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

Skin irritation:

The dermal irritation 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 using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor. The substance is 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 estimated to be not irritating to the skin of New Zealand White rabbits. Based on the estimated result 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) can be considered to be not irritating to skin and can be classified under the category “Not Classified” as per CLP regulation.

Eye irritation:

The ocular irritation 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 using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor. The substance is 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 estimated to be not irritating to the eye of New Zealand White rabbits. Based on the estimated result 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) can be considered to be not irritating to eye and can be classified under the category “Not Classified” as per CLP regulation.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: 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 (Q)SAR model, with limited documentation / justification, but validity of model and reliability of prediction considered adequate based on a generally acknowledged source

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-1,6-dihydro-2-hydroxy-4-methyl -6-oxo-3-pyridyl]azo]- 4-[[4-chloro-6-[[3-[[2- (sulphona tooxy)ethyl]sulphonyl]phenyl]amino]-1,3,5-triazin-2-yl]amino]benzenesulphonate.
- Molecular formula : C26H24ClN9Na2O12S3
- 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:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

No data available

Type of coverage:

not specified

Preparation of test site:

not specified

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

No data available

Duration of treatment / exposure:

No data available

Observation period:

No data available

Number of animals:

No data available

Irritation parameter:

overall irritation score

Basis:

mean

Score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

no skin irritation was observed in treated animals.

Estimation method: Takes mode value from the 5 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 ("i" and ( not "j") )  )  and ("k" and ( not "l") )  )  and ("m" and ( not "n") )  )  and "o" )  and ("p" and "q" )  )

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 Acylation >> Isocyanates and Isothiocyanates OR Acylation >> Isocyanates and Isothiocyanates >> Isocyanates 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 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 SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Aromatic azo 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 >> Episulfonium Ion Formation OR SN2 >> Episulfonium Ion Formation >> Mustards 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 High (Class III) by Toxic hazard classification by Cramer (with extensions) ONLY

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND Group All log Kow < -3.1 AND Group All Melting Point > 200 C AND Group All Molecular Weight > 650 g/mol by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as (!Undefined)Group CN Lipid Solubility < 0.4 g/kg OR (!Undefined)Group CNHal Lipid Solubility < 400 g/kg OR Group All Aqueous Solubility < 0.000005 g/L OR Group All Aqueous Solubility < 0.00002 g/L OR Group All log Kow > 9 OR Group CN Aqueous Solubility < 0.1 g/L OR Group CN log Kow > 4.5 OR Group CN Molecular Weight > 290 g/mol OR Group CNHal Aqueous Solubility < 0.004 g/L OR Group CNHal Aqueous Solubility < 0.1 g/L OR Group CNHal log Kow > 3.8 OR Group CNHal Molecular Weight > 370 g/mol OR Group CNS Aqueous Solubility < 0.006 g/l OR Group CNS log Kow > 1.5 OR Group CNS log Kow > 3.6 OR Group CNS Melting Point > 200 C OR Group CNS Melting Point > 50 C OR Group CNS Molecular Weight > 620 g/mol by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "k"

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

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Alkaline Earth OR Metalloids OR Transition Metals by Groups of elements

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Group 1 - Alkali Earth Li,Na,K,Rb,Cs,Fr AND Group 14 - Carbon C AND Group 15 - Nitrogen N AND Group 16 - Oxygen O AND Group 16 - Sulfur S AND Group 17 - Halogens Cl AND Group 17 - Halogens F,Cl,Br,I,At by Chemical elements

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Group 15 - Phosphorus P by Chemical elements

Domain logical expression index: "o"

Similarity boundary:Target: CCN1C(=O)C(C(N)=O)=C(C)C(=NNc2cc(Nc3nc(Nc4cccc(S(=O)(=O)CCOS(=O)(=O)O{-}.[Na]{+})c4)nc(Cl)n3)ccc2S(=O)(=O)O{-}.[Na]{+})C1=O
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of log Kow which is >= -7.01

Domain logical expression index: "q"

Parametric boundary:The target chemical should have a value of log Kow which is <= -2.41

Interpretation of results:

other: not irritating

Conclusions:

The substance is 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) estimated to be not irritating to the skin of New Zealand White rabbits.

