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

Endpoint summary

Description of key information

The skin sensitization potential of target chemical C.I. Pigment Red 23 (CAS No: 6471-49-4) was assessed in various experimental studies which were conducted on guinea and humans for target chemical C.I. Pigment Red 23 (CAS No: 6471-49-4) andits structurally similar read across substancesD & C Red No. 6 (CAS no: 5858-81-1)andD&C Red 36(CAS no: 2814-77-9). The predicted data using QSAR toolbox has also been compared with the experimental data. Based on the available data for the target and read across substances and applying the weight of evidence approach, it can be concluded that chemical C.I. Pigment Red 23 (CAS No: 6471-49-4) is unable to cause skin sensitization and thus can be considered as not sensitizing. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (LLNA)

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 version 3.3 and QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: estimated data

GLP compliance:

not specified

Type of study:

mouse local lymph node assay (LLNA)

Justification for non-LLNA method:

Prediction is done using QSAR Toolbox version 3.3

Specific details on test material used for the study:

- Name of test material : 3-hydroxy-4-[(E)-2-(2-methoxy-5-nitrophenyl)diazen-1-yl]-N-(3-nitrophenyl)naphthalene-2-carboxamide
- Common name : 3-hydroxy-4-[(2-methoxy-5-nitrophenyl)azo]-N-(3-nitrophenyl)naphthalene-2-carboxamide, C.I. Pigment Red 23
- Molecular formula : C24H17N5O7
- Molecular weight : 487.4263 g/mol
- Smiles notation : c12c(c(c(cc1cccc2)C(=O)Nc1cc(ccc1)[N+](=O)[O-])O)/N=N/c1c(ccc(c1)[N+](=O)[O-])OC
- InChl : 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+
- Substance type : Organic
- Physical state : Solid

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

female

Route:

intradermal and epicutaneous

Vehicle:

not specified

Concentration / amount:

No data available

Day(s)/duration:

No data available

Adequacy of induction:

not specified

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

not specified

Concentration / amount:

No data available

Day(s)/duration:

72 hours

Adequacy of challenge:

not specified

No. of animals per dose:

20

Details on study design:

No data available

Challenge controls:

No data available

Reading:

1st reading

Hours after challenge:

72

Group:

test chemical

Dose level:

No data available

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

No skin sensitization was observed in treated guinea pigs.

Remarks on result:

no indication of skin sensitisation

Cellular proliferation data / Observations:

No skin sensitization was observed in treated guinea pigs.

The prediction was based on dataset comprised from the following descriptors: "Skin Sensitisation"
Estimation method: Takes highest 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 ( not "i") )  )  and ("j" and ( not "k") )  )  and ("l" and ( not "m") )  )  and ("n" and ( not "o") )  )  and ("p" and "q" )  )

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 Side Chain by DNA binding by OASIS v.1.3

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 >> Ester aminolysis AND Acylation >> Ester aminolysis >> Amides by Protein binding by OASIS v1.3

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 Non-covalent interaction AND Non-covalent interaction >> DNA intercalation AND Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide Side Chain by DNA binding by OASIS v.1.3

