Disodium [3-[(4,5-dihydro-3-methyl-5-oxo-1-phenyl-1H-pyrazol-4-yl)azo]-4-hydroxybenzenesulphonato(3-)][1-[[2-hydroxy-5-(phenylazo)phenyl]azo]-2-naphtholato(2-)]chromate(2-)

Endpoint summary

Description of key information

FAT 21095/A is considered to be non- irritant to skin and eye of rabbits.

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:

1975

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

other: The procedure adopted was the patch-test 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).

Deviations:

yes

Remarks:

Testing under occluvive conditions represents an elevated testing condition and results obtained under such conditions need to be carefully taken ito account for the overall hazard and risk assessment.

Principles of method if other than guideline:

The purpose of this test was to determine the primary-irritation index, which serves as a measure of the acute irritation,provoked by the compound on the skin of the rabbits.

GLP compliance:

no

Specific details on test material used for the study:

Identification: FAT 21095/A
Purity: 80 %

Species:

rabbit

Strain:

other: Russian breed

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 1.5 to 2 kgs.
- Housing: In order to prevent injuries by bites the rabbits were kept separately in V2A wire mesh cages.
- Diet and water: they had access to food (NAFAG, Gossau SG, rabbit food) and water ad libitum.

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

other: Polyethylene glycol trituration (PEG 400)

Controls:

no

Amount / concentration applied:

0.5 g

Duration of treatment / exposure:

24 hours

Observation period:

72 hours

Number of animals:

6 rabbits (3 males and 3 females)

Details on study design:

The rabbits were shaved on the whole back and flanks two days before treatment with an electric clipper. The shaven skin on the left side was slightly scarified immediately before treatment. A gauze patch 2.5 x 2.5 cm was soaked with the test substance and immediately applied to the prepared skin. The patch was covered with a plastic film 5 x 5 cm, which was fixed to the body with adhesive tape.

FAT 21095/A was applied to each side in quantities of 0.5 g. Before application a 50 % polyethylene glycol trituration (PEG 400) was made. The gauze patches were removed 24 hours after the application. The reaction of the skin was appraised upon removal and 72 hours after it, on the basis of the following evaluation scheme.

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

TEST SITE
- Area of exposure: The shaven skin on the left side was slightly scarified immediately before treatment. A gauze patch 2.5 x 2.5 cm was soaked with the test substance and immediately applied to the prepared skin. The patch was covered with a plastic film 5 x 5 cm, which was fixed to the body with adhesive tape.
- Type of wrap if used: plastic film
- Time after start of exposure: 72 hours

Irritation parameter:

erythema score

Remarks:

Intact skin

Basis:

animal #1

Time point:

24 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Remarks:

Intact skin

Basis:

animal #1

Time point:

48 h

Remarks on result:

not measured/tested

Irritation parameter:

erythema score

Remarks:

Intact skin

Basis:

animal #1

Time point:

72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Remarks:

Intact skin

Basis:

animal #2

Time point:

24 h

Score:

1

Max. score:

4

Irritation parameter:

erythema score

Remarks:

Intact skin

Basis:

animal #2

Time point:

48 h

Remarks on result:

not measured/tested

Irritation parameter:

erythema score

Remarks:

Intact skin

Basis:

animal #2

Time point:

72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Remarks:

Intact skin

Basis:

animal #3

Time point:

24 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Remarks:

Intact skin

Basis:

animal #3

Time point:

48 h

Remarks on result:

not measured/tested

Irritation parameter:

erythema score

Remarks:

Intact skin

Basis:

animal #3

Time point:

72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Remarks:

Intact skin

Basis:

animal #4

Time point:

24 h

Score:

1

Max. score:

4

Irritation parameter:

erythema score

Remarks:

Intact skin

Basis:

animal #4

Time point:

48 h

Remarks on result:

not measured/tested

Irritation parameter:

erythema score

Remarks:

Intact skin

Basis:

animal #4

Time point:

72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Remarks:

Intact skin

Basis:

animal #5

Time point:

24 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Remarks:

Intact skin

Basis:

animal #5

Time point:

48 h

Remarks on result:

not measured/tested

Irritation parameter:

erythema score

Remarks:

Intact skin

Basis:

animal #5

Time point:

72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Remarks:

Intact skin

Basis:

animal #6

Time point:

24 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Remarks:

Intact skin

Basis:

animal #6

Time point:

48 h

Remarks on result:

not measured/tested

Irritation parameter:

erythema score

Remarks:

Intact skin

Basis:

animal #6

Time point:

72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Remarks:

Intact skin

Basis:

mean

Time point:

24 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Remarks:

Intact skin

Basis:

mean

Time point:

48 h

Remarks on result:

not measured/tested

Irritation parameter:

edema score

Remarks:

Intact skin

Basis:

mean

Time point:

72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

Compounds producing combined averages (primary irritation indexes) of 2 or less are only mildly irritating; whereas those with indexes from 2 to 5 are moderate irritants, and those with scores above 6 are considered severe irritants.

Interpretation of results:

GHS criteria not met

Conclusions:

The primary irritation index as the measure of the acute irritation to the skin of rabbits was found to be 0.29. Therefore, FAT 21095/A is to be considered as a non-irritant irritant to the skin of rabbits.

