Registration Dossier

Administrative data

Endpoint:
eye irritation, other
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1990
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Data source

Reference
Reference Type:
other company data
Title:
Unnamed
Year:
1990
Report Date:
1990

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: crystalline
Details on test material:
Sponsor's identification
Description
Batch number
Date received
Storage conditions
PCMX
cream coloured, crystalline solid
285/13847
27 September 2001
room temperature, in the dark
Specific details on test material used for the study:
For testing liquids, a dose of 0.1 ml will be used. In testing solids, pastes and particulate substances, the amount used should have a volume of 0.1 ml , or a weight of not more than 100 mg. If the test material is solid or granular
it should be ground to a fine dust .

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
0.1g of test material was added to one eye of each test animal.

Test system

Vehicle:
not specified
Controls:
yes
not specified
Amount / concentration applied:
0.1g
Duration of treatment / exposure:
24 hours
Observation period (in vivo):
21 days
Duration of post- treatment incubation (in vitro):
N/A
Number of animals or in vitro replicates:
6
Details on study design:
The eyes will be examined and graded for ocular reactions at approximately 1 hour , 24 , 48 and 72 hours, after application using the Draize method reproduced in Appendix I . Except for the 1 hour scoring and only if corneal opacity scores of 2 or less are noted , the eyes may be scored again for corneal opacity intensity and area using fluorescein. Following the 24-hour scoring all eyes may be rinsed with copious amounts ( at least 200 ml) of physiological saline only if necessary.

Results and discussion

In vitro

Results
Irritation parameter:
fluorescein retention score
Value:
>= 1 - <= 5
Vehicle controls valid:
not specified
Negative controls valid:
not specified
Positive controls valid:
not specified
Other effects / acceptance of results:

The test material produced corneal opacity persisting through day 21, iritis persisting through day 10 and conjunctiva irritation persisting through day 21 when applied to the eyes of six New Zealand White rabbits. In addition,
corneal vascularization became apparent at day 7 and persisted through day 21

In vivo

Results
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
72 h
Score:
>= 1 - <= 5
Max. score:
4
Reversibility:
not specified
Remarks on result:
positive indication of irritation
Irritant / corrosive response data:
Table 1

Primary Eye Irritation in Rabbits Following an Ocular Application of OT'D\S Extra


Animal Cornea Conjunctiva Total b Number Time A B Iris c D E Score


1-352
1 hr
0
0
1
1
2F
2
15
24 hr 2/2 1/4 1 2 4FL 2 31/61
48 hr 1/1 4/4 1 3 4FL 2 43/43
72 hr 2/2 4/4 1 3P 4FL 3 65/65
Day 4 2/2 4/4 1 3 4L 3 65/65
Day 7 2/2 4/4 lV 3 3L 3 63/63
Day 10 3 4 lV 3 3L 2 81
Day 13 3 4 ov 3L 3 2 76
Day 16 3 4 ov lL 3 1 70
Day 19 3 4 ov lL 3 2 72
Day 21 3 4 ov lL 2 2 70
2-353 1 hr 0 0 0 1 3F 2 12
24 hr 1/1 4/4 1 2 4FL 3 43/43
48 hr 1/1 4/4 1 3P 4FL 2 43/43
72 hr
Day 4 2/2
2/2 4/4
4/4 1
1 3P
3 4FL
4L 2
2 63/63
63/63
Day 7 3 4 lV 3 4L 2 83
Day 10 3 4 lV 2 3L 2 79
Day 13 3 4 ov lL 3 0 68
Day 16 3 4 ov lL 3 0 68
Day 19 3 4 ov lL 3 1 70
Day 21 3 4 ov OL 2 1 66
A = Degree of Opacity; B = Area Affected; c = Erythema; D = swelling; and E - Discharge .
b scoring key appended to report.
C Total Score is the sum of the following three sub-totals, with a maximum score of 110; ( / ) = score without/with sodium fluorescein:
1. Degree of opacity x area involved x 5 2.Iris score x 5
3.(Sum of scores for erythema, swelling, and discharge) x 2
F = Blistered appearance to conjunctiva . L = Blanched appearance to conjunctiva.
P = Eye gently pried open to aid in scoring. v = vascularization.