Executive summary:

The dermal irritation 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 using OECD QSAR toolbox version 3.3 with logPow 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 was estimated to be not irritating to the skin of New Zealand White rabbits. Based on the estimated result N 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) can be considered to be not irritating to skin and can be classified under the category “Not Classified” as per CLP regulation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: 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:

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-1,6-dihydro-2-hydroxy-4-methyl -6-oxo-3-pyridyl]azo]- 4-[[4-chloro-6-[[3-[[2- (sulphona tooxy)ethyl]sulphonyl]phenyl]amino]-1,3,5-triazin-2-yl]amino]benzenesulphonate.
- Molecular formula : C26H24ClN9Na2O12S3
- 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:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

No data available

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

No data available

Duration of treatment / exposure:

No data available

Observation period (in vivo):

No data available

Duration of post- treatment incubation (in vitro):

No data available

Number of animals or in vitro replicates:

No data available

Details on study design:

No data available

Irritation parameter:

overall irritation score

Basis:

mean

Score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No eye irritation was observed.

Estimation method: Takes 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" )  )

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 Acylation >> Isocyanates and Isothiocyanates OR Acylation >> Isocyanates and Isothiocyanates >> Isocyanates 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 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 SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Aromatic azo 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 >> 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"

Similarity boundary:Target: CCN1C(=O)C(C(N)=O)=C(C)C(=NNc2cc(Nc3nc(Nc4cccc(S(=O)(=O)CCOS(=O)(=O)O{-}.[Na]{+})c4)nc(Cl)n3)ccc2S(=O)(=O)O{-}.[Na]{+})C1=O
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "k"

Parametric boundary:The target chemical should have a value of log Kow which is >= -16.3

Domain logical expression index: "l"

Parametric boundary:The target chemical should have a value of log Kow which is <= 9.83

Interpretation of results:

other: not irritating

Conclusions:

The substance is 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) estimated to be not irritating to the eye of New Zealand White rabbits

Executive summary:

The ocular irritation 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 using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor. The substance is 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 estimated to be not irritating to the eye of New Zealand White rabbits. Based on the estimated result 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) can be considered to be not irritating to eye and can be classified under the category “Not Classified” as per CLP regulation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation:

Various studieshas been investigated for the test 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)to observe the potential for dermal irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits and humans for target 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 Ethylenebis(tetrabromophthalimide) (CAS No: 32588-76-4) andDisodium 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;

 

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the skin irritation potential was estimated for 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).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 estimated to be not irritating to skin of New Zealand White Rabbits.

 

The NTP; National Institute of Environmental Health Sciences (1999)and NTRL REPORT (1990) reported the dermal irritation study of structurally similar read across substance Ethylenebis(tetrabromophthalimide) (CAS No: 32588-76-4) on albino rabbits to determine the degree of irritation which supports the above result.In this study, 500 mg ofEthylenebis(tetrabromophthalimide) was applied to the abraded skin of three rabbits and the intact skin of the other three over the wide shaved area. One side of each rabbit’s back was slightly abraded at one site with a lancet sufficiently deep to penetrate the stratum corneum but not to enter the derma and produce bleeding. The other side of the back was left intact. The sites were covered with gauze pads and an impervious material was wrapped around the trunk of the animal to hold the pads in place. The dressing was removed at 24 hours and 72 hours in order to observe the sites.the skin reactions were observed according toDraize method. None of the treated rabbit producederythema, eschar, or edema at 24 or 72 hours with primary irritation index of 0. Hence the chemicalEthylenebis(tetrabromophthalimide) (CAS No: 32588-76-4)was considered to be not irritating to the skin ofalbinorabbits.

