Sodium 2-(2,3-dihydro-1,3-dioxo-1H-inden-2-yl)quinoline-6-sulphonate

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

The test material sodium 2-(2 3-dihydro-1 3-dioxo-1H-inden-2-yl)quinoline-6-sulphonate is not mutagenic in vitro.

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: Prediction is done using QSAR Toolbox version 3.3

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.3

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Species / strain / cell type:

S. typhimurium TA 1535

Details on mammalian cell type (if applicable):

no data

Additional strain / cell type characteristics:

not specified

Metabolic activation:

with

Metabolic activation system:

S9 fraction from liver of induced rats.

Test concentrations with justification for top dose:

313, 625, 1250, 2500, 5000 micromole/plate (common ratio of 2). Maximum concentration of 50 mg/mL of 3-cyanopyridine in injection-use water, the solution was diluted with the same solvent at a common ration of 2 for use.

Vehicle / solvent:

Water

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

yes

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

other: 2 aminoanthracene

Details on test system and experimental conditions:

The test was conducted in duplicate by the preincubation method. Into a test tube was poured 0.1 mL of test substance solution, 0.5 mL of 0.1 M sodium phosphate buffer solution (pH 7.4) and 0.1 mL of bacterial suspension were added, and the mixture was shaken for 20 min at 37 degrees C. When S9 was present, 0.5 mL of S9 mix was added instead of the 0.1 M sodium phosphate buffer solution. Following preincubation, 2 mL of top agar was admixed to the test tube and the contents tereof were layered on a minimum glucose agar plate medium. Once the layered top agar had solidified, the bacteria were cultured for 48 hours at 37 degrees C. The development of bacterial colonies was observed with a steromicroscope. After checking for the presence of antibackterial properties due to the test substance, the number of reverse mutation colonies on the plate was counted with an automatic colony counter. In the preliminaty tests, one plate was employed at each concentration. In the main test, three plates were employed at each concentration and the test was conducted twice to confirm reproducibility. Further, a negative control substance (solvent) and a positive control substance for each bacteria strain were employed in place of the test substance solution to provide control groups that were handled in the same manner as the test substance groups.

Evaluation criteria:

when the number of reverse mutation colonies (average value) accompanying an increase in test substance concentration increased to twice or more that of the negative control value, and that increase was found to be reproducible, the test substance was judged to be positive. All other cases were judged to be negative.

Statistics:

Statistical menthods were not employed to judge the test results.

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Remarks on result:

other: strain/cell type:

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 7 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 ("m" and ( not "n") )  )  and "o" )  and ("p" and ( not "q") )  )  and ("r" and ( not "s") )  )  and "t" )  and ("u" and ( not "v") )  )  and ("w" and ( not "x") )  )  and ("y" and "z" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Neutral Organics by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Aryl OR Diketone OR Fused carbocyclic aromatic OR Fused heterocyclic aromatic OR Indandione OR Pyridine OR Quinoline/ Isoquinoline OR Sulfonic acid by Organic Functional groups ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Aryl OR Fused carbocyclic aromatic OR Indandione OR Overlapping groups OR Quinoline/ Isoquinoline OR Sulfonic acid by Organic Functional groups (nested) ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Aliphatic Carbon [CH] OR Aromatic Carbon [C] OR Aromatic Nitrogen OR Carbonyl, aliphatic attach [-C(=O)-] OR Carbonyl, olefinic attach [-C(=O)-] OR Carbonyl, one aromatic attach [-C(=O)-] OR Hydroxy, sulfur attach [-OH] OR Miscellaneous sulfide (=S) or oxide (=O) OR Olefinic carbon [=CH- or =C<] OR Suflur {v+4} or {v+6} OR Sulfinic acid [-S(=O)OH] OR Sulfonate, aromatic attach [-SO2-O] OR Tertiary Carbon by Organic functional groups (US EPA) ONLY

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Aromatic compound OR Carbonyl compound OR Ketone OR Sulfonic acid OR Sulfonic acid derivative 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 OECD

