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Toxicological information

Eye irritation

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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: Guideline study conducted in accordance with GLP.

Data source

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

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
(1987)
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): TKA 40135 (CGI 819)

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Regal Group UK, Great Bookham, Surrey, England.
- Age at study initiation: 16 to 20 weeks
- Weight at study initiation: 3.6 to 4.0 kg
- Housing: individually in metal cages with perforated floors
- Diet (e.g. ad libitum): standard laboratory diet SDS Stanrab (P) Rabbit Diet, ad libitum
- Water (e.g. ad libitum): drinking water, ad libitum
- Acclimation period: yes

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 °C
- Humidity (%): 30 - 70 %
- Air changes (per hr): ca. 19
- Photoperiod (hrs dark / hrs light): 12 hrs / 12 hrs

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: the untreated eye of each animal served for control
Amount / concentration applied:
One animal was treated in advance of the others, to ensure that if a severe response was produced, no further animals would be exposed.
Approximately 73 mg of the test substance, corresponding to an application volume of 0.1 mL, was placed into the lower everted lid of one eye of each animal. The eyelids were then gently held together for one second before releasing.
Duration of treatment / exposure:
72 hours since no rinsing
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
Three animals were used
Details on study design:
REMOVAL OF TEST SUBSTANCE
After instillation, the test substance was not removed from the eye.

EXAMINATIONS
Examination of the eyes was made after 1 hour and 1, 2, 3 days (equivalent to 24, 48 and 72 hours) after instillation.
Moreover, the animals were observed daily for signs of ill health or toxicity.

SCORING SYSTEM
Ocular irritation was assessed using the prescribed numerical system:

Cornea
- 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 areas, details of iris slightly obscured 2
- Nacreous areas, 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

Conjunctivae redness
- 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
- 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


TOOL USED TO ASSESS SCORE
Observation of the eyes was aided by the use of a handheld light.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Remarks:
(mean value of the 3 reading time points)
Basis:
animal: 1, 2 and 3, respectively
Time point:
other: 24 - 48 - 72 hours
Score:
0
Max. score:
4
Reversibility:
other: not applicable as no effects
Remarks on result:
other: no signs of corneal opacity were seen at any of the reading time points in any of the three animals.
Irritation parameter:
iris score
Remarks:
(mean value of the 3 reading time points)
Basis:
animal: 1 and 3, respectively
Time point:
other: 24 - 48 - 72 hours
Score:
0
Max. score:
2
Reversibility:
other: not applicable as no effects
Remarks on result:
other: no signs of iritis were seen at any of the reading time points in any of these two animals.
Irritation parameter:
iris score
Remarks:
(mean value of the 3 reading time points)
Basis:
animal #2
Time point:
other: 24 - 48 - 72 hours
Score:
0.33
Max. score:
2
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: Iritis graded 1 was seen in the present animal at reading time point 24 hours only.
Irritation parameter:
conjunctivae score
Remarks:
(mean value of the 3 reading time points)
Basis:
animal #1
Time point:
other: 24 - 48 - 72 hours
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 4 days
Remarks on result:
other: redness graded 2 was seen after one hour; at each of the 3 following time points (24, 48 and 72 hours), redness was still evident but graded 1. After 4 days, redness had disappeared.
Irritation parameter:
conjunctivae score
Remarks:
(mean value of the 3 reading time points)
Basis:
animal #2
Time point:
other: 24 - 48 - 72 hours
Score:
1.66
Max. score:
3
Reversibility:
fully reversible within: 4 days
Remarks on result:
other: redness graded 2 was seen after one hour, 24 hours and 48 hours; at time point 72 hours redness was still evident but graded 1. After 4 days, redness had disappeared.
Irritation parameter:
conjunctivae score
Remarks:
(mean value of the 3 reading time points)
Basis:
animal #3
Time point:
other: 24 - 48 - 72 h
Score:
0.66
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: redness graded 2 was seen after one hour; at each of the 2 following time points (24 and 48 hours), redness was still evident but graded 1. At reading time point 72 hours, redness was no more seen.
Irritation parameter:
chemosis score
Remarks:
(mean of the 3 reading time points)
Basis:
animal #1
Time point:
other: 24 - 48 - 72 hours
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 4 days
Remarks on result:
other: chemosis graded 1 was seen after one hour, 24 hours, 48 hours and 72 hours. After 4 days, chemosis had disappeared.
Irritation parameter:
chemosis score
Remarks:
(mean of the 3 reading time points)
Basis:
animal #2
Time point:
other: 24 - 48 - 72 hours
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 4 days
Remarks on result:
other: chemosis graded 1 was seen after one hour, 24 hours, 48 hours and 72 hours. After 4 days, chemosis had disappeared.
Irritation parameter:
chemosis score
Remarks:
(mean of the 3 reading time points)
Basis:
animal #3
Time point:
other: 24 - 48 - 72 hours
Score:
0
Max. score:
4
Reversibility:
other: not applicable since no chemosis was seen at the reading time points of concern
Remarks on result:
other: chemosis graded 1 was seen after one hour, but no more after 24 hours, 48 hours and 72 hours.
Irritant / corrosive response data:
No corneal damage was observed.
Iridial inflammation (grade 1) was seen in one animal at reading time point 24 hours only.
A diffuse crimson colouration of the conjunctivae with slight swelling was seen in all animals within one hour of treatment. These reactions gradually ameliorated and the eyes were normal after 3 (i.e 72 hours) or 4 days following instillation.
Other effects:
There were no signs of toxicity or ill health in any rabbit during the observation period.

Any other information on results incl. tables

Eye reactions, scoring:

Animal

 

Effect

Reading time points

1 hour

Relevant for evaluation

4 days

24 h

48 h

72 h

1

Corneal opacity

0

0

0

0

0

Iris

0

0

0

0

0

Redness of conjunctivae

2

1

1

1

0

Chemosis

1

1

1

1

0

2

Corneal opacity

0

0

0

0

0

Iris

0

1

0

0

0

Redness of conjunctivae

2

2

2

1

0

Chemosis

1

1

1

1

0

3

Corneal opacity

0

0

0

0

-

Iris

0

0

0

0

-

Redness of conjunctivae

2

1

1

0

-

Chemosis

1

0

0

0

-

Applicant's summary and conclusion