Registration Dossier

Administrative data

Description of key information

Skin Irritation:

The dermal irritation potential of 4-{[4-({3-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]-4-sulfophenyl}amino)-6-chloro-1,3,5-triazin-2-yl]amino}-6-[(E)-2-(5-carbamoyl-1-ethyl-2-hydroxy-4 -methyl-6-oxo-1,6-dihydropyridin-3-yl)diazen-1-yl]benzene-1,3-disulfonic acid was estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor.

4-{[4-({3-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]-4-sulfophenyl}amino)-6-chloro-1,3,5-triazin-2-yl]amino}-6-[(E)-2-(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo-1,6-dihydropyridin-3-yl)diazen-1-yl]benzene-1,3-disulfonic acid was estimated to be not irritating to the skin of Himalayan rabbits.

Eye Irritation:

The ocular irritation potential of 4-{[4-({3-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]-4-sulfophenyl}amino)-6-chloro-1,3,5-triazin-2-yl]amino}-6-[(E)-2-(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo-1,6-dihydropyridin-3-yl)diazen-1-yl]benzene-1,3-disulfonic acid was estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor.

4-{[4-({3-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]-4-sulfophenyl}amino)-6-chloro-1,3,5-triazin-2-yl]amino}-6-[(E)-2-(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo-1,6-dihydropyridin-3-yl)diazen-1-yl]benzene-1,3-disulfonic acid was estimated to be not irritating to the eyes of Himalayan rabbits.

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 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
Reference:
Composition 1
Qualifier:
according to
Principles of method if other than guideline:
Prediction was done using OECD QSAR toolbox v3.3
GLP compliance:
not specified
Test material information:
Composition 1
Specific details on test material used for the study:
- Name of test material: 1,3-Benzenedisulfonic acid, 4-[[5-(aminocarbonyl)-1-ethyl-1,6-dihydro-2-hydroxy-4-methyl-6-oxo-3-pyridinyl]azo]-6-[[4-[[3-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]-4-sulfophenyl]amino]-6-chloro-1,3,5-triazin-2-yl]amino]-
- IUPAC name: 4-{[4-({3-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]-4-sulfophenyl}amino)-6-chloro-1,3,5-triazin-2-yl]amino}-6-[(E)-2-(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo-1,6-dihydropyridin-3-yl)diazen-1-yl]benzene-1,3-disulfonic acid
- Molecular formula: C27H24Cl2N14O12S3
- Molecular weight: 903.6766 g/mole
- Smiles : CCN1C(=O)C(=C(C(=NNC2=C(C=C(C(=C2)NC3=NC(=NC(=N3)NC4=CC(=C(C=C4)S(=O)
(=O)O)NC5=NC(=NC(=N5)N)Cl)Cl)S(=O)(=O)O)S(=O)(=O)O)C1=O)C)C(=O)N
- Inchl: 1S/C27H24Cl2N14O12S3/c1-3-43-20(45)17(19(30)44)9(2)18(21(43)46)42-41-13-7-12(15(57(50,51)52)8-16(13)58(53,54)55)34-27-38-23(29)37-25(40-27)32-10-4-5-14(56(47,48)49)11(6-10)33-26-36-22(28)35-24(31)39-26/h4-8,46H,3H2,1-2H3,(H2,30,44)(H,47,48,49)(H,50,51,52)(H,53,54,55)(H3,31,33,35,36,39)(H2,32,34,37,38,40)/b42-41+
- Substance type: Organic
- Physical state: Solid powder (red)
Species:
rabbit
Strain:
Himalayan
Details on test animals and environmental conditions:
no data available
Type of coverage:
semiocclusive
Preparation of test site:
abraded
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
500mg
Duration of treatment / exposure:
24 hours
Observation period:
24,48 and 72 hours
Number of animals:
6
Details on study design:
no data available
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
72 h
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
No signs of irritation observed

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" or "f" )  and ("g" and ( not "h") )  )  and ("i" and ( not "j") )  )  and "k" )  and "l" )  and ("m" and ( not "n") )  )  and ("o" and "p" )  )

Domain logical expression index: "a"

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

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 OR Acylation >> Direct Acylation Involving a Leaving group OR Acylation >> Direct Acylation Involving a Leaving group >> Acetates OR SNAr OR SNAr >> Nucleophilic aromatic substitution OR SNAr >> Nucleophilic aromatic substitution >> Halo-triazines by Protein binding by OECD ONLY