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> P450 Mediated Activation to Acyl Halides OR Acylation >> P450 Mediated Activation to Acyl Halides >> 1,1-Dihaloalkanes OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates 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 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 >> Polycyclic (PAHs) and heterocyclic (HACs) aromatic hydrocarbons-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated aldehydes 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 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 >> Direct Acting Schiff Base Formers OR Schiff base formers >> Direct Acting Schiff Base Formers >> Alpha-beta-dicarbonyl OR SN1 OR SN1 >> Carbenium Ion Formation OR SN1 >> Carbenium Ion Formation >> Alpha halo ethers (including alpha halo thioethers) OR SN1 >> Carbenium Ion Formation >> Hydrazine OR SN1 >> Carbenium Ion Formation >> N-Nitroso (alkylation) OR SN1 >> Carbenium Ion Formation >> Polycyclic (PAHs) and heterocyclic (HACs) aromatic hydrocarbons-SN1 OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines 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 aromatic amine OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine OR SN1 >> Nitrosation-SN1 OR SN1 >> Nitrosation-SN1 >> N-Nitroso-SN1 OR SN2 OR SN2 >> Direct Acting Epoxides and related OR SN2 >> Direct Acting Epoxides and related >> Epoxides OR SN2 >> Episulfonium Ion Formation OR SN2 >> Episulfonium Ion Formation >> 1,2-Dihaloalkanes OR SN2 >> Nitrosation-SN2 OR SN2 >> Nitrosation-SN2 >> Nitroso-SN2 OR SN2 >> SN2 at an sp3 Carbon atom OR SN2 >> SN2 at an sp3 Carbon atom >> Aliphatic halides by DNA binding by OECD

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 Non binder, impaired OH or NH2 group OR Non binder, MW>500 OR Non binder, non cyclic structure OR Strong binder, OH group OR Weak binder, OH group by Estrogen Receptor Binding

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 Acylation OR Acylation >> Direct Acylation Involving a Leaving group OR Acylation >> Direct Acylation Involving a Leaving group >> Acetates OR Michael addition OR Michael addition >> Polarised Alkenes OR Michael addition >> Polarised Alkenes >> Polarised alkene - aldehydes OR Michael addition >> Polarised Alkenes >> Polarised alkene - cyano OR Michael addition >> Polarised Alkenes >> Polarised alkene - ketones OR Michael addition >> Polarised Alkenes >> Polarised alkene - nitro 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 Schiff Base Formers OR Schiff Base Formers >> Direct Acting Schiff Base Formers OR Schiff Base Formers >> Direct Acting Schiff Base Formers >> Mono-carbonyls OR SN2 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 sp3 carbon atom OR SN2 >> SN2 reaction at sp3 carbon atom >> alpha-Halobenzyls (and related cyano, sulfate and sulphonate subs. chem.) OR SN2 >> SN2 reaction at sp3 carbon atom >> alpha-Halocarbonyls OR SN2 >> SN2 reaction at sp3 carbon atom >> Phosphates OR SNAr OR SNAr >> Nucleophilic aromatic substitution OR SNAr >> Nucleophilic aromatic substitution >> Activated halo-benzenes by Protein binding by OECD

Domain logical expression index: "l"

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

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Stable form by Tautomers unstable

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Conjugated keto(scy) - 1,5-H shift OR Conjugated ketoamine(scy) - 1,5-H shift OR Imidol form OR Imine - amine form(5-membered ring) - 1,3-H shift OR Imine form - 1,3-H shift by Tautomers unstable

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Group 1 - Alkali Earth Li,Na,K,Rb,Cs,Fr AND Group 14 - Carbon C AND Group 15 - Nitrogen N AND Group 16 - Oxygen O AND Group 16 - Sulfur S by Chemical elements

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Group 14 - Metals Sn,Pb OR Group 17 - Halogens Br OR Group 17 - Halogens Cl OR Group 17 - Halogens F OR Group 17 - Halogens F,Cl,Br,I,At OR Group 5 - Trans.Metals V,Nb,Ta OR Group 6 - Trans.Metals Cr,Mo,W OR Group 9 - Trans.Metals Co,Rh,Ir by Chemical elements

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as No alert found by in vitro mutagenicity (Ames test) alerts by ISS

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Anthrones OR Azide and triazene groups OR Heterocyclic Polycyclic Aromatic Hydrocarbons OR Polycyclic Aromatic Hydrocarbons OR Quinones OR Xanthones, Thioxanthones, Acridones by in vitro mutagenicity (Ames test) alerts by ISS

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Not calculated by Hydrolysis half-life (pH 6.5-7.4) ONLY

Domain logical expression index: "u"

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: "v"

Referential boundary: The target chemical should be classified as Low reactive OR Low reactive >> Alicyclic ketones by DPRA Cysteine peptide depletion

Domain logical expression index: "w"

Referential boundary: The target chemical should be classified as Not categorized by OECD HPV Chemical Categories

Domain logical expression index: "x"

Referential boundary: The target chemical should be classified as C10+ Aromatics hydrocarbon solvents OR C9 Aromatics hydrocarbon solvents by OECD HPV Chemical Categories

Domain logical expression index: "y"

Parametric boundary:The target chemical should have a value of log Kow which is >= -1.17

Domain logical expression index: "z"

Parametric boundary:The target chemical should have a value of log Kow which is <= 0.492

Conclusions:

Interpretation of results (migrated information):
negative with metabolic activation

The test material sodium 2-(2 3-dihydro-1 3-dioxo-1H-inden-2-yl)quinoline-6-sulphonate is not mutagenic in vitro in Salmonella typhimurium strain TA 1535 with S9 metabolic activation system.

