Registration Dossier

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: Study conducted to GLP and in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not effect the quality of the relevant results.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998

Materials and methods

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

Test material

Constituent 1
Reference substance name:
Substituted Quinone Methide
IUPAC Name:
Substituted Quinone Methide
Details on test material:
Storage: The test article was stored at room temperature and humidity.
Description: Yellow crystalline solid.

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: New Zealand White rabbits were received from Ace Animals, Boyertown, PA.
- Age at study initiation: Approx 3 months.
- Weight at study initiation: The pretest bodyweight range was 2.0-2.1 kg.
- Housing: The animals were housed 1 per cage in suspended cages. Bedding was placed beneath the cages and changed at least three times/week.
- Diet (e.g. ad libitum): Fresh Purina Rabbit Chow (Diet #5321) was provided daily.
- Water (e.g. ad libitum): Water was available ad libitum.
- Acclimation period: At least five days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): The animal room was temperature controlled.
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): The test article (0.1 ml equivalent (88 mg)) was placed by syringe-type applicator into the conjunctival sac which was formed by gently pulling the lower eyelid away from the eye. After instillation, the lids were held together for approximately one second to insure adequate distribution of the test article.

One eye of each rabbit was dosed. The contralateral eye served as a control.
Duration of treatment / exposure:
A single application of the test material.
Observation period (in vivo):
72 hours.
Number of animals or in vitro replicates:
6 females.
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): Not performed.


SCORING SYSTEM: Ocular reactions were graded according to the numerical Draize technique (see below).

TOOL USED TO ASSESS SCORE: Using a Mini-Maglite flashlight equipped with a high intensity bulb, the treated eye of each rabbit was
examined for irritation of the comea, iris and conjunctiva at 1, 24, 48, and 72 hours post dose. The eyes were scored again on day 7. Sodium fluorescein was used to determine corneal effects following the 24 hour observation and at each subsequent reading until there was no stain retention.

The eyes were not scored on day 4 as specified in the protocol. This did not effect the outcome of the study.

Other:
Body weights were recorded pretest.
The general health of the animals was monitored at each observation time.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
conjunctivae score
Remarks:
: redness
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0.72
Max. score:
3
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: Calculated on the basis of the scores at 24, 48, and 72 hours for ALL animals.
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0.17
Max. score:
4
Reversibility:
fully reversible within: 2 days
Remarks on result:
other: Calculated on the basis of the scores at 24, 48, and 72 hours for ALL animals.
Irritation parameter:
conjunctivae score
Remarks:
: discharge
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 2 days
Remarks on result:
other: Calculated on the basis of the scores at 24, 48, and 72 hours for ALL animals.
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0.11
Max. score:
4
Reversibility:
fully reversible within: 2 days
Remarks on result:
other: Calculated on the basis of the scores at 24, 48, and 72 hours for ALL animals.
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
2
Reversibility:
fully reversible within: 1 day
Remarks on result:
other: Calculated on the basis of the scores at 24, 48, and 72 hours for ALL animals.
Irritant / corrosive response data:
Corneal opacity, noted in 1/6 eyes, cleared by 48 hours. Iritis, noted in 2/6 eyes, cleared by 24 hours. Conjunctival irritation, noted in 6/6 eyes,
cleared by day 7.
There were no abnormal systemic observations.

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The substance is not classified as an eye irritant.
Executive summary:

Objective:

To determine the potential of the test article to produce ocular irritation when instilled in the eyes of New Zealand White rabbits. The study was designed to comply with the standards set forth by:

-EPA - Primary Eye Imtation, 40 CFR 798.4500 (latest revision -1995

-EC Official Journal of the European Communities. L 383 A, Part B, Method B.5 Acute Toxicity (Eye Initation) 12/29/92.

-OECD Guidelines for Testing of Chemicals, No. 405, Acute Eye Initation/Corrosion, adopted 2/24/87.

Method Synopsis:

Six healthy New Zealand White rabbits (females), free from evidence of ocular irritation and corneal abnormalities, as determined by pretest fluorescein procedures, were dosed with the test substance. The test article (0.1 ml equivalent (88 mg)) was placed into the conjunctival sac of one eye of each rabbit. The eyes were examined and scored by the Draize technique at 1, 24, 48 and 72

hours post dose. The eyes were scored again on day 7. Sodium fluorescein was used to determine corneal effects following the 24 hour observation and at each subsequent reading until there was no stain retention. Body weights were recorded pretest.

Summary:

Corneal opacity, noted in 1/6 eyes, cleared by 48 hours. Iritis, noted in 2/6 eyes, cleared by 24 hours. Conjunctival irritation, noted in 6/6 eyes, cleared by day 7.

There were no abnormal systemic observations.

Conclusion:

The test substance is not classified as an eye irritant.