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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:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
data is from authoritative databases and NTRL reports

Data source

Referenceopen allclose all

Reference Type:
other: Authoritative database
Title:
HSDB for the CAS: 28407-37-6
Author:
U.S National Library of Medicine
Year:
2003
Bibliographic source:
Hazardous Substances Databank [HSDB], U.S National Library of Medicine, last updated 2003
Reference Type:
secondary source
Title:
Report on Rabbit Eye Irritation for CAS- 28407-37-6
Author:
NTRL
Year:
1982
Bibliographic source:
OTS0206237, NTRL report, last updated 1982

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: As mentioned below
Principles of method if other than guideline:
To determine the primary irritation index of the test chemical when instilled to the eyes of rabbits
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: amorphous powder
Details on test material:
Name of the test chemical: Tetrasodium [μ-[[3,3'-[(3,3'-dihydroxy[1,1'-biphenyl]-4,4'-diyl)bis(azo)]bis[5-amino-4-hydroxynaphthalene-2,7-disulphonato]](8-)]]dicuprate(4-)
Common Name: C.I Direct Blue 218
IUPAC name: tetrasodium (3E)-5-amino-3-{2-[4-(4-{2-[(2E)-8-amino-1-oxo-3,6-disulfonato-1,2-dihydronaphthalen-2-ylidene]hydrazin-1-yl}-3- hydroxyphenyl)-2-hydroxyphenyl]hydrazin-1-ylidene}-4-oxo-3,4-dihydronaphthalene-2,7-disulfonate dicopper
Molecular Formula: C32H20Cu2N6Na4O16S4
Molecular Weight: 1087.84 g/mol
SMILES Notation: c12c3c(c(S(=O)(=O)[O-])cc1cc(S(=O)(=O)[O])cc2N)N=Nc1ccc(cc1O[Cu]O3)c1cc2c(N=Nc3c(cc4c(c3O[Cu]O2)c(cc(c4)S(=O) (=O)[O-])N)S(=O)(=O)[O-])cc1.[Na+].[Na+].[Na+].[Na+]
InChI: 1S/C32H24N6O16S4.2Cu.4Na/c33-19-11-17(55(43,44)45)5-15-9-25(57(49,50)51)29(31(41)27(15)19)37-35-21-3-1-13(7-23(21)39) 14-2-4-22(24(40)8-14)36-38-30-26(58(52,53)54)10-16-6-18(56(46,47)48)12-20(34)28(16)32(30)42;;;;;;/h1-12,39-42H,33-34H2,(H,43,44,45)(H,46,47,48)(H,49,50,51)(H,52,53,54);;;;;;/q;2*+2;4*+1/p-8/b37-35-,38-36-;;;;;;
Substance Type: Organic
Physical State: Solid Deep purple to dark blue amorphous powder

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Weight at study initiation: approximately 2.5 kg
- Housing: housed individually in suspended wire mesh cages
- Diet (e.g. ad libitum): Purina Rabbit Chow, ad libitum
- Water (e.g. ad libitum): water, ad libitum
- Acclimation period: After at least seven days equilibration

ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light): light controlled rooms

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
0.1g
Duration of treatment / exposure:
The lids were held closed for 1-second for even distribution of the test substance
Observation period (in vivo):
The eyes were examined and graded for irritation and corneal damage at 1, 24, 48 and 72 hours after instillation
Duration of post- treatment incubation (in vitro):
no data available
Number of animals or in vitro replicates:
6
Details on study design:
SCORING SYSTEM: The ocular reactions were graded and interpreted as described in –Appraisal of the Safety of Food. Drugs, and Cosmetics", Association of Food and Drug Officials of the United States. 1959 with the assistance of the "Illustrated Guide for Grading Eye Irritation by Hazardous Substances".

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 1 hour
Score:
11
Reversibility:
not specified
Remarks on result:
positive indication of irritation
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
24 h
Score:
9.7
Reversibility:
not specified
Remarks on result:
positive indication of irritation
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
48 h
Score:
14
Reversibility:
not specified
Remarks on result:
positive indication of irritation
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
72 h
Score:
8
Reversibility:
not specified
Remarks on result:
positive indication of irritation
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
7 d
Score:
3
Reversibility:
not specified
Remarks on result:
positive indication of irritation
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
14 d
Score:
1
Reversibility:
not specified
Remarks on result:
positive indication of irritation
Irritant / corrosive response data:
Moderately irritating to rabbit eyes

Any other information on results incl. tables

Table: Individual scores for the acute eye irritation study

Animal number

Tissue

Item

readings

Duration

1 hour

1 day

2 days

3 days

7 days

14 days

1

Cornea

A

 

0

0

0

0

0

0

B

 

0

0

0

0

0

0

Total

A*B*5

0

0

0

0

0

0

Iris

C

 

a

0a

1a

0

0

0

Total

C*5

 

0

5

0

0

0

Conjunctivae

D

Redness

A

3b

3b

3b

1

0

E

Chemosis

3

2

2

2

0

0

F

Discharge

3

2

2

1

1

0

Total

(D+E+F)*2

12

14

14

12

4

0

TOTALS ADDED

 

1+2+3

12

14

19

12

4

0

 

U.V Fluorescein scan

 

