Disodium 2-[[5-carbamoyl-1-ethyl-1,6-dihydro-2-hydroxy-4-methyl-6-oxo-3-pyridyl]azo]-4-[[4-chloro-6-[[3-[[2-(sulphonatooxy)ethyl]sulphonyl]phenyl]amino]-1,3,5-triazin-2-yl]amino]benzenesulphonate

Endpoint summary

Description of key information

The skin sensitization potential of disodium 2-[(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo-1,6-dihydropyridin-3-yl) diazenyl]-4-({4-chloro-6- [(3-{[2-(sulfonato oxy) ethyl]sulfonyl}phenyl)amino]-1,3,5-triazin-2-yl}amino)benzenesulfonate (CAS No: 84000-63-5) was estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor. The substance disodium 2-[(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo-1,6-dihydropyridin-3-yl) diazenyl]- 4-({4-chloro-6-[(3-{[2-(sulfonatooxy)ethyl]sulfonyl}phenyl) amino]-1,3,5-triazin-2-yl}amino) benzenesulfonate (CAS No: 84000-63-5) failed to induce skin sensitization effects on guinea pig skin and hence is considered to be not sensitizing to the skin.

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 version 3.3 and QMRF report has been attached.

Qualifier:

no guideline available

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.3

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material: disodium 2-[(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo-1,6-dihydropyridin-3-yl)diazenyl]-4-({4-chloro-6-[(3-{[2-(sulfonatooxy)ethyl] sulfonyl}phenyl)amino]-1,3,5-triazin-2-yl}amino)benzenesulfonate
- Molecular formula: C26H26ClN9O12S3.2Na
- Molecular weight: 832.1576 g/mol
- Smiles notation: CCn1c(c(c(c(c1=O)C(=O)N)C)/N=N/c2cc(ccc2S(=O)(=O)[O-])Nc3nc(nc(n3)Cl)Nc4cccc(c4)S(=O)(=O)CCOS(=O)(=O)[O-])O.[Na+].[Na+]
- InChI: 1S/C26H26ClN9O12S3.2Na/c1-3-36-22(38)19(21(28)37)13(2)20(23(36)39)35-34-17-12-15(7-8-18(17)50(42,43)44)30-26-32-24(27)31-25(33-26) 29-14-5-4-6-16(11-14)49(40,41)10-9-48-51(45,46)47;;/h4-8,11-12,39H,3,9-10H2,1-2H3,(H2,28,37)(H,42,43,44)(H,45,46,47)(H2,29,30,31,32,33);;/q;2*+1/p-2/b35-34+;;
- Substance type: Organic

Species:

guinea pig

Strain:

not specified

Sex:

not specified

Details on test animals and environmental conditions:

no data available

No. of animals per dose:

no data available

Details on study design:

no data available

Challenge controls:

no data available

Positive control substance(s):

not specified

Reading:

1st reading

Group:

test chemical

No. with + reactions:

0

Clinical observations:

no skin sensitizing effects were observed in treated animals.

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 7 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 "k" )  and ("l" and ( not "m") )  )  and ("n" and "o" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Imides (Acute toxicity) AND Substituted Triazines (Acute toxicity) AND Vinyl Sulfones by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Non-specific AND Non-specific >> Incorporation into DNA/RNA, due to structural analogy with  nucleoside bases    AND Non-specific >> Incorporation into DNA/RNA, due to structural analogy with  nucleoside bases    >> Specific Imine and Thione Derivatives AND Radical AND Radical >> Radical mechanism via ROS formation (indirect) AND Radical >> Radical mechanism via ROS formation (indirect) >> Specific Imine and Thione Derivatives AND SN1 AND SN1 >> Nucleophilic substitution on diazonium ions AND SN1 >> Nucleophilic substitution on diazonium ions >> Specific Imine and Thione Derivatives by DNA binding by OASIS v.1.3

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Iminium Ion Formation AND SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines by DNA binding by OECD

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 AND SNAr AND SNAr >> Nucleophilic aromatic substitution AND SNAr >> Nucleophilic aromatic substitution >> Halo-triazines by Protein binding by OECD

