tetrasodium 4-{4-[(9,10-dioxo-4-{[4-(2-sulfophenoxy)phenyl]amino}-9,10-dihydroanthracen-1-yl)amino]phenoxy}benzene-1-sulfonate 4-{4-[(9,10-dioxo-4-{[4-(4-sulfophenoxy)phenyl]amino}-9,10-dihydroanthracen-1-yl)amino]phenoxy}benzene-1-sulfonate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1979

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:

1979

Report date:

1979

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: United States Environmental Protection Agency (EPA) § 163.81-4 "Primary eye irritation study", Federal Register, Vol. 43, No; 163, August 22, 1978.

Deviations:

not specified

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Reaction mass of Disodium 2-{4-[(9,10-dioxo-4-{[4-(4-sulfonatophenoxy)phenyl]amino}-9,10-dihydroanthracen-1-yl)amino]phenoxy}benzenesulfonate and Disodium 4,4'-[(9,10-dioxo-9,10-dihydroanthracene-1,4-diyl)bis(iminobenzene-4,1-diyloxy)]dibenzenesulfonate

EC Number:

941-784-2

Molecular formula:

C38H26N2O10S2.2Na

IUPAC Name:

Reaction mass of Disodium 2-{4-[(9,10-dioxo-4-{[4-(4-sulfonatophenoxy)phenyl]amino}-9,10-dihydroanthracen-1-yl)amino]phenoxy}benzenesulfonate and Disodium 4,4'-[(9,10-dioxo-9,10-dihydroanthracene-1,4-diyl)bis(iminobenzene-4,1-diyloxy)]dibenzenesulfonate

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): FAT 21030/C.

Specific details on test material used for the study:

Identification: FAT 21030/C

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Healthy rabbits of the New Zealand White breed (IVANOVAS, 7964 Kisslegg/Allgäu, Germany and MADOERIN AG, 4414 Füllinsdorf, Switzerland) weighing 2 to 3 kgs were used for the experiment. The animals were housed individually in metal cages, numbered by ear tags, were kept at a constant room temperature of 22±2 °C, at a relative humidity of 55±10 % and on a 10 hour light cycle day. The animals had ad libitum access to standard rabbit food - NAFAG, No. 814, Gossau SG and water. Prior to treatment they were adapted to our laboratories for a minimum of 4 days. Only rabbits with normal ophthalmic findings were used for these tests.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

100 mg of the test compound

Duration of treatment / exposure:

In 3 of the 6 rabbits approximately 30 seconds after treatment the treated eye was flushed with 10 ml of physiological saline.

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

3 males and 3 females

Details on study design:

0.1 g of test material was inserted into the conjunctival sac of the left eye of the rabbits and the lids were gently closed for a few seconds. The right eye was not treated and served as an untreated control. In 3 of the 6 rabbits approximately 30 seconds after treatment the treated eye was flushed with 10 ml of physiological saline. The eye irritation was appraised with a slit-lamp on day 1, 2, 3, 4 and 7 and was scored for each individual rabbit.

SCORING SYSTEM:

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
A x B x 5 (Total maximum = 80)


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, hemorrhage, gross destruction (any or all of these): 2

A x 5 (Total maximum = 10)

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: 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

(A + B + C) x 2 (Total maximum = 20)

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0.11

Max. score:

4

Reversibility:

fully reversible within: 72 h

Remarks on result:

other: only 1/6 aimals had slight irritation, which reversed by 72 hours

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0.72

Max. score:

3

Reversibility:

fully reversible within: 72 h

Results 4

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.44

Max. score:

4

Reversibility:

fully reversible within: 72 h

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

FAT 21030/C is not irritating to the albino rabbit eyes.

Executive summary:

The purpose of this eye irritation study was to assess the possible irritation potential of FAT 21030/C when placed in the conjunctival sac of rabbit left eyes (3 males and 3 females). This experiment was done according to the Proposed Guidelines of the United States Environmental Protection Agency (EPA) § 163.81-4 "Primary eye irritation study", Federal Register, Vol. 43, No; 163, August 22, 1978.

100 mg of test compound was instilled into the conjunctival sac of the left eye of rabbits. The eyelids were then held closed for few second. The untreated right eye served as a control. In 3 of the 6 rabbits approximately 30 seconds after treatment the treated eye was flushed with 10 ml of physiological saline.

The eye irritation was appraised with a slit-lamp on day 1, 2, 3, 4 and 7 and was scored for each individual rabbit.

Slight irritation was observed in regards to corneal opacity, conjuctival redness and chemosis which was reversible within 72 hours. No irritation seen with iris. The mean scores obtained were below the threshold scores required for classification as set by the Regulation (EC) No. 1272/2008. Hence, it was concluded that FAT 21030/C was not irritating to the rabbit eyes.