Reaction mass of 4-tert-butyl-2,5-xylenol and 6-tert-butyl-2,4-xylenol

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Between 22 February 2010 and 11 March 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Meets the requirements of GLP. There are no deviations from the recommended guideline.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Reaction mass of 2-tert-butyl-4,6-dimethylphenol and 4-tert-butyl-2,5-dimethylphenol

EC Number:

911-254-5

Molecular formula:

Not applicable - Multiconstituent substance

IUPAC Name:

Reaction mass of 2-tert-butyl-4,6-dimethylphenol and 4-tert-butyl-2,5-dimethylphenol

Test material form:

liquid

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Elevage de Gérome (Quartier Labaste - F40260 Linxe)
- Age at study initiation: 12 or 13 weeks old
- Weight during the test: between 2.53 kg and 3.38 kg
- Housing: individual box installed in conventional air conditioned animal husbanding
- Diet (e.g. ad libitum): foodstuff (SDS - C15) was supplied freely
- Water (e.g. ad libitum): Drinking water (tap-water from public distribution system) was supplied freely
- Acclimation period: minimal 5-day acclimatisation period

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23°C
- Humidity (%): 30 to 70%
- Air changes (per hr): approximately fifteen changes per hour
- Photoperiod (hrs dark / hrs light): twelve hours continuous light (07.00 to 19.00) and twelve hours darkness

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

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

Duration of treatment / exposure:

Exposure: one instillation

Observation period (in vivo):

Ocular examinations were performed on both right and left eyes 1 hour, 24, 48 and 72 hours following treatment.
If no reaction is obsetyed 72 hours after instillation, the study is terminated. In case of persistent reactions, additional obsetvations can be carried out from D4 to D21 in order to determine the reversible character of the lesions observed.

Number of animals or in vitro replicates:

3 female animals

Details on study design:

SCORING SYSTEM: Eye examinations are carried out using the scale of lesion scores In the following order: chemosis, discharge, redness, iris, cornea (degree and extent of opacity).

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

chemosis score

Basis:

animal #1

Remarks:

animal A0016

Time point:

24/48/72 h

Score:

2.3

Max. score:

3

Reversibility:

fully reversible within: 10 days

Results 2

Irritation parameter:

chemosis score

Basis:

animal #2

Remarks:

animal A0022

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 8 days

Results 3

Irritation parameter:

chemosis score

Basis:

animal #3

Remarks:

animal A0024

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 8 days

Results 4

Irritation parameter:

conjunctivae score

Basis:

animal #1

Remarks:

animal A0016

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 11 days

Results 5

Irritation parameter:

conjunctivae score

Basis:

animal #2

Remarks:

animal A0022

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 10 days

Results 6

Irritation parameter:

conjunctivae score

Basis:

animal #3

Remarks:

animal A0024

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 10 days

Results 7

Irritation parameter:

iris score

Remarks:

lesion

Basis:

animal #1

Remarks:

animal A0016

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 4 days

Results 8

Irritation parameter:

iris score

Remarks:

lesion

Basis:

animal #2

Remarks:

animal A0022

Time point:

24/48/72 h

Score:

0.3

Max. score:

1

Reversibility:

fully reversible within: 2 days

Results 9

Irritation parameter:

iris score

Remarks:

lesion

Basis:

animal #3

Remarks:

animal A0024

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 7 days

Results 10

Irritation parameter:

cornea opacity score

Remarks:

opacity

Basis:

animal #1

Remarks:

animal A0016

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 7 days

Results 11

Irritation parameter:

cornea opacity score

Remarks:

opacity

Basis:

animal #2

Remarks:

animal A0022

Time point:

24/48/72 h

Score:

1.3

Max. score:

2

Reversibility:

fully reversible within: 7 days

Results 12

Irritation parameter:

cornea opacity score

Remarks:

opacity

Basis:

animal #3

Remarks:

animal A0024

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 7 days

Any other information on results incl. tables

The ocular reactions observed during the study have been moderate and totally reversible:

-  at the conjunctivae level: a moderate redness noted 1 hour after the test item instillation and totally reversible between days 10 and 11 associated with a moderate chemosis noted 24 hours after the test item instillation and totally reversible between days 8 and 10.

-  at the iris level: a congestion, noted 24 hours after the test item instillation, and totally reversible between days 2 and 7.

-  at the corneal level: a moderate corneal opacity, noted 24 hours after the test item instillation, and totally reversible at day 7.

Furthermore, a corneal neovascularisation was noted at day1 in one animal, between day 1 and day 3 in a second animal and between day 2 and day 8 in the last one.

Applicant's summary and conclusion

Interpretation of results:

other: Eye irritant (Cat 2) (CLP Regulation EC no. 1272/2008)

Conclusions:

In conclusion, the results obtained, under these experimental conditions, enable to conclude that the test item is irritating to eyes.

Executive summary:

The test item was instilled as supplied, into the eye of threeNew Zealandrabbits at the dose of 0.1 mL. The experimental protocol was established on the basis of the official method as defined in the O.E.C.D. guideline n° 405 and the test method B.5 of the council regulation n° 440/2008. The ocular reactions observed during the study have been moderate and totally reversible:

-  at the conjunctivae level: a moderate redness noted 1 hour after the test item instillation and totally reversible between days 10 and 11 associated with a moderate chemosis noted 24 hours after the test item instillation and totally reversible between days 8 and 10.

-  at the iris level: a congestion, noted 24 hours after the test item instillation, and totally reversible between days 2 and 7.

-  at the corneal level: a moderate corneal opacity, noted 24 hours after the test item instillation, and totally reversible at day 7.

Furthermore, a corneal neovascularisation was noted at day 1 in one animal, between day 1 and day 3 in a second animal and between day 2 and day 8 in the last one.

In conclusion, the results obtained, under these experimental conditions, enable to conclude that the test item is irritating to eyes.