3-[(4,5-dihydro-3-methyl-5-oxo-1-phenyl-1H-pyrazol-4-yl)azo]-N,N,N-trimethylanilinium chloride

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

The mutagenicity of Basic yellow 57 is estimated using QSAR toolbox 3.3.The substance Basic yellow 57 is estimated to be non-mutagenic in S. typhimurium TA 1535 in the presence of Rat liver S9 metabolic activation in a bacterial reverse mutation assay.

Link to relevant study records

Reference

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

The data is predicted using the OECD QSAR toolbox version 3.3.

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Species / strain / cell type:

S. typhimurium TA 1535

Additional strain / cell type characteristics:

not specified

Metabolic activation:

with

Metabolic activation system:

Rat liver S9

Test concentrations with justification for top dose:

No data available

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

not specified

Untreated negative controls validity:

not specified

Positive controls validity:

not specified

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

The prediction was based on dataset comprised from the following descriptors: "Gene mutation"
Estimation method: Takes highest mode value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

(((((((("a" or "b" or "c" or "d" or "e" )  and ("f" and ( not "g") )  )  and ("h" and ( not "i") )  )  and ("j" and ( not "k") )  )  and ("l" and ( not "m") )  )  and ("n" and ( not "o") )  )  and ("p" and ( not "q") )  )  and ("r" and "s" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Cationic (quaternary ammonium) surfactants by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Ammonium salt OR Aromatic amine OR Aryl OR Azo OR Pyrazolone OR Unsaturated heterocyclic amine OR Unsaturated heterocyclic fragment by Organic Functional groups ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Aromatic amine OR Aryl OR Azo OR Overlapping groups OR Pyrazolone by Organic Functional groups (nested) ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Aliphatic Carbon [CH] OR Aliphatic Carbon [-CH2-] OR Aliphatic Carbon [-CH3] OR Aliphatic Nitrogen, one aromatic attach [-N] OR Amide, aliphatic attach [-C(=O)N] OR Amino, aliphatic attach [-N<] OR Amino-carbonyl compound [NCC(=O)-C] OR Aromatic Carbon [C] OR Azo [-N=N-] OR Azomethine, aliphatic attach [-N=C] OR Carbonyl, aliphatic attach [-C(=O)-] OR Hydrazine [>N-N<] OR Miscellaneous sulfide (=S) or oxide (=O) OR Nitrogen, single bonds  [N{v+5}] OR Nitrogen, two or tree olefinic attach [>N-] OR Olefinic carbon [=CH- or =C<] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Anion OR Aromatic compound OR Carbonic acid derivative OR Carboxylic acid derivative OR Cation OR Heterocyclic compound OR Quaternary ammonium salt by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "f"