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Nucleophilic addition AND Nucleophilic addition >> Addition to carbon-hetero double bonds AND Nucleophilic addition >> Addition to carbon-hetero double bonds >> Ketones AND SNAr AND SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds AND 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: "f"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Iminium Ion Formation AND SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines 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 >> Alkyl carbamyl halides 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 of Heterocyclic Ring Systems >> Thiophenes-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 >> Alkyl phenols OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Arenes 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 >> Direct Acting Schiff Base Formers OR Schiff base formers >> Direct Acting Schiff Base Formers >> Mono aldehydes OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Aromatic nitro OR SN1 >> Nitrenium Ion formation >> Aromatic phenylureas OR SN1 >> Nitrenium Ion formation >> Primary aromatic amine OR SN1 >> Nitrenium Ion formation >> Secondary aromatic amine OR SN1 >> Nitrenium Ion formation >> Tertiary (unsaturated) heterocyclic 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 >> Epoxidation of Aliphatic Alkenes OR SN2 >> Epoxidation of Aliphatic Alkenes >> Halogenated polarised alkenes OR SN2 >> P450 Mediated Epoxidation OR SN2 >> P450 Mediated Epoxidation >> Thiophenes-SN2 by DNA binding by OECD

Domain logical expression index: "h"

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

Domain logical expression index: "i"

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 by Estrogen Receptor Binding

Domain logical expression index: "j"

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

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Not calculated by Hydrolysis half-life (Ka, pH 7)(Hydrowin) ONLY

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as No Data by Ultimate biodeg

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as > 100 days by Ultimate biodeg

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log Kow which is >= -9.74

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log Kow which is <= 11.4

Interpretation of results:

other: not sensitizing

Conclusions:

The skin sensitization potential of disodium 2-[(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo-1,6-dihydropyridin-3-yl) diazenyl]-4-({4-chloro-6-[(3-{[2-(sulfonatooxy) ethyl]sulfonyl}phenyl)amino]-1,3,5-triazin-2-yl}amino)benzenesulfonate (CAS No: 84000-63-5) was estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor. The substance disodium 2-[(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo-1,6-dihydropyridin-3-yl) diazenyl]-4-({4-chloro-6-[(3-{[2-(sulfonatooxy)ethyl]sulfonyl}phenyl) amino]-1,3,5-triazin-2-yl}amino) benzenesulfonate (CAS No: 84000-63-5) failed to induce skin sanitizating effects on guinea pig skin and hence is considered to be not sensitizing to the skin

Executive summary:

The skin sensitization potential of disodium 2-[(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo-1,6-dihydropyridin-3-yl) diazenyl]-4-({4-chloro-6-[(3-{[2-(sulfonatooxy) ethyl]sulfonyl}phenyl)amino]-1,3,5-triazin-2-yl}amino)benzenesulfonate (CAS No: 84000-63-5) was estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor. The substance disodium 2-[(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo-1,6-dihydropyridin-3-yl) diazenyl]-4-({4-chloro-6-[(3-{[2-(sulfonatooxy)ethyl]sulfonyl}phenyl) amino]-1,3,5-triazin-2-yl}amino) benzenesulfonate (CAS No: 84000-63-5) failed to induce skin sensitization effects on guinea pig skin and hence is considered to be not sensitizing to the skin.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Skin sensitization:

Various studies has been investigated for the test chemical disodium 2-[(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo-1,6-dihydropyridin-3-yl)diazenyl]-4-({4-chloro-6-[(3-{[2-(sulfonatooxy)ethyl]sulfonyl}phenyl)amino]-1,3,5-triazin-2-yl}amino)benzenesulfonate (CAS No: 84000-63-5) 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 chemical disodium 2-[(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo-1,6-dihydropyridin-3-yl)diazenyl]-4-({4-chloro-6-[(3-{[2-(sulfonatooxy)ethyl]sulfonyl}phenyl)amino]-1,3,5-triazin-2-yl}amino)benzenesulfonate (CAS No: 84000-63-5) and its structurally similar read across substances Dietheylenetria mine penta (methylene phosphonic acid (CAS No: 15827-60-8) and Disodium EDTA (CAS no: 139-33-3).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 disodium 2-[(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo-1,6-dihydropyridin-3-yl) diazenyl]-4-({4-chloro-6-[(3-{[2-(sulfonatooxy) ethyl]sulfonyl}phenyl)amino]-1,3,5-triazin-2-yl}amino)benzenesulfonate (CAS No: 84000-63-5) was estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor. The substance disodium 2-[(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo-1,6-dihydropyridin-3-yl) diazenyl]-4-({4-chloro-6-[(3-{[2-(sulfonatooxy)ethyl]sulfonyl}phenyl) amino]-1,3,5-triazin-2-yl}amino) benzenesulfonate (CAS No: 84000-63-5) failed to induce skin sensitization effects on guinea pig skin and hence is considered to be not sensitizing to the skin.

