Registration Dossier

Administrative data

Description of key information

Skin irritation

The dermal irritation potential of target chemical 7-[[2-[(aminocarbonyl)amino]-4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid (CAS No: 35642-64-9)  was assessedin various experimental studies which were conducted on rabbits and rats for target chemical7-[[2-[(aminocarbonyl)amino]-4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid (CAS No: 35642-64-9)   and its structurally similar read across substance aluminium, 6-hydroxy-5-[(2-methoxy-5-methyl-4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex (CAS No:68583-95-9) and functionally similar read across substancesdisodium 5-acetamido-4-hydroxy-3-(phenyldiazenyl)naphthalene-2,7-disulfonate [CAS: 3734-67-6], Disodium 3-[(2,4-dimethyl-5-sulphonatophenyl)azo]-4 -hydroxynaphthalene-1-sulphonate [CAS: 4548-53-2]andaluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex {CAS No: 15790-07-5}. The predicted data usingQSAR toolbox and Danish QSAR databasehas 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 7-[[2-[(aminocarbonyl)amino]-4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid (CAS No: 35642-64-9)   is unable to cause skin irritation and thus 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

An ocular irritation potential of target chemical 7-[[2-[(aminocarbonyl)amino]-4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid (CAS No: 35642-64-9)   was assessedin various experimental studies which were conducted on rabbits for target chemical7-[[2-[(aminocarbonyl)amino]-4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid (CAS No: 35642-64-9)   and its functionally similar read across substancealuminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex (CAS No: 15790-07-5), 7 -amino-4 -hydroxy-2 -naphthalenesulfonic acid(CAS No: 87 -02 -5), Disodium 3-[(2,4-dimethyl-5-sulphonatophenyl)azo]-4-hydroxynaphthalene-1-sulphonate [CAS: 4548-53-2] and disodium 5-amino-4-hydroxy-3-(phenylazo)naphthalene-2,7 -disulphonate[CAS: 3567-66-6]. 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 7-[[2-[(aminocarbonyl)amino]-4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid (CAS No: 35642-64-9)   is unable to cause eye damage and thus can be considered as not irritating. 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 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 v3.3 and the QMRF report has been attached
Reference:
Composition 0
Qualifier:
no guideline available
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 the test chemical: 7-[[2-[(aminocarbonyl)amino]-4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid
Molecular formula: C20H16ClN9O10S3
Molecular weight: 674.0504 g/mol
Smiles Notation: S(=O)(=O)(c1c(/N=N/c2c(NC(=O)N)cc(Nc3nc(nc(n3)Cl)N)cc2)cc2c(S(=O)(=O)O)cc(S(=O)(=O)O)cc2c1)O
InChI: 1S/C20H16ClN9O10S3/c21-17-26-18(22)28-20(27-17)24-9-1-2-12(13(5-9)25-19(23)31)29-30-14-7-11-8(4-16(14)43(38,39)40) 3-10(41(32,33)34)6-15(11)42(35,36)37/h1-7H,(H3,23,25,31)(H,32,33,34)(H,35,36,37)(H,38,39,40)(H3,22,24,26,27,28)/b30-29+
Substance Type: Organic
Physical State: Solid
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
no data available
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
0.5g
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
3
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

Estimation method: Takes mode value from the 8 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" and "q" )  )

Domain logical expression index: "a"

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

Domain logical expression index: "b"

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

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Aromatic phenylureas by DNA binding by OECD

Domain logical expression index: "d"

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

Referential boundary: The target chemical should be classified as SNAr AND SNAr >> Nucleophilic aromatic substitution AND SNAr >> Nucleophilic aromatic substitution >> Halo-triazines by Protein binding by OECD

Domain logical expression index: "f"