 

 

0

 

0

0

0

2

Cornea

A

 

0

0

0

0

0

0

 

B

 

0

0

0

0

0

0

 

Total

A*B*5

0

0

0

0

0

0

Iris

C

 

A

a

1a

0

0

0

 

Total

C*5

 

 

5

0

0

0

Conjunctivae

D

Redness

a

a

a

a

1a

a

 

E

Chemosis

3

3

3

2

2

2

 

F

Discharge

2

2

2

1

1

1

 

Total

(D+E+F)*2

10

10

10

6

6

6

TOTALS ADDED

 

1+2+3

10

10

15

6

8

6

 

 

U.V Fluorescein scan

 

 

 

0

 

0

0

0

3

Cornea

A

 

0

0

0

0

0

0

 

B

 

0

0

0

0

0

0

 

Total

A*B*5

0

0

0

0

0

0

Iris

C

 

A

a

1a

0

0

0

 

Total

C*5

 

 

5

0

0

0

Conjunctivae

D

Redness

A

a

a

a

a

0

 

E

Chemosis

3

3

3

2

0

0

 

F

Discharge

3

2

2

1

0

0

 

Total

(D+E+F)*2

12

10

10

6

0

0

TOTALS ADDED

 

1+2+3

12

10

15

6

0

0

 

U.V Fluorescein scan

 

 

 

1

 

0

0

0

4

Cornea

A

 

0

0

0

0

0

0

 

B

 

0

0

0

0

0

0

 

Total

A*B*5

0

0

0

0

0

0

Iris

C

 

a

a

0a

0

0

0

 

Total

C*5

 

 

0

0

0

0

Conjunctivae

D

Redness

a

a

1a

a

a

a

 

E

Chemosis

3

2

2

1

0

0

 

F

Discharge

2

2

1

1

0

0

 

Total

(D+E+F)*2

10

8

8

4

0

0

TOTALS ADDED

 

1+2+3

10

8

8

4

0

0

 

 

U.V Fluorescein scan

 

 

 

0

 

0

0

0

5

Cornea

A

 

A

0

0

0

0

0

 

 

B

 

0

0

0

0

0

0

 

Total

A*B*5

0

0

0

0

0

0

Iris

C

 

a

a

1a

0a

0

0

 

Total

C*5

 

 

5

0

0

0

Conjunctivae

D

Redness

a

a

a

a

a

a

 

E

Chemosis

3

2

2

2

1

0

 

F

Discharge

2

2

1

1

0

0

 

Total

(D+E+F)*2

10

8

6

6

6

2

TOTALS ADDED

 

1+2+3

10

8

11

6

2

0

 

U.V Fluorescein scan

 

 

 

0

 

0

0

0

6

 

                     

Cornea

A

 

0

0

0

0

0

0

 

B

 

0

0

0

0

0

0

 

Total

A*B*5

0

0

0

0

0

0

Iris

C

 

a

a

0a

0a

0

0

 

Total

C*5

 

 

0

0

0

0

Conjunctivae

D

Redness

a

a

2a

3ab

a

0

 

E

Chemosis

3

2

3

2

1

0

 

F

Discharge

3

2

3

2

1

0

 

Total

(D+E+F)*2

12

8

16

14

4

0

TOTALS ADDED

 

1+2+3

12

14

16

14

4

0

 

U.V Fluorescein scan

 

 

 

0

 

0

0

0


A = stained by material –unable to determine opacity

a- stained by material, b-brown spots

 

Applicant's summary and conclusion

Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Conclusions:
The Primary Irritation Index calculated at 1, 24, 48, 72 hours, 7 and 14 days were 11, 9.7, 14, 8, 3 and 1 respectively.
Based on the scores, the test chemical can be considered to be moderately irritating to rabbit eyes.
Executive summary:

A study was performed in rabbits to determine the ocular irritation potential of the test chemical.

6 New Zealand white rabbits were used for the study. The rabbits were equilibrated in the laboratory for at least seven days. Rabbits with irritated or damaged eyes were not used in this test. 0.1g test was instilled in the lower conjunctival sac of one eye of each rabbit and the lids held closed for approximately one second to insure even distribution of the test material over all surfaces of the eye. The other eye served as an untreated control. The eyes were examined and graded for irritation and corneal damage at 1, 24, 48 and 72 hours after instillation. Eyes not returning to a score of zero by 72 hours were graded on the seventh day after instillation. Eyes still not returning to a score of zero were graded on the fourteenth day after instillation. All eyes were examined by applying 1 drop of 2% fluorescein sodium ophthalmic solution, U.S.P., to the cornea pre-test, 24, 72 hours and 7 and 14 days after instillation. The fluorescein was rinsed from the eye with physiological saline.

The ocular reactions were graded and interpreted as described in –Appraisal of the Safety of Food. Drugs, and Cosmetics", Association of Food and Drug Officials of the United States, 1959 with the assistance of the "Illustrated Guide for Grading Eye Irritation by Hazardous Substances".

The Primary Irritation Index calculated at 1, 24, 48, 72 hours, 7 and 14 days were 11, 9.7, 14, 8, 3 and 1 respectively.

Based on the scores, the test chemical can be considered to be moderately irritating to rabbit eyes.