 

The above results were further supported by a patch test conducted by Cosmetic Ingredient Review Expert Panel (2002) on structurally similar read across substance Disodium EDTA (CAS no: 139-33-3) was in 26 volunteers to assess its skin irritancy potential.In this study, the test chemical was applied toupper outer arm of each volunteer at a dose of 200mg using 25 mm plain hill top chamber containing a moistened webril pad for 4 hours exposure period.Positive control used was 0.2ml of 20% sodium dodecyl sulfate. After exposure, patches were removed and skin reactions were graded at 24, 48 and 72 hoursusing a 4-point scale.Since none of the 26 volunteers treated with Disodium EDTA had skin irritation, compared to 21 of the 26 volunteers treated with SDS, the chemical Disodium EDTA (CAS no: 139-33-3)was considered to be not irritating to the skin of26 volunteers.

 

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 Ethylenebis(tetrabromophthalimide) (CAS No: 32588-76-4) 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 irritation and considered as not irritating.Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

 

 

Eye irritation:

In different studies,the test 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) has been investigated for potential for ocular irritationto a greater or lesser extent. The studies are based on in vivo experiments in rabbits for target 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 Ethylenebis(tetrabromophthalimide) (CAS No: 32588-76-4) andDisodium 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;

 

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the ocular irritation potential was estimated for test 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).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 estimated to be not irritating to eye of New Zealand White Rabbits.

 

The NTP; National Institute of Environmental Health Sciences (1999)and NTRL REPORT (1990) reported an eye irritation study of structurally similar read across substance Ethylenebis(tetrabromophthalimide) (CAS No: 32588-76-4) on six (3/sex) albino New Zealand rabbits to determine the degree of irritation produced by the test substance. About 100mg of Ethylenebis(tetrabromophthalimide) was installed into theconjunctival sac of right eye of each rabbit.24 hours prior to the application of the test material, the eyes of the rabbits were examined using 2% sodium fluorescein stain. Animals showing preexisting corneal injury were eliminated from the study. The left untreated eye served as control. The animals were observed for ocular lesions according to Draize scoring system at 1, 24, 48, and 72 hours and finally at day 7, when the study was terminated. Post-exposure positive responses occurred in all six rabbits at 1 hour, 2 rabbits at 24 hours, and none from 48 hours until the end of the study. Only the conjunctivae were affected. Ethylenebis(tetrabromophthalimide) received a Draize score of 3.0 at 1 hour, 0.3 at 72 hours and 0.0 at 7 days after exposure (maximum score =110). Since all the observed ocular lesions were cleared during 7 days post exposure period, Ethylenebis(tetrabromophthalimide) (CAS No: 32588-76-4)was considered to be not irritating to the eyes ofalbino New Zealandrabbit.

 

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 26 volunteers to assess its eye irritancy potential.In this study, the test chemical was administrated to the mucous membrane of each rabbit eye and later observed for any ocular changes.Since none of the treated rabbits showed any eye irritating reactions, the chemical Disodium EDTA (CAS no: 139-33-3)was considered to be not irritating to the eye of rabbits.

EUROPEAN COMMISSION – European Chemicals Bureau (2000) carried out an eye irritation study of structurally similar read across substance Ethylenebis(tetrabromophthalimide) (CAS No: 32588-76-4) on six albino rabbits which further supports the above results. Ethylenebis(tetrabromophthalimide) was placed into the right eye of each rabbit at concentration of 100mg.after administration of test substance, eyes were not rinsed and reactionswere scored for Conjunctival (redness, chemosis and discharge), iris and corneal (opacity, area).The treated animals had negative eye reactions with 0.0 score at all time points. Thus Ethylenebis(tetrabromophthalimide) (CAS No: 32588-76-4)was considered to be not irritating to the eyes ofalbino rabbits.

 

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 Ethylenebis(tetrabromophthalimide) (CAS No: 32588-76-4) 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 eye irritation and considered as not irritating.Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

Justification for classification or non-classification

The skin and eye irritation potential of 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) and its structurally similar read across substances Ethylenebis(tetrabromophthalimide) (CAS No: 32588-76-4) andDisodium EDTA (CAS no: 139-33-3)were observed in various studies. The results obtained from these studies indicates that the 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)is not likely to cause skin and eye irritation. Hencedisodium 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)can be classified under the category “Not Classified” for skin and eye as per CLP.

 

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