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

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >>  Michael-type addition, quinoid structures OR AN2 >>  Michael-type addition, quinoid structures >> Quinoneimines OR AN2 >>  Michael-type addition, quinoid structures >> Quinones OR AN2 >> Carbamoylation after isocyanate formation OR AN2 >> Carbamoylation after isocyanate formation >> N-Hydroxylamines OR AN2 >> Nucleophilic addition to alpha, beta-unsaturated carbonyl compounds OR AN2 >> Nucleophilic addition to alpha, beta-unsaturated carbonyl compounds >> alpha, beta-Unsaturated Aldehydes OR AN2 >> Schiff base formation OR AN2 >> Schiff base formation >> alpha, beta-Unsaturated Aldehydes OR AN2 >> Schiff base formation >> Dicarbonyl compounds OR AN2 >> Shiff base formation after aldehyde release OR AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters OR Michael addition OR Michael addition >> Quinone type compounds OR Michael addition >> Quinone type compounds >> Quinone methides OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> Aminoacridine DNA Intercalators OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide Side Chain OR Non-covalent interaction >> DNA intercalation >> Fused-Ring Primary Aromatic Amines OR Non-covalent interaction >> DNA intercalation >> Quinones 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 reactive oxygen species OR Radical >> Generation of reactive oxygen species >> Thiols 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 via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Conjugated Nitro Compounds OR Radical >> Radical mechanism via ROS formation (indirect) >> Fused-Ring Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Hydrazine Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> N-Hydroxylamines OR Radical >> Radical mechanism via ROS formation (indirect) >> p-Aminobiphenyl Analogs OR Radical >> Radical mechanism via ROS formation (indirect) >> Quinones 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 >> ROS formation after GSH depletion OR Radical >> ROS formation after GSH depletion (indirect) OR Radical >> ROS formation after GSH depletion (indirect) >> Quinoneimines OR Radical >> ROS formation after GSH depletion >> Quinone methides OR SN1 OR SN1 >> Alkylation after metabolically formed carbenium ion species OR SN1 >> Alkylation after metabolically formed carbenium ion species >> Polycyclic Aromatic Hydrocarbon Derivatives OR SN1 >> Nucleophilic attack after carbenium ion formation OR SN1 >> Nucleophilic attack after carbenium ion formation >> Acyclic Triazenes OR SN1 >> Nucleophilic attack after carbenium ion formation >> N-Nitroso Compounds 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 metabolic nitrenium ion formation >> N-Hydroxylamines OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> p-Aminobiphenyl Analogs OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines OR SN1 >> Nucleophilic attack after nitrenium and/or carbenium ion formation OR SN1 >> Nucleophilic attack after nitrenium and/or carbenium ion 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 substitution on diazonium ions OR SN1 >> Nucleophilic substitution on diazonium ions >> Specific Imine and Thione Derivatives OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> Specific Acetate Esters 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 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 >> Polycyclic Aromatic Hydrocarbon Derivatives OR SN2 >> Direct acting epoxides formed after metabolic activation OR SN2 >> Direct acting epoxides formed after metabolic activation >> Quinoline Derivatives OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate Esters OR SN2 >> SN2 at an activated carbon atom OR SN2 >> SN2 at an activated carbon atom >> Quinoline Derivatives by DNA binding by OASIS v.1.3

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Non binder, without OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Moderate binder, NH2 group OR Non binder, impaired OH or NH2 group OR Non binder, MW>500 OR Non binder, non cyclic structure OR Strong binder, NH2 group OR Weak binder, NH2 group by Estrogen Receptor Binding

Domain logical expression index: "j"

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 SN2 AND SN2 >> SN2 reaction at sp3 carbon atom AND SN2 >> SN2 reaction at sp3 carbon atom >> Alkyl diazo by Protein binding by OECD

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Michael addition OR Michael addition >> Acid imides OR Michael addition >> Acid imides >> Acid imides-MA OR Michael addition >> Polarised Alkenes OR Michael addition >> Polarised Alkenes >> Polarised alkene - ketones OR Michael addition >> Polarised Alkenes >> Polarised alkene - pyridines OR Michael addition >> Quinones and Quinone-type Chemicals OR Michael addition >> Quinones and Quinone-type Chemicals >> Pyranones (and related nitrogen chemicals) OR Michael addition >> Quinones and Quinone-type Chemicals >> Quinone-imine OR No alert found OR SN2 >> Epoxides and Related Chemicals OR SN2 >> Epoxides and Related Chemicals >> Sulfuranes OR SN2 >> SN2 reaction at a sp2 carbon atom OR SN2 >> SN2 reaction at a sp2 carbon atom >> Polarised alkenes with a halogen leaving group OR SN2 >> SN2 reaction at a sulphur atom OR SN2 >> SN2 reaction at a sulphur atom >> Isothiazol-3-ones (sulphur) by Protein binding by OECD

Domain logical expression index: "l"

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

Domain logical expression index: "m"

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

Domain logical expression index: "n"

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 17 - Halogens Cl AND Group 17 - Halogens F,Cl,Br,I,At by Chemical elements

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Group 16 - Selennm Se OR Group 16 - Sulfur S by Chemical elements

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules by DPRA Cysteine peptide depletion

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Low reactive OR Low reactive >> N-substituted aromatic amides by DPRA Cysteine peptide depletion

Domain logical expression index: "r"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.589

Domain logical expression index: "s"

Parametric boundary:The target chemical should have a value of log Kow which is <= 1.32

Conclusions:

Interpretation of results (migrated information):
negative

The substance Basic yellow 57 is estimated to be non-mutagenic in S. typhimurium TA 1535 in the presence of Rat liver S9 metabolic activation in a bacterial reverse mutation assay.