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Nucleophilic addition OR Nucleophilic addition >> Addition to carbon-hetero double bonds OR Nucleophilic addition >> Addition to carbon-hetero double bonds >> Ketones 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 ONLY

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Acid moiety OR Acrylamides OR Anilines (Unhindered) OR Hydrazines OR Imides OR Triazines, Aromatic by Aquatic toxicity classification by ECOSAR ONLY

Domain logical expression index: "g"

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: "h"

Referential boundary: The target chemical should be classified as (!Undefined)Group C Surface Tension > 62 mN/m OR (!Undefined)Group CN Lipid Solubility < 0.4 g/kg OR (!Undefined)Group CNHal Lipid Solubility < 4 g/kg OR (!Undefined)Group CNHal Lipid Solubility < 400 g/kg OR (!Undefined)Group CNS Surface Tension > 62 mN/m OR Exclusion rules not met OR Group All log Kow < -3.1 OR Group All log Kow > 9 OR Group C Aqueous Solubility < 0.0001 g/L OR Group C Melting Point > 55 C OR Group C Molecular Weight > 350 g/mol OR Group C Vapour Pressure < 0.0001 Pa OR Group CHal log Kow > 4.5 OR Group CHal Melting Point > 65 C OR Group CHal Molecular Weight > 280 g/mol OR Group CHal Molecular Weight > 370 g/mol OR Group CN Aqueous Solubility < 0.0001 g/L OR Group CN Aqueous Solubility < 0.1 g/L OR Group CN log Kow > 4.5 OR Group CN log Kow > 5.5 OR Group CN Melting Point > 180 C OR Group CN Molecular Weight > 290 g/mol OR Group CN Molecular Weight > 540 g/mol OR Group CN Vapour Pressure < 0.001 Pa OR Group CNHal Aqueous Solubility < 0.001 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 CNHal Molecular Weight > 380 g/mol OR Group CNS log Kow < 0.5 OR Group CNS log Kow < -2 OR Group CNS Melting Point > 120 C OR Group CNS Melting Point > 50 C OR Group CNS Molecular Weight > 620 g/mol by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "i"

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: "j"

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: "k"

Referential boundary: The target chemical should be classified as No superfragment by Superfragments ONLY

Domain logical expression index: "l"

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 ONLY

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Activated N-heterocycles AND Hydrazines,hydrazonium salts by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Inclusion rules not met by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log Kow which is >= -2.99

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of log Kow which is <= 0.323

Interpretation of results:
other: not irritating
Conclusions:
4-{[4-({3-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]-4-sulfophenyl}amino)-6-chloro-1,3,5-triazin-2-yl]amino}-6-[(E)-2-(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo-1,6-dihydropyridin-3-yl)diazen-1-yl]benzene-1,3-disulfonic acid was estimated to be not irritating to the skin of New Zealand White rabbits.
Executive summary:

The dermal irritation potential of 4-{[4-({3-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]-4-sulfophenyl}amino)-6-chloro-1,3,5-triazin-2-yl]amino}-6-[(E)-2-(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo-1,6-dihydropyridin-3-yl)diazen-1-yl]benzene-1,3-disulfonic acid was estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor.

4-{[4-({3-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]-4-sulfophenyl}amino)-6-chloro-1,3,5-triazin-2-yl]amino}-6-[(E)-2-(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo-1,6-dihydropyridin-3-yl)diazen-1-yl]benzene-1,3-disulfonic acid was estimated to be not irritating to the skin of New Zealand White rabbits.

