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Administrative data

Description of key information

Acute oral toxicity: 

Acute oral toxicity dose (LD50) of hexasodium 4,4'-{ethene-1,2-diylbis[(3-sulfonato-4,1-phenylene)imino(6-chloro-1,3,5-triazine-4,2-diyl)imino]}bis{6-[(5-carbamoyl-1-ethyl- 2-hydroxy-4-methyl-6-oxo- 1,6-dihydropyridin-3-yl)diazenyl]benzene-1,3-disulfonate} (CAS no: 68991-98-0) was predicted based on OECD QSAR toolbox 2933 mg/kg bw and different studies available on structurally similar read across substances 4,4'-bis[4,6-bis(anilino)-1,3,5-triazin-2-yl]aminostilbene-2,2'-disulphonic acid (CAS no: 88-38-0) >10000 mg/kg bw and 4,4'-bis[[6-anilino-4-(methylamino)-1,3,5-triazin-2-yl]amino]stilbene-2,2'-disulphonic acid (CAS no: 35632-99-6) >2500 mg/kg bw. All these studies concluded that the LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, hexasodium 4,4'-{ethene-1,2-diylbis[(3-sulfonato -4,1-phenylene)imino(6-chloro-1,3,5-triazine-4,2-diyl)imino]}bis{6-[(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo- 1,6-dihydropyridin-3-yl)diazenyl]benzene-1,3- disulfonate} cannot be classified for acute oral toxicity.

Acute Dermal toxicity: 

Acute Dermal toxicity dose (LD50) for hexasodium 4,4'-{ethene-1,2-diylbis[(3-sulfonato-4,1-phenylene)imino(6-chloro-1,3,5-triazine-4,2-diyl)imino]}bis{6-[(5-carbamoyl-1- ethyl-2-hydroxy-4-methyl-6-oxo- 1,6-dihydropyridin-3-yl)diazenyl]benzene-1,3-disulfonate} (CAS no: 68991-98-0) was predicted based on OECD QSAR toolbox 9930 mg/kg bw and study available for the structurally similar read across substance 4,4'-bis[4,6-bis(anilino)-1,3,5-triazin-2-yl]aminostilbene-2,2'-disulphonic acid (CAS no: 88-38-0) >3000 mg/kg bw. Both these studies concluded that the LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, hexasodium 4,4'-{ethene-1,2-diylbis[(3-sulfonato-4,1-phenylene)imino(6-chloro-1,3,5-triazine-4,2-diyl)imino]}bis{6-[(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo- 1,6-dihydropyridin-3-yl)diazenyl]benzene-1,3-disulfonate} cannot be classified for acute dermal toxicity.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
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 predicted using OECD QSAR toolbox version 3.4 and the supporting QMRF report has been attached
Reference:
Composition 0
Qualifier:
according to
Guideline:
other: estimated data
Principles of method if other than guideline:
Prediction is done using QSAR Toolbox version 3.4
GLP compliance:
not specified
Test type:
other: not specified
Limit test:
no
Test material information:
Composition 1
Specific details on test material used for the study:
- IUPAC Name: hexasodium 4,4'-{ethene-1,2-diylbis[(3-sulfonato-4,1-phenylene)imino(6-chloro-1,3,5-triazine-4,2-diyl)imino]}bis{6-[(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo- 1,6-dihydropyridin-3-yl)diazenyl]benzene-1,3-disulfonate}
- SMILES:CCN1C(O)=C(N=Nc2cc(Nc3nc(Nc4ccc(C=Cc5ccc(Nc6nc(Nc7cc(N=NC8=C(O)N(CC)C(=O)C(C(N)=O)=C8C)c(S(O)(=O)=O)cc7S(O)(=O)=O)nc(Cl)n6)cc5S(O)(=O)=O) c(S(O)(=O)=O)c4)nc(Cl)n3)c(S(O)(=O)=O)cc2S(O)(=O)=O)C(C)=C(C(N)=O)C1=O
- InChI:1S/C50H44Cl2N18O24S6/c1-5-69-41(73)35(39(53)71)19(3)37(43(69)75)67-65-27-15-25(31(97(83,84)85)17-33(27)99(89,90)91)57-49-61-45(51)59-47(63-49)55-23-11-9-21 (29(13-23)95(77,78)79)7-8-22-10-12-24(14-30(22)96(80,81)82)56-48-60-46(52)62-50(64-48)58-26-16-28(34(100(92,93)94)18-32(26)98(86,87)88)66-68-38-20(4)36(40(54)72)42(74)70(6-2)44(38)76/h7-18,75-76H,5-6H2,1-4H3,(H2,53,71)(H2,54,72)(H,77,78,79)(H,80,81,82)(H,83,84,85)(H,86,87,88)(H,89,90,91)(H,92,93,94)(H2,55,57,59,61,63)(H2,56,58,60,62,64)/b8-7?,67-65+,68-66+
- Molecular Formula: C50H44Cl2N18O24S6.6Na
- Molecular Weight: 1544.3016 g/mole
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
not specified
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
not specified
Doses:
2933 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not specified
Details on study design:
not specified
Statistics:
not specified
Preliminary study:
not specified
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 933 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 50% mortality was observed
Mortality:
not specified
Clinical signs:
not specified
Body weight:
not specified
Gross pathology:
not specified
Other findings:
not specified

