219 g, and the females 205 to 220g
- Fasting period before study: no
- Housing: in suspended polypropylene cages furnished with woodflakes. The animals were housed individually during the 24-hour exposure period and in groups of five, by sex, for the remainder of the study.
- Diet (e.g. ad libitum): ad libitum (Rat and Mouse Expanded Diet No.1, Special Diets Services Limited, Witham, Essex, UK)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25
- Humidity (%): 30 to 70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To:

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: back and flanks
- % coverage: approximately 10% of the total body surface area
- Type of wrap if used: A piece of surgical gauze was placed over the treatment area and semi-occluded with a piece of self-adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): After exposure period the bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with distilled water to remove any residual test material.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): The appropriate amount of the test material was applied to shorn skin using a graduated syringe.
- For solids, paste formed: For the purpose of the study the test material was warmed in a water bath set at 60°C to produce a liquid and allowed to cool at room temperature.

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed for deaths or overt signs of toxicity 1/2, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days. Individual bodyweights were recorded prior to application of the test material on Day 0 and on Days 7 and 14.
- Necropsy of survivors performed: yes. At the end of the study the animals were killed and subjected to gross pathological examination. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorde. No tissues were retained.
- Other examinations performed: clinical signs, body weights

Statistics:

Using the mortality data obtained, an estimate of the acute dermal median lethal dose (LD50) of the test material was made.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

There were no deaths.

Clinical signs:

other: No signs of toxicity were noted during the study.

Gross pathology:

Effects on organs:
No abnormalities were noted at necropsy.

Other findings:

Signs of toxicity (local):
No signs of dermal irritation were noted during the study.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information according to the EU labelling Regulations (Commission Directive 93/21/EEC) Criteria used for interpretation of results: EU

Conclusions:

The acute dermal median lethal dose (LD50) of the test material in the Sprague-Dawley CD strain rat was found to be greater than 2000 mg/kg bodyweight. No symbol and risk phrase are required according to EU labelling regulations.

Executive summary:

A study was performed to assess the acute dermal toxicity of the test material in the Sprague-Dawley CD strain rat. The method used followed that described in the OECD Guidelines for Testing of Chemicals No. 402 "Acute Dermal Toxicity" (adopted 24 February 1987) and Method 63 of Commission Directive 92/69/EEC (which constitutes Annex V of Council Directive 67/548/EEC). The results may be used as a basis for classification and labelling under Annex VI of Council Directive 67/548/EEC (as adapted to technical progress by Commission Directive 93/2 l/EEC) relating to the classification, packaging and labelling of dangerous substances.

A group of ten animals (five males and five females) was given a single 24-hour, semioccluded dermal application to intact skin at a dose level of 2000 mg/kg bodyweight. The animals were observed for fourteen days after the day of treatment and were then killed for gross pathological examination. There were no deaths. No signs of toxicity or dermal irritation were noted during the study. All animals showed expected gain in bodyweight during the study. No abnormalities were noted at necropsy. The acute dermal median lethal dose (LD50) of the test material in the Sprague- Dawley CD strain rat was found to be greater than 2000 mg/kg bodyweight.

No symbol and risk phrase are required.