Registration Dossier

Skin irritation:

The experimental skin irritation study for chemical Pigment Red 23 (CAS No: 6471-49-4) was designed and conducted by Sustainability Support Services (Europe) AB has letter of access (Report No. Siss 4393, 1974) onsix rabbits (3/sex) of Russian breed to determine the primary-irritation index.The primary irritation index of chemical TK 11451/ Pigment Red 23 (CAS No: 6471-49-4) was estimated to be 0. Thus based on the scores, the chemical Pigment Red 23 (CAS No: 6471-49-4) was considered to be not irritating to the rabbits’ skin and can be classified under the category ˋ Not Classified’ as per CLP regulation.

Eye irritation:

The experimental eye irritation study for chemical Pigment Red 23 (CAS No: 6471-49-4) was designed and conducted by Sustainability Support Services (Europe) AB has letter of access (Report No. Siss 4393, 1974) onsix rabbits (3/sex) of Russian breed to determine the primary-irritation index.The primary irritation index of chemical TK 11451/ Pigment Red 23 (CAS No: 6471-49-4) was estimated to be 0. The primary irritation index of chemical TK 11451/ Pigment Red 23 (CAS No: 6471-49-4) was estimated to be 0 for the cornea, 0 for the iris and 0 for the conjunctivae. Thus based on the scores, the chemical Pigment Red 23 (CAS No: 6471-49-4) was considered to be not irritating to the rabbits’ eye and can be classified under the category ˋ Not Classified’ as per CLP regulation.

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

Data is from experimental report

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).

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 Pigment Red 23 (CAS No: 6471-49-4)on the skin of the rabbits.

GLP compliance:

not specified

Specific details on test material used for the study:

Name: Pigment Red 23
InChI:1S/C24H17N5O7/c1-36-21-10-9-17(29(34)35)13-20(21)26-27-22-18-8-3-2-5-14(18)11-19(23(22)30)24(31)25-15-6-4-7-16(12-15)28(32)33/h2-13,30H,1H3,(H,25,31)/b27-26+
Smiles: c12c(c(c(cc1cccc2)C(=O)Nc1cc(ccc1) [N+](=O)[O-])O)/N=N/c1c(ccc(c1)[N+](=O)[O-])OC
- Name of test material:TK-11451
- Molecular formula:C24H17N5O7
- Molecular weight:213.2349 g/mol
- Substance type: Organic

Species:

rabbit

Strain:

other: Russian breed

Details on test animals or test system and environmental conditions:

- 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 cages
- Diet (e.g. ad libitum): (NAFAG, Gossau SG, rabbit food)
- Water (e.g. ad libitum): ad libitum

Type of coverage:

occlusive

Preparation of test site:

shaved

Remarks:

intact and scarified skin

Vehicle:

other: 50 % polyethylene glycol trituration (PEG 400)

Controls:

not specified

Amount / concentration applied:

500mg (0.5g)

Duration of treatment / exposure:

24 hours

Observation period:

24 and 72 hours

Number of animals:

6 (3/sex)

Details on study design:

- Area of exposure: whole back and flanks
- Type of wrap if used: The patch was covered with a plastic film 5 x 5 cm, which was fixed to the body with adhesive tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no data
- Time after start of exposure: 24 hours

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 24 and 72 hours

Score:

0

Max. score:

4

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

The primary irritation index as the measure of the acute skin irritation provoked by the substance was defined as the average of all the ratings found after 24 and 72 hours on the intact and slightly scarified skin. Compound producing combined averages (primary irritation indexes) of 2 or less were only mildly irritating; whereas those with indexes from 2 to 5 were moderate irritants, and those with scores above 6 were considered severe irritants.The primary irritation index of TK 11451/ Pigment Red 23 (CAS No: 6471-49-4) was 0.

Table 1: Evaluation of Skin Reactions

1. 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

Maximum possible = 4

2. edema Formation

No oedema......................................................................................... 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

Maximum possible = 4

Interpretation of results:

other: Not irritating

Conclusions:

The primary irritation index of chemical TK 11451/ Pigment Red 23 (CAS No: 6471-49-4) was estimated to be 0. Hence Pigment Red 23 (CAS No: 6471-49-4) was considered to be not irritating to the rabbits’ skin.

