Dihydrogen [2,4-dihydro-4-[(2-hydroxy-5-nitrophenyl)azo]-5-methyl-2-phenyl-3H-pyrazol-3-onato(2-)][3-hydroxy-4-[(2-hydroxy-1-naphthyl)azo]-7-nitronaphthalene-1-sulphonato(3-)]chromate(2-)

Endpoint summary

Description of key information

Skin Sensitization:

The skin sensitization potential of Dihydrogen [2,4-dihydro-4-[(2-hydroxy-5-nitrophenyl)azo]-5-methyl-2-phenyl-3H-pyrazol-3-onato(2-)][3-hydroxy-4-[(2-hydroxy-1-naphthyl)azo]-7-nitronaphthalene-1-sulphonato(3-)]chromate(2-) was estimated by SSS (2018) using OECD QSAR toolbox v3.4 with log kow as the primary descriptor.

Dihydrogen [2,4-dihydro-4-[(2-hydroxy-5-nitrophenyl)azo]-5-methyl-2-phenyl-3H-pyrazol-3-onato(2-)][3-hydroxy-4-[(2-hydroxy-1-naphthyl)azo]-7-nitronaphthalene-1-sulphonato(3-)]chromate(2-)

was predicted to be non sensitizing to the skin of female guinea pigs.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-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 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

Type of study:

guinea pig maximisation test

Specific details on test material used for the study:

- Name of test material: Dihydrogen [2,4-dihydro-4-[(2-hydroxy-5-nitrophenyl)azo]-5-methyl-2-phenyl-3H-pyrazol-3-onato(2-)][3-hydroxy-4-[(2-hydroxy-1-naphthyl)azo]-7-nitronaphthalene-1-sulphonato(3-)]chromate(2-)
- Molecular formula: C36H21CrN8O11S.2H
- Molecular weight: 827.6847 g/mole
- Smiles : [H+].[H+].Cc1c\2c(n(n1)c3ccccc3)O[Cr-2]45(Oc6ccc(cc6/N=N2)[N+](=O)[O-])Oc7ccc8ccccc8c7/N=N/c9c1ccc(cc1c(cc9O4)S(=O)(=O) O5)[N+](=O)[O-]
- Inchl: 1S/C20H13N3O7S.C16H13N5O4.Cr/c24-16-8-5-11-3-1-2-4-13(11)19(16)21-22-20-14-7-6-12(23(26)27)9-15(14)18(10-17(20)25)31(28,29)30;1-10-15(16(23)20(19-10)11-5-3-2-4-6-11)18-17-13-9-12(21(24)25)7-8-14(13)22;/h1-10,24-25H,(H,28,29,30);2-9,22-23H,1H3;/q;;+3/p-3/b22-21+;18-17+;
- Substance type: Organic
- Physical state: Solid

Species:

guinea pig

Strain:

not specified

Sex:

female

Details on test animals and environmental conditions:

no data available

Route:

epicutaneous, occlusive

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:

20

Details on study design:

no data available

Reading:

1st reading

Group:

test chemical

Clinical observations:

no signs of dermal sensitization observed

Remarks on result:

no indication of skin sensitisation

The prediction was based on dataset comprised from the following descriptors: "Skin Sensitisation"
Estimation method: Takes highest mode value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

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

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Naphthalene sulfonic acids, condensates by OECD HPV Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Michael addition to activated double bonds in heterocyclic ring systems OR AN2 >> Michael addition to activated double bonds in heterocyclic ring systems >> Pyrazolone and Pyrazolidine Derivatives OR AN2 >> Schiff base formation with carbonyl compounds (AN2) OR AN2 >> Schiff base formation with carbonyl compounds (AN2) >> Pyrazolone and Pyrazolidine Derivatives OR Schiff base formation OR Schiff base formation >> Schiff base on pyrazolones and pyrazolidinones OR Schiff base formation >> Schiff base on pyrazolones and pyrazolidinones >> Pyrazolones and Pyrazolidinones by Protein binding by OASIS v1.4 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 >> Aromatic azo OR SN1 >> Nitrenium Ion formation >> Aromatic nitro 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 Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> Fused-Ring Nitroaromatics OR Radical OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Fused-Ring Nitroaromatics OR SN1 OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Fused-Ring Nitroaromatics by DNA binding by OASIS v.1.4 ONLY

