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Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Based on the prediction done using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances, gene mutation was predicted for Hexasodium 4,4'-{ethene-1,2-diylbis[(3-sulfonato-4,1-phenylene)imino(6-chloro-1,3,5-triazine-4,2-diy... (68991-98-0). The study assumed the use of Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 with and without S9 metabolic activation system. Hexasodium 4,4'-{ethene- 1,2-diylbis[(3-sulfonato-4,1-phenylene)imino(6-chloro-1,3,5-triazine-4,2-diy...was predicted to not induce gene mutation in Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 in the presence and absence of S9 metabolic activation system and hence, according to the prediction made, it is not likely to classify as a gene mutant in vitro. Based on the predicted result it can be concluded that the substance is considered to not toxic as per the criteria mentioned in CLP regulation.

Link to relevant study records
Reference
Endpoint:
in vitro gene mutation study in bacteria
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification
Justification for type of information:
Data is from OECD QSAR Toolbox version 3.4 and the supporting QMRF report has been attached.
Reference:
Composition 0
Qualifier:
according to
Guideline:
other: As mention below
Principles of method if other than guideline:
Prediction is done using OECD QSAR Toolbox version 3.4, 2018.
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay
Test material information:
Composition 1
Specific details on test material used for the study:
- Name of test material : 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}
- Molecular formula : C50H44Cl2N18O24S6.6Na
- Molecular weight : 1544.3016 g/mol
- Smiles notation : CCN1C(=C(C(=C(C1=O)N=NC2=CC(=C(C=C2S(=O)(=O)O)S(=O)(=O)O)NC3=NC(=NC(=N3)NC4=CC(=C(C=C4)C=CC5=C(C=C(C=C5)NC6=NC(=NC(=N6)Cl)NC7=C(C=C(C(=C7)N=NC8=C(C(=C(N(C8=O)CC)[O-])C(=N)[O-])C)S(=O)(=O)O)S(=O)(=O)O)S(=O)(=O)[O-])S(=O)(=O)[O-])Cl)C)C(=N)[O-])[O-].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+]
- InChl : 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+
- Substance type : Organic
- Physical state : Solid
Target gene:
Histidine
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102
Details on mammalian cell lines (if applicable):
Not applicable.
Additional strain characteristics:
not specified
Cytokinesis block (if used):
not specified
Metabolic activation:
with
Metabolic activation system:
S9 metabolic activation
Test concentrations with justification for top dose:
not specified
Vehicle:
not specified
Negative controls:
not specified
Solvent controls:
not specified
True negative controls:
not specified
Positive controls:
not specified
Details on test system and conditions:
not specified
Rationale for test conditions:
not specified
Evaluation criteria:
Prediction was done considering a dose dependent increase in the number of revertants/plate.
Statistics:
not specified
Species / strain:
other: TA 1535, TA 1537, TA 98, TA 100 and TA 102
Metabolic activation:
with
Genotoxicity:
negative
Cytotoxicity:
not specified
Vehicle controls valid:
not specified
Negative controls valid:
not specified
Positive controls valid:
not specified
Remarks on result:
other: No mutagenic effect were observed

The prediction was based on dataset comprised from the following descriptors: "Gene mutation"
Estimation method: Takes highest mode 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 ("l" and ( not "m") )  )  and ("n" and "o" )  )

