N-(4-chlorophenyl)-3-hydroxy-4-[(2-methyl-5-nitrophenyl)azo]naphthalene-2-carboxamide

Endpoint summary

Description of key information

Skin irritation:

The dermal irritation potential of N-(4-chlorophenyl)-3-hydroxy-4-[(E)-2-(2-methyl-5-nitrophenyl)diazen-1-yl]naphthalene-2-carboxamide (CAS No: 6410-30-6) was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor. The substance N-(4-chlorophenyl)-3-hydroxy-4-[(E)-2-(2-methyl-5-nitrophenyl)diazen-1-yl]naphthalene-2-carboxamide (CAS No: 6410-30-6) was estimated to be not irritating to the skin of New Zealand White rabbits. Based on the estimated result N-(4-chlorophenyl)-3-hydroxy-4-[(E)-2-(2-methyl-5-nitrophenyl)diazen-1-yl]naphthalene-2-carboxamide (CAS No: 6410-30-6) can be considered to be not irritating to skin and can be classified under the category ˋ Not Classified’ as per CLP regulation.

 

Eye irritation:

The ocular irritation potential of N-(4-chlorophenyl)-3-hydroxy-4-[(E)-2-(2-methyl-5-nitrophenyl)diazen-1-yl]naphthalene-2-carboxamide (CAS No: 6410-30-6) was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor. The substance N-(4-chlorophenyl)-3-hydroxy-4-[(E)-2-(2-methyl-5-nitrophenyl)diazen-1-yl]naphthalene-2-carboxamide (CAS No: 6410-30-6) was estimated to be not irritating into the eyes of New Zealand White rabbits. Based on the estimated result N-(4-chlorophenyl)-3-hydroxy-4-[(E)-2-(2-methyl-5-nitrophenyl)diazen-1-yl]naphthalene-2-carboxamide (CAS No: 6410-30-6) can be considered to be not irritating to eye and can be classified under the category ˋ Not Classified’ as per CLP regulation.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification

Justification for type of information:

data is from OECD QSAR toolbox v3.4 and the QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: Estimated data

Principles of method if other than guideline:

Prediction was done using OECD QSAR toolbox v3.4

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material: N-(4-chlorophenyl)-3-hydroxy-4-[(E)-2-(2-methyl-5-nitrophenyl)diazen-1-yl]naphthalene-2-carboxamide
- Molecular formula: C24H17ClN4O4
- Molecular weight: 460.875 g/mol
- Smiles notation: c12c(c(c(C(Nc3ccc(Cl)cc3)=O)cc1cccc2)O)\N=N\c1cc(ccc1C)[N+](=O)[O-]
- InChl: 1S/C24H17ClN4O4/c1-14-6-11-18(29(32)33)13-21(14)27-28-22-19-5-3-2-4-15(19)12-20(23(22)30)24(31)26-17-9-7-16(25)8-10-17/h2-13,30H,1H3,(H,26,31)/b28-27+
- Substance type: Organic
- Physical state: Solid

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

no data available

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

500 mg

Duration of treatment / exposure:

4 hours

Observation period:

72hours

Number of animals:

3

Details on study design:

no data available

Other effects / acceptance of results:

no data available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

72 h

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No signs of irritation observed

Estimation method: Takes mode value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

((((((((("a" or "b" or "c" or "d" or "e" )  and ("f" and ( not "g") )  )  and "h" )  and "i" )  and ("j" and ( not "k") )  )  and "l" )  and "m" )  and "n" )  and ("o" and "p" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Non-covalent interaction AND Non-covalent interaction >> DNA intercalation AND Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide and Aminoalkylamine Side Chain by DNA binding by OASIS v.1.4

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Aromatic azo AND SN1 >> Nitrenium Ion formation >> Aromatic nitro by DNA binding by OECD

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Acylation involving an activated (glucuronidated) carboxamide group AND Acylation >> Acylation involving an activated (glucuronidated) carboxamide group >> Carboxylic Acid Amides AND Acylation >> Direct acylation involving a leaving group AND Acylation >> Direct acylation involving a leaving group >> Carboxylic Acid Amides AND Acylation >> Ester aminolysis AND Acylation >> Ester aminolysis >> Amides AND AN2 AND AN2 >> Michael-type addition to quinoid structures  AND AN2 >> Michael-type addition to quinoid structures  >> Carboxylic Acid Amides by Protein binding by OASIS v1.4

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Direct Acylation Involving a Leaving group AND Acylation >> Direct Acylation Involving a Leaving group >> Acetates by Protein binding by OECD