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

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.3

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide Side Chain OR Non-covalent interaction >> DNA intercalation >> Fused-Ring Nitroaromatics OR Non-covalent interaction >> DNA intercalation >> Fused-Ring Primary Aromatic Amines OR Radical OR Radical >> Radical mechanism by ROS formation OR Radical >> Radical mechanism by ROS formation >> Polynitroarenes OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Fused-Ring Nitroaromatics OR Radical >> Radical mechanism via ROS formation (indirect) >> Fused-Ring Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroaniline Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroarenes with Other Active Groups OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR SN1 OR SN1 >> Carbenium ion formation OR SN1 >> Carbenium ion formation >> Alpha-Haloethers OR SN1 >> Nucleophilic attack after diazonium or carbenium ion formation OR SN1 >> Nucleophilic attack after diazonium or carbenium ion formation >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Fused-Ring Primary Aromatic Amines OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Fused-Ring Nitroaromatics OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitroaniline Derivatives OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Polynitroarenes OR SN2 OR SN2 >> Direct acting epoxides formed after metabolic activation OR SN2 >> Direct acting epoxides formed after metabolic activation >> Quinoline Derivatives OR SN2 >> SN2 at an activated carbon atom OR SN2 >> SN2 at an activated carbon atom >> Quinoline Derivatives OR SN2 >> SN2 at sp3-carbon atom OR SN2 >> SN2 at sp3-carbon atom >> Alpha-Haloethers OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 >> Nitroarenes with Other Active Groups by DNA binding by OASIS v.1.3

Domain logical expression index: "i"

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

Domain logical expression index: "j"

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

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 Not bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "m"

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

Domain logical expression index: "n"

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

Domain logical expression index: "o"

Similarity boundary:Target: NC(=O)Nc1cc(Nc2nc(N)nc(Cl)n2)ccc1N=Nc1cc2c(cc1S(O)(=O)=O)cc(S(O)(=O)=O)cc2S(O)(=O)=O
Threshold=10%,
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 >= -3

Domain logical expression index: "q"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.24

Interpretation of results:
other: not irritating
Conclusions:
7-[[2-[(aminocarbonyl)amino]-4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid was estimated to be not irritating to the skin of New Zealand White rabbits.
Executive summary:

The dermal irritation potential of 7-[[2-[(aminocarbonyl)amino]-4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid was estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor.

7-[[2-[(aminocarbonyl)amino]-4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid was estimated to be not irritating to the skin of New Zealand White rabbits.

Based on the estimated results, 7-[[2-[(aminocarbonyl)amino]-4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid 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 v3.3 and the QMRF report has been attached
Reference:
Composition 0
Qualifier:
no guideline available
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 the test chemical: 7-[[2-[(aminocarbonyl)amino]-4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid
Molecular formula: C20H16ClN9O10S3
Molecular weight: 674.0504 g/mol
Smiles Notation: S(=O)(=O)(c1c(/N=N/c2c(NC(=O)N)cc(Nc3nc(nc(n3)Cl)N)cc2)cc2c(S(=O)(=O)O)cc(S(=O)(=O)O)cc2c1)O
InChI: 1S/C20H16ClN9O10S3/c21-17-26-18(22)28-20(27-17)24-9-1-2-12(13(5-9)25-19(23)31)29-30-14-7-11-8(4-16(14)43(38,39)40) 3-10(41(32,33)34)6-15(11)42(35,36)37/h1-7H,(H3,23,25,31)(H,32,33,34)(H,35,36,37)(H,38,39,40)(H3,22,24,26,27,28)/b30-29+
Substance Type: Organic
Physical State: Solid
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
no data available
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
0.1ml
Duration of treatment / exposure:
72 hours
Observation period (in vivo):
72 hours
Duration of post- treatment incubation (in vitro):
no data available
Number of animals or in vitro replicates:
3
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 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 ("j" and ( not "k") )  )  and ("l" and ( not "m") )  )  and "n" )  and "o" )  and ("p" and ( not "q") )  )  and ("r" and ( not "s") )  )  and ("t" and "u" )  )

Domain logical expression index: "a"

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

Domain logical expression index: "b"

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

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Aromatic phenylureas by DNA binding by OECD

Domain logical expression index: "d"

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

Referential boundary: The target chemical should be classified as SNAr AND SNAr >> Nucleophilic aromatic substitution AND SNAr >> Nucleophilic aromatic substitution >> Halo-triazines by Protein binding by OECD

Domain logical expression index: "f"