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Non binder, MW>500 by Estrogen Receptor Binding

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Non binder, impaired OH or NH2 group OR Non binder, non cyclic structure OR Non binder, without OH or NH2 group OR Strong binder, OH group OR Very strong binder, OH group OR Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules (GSH) by Protein binding potency

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Highly reactive (GSH) OR Highly reactive (GSH) >> Alkyl vinyl sulfones (MA) by Protein binding potency

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Metal atoms were identified AND Metals (1a) AND Not covered by current version of the decision tree by DART scheme v.1.0

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Not known precedent reproductive and developmental toxic potential by DART scheme v.1.0

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Non-Metals AND Transition Metals by Groups of elements

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Alkali Earth by Groups of elements

Domain logical expression index: "m"

Parametric boundary:The target chemical should have a value of Molecular weight which is >= 657 Da

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of Molecular weight which is <= 842 Da

Interpretation of results:

other: Negative

Conclusions:

Dihydrogen [2,4-dihydro-4-[(2-hydroxy-5-nitrophenyl)azo]-5-methyl-2-phenyl-3H-pyrazol-3-onato(2-)][3-hydroxy-4-[(2-hydroxy-1-naphthyl)azo]-7-nitronaphthalene-1-sulphonato(3-)]chromate(2-)
was predicted to be non sensitizing to the skin of female guinea pigs.

Executive summary:

The skin sensitization potential of Dihydrogen [2,4-dihydro-4-[(2-hydroxy-5-nitrophenyl)azo]-5-methyl-2-phenyl-3H-pyrazol-3-onato(2-)][3-hydroxy-4-[(2-hydroxy-1-naphthyl)azo]-7-nitronaphthalene-1-sulphonato(3-)]chromate(2-) was estimated by SSS (2018) using OECD QSAR toolbox v3.4 with log kow as the primary descriptor.

Dihydrogen [2,4-dihydro-4-[(2-hydroxy-5-nitrophenyl)azo]-5-methyl-2-phenyl-3H-pyrazol-3-onato(2-)][3-hydroxy-4-[(2-hydroxy-1-naphthyl)azo]-7-nitronaphthalene-1-sulphonato(3-)]chromate(2-)

was predicted to be non sensitizing to the skin of female guinea pigs.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Skin sensitization:

Various studies have been investigated to ascertain the degree of dermal sensitization caused by the target chemical Dihydrogen [2,4-dihydro-4-[(2-hydroxy-5 -nitrophenyl)azo]-5-methyl-2-phenyl-3H-pyrazol-3-onato(2-)][3-hydroxy-4-[(2-hydroxy-1-naphthyl)azo]-7-nitronaphthalene-1-sulphonato(3-)]chromate(2-) (CAS No. 52953-39-6) . These include in vivo experiments in guinea pigs for the target chemical as well as its functionally similar read across chemicals, chromium(3+) ion hydrogen bis([(6E)-6-{2-[(4Z)-3-methyl-5-oxo-1-phenyl-4 ,5-dihydro-1H-pyrazol-4-ylidene]hydrazin-1 -ylidene}cyclohexa-2,4-dien-1- ylidene]methanebis(olate) [CAS: 5601-29-6] and Sodium 3-hydroxy-4-[(2-hydroxynaphthyl)azo]-7-nitronaphthalene-1-sulphonate [CAS: 3618-58-4]. The experimental results have also been compared with the predictions obtained from OECD QSAR toolbox.

The skin sensitization potential of Dihydrogen [2,4-dihydro-4-[(2-hydroxy-5-nitrophenyl)azo]-5-methyl-2-phenyl-3H-pyrazol-3-onato(2-)][3-hydroxy-4-[(2-hydroxy-1-naphthyl)azo]-7 -nitronaphthalene-1-sulphonato(3-)]chromate(2-) was estimated by SSS (2018) using OECD QSAR toolbox v3.4 with log kow as the primary descriptor.

