Registration Dossier

Skin Irritation:

Based on the available data for the structurally similar read across substances and applying the weight of evidence approach, it can be concluded that the target chemical will also tend to behave in a similar manner that of the read across substances. Therefore the target chemical was estimated to be not irritating to skin and it can be further classified under the category “Not Classified” as per CLP regulation.

Eye Irritation:

Based on the available data for the structurally similar read across substances and applying the weight of evidence approach, it can be concluded that the target chemical will also tend to behave in a similar manner that of the read across substances. Therefore the target chemical was estimated to be not irritating to eyes and it can be further classified under the category “Not Classified” as per CLP regulation.

Reference

Endpoint:

skin irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Weight of evidence approach based on the structurally similar chemicals

Justification for type of information:

Weight of evidence approach based on the structurally similar chemicals

Reason / purpose for cross-reference:

read-across: supporting information

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

according to guideline

Guideline:

other: Weight of evidence based on structurally similar substances

Principles of method if other than guideline:

The weight of evidence report has been prepared based on the read across substances identified based on structural and functional similarity to assess the dermal irritation potential of N-(2-ethylhexyl)-1-[[2-methyl-4-[(4-methylphenyl)azo]phenyl]azo]naphthalen-2-amine

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of the test material: N-(2-ethylhexyl)-1-[[2-methyl-4-[(4-methylphenyl)azo]phenyl]azo]naphthalen-2-amine
- Regulatory name: N-(2-ethylhexyl)-1-[[2-methyl-4-[(4-methylphenyl)azo]phenyl]azo]naphthalen-2-amine
- Molecular formula: C32H37N5
- Molecular weight: 491.6793 g/mol
- Smiles: CCCCC(CC)CNc1ccc2ccccc2c1/N=N/c3ccc(cc3C)/N=N/c4ccc(cc4)C
- InChI: 1S/C32H37N5/c1-5-7-10-25(6-2)22-33-31-19-15-26-11-8-9-12-29(26)32(31)37-36-30-20-18-28(21-24(30)4)35-34-27-16-13-23(3)14-17-27/h8-9,11-21,25,33H,5-7,10,22H2,1-4H3/b35-34+,37-36+
- Substance type: Organic
Physical form: Dark red clear liquid

Species:

other: rabbits and humans

Strain:

not specified

Type of coverage:

other: Entire inner surface of one ear

Preparation of test site:

other: A colony of rabbits that had genetically good ears and which were free from mites were used for the assay

Vehicle:

other: propylene glycol, water

Controls:

yes, concurrent no treatment

Amount / concentration applied:

1. neat or as a 25% aqueous solution to the skin
2. Dose of 1ml of the test material was applied once daily for five days per week for 2 weeks

Duration of treatment / exposure:

1. 72 hours, and this was followed by a 24-hour application 10 to 14 days later
2. 2 weeks

Observation period:

2. 2 weeks

Number of animals:

1. 200 human volunteers
2. 3

Details on study design:

The study is based on weight of evidence approach from the read across values

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 14 days

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

no signs of irritation observed

Interpretation of results:

other: not irritating

Conclusions:

On the basis of available studies for the structurally similar read across substances, the weight of evidence approach was applied to assess the dermal irritation potential for target substance.
N-(2-ethylhexyl)-1-[[2-methyl-4-[(4-methylphenyl)azo]phenyl]azo]naphthalen-2-amine was estimated to be not irritating to rabbit skin.

Executive summary:

Based on the available studies for the structurally similar read across chemicals, weight of evidence approach was applied to assess the dermal irritation potential of N-(2-ethylhexyl)-1-[[2 -methyl-4-[(4-methylphenyl)azo]phenyl]azo]naphthalen-2-amine.

A prophetic patch test was conducted (Joint FAO/WHO Expert Committee on Food Additives, 2004) on 200 human volunteers to assess the dermal irritation potential of the test chemical.

The test chemical was applied on the human skin in the concentration 25% neat or in aqueous solution for 72 hours followed by one 48 hours application 10-14 days later. None of the subjects exhibited compound induced irritation. Hence, the test chemical was considered to be not irritating to human skin.

