Hydrogen bis[2-(3-chlorophenyl)-2,4-dihydro-4-[[2-hydroxy-5-mesylphenyl]azo]-5-methyl-3H-pyrazol-3-onato(2-)]chromate(1-)

Endpoint summary

Description of key information

The skin sensitization potential of target chemical chromium(3+) ion hydrogen bis(1-(3-chlorophenyl)-4-[(E)-2-(5-methanesulfonyl-2-oxidophenyl)diazen-1-yl]-3-methyl-1H-pyrazol-5-olate) (CAS No: 71598-35-1)    was assessedin various experimental studies which were conducted on guinea pigs and humans for target chemicalchromium(3+) ion hydrogen bis(1-(3-chlorophenyl)-4-[(E)-2-(5-methanesulfonyl-2-oxidophenyl)diazen-1-yl]-3-methyl-1H-pyrazol-5-olate) (CAS No: 71598-35-1)    and its structurally similar read across substances Toluidine Red (CAS No: 2425-85-6) and D & C Red No. 6 (CAS no: 5858-81-1). The predicted data usingQSAR toolboxhas 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 chromium(3+) ion hydrogen bis(1-(3-chlorophenyl)-4-[(E)-2-(5-methanesulfonyl-2-oxidophenyl)diazen-1-yl]-3-methyl-1H-pyrazol-5-olate) (CAS No: 71598-35-1)    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

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 version 3.3 and QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: estimated data

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.3

GLP compliance:

not specified

Type of study:

Buehler test

Justification for non-LLNA method:

not specified

Specific details on test material used for the study:

Name: chromium(3+) ion hydrogen bis(1-(3-chlorophenyl)-4-[(E)-2-(5-methanesulfonyl-2-oxidophenyl)diazen-1-yl]-3-methyl-1H-pyrazol-5-olate)
SMILES:CC1C{-}(N=Nc2cc(S(C)(=O)=O)ccc2O{-}.[Cr]{3+}2.C{-}3(C(C)=NN(c4cccc(Cl)c4)C3=O)N=Nc3cc(S(C)(=O)=O)ccc3O{-}.2)C(=O)N(c2cccc(Cl)c2)N=1
InChI:1S/2C17H14ClN4O4S.Cr/c2*1-10-16(17(24)22(21-10)12-5-3-4-11(18)8-12)20-19-14-9-13(27(2,25)26)6-7-15(14)23;/h2*3-9,23H,1-2H3;/q2*-1;+3/p-1/b2*20-19+;
Molecular Formula: C34H26Cl2CrN8O8S2.H
Molecular Weight: 862.669 g/mole

Species:

guinea pig

Strain:

not specified

Sex:

not specified

Details on test animals and environmental conditions:

No data available

Route:

other: No data available

Vehicle:

not specified

Route:

other: No data available

No. of animals per dose:

10

Reading:

1st reading

Group:

test chemical

Dose level:

No data available

No. with + reactions:

0

Total no. in group:

10

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 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 "l" )  )

Domain logical expression index: "a"

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

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Schiff base formation AND Schiff base formation >> Pyrazolones and Pyrazolidinones derivatives AND Schiff base formation >> Pyrazolones and Pyrazolidinones derivatives >> Pyrazolones and Pyrazolidinones  by Protein binding by OASIS v1.3

Domain logical expression index: "c"

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: "d"

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 >> Unsaturated heterocyclic azo by DNA binding by OECD

Domain logical expression index: "e"

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 >> Unsaturated heterocyclic azo by DNA binding by OECD

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Acylation 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 SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation >> Aromatic nitro 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 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 >> Sulfonates by DNA binding by OECD

Domain logical expression index: "g"

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

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Non binder, impaired OH or NH2 group OR Non binder, without OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Metal atoms were identified 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"

Parametric boundary:The target chemical should have a value of Molecular weight which is >= 754 Da

Domain logical expression index: "l"

Parametric boundary:The target chemical should have a value of Molecular weight which is <= 931 Da

Interpretation of results:

other: Not sensitizing

Conclusions:

The chemical chromium(3+) ion hydrogen bis(1-(3-chlorophenyl)-4-[(E)-2-(5-methanesulfonyl-2-oxidophenyl)diazen-1-yl]-3-methyl-1H-pyrazol-5-olate) (CAS No: 71598-35-1) was estimated to be not sensitizing to the guinea pigs. Based on the estimated result chromium(3+) ion hydrogen bis(1-(3-chlorophenyl)-4-[(E)-2-(5-methanesulfonyl-2-oxidophenyl)diazen-1-yl]-3-methyl-1H-pyrazol-5-olate) (CAS No: 71598-35-1) failed to induce skin sanitization effects and hence is considered to be not sensitizing to guinea pigs.