Executive summary:

The mutagenicity of Basic yellow 57 is estimated using QSAR toolbox 3.3.

The substance Basic yellow 57 is estimated to be non-mutagenic in S. typhimurium TA 1535 in the presence of Rat liver S9 metabolic activation in a bacterial reverse mutation assay.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

Additional information from genetic toxicity in vitro:

Target CAS no. 68391-31-1 – Basic yellow 57 : Summary

Genetic toxicity in vitro

In a weight of evidence study (Prediction report - Sustainability Support Services (Europe) AB, 2016):

1) The mutagenicity of Basic yellow 57 is estimated using QSAR toolbox 3.3.The substance Basic yellow 57 is estimated to be non-mutagenic in S. typhimurium TA 1535 in the presence of Rat liver S9 metabolic activation in a bacterial reverse mutation assay.

2) The mutagenicity of Basic yellow 57 is estimated using QSAR toolbox 3.3.The substance Basic yellow 57 is estimated to be non-mutagenic in S. typhimurium TA 1538 in the absence of Rat liver S9 metabolic activation in a bacterial reverse mutation assay.

In a weight of evidence study (SCCS report, 2009):

 

·     Bacterial gene mutation assay was performedby the plate incorporation and pre-incubation method usingSalmonella typhimuriumstrainTA98, TA100, TA102, TA1535 and TA1537.DMSO solution was used as a vehicle. Test chemical conc. used were 3.16, 10, 31.6, 100, 316 and 1000 μg/plate with and without S9-mix.

 

Although cytotoxicity was noted in both the 1^stand 2^ndexperiment, no significant increase in the number of revertant colonies was observed in any of the tester strains neither with nor without metabolic activation.

 

·     Mammalian cell gene mutation assay (tk locus) was carried out usingL5178Y Mouse lymphoma cells.Test chemical conc. used for the two experiment were -

Experiment I

without S9-mix:118.8, 237.5, 475.0, 712.5, 950.0 μg/ml

with S9-mix:118.8, 237.5, 475.0, 712.5, 950.0 μg/ml

 

Experiment II

without S9-mix:59.4, 118.8, 237.5, 475.0, 950.0 μg/ml

 

Experiment IIA:

without S9-mix:400, 500, 600, 700 μg/ml

 

Deionised water was used as a vehicle.

 

Experiment I was performed with and without S9-mix and a treatment period of 4 hours. Experiment II was performed solely without metabolic activation and a treatment period of 24 hours. 

 

The test substanceBasic yellow 57did not induce the mutation at the tk locus in theL5178Y Mouse lymphoma cells(with and without metabolic activation system). 

 

·     In vitro micronucleus test was carried out using Chinese hamster V79 cells.Different conc. of test chemical was used in the various experiment. They are-

Experiment I:

without S9-mix:1000, 1500, 2000 μg/ml

with S9-mix:1000, 1200, 1400 μg/ml

 

Experiment II

without S9-mix:1000, 1500, 2000 μg/ml

Dulbecco’s Modified Eagle Medium(DMEM) was used as a vehicle. Positive substance used for the study are Mitomycin C (- S9-mix) and Cyclophosphamide monohydrate (+ S9-mix), respectively.Test chemical conc. used for the study was determined from the pre-test. Liver S9 fraction from phenobarbital/β-naphthoflavone-induced rats was used as exogenous metabolic activation system.

 

No signs of precipitation were observed at the end of incubation. No decrease in the number of attached cells was observed at the end of incubation of both tests.