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Amides AND Phenol Amines AND Phenols by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Aromatic azo AND SN1 >> Nitrenium Ion formation >> Aromatic nitro by DNA binding by OECD

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Direct Addition of an Acyl Halide OR Acylation >> Direct Addition of an Acyl Halide >> Acyl halide OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates >> Formamides OR Michael addition OR Michael addition >> P450 Mediated Activation of Heterocyclic Ring Systems OR Michael addition >> P450 Mediated Activation of Heterocyclic Ring Systems >> Furans OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Alkyl phenols OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Arenes OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Hydroquinones OR Michael addition >> Polarised Alkenes-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated amides OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated esters OR No alert found OR Schiff base formers OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal  OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal  >> Ethanolamines (including morpholine) OR Schiff base formers >> Direct Acting Schiff Base Formers OR Schiff base formers >> Direct Acting Schiff Base Formers >> Alpha-beta-dicarbonyl OR Schiff base formers >> Direct Acting Schiff Base Formers >> Mono aldehydes OR SN1 >> Carbenium Ion Formation OR SN1 >> Carbenium Ion Formation >> Allyl benzenes OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation >> Aromatic phenylureas OR SN1 >> Nitrenium Ion formation >> Primary (unsaturated) heterocyclic amine OR SN1 >> Nitrenium Ion formation >> Primary aromatic amine OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine OR SN1 >> Nitrenium Ion formation >> Unsaturated heterocyclic azo OR SN2 OR SN2 >> Direct Acting Epoxides and related OR SN2 >> Direct Acting Epoxides and related >> Epoxides OR SN2 >> P450 Mediated Epoxidation OR SN2 >> P450 Mediated Epoxidation >> Coumarins OR SN2 >> SN2 at an sp3 Carbon atom OR SN2 >> SN2 at an sp3 Carbon atom >> Aliphatic halides OR SN2 >> SN2 at an sp3 Carbon atom >> Sulfonates by DNA binding by OECD

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as No superfragment by Superfragments ONLY

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Not bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Group 14 - Carbon C AND Group 15 - Nitrogen N AND Group 16 - Oxygen O AND Group 17 - Halogens Cl AND Group 17 - Halogens F,Cl,Br,I,At by Chemical elements

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Group 16 - Sulfur S by Chemical elements

Domain logical expression index: "l"

Similarity boundary:Target: Cc1ccc(N(=O)=O)cc1N=Nc1c2ccccc2cc(C(=O)Nc2ccc(Cl)cc2)c1O
Threshold=50%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "m"

Similarity boundary:Target: Cc1ccc(N(=O)=O)cc1N=Nc1c2ccccc2cc(C(=O)Nc2ccc(Cl)cc2)c1O
Threshold=60%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "n"

Similarity boundary:Target: Cc1ccc(N(=O)=O)cc1N=Nc1c2ccccc2cc(C(=O)Nc2ccc(Cl)cc2)c1O
Threshold=50%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log Kow which is >= 7.29

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of log Kow which is <= 9.41

Interpretation of results:

other: not irritating

Conclusions:

N-(4-chlorophenyl)-3-hydroxy-4-[(E)-2-(2-methyl-5-nitrophenyl)diazen-1-yl]naphthalene-2-carboxamide was estimated to be not irritating to the skin of New Zealand White rabbits.

Executive summary:

The dermal irritation potential of N-(4-chlorophenyl)-3-hydroxy-4-[(E)-2-(2-methyl-5-nitrophenyl)diazen-1-yl]naphthalene-2-carboxamide (CAS No: 6410-30-6) was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor. The substance N-(4 -chlorophenyl)-3-hydroxy-4-[(E)-2-(2-methyl-5-nitrophenyl)diazen-1-yl]naphthalene-2-carboxamide (CAS No: 6410-30-6) was estimated to be not irritating to the skin of New Zealand White rabbits. Based on the estimated result N-(4-chlorophenyl)-3-hydroxy-4-[(E)-2-(2-methyl-5-nitrophenyl)diazen-1-yl]naphthalene-2-carboxamide (CAS No: 6410-30-6) can be considered to be not irritating to skin and can be classified under the category ˋ Not Classified’ as per CLP regulation.

