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

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

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 22 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 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

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 this study the test material was warmed in a water bath set at 60°C to produce a liquid. The test material was allowed to reach room temperature before use.

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: David Percival Ltd, Moston, Sandbach, Cheshire, UK
- Age at study initiation: twelve to sixteen weeks old.
- Weight at study initiation: 2.90 to 3.20 kg
- Housing: individually in suspended metal cages
- Diet (e.g. ad libitum): ad libitum (STANRAB SQC Rabbit Diet, Special Diets Services Ltd, Witham, Essex, UK)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23
- Humidity (%): 30 to 70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To:

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: The left eye remained untreated and was used for control purposes.

Amount / concentration applied:

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

Duration of treatment / exposure:

single treatment

Observation period (in vivo):

Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment.

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no


SCORING SYSTEM:
Assessment of ocular damage/irritation was made according to the numerical evaluation (from Draize J. H. (1977) “Dermal and Eye Toxicity Tests” in: Principles and Procedures for Evaluating the Toxicity of Household Substances, National Academy of Sciences, Washington DC p.48 to 49).

TOOL USED TO ASSESS SCORE: light source from a standard ophthalmoscope.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #1

Time point:

other: overall at 1, 24, 48 and 72 h

Score:

0

Max. score:

1

Reversibility:

fully reversible within: 24 h

Remarks on result:

other: max.score at 1 h

Results 2

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #2

Time point:

other: overall at 1, 24, 48 and 72 h

Score:

0

Max. score:

1

Reversibility:

fully reversible within: 24 h

Remarks on result:

other: max. score at 1h

Results 3

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #3

Time point:

other: overall at 1, 24, 48 and 72 h

Score:

0

Max. score:

1

Reversibility:

fully reversible within: 24 h

Remarks on result:

other: max. score at 1 h

Results 4

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: overall at 1, 24, 48 and 72 h

Score:

0

Max. score:

1

Reversibility:

fully reversible within: 24 h

Remarks on result:

other: max.score at 1h

Results 5

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

other: overall at 1, 24, 48 and 72 h

Score:

0

Max. score:

1

Reversibility:

fully reversible within: 24 h

Remarks on result:

other: max. score at 1 h

Results 6

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

other: overall at 1, 24, 48 and 72 h

Score:

0

Max. score:

1

Reversibility:

fully reversible within: 24 h

Remarks on result:

other: max. score at 1 h

Results 7

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: overall at 1, 24, 48 and 72 h

Score:

0

Max. score:

0

Results 8

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

other: overall at 1, 24, 48 and 72 h

Score:

0

Max. score:

0

Results 9

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

other: overall at 1, 24, 48 and 72 h

Score:

0

Max. score:

0

Results 10

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: overall at 1, 24, 48 and 72 h

Score:

0

Max. score:

0

Results 11

Irritation parameter:

iris score

Basis:

animal #2

Time point:

other: overall at 1, 24, 48 and 72 h

Score:

0

Max. score:

0

Results 12

Irritation parameter:

iris score

Basis:

animal #3

Time point:

other: overall at 1, 24, 48 and 72 h

Score:

0

Max. score:

0

Irritant / corrosive response data:

No corneal or iridial reactions were noted during the study.
Minimal conjunctival irritation was noted in all treated eyes at the 1-hour observation.
All treated eyes appeared normal at the 24-hour observation.

Other effects:

No

Any other information on results incl. tables

TABLE 2
INDIVIDUAL SCORES AND INDIVIDUAL TOTAL SCORES FOR OCULAR IRRITATION
Rabbit Number and Sex (Bodyweight kg)	IPR = 1				IPR = 1				IPR = 1
	132 Male (3.20)				23 Male (2.90)				25 Male (2.99)
Time After Treatment	1 hr	24 hr	48 hr	72 hr	1 hr	24 hr	48 hr	72 hr	1 hr	24 hr	48 hr	72 hr
CORNEA
- Degree of Opacity	0	0	0	0	0	0	0	0	0	0	0	0
- Area of Opacity	0	0	0	0	0	0	0	0	0	0	0	0
Score (E x F) x 5	0	0	0	0	0	0	0	0	0	0	0	0
IRIS
	0	0	0	0	0	0	0	0	0	0	0	0
Score (D x 5)	0	0	0	0	0	0	0	0	0	0	0	0
CONJUNCTIVAE
- Redness	1	0	0	0	1	0	0	0	1	0	0	0
- Chemosis	1	0	0	0	1	0	0	0	1	0	0	0
- Discharge	0	0	0	0	1	0	0	0	1	0	0	0
Score (A + B + C) x 2	4	0	0	0	6	0	0	0	6	0	0	0
Total Score	4	0	0	0	6	0	0	0	6	0	0	0
Key: hr - hour(s), IPR - initial pain reaction

Applicant's summary and conclusion

Interpretation of results:

other: not classified according to the EU Directive 67/548/EEC

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The test material, OS 144267, produced a maximum group mean score of 5.3 and was classified as a MINIMAL IRRITANT (CLASS 3 ON A 1 TO 8 SCALE) to the rabbit eye according to a modified Kay and Calandra classification system.
The test material did not produce positive criteria in any rabbit according to the EU labelling regulations. No symbol and risk phrase are therefore required.

Executive summary:

A GLP study was performed to assess the irritancy potential of the test material to the eye of the New Zealand White rabbit. The method used followed that described in the OECD guideline 405 and in the EU Method B.5. A single instillation of 0.1 mL of undiluted test material to the non-irrigated eye of three rabbits produced minimal conjunctival irritation. All treated eyes appeared normal at the 24-hour observation. No control animals were used. One eye of each animal remained untreated and was used for control purposes. The test material produced a maximum group mean score of 5.3 and was classified as a minimal irritant (Class 3 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system. However the test material did not meet the criteria for classification as irritant according to EU labelling regulations (Directive 67/548/EEC). No symbol and risk phrase are required.