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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
Study period:
17th May 1993 to 10th June 1993
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report Date:
1993

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
EPA OPP 81-4 (Acute Eye Irritation)
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Age at study initiation: Young adult
- Weight at study initiation: 2477 to 3420 g
- Housing: Individual suspended mesh-bottom cages
- Diet: ad libitum
- Water: ad libitum, tap water
- Acclimation period: a minimum of 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-24 °C
- Humidity (%): 42-84 %
- 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): 0.1 mL
Observation period (in vivo):
14 days
Number of animals or in vitro replicates:
6 (3 males and 3 females)
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): Washing was not performed

SCORING SYSTEM:
1. Cornea:
(A) Opacity- Degree of density (area most dense taken for reading)
No ulceration or opacity – 0
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*
(B) Area of cornea involved
No ulceration or opacity – 0
One quarter or less but not zero – 1*
Greater than one quarter, but less than half – 2*
Greater than half, but less than three quarters – 3*
Greater than three quarters up to whole area – 4*
Score equals A X B X 5
Total Maximum = 80
2. Iris
(A) Values
Normal – 0
Markedly deepened rugae, congestion, swelling, circumcorneal injection (any or all 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*
Score equals A X 5
Totally maximum = 10
Conjunctivae
(A) Redness (refers to palpebral and bulbar conjunctivae excluding cornea and iris)
Blood vessels normal – 0
Some blood vessels definitely hyperaemic (injected above) normal – 1
Diffuse, deeper crimson colour, individual vessels not easily discernible – 3*
Diffuse beefy red – 3*
(B) Chemosis (lids and/or nictitating membranes)
No swelling – 0
Any swelling above normal (includes nictitating membrane) – 1
Obvious swelling with partial eversion of lids – 2*
Swelling with lids about half closed – 3*
Swelling with lids more than half closed - 4*
(C) Discharge
No discharge – 0
Any amount of different from normal (does not include small amounts observed in inner canthus of normal animals) -1
Discharge with moistening of the lids and hairs just adjacent to the lids – 2
Discharge with moistening of the lids and hair, and considerable area around the eye – 3
Score equals (A + B + C) X 2
Total maximum = 20
Total maximum score possible = 110
* Indicates a positive reaction


TOOL USED TO ASSESS SCORE: Both eyes of all rabbits were examined for ocular abnormalities prior to study initiation. The pre-initiation examination was performed using sodium fluorescein and ultraviolet light. Only rabbits with no pre-existing ocular abnormalities were used.
Both eye of all rabbits were examined macroscopically for ocular irritation using a hand-held penlight at approximately one, 24, 48 and 72 hours after dosing and at 4, 7, 14 and 21 days. In addition, both eye of all animals were further examined at 72 hours and 7, 14 and 21 days with sodium fluorescein and ultraviolet light.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
cornea opacity score
Basis:
animal #4
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
cornea opacity score
Basis:
animal #5
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
cornea opacity score
Basis:
animal #6
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.33
Max. score:
2
Reversibility:
fully reversible within: 4 days
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 21 days
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.67
Max. score:
2
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
iris score
Basis:
animal #4
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 21 days
Irritation parameter:
iris score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0.67
Max. score:
2
Reversibility:
fully reversible within: 21 days
Irritation parameter:
iris score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0.33
Max. score:
2
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2.67
Max. score:
3
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2.67
Max. score:
3
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
conjunctivae score
Basis:
animal #4
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
conjunctivae score
Basis:
animal #5
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
conjunctivae score
Basis:
animal #6
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2.33
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2.67
Max. score:
4
Reversibility:
fully reversible within: 21 days
Irritation parameter:
chemosis score
Basis:
animal #4
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
chemosis score
Basis:
animal #5
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
chemosis score
Basis:
animal #6
Time point:
24/48/72 h
Score:
2.67
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Irritant / corrosive response data:
None of the rabits vocalised upon instillation of the test material.
There were no significant changes or differences observed in body weights during the study period (measured on day 0 and 21).
There were no unscheduled deaths during the study.

