Sodium 1-amino-4-[[3,5-bis[[(chloroacetyl)amino]methyl]-2,4,6-trimethylphenyl]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:

1974

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

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:

no

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Sodium 1-amino-4-[[3,5-bis[[(chloroacetyl)amino]methyl]-2,4,6-trimethylphenyl]amino]-9,10-dihydro-9,10-dioxoanthracene-2-sulphonate

EC Number:

279-365-5

EC Name:

Sodium 1-amino-4-[[3,5-bis[[(chloroacetyl)amino]methyl]-2,4,6-trimethylphenyl]amino]-9,10-dihydro-9,10-dioxoanthracene-2-sulphonate

Cas Number:

80010-51-1

Molecular formula:

C29H28Cl2N4O7S.Na

IUPAC Name:

sodium 1-amino-4-[(3,5-bis{[(chloroacetyl)amino]methyl}-2,4,6-trimethylphenyl)amino]-9,10-dioxo-9,10-dihydroanthracene-2-sulfonate

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

Test substance name: FAT 21036/A

Specific details on test material used for the study:

Name: 21036 / A
Purity: 79.9%

Test animals / tissue source

Species:

rabbit

Strain:

other: Russian Breed

Details on test animals or tissues and environmental conditions:

The substance was tested on 6 rabbits (3 males/3 females) of the Russian breed, which were kept separately in V2A wire cages and fed on NAFAG, Gossau SG, rabbit food and water ad libitum. Only rabbits showing normal ophthalmic findings were included in the test.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

0.1 g

Duration of treatment / exposure:

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.

Observation period (in vivo):

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.

Number of animals or in vitro replicates:

6 rabbits (3 males/3 females)

Details on study design:

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


Iris

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

Conjunctivae
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


Chemosis
No swelling...............................................................................................................................0
Any swelling above normal (includes nictitating membrane)...........................................................1
Obvious swelling with partial eversion of lids Swelling with lids about half closed..............................2
Swelling with lids about half closed to completely closed...............................................................3

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


TOOL USED TO ASSESS SCORE: hand-slit lamp

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

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

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

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 h

Results 4

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

3

Remarks on result:

no indication of irritation

Results 5

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 h

Results 6

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48h

Results 7

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 8

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48h

Any other information on results incl. tables

Table: Scores when eyes were not rinsed

Days after application	Rabbit 4			Rabbit 5			Rabbit 6
	Cornea	iris	Conjunctiva	Cornea	iris	Conjunctiva	Cornea	iris	Conjunctiva
1	20	0	12	15	0	12	15	0	12
2	20	0	10	10	0	10	15	0	10
3	15	0	10	10	0	10	10	0	10
4	5	0	8	10	0	8	10	0	6
7	5	0	6	5	0	8	10	0	6

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

FAT 21036/A is to be considered as a non-irritant to the eye of rabbits.

Executive summary:

A key study was performed to determine the eye irritation potential of FAT 21036/A in rabbits. The procedure adopted was 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. 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. Cornea and Iris scores were zero at all time intervals. slight conjuctival irritation was observed in two rabbits which were reversible within 48 h. The irritation index was found to be 5.8 for the cornea, 0 the iris and 5 for the conjunctivae. According to the EC classification of the results obtained, FAT 21036/A can be classified as non irritant to albino rabbit's eye.