This is supported by a study performed by JAMES E. FULTON, JR to determine the Comedogenicity and irritancy potential of the structurally similar read across chemical. The dyes were mixed in propylene glycol at a 9 to 1 dilution for testing unless otherwise indicated (10% concentration). A colony of New Zealand albino rabbits that have genetically good ears and free from mites were used. Three rabbits, weighing two to three kilograms, were used for each assay. Animals were housed singly in suspended cages and fed Purina Rabbit Chow and water ad libitum. Animals were maintained on a 12-hour light and 12-hour dark cycle. A dose of 1 ml of the test material was applied and spread once daily to the entire inner surface of once for five days per week for two weeks. The opposite untreated ear of each animal served as an untreated control. The irritancy produced by repeated application of the chemical on the surface epidermis in the rabbit ear is evaluated on a scale of 0 to 5. The grades are summarized as follows:

0 = No irritation; 1 = few scales, no Erythema; 2 = diffuse scaling, no Erythema; 3 = Generalized scaling with Erythema; 4 = Scaling, Erythema and Edema; 5 = Epidermal necrosis and slough.

The test chemical was graded 0 (no irritation observed). Hence, it can be considered to be not irritating to rabbit skin.

Based on the available data for the structurally similar read across substances and applying the weight of evidence approach, it can be concluded that the target chemical will also tend to behave in a similar manner that of the read across substances. Therefore the target chemical was estimated to be not irritating to skin and it can be further classified under the category “Not Classified” as per CLP regulation.

Endpoint conclusion:

no adverse effect observed (not irritating)

Reference

Endpoint:

eye irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Weight of evidence based on structurally similar substances

Justification for type of information:

Weight of evidence based on structurally similar substances

Reason / purpose for cross-reference:

read-across: supporting information

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

according to guideline

Guideline:

other: Weight of evidence based on structurally similar substances

Principles of method if other than guideline:

The weight of evidence report has been prepared based on the read across substances identified based on structural and functional similarity to assess the dermal irritation potential of N-(2-ethylhexyl)-1-[[2-methyl-4-[(4-methylphenyl)azo]phenyl]azo]naphthalen-2-amine

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of the test material: N-(2-ethylhexyl)-1-[[2-methyl-4-[(4-methylphenyl)azo]phenyl]azo]naphthalen-2-amine
- Regulatory name: N-(2-ethylhexyl)-1-[[2-methyl-4-[(4-methylphenyl)azo]phenyl]azo]naphthalen-2-amine
- Molecular formula: C32H37N5
- Molecular weight: 491.6793 g/mol
- Smiles: CCCCC(CC)CNc1ccc2ccccc2c1/N=N/c3ccc(cc3C)/N=N/c4ccc(cc4)C
- InChI: 1S/C32H37N5/c1-5-7-10-25(6-2)22-33-31-19-15-26-11-8-9-12-29(26)32(31)37-36-30-20-18-28(21-24(30)4)35-34-27-16-13-23(3)14-17-27/h8-9,11-21,25,33H,5-7,10,22H2,1-4H3/b35-34+,37-36+
- Substance type: Organic
Physical form: Dark red clear liquid

Species:

rabbit

Strain:

not specified

Details on test animals or tissues and environmental conditions:

no data available

Vehicle:

other: 1. saline, 2. water

Controls:

not specified

Amount / concentration applied:

1. 0.1 ml of a 1.0% aqueous solution
2. The test chemical was used in 0.25 ml of a filtrate from a digest in aqueous saline prepared at 40°C.

Duration of treatment / exposure:

not specified

Observation period (in vivo):

not specified

Duration of post- treatment incubation (in vitro):

not specified

Number of animals or in vitro replicates:

not specified

Details on study design:

The study is based on weight of evidence approach from the read across values

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: not specified

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

no irritation observed

Interpretation of results:

other: not irritating

Conclusions:

On the basis of available studies for the structurally similar read across substances, the weight of evidence approach was applied to assess the ocular irritation potential of N-(2-ethylhexyl)-1-[[2-methyl-4-[(4-methylphenyl)azo]phenyl]azo]naphthalen-2-amine.N-(2-ethylhexyl)-1-[[2-methyl-4-[(4-methylphenyl)azo]phenyl]azo]naphthalen-2-amine was estimated to be not irritating to eyes.

Executive summary:

Based on the available studies for the structurally similar read across chemicals, weight of evidence approach was applied to assess the ocular irritation potential of N-(2-ethylhexyl)-1-[[2-methyl-4-[(4-methylphenyl)azo]phenyl]azo]naphthalen-2-amine.

Various studies have been summarized in Scientific Committee on Cosmetology (seventh series), 1988 to evaluate the irritation potential of the structurally similar read across chemicals.