Page 13 of 16

Ferro Corporation
Ref .: 89-3983-21 (C) February 2, 1990

Table 1 ( Cont. )

Primary Eye Irritation in Rabbits Following
an Ocular Application of Extra












Day 13 3 4N ov lL 2 1 68
Day 16 3 4N ov OL 2 0 64
Day 19 3 4N ov OL 2 1 66
Day 21 3 4N ov 0 2 0 64
4-364 1 hr 1 2 1 1 3F 3 29
24 hr 2/2 4/4 1 2P 4FL 0 57/57
48 hr 2/2 4/4 1 3P 4FL 1 61/61
72 hr 3 4 1 3P 4FL 0 79
Day 4 3 4 1 3P 4L 0 79
Day 7 3 4 lV 2 3L 2 79
Day 10 3 4 ov 2L 2 1 70
Day 13 3 4 ov lL 2 0 66
Day 16 3 4 ov lL 2 0 66
Day 19 3 4 ov 1 2 0 66
Day 21 3 4 ov 0 2 0 64


A = Degree of Opacity; B = Area Affected; c = Erythema; D = Swelling;
and E =- Discharge.
B scoring key appended to report.
C Total Score is the sum of the following three sub-totals, with a maximum score of 110; (/ )= score without,/with sodium fluorescein:
1. Degree of opacity x area involved x 5 2.Iris score x 5
3.(Sum of scores for erythema, swelling, and discharge) x 2
F = Blistered appearance to conjunctiva. L = Blanched appearance to conjunctiva .
N .. A small white pannus-like area on cornea. P = Eye gently pried open to aid in scoring. v = Vascularization.

Page 14 of 16

Ferro Corporation
Ref .: 89-3983-21 (C) February 2, 1990

Table 1

Primary Eye Irritation in Rabbits Following an Ocular Application of O'I"l2\S Extra


Animal Cornea Conjunctiva Total b C Number Time A B Iris c D E Score


5-365 1 hr 0 0 0 1 3F 3 14
24 hr 2/2 1/4 1 2P 4FL 0 27/57
48 hr 1/1 4/4 1 2 4FL 1 39/39
72 hr 2/2 4/4 1 3 4FL 1 61/61
Day 4 2/2 4/2 1 2 3L 3 61/41
Day 7 2/2 4/2 lV 1 2L 1 53/33
Day 10 2/2 1/1 ov 1 lL 0 14/14
Day 13 2/2 1/1 ov OL 1 0 12/12
Day 16 1/1 1/1 ov 0 1 0 7/7
Day 19 1/1 1/1 ov 0 1 0 7/7
Day 21 1/1 1/1 ov 0 0 0 5/5
6-366 1 hr 1 1 1 1 3F 3 24
24 hr 1/1 4/4 1 2 4FL 2 41/41
48 hr 1/1 4/4 1 3P 4FL 2 43/43
72 hr 2/2 4/4 1 3P 4FL 1 61/61
Day 4 2/2 4/4 1 3 4FL 2 63/63
Day 7 3 4 lV 3 4L 2 83
Day 10 3 4 lV 2 4L 2 81
Day 13 3 4 ov lL 4 2 74
Day 16 3 3 ov lL 2 1 53
Day 19 3 3 ov 1 2 0 51
Day 21 3 3 ov 0 2 0 49
A = Degree of Opacity; B = Area Affected; C = Erythema; D = Swelling; and E - Discharge.
B scoring key appended to report.
C Total Score is the sum of the following three sub-totals, with a maximum score of 110; ( / ) = score without,/'with sodium fluorescein :
1. Degree of opacity x area involved x 5 2.Iris score x 5
3. (Sum of scores for erythema, swelling, and discharge) x 2
F = Blistered appearance to conjunctiva . L = Blanched appearance to conjunctiva .
P = Eye gently pried open to aid in scoring . v = vascularization.
Other effects:
Maximum total irritation scores in individual animals ranged from 61 to 83.
Any changes noted to the eyes themselves may be found in the raw data in Appendix 2.
No evidence of corrosion was noted.
The test material is classified in Toxicity Category I (40 CFR 156, Proposed)
by ocular administration.