Executive summary:

The skin sensitization potential of chromium(3+) ion hydrogen bis(1-(3-chlorophenyl)-4-[(E)-2-(5-methanesulfonyl-2-oxidophenyl)diazen-1-yl]-3-methyl-1H-pyrazol-5-olate) (CAS No: 71598-35-1) was estimated using OECD QSAR toolbox version 3.3 with log Pow as the primary descriptor. The chemical chromium(3+) ion hydrogen bis(1-(3-chlorophenyl)-4-[(E)-2-(5-methanesulfonyl-2-oxidophenyl)diazen-1-yl]-3-methyl-1H-pyrazol-5-olate) (CAS No: 71598-35-1) was estimated to be not sensitizing to the guinea pigs. Based on the estimated result chromium(3+) ion hydrogen bis(1-(3-chlorophenyl)-4-[(E)-2-(5-methanesulfonyl-2-oxidophenyl)diazen-1-yl]-3-methyl-1H-pyrazol-5-olate) (CAS No: 71598-35-1) 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 studieshas been investigated for the test chemicalchromium(3+) ion hydrogen bis(1-(3-chlorophenyl)-4-[(E)-2-(5-methanesulfonyl-2-oxidophenyl)diazen-1-yl]-3-methyl-1H-pyrazol-5-olate) (CAS No: 71598-35-1)     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 chemicalchromium(3+) ion hydrogen bis(1-(3-chlorophenyl)-4-[(E)-2-(5-methanesulfonyl-2-oxidophenyl)diazen-1-yl]-3-methyl-1H-pyrazol-5-olate) (CAS No: 71598-35-1)     and its structurally similar read across substancesToluidine Red (CAS No: 2425-85-6) and D & C Red No. 6 (CAS no: 5858-81-1). 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 chromium(3+) ion hydrogen bis(1-(3-chlorophenyl)-4-[(E)-2-(5-methanesulfonyl-2-oxidophenyl)diazen-1-yl]-3-methyl-1H-pyrazol-5-olate) (CAS No: 71598-35-1)     was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor. chromium(3+) ion hydrogen bis(1-(3-chlorophenyl)-4-[(E)-2-(5-methanesulfonyl-2-oxidophenyl)diazen-1-yl]-3-methyl-1H-pyrazol-5-olate) (CAS No: 71598-35-1)     was estimated to be not sensitizing to the skin of guinea pigs. Based on the estimated result chromium(3+) ion hydrogen bis(1-(3-chlorophenyl)-4-[(E)-2-(5-methanesulfonyl-2-oxidophenyl)diazen-1-yl]-3-methyl-1H-pyrazol-5-olate) (CAS No: 71598-35-1)     can be considered to be not sensitizing to guinea pigs.

 

The TAKEHITO KGZUKA et al., {Contact Dermatitis; Volume 6; Pg. no. 330-336; 1980} conducted skin sensitization study in human patients suffering from pigmented contact dermatitis caused by the commercial Brilliant Lake Red R for read across substance Toluidine Red (CAS No: 2425-85-6) to detect its contact sensitivity. The patch of Toluidine Red was applied onto the back of each patient for24 hours by using Finn Chambers® on Scanpor® (Epitest, Ltd. Oy) at a dose of 1% in petrolatum. After removal of patch, skin reactions were assessed according to the ICDRG classification for 2 days. Twenty-eight healthy female volunteers, aged 20 and 21, were also tested with the sample as controls. None gave a positive reaction. The negative skin sensitizing effects were observed in all treated patients. Thus the test chemical Toluidine Red(CAS No: 2425-85-6)was considered to be not sensitizing in human patients suffering from pigmented contact dermatitis caused by the commercial Brilliant Lake Red R.

 

The above results were further supported by the skin sensitization study conducted by Guin JD. (Contact Dermatitis 2003: 49: 217–218) forread across substanceD & C Red No. 6 (CAS no: 5858-81-1) to determine the allergic contact dermatitis caused by the chemical via performing patch test on human patients. The dye was applied on 15patients 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. Hence the chemical D & C Red No. 6 (CAS no: 5858-81-1) can be considered as non-sensitizer to human skin.

 

Thus on the basis of available data for thetarget chemicalchromium(3+) ion hydrogen bis(1-(3-chlorophenyl)-4-[(E)-2-(5-methanesulfonyl-2-oxidophenyl)diazen-1-yl]-3-methyl-1H-pyrazol-5-olate) (CAS No: 71598-35-1)     and its structurally similar read across substances Toluidine Red (CAS No: 2425-85-6) and D & C Red No. 6 (CAS no: 5858-81-1),it can be concluded thatchemical chromium(3+) ion hydrogen bis(1-(3-chlorophenyl)-4-[(E)-2-(5-methanesulfonyl-2-oxidophenyl)diazen-1-yl]-3-methyl-1H-pyrazol-5-olate) (CAS No: 71598-35-1)  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 chromium(3+) ion hydrogen bis(1-(3-chlorophenyl)-4-[(E)-2-(5-methanesulfonyl-2-oxidophenyl)diazen-1-yl]-3-methyl-1H-pyrazol-5-olate) (CAS No: 71598-35-1)      and its structurally similar read across substanceits structurally similar read across substanceToluidine Red (CAS No: 2425-85-6) and D & C Red No. 6 (CAS no: 5858-81-1) were observed in various studies. From the results obtained from these studies it is concluded that the chemical chromium(3+) ion hydrogen bis(1-(3-chlorophenyl)-4-[(E)-2-(5-methanesulfonyl-2-oxidophenyl)diazen-1-yl]-3-methyl-1H-pyrazol-5-olate) (CAS No: 71598-35-1)     is not likely to cause skin sensitization and hence can be classified as non-skin sensitizer.