4-[(5-amino-3-methyl-1-phenyl-1H-pyrazol-4-yl)azo]-2,5-dichlorobenzenesulphonic acid

Endpoint summary

Description of key information

Skin Sensitization

The skin sensitization potential of Acid Yellow 49 was estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor. Acid Yellow 49 was predicted to be not sensitizing to the skin of female Pirbright-Hartley guinea pigs.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation

Remarks:

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 v3.3 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 v3.3

GLP compliance:

not specified

Type of study:

other: Estimated data

Specific details on test material used for the study:

- Name of test material: 4-[(5-amino-3-methyl-1-phenyl-1H-pyrazol-4-yl)azo]-2,5-dichlorobenzenesulphonic acid
- Common Name: Acid Yellow 49
- IUPAC name: 4-[(5-amino-3-methyl-1-phenyl-1H-pyrazol-4-yl)azo]-2,5-dichlorobenzenesulphonic acid
- Molecular formula: C16H13Cl2N5O3S
- Molecular weight: 426.283 g/mole
- Smiles :n1(c2ccccc2)c(c(\N=N\c2c(cc(S(O)(=O)=O)c(c2)Cl)Cl)c(n1)C)N
- InChl: 1S/C16H13Cl2N5O3S/c1-9-15(16(19)23(22-9)10-5-3-2-4-6-10)21-20-13-7-12(18)14(8-11(13)17)27(24,25)26/h2-8H,19H2,1H3,(H,24,25,26)/b21-20+
- Substance type: Organic
- Physical state: Solid powder (yellow)

Species:

guinea pig

Strain:

Pirbright-Hartley

Sex:

female

Details on test animals and environmental conditions:

no data available

Route:

intradermal and epicutaneous

Vehicle:

not specified

Adequacy of induction:

not specified

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

not specified

Adequacy of challenge:

not specified

No. of animals per dose:

10

Details on study design:

no data available

Challenge controls:

no data available

Positive control substance(s):

not specified

Vehicle:

not specified

Concentration:

no data available

No. of animals per dose:

no data available

Details on study design:

no data available

Positive control substance(s):

not specified

Statistics:

no data available

Positive control results:

no data available

Reading:

1st reading

Group:

test chemical

Dose level:

no data available

Clinical observations:

no signs of dermal sensitization observed

Remarks on result:

no indication of skin sensitisation

Cellular proliferation data / Observations:

no data available

The prediction was based on dataset comprised from the following descriptors: "Skin sensitisation"
Estimation method: Takes highest mode value from the 7 nearest neighbours
Domain  logical expression:Result: In Domain

(((((((((((("a" or "b" or "c" )  and ("d" and ( not "e") )  )  and ("f" and ( not "g") )  )  and ("h" and ( not "i") )  )  and ("j" and ( not "k") )  )  and ("l" and ( not "m") )  )  and "n" )  and ("o" and ( not "p") )  )  and ("q" and ( not "r") )  )  and ("s" and ( not "t") )  )  and ("u" and ( not "v") )  )  and ("w" and "x" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Acid moiety OR Anilines (Unhindered) OR Pyrazoles/Pyrroles by Aquatic toxicity classification by ECOSAR ONLY

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as SNAr OR SNAr >> Nucleophilic aromatic substitution OR SNAr >> Nucleophilic aromatic substitution >> Activated halo-benzenes by Protein binding by OECD ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as SN1 OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Primary (unsaturated) heterocyclic amine OR SN1 >> Nitrenium Ion formation >> Unsaturated heterocyclic azo by DNA binding by OECD ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.3

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Radical OR Radical >> Radical mechanism by ROS formation OR Radical >> Radical mechanism by ROS formation >> Polynitroarenes OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Hydrazine Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroaniline Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroarenes with Other Active Groups OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR SN1 OR SN1 >> Carbenium ion formation OR SN1 >> Carbenium ion formation >> Alpha-Haloethers 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 >> 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 >> Nitroaniline Derivatives 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 >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Polynitroarenes OR SN2 OR SN2 >> SN2 at sp3-carbon atom OR SN2 >> SN2 at sp3-carbon atom >> Alpha-Haloethers 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: "f"

Referential boundary: The target chemical should be classified as No alert found by Protein binding by OASIS v1.3

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Amides OR Michael Addition OR Michael Addition >> Michael addition on conjugated systems with electron withdrawing group OR Michael Addition >> Michael addition on conjugated systems with electron withdrawing group >> Cyanoalkenes OR SNAr OR SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds OR SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds >> Activated aryl and heteroaryl compounds by Protein binding by OASIS v1.3

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as No alert found by Protein binding alerts for Chromosomal aberration by OASIS v1.1

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Michael addition to the quinoid type structures OR AN2 >> Michael addition to the quinoid type structures >> N-Subsituted Aromatic Amines OR AN2 >> Michael addition to the quinoid type structures >> Substituted Anilines by Protein binding alerts for Chromosomal aberration by OASIS v1.1