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 >> Hydroxamic Acids OR AN2 >> Carbamoylation after isocyanate formation >> N-Hydroxylamines OR AN2 >> Schiff base formation 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 >> Bleomycin and Structurally Related Compounds 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 >> Organic Azides 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 by ROS formation >> Organic Azides 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) >> Bleomycin and Structurally Related Compounds OR Radical >> Radical mechanism via ROS formation (indirect) >> C-Nitroso Compounds OR Radical >> Radical mechanism via ROS formation (indirect) >> Conjugated Nitro Compounds 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) >> N,N-Dialkyldithiocarbamate Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> N-Hydroxylamines 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) >> 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 >> 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 nitrene formation OR SN1 >> Nucleophilic attack after nitrene formation >> Organic Azides 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 >> p-Substituted Mononitrobenzenes OR SN1 >> Nucleophilic substitution after glutathione-induced nitrenium ion formation OR SN1 >> Nucleophilic substitution after glutathione-induced nitrenium ion formation >> C-Nitroso Compounds 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 >> Hydroxamic Acids 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, 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 >> Specific 5-Substituted Uracil Derivatives OR SN2 >> Direct acting epoxides formed after metabolic activation 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 >> 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 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 >> P450 Mediated Activation to Isocyanates or Isothiocyanates OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates >> Benzylamines-Acylation 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 Michael addition >> Quinones and Quinone-type Chemicals OR Michael addition >> Quinones and Quinone-type Chemicals >> Quinones OR No alert found OR Schiff base formers OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal  OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal  >> Ethanolamines (including morpholine) OR Schiff base formers >> Chemicals Activated by P450 to Mono-aldehydes OR Schiff base formers >> Chemicals Activated by P450 to Mono-aldehydes >> Thiazoles OR Schiff base formers >> Direct Acting Schiff Base Formers OR Schiff base formers >> Direct Acting Schiff Base Formers >> Mono aldehydes OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Aromatic nitro OR SN1 >> Nitrenium Ion formation >> Aromatic phenylureas OR SN1 >> Nitrenium Ion formation >> Primary (unsaturated) heterocyclic amine OR SN1 >> Nitrenium Ion formation >> Primary aromatic amine OR SN1 >> Nitrenium Ion formation >> Secondary aromatic amine OR SN1 >> Nitrenium Ion formation >> Tertiary (unsaturated) heterocyclic amine  OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine OR SN2 OR SN2 >> Epoxidation of Aliphatic Alkenes OR SN2 >> Epoxidation of Aliphatic Alkenes >> Halogenated polarised alkenes OR SN2 >> P450 Mediated Epoxidation OR SN2 >> P450 Mediated Epoxidation >> Thiophenes-SN2 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 by DNA binding by OECD

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as alpha,beta-unsaturated carbonyls by in vitro mutagenicity (Ames test) alerts by ISS

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Aliphatic halogens OR Alkyl carbamate and thiocarbamate OR Aromatic N-acyl amine OR Aromatic ring N-oxide OR Heterocyclic Polycyclic Aromatic Hydrocarbons OR Hydrazine OR Monohaloalkene OR N-methylol derivatives OR No alert found OR Polycyclic Aromatic Hydrocarbons OR Primary aromatic amine,hydroxyl amine and its derived esters by in vitro mutagenicity (Ames test) alerts by ISS

Domain logical expression index: "k"

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: "l"

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: "m"

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

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log Kow which is >= -0.0225

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.43

Conclusions:
Hexasodium 4,4'-{ethene-1,2-diylbis[(3-sulfonato-4,1-phenylene)imino(6-chloro-1,3,5-triazine-4,2-diy... (68991-98-0) was predicted to not induce gene mutation in Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 in the presence of S9 metabolic activation system and hence, according to the prediction made, it is not likely to classify as a gene mutant in vitro.
Executive summary:

Based on the prediction done using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances, gene mutation was predicted forHexasodium 4,4'-{ethene-1,2-diylbis[(3-sulfonato-4,1-phenylene)imino(6-chloro-1,3,5-triazine-4,2-diy... (68991-98-0). The study assumed the use of Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 with S9 metabolic activation system. Hexasodium 4,4'-{ethene-1,2-diylbis[(3-sulfonato-4,1-phenylene) imino(6-chloro-1,3,5-triazine-4,2-diy...was predicted to not induce gene mutation in Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 in the presence of S9 metabolic activation system and hence, according to the prediction made, it is not likely to classify as a gene mutant in vitro. Based on the predicted result it can be concluded that the substance is considered to not toxic as per the criteria mentioned in CLP regulation.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Prediction model based estimation and data from read across chemical have been reviewed to determine the mutagenic nature of target substance Hexasodium 4,4'-{ethene-1,2-diylbis[(3-sulfonato-4,1-phenylene)imino(6-chloro-1,3,5-triazine-4,2-diy... (68991-98-0).The studies are as mentioned below

Based on the prediction done using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances, gene mutation was predicted for Hexasodium 4,4'-{ethene-1,2-diylbis[(3-sulfonato-4,1-phenylene)imino(6-chloro-1,3,5-triazine-4,2-diy... (68991-98-0). The study assumed the use of Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 with and without S9 metabolic activation system. Hexasodium 4,4'-{ethene-1,2-diylbis[(3-sulfonato-4,1-phenylene)imino(6-chloro-1,3,5-triazine-4,2-diy...was predicted to not induce gene mutation in Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 in the presence and absence of S9 metabolic activation system and hence, according to the prediction made, it is not likely to classify as a gene mutant in vitro. Based on the predicted result it can be concluded that the substance is considered to not toxic as per the criteria mentioned in CLP regulation.

