2,2',6,6'-tetra-tert-butyl-4,4'-methylenediphenol

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: Equivalent to OECD 402. GLP study.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2,2',6,6'-tetra-tert-butyl-4,4'-methylenediphenol

EC Number:

204-279-1

EC Name:

2,2',6,6'-tetra-tert-butyl-4,4'-methylenediphenol

Cas Number:

118-82-1

Molecular formula:

C29H44O2

IUPAC Name:

2,6-di-tert-butyl-4-[(3,5-di-tert-butyl-4-hydroxyphenyl)methyl]phenol

Details on test material:

- Physical state: Pale yellow powder
- Analytical purity: 99.04%
- Lot/batch No.: 5/87; Indent 9200/9622
- Storage condition of test material: Following its arrival in Compound Control this test substance was stored in the dark at ambient temperature.
- Stability: Infra-red spectra of the test substance were taken. There were no significant differences between the spectra and so, on this basis, the test substance was judged to have been stable for the duration of this study.

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River U.K. Ltd.
- Age at study initiation: 9-11 weeks old
- Weight at study initiation: males: 204-227 g; females: 145-157 g
- Fasting period before study: All animals were fasted overnight (18 hours).
- Housing: On arrival, animals were housed in single sex groups of up to 12 to a cage; each cage measured 56 cm x 38 cm x 18 cm. Prior to experimentation the animals were rehoused (as single sex groups of four) in cages with stainless-steel wire-mesh floors and tops; each cage measured 38 cm x 25 cm x 18 cm. At least two days before dosing, the rats were housed in groups of two or three animals of the same sex per cage.
- Diet (e.g. ad libitum): PRD, Labsure Animal Foods, Dorset, ad libitum.
- Water (e.g. ad libitum): Filtered water from the public supply, ad libitum.
- Acclimation period: Two weeks


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25 ºC
- Humidity (%): Not documented.
- Air changes (per hr): Not documented.
- Photoperiod (hrs dark / hrs light): Lighting was automatically switched on for the day (06.00 to 18.00 hours GMT) and off for the night (18.00 to 06.00 hours GMT)

Administration / exposure

Vehicle:

other: moistened

Details on dermal exposure:

The day before dosing, approximately 60% of the dorsal hair of all animals was closely shorn with fine electric clippers. Before application of the tst material, the skin was visually inspected to ensure that all micro-abrasions of the stratum corneum had healed.

The calculated dose was weighed onto a piece of aluminium foil lined with gauze and applied to the shorn skin. The foil was held in place by a double overwrap of waterproof adhesive tape.

After the 24 h exposure, the tape and foil were removed and the skin washed with warm dilute detergent solution and then dried.

Duration of exposure:

24 hours

Doses:

2000 mg/kg

No. of animals per sex per dose:

Five animals per sex

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed for signs of toxicity three times a day for the first three days and daily thereafter for the remainder of the 14 day observation period. Initial (Day 1), Day 7 and Day 14 body weights were recorded.
- Necropsy of survivors performed: necropsies were not conducted.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

None of the rats died.

Clinical signs:

other: There were no clinical signs observed.

Any other information on results incl. tables

Table 7.2.3:      Summary of Acute Dermal Toxicity

Males			Females
Dose	Mortality	Time of death	Dose	Mortality	Time of death
2000 mg/kg	0/5	--	2000 mg/kg	0/5	--

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute (24 h) percutaneous LD50 of the test powder in rats was greater than 2000 mg/kg.

Executive summary:

Five rats per sex were dermally dosed at 2000 mg/kg. Animals were observed for clinical signs three times a day for the first three days and daily thereafter for the remainder of the 14 day observation period. The initial (Day 1), Day 7 and Day 14 body weights were recorded. None of the rats died. There were no clinical signs observed. The acute dermal LD50 of the test material in rats was greater than 2000 mg/kg.