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:
1995-09-21 to 1996-03-5
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was performed under GLP and the study was conducted in general compliance with the US EPA OPP (Section 81-4) and TSCA Health Effects Test Guidelines, 40 CFR 798.4500

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Report Date:
1996

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
other: US EPA Pesticide Assessment Guidelines, Subdivision F, Hazard Evaluation: Human and Domestic Aminals, Section 81-4.
Qualifier:
according to
Guideline:
other: TSCA Health Effects Test Guidelines, 40 CFR 798.4500
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Y-4036
- Physical state: clear, colourless liquid
- Analytical purity: 98.3 %
- Purity test date: 1995-09-27
- Lot/batch No.: 16912-29
- Storage condition of test material: original container at room temperature, under these conditions the substance is stable for several years

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Hazleton Research Products, Inc. Denver, PA
- Age at study initiation: Young adult
- Weight at study initiation: 2379 to 2688 grams
- Housing: Individual suspended wire-mesh cages. The animals were maintained by the animal husbandry staff of WIL Research Laboratories, Inc., in accordance with Standard Operating Procedures.
- Diet (e.g. ad libitum): Purina® Certified Rabbit Chow® #5322 ad libitum
- Water (e.g. ad libitum): municipal water ad libitum
- Acclimation period: a minimum of six days

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 67.9 - 68.1 °F)
- Humidity (%): 38.2 - 61.1%
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml/right eye
Duration of treatment / exposure:
1 second. The test material was placed directly into the cupped lower conjunctival sac of the rabbit´s right (test) eye. The eyelid was held closed for approximately one second after instillation. Left eyes were manipulated in a similar manner as the right eyes and served as contralateral controls. The eyes of all rabbits remained unwashed.
Observation period (in vivo):
1, 24, 48 and 72 hours after dosing
Number of animals or in vitro replicates:
6, three males and three females
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): no


SCORING SYSTEM: Draize scale for scoring ocular lesions, as published in the guidelines in Subsection F. Hazard Evaluation: Human and Domestic Animals distributed in 1982 and the OECD Guidelines for Testing of Chemicals distributed in 1987.

TOOL USED TO ASSESS SCORE: After 1, 24,48 and 72 hours after dosing both eyes of the rabbits were examined macroscopically for ocular irritation using a hand-held penlight. In addition sodium fluorescein and ultraviolet light were used prior to the study initiation and after 72h.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
other: M.A.S - Maximum Average Score
Basis:
mean
Time point:
other: 1 h
Score:
5.2
Reversibility:
fully reversible within: 72h
Irritation parameter:
other: M.A.S - Maximum Average Score
Basis:
mean
Time point:
other: 24h
Score:
1
Reversibility:
fully reversible
Irritation parameter:
other: M.A.S - Maximum Average Score
Basis:
mean
Time point:
other: 48h
Score:
0.7
Reversibility:
fully reversible
Irritation parameter:
other: M.A.S - Maximum Average Score
Basis:
mean
Time point:
other: 72h
Score:
0

Any other information on results incl. tables

An iris reaction was noted in the treated eye of one animal. Minor conjunctival irritation was noted for all rabbits.

       0.1 ml/right eye, unwashed                Examination intervals                   
 Animl  Sex  Tissue        1h        24h        48h       72h* 
 19702  M Cornea (O-A)  0  0    0  0    0  0    0  0  
     Iris  0      0      0      0    
     Conjunctiva (R-C-D)  1  1  0  1  0  0  1  0  0  0  0  0
 19853  M  Cornea (O-A)  0  0    0  0    0  0    0  0  
     Iris  0      0      0      0    
     Conjunctiva (R-C-D)  1  1  0  0  0  0  0  0  0  0  0  0
 19855  M  Cornea (O-A)  0  0    0  0    0  0    0  0  
     Iris  0      0      0      0    
    Conjunctiva (R-C-D)  1  1  0  1  0  0  0  0  0  0  0  0
 19870  F  Cornea (O-A)  0  0    0  0    0  0    0  
     Iris  0      0      0      0    
     Conjunctiva (R-C-D)  1  1  0  0  0  0  0  0  0  0  0  0
 19871  F  Cornea (O-A)  0  0    0  0    0  0    0  0  
     Iris  1      0      0      0    
     Conjunctiva (R-C-D)  1  1  0  0  0  0  0  0  0  0  0
 19872  F  Cornea (O-A)  0  0    0  0    0    0  0  
     Iris  0      0      0      0    
     Conjunctiva (R-C-D)  1  1  1  1  0  0  1  0  0  0  0  0
                           
 Total    

 31.0      

       6.0        4.0       0.0 
 Mean          5.2          1.0        0.7        0.0

O = Opacity; A = Area; R = Redness; C = Chemosis; D = Discharge

*Fluorescein solution applied

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: other: Draize scale for scoring ocular lesions
Conclusions:
The Maximum Average Score for Y-4036 was 5.2 at one hour post-instillation. An iris reaction was noted in the treated eye of one female animal. There were no corneal findings. Minor conjunctival irritation was noted for all rabbits. All irritation was reversible and completely subsided by termination (day 3) or earlier.
Executive summary:

The primary ocular irritation potential of Y-4036 was evaluated in this study using New Zealand White rabbits.

Single 0.1 -ml doses of the test material were instilled into the lower conjunctival sac of the right eye of three male and three female albino rabbits. The eyelids were held closed for approximately one second and released. Left eyes were manipulated in a similar manner as the right eyes and served as contralateral controls. The eyes of all rabbits remained unwashed.

The eyes were examined for ocular reactions in accordance with the method of Draize at approximately one, 24, 48 and 72 hours after dosing. Sodium fluorescein was used to aid in revealing possible corneal damage at 72 hours.

The Maximum Average Score of Y-4036 was 5.2 at one hour post-instillation. An iris reaction was noted in the treated eye of one female animal. Minor conjunctival irritation was noted for all rabbits. There were no corneal findings. All irritation was reversible and completely subsided by day 3 or earlier.

There were no deaths or remarkable changes in body weights during the study period.