Based on the prediction done using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances, chromosomal aberration was predicted for Hexasodium 4,4'-{ethene-1,2-diylbis[(3-sulfonato-4,1-phenylene)imino(6-chloro-1,3,5-triazine-4,2-diy... (68991-98-0) .The study assumed the use of Chinese hamster ovary (CHO) cell line with and without S9 metabolic activation system Hexasodium 4,4'-{ethene-1,2-diylbis[(3-sulfonato-4,1-phenylene)imino(6-chloro-1,3,5-triazine-4,2-diy... was predicted to not induce chromosomal aberrations in Chinese hamster ovary (CHO) cell line in the presence and absence of S9 metabolic activation system and hence, according to the prediction made, it is not likely to classify as a gene mutant in vitro. Based on the predicted result it can be concluded that the substance is considered to not toxic as per the criteria mentioned in CLP regulation.

 In a study performed by Zeiger et al (Environmental and Molecular Mutagenesis, 1998) AMES Mutagenicity assay was performed to evaluate the mutagenic nature of the structurally and functionally similar read across chemical Pigment yellow 100 (12225-21-7)IUPAC Name; aluminum tris(4-{[3-carboxy-5-oxo-1-(4-sulfophenyl)-4,5-dihydro-1H-pyrazol-4-yl]diazenyl}benzenesulfonate). The test compound was dissolved in DMSO and was tested at concentration of 0, 100, 333, 1000, 3333, 6666 or 10000 µg/plate using Salmonella typhimurium TA100, TA1535, TA1537, TA97 and TA98 in the presence and absence of 10 % and 30 % rat and hamster liver S9 metabolic activation system. Preincubation assay was performed with a preicubation for 20 mins. The plates were observed for histidine independence after 2 days incubation period. Concurrent solvent and positive controls were included in the study. Pigment yellow 100 is not mutagenic to the Salmonella typhimurium TA100, TA1535, TA1537, TA97 and TA98 in the presence and absence of rat and hamster liver S9 metabolic activation system  and hence it is not likely to classify as a gene mutant in vitro.

In a study performed by Das and Mukherjee (Human Genetics, 2004) Ames mutagenicity assay was performed to evaluate the mutagenic nature of the structurally and functionally similar read across chemical tartrazine (RA CAS no 1934 -21 -0; IUPAC name: Trisodium 5-hydroxy-1-(4-sulphophenyl)-4-(4-sulphophenylazo)pyrazole-3-carboxylate) using the plate incorporation assay. Tartrazine was dissolved in sterile double distilled water and was tested at a concentration of 0, 100, 250, 500 and 1000 μg /plate. The plates were inverted within an hour and placed in a dark vented incubator at 37⁰C for 48 hours. Positive controls (for TA97a and TA98, 20 μg/plate nitro phenylene diamine and for TA100, 1.5 μg/plate sodium azide) and negative controls were maintained concurrently for all the experiments. Three plates were used for each set. After 48 hours of incubation, the revertant colonies were counted. Tartrazine did not induce gene mutation in Salmonella typhimurium strains TA97a, TA98 and TA100 and hence it is not likely to classify as a gene mutant in vitro.

Based on the data available for the target chemical and its read across substance and applying weight of evidence of Hexasodium 4,4'-{ethene-1,2-diylbis[(3-sulfonato-4,1-phenylene)imino(6-chloro-1,3,5-triazine-4,2-diy... (68991-98-0) does not exhibit gene mutation in vitro. Hence the test chemical is not likely to classify as a gene mutant in vitro.

Justification for classification or non-classification

Thus based on the above annotation and CLP criteria for the target chemical and its read across substance and applying weight of evidence of Hexasodium 4,4'-{ethene-1,2-diylbis [(3-sulfonato-4,1-phenylene)imino(6-chloro-1,3,5-triazine-4,2-diy... (68991-98-0) does not exhibit gene mutation in vitro. Hence the test chemical is not likely to classify as a gene mutant in vitro.