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:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification

Justification for type of information:

data is from OECD QSAR toolbox v3.4 and the QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: Estimated data

Principles of method if other than guideline:

Prediction was done using OECD QSAR toolbox v3.4

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material: N-(4-chlorophenyl)-3-hydroxy-4-[(E)-2-(2-methyl-5-nitrophenyl)diazen-1-yl]naphthalene-2-carboxamide
- Molecular formula: C24H17ClN4O4
- Molecular weight: 460.875 g/mol
- Smiles notation: c12c(c(c(C(Nc3ccc(Cl)cc3)=O)cc1cccc2)O)\N=N\c1cc(ccc1C)[N+](=O)[O-]
- InChl: 1S/C24H17ClN4O4/c1-14-6-11-18(29(32)33)13-21(14)27-28-22-19-5-3-2-4-15(19)12-20(23(22)30)24(31)26-17-9-7-16(25)8-10-17/h2-13,30H,1H3,(H,26,31)/b28-27+
- Substance type: Organic
- Physical state: Solid

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

no data available

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

no data available

Duration of treatment / exposure:

24 hours

Observation period (in vivo):

1 hour, 24 hours, 48 hours, 72 hours

Duration of post- treatment incubation (in vitro):

no data available

Number of animals or in vitro replicates:

6

Details on study design:

no data available

Other effects / acceptance of results:

no data available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

72 h

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

no signs of irritation observed

Estimation method: Takes mode value from the 6 nearest neighbours
Domain  logical expression:Result: In Domain

(((((((("a" or "b" or "c" or "d" or "e" )  and ("f" and ( not "g") )  )  and "h" )  and "i" )  and "j" )  and "k" )  and ("l" and ( not "m") )  )  and ("n" and "o" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Non-covalent interaction AND Non-covalent interaction >> DNA intercalation AND Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide and Aminoalkylamine Side Chain by DNA binding by OASIS v.1.4

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Aromatic azo AND SN1 >> Nitrenium Ion formation >> Aromatic nitro by DNA binding by OECD

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Acylation involving an activated (glucuronidated) carboxamide group AND Acylation >> Acylation involving an activated (glucuronidated) carboxamide group >> Carboxylic Acid Amides AND Acylation >> Direct acylation involving a leaving group AND Acylation >> Direct acylation involving a leaving group >> Carboxylic Acid Amides AND Acylation >> Ester aminolysis AND Acylation >> Ester aminolysis >> Amides AND AN2 AND AN2 >> Michael-type addition to quinoid structures  AND AN2 >> Michael-type addition to quinoid structures  >> Carboxylic Acid Amides by Protein binding by OASIS v1.4

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Direct Acylation Involving a Leaving group AND Acylation >> Direct Acylation Involving a Leaving group >> Acetates by Protein binding by OECD

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Amides AND Phenol Amines AND Phenols by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Aromatic azo AND SN1 >> Nitrenium Ion formation >> Aromatic nitro by DNA binding by OECD

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Direct Addition of an Acyl Halide OR Acylation >> Direct Addition of an Acyl Halide >> Acyl halide OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates >> Formamides OR Michael addition OR Michael addition >> P450 Mediated Activation of Heterocyclic Ring Systems OR Michael addition >> P450 Mediated Activation of Heterocyclic Ring Systems >> Furans OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Alkyl phenols OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Arenes OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Hydroquinones OR Michael addition >> Polarised Alkenes-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated amides OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated esters OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated ketones OR No alert found OR Schiff base formers OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal  OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal  >> Ethanolamines (including morpholine) OR SN1 >> Carbenium Ion Formation OR SN1 >> Carbenium Ion Formation >> Allyl benzenes OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation >> Aromatic phenylureas OR SN1 >> Nitrenium Ion formation >> Primary (unsaturated) heterocyclic amine OR SN1 >> Nitrenium Ion formation >> Primary aromatic amine OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine OR SN1 >> Nitrenium Ion formation >> Unsaturated heterocyclic azo OR SN2 OR SN2 >> P450 Mediated Epoxidation OR SN2 >> P450 Mediated Epoxidation >> Coumarins OR SN2 >> SN2 at an sp3 Carbon atom OR SN2 >> SN2 at an sp3 Carbon atom >> Aliphatic halides OR SN2 >> SN2 at an sp3 Carbon atom >> Sulfonates by DNA binding by OECD

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Discrete chemical by Substance Type ONLY

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Not bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "j"

Similarity boundary:Target: Cc1ccc(N(=O)=O)cc1N=Nc1c2ccccc2cc(C(=O)Nc2ccc(Cl)cc2)c1O
Threshold=50%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "k"

Similarity boundary:Target: Cc1ccc(N(=O)=O)cc1N=Nc1c2ccccc2cc(C(=O)Nc2ccc(Cl)cc2)c1O
Threshold=80%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Not categorized by Repeated dose (HESS)

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as 3-Methylcholantrene (Hepatotoxicity) Alert by Repeated dose (HESS)

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log Kow which is >= 7.79

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log Kow which is <= 9.41

Interpretation of results:

other: not irritating

Conclusions:

N-(4-chlorophenyl)-3-hydroxy-4-[(E)-2-(2-methyl-5-nitrophenyl)diazen-1-yl]naphthalene-2-carboxamide was estimated to be not irritating to the eyes of New Zealand White rabbits.