                                                  

Test chemical did not induce an increase in the number of cells with micronuclei either with or without metabolic activation in the first test or in the second test after a continuous treatment time of 24 h without S9-mix.

 

In SCCNFP report, 2003:

 

·     Bacterial gene mutation assay was performedby the plate incorporation method usingSalmonella typhimuriumstrainTA98, TA100, TA1535 and TA1537.

 

5 concentrations of test chemical were used – direct plate incorporation assay. with and without metabolic activation.

 

Test #1 :4, 20, 100, 500, 2500 µg/plate

Test #2 :8, 40, 200, 1000, 5000 µg/plate

 

DMSO solution was used as a vehicle. No increase in number of revertants/plate of at least one tester strain was found.

 

·     In vitro mammalian chromosome aberration test was carried out using Chinese hamster V79 cells. Test concentration used was 200-1200 µg/ml with and without metabolic activation.Deionised water was used as a vehicle.

Liver S9 fraction from phenobarbital/β-naphthoflavone-induced rats was used as exogenous metabolic activation system. The test concentrations were established from a preliminary toxicity study.

 

In both independent experiments, no statistically and/or biologically significant relevant increase in the number of aberrant cells were observed as compared to the corresponding solvent control at any dose and treatment time in the presence or absence of activation system. In both experiments, positive control showed distinct increases in the number of aberrant cells and type of aberrations.

 

In a study on similar substance (CAS no. 68391-32-2);

 

In SCCP report, 2008:

 

·     The test chemical was found to be negative (with and without S9 mix) in mouse lymphoma L5178 cells. The test was performed according to OECD 476 guideline.

 

·     In vitro mammalian chromosome aberration test was carried out using Chinese hamster V79 cells according to OECD guideline 487 and 473. The test chemical did not induce an increase in micronucleus cells.

 

In SCCS report, 2014: Test chemical failed to induce mutation at the TK locus in the Mouse lymphoma L5178 cells by the In vitro Mammalian Cell Gene Mutation assay performed.

 

In another study on similar substance (CAS no. 68391-30-0);

 

In SCCS Opinion, 2011:

 

·        Bacterial gene mutation assay was performed according to OECD guideline 471 using S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102. No increase in revertant colonies was observed in the absence or presence of metabolic activation system.

 

·        Test chemical is considered to be not mutagenic in mammalian cell gene mutation assay performed according to the OECD guideline 476 using L5178Y TK +/- mouse lymphoma cells.

 

In SCCNFP report, 2003: No mutagenic response of test chemical Basic Red 76 was determined in the gene mutation tests in Chinese hamster lung fibroblasts (V79).

 

 

In another study on similar substance (CAS no. 26381-41-9);

 

In SCCS report, 2013:

1) In vitro bacterial reverse mutation test was performed according to OECD guideline 471 using S. typhimurium TA1535, TA1537, TA98, TA100 and TA102 by plate incorporation method with and without S9 -mix. The test was evaluated to be negative.

2) No mutagenic response was observed in mammalian cell gene mutation assay performed using V79 cells.

3) In vitro Single cell gel electrophoresis assay (COMET) assay of Basic brown 16 was performed by using EpidermTM reconstructed human skin tissue. In the first and third experiment, no significant increase in percentage tail DNA was observed whereas, in the second experiment, statistical significant increase in the percentage DNA was noted.

 

On the basis of overall reported genetic toxicity studies of Basic yellow 57 and its read-across substances, indicate that test substance Basic yellow 57 is not likely to exhibit genetic toxicity and can be classified as 'non-hazardous' as per the CLP classification criteria. 

Justification for selection of genetic toxicity endpoint
The mutagenicity of Basic yellow 57 is estimated using QSAR toolbox 3.3.The substance Basic yellow 57 is estimated to be non-mutagenic in S. typhimurium TA 1535 in the presence of Rat liver S9 metabolic activation in a bacterial reverse mutation assay.

Justification for classification or non-classification

On the basis of the available data, the substance Basic yellow 57 can be considered to be non-mutagenic and hence can be classified as non-hazardous as per the CLP criteria.