Executive summary:

The purpose of this test was to determine the primary-irritation index, which serves as a measure of the acute irritation, provoked by the compound on the skin of the rabbits. The procedure adopted was the patch-test 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). Six rabbits (3 males/3 females) of the Russian breed, were shaved on the whole back and flanks two days before treatment with an electric clipper. The shaven skin on the left side was slightly scarified immediately before treatment. A gauze patch was soaked with the test substance FAT 21095/A (0.5 g) and immediately applied to the prepared skin. The patch was covered with a plastic film (occlusive). FAT 21095/A was applied to each side in quantities of 0.5 g. Before application a 50 % polyethylene glycol trituration (PEG 400) was made. The gauze patches were removed 2 4 hours after the application. The reaction of the skin was appraised upon removal and 72 hours after it. Slight erythema was observed in Intact and abraded skin which was reversible within 72 hours. No edema was observed at any observation time points. The primary irritation index as the measure of the acute irritation to the skin of rabbits was determined to be 0.29. Therefore, FAT 21095/A is to be considered as non-irritant to the skin of rabbits.

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:

1975

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

other: The procedure adopted was the technique described in the "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetic (1959) of the US Association of Food and Drug Officials (AFDO).

Deviations:

not specified

GLP compliance:

no

Specific details on test material used for the study:

Identification:21095/A
Purity: 80 %

Species:

rabbit

Strain:

other: Russian breed

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Housing: Rabbits were kept separately in V2A wire-mesh cages
- Diet (e.g. ad libitum):Rabbits were fed on NAFAG, Gossau SG, rabbit food
- Water (e.g. ad libitum): ad libitum

Vehicle:

unchanged (no vehicle)

Controls:

other: Yes, right eye of rabbit served as control.

Amount / concentration applied:

0.1 g

Duration of treatment / exposure:

30 seconds

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

6 rabbits (3 males and 3 females)

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The treated eyes of three rabbits were each rinsed with 10 ml lukewarm water about 30 seconds after treatment.
- Time after start of exposure: 24 hours

SCORING SYSTEM:
Evaluation of the Eye Reactions
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

Ax5

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


TOOL USED TO ASSESS SCORE: hand-slit lamp

Irritation parameter:

iris score

Basis:

mean

Remarks:

3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

other: Eyes rinsed

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

3 animals

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: Eyes rinsed

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

3 animals

Time point:

24/48/72 h

Score:

1.11

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: Eyes rinsed

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

3 animals

Time point:

24/48/72 h

Score:

0.88

Max. score:

3

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: Eyes rinsed

Irritation parameter:

iris score

Basis:

mean

Remarks:

3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

other: Eyes not rinsed

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

3 animals

Time point:

24/48/72 h

Score:

1.89

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Remarks on result:

other: Eyes not rinsed

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

3 animals

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Remarks on result:

other: Eyes not rinsed

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

3 animals

Time point:

24/48/72 h

Score:

1.78

Max. score:

3

Reversibility:

not fully reversible within: 7 days

Remarks on result:

other: Eyes not rinsed

Irritant / corrosive response data:

The total maximum is 80 for the cornea, 10 for the iris and 20 for the conjunctivae.
The irritation index was found to be 7.8 for the cornea, 0 for the iris and 5.8 for the conjunctivae.

Interpretation of results:

GHS criteria not met

Conclusions:

FAT 21095/A is considered to be not irritating to rabbit eyes.

Executive summary:

FAT 21095/A was tested for eye irritation potential on rabbits eye. This test was conducted in accordance with "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" (1959) of the AFDO. The substance was tested on 6 rabbits (3 males/3 females) of the Russian breed. Only rabbits showing normal ophthalmic findings were included in the test. Amounts of 0.1 g of the test substance were introduced into the conjunctival sac of the left eye with a spatula. After application, they 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. In rinsed eyes, effects were observed on conjuctivae and cornea which were reversible within 7 days. Similar effects were observed in unrinsed eyes which were not reversible within 7 days. No effect on Iris was observed in both rinsed and unrinsed eye. Based on the findings of the study, FAT 21095/A is considered to be not irritating to rabbit eyes.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

A study was conducted to assess the potential of FAT 21095/A to cause acute irritation on the rabbit skin. The procedure adopted was the patch-test 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). Six rabbits (3 males/3 females) of the Russian breed were used in the occlusive patch test. FAT 21095/A was applied to each side in quantities of 0.5 g. Before application a 50 % polyethylene glycol trituration (PEG 400) was made. The gauze patches were removed 24 hours after the application. The reaction of the skin was appraised upon removal and 72 hours after it. The primary irritation index as the measure of the acute irritation to the skin of rabbits was found to be 0.29. It is necessary to note that testing under occlusive conditions represents an elevated testing condition compared to OECD guideline. Nevertheless, no signs of irritation have been noted. Therefore, the test is regarded to be valid for assessment. Hence, FAT 21095/A is to be considered as non-irritant to the skin of rabbits.

To assess the acute eye irritation potential of FAT 21095/A when exposed to rabbit eye, a study was performed in accordance to the procedure mentioned in "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" (19 59) of the 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, they 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" (19 59) of the AFDO. The primary-irritation index, which serves as a measure of the acute irritation provoked by the substance, was found to be 7.8 for the cornea, 0 for the iris and 5.8 for the conjunctivae. Therefore, FAT 21095/A is to be considered to be non-irritant to rabbit eyes.

Justification for selection of skin irritation / corrosion endpoint: Basic data given, acceptable for assessment

Justification for selection of eye irritation endpoint: Basic data given, acceptable for assessment

Justification for classification or non-classification

FAT 21095/A is considered to be non-irritant to skin and eye of rabbits. Considering that the reaction in the eye to be fully reversible, FAT 21095/A is classified as non-irritant in eye.