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

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.3

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide Side Chain OR Non-covalent interaction >> DNA intercalation >> Fused-Ring Nitroaromatics OR Non-covalent interaction >> DNA intercalation >> Fused-Ring Primary Aromatic Amines OR Radical OR Radical >> Radical mechanism by ROS formation OR Radical >> Radical mechanism by ROS formation >> Polynitroarenes OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Fused-Ring Nitroaromatics OR Radical >> Radical mechanism via ROS formation (indirect) >> Fused-Ring Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroaniline Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroarenes with Other Active Groups OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR SN1 OR SN1 >> Carbenium ion formation OR SN1 >> Carbenium ion formation >> Alpha-Haloethers OR SN1 >> Nucleophilic attack after diazonium or carbenium ion formation OR SN1 >> Nucleophilic attack after diazonium or carbenium ion formation >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Fused-Ring Primary Aromatic Amines OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Fused-Ring Nitroaromatics OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitroaniline Derivatives OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Polynitroarenes OR SN2 OR SN2 >> Direct acting epoxides formed after metabolic activation OR SN2 >> Direct acting epoxides formed after metabolic activation >> Quinoline Derivatives OR SN2 >> SN2 at an activated carbon atom OR SN2 >> SN2 at an activated carbon atom >> Quinoline Derivatives OR SN2 >> SN2 at sp3-carbon atom OR SN2 >> SN2 at sp3-carbon atom >> Alpha-Haloethers OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 >> Nitroarenes with Other Active Groups by DNA binding by OASIS v.1.3

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 Halogens AND Non-Metals by Groups of elements

Domain logical expression index: "k"

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

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 15 - Phosphorus P OR Group 17 - Halogens Br OR Group 17 - Halogens F by Chemical elements

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Aliphatic Nitrogen, one aromatic attach [-N] AND Aliphatic Nitrogen, two aromatic attach [-N-] AND Amino Triazine/Pyrazine/Pyrimidine  AND Aromatic Carbon [C] AND Aromatic Nitrogen AND Azo [-N=N-] AND Chlorine, aromatic attach [-Cl] AND Chlorine, olefinic attach [-Cl] AND Hydroxy, sulfur attach [-OH] AND Miscellaneous sulfide (=S) or oxide (=O) AND Nitrogen, two or tree olefinic attach [>N-] AND Olefinic carbon [=CH- or =C<] AND Suflur {v+4} or {v+6} AND Sulfinic acid [-S(=O)OH] AND Sulfonate, aromatic attach [-SO2-O] AND Sym-Triazine ring  AND Urea [-OC(=O)N-] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "o"

Similarity boundary:Target: NC(=O)Nc1cc(Nc2nc(N)nc(Cl)n2)ccc1N=Nc1cc2c(cc1S(O)(=O)=O)cc(S(O)(=O)=O)cc2S(O)(=O)=O
Threshold=30%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Not categorized by Repeated dose (HESS)

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Chlorphentermine (Hepatotoxicity) Alert OR Halobenzenes (Hepatotoxicity) Rank A by Repeated dose (HESS)

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Not categorized by Repeated dose (HESS)

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as 3-Methylcholantrene (Hepatotoxicity) Alert OR Anilines (Hemolytic anemia with methemoglobinemia) Rank A by Repeated dose (HESS)

Domain logical expression index: "t"

Parametric boundary:The target chemical should have a value of log Kow which is >= -2.08

Domain logical expression index: "u"

Parametric boundary:The target chemical should have a value of log Kow which is <= 0.382

Interpretation of results:
other: not irritating
Conclusions:
7-[[2-[(aminocarbonyl)amino]-4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid was estimated to be not irritating to the eyes of rabbits.
Executive summary:

The ocular irritation potential of 7-[[2-[(aminocarbonyl)amino]-4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid was estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor.

7-[[2-[(aminocarbonyl)amino]-4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid was estimated to be not irritating to the eyes of rabbits.

Based on the estimated results, 7-[[2-[(aminocarbonyl)amino]-4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid can be considered to be 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:

Various studieshas been investigated for the test chemical7-[[2-[(aminocarbonyl)amino]-4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid (CAS No: 35642-64-9)    to observe the potential for dermal irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits and rats for target chemical7-[[2-[(aminocarbonyl)amino]-4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid (CAS No: 35642-64-9)    and its structurally similar read across substance aluminium, 6-hydroxy-5-[(2-methoxy-5-methyl-4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex (CAS No:68583-95-9) and functionally similar read across substancesdisodium 5-acetamido-4-hydroxy-3-(phenyldiazenyl)naphthalene-2,7-disulfonate [CAS: 3734-67-6], Disodium 3-[(2,4-dimethyl-5-sulphonatophenyl)azo]-4 -hydroxynaphthalene-1-sulphonate [CAS: 4548-53-2]andaluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex {CAS No: 15790-07-5} .The predicted data using the OECD QSAR toolbox andDanish QSAR databasehas 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 chemical7-[[2-[(aminocarbonyl)amino]-4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid (CAS No: 35642-64-9)  . The chemical 7-[[2-[(aminocarbonyl)amino]-4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid (CAS No: 35642-64-9)    is estimated to be not irritating to skin of New Zealand White rabbits.