The prediction was based on dataset comprised from the following descriptors: LD50
Estimation method: Takes average value from the 6 nearest neighbours
Domain  logical expression:Result: In Domain

(((((((((((((((((("a" or "b" or "c" or "d" )  and ("e" and ( not "f") )  )  and ("g" and ( not "h") )  )  and ("i" and ( not "j") )  )  and ("k" and ( not "l") )  )  and ("m" and ( not "n") )  )  and ("o" and ( not "p") )  )  and ("q" and ( not "r") )  )  and "s" )  and ("t" and ( not "u") )  )  and ("v" and ( not "w") )  )  and ("x" and ( not "y") )  )  and ("z" and ( not "aa") )  )  and ("ab" and ( not "ac") )  )  and ("ad" and ( not "ae") )  )  and ("af" and ( not "ag") )  )  and ("ah" and ( not "ai") )  )  and ("aj" and "ak" )  )

Domain logical expression index: "a"

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: "b"

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 v1.4

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Direct Acylation Involving a Leaving group AND Acylation >> Direct Acylation Involving a Leaving group >> Acetates AND SNAr AND SNAr >> Nucleophilic aromatic substitution AND SNAr >> Nucleophilic aromatic substitution >> Halo-triazines by Protein binding by OECD

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Acid moiety AND Acrylamides AND Triazines, Aromatic AND Vinyl/Allyl Alcohols by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.4

