Disodium 1-amino-4-[[4-[(2-bromo-1-oxoallyl)amino]-2-sulphonatophenyl]amino]-9,10-dihydro-9,10-dioxoanthracene-2-sulphonate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

21 October, 1974

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1974

Report date:

1974

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" (1959) of the US Association of Food and Drug Officials (AFDO).

Deviations:

not specified

Principles of method if other than guideline:

As per the guideline

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Disodium 1-amino-4-[[4-[(2-bromo-1-oxoallyl)amino]-2-sulphonatophenyl]amino]-9,10-dihydro-9,10-dioxoanthracene-2-sulphonate

EC Number:

274-397-6

EC Name:

Disodium 1-amino-4-[[4-[(2-bromo-1-oxoallyl)amino]-2-sulphonatophenyl]amino]-9,10-dihydro-9,10-dioxoanthracene-2-sulphonate

Cas Number:

70209-99-3

Molecular formula:

C23H16BrN3O9S2.2Na

IUPAC Name:

disodium 1-amino-4-[[4-[(2-bromo-1-oxoallyl)amino]-2-sulphonatophenyl]amino]-9,10-dihydro-9,10-dioxoanthracene-2-sulphonate

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

FAT 40068/A

Specific details on test material used for the study:

Test material identified as: FAT 40068/A

Test animals / tissue source

Species:

rabbit

Strain:

other: Russian breed

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Housing: separately in V2A wire cages
- Diet: NAFAG, Gossau SG, rabbit food ad libitum
- Water: ad libitum

IN-LIFE DATES: 1974

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.1 g

Duration of treatment / exposure:

After application, the eyelids were held open for a few seconds. The treated eyes of three rabbits were each rinsed with 10 mL lukewarm water about 30 seconds after treatment.

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

3 males and 3 females

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: The treated eyes of three rabbits (out of 6) were each rinsed with 10 mL lukewarm water about 30 seconds after treatment.

SCORING SYSTEM: Scale for scoring Ocular Lesions.
1.Cornea
(A) Opacity-degree of density (area most dense taken for reading)
- No opacity: 0
- Scattered or diffuse area, details of iris clearly visible: 1
- Easily discernible translucent areas, details of iris slightly obscured: 2
- Opalescent areas, no details of iris visible, size of pupil barely discernible: 3
- Opaque, iris invisible: 4

(B) Area of cornea involved
- 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

AxBx5 Total maximum=80

2.Iris
(A) Values
- Normal: 0
- Folds above normal, 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
Ax5 Total maximum=10

3.Conjunctivae
(A) Redness (refers to palpebral and bulbar conjunctivae excluding cornea and iris)
- Vessels normal: 0
- Vessels definitely injected above normal: 1
- More diffuse, deeper crimson red, individual vessels not easily discernible: 2
- Diffuse beefy red: 3

(B) Chemosis
- 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 about half closed to completely closed: 4

(C) Discharge'
- No discharge: 0
- Any amount 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 lids: 2
- Discharge with moistening of the lids and hairs, and considerable area around the eye: 3
Score (a+b+c)x 2 Total maximum=20

TOOL USED TO ASSESS SCORE: slit lamp

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Remarks:

Rinsed eyes

Basis:

mean

Remarks:

3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

iris score

Remarks:

Rinsed eyes

Basis:

mean

Remarks:

3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

conjunctivae score

Remarks:

Rinsed eyes

Basis:

mean

Remarks:

3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

3

Remarks on result:

no indication of irritation

Results 4

Irritation parameter:

chemosis score

Remarks:

Rinsed eyes

Basis:

mean

Remarks:

3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 5

Irritation parameter:

cornea opacity score

Remarks:

Unrinsed eye

Basis:

mean

Remarks:

3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 6

Irritation parameter:

iris score

Remarks:

Unrinsed eye

Basis:

mean

Remarks:

3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Results 7

Irritation parameter:

conjunctivae score

Remarks:

Unrinsed eye

Basis:

mean

Remarks:

3 animals

Time point:

24/48/72 h

Score:

0.55

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Remarks on result:

no indication of irritation

Results 8

Irritation parameter:

chemosis score

Remarks:

Un rinsed eye

Basis:

mean

Remarks:

3 animals

Time point:

24/48/72 h

Score:

0.55

Max. score:

4

Reversibility:

fully reversible within: 72h

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

The primary-irritation index, which serves as a measure of the acute irritation provoked by the substance, was found to be 0 for the cornea, 0 for the iris and 1 for the conjunctiva.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The test substance does not meet the GHS criteria for classification, hence can be considered as not an irritant to eye.

Executive summary:

A study was conducted to evaluate the eye irritation potential of the test substance. The procedure adopted was as per the technique described in the "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" (1959) of the US Association of Food and Drug Officials (AFDO). The substance was tested on 6 rabbits (3 males/3 females) of the Russian breed. Amounts of 0.1 g of the test substance were introduced into the conjunctival sac of the left eye with a spatula. After application, the eyelids were held open for a few seconds. The right eye served as a control. The treated eyes of three rabbits were each rinsed with 10 mL lukewarm water about 30 seconds after treatment. The reactions were appraised with a slit-lamp after 24 hours and after 2, 3, 4 and 7 days on the basis of the "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" (1959) of the AFDO. No cornea, iris or conjuctival irritation was observed for rinsed eyes. Slight conjuctvial irritation was reported in the animals with eyes not rinsed, which was completely reversed by 72h. The irritation index was found to be 0 for the cornea, 0 for the iris and 1 for the conjunctivae. Based on the findings of the study, the test substance does not meet the GHS criteria for classification, hence can be considered as not an irritant to eye.