Any other information on results incl. tables

Table 1

Primary Eye  Irritation in Rabbits Following an Ocular Application of OT'D\S Extra

Animal                            Cornea                                   Conjunctiva              Total b Number       Time              A              B              Iris              c              D       E              Score

1-352       

1 hr       

0       

0       

1       

1       

2F       

2       

15

      24  hr       2/2       1/4       1       2       4FL       2       31/61

      48 hr       1/1       4/4       1       3       4FL       2       43/43

      72 hr       2/2       4/4       1       3P       4FL       3       65/65

      Day 4       2/2       4/4       1       3       4L       3       65/65

      Day 7       2/2       4/4       lV       3       3L       3       63/63

      Day 10       3       4       lV       3       3L       2       81

      Day 13       3       4       ov       3L       3       2       76

      Day 16       3       4       ov       lL       3       1       70

      Day 19       3       4       ov       lL       3       2       72

      Day 21       3       4       ov       lL       2       2       70

2-353       1 hr       0       0       0       1       3F       2       12

      24  hr       1/1       4/4       1       2       4FL       3       43/43

      48 hr       1/1       4/4       1       3P       4FL       2       43/43

      72 hr

Day 4       2/2

2/2       4/4

4/4       1

1       3P

3       4FL

4L       2

2       63/63

63/63

      Day       7       3       4       lV       3       4L       2       83

      Day       10       3       4       lV       2       3L       2       79

      Day       13       3       4       ov       lL       3       0       68

      Day       16       3       4       ov       lL       3       0       68

      Day       19       3       4       ov       lL       3       1       70

      Day       21       3       4       ov       OL       2       1       66

A = Degree of Opacity; B = Area Affected; c = Erythema; D = swelling; and E - Discharge .

b scoring key appended to report.

C Total Score is the sum of the following three sub-totals, with a maximum score of 110; ( / ) = score without/with sodium fluorescein:

1.       Degree of opacity x area involved x 5 2.Iris score x 5

3.(Sum of scores for erythema, swelling, and discharge) x 2

F = Blistered appearance to conjunctiva . L = Blanched appearance to conjunctiva.

P = Eye gently pried open to aid in scoring. v = vascularization.

Page 13 of 16

Ferro Corporation

Ref .: 89-3983-21 (C)       February 2, 1990

Table 1 ( Cont. )

Primary Eye  Irritation in Rabbits Following

an Ocular Application of       Extra

Day 13       3       4N       ov       lL       2       1       68

Day 16       3       4N       ov       OL       2       0       64

Day 19       3       4N       ov       OL       2       1       66

Day 21       3       4N       ov       0       2       0       64

4-364       1 hr       1       2       1       1       3F       3       29

24 hr       2/2       4/4       1       2P       4FL       0       57/57

48 hr       2/2       4/4       1       3P       4FL       1       61/61

72 hr       3       4       1       3P       4FL       0       79

Day 4       3       4       1       3P       4L       0       79

Day 7       3       4       lV       2       3L       2       79

Day 10       3       4       ov       2L       2       1       70

Day 13       3       4       ov       lL       2       0       66

Day 16       3       4       ov       lL       2       0       66

Day 19       3       4       ov       1       2       0       66

Day 21       3       4       ov       0       2       0       64

A = Degree of Opacity; B = Area Affected; c = Erythema; D = Swelling;

and E =- Discharge.

B scoring key appended to report.

