Registration Dossier

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
October 13, 1983 - October 20, 1983
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study following OECD guideline 405

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Report Date:
1983

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
(1981)
GLP compliance:
yes
Remarks:
CIBA-GEIGT LTD/ GU2 TOXICOLOGY

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Physical state: viscous liquid
- Analytical purity: commercial grade
- Storage condition of test material: room temperature

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Kleintierfarm Madoerin AG, CH-4414 Fuellinsdorf
- Age at study initiation: 12 - 14 weeks
- Weight at study initiation: 2050-2210 g
- Housing: individually in metal cages
- Diet: Rabbit food, NAFAG, No. 814 Tox, NAFAG AG, Gossau, SG (Switzerland) provided ad libitum
- Water: ad libitum
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20±3
- Humidity (%): 30-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 hours light/day

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: The left eye remained untreated and served as the control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml
Duration of treatment / exposure:
The test article was placed into the conjunctival sac of the right eye of each animal, after gently pulling away the lower lid from the eyeball. The lids were then held together for about one second in order to prevent loss of the test material.
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
3 males
Details on study design:
SCORING SYSTEM:
Evaluation score for ocular lesions

CORNEA
Opacity: degree of density (area most dense taken for reading).
No ulceration or opacity = 0
Scattered or diffuse areas of opacity (other than slight dulling of normal lustre), details of iris clearly visible = 1*
Easily discernible translucent area, details of iris slightly obscured = 2*
Nacrous area, no details of iris visible, size of pupil barely discernible = 3*
Opaque cornea, iris not discernible through the opacity = 4*

IRIS
Normal = 0
Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia, or injection, any of these or combination of any thereof, iris still reacting to light (sluggish reaction is positive) = 1*
No reaction to light, haemorrhage, gross destruction (any or all of these) = 2*

CONJUCTIVAE
Redness: (refers to palpebral and bulbar conjuctivae, cornea and iris)
Blood vessels normal = 0
Some blood vessels definitely hyperaemic (injected) = 1
Diffuse, crimson colour, individual vessels not easily discernible = 2*
Diffuse beefy red = 3*

CHEMOSIS
Lids and/or nictating membranes
No swelling = 0
Any swelling above normal (includes nictating membranes) = 1
Obvious swelling with partial eversion of lids = 2*
Swelling with lids about half closed = 3*
Swelling with lids more than half closed = 4*

* Starred figures indicate positive effect

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: 24, 48 and 72 h
Score:
2.3
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: 24, 48 and 72 h
Score:
2.7
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
other: 24, 48 and 72 h
Score:
2.7
Max. score:
4
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: 24, 48 and 72 h
Score:
1
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: 24, 48 and 72 h
Score:
1.7
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #3
Time point:
other: 24, 48 and 72 h
Score:
1.7
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 24, 48 and 72 h
Score:
2.7
Max. score:
3
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: 24, 48 and 72 h
Score:
3
Max. score:
3
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: 24, 48 and 72 h
Score:
3
Max. score:
3
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 24, 48 and 72 h
Score:
3.3
Max. score:
4
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: 24, 48 and 72 h
Score:
4
Max. score:
4
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: 24, 48 and 72 h
Score:
4
Max. score:
4
Irritant / corrosive response data:
The test article is severely irritant and corrosive when applied to the rabbit eye mucosa. The eyes reacted with spontaneous swellings and hyperemias upon instillation of the test substance. 24 to 48 hours after administration these symptoms had deteriorated to severe irritations in the corneas and corrosions in the conjunctivas of all 3 animals. Due to this extreme irritation the animals were killed after the 72 h scoring out of animal protection reasons.
Other effects:
There was no tendency of recovery towards the end of the observation period of 3 days. The animals showed a normal body weight development.

Any other information on results incl. tables

Table 1 - Evaluation of the eye reactions

Animal No./Sex 75 / M 76 / M 77 / M  
After 1 h 2 2 2 Cornea
After 24 h 2 2 2
After 48 h 2 3 3
After 72 h 2 3 3
After 1 h 1 1 1 Iris
After 24 h 1 1 1
After 48 h 1 2 2
After 72 h 1 2 2
After 1 h 2 2 2 Conjunctivae
After 24 h 2 3 3
After 48 h 3+ 3+ 3+
After 72 h 3+ 3+ 3+
After 1 h 2 3 3 Chemosis
After 24 h 3 4 4
After 48 h 3 4 4
After 72 h 4 4 4

+ = corrosion

Applicant's summary and conclusion

Interpretation of results:
highly irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the present experiment the test substance was found to be severely irritant and corrosive when applied to the rabbit eye mucosa.
Executive summary:

In a GLP-compliant study following the OECD guideline 405, the test article's potential for irritation to the rabbit eye was investigated in three New Zealand White rabbits. 0.1 ml of the test substance was placed into the conjunctival sac of the right eye of each animal while the left eyes were kept untreated and served as a control. The ocular reactions were examined 1, 24, 48, and 72 hours after substance instillation and again during the following observation period. Under the conditions of the present experiment, the test substance was found to be severely irritant and corrosive when applied to the rabbit eye mucosa. There was no tendency of recovery towards the end of the observation period of 3 days.