Sodium 1-amino-9,10-dihydro-9,10-dioxo-4-[[3-[(1-oxopropyl)amino]phenyl]amino]anthracene-2-sulphonate

Endpoint summary

Description of key information

FAT 20242 did not induce skin irritation in test animals, however it showed remarkable symptoms of eye irritation in test animals.

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:

1986

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

no

Specific details on test material used for the study:

Code No.: FAT 20242/E
Batch No.: EN 1500.52
Contents of active ingredients: 100%
Validity: April 1991
Description: Solid/powder; Solubility in water: Approx. (10 g/L at 20°C, pH 7.3)
Safety precautions : Golve and face masks.
Test article received: June 2, 1986.

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source:Kleintierfarm Madoerin AG, CH-4414 Fuellinsdorf
- Age at study initiation:approx. 12-14 weeks old
- Weight at study initiation: 2220 to 2360 g
- Housing:The animals were housed individually in metal cages, identified with individually numbered ear tags.
- Diet: The rabbits received ad libitum standard rabbit pellet - Nafag No. 814, Gossau, Switzerland
- Water: fresh water, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature: 20 ± 3 °C
- Humidity: 30-70 %
- Photoperiod:12 hours light cycle day.

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

water

Remarks:

Distilled

Controls:

yes, concurrent vehicle

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g

Duration of treatment / exposure:

4 hours

Observation period:

14 days

Number of animals:

3 male rabbits

Details on study design:

An area of at least 6 cm² was shaved on both flanks of the animals approximately 24 hours before treatment. A gauze patch (20cm²) bearing 0.5g of the test substance was applied to the flank. A control gauze patch was applied to the contralateral flank. Both gauze patches were moistened before application with distilled water.

The patches were loosely covered with an aluminium foil (36 cm²) and held in place for 4 hours by an adhesive tape (Isoplast, Isoplast AG, CH-5200 Brugg).

- The animals were checked daily for systemic symptoms and mortality.
- The skin reactions were evaluated 1, 24, 48, and 72 hours after removing the gauze patches according to the OECD scoring system.
- The body weight was recorded at start and on days 3, 7 and 14 of the test.

SCORING SYSTEM:

Erythema and eschar formation
- No erythema: 0
- Very slight erythema (barely perceptible): 1
- Well defined erythema: 2
- Moderate to severe erythema: 3
- Severe erythema (beet redness) to slight eschar formation (injuries in depth): 4
Total possible erythema score 4

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

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: Blue - staining (substance related)

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No edema formation was observed during an observation period of 14 days.

Other effects:

The application area was stained blue (substance-related) up to the end of the observation period. Therefore the evaluation of a possible slight erythema formation was impeded. However, a marked erythema formation was not noted and on the unstained marginal zone of the application area no erythema was recorded.

None

Interpretation of results:

GHS criteria not met

Conclusions:

FAT 20242/E can be classified as non-irritant in albino rabbits.

Executive summary:

The test was performed on 3 male rabbits to determine the irritation or corrosive potency of FAT 20242/E. This test was concucted as per OECD Guideline 404.

A gauze patch (20 cm2) bearing 0.5 g of the test substance was applied to shaved area on the flank.

No edema formation was observed during an observation period of 14 days. The application area was stained blue (substance-related) up to the end of the observation period. Therefore the evaluation of a possible slight erythema formation was impeded. However, a marked erythema formation was not noted and on the unstained marginal zone of the application area no erythema was recorded.

Hence it can be concluded that under the experimental conditions, FAT 20242/E did not induce skin irritation when applied to the shaved albino rabbit 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:

1986

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

no

Specific details on test material used for the study:

Code No.: FAT 20242/E
Batch No.: EN 1500.52
Contents of active ingredients: 100%
Validity: April 1991
Description: Solid/powder; Solubility in water: Approx. (10g/L at 20°C, pH 7.3)
Safety precautions : Golve and face masks.
Test article received: June 2, 1986.

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Kleintierfarm Madoerin AG, CH-4414 Fuellinsdorf
- Age at study initiation: approx. 12-14 weeks old
- Weight at study initiation: between 2200 to 2510 g
- Housing: The animals were housed individually in metal cages, identified with individually numbered ear tags.
- Diet: The rabbits received ad libitum standard rabbit pellet - Nafag No. 814, Gossau, Switzerland
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20±3 °C
- Humidity: 30-70 %
- Photoperiod: 12 hours light cycle day.