Executive summary:

The ocular irritation potential of N-(4-chlorophenyl)-3-hydroxy-4-[(E)-2-(2-methyl-5-nitrophenyl)diazen-1-yl]naphthalene-2-carboxamide (CAS No: 6410-30-6) was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor. The substance N-(4-chlorophenyl)-3-hydroxy-4-[(E)-2-(2-methyl-5-nitrophenyl)diazen-1-yl]naphthalene-2-carboxamide (CAS No: 6410-30-6) was estimated to be not irritating into the eyes of New Zealand White rabbits. Based on the estimated result N-(4-chlorophenyl)-3-hydroxy-4-[(E)-2-(2-methyl-5-nitrophenyl)diazen-1-yl]naphthalene-2-carboxamide (CAS No: 6410-30-6) can be considered to be not irritating to eye and can be classified under the category ˋ Not Classified’ as per CLP regulation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation:

Various studieshas been investigated for the test chemicalN-(4-chlorophenyl)-3-hydroxy-4-[(E)-2-(2-methyl-5-nitrophenyl)diazen-1-yl]naphthalene-2-carboxamide (CAS No: 6410-30-6) to observe the potential for dermal irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits for target chemicalN-(4-chlorophenyl)-3-hydroxy-4-[(E)-2-(2-methyl-5-nitrophenyl)diazen-1-yl]naphthalene-2-carboxamide (CAS No: 6410-30-6) and its structurally similar read across substances2-Nitro-4’-hydroxydiphenylamine (CAS No: 54381-08-7)andC.I. Pigment Red 3(CAS No: 2425-85-6).The predicted data using the OECD QSAR toolbox has also been compared with the experimental data and summarized as below;

 

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the skin irritation potential was estimated for test chemicalN-(4-chlorophenyl)-3-hydroxy-4-[(E)-2-(2-methyl-5-nitrophenyl)diazen-1-yl]naphthalene-2-carboxamide (CAS No: 6410-30-6)  .The chemical N-(4-chlorophenyl)-3-hydroxy-4-[(E)-2-(2-methyl-5-nitrophenyl)diazen-1-yl]naphthalene-2-carboxamide (CAS No: 6410-30-6) is estimated to be not irritating to skin of New Zealand White rabbits.

 

The Cosmetic Ingredient Review Expert Panel (1988) conducted Skin irritation studyfor structurally similar read across substance2-Nitro-4’-hydroxydiphenylamine (CAS No: 54381-08-7) on intact skin of six New Zealand White rabbits.In this study, aqueous slurry of 500 mg of2-Nitro-4’-hydroxydiphenylaminewas applied tointact skin of each rabbit for 24 hours under non-occlusive condition.The slurry was removed after 24 hours and reactions were scored at 24 or 72 hours.Since there wereno evidence of erythema or edema observed at 24 or 72 hours,the chemical2-Nitro-4’-hydroxydiphenylamine (CAS No: 54381-08-7) wasconsidered to be not irritating to the intact skin ofNew Zealand Whiterabbits.

 

The above results were further supported by the experimental study conducted by European Commission (EC) - Scientific Committee on Cosmetology (SCC) (1988)for structurally similar read across substanceC.I. Pigment Red 3(CAS No: 2425-85-6) on rabbits to assess its skin irritancy. The C.I. Pigment Red 3 was applied on abraded and non abraded skin of each rabbits under occlusive condition. No indication of skin irritation was observed. Hence the chemical C.I. Pigment Red 3(CAS No: 2425-85-6) was considered to be not irritating to the abraded and non abraded skin of rabbits under occlusive condition.