 

According to Danish QSAR database , the skin irritation effects were estimated by using four different models i.e, Battery, Leadscope, SciQSAR and CASE Ultra for 7-[[2-[(aminocarbonyl)amino]-4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid (CAS No: 35642-64-9)  . Based on estimation, no skin irritation reactions were observed in rabbits. Therefore, 7-[[2-[(aminocarbonyl)amino]-4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid (CAS No: 35642-64-9)   was considered to be not irritating.

Both the estimated results are agreement with each other indicating the possibility of 7-[[2-[(aminocarbonyl)amino]-4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid being not irritating to skin.

 

These results were supported by the experimental studies designed and conducted by Sustainability Support Services (Europe) AB for the read across substancesaluminium, 6-hydroxy-5-[(2-methoxy-5-methyl-4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex (CAS No:68583-95-9),disodium 5-acetamido-4-hydroxy-3-(phenyldiazenyl)naphthalene-2,7-disulfonate [CAS: 3734-67-6] and Disodium 3-[(2,4-dimethyl-5-sulphonatophenyl)azo]-4 -hydroxynaphthalene-1-sulphonate [CAS: 4548-53-2] in Sprague Dawley rats. Each study was performed as per OECD Guidelines 402 and complying to the GLP procedures on ten rats (5 male and 5 female). The test item was applied to shorn skin of 5 male and 5 female animals at 2000 mg/kg body weight in each study. Administration of the test item at 2000 mg/kg did not result in any skin reaction at the site of application during the study period of 14 days. Administration of the test item did not result in any signs of toxicity and mortality during the study period of 14 days. Animals exhibited normal body weight gain through the study period of 14 days. Gross pathological examination did not reveal any abnormalities attributable to the treatment.  The overall irritation score of the substance was determined to be 0 and no erythema and edema (skin irritation) were found at the end of 14 days observation period after patch removal. Hence, it was concluded that Tetra sodium 1-acetamido-2-hydroxy-3-(4-((4-sulphonatophenylazo)-7-sulphonato-1-naphthylazo))naphthalene-4,6-disulphonate was Non-Irritating to the skin of Sprague Dawley rats under the experimental conditions tested.

 

The above results were further supported by another dermal irritation study conducted by Sustainability Support Services (Europe) AB, 2017 on three New Zealand white rabbits in accordance with OECD 404 to assess the irritation parameter of read across chemical aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex {CAS No: 15790-07-5} that supported the above mentioned results. The animals were prepared 24 hours prior to application of test product. The furs from the dorsal area of trunk of animals were removed with electric clippers exposing an area measuring approximately 6 cm2 of body surface area of animal. The care was taken such that abrasion penetrated the Stratum corneum only and not dermis. 500gm (0.5g) of test compound was applied on a small area (approximately 6 cm2) of intact skin site. Each site of application was covered with impervious dressing which was secured in position with adhesive tape. The intact skin site of application of each animal was observed for signs of erythema and oedema at 60 min., 24, 48 and 72 hours after application and the responses were scored according to Draize method. The Primary Irritation Index (PII) foraluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex {CAS No: 15790-07-5}after 14 days of observation was 0.0.Alsoaluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex {CAS No: 15790-07-5}Bdid not produce pain and any clinical signs of toxicity throughout the examination period of 14 days. Hence, under the test conditions, aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex {CAS No: 15790-07-5}can be concluded to be not irritating to New Zealand White rabbit skin.

 

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 7-[[2-[(aminocarbonyl)amino]-4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid (CAS No: 35642-64-9)   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 chemical7-[[2-[(aminocarbonyl)amino]-4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid (CAS No: 35642-64-9)    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 chemical7-[[2-[(aminocarbonyl)amino]-4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid (CAS No: 35642-64-9)    andits functionally similar read across substancealuminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex (CAS No: 15790-07-5), 7 -amino-4 -hydroxy-2 -naphthalenesulfonic acid(CAS No: 87 -02 -5), Disodium 3-[(2,4-dimethyl-5-sulphonatophenyl)azo]-4-hydroxynaphthalene-1-sulphonate [CAS: 4548-53-2] and disodium 5-amino-4-hydroxy-3-(phenylazo)naphthalene-2,7 -disulphonate[CAS: 3567-66-6].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 eye irritation potential was estimated for test chemical7-[[2-[(aminocarbonyl)amino]-4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid (CAS No: 35642-64-9)  . The chemical 7-[[2-[(aminocarbonyl)amino]-4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid (CAS No: 35642-64-9)    is estimated to be not irritating to eye of New Zealand White rabbits.