Vehicle:

unchanged (no vehicle)

Controls:

other: Left eye of each rabbit remained untreated and served as a control.

Amount / concentration applied:

0.1 ml

Duration of treatment / exposure:

One single application

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

3 female rabbits

Details on study design:

0.1 ml of FAT 20242/E was placed into the conjunctival sac of the right eye of each animal after gently pulling away the lower lid from the eyeball.
The lids were then held together for about one second in order to prevent loss of the test material. The left eye was kept untreated and served as a control.
The animals were checked daily for systemic symptoms and mortality.

The ocular reactions were evaluated 1, 24, 48, and 72 hours after the instillation of FAT 20242/E according to the OECD scoring system.

TOOL USED TO ASSESS SCORE: A slit-lamp was used to facilitate the evaluation.

SCORING SYSTEM:
CORNEA
Opacity: degree of density (area most dense taken for reading).
- No ulceration or opacity:...................................................................................................................................... 0
- Scattered or diffuse areas of opacity (other than slight dulling of normal lustre), details of iris clearly visible:................ 1
- Easily discernible translucent area, details of iris slightly obscured:......................................................................... 2
- Nacrous area, no details of iris visible, size of pupil barely discernible:..................................................................... 3
- Opaque cornea, iris not discernible through the opacity:......................................................................................... 4

IRIS
- Normal:............................................................................................................................................................... 0
- Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia, or injection, any 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

CONJUNCTIVAE
Redness: (refers to palpebral and bulbar conjunctivae, cornea and iris)
- Blood vessels normal:............................................................................... 0
- Some blood vessels definitely hyperaemic (injected):................................... 1
- Diffuse, crimson colour, individual vessels not easily discernible:................... 2
- Diffuse, beefy red:..................................................................................... 3

Chemosis: lids and/or nictitating membranes
- No swelling..................................................................................... 0
- Any swelling above normal (includes nictitating membranes)............... 1
- Obvious swelling with partial eversion of lids....................................... 2
- Swelling with lids about half closed.................................................... 3
- Swelling with lids more than, half closed............................................. 4

Basis:

mean

Time point:

other: 24-72 hours

Reversibility:

other: expected to be not fully reversible within 21 days

Remarks on result:

other: Because of maximal opacity of the cornea in animals No. 66 and 67, the evaluation of possible iris reactions was impeded

Irritation parameter:

cornea opacity score

Basis:

animal #1

Remarks:

test eye

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not fully reversible within: 72 hours

Remarks on result:

other: Animal number 66

Irritation parameter:

cornea opacity score

Basis:

animal #2

Remarks:

test eye

Time point:

24/48/72 h

Score:

3.66

Max. score:

4

Reversibility:

not fully reversible within: 72 hours

Remarks on result:

other: Animal number 67

Irritation parameter:

cornea opacity score

Basis:

animal #3

Remarks:

test eye

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

not fully reversible within: 72 hours

Remarks on result:

other: Animal number 68

Irritation parameter:

iris score

Basis:

animal #1

Remarks:

test eye

Time point:

24/48/72 h

Reversibility:

not fully reversible within: 72 hours

Remarks on result:

other: No evaluation possible because of maximal opacity of cornea

Irritation parameter:

iris score

Basis:

animal #2

Remarks:

test eye

Time point:

24/48/72 h

Reversibility:

not fully reversible within: 72 hours

Remarks on result:

other: No evaluation possible because of maximal opacity of cornea

Irritation parameter:

iris score

Basis:

animal #3

Remarks:

test eye

Time point:

24/48/72 h

Score:

0.33

Max. score:

2

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

conjunctivae score

Basis:

animal #1

Remarks:

test eye

Time point:

24/48/72 h

Score:

2.33

Max. score:

3

Reversibility:

not fully reversible within: 72 hours

Remarks on result:

other: 1 hour after application: Blue-staining (substance related)

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

test eye

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

not fully reversible within: 72 hours

Remarks on result:

other: 1 hour after application: Blue-staining (substance related)

Irritation parameter:

conjunctivae score

Basis:

animal #3

Remarks:

test eye

Time point:

24/48/72 h

Score:

1.33

Max. score:

3

Reversibility:

not fully reversible within: 72 hours

Irritation parameter:

chemosis score

Basis:

animal #1

Remarks:

test eye

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 72 hours

Irritation parameter:

chemosis score

Basis:

animal #2

Remarks:

test eye

Time point:

24/48/72 h

Score:

2.33

Max. score:

4

Reversibility:

not fully reversible within: 72 hours

Irritation parameter:

chemosis score

Basis:

animal #3

Remarks:

test eye

Time point:

24/48/72 h

Score:

0.66

Max. score:

4

Reversibility:

not fully reversible within: 72 hours

Irritant / corrosive response data:

Cornea and conjunctiva of the treated eye of animals No. 66 and 67 and the cornea of animal No. 68 were blue-stained (substance-related) one hour after the application of the test compound.