Based on the estimated results, 4-{[4-({3-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]-4-sulfophenyl}amino)-6-chloro-1,3,5-triazin-2-yl]amino}-6-[(E)-2-(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo-1,6-dihydropyridin-3-yl)diazen-1-yl]benzene-1,3-disulfonic acid can be considered 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 v3.3 and the QMRF report has been attached
Reference:
Composition 1
Qualifier:
according to
Guideline:
other: estimated data
Principles of method if other than guideline:
Prediction was done using OECD QSAR toolbox v3.3
GLP compliance:
not specified
Test material information:
Composition 1
Specific details on test material used for the study:
- Name of test material: 1,3-Benzenedisulfonic acid, 4-[[5-(aminocarbonyl)-1-ethyl-1,6-dihydro-2-hydroxy-4-methyl-6-oxo-3-pyridinyl]azo]-6-[[4-[[3-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]-4-sulfophenyl]amino]-6-chloro-1,3,5-triazin-2-yl]amino]-
- IUPAC name: 4-{[4-({3-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]-4-sulfophenyl}amino)-6-chloro-1,3,5-triazin-2-yl]amino}-6-[(E)-2-(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo-1,6-dihydropyridin-3-yl)diazen-1-yl]benzene-1,3-disulfonic acid
- Molecular formula: C27H24Cl2N14O12S3
- Molecular weight: 903.6766 g/mole
- Smiles : CCN1C(=O)C(=C(C(=NNC2=C(C=C(C(=C2)NC3=NC(=NC(=N3)NC4=CC(=C(C=C4)S(=O)
(=O)O)NC5=NC(=NC(=N5)N)Cl)Cl)S(=O)(=O)O)S(=O)(=O)O)C1=O)C)C(=O)N
- Inchl: 1S/C27H24Cl2N14O12S3/c1-3-43-20(45)17(19(30)44)9(2)18(21(43)46)42-41-13-7-12(15(57(50,51)52)8-16(13)58(53,54)55)34-27-38-23(29)37-25(40-27)32-10-4-5-14(56(47,48)49)11(6-10)33-26-36-22(28)35-24(31)39-26/h4-8,46H,3H2,1-2H3,(H2,30,44)(H,47,48,49)(H,50,51,52)(H,53,54,55)(H3,31,33,35,36,39)(H2,32,34,37,38,40)/b42-41+
- Substance type: Organic
- Physical state: Solid powder (red)
Species:
rabbit
Strain:
Himalayan
Details on test animals or tissues and environmental conditions:
no data available
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
100mg
Duration of treatment / exposure:
single instillation
Observation period (in vivo):
1,24,48 and 72 hours
Duration of post- treatment incubation (in vitro):
no data available
Number of animals or in vitro replicates:
6
Details on study design:
no data available
Other effects / acceptance of results:
no data available
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
72 h
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
no signs of irritation 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" or "f" )  and ("g" and ( not "h") )  )  and "i" )  and ("j" and ( not "k") )  )  and ("l" and ( not "m") )  )  and "n" )  and ("o" and "p" )  )

Domain logical expression index: "a"

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

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 OR Acylation >> Direct Acylation Involving a Leaving group OR Acylation >> Direct Acylation Involving a Leaving group >> Acetates OR SNAr OR SNAr >> Nucleophilic aromatic substitution OR SNAr >> Nucleophilic aromatic substitution >> Halo-triazines by Protein binding by OECD ONLY

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Nucleophilic addition OR Nucleophilic addition >> Addition to carbon-hetero double bonds OR Nucleophilic addition >> Addition to carbon-hetero double bonds >> Ketones 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 ONLY

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Acid moiety OR Acrylamides OR Anilines (Unhindered) OR Hydrazines OR Imides OR Triazines, Aromatic by Aquatic toxicity classification by ECOSAR ONLY

Domain logical expression index: "g"

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 AND Group All Molecular Weight > 650 g/mol by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "h"

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 Exclusion rules not met OR Group All Aqueous Solubility < 0.000005 g/L OR Group All Aqueous Solubility < 0.00002 g/L OR Group All log Kow < -3.1 OR Group All log Kow > 9 OR Group C Aqueous Solubility < 0.0001 g/L OR Group C Aqueous Solubility < 0.0005 g/L OR Group C Melting Point > 55 C OR Group C Molecular Weight > 380 g/mol OR Group CHal log Kow > 4.5 OR Group CHal Melting Point > 65 C OR Group CHal Molecular Weight > 280 g/mol OR Group CHal Molecular Weight > 370 g/mol 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 < -2 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: "i"

Referential boundary: The target chemical should be classified as No superfragment by Superfragments ONLY

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Moderate reactive AND Moderate reactive >> Activated 1,3,5-triazine derivatives by DPRA Cysteine peptide depletion

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as High reactive OR High reactive >> Activated haloarenes OR High reactive >> alpha,beta-carbonyl compounds with polarized multiple bonds OR High reactive >> Unsaturated acid anhydrides by DPRA Cysteine peptide depletion

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as 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: "m"