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Carbamoylation after isocyanate formation OR AN2 >> Carbamoylation after isocyanate formation >> N-Hydroxylamines OR AN2 >> Michael-type addition on alpha, beta-unsaturated carbonyl compounds OR AN2 >> Michael-type addition on alpha, beta-unsaturated carbonyl compounds >> Four- and Five-Membered Lactones OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation >> Geminal Polyhaloalkane Derivatives OR AN2 >> Shiff base formation after aldehyde release OR AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters OR AN2 >> Shiff base formation for aldehydes OR AN2 >> Shiff base formation for aldehydes >> Geminal Polyhaloalkane Derivatives OR No alert found OR Non-covalent interaction >> DNA intercalation >> Coumarins OR Non-specific OR Non-specific >> Incorporation into DNA/RNA, due to structural analogy with  nucleoside bases    OR Non-specific >> Incorporation into DNA/RNA, due to structural analogy with  nucleoside bases    >> Specific Imine and Thione Derivatives OR Radical OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Coumarins OR Radical >> Radical mechanism via ROS formation (indirect) >> Geminal Polyhaloalkane Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> N-Hydroxylamines OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitro Azoarenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroarenes with Other Active Groups OR Radical >> Radical mechanism via ROS formation (indirect) >> p-Substituted Mononitrobenzenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Specific Imine and Thione Derivatives OR SN1 OR SN1 >> Alkylation after metabolically formed carbenium ion species OR SN1 >> Alkylation after metabolically formed carbenium ion species >> Polycyclic Aromatic Hydrocarbon Derivatives OR SN1 >> Nucleophilic attack after carbenium ion formation OR SN1 >> Nucleophilic attack after carbenium ion formation >> Specific Acetate Esters OR SN1 >> Nucleophilic attack after diazonium or carbenium ion formation OR SN1 >> Nucleophilic attack after diazonium or carbenium ion formation >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> N-Hydroxylamines OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitro Azoarenes OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> p-Substituted Mononitrobenzenes OR SN1 >> Nucleophilic substitution on diazonium ions OR SN1 >> Nucleophilic substitution on diazonium ions >> Specific Imine and Thione Derivatives OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> Specific Acetate Esters OR SN2 >> Acylation involving a leaving group  OR SN2 >> Acylation involving a leaving group  >> Geminal Polyhaloalkane Derivatives OR SN2 >> Acylation involving a leaving group after metabolic activation OR SN2 >> Acylation involving a leaving group after metabolic activation >> Geminal Polyhaloalkane Derivatives OR SN2 >> Alkylation, direct acting epoxides and related OR SN2 >> Alkylation, direct acting epoxides and related >> Epoxides and Aziridines OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation >> Polycyclic Aromatic Hydrocarbon Derivatives OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Sulfonates and Sulfates OR SN2 >> Alkylation, ring opening SN2 reaction OR SN2 >> Alkylation, ring opening SN2 reaction >> Four- and Five-Membered Lactones OR SN2 >> Direct acting epoxides formed after metabolic activation OR SN2 >> Direct acting epoxides formed after metabolic activation >> Coumarins OR SN2 >> Direct acylation involving a leaving group OR SN2 >> Direct acylation involving a leaving group >> Acyl Halides OR SN2 >> DNA alkylation OR SN2 >> DNA alkylation >> Alkylphosphates, Alkylthiophosphates and Alkylphosphonates OR SN2 >> DNA alkylation >> Vicinal Dihaloalkanes OR SN2 >> Internal SN2 reaction with aziridinium and/or cyclic sulfonium ion formation (enzymatic) OR SN2 >> Internal SN2 reaction with aziridinium and/or cyclic sulfonium ion formation (enzymatic) >> Vicinal Dihaloalkanes OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate Esters OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation >> Geminal Polyhaloalkane Derivatives OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 >> Nitroarenes with Other Active Groups by DNA binding by OASIS v.1.3

Domain logical expression index: "h"

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: "i"

Referential boundary: The target chemical should be classified as Michael addition OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Hydroquinones OR No alert found OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation >> Primary aromatic amine by DNA binding by OECD

Domain logical expression index: "j"

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: "k"

Referential boundary: The target chemical should be classified as SN2 OR SN2 >> SN2 reaction at sp3 carbon atom OR SN2 >> SN2 reaction at sp3 carbon atom >> Alkyl diazo by Protein binding by OECD

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Phenols by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Inclusion rules not met by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as No alert found by Respiratory sensitisation

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Pro-Michael Addition OR Pro-Michael Addition >> Pro-quinone and related OR Pro-Michael Addition >> Pro-quinone and related >> Phenylenediamines by Respiratory sensitisation

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of log Kow which is >= 6.04

Domain logical expression index: "q"

Parametric boundary:The target chemical should have a value of log Kow which is <= 8.71

Interpretation of results:

other: Not sensitizing

Conclusions:

The substance C.I. Pigment Red 23 (CAS No: 6471-49-4) was estimated to be not sensitizing to the skin of guinea pigs. Based on the estimated result C.I. Pigment Red 23 (CAS No: 6471-49-4) failed to induce skin sanitization effects and hence is considered to be not sensitizing to guinea pigs.