Dihydrogen [2,4-dihydro-4-[(2-hydroxy-5-nitrophenyl)azo]-5-methyl-2-phenyl-3H-pyrazol-3-onato(2-)][3-hydroxy-4-[(2-hydroxy-1-naphthyl)azo]-7-nitronaphthalene-1-sulphonato(3-)]chromate(2-) was predicted to be non sensitizing to the skin of female guinea pigs.

This is supported by the experimental study summarized in Environment and Quality of Life - Reports (Seventh Series) for Acid Yellow 121 European Commission (EC) - Scientific Committee on Cosmetology (SCC), 1988; for the functionally similar read across chemical, chromium(3+) ion hydrogen bis([(6E)-6-{2-[(4Z)-3-methyl-5-oxo-1-phenyl-4 ,5-dihydro-1H-pyrazol-4-ylidene]hydrazin-1 -ylidene}cyclohexa-2,4-dien-1- ylidene]methanebis(olate)[CAS: 5601-29-6]. The test material in induction treatment was subjected onto the skin of guinea pig by intra-cutaneous injections of 0.1 ml of 0.1 % aqueous solution three times per day for 5 successive days followed by one intracutaneous challenge injection of the same solution after 4 weeks of induction treatment. No skin allergic reactions were observed. Hence,Chromium complex of 1-phenyL-3-methyL-4-(2'-carboxy phenylazo)-5-hydroxy pyrazole was considered to be not skin sensitizing.

 

The above experimental results were further supported by experimental data summarized in Reports of The Scientific Committee on Cosmetology (NINTH SERIES), Scientific Committee on Cosmetology, 2000 for the functionally similar read across chemical, Sodium 3-hydroxy-4-[(2-hydroxynaphthyl)azo]-7-nitronaphthalene-1-sulphonate [CAS: 3618 -58-4].  In the induction phase 3 series of intradermal injections were given in the clipped dorsal shoulder region of the guinea pigs. The intradermal injections were divided as follows: 2 injections of 0.05 ml of a 10 % solution of the test substance in aqua dest., 2 injections of 0.05 ml of the test substance (10 %) in Freund’s Complete Adjuvant (FCA) and 2 injections of 0.05 ml FCA. The control group received the vehicle. 0.5 g of the test material was applied to the skin of the guinea pigs for 48 hours under occlusion. After a certain rest phase, the challenge phase started. The left shoulder was treated with 0.2 g of the test substance (100 %) in a 24 hours closed patch test, while the right shoulder was treated with the vehicle. The control animals were treated the same way, using the vehicle only.

Observations were noted 48 hours after the end of the challenge exposure. No skin reactions were observed after induction and challenge treatment. Hence, Sodium 3-hydroxy-4-[(2-hydroxynaphthyl)azo]-7-nitronaphthalene-1-sulphonate was considered to be not sensitizing to skin.

Based on the available studies for the target as well as the functionally similar read across chemicals and applying the weight of evidence approach, Dihydrogen [2,4-dihydro-4-[(2-hydroxy-5-nitrophenyl)azo]-5-methyl-2-phenyl-3H-pyrazol-3-onato(2-)][3-hydroxy-4-[(2-hydroxy-1-naphthyl)azo]-7-nitronaphthalene-1-sulphonato(3-)]chromate(2-) [CAS: 52953-39-6]can be considered to be not sensitizing to skin and can be classified under the category “Not Classified” as per CLP regulation.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Available data for Dihydrogen [2,4-dihydro-4-[(2-hydroxy-5-nitrophenyl)azo]-5-methyl-2-phenyl-3H-pyrazol-3-onato(2-)][3-hydroxy-4-[(2-hydroxy-1-naphthyl)azo]-7-nitronaphthalene-1-sulphonato(3-)]chromate(2-) suggests that it is not likely to cause any dermal sensitization.

Dihydrogen [2,4-dihydro-4-[(2-hydroxy-5-nitrophenyl)azo]-5-methyl-2-phenyl-3H-pyrazol-3-onato(2-)][3-hydroxy-4-[(2-hydroxy-1-naphthyl)azo]-7-nitronaphthalene-1-sulphonato(3-)]chromate(2-) can be considered to be not sensitizer to skin and can be classified under the category “Not Classified” as per CLP regulation.