Referential boundary: The target chemical should be classified as Group 11 - Trans.Metals Cu,Ag,Au OR Group 12 - Trans.Metals Zn,Cd,Hg by Chemical elements

Domain logical expression index: "n"

Similarity boundary:Target: CCN1C(=O)C(C(N)=O)=C(C)C(=NNc2cc(Nc3nc(Nc4ccc(S(O)(=O)=O)c(Nc5nc(N)nc(Cl)n5)c4)nc(Cl)n3)c(S(O)(=O)=O)cc2S(O)(=O)=O)C1=O
Threshold=10%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log Kow which is >= -2.99

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of log Kow which is <= 0.744

Interpretation of results:
other: not irritating
Conclusions:
4-{[4-({3-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]-4-sulfophenyl}amino)-6-chloro-1,3,5-triazin-2-yl]amino}-6-[(E)-2-(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo-1,6-dihydropyridin-3-yl)diazen-1-yl]benzene-1,3-disulfonic acid was estimated to be not irritating to the eyes of Himalayan rabbits.
Executive summary:

The ocular irritation potential of 4-{[4-({3-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]-4-sulfophenyl}amino)-6-chloro-1,3,5-triazin-2-yl]amino}-6-[(E)-2-(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo-1,6-dihydropyridin-3-yl)diazen-1-yl]benzene-1,3-disulfonic acid was estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor.

4-{[4-({3-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]-4-sulfophenyl}amino)-6-chloro-1,3,5-triazin-2-yl]amino}-6-[(E)-2-(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo-1,6-dihydropyridin-3-yl)diazen-1-yl]benzene-1,3-disulfonic acid was estimated to be not irritating to the eyes of Himalayan rabbits.

Based on the estimated results, 4-{[4-({3-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]-4-sulfophenyl}amino)-6-chloro-1,3,5-triazin-2-yl]amino}-6-[(E)-2-(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo-1,6-dihydropyridin-3-yl)diazen-1-yl]benzene-1,3-disulfonic acid can be considered not irritating to eyes 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:

In different studies, 4-{[4-({3-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]-4-sulfophenyl}amino)-6-chloro-1,3,5-triazin-2-yl]amino}-6-[(E)-2-(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo-1,6-dihydropyridin-3-yl)diazen-1-yl]benzene-1,3-disulfonic acid has been investigated for potential for dermal irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits along with predicted data for target chemical and closely related read across substances, Reactive deep green KE-4BD [CAS: 61931-49-5] and Trisodium (2-((4,6-dichloro-1,3,5-triazin-2-yl)amino)-5-hydroxy-6-((2-hydroxy-5-sulphophenyl)azo)naphthalene-1,7-disulphonato(5-))cuprate(3-) [CAS: 16038-15-6] . The predicted data using the OECD QSAR toolbox has also been compared with the experimental data.

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 for4-{[4-({3-[(4-amino-6-chloro-1,3,5 -triazin-2-yl)amino]-4-sulfophenyl}amino)-6-chloro-1,3,5-triazin-2-yl]amino}-6-[(E)-2-(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo-1,6-dihydropyridin-3-yl)diazen-1-yl]benzene-1,3 -disulfonic acid. 4-{[4-({3-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]-4-sulfophenyl}amino)-6-chloro-1,3,5-triazin-2-yl]amino}-6-[(E)-2-(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo-1,6 -dihydropyridin-3-yl)diazen-1-yl]benzene-1,3-disulfonic acidwas not irritating to Himalayan rabbit skin.

 

Skin irritation effects were also estimated by four different models i.e, Battery, Leadscope, SciQSAR and CASE Ultra used within Danish QSAR database for 1,3-Benzenedisulfonic acid, 4-[[5-(aminocarbonyl)-1-ethyl-1,6-dihydro-2-hydroxy-4-methyl-6-oxo-3-pyridinyl]azo]-6-[[4-[[3-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]-4-sulfophenyl]amino]-6-chloro-1,3,5-triazin-2-yl]amino]-. Based on estimation, no severe skin irritation effects were known when1,3-Benzenedisulfonic acid, 4-[[5-(aminocarbonyl)-1-ethyl-1,6-dihydro-2-hydroxy-4-methyl-6-oxo-3 -pyridinyl]azo]-6-[[4-[[3-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]-4-sulfophenyl]amino]-6-chloro-1,3,5-triazin-2-yl]amino]- was exposed to rabbit skin.Hence,1,3-Benzenedisulfonic acid, 4-[[5-(aminocarbonyl)-1-ethyl-1,6-dihydro-2-hydroxy-4-methyl-6-oxo-3-pyridinyl]azo]-6-[[4-[[3-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]-4-sulfophenyl]amino]-6-chloro-1,3,5-triazin-2-yl]amino]- can be considered not irritating to skin.

