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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:
July 1982
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to the guideline study with acceptable restrictions.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1982
Report Date:
1982

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
other: USA Interagency Regulatory Liaison Group (IRLG, January 1981)
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: Liquid
Details on test material:
The test material was a 48% aqueous solution of the substance

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: H. Fortkamp, 4540 Lengerich, Germany
- Weight at study initiation: 2.20 - 2.35 kg
- Age: 11-17 weeks
- Housing: single caging, metal cages
- Diet: ad libitum, Rabbit Diet, Ssniff Versuchstier Diäten GmbH, 4770 Soest/Westfalen, Germany
- Water: ad libitum
- Acclimation period: 20 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-23
- Humidity (%): 40-70
- Air changes (per hr): 10 per hour
- Photoperiod: 12 hours daily

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: Each animal served as its one control. The test article was introduced into the conjunctival sac of one eye, the untreated eye serving as a control
Amount / concentration applied:
0.1 ml of the test material was instilled into the conjunctival sac of the left eye while the right eye served as control.
Duration of treatment / exposure:
not rinsed
Observation period (in vivo):
Readings of ocular reactions were made 1-2 h, 24 h, 48 h, 72 h, 4 days, 7 days after treatment.
Number of animals or in vitro replicates:
6
Details on study design:
PREPARATION OF ANIMALS
- 24 h before treatment eyes were examined for corneal lesions after application of one drop of fluorescein-sodium solution (2%)

APPLICATION OF TEST SUBSTANCE
- 0.1 mL test substance was instilled into the conjunctival sac of the left eye. The lids were then held together for 1-2 seconds. The untreated right eye served as control. Because one of test animals showed a moderate pain reaction (score 3; see table 1), all remaining rabbits received a local anaesthetic in both eyes shortly before the application of the test substance.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the treated eye was not rinsed after treatment

SCORING SYSTEM (modified Draize system): the ocular reactions were assessed using the following numerical scoring system (see table 2)

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
#1, #3, #5, #6
Time point:
other: 24 h, 48 h, 72 h
Score:
1
Max. score:
4
Reversibility:
not reversible
Remarks:
within 7 days
Remarks on result:
other: Pannus
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
#2, #4
Time point:
other: 24 h, 48 h, 72 h
Score:
0
Max. score:
4
Reversibility:
other: delayed opacity formation after 7 days
Remarks on result:
other: Pannus
Irritation parameter:
iris score
Basis:
mean
Remarks:
#1, #2, #3, #4, #5, #6
Time point:
other: 24 h, 48 h, 72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
#2, #3, #4, #5, #6
Time point:
other: 24 h, 48 h, 72 h
Score:
2
Max. score:
3
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
#1
Time point:
other: 24 h, 48 h, 72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
#1, #2, #3, #4, #5, #6
Time point:
other: 24 h, 48 h, 72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
#1
Time point:
other: 24 h, 48 h, 72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritant / corrosive response data:
The most remarkable reaction to the instillation of the test substance was a not discernible iris through cornea opacity in one animal on day 7 after the application. The investigation of the remaining animals showed Pannus formations also on day 7 after the application. As the post exposure observation period was less then 21 days reversibility of effects could not be determined.
Other effects:
no data