Executive summary:

The skin irritation study was conducted on six rabbits (3/sex) of Russian breed to determine the primary-irritation index, which serves as a measure of the acute irritation, provoked by the compound Pigment Red 23 (CAS No: 6471-49-4) on the skin of the rabbits.

In this test,each 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 chemical was applied to the each side at a dose of 500 mg (0.5g) in 50 % polyethylene glycol trituration (PEG 400). The gauze patches were removed 24 hours after the application.

The reaction of the skin was appraised upon removal and after 72 hours.

The primary irritation index as the measure of the acute skin irritation provoked by the substance was defined as the average of all the ratings found after 24 and 72 hours on the intact and slightly scarified skin. Compound producing combined averages (primary irritation indexes) of 2 or less were only mildly irritating; whereas those with indexes from 2 to 5 were moderate irritants, and those with scores above 6 were considered severe irritants.

The primary irritation index of chemical TK 11451/ Pigment Red 23 (CAS No: 6471-49-4) was estimated to be 0. Hence Pigment Red 23 (CAS No: 6471-49-4) was considered to be not irritating to the rabbits’ skin.

Endpoint conclusion:

no adverse effect observed (not irritating)

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

Data is from experimental study report

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 Cosmetics" (1959) of the US Association of Food and Drug Officials (AFDO).

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 Pigment Red 23 (CAS No: 6471-49-4) into the eye of the rabbits.

GLP compliance:

not specified

Specific details on test material used for the study:

Name: Pigment Red 23
InChI:1S/C24H17N5O7/c1-36-21-10-9-17(29(34)35)13-20(21)26-27-22-18-8-3-2-5-14(18)11-19(23(22)30)24(31)25-15-6-4-7-16(12-15)28(32)33/h2-13,30H,1H3,(H,25,31)/b27-26+
Smiles: c12c(c(c(cc1cccc2)C(=O)Nc1cc(ccc1) [N+](=O)[O-])O)/N=N/c1c(ccc(c1)[N+](=O)[O-])OC
- Name of test material:TK-11451
- Molecular formula:C24H17N5O7
- Molecular weight:213.2349 g/mol
- Substance type: Organic

Species:

rabbit

Strain:

other: Russian breed

Details on test animals or tissues and environmental conditions:

- 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 cages
- Diet (e.g. ad libitum): (NAFAG, Gossau SG, rabbit food)
- Water (e.g. ad libitum): ad libitum

Vehicle:

not specified

Controls:

yes

Amount / concentration applied:

100mg (0.1g)

Duration of treatment / exposure:

7 days

Observation period (in vivo):

after 24 hours and after 2,3,4 and 7 days

Number of animals or in vitro replicates:

6 (3/sex)

Details on study design:

TEST SITE
- Area of exposure: the conjunctival sac of the left eye
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: after 24 hours
SCORING SYSTEM: the reactions were scored on the basis of the "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" (1959) of the AFDO.

Irritation parameter:

other: primary irritation index

Basis:

mean

Time point:

other: after 24 hours and after 2,3,4 and 7 days

Score:

0

Max. score:

110

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

The irritation index was found to be 0 for the cornea, 0 for the iris and 0 for the conjunctivae.

Table 1: RESULTS OF RABBITS WITH EYE RINSED

Days after application	Rabbit 1 (female)			Rabbit 2 (female)			Rabbit 3 (female)
Days after application	Cornea	Iris	conjunctivae	Cornea	Iris	conjunctivae	Cornea	Iris	conjunctivae
1	0	0	0	0	0	0	0	0	0
2	0	0	0	0	0	0	0	0	0
3	0	0	0	0	0	0	0	0	0
4	0	0	0	0	0	0	0	0	0
7	0	0	0	0	0	0	0	0	0

Table 2: RESULTS OF RABBITS WITH EYE NOT RINSED

Days after application	Rabbit 4 (male)			Rabbit 5 (male)			Rabbit 6 (male)
Days after application	Cornea	Iris	conjunctivae	Cornea	Iris	conjunctivae	Cornea	Iris	conjunctivae
1	0	0	0	0	0	0	0	0	0
2	0	0	0	0	0	0	0	0	0
3	0	0	0	0	0	0	0	0	0
4	0	0	0	0	0	0	0	0	0
7	0	0	0	0	0	0	0	0	0

Interpretation of results:

other: Not irritating

Conclusions:

The primary irritation index of chemical TK 11451/ Pigment Red 23 (CAS No: 6471-49-4) was estimated to be 0 for the cornea, 0 for the iris and 0 for the conjunctivae. Hence Pigment Red 23 (CAS No: 6471-49-4) was considered to be not irritating to the rabbits’ eye.

