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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study performed to a reliable method but not to GLP

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1985

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: Guideline used: Interagency Regulatory Liaison Group, "Recommended Guidelines for Acute Eye Irritation Testing," U.S. Consumer Product Safety Commission, Washington, DC, 20207, January 1981.
Principles of method if other than guideline:
Six New Zealand rabbits were used in this facet of the study. The pure compound was instilled in 100 mg quantities into the conjunctival envelope of the left eye of each rabbit; the right eye served as a control . Two of the rabbits had the compound washed from the eye 30 seconds after instillation; two, 5 min after instillation ; and two did not have the compound washed from the eye. Each eye was graded for ocular lesions at 1 and 4 h on the day of the application and again at 24, 48, and 72 h.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: crystalline
Details on test material:
- Name of test material : 3-NITRO-1 ,2,4-TRIAZOL-5-0NE (NTO)
- Substance type: energetic explosive
- Physical state: light green to white crystalline solid with no odor
- Purity ca.99%
Specific details on test material used for the study:
Batch No.: not specified
Purity: not specified

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2.4-2.8 kg

No additional data

Test system

Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg

No additional data
Duration of treatment / exposure:
72 hours
Observation period (in vivo):
1, 4, 24, 48, 72 hours
Number of animals or in vitro replicates:
6
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: Two of the rabbits had the compound washed from the eye 30 seconds after instillation; two, 5 min after instillation; and two did not have the compound washed from the eye.

SCORING SYSTEM: Draize

No additional data

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: mean of 24, 48 and 72 hours
Score:
0
Max. score:
0
Remarks on result:
other: Wash at 30 sec
Irritation parameter:
iris score
Basis:
mean
Time point:
other: mean of 24, 48 and 72 hours
Score:
0
Max. score:
0
Remarks on result:
other: Wash at 30 sec
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: mean of 24, 48 and 72 hours
Score:
0
Max. score:
0
Remarks on result:
other: Wash at 30 sec
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: mean of 24, 48 and 72 hours
Score:
0
Max. score:
0
Remarks on result:
other: Wash at 5 min
Irritation parameter:
iris score
Basis:
mean
Time point:
other: mean of 24, 48 and 72 hours
Score:
1.25
Max. score:
2.5
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other: Wash at 5 min
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: mean of 24, 48 and 72 hours
Score:
2.83
Max. score:
8
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other: Wash at 5 min
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: mean of 24, 48 and 72 hours
Score:
0
Max. score:
0
Remarks on result:
other: No wash
Irritation parameter:
iris score
Basis:
mean
Time point:
other: mean of 24, 48 and 72 hours
Score:
0
Max. score:
0
Remarks on result:
other: No wash
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: mean of 24, 48 and 72 hours
Score:
1.17
Max. score:
4
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other: No wash
Irritant / corrosive response data:
All rabbit eyes showed erythemia or redness (vascular congestion) of conjunctival vessels for the 1 and 4 h observations. One rabbit eye, from the 5 min "wash" group, had slight cornea opacity after 1 h and severe chemosis at 4 h preventing observation until 24 h. Then the cornea appeared clear, while the iris showed congestion with the pupil reacting slowly t o light. This condition continued through the test period with redness, chemosis, and discharge. The iris congestion was still present after 7 days. After 18 days, the rabbit was killed and tissues were taken for histological studies. When examined microscopically, the eye from the animal had a chronic granulomatous iritis with prominent infiltrations of large mononuclear inflammatory cells.
This iris response is considered a positive reaction but 1 positive response from 6 rabbits is considered a negative result for eye irritation studies according to classical guidelines. After 48 h, one of the remaining rabbits showed slight chemosis which was negative after 72 h.
Other effects:
No information provided

Any other information on results incl. tables

Eye Irritation Responses in Rabbits Treated with Test substancea

Tissue Gradedb

Time to Score

Time to Score

1 hours

2 hours

1 days

2 days

3 days

Wash at 30 sec

Cornea

Iris

Conjunctive

 

0

0

2.0

 

0

0

4.0

 

0

0

0

 

0

0

0

 

0

0

0

Wash at 5 min

Cornea

Iris

Conjunctive

 

12.5

0

8.0

 

*

*

11.0

 

0

2.5

8.0

 

0

2.5

5.0

 

0

2.5

4.0

No Wash

Cornea

Iris

Conjunctive

 

0

0

7.0

 

0

0

7.0

 

0

0

4.0

 

0

0

2.0

 

0

0

1.0

aTwo rabbits per wash conditions.

bMaximum cornea response = 80; maximum iris response = 10 ; maximum conjunctivae response = 20.

*Unable to score cornea and/or iris for swelling

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
With the scoring scheme, the rabbit eye test was considered negative; however, transient conjunctival and corneal irritation did result from the test substance application in several animals and one developed a chronic anterior uveitis.