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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: According to guideline; under GLP conditions.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1995
Report date:
1995

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
EPA OPP 81-4 (Acute Eye Irritation)
Deviations:
no
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
1-(allyloxy)-2-methyl-1-oxopropan-2-yl 2-chloro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-3,6-dihydropyrimidin-1(2H)-yl]benzoate
EC Number:
603-837-5
Cas Number:
134605-64-4
Molecular formula:
C20H18ClF3N2O6
IUPAC Name:
1-(allyloxy)-2-methyl-1-oxopropan-2-yl 2-chloro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-3,6-dihydropyrimidin-1(2H)-yl]benzoate
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Physical state: solid (tan powder)
- Storage condition of test material: stored at room temperature.

Test animals / tissue source

Species:
rabbit
Strain:
other: Hra:(NZW)SPF
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Recognised animal supplier.
- Age at study initiation: Not reported.
- Weight at study initiation: 2553 - 2948 g
- Housing: housed in screen-bottom stainless steel cages
- Diet (e.g. ad libitum): Certified rabbit diet, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: At least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 23
- Humidity (%): 50 +/- 20
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12h light/12h dark

IN-LIFE DATES: From: To: 1995-07-11 to 1995-07-15

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 61 mg (0.1 ml weight equivalent).

VEHICLE
- Amount(s) applied (volume or weight with unit): The test material was administered as received.
- Concentration (if solution): n/a
- Lot/batch no. (if required): n/a
- Purity: n/a
Duration of treatment / exposure:
The eyes of the rabbits in Group 1 remained unflushed immediately after treatment while the treated eyes of the rabbits in Group 2 were flushed with lukewarm tap water for 1 minute starting 30 seconds after test material instillation.
Observation period (in vivo):
The treated eyes of both groups were observed for ocular irritation at 1, 24, 48, and 72 hours after treatment. Additional observations were made at 96 hours after treatment for the animals in Group 1. Irritation was graded and scored according to the Draize technique using a penlight as the source of illumination. A sodium fluorescein examination was used to aid in revealing possible corneal injury at 24 hours.
Number of animals or in vitro replicates:
Five male and four female rabbits were used in total. The rabbits were divided into two groups consisting of six rabbits in Group 1 and three rabbits
in Group 2.
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): The eyes of the rabbits in Group 1 remained unflushed immediately after treatment while the treated eyes of the rabbits in Group 2 were flushed with lukewarm tap water for 1 minute starting 30 seconds after test material instillation.

SCORING SYSTEM: Draize scoring system and ocular irritation scoring scale (based on the method of Draize).

TOOL USED TO ASSESS SCORE: penlight and fluorescein

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
other: Average Primary eye irritation score
Basis:
mean
Time point:
other: 1h
Score:
9.7
Max. score:
110
Reversibility:
fully reversible
Remarks on result:
other: Group 1
Irritation parameter:
other: Average Primary eye irritation score
Basis:
mean
Time point:
other: 24h
Score:
4
Max. score:
110
Reversibility:
fully reversible
Remarks on result:
other: Group 1
Irritation parameter:
other: Average Primary eye irritation score
Basis:
mean
Time point:
other: 48h
Score:
2.7
Max. score:
110
Reversibility:
fully reversible
Remarks on result:
other: Group 1
Irritation parameter:
other: Average Primary eye irritation score
Basis:
mean
Time point:
other: 72h
Score:
0.3
Max. score:
110
Reversibility:
fully reversible
Remarks on result:
other: Group 1
Irritation parameter:
other: Average Primary eye irritation score
Basis:
mean
Time point:
other: 96h
Score:
0
Max. score:
110
Remarks on result:
other: Group 1
Irritation parameter:
other: Average Primary eye irritation score
Basis:
mean
Time point:
other: 1h
Score:
7.7
Max. score:
110
Reversibility:
fully reversible
Remarks on result:
other: Group 2
Irritation parameter:
other: Average Primary eye irritation score
Basis:
mean
Time point:
other: 24h
Score:
2.7
Max. score:
110
Reversibility:
fully reversible
Remarks on result:
other: Group 2
Irritation parameter:
other: Average Primary eye irritation score
Basis:
mean
Time point:
other: 48h
Score:
0
Max. score:
110
Remarks on result:
other: Group 2
Irritation parameter:
other: Average Primary eye irritation score
Basis:
mean
Time point:
other: 72h
Score:
0
Max. score:
110
Remarks on result:
other: Group 2
Irritant / corrosive response data:
All unwashed treated eyes (Group 1) had returned to a normal appearance by 96 hours after treatment. In the treated eyes receiving a washout approximately 30 seconds after instillation (Group 2), the test material produced iridal involvement and slight to moderate conjunctival irritation. All treated eyes in this group returned to a normal appearance by 48 hours after treatment.

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study, the test material produced very mild eye irritating effects which fully reversed by 96h.
Executive summary:

The study was performed to assess the irritancy potential of the test material to the eye following a single application in the New Zealand White rabbit. The study was performed to GLP and the method was designed to meet the requirements of EPA Guideline 81 -4. A total of 9 animals were used and split into two groups with group 1 containing 6 animals and group 2 containing 3 animals. A volume of 0.1 ml (61mg) of the test material was placed into the conjunctival sac of the right eye of all 9 animals. The left eye remained untreated and was used for control purposes. The eyes of the rabbits in Group 1 remained unflushed immediately after treatment while the treated eyes of the rabbits in Group 2 were flushed with lukewarm tap water for 1 minute starting 30 seconds after test material instillation. Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment. Additional observations were made at 96 hours after treatment for the animals in Group 1. Irritation was graded and scored according to the Draize technique using a penlight as the source of illumination. A sodium fluorescein examination was used to aid in revealing possible corneal injury at 24 hours.

In the group 1 test animals, no corneal effects (opacity) were noted during the study. Iridial inflammation (grade 1) was noted for four animals at one hour. Minimal to moderate (grade 1 to 2) conjunctival irritation was noted for all animals one hour after treatment and at the 24 to 72 -hour observations. All treated eyes appeared normal at the 96h observation. In the group 2 test animals, no corneal effects (opacity) were noted during the study. Iridial inflammation (grade 1) was noted in 1 animal at one hour. Minimal to moderate (grade 1 to 2) conjunctival irritation was noted for all animals one hour after treatment and at the 24 -hour observations. All treated eyes appeared normal at the 48h observation. The test material produced a maximum group mean score of 9.7. Based on these results and according to the classification scheme of Kay and Calandra (1962), the test material is mildly irritating to eyes unwashed immediately after treatment and minimally irritating to eyes receiving a washout after treatment. The test material is considered to be non irritating according to the Commission Directive 93/21/EEC.

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