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >>  Michael-type addition, quinoid structures OR AN2 >>  Michael-type addition, quinoid structures >> Flavonoids OR AN2 >>  Michael-type addition, quinoid structures >> Quinoneimines OR AN2 >>  Michael-type addition, quinoid structures >> Quinones and Trihydroxybenzenes OR AN2 >> Carbamoylation after isocyanate formation OR AN2 >> Carbamoylation after isocyanate formation >> N-Hydroxylamines OR AN2 >> Michael-type addition on alpha, beta-unsaturated carbonyl compounds OR AN2 >> Michael-type addition on alpha, beta-unsaturated carbonyl compounds >> Four- and Five-Membered Lactones OR AN2 >> Nucleophilic addition reaction with cycloisomerization OR AN2 >> Nucleophilic addition reaction with cycloisomerization >> Hydrazine Derivatives OR AN2 >> Schiff base formation OR AN2 >> Schiff base formation >> Dicarbonyl compounds OR AN2 >> Schiff base formation >> Polarized Haloalkene Derivatives OR AN2 >> Schiff base formation >> Specific 5-Substituted Uracil Derivatives OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation >> Geminal Polyhaloalkane Derivatives OR AN2 >> Shiff base formation after aldehyde release OR AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters OR AN2 >> Thioacylation via nucleophilic addition after cysteine-mediated thioketene formation OR AN2 >> Thioacylation via nucleophilic addition after cysteine-mediated thioketene formation >> Haloalkenes with Electron-Withdrawing Groups OR AN2 >> Thioacylation via nucleophilic addition after cysteine-mediated thioketene formation >> Polarized Haloalkene Derivatives OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> Acridone, Thioxanthone, Xanthone and Phenazine Derivatives OR Non-covalent interaction >> DNA intercalation >> Aminoacridine DNA Intercalators OR Non-covalent interaction >> DNA intercalation >> Coumarins OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide and Aminoalkylamine Side Chain OR Non-covalent interaction >> DNA intercalation >> Fused-Ring Nitroaromatics OR Non-covalent interaction >> DNA intercalation >> Fused-Ring Primary Aromatic Amines OR Non-covalent interaction >> DNA intercalation >> N-Hydroxyethyl Lactams OR Non-covalent interaction >> DNA intercalation >> Polycyclic Aromatic Hydrocarbon and Naphthalenediimide Derivatives OR Non-covalent interaction >> DNA intercalation >> Quinolone Derivatives OR Non-covalent interaction >> DNA intercalation >> Quinones and Trihydroxybenzenes OR Non-covalent interaction >> DNA intercalation >> Specific 5-Substituted Uracil Derivatives OR Non-specific OR Non-specific >> Incorporation into DNA/RNA, due to structural analogy with  nucleoside bases    OR Non-specific >> Incorporation into DNA/RNA, due to structural analogy with  nucleoside bases    >> Specific Imine and Thione Derivatives OR Radical OR Radical >> Generation of ROS by glutathione depletion (indirect) OR Radical >> Generation of ROS by glutathione depletion (indirect) >> Haloalkanes Containing Heteroatom OR Radical >> Radical mechanism by ROS formation OR Radical >> Radical mechanism by ROS formation (indirect) or direct radical attack on DNA OR Radical >> Radical mechanism by ROS formation (indirect) or direct radical attack on DNA >> Organic Peroxy Compounds OR Radical >> Radical mechanism by ROS formation >> Five-Membered Aromatic Nitroheterocycles OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Acridone, Thioxanthone, Xanthone and Phenazine Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Conjugated Nitro Compounds OR Radical >> Radical mechanism via ROS formation (indirect) >> Coumarins OR Radical >> Radical mechanism via ROS formation (indirect) >> Flavonoids 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) >> Geminal Polyhaloalkane Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Hydrazine Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> N,N-Dialkyldithiocarbamate Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> N-Hydroxylamines OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitrobiphenyls and Bridged Nitrobiphenyls OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR Radical >> Radical mechanism via ROS formation (indirect) >> p-Substituted Mononitrobenzenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Quinones and Trihydroxybenzenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Specific Imine and Thione Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Thiols OR Radical >> ROS formation after GSH depletion (indirect) OR Radical >> ROS formation after GSH depletion (indirect) >> Haloalcohols OR Radical >> ROS formation after GSH depletion (indirect) >> Quinoneimines OR SN1 OR SN1 >> Alkylation after metabolically formed carbenium ion species OR SN1 >> Alkylation after metabolically formed carbenium ion species >> Polycyclic Aromatic Hydrocarbon and Naphthalenediimide Derivatives OR SN1 >> Carbenium ion formation OR SN1 >> Carbenium ion formation >> Alpha-Haloethers OR SN1 >> Nucleophilic attack after carbenium ion formation OR SN1 >> Nucleophilic attack after carbenium ion formation >> N-Nitroso Compounds OR SN1 >> Nucleophilic attack after carbenium ion formation >> Pyrrolizidine Derivatives OR SN1 >> Nucleophilic attack after carbenium ion formation >> Specific Acetate Esters 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 nitrenium ion formation OR SN1 >> Nucleophilic attack after nitrenium ion formation >> N-Hydroxylamines OR SN1 >> Nucleophilic attack after nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines OR SN1 >> Nucleophilic attack after nitrosonium cation formation OR SN1 >> Nucleophilic attack after nitrosonium cation formation >> N-Nitroso Compounds OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Conjugated Nitro Compounds OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Fused-Ring Nitroaromatics OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitrobiphenyls and Bridged Nitrobiphenyls 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 >> p-Substituted Mononitrobenzenes OR SN1 >> Nucleophilic substitution after carbenium ion formation OR SN1 >> Nucleophilic substitution after carbenium ion formation >> Monohaloalkanes OR SN1 >> Nucleophilic substitution on diazonium ion OR SN1 >> Nucleophilic substitution on diazonium ion >> Specific Imine and Thione Derivatives OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> N-Hydroxylamines OR SN2 >> Acylation >> Specific Acetate Esters OR SN2 >> Acylation involving a leaving group after metabolic activation OR SN2 >> Acylation involving a leaving group after metabolic activation >> Geminal Polyhaloalkane Derivatives OR SN2 >> Alkylation OR SN2 >> Alkylation >> Alkylphosphates, Alkylthiophosphates and Alkylphosphonates OR SN2 >> Alkylation by epoxide metabolically formed after E2 reaction OR SN2 >> Alkylation by epoxide metabolically formed after E2 reaction >> Haloalcohols OR SN2 >> Alkylation by epoxide metabolically formed after E2 reaction >> Monohaloalkanes OR SN2 >> Alkylation, direct acting epoxides and related OR SN2 >> Alkylation, direct acting epoxides and related >> Epoxides and Aziridines OR SN2 >> Alkylation, direct acting epoxides and related after cyclization OR SN2 >> Alkylation, direct acting epoxides and related after cyclization >> Nitrogen and Sulfur Mustards OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation >> Haloalkenes with Electron-Withdrawing Groups OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation >> Polarized Haloalkene Derivatives OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation >> Polycyclic Aromatic Hydrocarbon and Naphthalenediimide Derivatives OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Haloalkanes Containing Heteroatom OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Monohaloalkanes OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Specific 5-Substituted Uracil Derivatives OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Sulfonates and Sulfates OR SN2 >> Alkylation, ring opening SN2 reaction OR SN2 >> Alkylation, ring opening SN2 reaction >> Four- and Five-Membered Lactones OR SN2 >> Direct acting epoxides formed after metabolic activation OR SN2 >> Direct acting epoxides formed after metabolic activation >> Coumarins OR SN2 >> Direct acting epoxides formed after metabolic activation >> Quinoline Derivatives OR SN2 >> Direct acylation involving a leaving group OR SN2 >> Direct acylation involving a leaving group >> Acyl Halides OR SN2 >> Direct nucleophilic attack on diazonium cation OR SN2 >> Direct nucleophilic attack on diazonium cation >> Hydrazine Derivatives OR SN2 >> DNA alkylation OR SN2 >> DNA alkylation >> Vicinal Dihaloalkanes OR SN2 >> Internal SN2 reaction with aziridinium and/or cyclic sulfonium ion formation (enzymatic) OR SN2 >> Internal SN2 reaction with aziridinium and/or cyclic sulfonium ion formation (enzymatic) >> Vicinal Dihaloalkanes OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Haloalkanes Containing Heteroatom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate Esters OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation >> Geminal Polyhaloalkane Derivatives OR SN2 >> SN2 at an activated carbon atom OR SN2 >> SN2 at an activated carbon atom >> Quinoline Derivatives OR SN2 >> SN2 at sp3 and activated sp2 carbon atom OR SN2 >> SN2 at sp3 and activated sp2 carbon atom >> Polarized Haloalkene Derivatives OR SN2 >> SN2 at sp3-carbon atom OR SN2 >> SN2 at sp3-carbon atom >> Alpha-Haloethers by DNA binding by OASIS v.1.4