 

An ocular irritation study was conducted by Sustainability Support Services (Europe) AB, 2017 on three New Zealand white rabbits in accordance with OECD 405 to assess the irritation parameter of read across chemical aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex (CAS No: 15790-07-5). About 0.1g of the undiluted test chemical was instilled in the conjunctival sac of rabbits after gently pulling the lower lid away from the eyeball. The other eye which remained untreated served as a control. The ocular lesions were evaluated at 1, 24, 48 and 72 hours after the treatment. The grades of ocular reactions (conjunctiva, cornea and iris) were recorded at each observation. To determine the reversibility of the effect the animals were observed normally for 21 days. Any other lesions in the eye viz pannus, staining were observed and scored accordingly. Examination of reactions was facilitated by use of biomicroscope and hand slit lamp. Individual animal weights before and during the study was observed. The overall irritation index of aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex (CAS No: 15790-07-5) was 0.0 after 72 hours. Also aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex (CAS No: 15790-07-5) did not produce any clinical signs of toxicity throughout the examination period of 21 days. Hence, under the test conditions, aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex (CAS No: 15790-07-5) can be concluded  to be not irritating to New Zealand White rabbit eyes.

 

The GREIM H., et.al. (Chemosphere Vol. 28, No. 12, pp. 2203.2236, 1994) and BG Chemie (TOXIKOLOGISCHE BEWERTUNGEN; TOXICOLOGICAL EVALUATION last updated: 06/2000) conducted an eye irritation study for read across substance7-Amino-4-hydroxy-2-naphthalenesulfonic acid (CAS No: 87-02-5) in rabbits. In this study, 50 mg 7-amino-4-hydroxy-2-naphthalenesulfonic acid (I acid) was instilled into the conjunctival sac of 2 animals and each were observed for 7 days. No eye irritation was observed after 7 days. Hence the chemical 7-amino-4-hydroxy-2-naphthalenesulfonic acid (CAS No: 87-02-5) can be considered non-irritant to rabbit eyes.

 

These results were supported by the experimental study reported by Scientific Committee on Cosmetology (seventh series), 1988; for read across substance, Disodium 3-[(2,4-dimethyl-5-sulphonatophenyl)azo]-4-hydroxynaphthalene-1-sulphonate [CAS: 4548-53-2]. Ponceau SX 5% in formulation was instilled into the eyes of rabbits and observed for signs of irritation (duration not mentioned). Ponceau SX 5% in formulation did not cause any irritation to rabbit eyes. Hence, Ponceau SX can be considered not irritating to rabbit eyes.

 

The above results were further supported by the experimental study summarized in by the experimental study summarized in Scientific Committee on Consumer Safety (SCCS)-SCCP/1102/07; for the structurally similar read across substance, disodium 5-amino-4-hydroxy-3-(phenylazo)naphthalene-2,7-disulphonate/ Acid red 33 [CAS: 3567-66-6]. 0.2 ml of a 10% aqueous solution (20 mg) or suspension of Acid red 33 was applied twice daily, five times weekly, for four weeks to the conjunctival sac of one eye of each of a group of six or more albino rabbits (40 applications). One hour after each application, the eyes were examined for evidence of staining and the irritation was scored according to Draize. Acid Red 33 caused intense colouring of the iris, lasting for 2 to 7 days. The mean Draize score 3 days after last application was 0.0. Based on the observations and Draize scores, Acid Red 33 was considered to be not irritating to rabbit eyes.

 

Thus 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 7-[[2-[(aminocarbonyl)amino]-4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid (CAS No: 35642-64-9)   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 7-[[2-[(aminocarbonyl)amino]-4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid (CAS No: 35642-64-9)    and its structurally and functionally similar read across substanceswere observed in various studies. The results obtained from these studies indicate that the chemical 7-[[2-[(aminocarbonyl)amino]-4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid (CAS No: 35642-64-9)   is unlikely to cause skin and eye irritation. Hence 7-[[2-[(aminocarbonyl)amino]-4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid (CAS No: 35642-64-9)    can be classified under the category “Not Classified” for skin and eye as per CLP.