 

 

Thus on the basis of available data for thetargetN-(4-chlorophenyl)-3-hydroxy-4-[(E)-2-(2-methyl-5-nitrophenyl)diazen-1-yl]naphthalene-2-carboxamide (CAS No: 6410-30-6) and its structurally similar read across substances2-Nitro-4’-hydroxydiphenylamine (CAS No: 54381-08-7)andC.I. Pigment Red 3(CAS No: 2425-85-6),it can be concluded thatchemical N-(4-chlorophenyl)-3-hydroxy-4-[(E)-2-(2-methyl-5-nitrophenyl)diazen-1-yl]naphthalene-2-carboxamide (CAS No: 6410-30-6) is unable to cause skin irritation and considered as not irritating.Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

 

 

Eye irritation:

In different studies,the test chemicalN-(4-chlorophenyl)-3-hydroxy-4-[(E)-2-(2-methyl-5-nitrophenyl)diazen-1-yl]naphthalene-2-carboxamide (CAS No: 6410-30-6) has been investigated for potential for ocular irritationto a greater or lesser extent. The studies are based on in vivo experiments in rabbits for target chemicalN-(4-chlorophenyl)-3-hydroxy-4-[(E)-2-(2-methyl-5-nitrophenyl)diazen-1-yl]naphthalene-2-carboxamide (CAS No: 6410-30-6)and its structurally similar read across substances C.I. Pigment Red 3(CAS No: 2425-85-6)and C.I. Pigment Red 112 (CAS No: 6535-46-2).The predicted data using the OECD QSAR toolbox has also been compared with the experimental data and summarized as below;

 

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the eye irritation potential was estimated for test chemicalN-(4-chlorophenyl)-3-hydroxy-4-[(E)-2-(2-methyl-5-nitrophenyl)diazen-1-yl]naphthalene-2-carboxamide (CAS No: 6410-30-6) .The chemical N-(4-chlorophenyl)-3-hydroxy-4-[(E)-2-(2-methyl-5-nitrophenyl)diazen-1-yl]naphthalene-2-carboxamide (CAS No: 6410-30-6) is estimated to be not irritating to eye of New Zealand White rabbits.

 

The above result was further supported by the two experimental studies conducted by European Commission (EC) - Scientific Committee on Cosmetology (SCC) (1988)for structurally similar read across substancesC.I. Pigment Red 3(CAS No: 2425-85-6) andC.I. Pigment Red 112 (CAS No: 6535-46-2) as below;

An ocular irritation study of chemical C.I. Pigment Red 3(CAS No: 2425-85-6) was conducted on rabbits.The undiluted 100mg ofC.I. Pigment Red 3 was installed into the eye of each rabbits which produced Slight conjunctival changes only after one hour. Since the observed effects were cleared, the chemical C.I. Pigment Red 3(CAS No: 2425-85-6)was considered to be not irritating to therabbits’ eye.

 

In an eye irritation study of chemical C.I. Pigment Red 112 (CAS No: 6535-46-2) which was conducted on guinea pigs, about 0.8 mg of C.I. Pigment Red 112 in an aqueous preparation was installed into the eye of each guinea pig and later observed for ocular lesion. None of the treated guinea pig produced any ocular effects. Hence the chemical C.I. Pigment Red 112 (CAS No: 6535-46-2)was considered to be not irritating to guinea pigs’ eyes.

 

Thus on the basis of available data for thetarget chemicalN-(4-chlorophenyl)-3-hydroxy-4-[(E)-2-(2-methyl-5-nitrophenyl)diazen-1-yl]naphthalene-2-carboxamide (CAS No: 6410-30-6) and its structurally similar read across substancesC.I. Pigment Red 3(CAS No: 2425-85-6)and C.I. Pigment Red 112 (CAS No: 6535-46-2), it can be concluded that the chemical N-(4-chlorophenyl)-3-hydroxy-4-[(E)-2-(2-methyl-5-nitrophenyl)diazen-1-yl]naphthalene-2-carboxamide is unable to cause eye irritation and considered as not irritating.Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

Justification for classification or non-classification

The skin and eye irritation potential of test chemical N-(4-chlorophenyl)-3-hydroxy-4-[(E)-2-(2-methyl-5-nitrophenyl)diazen-1-yl]naphthalene-2-carboxamide (CAS No: 6410-30-6) and its structurally similar read across substanceswere observed in various studies. The results obtained from these studies indicate that the chemicalN-(4-chlorophenyl)-3-hydroxy-4-[(E)-2-(2-methyl-5-nitrophenyl)diazen-1-yl]naphthalene-2-carboxamide is unlikely to cause skin and eye irritation. HenceN-(4-chlorophenyl)-3-hydroxy-4-[(E)-2-(2-methyl-5-nitrophenyl)diazen-1-yl]naphthalene-2-carboxamide (CAS No: 6410-30-6) can be classified under the category “Not Classified” for skin and eye as per CLP.