Domain logical expression index: "g"

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: "h"

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 >> Benzylamines-Acylation OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates >> Formamides OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates >> Sulfonylureas 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 >> 5-alkoxyindoles OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Alkyl phenols OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Arenes OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Hydroquinones OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Methylenedioxyphenyl 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 Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated ketones OR No alert found OR Schiff base formers OR Schiff base formers >> Direct Acting Schiff Base Formers OR Schiff base formers >> Direct Acting Schiff Base Formers >> Mono aldehydes OR SN1 >> Carbenium Ion Formation OR SN1 >> Carbenium Ion Formation >> Allyl benzenes 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 (unsaturated) heterocyclic amine OR SN1 >> Nitrenium Ion formation >> Primary aromatic amine OR SN1 >> Nitrenium Ion formation >> Secondary (unsaturated) heterocyclic 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 SN1 >> Nitrenium Ion formation >> Unsaturated heterocyclic phenylureas OR SN2 OR SN2 >> P450 Mediated Epoxidation OR SN2 >> P450 Mediated Epoxidation >> Thiophenes-SN2 OR SN2 >> SN2 at an sp3 Carbon atom OR SN2 >> SN2 at an sp3 Carbon atom >> Aliphatic halides OR SN2 >> SN2 at an sp3 Carbon atom >> Alkyl carbamates OR SN2 >> SN2 at an sp3 Carbon atom >> Phosphates OR SN2 >> SN2 at an sp3 Carbon atom >> Sulfonates by DNA binding by OECD

Domain logical expression index: "i"

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

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Moderate binder, OH grooup OR 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 OR Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "k"

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: "l"

Referential boundary: The target chemical should be classified as Acylation >> Ring Opening Acylation OR Acylation >> Ring Opening Acylation >> alpha-Lactams OR No alert found OR SN2 OR SN2 >> SN2 reaction at a sulphur atom OR SN2 >> SN2 reaction at a sulphur atom >> Disulfides OR SN2 >> SN2 reaction at sp3 carbon atom OR SN2 >> SN2 reaction at sp3 carbon atom >> Allyl acetates and related chemicals OR SNAr >> Nucleophilic aromatic substitution >> Activated halo-benzenes by Protein binding by OECD

Domain logical expression index: "m"

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: "n"

Referential boundary: The target chemical should be classified as Moderately reactive (GSH) OR Moderately reactive (GSH) >> 2-Vinyl carboxamides (MA) by Protein binding potency

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as No alert found by Protein binding alerts for Chromosomal aberration by OASIS v.1.2

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Michael type addition to activated double bond of pyrimidine bases OR AN2 >> Michael type addition to activated double bond of pyrimidine bases >> Pyrimidines and Purines OR AN2 >> Shiff base formation with carbonyl group of pyrimidine or purine bases OR AN2 >> Shiff base formation with carbonyl group of pyrimidine or purine bases >> Pyrimidines and Purines OR Radical mechanism OR Radical mechanism >> ROS generation OR Radical mechanism >> ROS generation >> Sterically Hindered Piperidine Derivatives by Protein binding alerts for Chromosomal aberration by OASIS v.1.2

Domain logical expression index: "q"

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: "r"

Referential boundary: The target chemical should be classified as Group 17 - Halogens F by Chemical elements

Domain logical expression index: "s"