In case of the first chemical, 0.1 ml of 1.0% aqueous solution of the test chemical did not induce any ocular changes in the rabbits. Whereas in case of the second chemical,0.25 ml of a filtrate from a digest in aqueous saline prepared at 40 deg C revealed slight and reversible redness of the mucous membrane in rabbits.

Since the effects caused in both the studies were reversible in nature, it was considered that both the test chemicals were not irritating to rabbit eyes.

Based on the available data for the structurally similar read across substances and applying the weight of evidence approach, it can be concluded that the target chemical will also tend to behave in a similar manner that of the read across substances. Therefore the target chemical was estimated to be not irritating to eyes and it can be further classified under the category “Not Classified” as per CLP regulation.

Endpoint conclusion:

no adverse effect observed (not irritating)

Endpoint conclusion:

no study available

Skin Irritation:

Based on the available studies for the structurally similar read across chemicals, weight of evidence approach was applied to assess the dermal irritation potential of N-(2-ethylhexyl)-1-[[2-methyl-4-[(4-methylphenyl)azo]phenyl]azo]naphthalen-2-amine.

A prophetic patch test was conducted on 200 human volunteers to assess the dermal irritation potential of the test chemical.

The test chemical was applied on the human skin in the concentration 25% neat or in aqueous solution for 72 hours followed by one 48 hours application 10-14 days later. None of the subjects exhibited compound induced irritation. Hence, the test chemical was considered to be not irritating to human skin.

This is supported by a study performed to determine the Comedogenicity and irritancy potential of the structurally similar read across chemical. The dyes were mixed in propylene glycol at a 9 to 1 dilution for testing unless otherwise indicated (10% concentration). A colony of New Zealand albino rabbits that have genetically good ears and free from mites were used. Three rabbits, weighing two to three kilograms, were used for each assay. Animals were housed singly in suspended cages and fed Purina Rabbit Chow and water ad libitum. Animals were maintained on a 12-hour light and 12-hour dark cycle. A dose of 1 ml of the test material was applied and spread once daily to the entire inner surface of once for five days per week for two weeks. The opposite untreated ear of each animal served as an untreated control. The irritancy produced by repeated application of the chemical on the surface epidermis in the rabbit ear is evaluated on a scale of 0 to 5. The grades are summarized as follows:

0 = No irritation; 1 = few scales, no Erythema; 2 = diffuse scaling, no Erythema; 3 = Generalized scaling with Erythema; 4 = Scaling, Erythema and Edema; 5 = Epidermal necrosis and slough.

The test chemical was graded 0 (no irritation observed). Hence, it can be considered to be not irritating to rabbit skin.

Based on the available data for the structurally similar read across substances and applying the weight of evidence approach, it can be concluded that the target chemical will also tend to behave in a similar manner that of the read across substances. Therefore the target chemical was estimated to be not irritating to skin and it can be further classified under the category “Not Classified” as per CLP regulation.

Eye Irritation:

Based on the available studies for the structurally similar read across chemicals, weight of evidence approach was applied to assess the ocular irritation potential of N-(2-ethylhexyl)-1-[[2 -methyl-4-[(4-methylphenyl)azo]phenyl]azo]naphthalen-2-amine.

Various studies have been summarized in Scientific Committee on Cosmetology (seventh series), 1988 to evaluate the irritation potential of the structurally similar read across chemicals.

In case of the first chemical, 0.1 ml of 1.0% aqueous solution of the test chemical did not induce any ocular changes in the rabbits. Whereas in case of the second chemical,0.25 ml of a filtrate from a digest in aqueous saline prepared at 40 deg C revealed slight and reversible redness of the mucous membrane in rabbits.

Since the effects caused in both the studies were reversible in nature, it was considered that both the test chemicals were not irritating to rabbit eyes.

Based on the available data for the structurally similar read across substances and applying the weight of evidence approach, it can be concluded that the target chemical will also tend to behave in a similar manner that of the read across substances. Therefore the target chemical was estimated to be not irritating to eyes and it can be further classified under the category “Not Classified” as per CLP regulation.

The results of the experimental studies from the structurally similar read across substances indicate a possibility that N -(2-ethylhexyl)-1-[[2-methyl-4-[(4-methylphenyl)azo]phenyl]azo]naphthalen-2-amine can be not irritating to eyes and skin.

Hence by applying the weight of evidence approach, N-(2-ethylhexyl)-1-[[2-methyl-4-[(4-methylphenyl)azo]phenyl]azo]naphthalen-2-amine can be considered to be not irritating to eyes and skin. It can be classified under the category “Not Classified” as per CLP regulation.