Executive summary:

The skin sensitization potential of C.I. Pigment Red 23 (CAS No: 6471-49-4) was estimated using OECD QSAR toolbox version 3.4 with log Pow as the primary descriptor. The substance C.I. Pigment Red 23 (CAS No: 6471-49-4) was estimated to be not sensitizing to the skin of guinea pigs. Based on the estimated result C.I. Pigment Red 23 (CAS No: 6471-49-4) failed to induce skin sanitization effects and hence is considered to be not sensitizing to guinea pigs and can be classified under the category ˋ Not Classified’ as per CLP regulation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Various studies has been investigated for the test chemicalC.I. Pigment Red 23 (CAS No: 6471-49-4)to observe the potential for skin sensitization to a greater or lesser extent. The studies are based on in vivo experiments in guinea pigs and humans for target chemicalC.I. Pigment Red 23 (CAS No: 6471-49-4) and its structurally similar read across substancesD & C Red No. 6 (CAS no: 5858-81-1)andD&C Red 36(CAS no: 2814-77-9) .The predicted data using the OECD QSAR toolbox has also been compared with the experimental data and summarized as below;

 

The skin sensitization potential of C.I. Pigment Red 23 (CAS No: 6471-49-4) was estimated using OECD QSAR toolbox version 3.4 with log Pow as the primary descriptor. The substance C.I. Pigment Red 23 (CAS No: 6471-49-4) was estimated to be not sensitizing to the skin of guinea pigs. Based on the estimated result C.I. Pigment Red 23 (CAS No: 6471-49-4) failed to induce skin sanitization effects and hence is considered to be not sensitizing to guinea pigs.

 

The above result was further supported by the patch test conducted by the Guin JD. (2003) forstructurally similar read across substanceD & C Red No. 6 (CAS no: 5858-81-1) andD&C Red 36(CAS no: 2814-77-9) to determine the allergic contact dermatitis caused by the chemicals on human patients. These patch tests were conducted on 15 patients for chemical D & C Red No. 6 (CAS no: 5858-81-1) while for chemicalD&C Red 36(CAS no: 2814-77-9) this test was conducted on 14 patients. Each dye was applied in Finn Chambers and read first at 2 or (more commonly) 3 days and again at 4–7 days. The reactions of the patients were graded as ‘?+ ‘ , ‘+’ and ‘++’ categories. None of the treated patients showed any signs of allergic contact dermatitis for both the chemicals. Hence the chemicals D & C Red No. 6 (CAS no: 5858-81-1) andD&C Red 36(CAS no: 2814-77-9) can be considered as non-sensitizer to human skin.

 

Thus on the basis of available data for thetarget chemicalC.I. Pigment Red 23 (CAS No: 6471-49-4) and its structurally similar read across substancesD & C Red No. 6 (CAS no: 5858-81-1)andD&C Red 36(CAS no: 2814-77-9),it can be concluded thatchemical C.I. Pigment Red 23 (CAS No: 6471-49-4) is unable to cause skin sensitization and considered as non-skin sensitizer.Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The skin sensitization potential of test substance C.I. Pigment Red 23 (CAS No: 6471-49-4) and its structurally similar read across substancesD & C Red No. 6 (CAS no: 5858-81-1)andD&C Red 36(CAS no: 2814-77-9) were observed in various studies. From the results obtained from these studies it is concluded that the chemical C.I. Pigment Red 23 (CAS No: 6471-49-4) is not likely to cause skin sensitization and hence can be classified as non-skin sensitizer.