Similarity boundary:Target: CCN1C(O)=C(N=Nc2cc(Nc3nc(Nc4ccc(C=Cc5ccc(Nc6nc(Nc7cc(N=NC8=C(O)N(CC)C(=O)C(C(N)=O)=C8C)c(S(O)(=O)=O)cc7S(O)(=O)=O)nc(Cl)n6)cc5S(O)(=O)=O)c(S(O)(=O)=O)c4)nc(Cl)n3)c(S(O)(=O)=O)cc2S(O)(=O)=O)C(C)=C(C(N)=O)C1=O
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Aromatic compound AND Carbonic acid derivative AND CO2 derivative (general) AND Halogen derivative AND Heterocyclic compound AND Oxohetarene AND Sulfonic acid AND Sulfonic acid derivative by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as Carboxylic acid by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as Aromatic compound AND Carbonic acid derivative AND CO2 derivative (general) AND Halogen derivative AND Heterocyclic compound AND Oxohetarene AND Sulfonic acid AND Sulfonic acid derivative by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "w"

Referential boundary: The target chemical should be classified as Carboxylic acid imide by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "x"

Referential boundary: The target chemical should be classified as Acrylamide AND Alkene AND Allyl AND Aromatic amine AND Aromatic heterocyclic halide AND Aryl AND Aryl halide AND Azo AND Cyclo conjugated system AND Enol AND Lactams AND Organic amide and thioamide AND Oxopyridine AND Pyridone AND Sulfonic acid AND Triazine AND Unsaturated heterocyclic amine AND Unsaturated heterocyclic fragment by Organic Functional groups

Domain logical expression index: "y"

Referential boundary: The target chemical should be classified as Tetrahydrophthalimide by Organic Functional groups

Domain logical expression index: "z"

Referential boundary: The target chemical should be classified as Acrylamide AND Alkene AND Allyl AND Aromatic amine AND Aromatic heterocyclic halide AND Aryl AND Aryl halide AND Azo AND Cyclo conjugated system AND Enol AND Lactams AND Organic amide and thioamide AND Oxopyridine AND Pyridone AND Sulfonic acid AND Triazine AND Unsaturated heterocyclic amine AND Unsaturated heterocyclic fragment by Organic Functional groups

Domain logical expression index: "aa"

Referential boundary: The target chemical should be classified as Piperazine by Organic Functional groups

Domain logical expression index: "ab"

Referential boundary: The target chemical should be classified as Acrylamide AND Alkene AND Allyl AND Aromatic amine AND Aromatic heterocyclic halide AND Aryl AND Aryl halide AND Azo AND Cyclo conjugated system AND Enol AND Lactams AND Organic amide and thioamide AND Oxopyridine AND Pyridone AND Sulfonic acid AND Triazine AND Unsaturated heterocyclic amine AND Unsaturated heterocyclic fragment by Organic Functional groups

Domain logical expression index: "ac"

Referential boundary: The target chemical should be classified as Ketoxime derivatives by Organic Functional groups

Domain logical expression index: "ad"

Referential boundary: The target chemical should be classified as Aromatic compound AND Carbonic acid derivative AND CO2 derivative (general) AND Halogen derivative AND Heterocyclic compound AND Oxohetarene AND Sulfonic acid AND Sulfonic acid derivative by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "ae"

Referential boundary: The target chemical should be classified as Enolether by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "af"

Referential boundary: The target chemical should be classified as (N/A) by Database Affiliation

Domain logical expression index: "ag"

Referential boundary: The target chemical should be classified as Bacterial mutagenicity ISSSTY by Database Affiliation

Domain logical expression index: "ah"

Referential boundary: The target chemical should be classified as (N/A) by Database Affiliation

Domain logical expression index: "ai"

Referential boundary: The target chemical should be classified as Experimental pKa by Database Affiliation

Domain logical expression index: "aj"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.417

Domain logical expression index: "ak"

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

Interpretation of results:
other: Not classified
Conclusions:
LD50 was estimated to be 2933 mg/kg bw, when 5 male and female Wistar rats were treated with hexasodium 4,4'-{ethene-1,2-diylbis[(3-sulfonato-4,1-phenylene)imino(6-chloro-1,3,5-triazine-4,2-diyl)imino]}bis{6-[(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo- 1,6-dihydropyridin-3-yl)diazenyl]benzene-1,3-disulfonate} (CAS no: 68991-98-0) via oral gavage route.
Executive summary:

In a prediction done by SSS (2018) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for hexasodium 4,4'-{ethene-1,2-diylbis[(3-sulfonato-4,1-phenylene)imino(6-chloro-1,3,5-triazine-4,2-diyl)imino]}bis{6-[(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo- 1,6-dihydropyridin-3-yl)diazenyl]benzene-1,3-disulfonate} (CAS no: 68991-98-0). The LD50 was estimated to be 2933 mg/kg bw, when 5 male and female Wistar rats were treated with hexasodium 4,4'-{ethene-1,2-diylbis[(3-sulfonato-4,1-phenylene)imino(6-chloro-1,3,5-triazine-4,2-diyl)imino]}bis{6-[(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-