Any other information on results incl. tables

Table 3: Irritant/corrosive response for each animal at each observation time

Score at time point / Reversibility

Cornea opacity

Cornea area

Iris

Conjunctivae

Redness

Conjunctivae

Chemosis

Conjunctivae

discharge

Max. score: 4

Max. score: 4

Max. score: 2

Max. score: 3

Max. score: 4

Max. score: 3

1-2 hours

1/0/1/0/1/1

2/0/2/0/2/2

1/1/1/1/1/1

2/2/2/2/2/2

2/2/2/2/2/2

1/1/1/1/1/1

1 day

1/0/1/0/1/1

2/0/2/0/2/2

1/1/1/1/1/1

2/2/2/2/2/2

2/2/2/2/2/2

2/2/2/2/2/2

2 days

1/0/1/0/1/1

2/0/2/0/2/2

1/1/1/1/1/1

2/2/2/2/2/2

2/2/2/2/2/2

2/2/2/2/2/2

3 days

1/0/1/0/1/1

2/0/2/0/2/2

1/1/1/1/1/1

2/2/2/2/2/2

2/2/2/2/2/2

2/2/2/2/2/2

4 days

1/0/1/0/1/1

2/0/2/0/2/2

1/1/1/1/1/1

1/2/2/1/2/2

1/2/2/1/2/2

1/2/2/1/2/2

7 days

1/2/2/1/3/4

4P/4P/4P/4P/4P/4P

0/0/0/0/0/*

0/1/1/1/2/2

0/1/1/1/2/2

0/1/1/0/1/2

Average 24h, 48h, 72h

1/0/1/0/1/1

2/0/2/0/2/2

1/1/1/1/1/1

2/2/2/2/2/2

2/2/2/2/2/2

2/2/2/2/2/2

Reversibility

n./n./n./n./n./n.

n./n./n./n./n./n.

c./c./c./c./c./*

c./n.c./n.c./n.c./n./n.

c./n.c./n.c./n.c./n./n.

c./n.c./n.c./c./n.c./n.

 

P = Pannus,

* Evaluation is not possible because of corneal opacity

c. = completely reversible

n.c. = not completely reversible

n.= not reversible

Reactions observed at 2 hours reading after the application

- Clear redness and chemosis of the conjunctiva (score 2)

- Light ocular secretion production (score 1)

- Isolated small diffuse areas in more as a quarter of a cornea (score 1) observed in 4/6 rabbits.

 

Reactions observed within 1 – 7 days after the application

- Clear redness and chemosis of the conjunctiva (score 2), decreased in 4 animals by the end of the study.

- Moderate pericorneal Hyperaemia of iris (score 1), decreased within the 7 days after the treatment

- Isolated small diffuse areas in more as a quarter of a cornea (score 1) observed in 4/6 rabbits turned into the corneal opacity in all animals by the end of the study.

- Conjunctivae discharge with moistening of the lids and hairs just adjacent to the lids (score 2), decreased in 5/6 of the rabbits by the end of the study.

Table 4: Assessment of results (mean values)

Days after treatment

Mean values

Conjunctivae (max. 20)

Iris (max. 10)

Cornea (max. 80)

Mean total score (max. 110)

0 (2 h)

10

5

6.7

21.7

1

12

5

6.7

23.7

2

12

5

6.7

23.7

3

12

5

6.7

23.7

4

10

5

6.7

21.7

7

6.3

0*

43.3

49.6

*Evaluation is not possible because of corneal opacity

 

Applicant's summary and conclusion

Interpretation of results:
Category 1 (irreversible effects on the eye)
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
The test material caused serious damage to eyes in this study
Executive summary:

A primary eye irritation study, performed according to the test plan P 4/152, 3-rd revision, refers to the recommended guidelines of the USA Interagency Regulatory Liaison Group (IRLG, January, 1981). Study performance is comparable to the guideline study.

0.1 ml of the substance (48 % a.i) undiluted were instilled into the conjunctival sac of one eye of 6 young female adult New Zealand White rabbits. Eyes were not washed. Animals then were observed for 7 days. Irritation was scored by the method of Draize.

Calculated mean scores following grading at 24, 48 and 72 hours after installation of the test material for effects on the cornea opacity are 1 for 4 of 6 animals and 0 for 2 of 6 animals. Mean scores for effects on the conjunctiva (redness) and chemosis were 2 for all animals; the effects decreased in 3 of 6 animals were reversible in one animal within 7 days. Mean scores for effects on the iris were 1 for all animals and were fully reversible within 7 days.

 

As the most remarkable reaction to the instillation of the test substance was cornea opacity (score 4) in one of 6 animals and pannus in all animals at day 7 after application. As the post exposure observation period was less then 21 days reversibility of effects could not be determined.

 

In this study, the substance (48 % a.i) induced serious damage to eyes.