Registration Dossier

Toxicological information

Eye irritation

Currently viewing:

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
16th to 29th September 1996
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study following GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1997
Report Date:
1997

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
122384-85-4/68855-45-8
Phenol, tetrapropenyl-, sulfurized, calcium salts
Test material dosed as received, purity not provided.

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Adult albino rabbits of the Hra:(NZW)SPF strain were procured from HRP, Inc., Kalamazoo, Michigan on September 4, 1996.
- Age at study initiation: approximately 14 to 18 weeks of age
- Weight at study initiation: weighing from 2,209 to 2,514 g
- Housing: the animals were individually housed in suspended stainless steel cages
- Diet/water (e.g. ad libitum): The animals were provided access to water ad libitum and a measured amount of Laboratory Rabbit Diet HF #5326, PMI Feeds, Inc. The feed is routinely analyzed by the manufacturer for nutritional components and environmental contaminants. Samples of the water are periodically analyzed. There were no known contaminants in the feed or water at levels that could be expected to interfere with or affect the results of the study.
- Acclimation period: After receipt, the animals were acclimated for a period of at least 7 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19° to 23°C
- Humidity (%): 50% ±20%
- Photoperiod (hrs dark / hrs light): 12-hour light/12¬hour dark lighting cycle

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
Dose level: 0.1 ml/one eye/animal
(Group 1, eyes unwashed post dosing N=6, Group 2, eyes washed post dosing N=3),

Duration of treatment / exposure:
The test material was not washed from the eyes of the animals in Group 1. 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):
Treated eyes were examined at 1, 24, 48 and 72 hours after treatment. An additional observation was made at 96 hours after treatment for the
Group 1 animals (unwashed).
Number of animals or in vitro replicates:
5 males; 4 females (six were used for group 1 and 3 for 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: 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 the observation conducted at 24 hours.

TOOL USED TO ASSESS SCORE: sodium fluorescein

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24, 48 & 72 hours
Score:
0
Reversibility:
other: no effects seen
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48 & 72 hours
Score:
0
Reversibility:
other: no effects seen
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24 hours
Score:
1.8
Max. score:
2
Reversibility:
fully reversible within: 96 hours
Remarks on result:
other: Redness
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 48 hours
Score:
0.8
Max. score:
1
Reversibility:
fully reversible within: 96 hours
Remarks on result:
other: Redness
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 72 hours
Score:
0.2
Max. score:
1
Reversibility:
fully reversible within: 96 hours
Remarks on result:
other: Redness
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24 hours
Score:
0.3
Max. score:
1
Reversibility:
fully reversible within: 48 hours
Irritant / corrosive response data:
The test material when evaluated for its primary eye irritation potential in rabbits, produced a corneal opacity in one animal and conjunctival irritation in all treated eyes that were unwashed after treatment.
Other effects:
Two animals exhibited hair loss around the treated eye

Any other information on results incl. tables

The potential eye-irritancy of the substance was investigated in a study conduted in line with OECD guideline 405 under conditions of GLP. The test material when evaluated for its primary eye irritation potential in rabbits, produced a corneal opacity in one animal and conjunctival irritation in all treated eyes that were unwashed after treatment. All treated eyes in this group returned to a normal appearance by 96 hours after treatment with the exception that two animals exhibited hair loss around the treated eye. Positive irritation reactions were observed in five of the six animals with unwashed eyes which cleared in all animals by the 48-hour observation. In treated eyes receiving a washout after test material instillation, the test material produced only conjunctival irritation. All treated eyes in this group returned to a normal appearance by 72 hours after treatment. Positive irritation reactions were observed in two of the three animals with washed eyes which cleared in all animals by the 48-hour observation. Rinsing the eyes after treatment did not have a substantial effect on the severity and persistence of ocular irritation.

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test material when evaluated for its primary eye irritation potential in rabbits, produced a corneal opacity in one animal and conjunctival irritation in all treated eyes that were unwashed after treatment. All treated eyes in this group returned to a normal appearance by 96 hours after treatment with the exception that two animals exhibited hair loss around the treated eye. Positive irritation reactions were observed in five of the six animals with unwashed eyes which cleared in all animals by the 48-hour observation.
Executive summary:

The primary eye irritation potential of the test material was evaluated when 0.1 mL was instilled into one eye of each of nine rabbits (six with treated eyes unwashed and three with treated eyes washed for 1 minute starting 30 seconds after instillation). The test material produced a corneal opacity in one animal and conjunctival irritation in all unwashed eyes which cleared in all animals by 96 hours after treatment. Positive irritation reactions were observed in five of the six animals with unwashed eyes which cleared in all animals by the 48-hour observation. In treated eyes receiving a washout, the test material produced only conjunctival irritation which cleared in all animals by 72 hours after treatment. Positive irritation reactions were observed in two of the three animals with washed eyes which cleared in all animals by the 48-hour observation. Rinsing the eyes after treatment did not have a substantial effect on the severity and persistence of ocular irritation.

The mean value of the scores for cornea opacity, iris lesions, redness & oedema of the conjuctivae, for 24, 48 and 72 hours was calculated and was considered to be non-irritating according to the dangerous substances directive, 67/548/EEC.