6-oxo- 1,6-dihydropyridin-3-yl)diazenyl]benzene-1,3-disulfonate} via oral gavage route.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 933 mg/kg bw
Quality of whole database:
Data is Klimisch 2 and from QSAR toolbox 3.4.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
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 predicted using OECD QSAR toolbox version 3.4 and the supporting QMRF report has been attached.
Reference:
Composition 0
Qualifier:
according to
Guideline:
other: estimated data
Principles of method if other than guideline:
Prediction is done using QSAR Toolbox version 3.4
GLP compliance:
not specified
Test type:
other: not specified
Limit test:
no
Test material information:
Composition 1
Specific details on test material used for the study:
- IUPAC Name: hexasodium 4,4'-{ethene-1,2-diylbis[(3-sulfonato-4,1-phenylene)imino(6-chloro-1,3,5-triazine-4,2-diyl)imino]}bis{6-[(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo- 1,6-dihydropyridin-3-yl)diazenyl]benzene-1,3-disulfonate}
- SMILES:CCN1C(O)=C(N=Nc2cc(Nc3nc(Nc4ccc(C=Cc5ccc(Nc6nc(Nc7cc(N=NC8=C(O)N(CC)C(=O)C(C(N)=O)=C8C)c(S(O)(=O)=O)cc7S(O)(=O)=O)nc(Cl)n6)cc5S(O)(=O)=O) c(S(O)(=O)=O)c4)nc(Cl)n3)c(S(O)(=O)=O)cc2S(O)(=O)=O)C(C)=C(C(N)=O)C1=O
- InChI:1S/C50H44Cl2N18O24S6/c1-5-69-41(73)35(39(53)71)19(3)37(43(69)75)67-65-27-15-25(31(97(83,84)85)17-33(27)99(89,90)91)57-49-61-45(51)59-47(63-49)55-23-11-9-21 (29(13-23)95(77,78)79)7-8-22-10-12-24(14-30(22)96(80,81)82)56-48-60-46(52)62-50(64-48)58-26-16-28(34(100(92,93)94)18-32(26)98(86,87)88)66-68-38-20(4)36(40(54)72)42(74)70(6-2)44(38)76/h7-18,75-76H,5-6H2,1-4H3,(H2,53,71)(H2,54,72)(H,77,78,79)(H,80,81,82)(H,83,84,85)(H,86,87,88)(H,89,90,91)(H,92,93,94)(H2,55,57,59,61,63)(H2,56,58,60,62,64)/b8-7?,67-65+,68-66+
- Molecular Formula: C50H44Cl2N18O24S6.6Na
- Molecular Weight: 1544.3016 g/mole
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
not specified
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
not specified
Duration of exposure:
24 hours
Doses:
9930 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not specified
Details on study design:
not specified
Statistics:
not specified
Preliminary study:
not specified
Sex:
male/female
Dose descriptor:
LD50
Effect level:
9 930 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 50% mortality was observed
Mortality:
not specified
Clinical signs:
not specified
Body weight:
not specified
Gross pathology:
not specified
Other findings:
not specified

The prediction was based on dataset comprised from the following descriptors: LD50
Estimation method: Takes average value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

(((((("a" or "b" or "c" or "d" )  and ("e" and ( not "f") )  )  and ("g" and ( not "h") )  )  and ("i" and ( not "j") )  )  and "k" )  and ("l" and "m" )  )

Domain logical expression index: "a"

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: "b"

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 v1.4

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Direct Acylation Involving a Leaving group AND Acylation >> Direct Acylation Involving a Leaving group >> Acetates AND SNAr AND SNAr >> Nucleophilic aromatic substitution AND SNAr >> Nucleophilic aromatic substitution >> Halo-triazines by Protein binding by OECD

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Acid moiety AND Acrylamides AND Triazines, Aromatic AND Vinyl/Allyl Alcohols by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.4

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Radical OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> N,N-Dialkyldithiocarbamate Derivatives by DNA binding by OASIS v.1.4

Domain logical expression index: "g"

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: "h"

Referential boundary: The target chemical should be classified as 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 >> 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 by DNA binding by OECD

Domain logical expression index: "i"

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: "j"

Referential boundary: The target chemical should be classified as No alert found by Protein binding by OECD

Domain logical expression index: "k"

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

Domain logical expression index: "l"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.245

Domain logical expression index: "m"

Parametric boundary:The target chemical should have a value of log Kow which is <= 5.31

Interpretation of results:
other: Not classified
Conclusions:
LD50 was estimated to be 9930 mg/kg bw, when 5 male and female New Zealand White rabbits were treated with hexasodium 4,4'-{ethene-1,2-diylbis[(3-sulfonato-4,1-phenylene)imino(6-chloro-1,3,5-triazine-4,2-diyl)imino]}bis{6-[(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo- 1,6-dihydropyridin-3-yl)diazenyl]benzene-1,3-disulfonate} (CAS no: 68991-98-0) for 24 hours by dermal application semiocclusively.
Executive summary:

In a prediction done by SSS (2018) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute dermal toxicity was estimated for hexasodium 4,4'-{ethene-1,2-diylbis[(3-sulfonato-4,1-phenylene)imino(6-chloro-1,3,5-triazine-4,2-diyl)imino]}bis{6-[(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo- 1,6-dihydropyridin-3-yl)diazenyl]benzene-1,3-disulfonate} (CAS no: 68991-98-0). The LD50 was estimated to be 9930 mg/kg bw, when 5 male and female New Zealand White rabbits were treated with hexasodium 4,4'-{ethene-1,2-diylbis[(3-sulfonato-4,1-phenylene)imino(6-chloro-1,3,5-triazine-4,2-diyl)imino]}bis{6-[(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo- 1,6-dihydropyridin-3-yl)diazenyl]benzene-1,3-disulfonate} for 24 hours by dermal application semiocclusively.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
9 930 mg/kg bw
Quality of whole database:
Data is Klimisch 2 and from QSAR toolbox 3.4.

Additional information

Acute oral toxicity:

In different studies, hexasodium 4,4'-{ethene-1,2-diylbis[(3-sulfonato-4,1-phenylene)imino(6-chloro-1,3,5-triazine-4,2-diyl)imino]}bis{6-[(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo- 1,6-dihydropyridin-3-yl)diazenyl]benzene-1,3-disulfonate} (CAS no: 68991-98-0) has been investigated for acute oral toxicity to a greater or lesser extent. Often are the studies based on in-vivo experiments in rodents, i.e. most commonly in rats for hexasodium 4,4'-{ethene-1,2-diylbis[(3-sulfonato-4,1-phenylene)imino(6-chloro-1,3,5-triazine-4,2-diyl)imino]}bis{6-[(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo- 1,6-dihydropyridin-3-yl)diazenyl]benzene-1,3-disulfonate} along with the study available on structurally similar read across substances 4,4'-bis[4,6-bis(anilino)-1,3,5-triazin-2-yl]aminostilbene-2,2'-disulphonic acid (CAS no: 88-38-0) and 4,4'-bis[[6-anilino-4-(methylamino)-1,3,5-triazin-2-yl]amino]stilbene-2,2'-disulphonic acid (CAS no: 35632-99-6). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies. The studies are summarized as below –

In a prediction done by SSS (2018) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for hexasodium 4,4'-{ethene-1,2-diylbis[(3-sulfonato-4,1-phenylene)imino(6-chloro-1,3,5-triazine-4,2-diyl)imino]}bis{6-[(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo- 1,6-dihydropyridin-3-yl)diazenyl]benzene-1,3-disulfonate} (CAS no: 68991-98-0). The LD50 was estimated to be 2933 mg/kg bw, when 5 male and female Wistar rats were treated with hexasodium 4,4'-{ethene-1,2-diylbis[(3-sulfonato-4,1-phenylene)imino(6-chloro-1,3,5-triazine-4,2-diyl)imino]}bis{6-[(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo- 1,6-dihydropyridin-3-yl)diazenyl]benzene-1,3-disulfonate} via oral gavage route.

The above study is supported by U.S. National Library of Medicine (ChemIDplus, 2017), for the structurally similar read across substance 4,4'-bis[4,6-bis(anilino)-1,3,5-triazin-2-yl]aminostilbene-2,2'-disulphonic acid (CAS no: 88-38-0).Acute oral toxicity study was conducted in rats at the concentration of 10000 mg/kg bw. No mortality was observed in treated rats at 10000 mg/kg bw. Therefore, LD50 was considered to be >10000 mg/kg bw, when rats were treated with4,4'-bis[4,6-bis(anilino)-1,3,5-triazin-2-yl]aminostilbene-2,2'-disulphonic acid via oral route.

This study is further supported byU.S. National Library of Medicine (ChemIDplus, 2017), for the structurally similar read across substance 4,4'-bis[[6-anilino-4-(methylamino)-1,3,5-triazin-2-yl]amino]stilbene-2,2'-disulphonic acid (CAS no: 35632-99-6).Acute oral toxicity study was conducted in rats at the concentration of 2500 mg/kg bw. No mortality was observed in treated rats at 2500mg/kg bw. Therefore, LD50 was considered to be >2500 mg/kg bw, when rats were treated with4,4'-bis[[6-anilino-4-(methylamino)-1,3,5-triazin-2-yl]amino]stilbene-2,2'-disulphonic acid via oral route.

