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

Endpoint summary

Description of key information

The substance is not irritating to skin or eyes.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin 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

Qualifier:

according to guideline

Guideline:

other: United States Environmental Agency (EPA) § 163.81- 5 "Primary dermal irritation study", Federal Register, Vol. 43, No. 163, August 22, 1978

Deviations:

not specified

GLP compliance:

no

Specific details on test material used for the study:

Identified as: FAT 21030/C

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

The test was performed on 3 males and 3 females adult rabbits of the New Zealand White breed (IVANOVAS, 7964 Kisslegg/Allgäu, Germany and MADOERIN AG, 4414 Füllinsdorf, Switzerland) weighing 2 to 3 kgs. They 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 hours light cycle day. The animals received ad libitum 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.

Type of coverage:

occlusive

Preparation of test site:

other: Shaved and abraded

Vehicle:

other: Propylene glycol+saline (70:30)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g of the test material were applied to the prepared abraded and intact skin.
- Concentration (if solution): 50 %

Duration of treatment / exposure:

24 hours

Observation period:

7 days

Number of animals:

3 males and 3 females

Details on study design:

Before treatment the entire back and the flank of the rabbits were shaved with an electric clipper and immediately before treatment the shaven skin on one side was slightly shaved with the help of a "Schröpfschnapper" Aesculap, Switzerland. Gauze patches of 2.5 x 2.5 cm laden with 0.5 g of the test material were applied to the prepared abraded and intact skin.

The patches were covered with an impermeable material and were fastened to the body of the rabbit with adhesive tape. The dressings were removed after a 24 hour application.
The skin reaction was appraised upon removal and during an observation period of 7 days on the basis of the following evaluation scheme.

SCORING SYSTEM:

*Erythema and Eschar Formation
- No erythema: 0
- Slight erythema (barely perceptible): 1
- Well defined erythema: 2
- Moderate to severe erythema: 3
- Severe erythema (beet red) to slight eschar formation: 4
Total possible erythema score: 4

*Oedema Formation
- No-oedema: 0
- Very slight oedema (barely perceptible): 1
- Slight oedema (edges of area well defined by definite raising): 2
- Moderate oedema (raised approximately 1 mm): 3
- Severe-oedema (raised more than 1 mm. and extending beyond the area of exposure): 4
Total possible edema score: 4

Irritation parameter:

erythema score

Basis:

mean

Remarks:

3 males and 3 females

Time point:

24 h

Score:

0

Max. score:

4

Remarks on result:

other: Intact skin

Irritation parameter:

erythema score

Basis:

mean

Remarks:

3 male and 3 female

Time point:

48 h

Score:

0.167

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Remarks on result:

other: Intact skin

Irritation parameter:

erythema score

Basis:

mean

Remarks:

3 males and 3 females

Time point:

72 h

Score:

0

Max. score:

4

Remarks on result:

other: Intact skin

Irritation parameter:

erythema score

Basis:

mean

Remarks:

3 males and 3 females

Time point:

24 h

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Remarks on result:

other: Abraded skin

Irritation parameter:

erythema score

Basis:

mean

Remarks:

3 male and 3 female

Time point:

48 h

Score:

0.83

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Remarks on result:

other: Abraded skin

Irritation parameter:

erythema score

Basis:

mean

Remarks:

3 males and 3 females

Time point:

72 h

Score:

0

Max. score:

4

Remarks on result:

other: Abraded skin

Irritation parameter:

edema score

Basis:

mean

Remarks:

3 males and 3 females

Time point:

24 h

Score:

0

Max. score:

4

Remarks on result:

other: Intact skin

Irritation parameter:

edema score

Basis:

mean

Remarks:

3 male and 3 female

Time point:

48 h

Score:

0

Max. score:

4

Remarks on result:

other: Intact skin

Irritation parameter:

edema score

Basis:

mean

Remarks:

3 males and 3 females

Time point:

72 h

Score:

0

Max. score:

4

Remarks on result:

other: Intact skin

Irritation parameter:

edema score

Basis:

mean

Remarks:

3 males and 3 females

Time point:

24 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Remarks on result:

other: Abraded skin

Irritation parameter:

edema score

Basis:

mean

Remarks:

3 male and 3 females

Time point:

48 h

Score:

0

Max. score:

4

Remarks on result:

other: Abraded skin

Irritation parameter:

edema score

Basis:

mean

Remarks:

3 male and 3 females

Time point:

72 h

Score:

0

Max. score:

4

Remarks on result:

other: Abraded skin

Interpretation of results:

GHS criteria not met

Conclusions:

FAT 21030/C is not an irritant to skin.

