Reaction mass of 2,6-di-tert-butylphenol and 2,4,6-tri-tert-butylphenol

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From November 26, 1900 to November 29, 1990

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The animal was killed before the end of the observation period. No GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

2,4,6-tri-tert-butylphenol; 2,6-di-tert-butylphenol

EC Number:

907-745-9

Molecular formula:

Not applicable - Multiconstituent substance

IUPAC Name:

2,4,6-tri-tert-butylphenol; 2,6-di-tert-butylphenol

Details on test material:

- Physical state: Clear pale yellow liquid on receipt, but solidified on storage at 0-5 ºC.
- Storage condition of test material: On its arrival the test substance was stored in the dark at ambient temperature. Following receipt of further information, the storage conditions were changed on 13th September 1990 to in the dark at between 0-5 ºC.

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Froxfield Farms U.K. Ltd.
- Age at study initiation: 3.5 to 5.5 months
- Weight at study initiation: male: 3.57 kg
- Housing: Animals were singly housed in hanging, stainless steel cages with perforated dimple or wire-mesh flooring. Sawdust-filled undertrays for excreta were placed beneath each cage and changed twice weekly. Each cage measured 91 cm x 66 cm x 45 cm.
- Diet (e.g. ad libitum): Pelleted diet (Standard Rabbit Diet, S.Q.C. Special Diet Services Ltd. ), ad libitum.
- Water (e.g. ad libitum): From public supply, ad libitum.
- Acclimation period: two weeks.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 15-20 ºC.
- Humidity (%): Animal room humidity exceeded the target range of 30-70% for more than two consecutirve (four hourly) recordings on six days of the study. The raised humidity had no overt effect upon the health of the rabbits.
- Air changes (per hr): not documented.
- Photoperiod (hrs dark / hrs light): 12 hours day and 12 hours night.


IN-LIFE DATES: From November 26, 1900 to November 29, 1990

Test system

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml

Duration of treatment / exposure:

The undiluted test material (0.1 ml) was placed into the lower conjunctival sac of one eye. The treated eye was gently held closed for a few seconds to prevent loss of the test material. The eyes were not irrigated.

Observation period (in vivo):

The irritation scores were recorded at 1, 4, 24 and 48 h.

Number of animals or in vitro replicates:

One animal (male).

Details on study design:

SCORING SYSTEM:
The immediate reactions of the rabbit were scored as an initial pain response using a six point scale. Other ocular reactions to treatment were noted and scored using standard grades (Study report - Attachment A).

Results and discussion

In vivo

Irritant / corrosive response data:

The conjunctivae developed a crimson-red appearance, an ocular discharge and chemosis sufficient to cause partial eversion of the eyelids within one hour of ocular instillation. Intensification of the conjunctival responses caused a beefy-red appearance and chemosis obscuring part of the cornea within 4 hours of treatment.
Minor corneal opacity had developed on the day after ocular instillation and persisted at subsequent examination.
As the conditions of the conjunctivae showed very little improvement during the two days after treatment the rabbit was killed on humane grounds.

Other effects:

Installation of 0.1 ml undiluted test substance into one eye of a single rabbit resulted in a moderate initial pain response.

Any other information on results incl. tables

Table 7.3.2: Eye irritation scores

	Redness	Chemosis	Opacity	Iris
1 hour	2	2a	0	0
4 hours	3	3a	0	0
24 hours	3	2b	1c	1
48 hours	3	2a	1d	1
a – Slight ocular discharge b – Ocular discharge c – Opacity affecting 25-50% of cornea d – Opacity affecting < 25% of cornea

Applicant's summary and conclusion

Interpretation of results:

Category 1 (irreversible effects on the eye)

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Since the rabbit was killed two days after the treatment, it it not possible to confirm if the ocular lesions were still present at the end of the observation period.
The substance is classified as "Irreversible effects on the eye, Cat 1" applying the precautionary principle.

Executive summary:

The aim of the study was to investigate the eye irritation potential of the test material.

The test procedure used was OECD Guideline 405 (Acute Eye Irritation / Corrosion).

Instillation of the undiluted test material into the eye of a single rabbit caused severe conjunctival irritation reactions within four hours of treatment. As there was little improvement in the condition of the conjunctivae, the rabbit was killed two days later. No further rabbits were treated because it was considered that the marked irritancy had been adequately demonstrated. Since the rabbit was killed two days after the treatment, it it not possible to confirm if the ocular lesions were still present at the end of the observation period.

The substance is classified as "Irreversible effects on the eye, Cat 1" applying the precautionary principle.