Both the estimated results are in agreement with each other indicating a possibility of 1,3-Benzenedisulfonic acid, 4-[[5-(aminocarbonyl)-1-ethyl-1,6-dihydro-2-hydroxy-4-methyl-6-oxo-3 -pyridinyl]azo]-6-[[4-[[3-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]-4-sulfophenyl]amino]-6-chloro-1,3,5-triazin-2-yl]amino]- being not irritating to skin.

These results are supported by the experimental study summarized in Fiber Reactive Dyes Toxicological Profiles December 1981,PB83-168732; for the closely related read across substance, Reactive deep green KE-4BD [CAS: 61931-49-5].Reactive deep green KE-4BD was applied to the skin of rabbits and observed for signs of irritation(dose, duration not mentioned). No skin irritation effects were observed when Reactive deep green KE-4BD was applied to rabbit skin.

Hence, Reactive deep green KE-4BD can be considered to be not irritating to skin.

The above results are further supported by the experimental study summarized in Fiber Reactive Dyes Toxicological Profiles December 1981,PB83-168732; for the closely related read across substance, Trisodium (2-((4,6-dichloro-1,3,5-triazin-2-yl)amino)-5-hydroxy-6-((2-hydroxy-5-sulphophenyl)azo)naphthalene-1,7-disulphonato(5-))cuprate(3-) [CAS: 16038-15-6]. Trisodium (2-((4,6-dichloro-1,3,5-triazin-2-yl)amino)-5-hydroxy-6-((2-hydroxy-5-sulphophenyl)azo)naphthalene-1,7-disulphonato(5-))cuprate(3-)was applied to the skin of rabbits and observed for signs of irritation(dose, duration not mentioned). No skin irritation effects were observed when Trisodium (2-((4,6-dichloro-1,3,5-triazin-2-yl)amino)-5-hydroxy-6-((2-hydroxy-5-sulphophenyl)azo)naphthalene-1,7-disulphonato(5-))cuprate(3-)was applied to rabbit skin.

Hence, Trisodium (2-((4,6-dichloro-1,3,5-triazin-2-yl)amino)-5-hydroxy-6-((2-hydroxy-5-sulphophenyl)azo)naphthalene-1,7-disulphonato(5-))cuprate(3-)can be considered to be not irritating to skin.

Based on the available data for the target and read across substances and applying the weight of evidence approach, 1,3-Benzenedisulfonic acid, 4-[[5-(aminocarbonyl)-1-ethyl-1,6 -dihydro-2-hydroxy-4-methyl-6-oxo-3-pyridinyl]azo]-6-[[4-[[3-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]-4-sulfophenyl]amino]-6-chloro-1,3,5-triazin-2-yl]amino]- can be considered to be not irritating to skin.Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

Eye irritation:

In different studies, 4-{[4-({3-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]-4-sulfophenyl}amino)-6-chloro-1,3,5-triazin-2-yl]amino}-6-[(E)-2-(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo-1,6-dihydropyridin-3-yl)diazen-1-yl]benzene-1,3-disulfonic acid has been investigated for potential for ocular irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits along with predicted data for target chemical and closely related read across substances, 4-[[4-[(4,6-dichloro-1,3,5-triazin-2-yl)amino]-2-sulphophenyl]azo]-4,5 -dihydro-5-oxo-1-(4-sulphophenyl)-1H-pyrazole-3-carboxylic acid[CAS: 12225-86-4]and Trisodium (2-((4,6-dichloro-1,3,5-triazin-2-yl)amino)-5-hydroxy-6-((2-hydroxy-5-sulphophenyl)azo)naphthalene-1,7-disulphonato(5-))cuprate(3-) [CAS: 16038-15-6] . The predicted data using the OECD QSAR toolbox has also been compared with the experimental data.