Any other information on results incl. tables

Table 1: Results

Animal

Sex

Observation

Examination

1

hour

24

hours

48

hours

72

hours

4

days

7

days

14

days

21

days

1

Male

Cornea - opacity

0

1

1

2

2

2

0

0

Cornea - area

0

1

2

3

4

4

0

0

Iris

1

0

0

1

0

0

0

0

Conjunctivae - Redness

2

3

2

3

2

2

1

1

Conjunctivae - Chemosis

3

2

2

3

3

2

1

1

Conjunctivae - Discharge

3

2

2

2

2

1

0

0

2

Male

Cornea - opacity

1

1

1

1

2

2

2

1

Cornea - area

2

3

4

4

4

4

2

1

Iris

1

1

1

1

1

1

1

0

Conjunctivae - Redness

2

2

3

3

3

3

2

1

Conjunctivae - Chemosis

3

3

3

3

3

4

3

2

Conjunctivae - Discharge

3

2

1

1

2

1

1

1

3

Male

Cornea - opacity

1

1

1

1

1

0

1

1

Cornea - area

1

3

3

2

1

0

1

1

Iris

1

1

1

0

0

0

1

0

Conjunctivae - Redness

2

3

3

3

2

1

2

1

Conjunctivae - Chemosis

2

3

3

2

2

1

1

0

Conjunctivae - Discharge

2

2

0

0

0

0

0

0

4

Female

Cornea - opacity

1

1

1

2

3

3

3

2

Cornea - area

1

3

4

4

4

4

4

2

Iris

1

1

1

1

1

0

1

0

Conjunctivae - Redness

2

2

2

2

2

2

3

1

Conjunctivae - Chemosis

2

2

2

2

2

3

3

2

Conjunctivae - Discharge

2

2

2

2

2

0

1

0

5

Female

Cornea - opacity

1

1

1

1

2

2

2

2

Cornea - area

3

4

4

4

4

4

4

4

Iris

1

0

1

1

1

0

1

0

Conjunctivae - Redness

2

3

3

3

3

3

2

2

Conjunctivae - Chemosis

3

3

3

3

4

4

4

3

Conjunctivae - Discharge

3

2

2

2

3

3

2

1

6

Female

Cornea - opacity

1

1

1

1

2

2

2

1

Cornea - area

3

3

3

3

2

2

1

1

Iris

1

1

0

0

0

0

0

0

Conjunctivae - Redness

2

3

3

3

2

2

2

1

Conjunctivae - Chemosis

3

3

2

3

3

3

1

1

Conjunctivae - Discharge

3

1

1

0

1

1

0

0

Total

168

191

198

235

302

277

213

111

Mean

28.0

31.8

33.0

39.2

50.3

46.2

35.5

18.5

 

Table 2: Individual observations

Animal

Sex

Time

Observation

1

Male

1 hour

b

24 hours

b,e(20 %)

48 hours

b,e(40 %),i(40 %)

72 hours

a,c,e(80 %),r(80 %)

4 days

b,e(80 %),j

7 days

b,e(40 %),j,r(40 %)

14 days

r(0 %)

21 days

r(0 %)

2

Male

1 hour

b,e(25 %)

24 hours

b

48 hours

b

72 hours

a,r(90 %)

4 days

b,e(90 %),j

7 days

b,e(50 %),j,r(50 %)

14 days

b,e(20 %),k,r(20 %)

21 days

b,k,r(0 %)

3

Male

1 hour

b,e(30 %)

24 hours

b,e(80 %)

48 hours

e(80 %)

72 hours

e(50 %),r(50 %)

4 days

e(40 %)

7 days

e(5 %),r(5 %)

14 days

e(20 %),k,r(20 %)

21 days

r(0 %)

4

Female

1 hour

b,e(20 %)

24 hours

b,e(25 %)

48 hours

b

72 hours

b,e(85 %),r(85 %)

4 days

b,e(85 %),j

7 days

e(40 %),j,k,r(40 %)

14 days

a,e(35 %),k,r(35 %)

21 days

e(20 %),k,r(20 %)

5

Female

1 hour

b,e(40 %)

24 hours

b,e(80 %)

48 hours

a,e(80 %)

72 hours

a,c,e(100 %),r(100 %)

4 days

b,e(100%),j

7 days

b,e(90 %),k,r(90 %)

14 days

b,e(70 %),k,r(70 %)

21 days

a,e(5 %),k,r(5 %)

6

Female

1 hour

b,e(20 %)

24 hours

b,e(50 %)

48 hours

a,e(40 %)

72 hours

c,e(40 %),r(40 %)

4 days

b,e(40 %)

7 days

b,e(25 %),j,r(25 %)

14 days

e(20 %),k,r(20 %)

21 days

e(10 %),k,r(10 %)

a = Purulent discharge
b = Clear discharge
c = Petite haemmorhage
e = Corneal epithelial damage, peeling (% of area)
j = Pannus
k = Corneal neovascularisation
r = Sodium fluorescein stain retention (% of area)

 

 

Applicant's summary and conclusion

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
Under the conditions of the test, positive irritation was present for all ocular tissues examined. Iridial irritation subsided by day 21 or earlier in all animals.Corneal irritation persisted throughout the study until termination in five rabbits. Conjunctival irritation for all animals includede positive reaction for three animals persisted through to the termination of the study. The test material was concluded to induce irreversible ocular irritation under the conditions of the test.
Executive summary:

The eye irritation potential of the test material was evaluated in an in vivo study conducted in accordance with OECD 405, EU Method B.5 and EPA OPP 81 -4. Six albino rabbits (3 male and 3 females) were instilled with 0.1 mL undiluted test material and observed for 21 days. Under the conditions of the test, positive irritation was present for all ocular tissues examined. Iridial irritation subsided by day 21 or earlier in all animals.Corneal irritation persisted throughout the study until termination in five rabbits. Conjunctival irritation for all animals includede positive reaction for three animals persisted through to the termination of the study. The test material was concluded to induce irreversible ocular irritation under the conditions of the test.