Executive summary:

Gene mutation was predicted using SSS QSAR prediction model, 2016. The study used Salmonella typhimurium TA1535 strain and S9 metabolic activation system. The test material sodium 2-(2 3-dihydro-1 3-dioxo-1H-inden-2-yl)quinoline-6-sulphonate is not mutagenic in vitro in Salmonella typhimurium strain TA 1535 with S9 metabolic activation system.

As per the CLP classification, the test material is not mutagenic in vitro.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

Additional information from genetic toxicity in vitro:

Gene toxicity in vitro:

Prediction model based estimation and the data from read across (CAS no 8004 -92 -0) is used to predict the mutagenic nature of the test compound CAS no 84864 -68 -6. The summary is as below:

Gene mutation was predicted using SSS QSAR prediction model, 2016. The study used Salmonella typhimurium TA1535 strain and with S9 metabolic activation system. The test material sodium 2-(2 3-dihydro-1 3-dioxo-1H-inden-2-yl)quinoline-6-sulphonate is not mutagenic in vitro in Salmonella typhimurium strain TA 1535 with S9 metabolic activation system. In another study, Salmonella typhimurium TA102 strain was used without S9 metabolic activation system. The test material sodium 2-(2 3-dihydro-1 3-dioxo-1H-inden-2-yl)quinoline-6-sulphonate is not mutagenic in vitro in Salmonella typhimurium strain TA 102 without S9 metabolic activation system. In yet another study, Chinese hamster cell line was used without S9 metabolic activation system. In all the studies conducted the test material sodium 2-(2 3-dihydro-1 3-dioxo-1H-inden-2-yl)quinoline-6-sulphonate is not mutagenic in vitro.

Spot test was performed by Blevins et al (1982) to determine the mutagenic potential of the test compound D & C yellow no 10 (RA 8004 -92 -0). Following cosmetic ingredient treatment of the individual Salmonella strains, the strains were plated on Vogel Bonner Medium E minimal agar plates and incubated for 48 hr at 37°C. The toxicity of the cosmetic ingredient was evidenced by either a clearing of the bacterial lawns (the reduction of colony counts below the range of spontaneous revertants) or the appearance of pinpoint his colonies.Prior to and following chemical cosmetic ingredient exposure, plate counts were done to determine percentage survival of colony-forming units per complete growth medium plates.The cosmetic ingredient was considered mutagenic if there was a significant increase (a reproducible dose related increase in the number of revertant colonies) in the number of colonies on the plate compared with both the nontreated and cosmetic ingredient treated plates. Colonies with a diameter of more than 0.2 mm were counted. The test compoundD & C yellow no 10 did not induce mutation in theSalmonella typhimuriumLT2 - hisTA98, hisTA100, hisTA1535, hisTA1537, and hisTA1538 in the spot test performed and hence is negative for mutation in vitro.

OECD 471 guideline was followed (SCCS, 2004) to determine the mutagenic nature of the test compound Acid yellow 3 (RA CAS no 8004 -92 -0). The chemical was tested at 6 concentrations from 33-5000 μg/plates. In a preliminary experiment with 8 doses, no toxicity was observed, although some toxicity was observed in the first experiment at the high doses. There was no increase in the number of revertants in all strains and in the two experiments in all conditions. The test compound D & C yellow no 10 is not mutagenic in the S. typhimurium TA 98, TA 100, TA 1535, TA 1537; E. coli WP2 uvr A in the mutagenic study performed.

OECD 476 guideline was used (SCCS, 2004) to determine the mutagenic potential of the test compound D & C yellow no 10 (RA CAS no 8004 -92 -0) to mouse lymphoma L5178Y (Thymidine kinase locus) with and without S9 activation system. The test material was tested at concentration of 118-3800 μg/ml. No toxicity was observed until the dose of 3800 μg/ml. The test item did not induce a significant increase of the number of mutant colonies (small and large) in the presence and in the absence of a metabolic activation system in the replicated cultures. The test compound D & C yellow no 10 is not mutagenic/clastogenic to mouse lymphoma L5178Y (Thymidine kinase locus) with and without S9 activation system.

 

 

Justification for selection of genetic toxicity endpoint
The test material sodium 2-(2 3-dihydro-1 3-dioxo-1H-inden-2-yl)quinoline-6-sulphonate is not mutagenic in vitro in Salmonella typhimurium strain TA 1535 with S9 metabolic activation system.

Justification for classification or non-classification

As per the CLP classification, the test material sodium 2-(2 3-dihydro-1 3-dioxo-1H-inden-2-yl)quinoline-6-sulphonate does not classify for mutagen in vitro.

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