Executive summary:

An ocular irritation study was conducted on six rabbits (3/sex) of Russian breed to determine the primary-irritation index, which serves as a measure of the acute irritation, provoked by the compound Pigment Red 23 (CAS No: 6471-49-4) on the eye of the rabbits.

In this test, about (0.1g) of the test substance Pigment Red 23 (CAS No: 6471-49-4) 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 on the basis of the "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" (1959) of the AFDO.

The primary irritation index of chemical TK 11451/ Pigment Red 23 (CAS No: 6471-49-4) was estimated to be 0 for the cornea, 0 for the iris and 0 for the conjunctivae. Hence Pigment Red 23 (CAS No: 6471-49-4) was considered to be not irritating to the rabbits’ eye.

Endpoint conclusion:

no adverse effect observed (not irritating)

Endpoint conclusion:

no study available

Skin irritation

The experimental skin irritation study for chemical Pigment Red 23 (CAS No: 6471-49-4) was designed and conducted by Sustainability Support Services (Europe) AB has letter of access (Report No. Siss 4393, 1974) onsix rabbits (3/sex) of Russian breed to determine the primary-irritation index, which serves as a measure of the acute irritation, provoked by the chemical.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).

In this test,each 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 chemical was applied to the each side at a dose of 500 mg (0.5g) in 50 % polyethylene glycol trituration (PEG 400). The gauze patches were removed 24 hours after the application. The reaction of the skin was appraised upon removal and after 72 hours.The primary irritation index as the measure of the acute skin irritation provoked by the substance was defined as the average of all the ratings found after 24 and 72 hours on the intact and slightly scarified skin. Compound producing combined averages (primary irritation indexes) of 2 or less were only mildly irritating; whereas those with indexes from 2 to 5 were moderate irritants, and those with scores above 6 were considered severe irritants.

The primary irritation index of chemical TK 11451/ Pigment Red 23 (CAS No: 6471-49-4) was estimated to be 0. Thus based on the scores, the chemical Pigment Red 23 (CAS No: 6471-49-4) was considered to be not irritating to the rabbits’ skin and can be classified under the category ˋ Not Classified’ as per CLP regulation.

Eye irritation

The experimental eye irritation study for chemical Pigment Red 23 (CAS No: 6471-49-4) was designed and conducted by Sustainability Support Services (Europe) AB has letter of access (Report No. Siss 4393, 1974) onsix rabbits (3/sex) of Russian breed to determine the primary-irritation index, which serves as a measure of the acute irritation, provoked by the chemical.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).

In this test, about (0.1g) of the test substance Pigment Red 23 (CAS No: 6471-49-4) 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 on the basis of the "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" (1959) of the AFDO.

The primary irritation index of chemical TK 11451/ Pigment Red 23 (CAS No: 6471-49-4) was estimated to be 0 for the cornea, 0 for the iris and 0 for the conjunctivae. Thus based on the scores, the chemical Pigment Red 23 (CAS No: 6471-49-4) was considered to be not irritating to the rabbits’ eye and can be classified under the category ˋ Not Classified’ as per CLP regulation.

The skin and eye irritation potential of test chemicalC.I. Pigment Red 23 (CAS No: 6471-49-4) was observed in experimental study conducted by Sustainability Support Services (Europe) AB has letter of access (Report No. Siss 4393, 1974).The results obtained from these studies indicate that the chemicalC.I. Pigment Red 23 (CAS No: 6471-49-4)is unlikely to cause skin and eye irritation. HenceC.I. Pigment Red 23 (CAS No: 6471-49-4)can be classified under the category “Not Classified” for skin and eye as per CLP.