Executive summary:

An experiment was performed to determine the skin irritation potential of FAT 21030/C in New Zealand White rabbits. The test was carried out according to the method given in the United States Environmental Agency (EPA) § 163.81- 5 "Primary dermal irritation study", Federal Register, Vol. 43, No. 163, August 22, 1978.

Before treatment the entire back and the flank of the rabbits were shaved with an electric clipper and immediately before treatment the shaven skin on one side was slightly scarified with the help of a "Schröpfschnapper" Aesculap, Switzerland. Gauze patches of 2.5 x 2.5 cm laden with 0.5 g of the test material were applied to the prepared abraded and intact skin. The patches were covered with an impermeable material and were fastened to the body of the rabbit with adhesive tape. The dressings were removed after a 24 hour application. The skin reactions were appraised upon removal and during an observation period of 7 days.

At 24/48/72h time points, FAT 21030/C did not cause irritation to intact skin. Slight irritation was observed on abraded skin which was reversible within 72 hours. The primay irritation index was found to be 0.25. Hence, based on the findings of the study, it can be concluded that FAT 21030/C is not an irritant to skin.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

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

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

Specific details on test material used for the study:

Identification: FAT 21030/C

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.

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)

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

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0.72

Max. score:

3

Reversibility:

fully reversible within: 72 h

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

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Additional information

The studies performed with FAT21030 demonstrated that the test substance was not skin or eye irritation and all irritation was fully reversed fully within 24 hours after dosing.

Skin irritation:

The study (1975) designated to be key, was carried out using 6 New Zealand White rabbits according to the method given in the United States Environmental Agency (EPA) § 163.81- 5 "Primary dermal irritation study", Federal Register, Vol. 43, No. 163, August 22, 1978. No irritation was seen when the intact skin was exposed to the test substance. Slight irritation was observed on abraded skin which was reversible within 72 hours. The primay irritation index was found to be 0.25. Hence, based on the findings of the study, it was concluded that FAT 21030/C is not an irritant to skin.

In the experiment designated to be supporting study, the primary skin irritation potential of FAT 21030/A was assessed in New Zealand White rabbits using the method given in the "Hazardous Substances Regulations" under the U.S. Federal Hazardous Substances Labelling Act Sect. 191.11 (February 1965). Slight erythema was observed in 3/6 animals at 24 hours when test substance was exposed to intact skin, this was found to have been reversed by 72 hours. Very slight to moderate edema was seen with intact skin at 24 hours, which was reversed by 72 hours for intact skin. Hence, FAT 21030/A is considered to be not a skin irritant.

Eye irritation:

In the study (1979) designated as key, the irritation potential of FAT 21030/C was assessed 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. 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.

The purpose of this eye irritation study was to assess the irritation potential of FAT 21030/A when placed in the conjunctival sac of rabbit left eyes (3 males and 3 females, 0.1 g/animal). This experiment was done according to the "Hazardous Substances Regulations" under the U.S.A. Federal Hazardous Substances Labelling Act Sect. 191.12 (February 1965). The mean scores obtained for corneal opacity, iris, conjunctival redness and chemosis were 0.5, 0.06, 1.72 and 1.28, respectively. These scores were found to not fulfil the classification criteria as set by Regulation (EC) no. 1272/2008. Hence it can be concluded that, FAT 21030/A was not irritating when applied to the eyes of rabbits.

Justification for classification or non-classification

Based on the negative outcome of skin and eye irritation studies, FAT 21030 does not need to be classified according to the criteria of Regulation (EC) No. 1272/2008.