Thus, based on the above studies on hexasodium 4,4'-{ethene-1,2-diylbis[(3-sulfonato-4,1-phenylene)imino(6-chloro-1,3,5-triazine-4,2-diyl)imino]}bis{6-[(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo- 1,6-dihydropyridin-3-yl)diazenyl]benzene-1,3-disulfonate} (CAS no: 68991-98-0) and it’s read across substances, it can be concluded that LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, hexasodium 4,4'-{ethene-1,2-diylbis[(3-sulfonato-4,1-phenylene)imino(6-chloro-1,3,5-triazine-4,2-diyl)imino]}bis{6-[(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo- 1,6-dihydropyridin-3-yl)diazenyl]benzene-1,3-disulfonate} cannot be classified for acute oral toxicity.

Acute Dermal toxicity:

In different studies, hexasodium 4,4'-{ethene-1,2-diylbis[(3-sulfonato-4,1-phenylene)imino(6-chloro-1,3,5-triazine-4,2-diyl)imino]}bis{6-[(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo- 1,6-dihydropyridin-3-yl)diazenyl]benzene-1,3-disulfonate} (CAS no: 68991-98-0) has been investigated for acute dermal toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments in rodents, i.e. most commonly in rabbits for hexasodium 4,4'-{ethene-1,2-diylbis[(3-sulfonato-4,1-phenylene)imino(6-chloro-1,3,5-triazine-4,2-diyl)imino]}bis{6-[(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo- 1,6-dihydropyridin-3-yl)diazenyl]benzene-1,3-disulfonate} along with the study available on the structurally similar read across substance 4,4'-bis[4,6-bis(anilino)-1,3,5-triazin-2-yl]aminostilbene-2,2'-disulphonic acid (CAS no: 88-38-0).The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies. The studies are summarized as below –

In a prediction done by SSS (2018) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute dermal toxicity was estimated for hexasodium 4,4'-{ethene-1,2-diylbis[(3-sulfonato-4,1-phenylene)imino(6-chloro-1,3,5-triazine-4,2-diyl)imino]}bis{6-[(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo- 1,6-dihydropyridin-3-yl)diazenyl]benzene-1,3-disulfonate} (CAS no: 68991-98-0). The LD50 was estimated to be 9930 mg/kg bw, when 5 male and female New Zealand White rabbits were treated with hexasodium 4,4'-{ethene-1,2-diylbis[(3-sulfonato-4,1-phenylene)imino(6-chloro-1,3,5-triazine-4,2-diyl)imino]}bis{6-[(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo- 1,6-dihydropyridin-3-yl)diazenyl]benzene-1,3-disulfonate} for 24 hours by dermal application semiocclusively.

This study is supported by U.S. National Library of Medicine (ChemIDplus, 2017), for the structurally similar read across substance 4,4'-bis[4,6-bis(anilino)-1,3,5-triazin-2-yl]aminostilbene-2,2'-disulphonic acid (CAS no: 88-38-0).Acute Dermal toxicity study was conducted in rats at the concentration of 3000 mg/kg bw. No mortality was observed in treated rats at 3000 mg/kg bw. Therefore, LD50 was considered to be >3000 mg/kg bw, when rats were treated with4,4'-bis[4,6-bis(anilino)-1,3,5-triazin-2-yl]aminostilbene-2,2'-disulphonic acid by dermal application.

Thus, based on the above studies on hexasodium 4,4'-{ethene-1,2-diylbis[(3-sulfonato-4,1-phenylene)imino(6-chloro-1,3,5-triazine-4,2-diyl)imino]}bis{6-[(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo- 1,6-dihydropyridin-3-yl)diazenyl]benzene-1,3-disulfonate} (CAS no: 68991-98-0) and it’s read across substance, it can be concluded that LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, hexasodium 4,4'-{ethene-1,2-diylbis[(3-sulfonato-4,1-phenylene)imino(6-chloro-1,3,5-triazine-4,2-diyl)imino]}bis{6-[(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo- 1,6-dihydropyridin-3-yl)diazenyl]benzene-1,3-disulfonate} cannot be classified for acute dermal toxicity.

Justification for classification or non-classification

Based on the above studies and prediction on hexasodium 4,4'-{ethene-1,2-diylbis[(3-sulfonato-4,1-phenylene)imino(6-chloro-1,3,5-triazine-4,2-diyl)imino]}bis{6-[(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo- 1,6-dihydropyridin-3-yl)diazenyl]benzene-1,3-disulfonate} (CAS no: 68991-98-0) and it’s read across substances, it can be concluded that LD50 value is >2000 mg/kg bw for acute oral and dermal toxicity. Thus, comparing this value with the criteria of CLP regulation, hexasodium 4,4'-{ethene-1,2-diylbis[(3-sulfonato-4,1-phenylene)imino(6-chloro-1,3,5-triazine-4,2-diyl)imino]}bis{6-[(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo- 1,6-dihydropyridin-3-yl)diazenyl]benzene-1,3-disulfonate} cannot be classified for acute oral and dermal toxicity.