The above results were further supported by experimental study conducted by Cosmetic Ingredient Review Expert Panel (2002) on structurally similar read across substance Disodium EDTA (CAS no: 139-33-3) in five male guinea pigs to determine its sensitization potential by using intracutaneous application.During induction, each guinea pig revied 0.1 ml andthen 9 volumes of 0.2 ml Disodium EDTA intacutaneously on alternate days. After 2 weeks of last induction injection, animals were challenged intradermally with 0.1ml of Disodium EDTA for 24 hours. Skin reactions were evaluated after 24 hours. None of the guinea pig had showed any signs of allergic reaction. Therefore Disodium EDTA (CAS no: 139-33-3) was considered to be not sensitizing to the skin of guinea pigs when injected intracutaneous.

 

EUROPEAN COMMISSION – European Chemicals Bureau (2000) carried out Buehler test of structurally similar read across substance Dietheylene triamine penta (methylene phosphonic acid (CAS No: 15827-60-8) in guinea pigs according to OECD Guideline 406 "Skin Sensitization which further supports the above result. The guinea pigs were exposed to 50% of Dietheylenetriamine penta (methylene phosphonic acid in water and then observed for skin sensitizing effects. As no known skin sensitizing effects were observed, the chemical Dietheylenetriamine penta (methylene phosphonic acid (CAS No: 15827-60-8) was considered to be not sensitizing on skin guinea pigs.

Based on the available data for thetarget chemicaldisodium 2-[(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo-1,6-dihydropyridin-3-yl)diazenyl]-4-({4-chloro-6-[(3-{[2-(sulfonatooxy)ethyl]sulfonyl}phenyl)amino]-1,3,5-triazin-2-yl}amino)benzenesulfonate (CAS No: 84000-63-5) and its structurally similar read across substances Dietheylenetriamine penta (methylene phosphonic acid (CAS No: 15827-60-8)andDisodium EDTA (CAS no: 139-33-3),it can be concluded thatchemical disodium 2-[(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo-1,6-dihydropyridin-3-yl)diazenyl]-4-({4-chloro-6-[(3-{[2-(sulfonatooxy)ethyl]sulfonyl}phenyl)amino]-1,3,5-triazin-2-yl}amino)benzenesulfonate (CAS No: 84000-63-5) is unable to cause skin sensitization and considered as non skin sensitizer.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The skin sensitization potential of test substance disodium 2-[(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo-1,6-dihydropyridin-3-yl) diazenyl]-4- ({4-chloro-6- [(3-{[2-(sulfonatooxy)ethyl]sulfonyl}phenyl)amino]-1,3,5-triazin-2-yl}amino)benzenesulfonate (CAS No: 84000-63-5) and its structurally similar read across substances Dietheylenetriamine penta (methylene phosphonic acid (CAS No: 15827-60-8)andDisodium EDTA (CAS no: 139-33-3) were observed in various studies. From the results obtained from these studies it is concluded that the chemical disodium 2-[(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo-1 ,6-dihydropyridin-3-yl)diazenyl]-4-({4-chloro-6-[(3-{[2-(sulfonatooxy)ethyl]sulfonyl}phenyl)amino]-1,3,5-triazin-2-yl}amino)benzenesulfonate (CAS No: 84000-63-5)is unable to cause skin sensitization and hence can be classified as non skin sensitizer.