C Total Score is the sum of the following three sub-totals, with a maximum score of 110; (/ )= score without,/with sodium fluorescein:

1. Degree of opacity x area involved x 5 2.Iris score x 5

3.(Sum of scores for erythema, swelling, and discharge) x 2

F = Blistered appearance to conjunctiva. L = Blanched appearance to conjunctiva .

N .. A small white pannus-like area on cornea. P = Eye gently pried open to aid in scoring. v = Vascularization.

Page 14 of 16

Ferro Corporation

Ref .: 89-3983-21 (C)       February 2, 1990

Table 1

Primary Eye Irritation in Rabbits Following an Ocular Application of O'I"l2\S Extra

Animal                            Cornea                                   Conjunctiva              Total b C Number       Time              A              B              Iris              c              D       E              Score

5-365       1 hr       0       0       0       1       3F       3       14

      24 hr       2/2       1/4       1       2P       4FL       0       27/57

      48 hr       1/1       4/4       1       2       4FL       1       39/39

      72 hr       2/2       4/4       1       3       4FL       1       61/61

      Day 4       2/2       4/2       1       2       3L       3       61/41

      Day 7       2/2       4/2       lV       1       2L       1       53/33

      Day 10       2/2       1/1       ov       1       lL       0       14/14

      Day 13       2/2       1/1       ov       OL       1       0       12/12

      Day 16       1/1       1/1       ov       0       1       0       7/7

      Day 19       1/1       1/1       ov       0       1       0       7/7

      Day 21       1/1       1/1       ov       0       0       0       5/5

6-366       1 hr       1       1       1       1       3F       3       24

      24 hr       1/1       4/4       1       2       4FL       2       41/41

      48 hr       1/1       4/4       1       3P       4FL       2       43/43

      72 hr       2/2       4/4       1       3P       4FL       1       61/61

      Day 4       2/2       4/4       1       3       4FL       2       63/63

      Day       7       3       4       lV       3       4L       2       83

      Day       10       3       4       lV       2       4L       2       81

      Day       13       3       4       ov       lL       4       2       74

      Day       16       3       3       ov       lL       2       1       53

      Day       19       3       3       ov       1       2       0       51

      Day       21       3       3       ov       0       2       0       49

A = Degree of Opacity; B = Area Affected; C = Erythema; D = Swelling; and E - Discharge.

B scoring key appended to report.

C Total Score is the sum of the following three sub-totals, with a maximum score of 110; ( / ) = score without,/'with sodium fluorescein :

1. Degree of opacity x area involved x 5 2.Iris score x 5

3. (Sum of scores for erythema, swelling, and discharge) x 2

F = Blistered appearance to conjunctiva . L = Blanched appearance to conjunctiva .

P = Eye gently pried open to aid in scoring . v = vascularization.

Applicant's summary and conclusion

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
The test material produced corneal opacity persisting through day 21, iritis persisting through day 10 and conjunctiva irritation persisting through day 21 when applied to the eyes of six New Zealand White rabbits. In addition,
corneal vascularization became apparent at day 7 and persisted through day 21.

Maximum total irritation scores in individual animals ranged from 61 to 83.
Executive summary:

SUMMARY/CONCLUSIONS

The primary ocular irritancy was evaluated in compliance with the conditions specified in the regulation for the enforcement of the Federal Insecticide, Fungicide, and Rodenticide Act (40 CFR), the Toxic Substances Control Act (40 CFR), and the OECD Guidelines.

The test material produced corneal opacity persisting through day 21, iritis persisting through day 10 and conjunctiva       irritation persisting through day 21 when applied to the eyes of six New Zealand White rabbits. In addition,

corneal vascularization became apparent at day 7 and persisted through day 21.

Maximum total irritation scores in individual animals ranged from 61 to 83.

Any changes noted to the eyes themselves may be found in the raw data in Appendix 2.

No evidence of corrosion was noted.

The test material is classified in Toxicity Category I (40 CFR 156, Proposed)

by ocular administration.