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Aromatic diazo AND H-acceptor-path3-H-acceptor AND Hydrazine AND Primary aromatic amine, hydroxyl amine and its derived esters by in vivo mutagenicity (Micronucleus) alerts by ISS

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as 1-phenoxy-benzene OR Aliphatic halogen OR No alert found by in vivo mutagenicity (Micronucleus) alerts by ISS

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Aromatic diazo AND Hydrazine AND Primary aromatic amine,hydroxyl amine and its derived esters by in vitro mutagenicity (Ames test) alerts by ISS

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as No alert found by in vitro mutagenicity (Ames test) alerts by ISS

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND Group All Melting Point > 200 C by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Group CNHal Aqueous Solubility < 0.1 g/L by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "q"

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

Domain logical expression index: "r"

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

Domain logical expression index: "s"

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

Domain logical expression index: "t"

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

Domain logical expression index: "u"

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

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as Thiocarbamates/Sulfides (Hepatotoxicity) No rank by Repeated dose (HESS)

Domain logical expression index: "w"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.609

Domain logical expression index: "x"

Parametric boundary:The target chemical should have a value of log Kow which is <= 1.88

Interpretation of results:

other: Negative

Conclusions:

Acid Yellow 49 was predicted to be not sensitizing to the skin of female Pirbright-Hartley guinea pigs.

Executive summary:

The skin sensitization potential of Acid Yellow 49 was estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor. Acid Yellow 49 was predicted to be not sensitizing to the skin of female Pirbright-Hartley guinea pigs.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Skin Sensitization:

Various studies have been evaluated to ascertain the degree of dermal sensitization caused byAcid Yellow 49 in living organisms. The studies are based on in vivo experiments along with predicted data for target chemical and its structurally similar read across substances, Sodium 4-(3-hydroxy-5-methyl-4-phenylazopyrazol-2-yl)benzenesulphonate(Acid Yellow 11)[CAS: 6359-82-6] and 3-hydroxy-N-(2-methylphenyl)-4-[(E)-2-(2,4,5-trichlorophenyl)diazen-1-yl]naphthalene-2-carboxamide(C.I. Pigment Red 112)[CAS: 6535-46-2]. The predicted data using the OECD QSAR toolbox has also been compared with the experimental data.

The skin sensitization potential of Acid Yellow 49 was estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor. Acid Yellow 49 was predicted to be not sensitizing to the skin of female Pirbright-Hartley guinea pigs.

This result is supported by the experimental study summarized in Scientific Committee on Cosmetology (seventh series), 1988; for thestructurally similar read across substance, Sodium 4-(3-hydroxy-5-methyl-4-phenylazopyrazol-2-yl)benzenesulphonate(Acid Yellow 11)[CAS: 6359-82-6]. Guinea pigs were induced intradermally with injections of 0.1 ml of 0.5% aqueous solution of test chemical 3 times per day for 5 consecutive days. After a rest period of 4 weeks, animals were challenged with the same concentration and then observed for allergic effects. The treated guinea pigs did not reveal any sensitization potential. Hence, Sodium 4-(3-hydroxy-5-methyl-4-phenylazopyrazol-2-yl)benzenesulphonate(CAS No:6359-82-6) was considered to be not sensitizing to the skin of treated guinea pigs.

The above results are also supported by the experimental study summarized in Scientific Committee on Cosmetology (seventh series), 1988; for thestructurally similar read across substance, 3-hydroxy-N-(2-methylphenyl)-4-[(E)-2-(2,4,5-trichlorophenyl)diazen-1-yl]naphthalene-2-carboxamide(C.I. Pigment Red 112)[CAS: 6535-46-2]. Guinea pigs were induced intradermally with injections of 0.1 ml of 0.5% aqueous solution of 3-hydroxy-N-(2-methylphenyl)-4-[(2,4,5-trichlorophenyl)diazenyl]-2-naphthamide 3 times per day for 5 consecutive days. After a rest period of 4 weeks, animals were challenged with the upto 0.2% of a 40% color paste and then observed for allergic effects.

No skin allergic reactions were observed. Hence, 3-hydroxy-N-(2-methylphenyl)-4-[(2,4,5-trichlorophenyl)diazenyl]-2-naphthamide was considered not to be skin sensitizing.

Based on the available data for the target as well as it read across substances;and applying the weight of evidence approach, it can be concluded thatAcid Yellow 49 was not sensitizing to skin.Comparing the above annotations with the criteria of CLP regulation,Acid Yellow 49 can be classified under the category “Not Classified”.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Available data for Acid Yellow 49 indicates that it is not likely to cause any dermal sensitization to skin.

Acid Yellow 49 can be considered to be not sensitizer to skin and can be classified under the category “Not Classified” as per CLP regulation.