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Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study (OECD 405)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Phenol, 2,6-bis(1,1-dimethylethyl)
- Substance type: di-alkylphenol
- Physical state: white crystalline solid
- Analytical purity: 99.26% (GC)
- Purity test date: 03/10/1990
- Lot/batch No.: 2,6-AP/308
- Storage condition of test material: in original container at room temperature in the dark

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: approximately twelve to sixteen weeks old
- Weight at study initiation: 2.64-3.14 kg
- Housing: The animals were individually housed in suspended metal cages
- Diet: ad libitum (Spillers Rabbit Diet, Dalgety Agriculture Ltd., Almondsbury, Bristol)
- Water: ad libitum, drinking water
- Acclimation period:minimum acclimatisation period of five days

Immediately before the start of the test, both eyes of the three provisionally selected test rabbits were examined for evidence of ocular irritation or defect with the aid of a light source from a standard ophthalmoscope. Animals showing evidence of ocular lesions were rejected and replaced.

ENVIRONMENTAL CONDITIONS
- Temperature: the animal room was maintained at 18-20°C
- Humidity: 49-61%
- Air changes: approximately 15 changes per hour
- Photoperiod: 12 hrs dark / 12 hrs light

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: The left eye remained untreated and was used for control purposes
Amount / concentration applied:
A volume of 0.1 ml of the test material, which was found to weigh approximately 67 mg (as measured by gently compacting the required volume into an adapted syringe
Duration of treatment / exposure:
1 second
Observation period (in vivo):
1, 24, 48 and 72 hours
Number of animals or in vitro replicates:
3
Details on study design:
The test material was placed into the conjunctival sac of the right eye, formed by gently pulling the lower lid away from the eyeball. The upper and lower eyelids were held together for about one second immediately after application, to prevent loss of the test material, and then released. Immediately after administration of the test material, an assessment of the initial pain reaction was made.

SCORING SYSTEM: Assessment of ocular damage/irritation was made according to the numerical evaluation given by Draize J. H. 1959, Association of Food and Drug Officials of the United states, Austin, Texas, "The Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics"

Any other adverse ocular effects were also noted.

TOOL USED TO ASSESS SCORE: Examination of the eye was facilitated by use of the light source from a standard ophthalmoscope

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Remarks:
E = degree of opacity
Basis:
animal: #1, #2, #3
Time point:
other: 1, 24, 48, 72 hours
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Remarks:
F = area of opacity
Basis:
animal: #1, #2, #3
Time point:
other: 1, 24, 48, 72 hours
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
animal: #1, #2, #3
Time point:
other: 1, 24, 48, 72 hours
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Remarks:
A = redness
Basis:
animal: #1, #2, #3
Time point:
other: 1, 24, 48, 72 hours
Score:
0 - 2
Max. score:
3
Reversibility:
fully reversible
Remarks:
2 animals: within 24 hours. 1 animal: within 48 hours
Irritation parameter:
chemosis score
Remarks:
B = Conjunctivae chemosis
Basis:
animal: #1, #2, #3
Time point:
other: 1, 24, 48, 72 h
Score:
0 - 1
Max. score:
4
Reversibility:
fully reversible within: 24 hours
Irritation parameter:
conjunctivae score
Remarks:
C = discharge
Basis:
animal: #1, #2, #3
Time point:
other: 1, 24, 48, 72 hours
Score:
0
Max. score:
3
Irritant / corrosive response data:
No adverse corneal or iridial effects were noted during the study.
Minimal conjunctival irritation was noted in all treated eyes one hour after treatment and in one treated eye at the 24-hour observation.
All treated eyes appeared normal 48 hours after treatment.

Any other information on results incl. tables

Individual total scores and group mean scores for ocular irritation

Rabbit number and sex

Individual total scores at:

1 hr

24 hr

48 hr

72 hr

172 Female

4

0

0

0

193 Female

4

0

0

0

154 Male

6

2

0

0

Group total

14

2

0

0

Group mean score

4.7

1 hr

0.7

24 hr

0.0

48 hr

0.0

72 hr

Individual & mean scores for cornea, iris & conjunctivae required for EEC labelling regulations

Rabbit number and sex               (bodyweight Kg)

Time after treatment

Corneal opacity

Iridial inflammation

Conjunctival redness

Conjunctival chemosis

172 Female

(3.14)

24 hr

0

0

0

0

48 hr

0

0

0

0

72 hr

0

0

0

0

Total

 

0

0

0

0

Mean

 

0.0

0.0

0.0

0.0

193 Female

(2.64)

24 hr

0

0

0

0

48 hr

0

0

0

0

72 hr

0

0

0

0

Total

 

0

0

0

0

Mean

 

0.0

0.0

0.0

0.0

154 Male

(2.84)

24 hr

0

0

1

0

48 hr

0

0

0

0

72 hr

0

0

0

0

Total

 

0

0

1

0

Mean

 

0.0

0.0

0.3

0.0

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The test material produced a maximum group mean score of 4.7 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 produced positive criteria in any rabbit according to the EEC labelling regulations and was classified as non-orritant to the rabbit eye. No symbol and risk phrase are therefore required.
Executive summary:

A study was performed to assess the irritancy potential of the test material, DTBH, to the eye of the New Zealand White rabbit. The method used followed that described in the OECD Guidelines for testing of Chemicals (1987) No. 405 "Acute Eye Irritation/Corrosion" referenced as Method B5 in Commission Directive 84/449/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 83/467/EEC).

A single application of the test material to the non-irrigated eye of three rabbits produced minimal conjunctival irritation. All treated eyes appeared normal 48 hours after treatment.

The test material produced a maximum group mean score of 4.7 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 was also classified as non-irritant according to the EEC labelling regulations. No symbol and risk phrase are required.