Because of maximal opacity of the cornea in animals No. 66 and 67, the evaluation of possible iris reactions was impeded.

FAT 20242/E induced maximal irritant effects in animals No. 66 and 67 which were expected not be reversible within 21 days. The animals were sacrificed for protective reasons 72 hours after instillation of the test compound.

Other effects:

None

Body weight:

Animal no.	66/F	67/F	68/F
At start of test	2200	2380	2510
After 3 days (end)	2270	2500	2570

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Conclusions:

FAT 20242/E is concluded to pose risk of serious damage to eyes.

Executive summary:

An acute eye irritation/corrosion study was performed to determine the irritant or corrosive potency of FAT 20242/E. This test was conducted based on the OECD Guideline No. 405. The substance was tested undiluted to determine the irritant potency on 3 female rabbit eyes.

0.1 ml of FAT 20242/E was placed into the conjunctival sac of the right eye of each animal, after gently pulling away the lower lid from the eyeball. The lids were then held together for about one second in order to prevent loss of the test material. The left eye remained untreated and served as a control.

Cornea and conjunctiva of the treated eye of animals No. 66 and 67 and the cornea of animal No. 68 were blue-stained (substance-related) one hour after the application of the test compound. Because of maximal opacity of the cornea in animals No. 66 and 67, the evaluation of possible iris reactions was impeded. FAT 20242/E induced maximal irritant effects in animals No. 66 and 67 which were expected not be reversible within 21 days. The animals were sacrificed for animal protective reasons 72 hours after instillation of the test compound. Hence it can be concluded that, under the experimental conditions employed, FAT 20242/E induced strong irritation of the cornea and conjunctiva. The test compound possess the risk of serious damage to the eyes

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin:

A study performed on male rabbits, checked for skin conditions to determine the irritant or corrosive potency of FAT 20242/E on the albino rabbit skin. This test was based on the OECD guideline No. 404. The results showed no edema formation during an observation period of 14 days. However, at the application area blue-stains (substance-related) were observed up to the end of the observation period. Therefore the evaluation of a possible slight erythema formation was impeded. A marked erythema formation was not noted and on the unstained marginal zone of the application area no erythema was recorded. Hence, it was concluded , that under the experimental conditions FAT 20242/E did not induce irritation when applied to the shaved albino rabbit skin.

The supporting study was done according to the "Primary dermal Irritation study", Federal Register, Vol. 43, No. 163, August 22, 1978. New Zealand White rabbits (3 males and 3 females), were used for the experiment. 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 "SchröpfSchnäpper", 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 and exposure lasted for 24 hours. No erythema or edema was seen at the application sites throughout the observation period. In conclusion, the primary irritation index as the measure of the acute irritation to the skin of rabbits was found to be 0. Therefore FAT 20242/A is considered as not irritant to the skin of rabbits.

Eye:

In a study (Key study), based on the OECD guideline No. 405, cornea and conjunctiva of the treated animals were blue-stained (substance-related) one hour after the application of the test compound. Because of maximal opacity of the cornea in animals, the evaluation of possible iris reactions was impeded. FAT 20242/E induced maximal irritant effects in 2 animals which were expected not be reversible within 21 days. The animals were killed for animal welfare reasons 72 hours after instillation of the test compound. On account of the mean value obtained 24 to 72 hours after instillation of the test compound the risk of serious damage to eyes is expected. Based on these findings, it was concluded that FAT 20242/E possess the risk of serious damage to eyes.

Couple of supporting studies carried out in 1980 -1981 and 1987 are available. The test item was found to have minimal irritation to eyes in these studies.

Justification for classification or non-classification

FAT 20242 did not induce skin irritation in animals, however found to be irritating to eyes. Hence it needs to be classified as causing eye damage (cat 1) as per the criteria of Regulation (EC) No. 1272/2008 (CLP).