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the eye irritation potential was estimated for4-{[4-({3-[(4-amino-6-chloro-1,3,5 -triazin-2-yl)amino]-4-sulfophenyl}amino)-6-chloro-1,3,5-triazin-2-yl]amino}-6-[(E)-2-(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo-1,6-dihydropyridin-3-yl)diazen-1-yl]benzene-1,3 -disulfonic acid. 4-{[4-({3-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]-4-sulfophenyl}amino)-6-chloro-1,3,5-triazin-2-yl]amino}-6-[(E)-2-(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo-1,6 -dihydropyridin-3-yl)diazen-1 -yl]benzene-1,3-disulfonic acidwas not irritating to Himalayan rabbit eyes.

 

This result is supported by the experimental study summarized inFiber Reactive Dyes Toxicological Profiles December 1981,PB83-168732; for the closely related read across substance, 4-[[4-[(4,6-dichloro-1,3,5-triazin-2-yl)amino]-2-sulphophenyl]azo]-4,5-dihydro-5-oxo-1-(4-sulphophenyl)-1H-pyrazole-3-carboxylic acid[CAS: 12225-86-4]. 4-[[4-[(4,6-dichloro-1,3,5-triazin-2-yl)amino]-2-sulphophenyl]azo]-4,5-dihydro-5-oxo-1-(4-sulphophenyl)-1H-pyrazole-3-carboxylic acidwas instilled in to the eyes of rabbits and observed for signs of irritation(dose, duration not mentioned).

No signs of irritation were observed when4-[[4-[(4,6-dichloro-1,3,5-triazin-2-yl)amino]-2-sulphophenyl]azo]-4,5-dihydro-5-oxo-1-(4-sulphophenyl)-1H-pyrazole-3-carboxylic acid was applied to rabbit eyes.

Hence,4-[[4-[(4,6-dichloro-1,3,5-triazin-2-yl)amino]-2-sulphophenyl]azo]-4,5-dihydro-5-oxo-1-(4-sulphophenyl)-1H-pyrazole-3-carboxylic acid can be considered to be not irritating to eyes.

 

These results are also supported by the experimental study summarized in Fiber Reactive Dyes Toxicological Profiles December 1981,PB83-168732; for the closely related read across substance,

Trisodium (2-((4,6-dichloro-1,3,5-triazin-2-yl)amino)-5-hydroxy-6-((2-hydroxy-5-sulphophenyl)azo)naphthalene-1,7-disulphonato(5-))cuprate(3-) [CAS: 16038-15-6] . Trisodium (2-((4,6 -dichloro-1,3,5-triazin-2-yl)amino)-5-hydroxy-6-((2-hydroxy-5-sulphophenyl)azo)naphthalene-1,7-disulphonato(5-))cuprate(3-)was instilled in to the eyes of rabbits and observed for signs of irritation(dose, duration not mentioned).

No signs of irritation were observed when Trisodium (2-((4,6-dichloro-1,3,5-triazin-2-yl)amino)-5-hydroxy-6-((2-hydroxy-5-sulphophenyl)azo)naphthalene-1,7-disulphonato(5-))cuprate(3 -) was applied to rabbit eyes.

Hence, Trisodium (2-((4,6-dichloro-1,3,5-triazin-2-yl)amino)-5-hydroxy-6-((2-hydroxy-5-sulphophenyl)azo)naphthalene-1,7-disulphonato(5-))cuprate(3-)can be considered to be not irritating to eyes.

Based on the available data for the target and read across substances and applying the weight of evidence approach, 1,3-Benzenedisulfonic acid, 4-[[5-(aminocarbonyl)-1-ethyl-1,6-dihydro-2-hydroxy-4-methyl-6-oxo-3-pyridinyl]azo]-6-[[4-[[3-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]-4-sulfophenyl]amino]-6-chloro-1,3,5-triazin-2-yl]amino]- can be considered to be not irritating to eyes.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

Available data for4-{[4-({3-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]-4-sulfophenyl}amino)-6-chloro-1,3,5-triazin-2-yl]amino}-6-[(E)-2-(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo-1,6-dihydropyridin-3-yl)diazen-1-yl]benzene-1,3-disulfonic acid suggests that it is not likely to cause any irritation to eyes and skin.

4-{[4-({3-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]-4-sulfophenyl}amino)-6-chloro-1,3,5-triazin-2-yl]amino}-6-[(E)-2-(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo-1,6-dihydropyridin-3-yl)diazen-1-yl]benzene-1,3-disulfonic acid can be classified under the category “Not Classified” as per CLP regulation.