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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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report Date:
1989

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
not specified
Remarks:
SIAR (2003) notes that this laboratory was GLP certified at the date of this study

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
- Source: no details given
- Age at study initiation: : no details given
- Weight at study initiation: no details given
- Housing: no details given
- Diet: standard diet ad libitum
- Water : drinking water ad libitum
- Acclimation period: no details

ENVIRONMENTAL CONDITIONS
no details given

IN-LIFE DATES: no details given

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: the untreated eye usually serves as the control
Amount / concentration applied:
undiluted
Amount applied: 0.1 ml, 0.005 ml
Duration of treatment / exposure:
Eyes unwashed.
Observation period (in vivo):
Observation to 21 days in some cases
Number of animals or in vitro replicates:
6 (3/sex)
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: unwashed

SCORING SYSTEM: after Draize, 1959


TOOL USED TO ASSESS SCORE: fluorescein (for 1-day reading)

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Remarks:
0.1 ml
Time point:
24/48/72 h
Score:
2.33
Max. score:
4
Reversibility:
not reversible
Remarks:
Score of 4 at 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #2
Remarks:
0.1 ml
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks:
Score of 4 at 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #3
Remarks:
0.1 ml
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not reversible
Remarks:
Score of 4 at 7.0 days
Remarks on result:
positive indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #4
Remarks:
0.1 ml
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not reversible
Remarks:
Score of 4 at 7.0 days
Remarks on result:
positive indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #5
Remarks:
0.1 ml
Time point:
24/48/72 h
Score:
3.33
Max. score:
4
Reversibility:
not reversible
Remarks:
Score of 4 at 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #6
Remarks:
0.1 ml
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not reversible
Remarks:
Score of 2 at 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Remarks:
0.1 ml
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
not reversible
Remarks:
Score of 1 at 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #2
Remarks:
0.1 ml
Time point:
24/48/72 h
Score:
2.33
Max. score:
3
Reversibility:
not reversible
Remarks:
Score of 2 at 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #3
Remarks:
0.1 ml
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
not reversible
Remarks:
Score of 1 at 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #4
Remarks:
0.1 ml
Time point:
24/48/72 h
Score:
2.33
Max. score:
3
Reversibility:
not reversible
Remarks:
Score of 2 at 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #5
Remarks:
0.1 ml
Time point:
24/48/72 h
Score:
2.66
Max. score:
3
Reversibility:
not reversible
Remarks:
Score of 2 at 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #6
Remarks:
0.1 ml
Time point:
24/48/72 h
Score:
2.33
Max. score:
3
Reversibility:
not reversible
Remarks:
Score of 1 at 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #1
Remarks:
0.1 ml
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not reversible
Remarks:
Score of 1 at 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #2
Remarks:
0.1 ml
Time point:
24/48/72 h
Score:
1.66
Max. score:
4
Reversibility:
not reversible
Remarks:
Score of 1 at 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #3
Remarks:
0.1 ml
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not reversible
Remarks:
Score of 1 at 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #4
Remarks:
0.1 ml
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not reversible
Remarks:
Score of 1 at 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #5
Remarks:
0.1 ml
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not reversible
Remarks:
Score of 2 at 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #6
Remarks:
0.1 ml
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not reversible
Remarks:
Score of 1 at 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
iris score
Basis:
animal #1
Remarks:
0.1 ml
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
other: Scoring not possible at 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
iris score
Basis:
animal #2
Remarks:
0.1 ml
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
other: Scoring not possible at 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
iris score
Basis:
animal #3
Remarks:
0.1 ml
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
other: Scoring not possible at 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
iris score
Basis:
animal #4
Remarks:
0.1 ml
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
other: Scoring not possible at 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
iris score
Basis:
animal #5
Remarks:
0.1 ml
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
other: Scoring not possible at 72 hours and 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
iris score
Basis:
animal #6
Remarks:
0.1 ml
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Irritant / corrosive response data:
0.1 ml: severe corneal injury, iritis, severe conjuctival irritation and necrosis of the conjunctivae within 1 h. Because of the severe, possibly irreversible, irritation at 7 days all animals were sacrificed. See table 1.

0.005 ml: minor to severe corneal injury with necrosis of the conjunctivae within 1 h. Two of six had recovered at 7 days and only 2 showed clear effects at 14 and 21 days. See table 2.

Any other information on results incl. tables

Table 1: Irritant/corrosive response data, mean for 6 animals, dose 0.1 ml

Score at time point / Reversibility

Cornea

Iris

Conjunctivae

Chemosis

Discharge

Opacity

Max. score: 4

Area involved

Max. score 4

Congestion/swelling

Max. score: 2

Redness

Max. score: 3

Chemosis

Max. score: 4

Discharge

Max. score: 3

1 h

2.7

3.3

*1

2.0

1.7

3.0

4 h

2.8

2.7

*1

2.0

2.0

2.0

24 h

2.5

2.2

1.0

2.2

1.7

3.0

48 h

2.8

2.2

1.0

2.3

1.5

2.8

72 h

3.0

2.5

*1

2.3

1.7

2.7

7 days

3.7

3.7

*

1.5

1.2

1.7

Mean for 24, 48, 72 h

2.8

*

2.3

1.6

Reversibility

Considered possibly irreversible

* scoring not possible for 1 or more animals, mean for the remainder is given

Table 2: Irritant/corrosive response data, mean for 6 animals, dose 0.005 ml (data from selected time intervals are presented here)

Score at time point / Reversibility

Cornea

Iris

Conjunctivae

Chemosis

Discharge

Opacity

Max. score: 4

Area involved

Max. score 4

Congestion/swelling

Max. score: 2

Redness

Max. score: 3

Chemosis

Max. score: 4

Discharge

Max. score: 3

1 h

1.7

2.2

1.0

2.0

1.3

2.7

24 h

1.5

2.0

1.0

2.0

1.0

2.3

48 h

1.5

2.2

1.0

2.0

1.0

2.0

72 h

1.0

1.8

1.0

1.5

0.7

1.2

7 days

1.2

1.7

0.5

0.7

0

0.7

21 days

0.6

0.6

0

0

0

0

Reversibility

Not fully reversible within 21 days

Applicant's summary and conclusion

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
A reliable study, conducted largely according to OECD 405, but not GLP, reported severe eye irritation with necrosis in rabbits. The study was terminated for humane reasons at 7 days, when clear effects were still evident in all six animals.