5-amino-2-anilinobenzenesulphonic acid

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

The chemical 5-Amino-2-anilinobenzenesulfonic acid is not likely to classify as a gene mutant in vitro

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:

The supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: Prediction is done using QSAR Toolbox version 3.4

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.4

GLP compliance:

no

Specific details on test material used for the study:

- Name of test material: 5-amino-2-anilinobenzenesulphonic acid
- Molecular formula: C12H12N2O3S
- Molecular weight: 264.304 g/mol
- Smiles notation: O=S(=O)(O)c1c(Nc2ccccc2)ccc(N)c1
- Substance type: Organic

Target gene:

Histidine

Species / strain / cell type:

S. typhimurium TA 100

Details on mammalian cell type (if applicable):

not specified

Additional strain / cell type characteristics:

not specified

Cytokinesis block (if used):

not specified

Metabolic activation:

with

Metabolic activation system:

S9 metabolic activation system

Test concentrations with justification for top dose:

No data

Vehicle / solvent:

No data

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

not specified

True negative controls:

not specified

Positive controls:

not specified

Positive control substance:

not specified

Remarks:

not specified

Details on test system and experimental conditions:

No data

Rationale for test conditions:

No data

Evaluation criteria:

A dose dependent increase in the number of revertants

Statistics:

No data

Species / strain:

S. typhimurium TA 100

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

Additional information on results:

not specified

The prediction was based on dataset comprised from the following descriptors: "Gene mutation"
Estimation method: Takes highest mode value from the 8 nearest neighbours
Domain  logical expression:Result: In Domain

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

Domain logical expression index: "a"

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

Domain logical expression index: "b"

Referential boundary:The target chemical should be classified as Aniline AND Aryl AND Sulfonic acid by Organic Functional groups

Domain logical expression index: "c"

Referential boundary:The target chemical should be classified as Aniline AND Aryl AND Overlapping groups AND Sulfonic acid by Organic Functional groups (nested)

Domain logical expression index: "d"

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

Domain logical expression index: "e"

Referential boundary:The target chemical should be classified as Amine AND Aromatic compound AND Primary amine AND Primary aromatic amine AND Secondary amine AND Secondary aromatic amine AND Sulfonic acid AND Sulfonic acid derivative by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "f"

Referential boundary:The target chemical should be classified as Strong binder, NH2 group by Estrogen Receptor Binding

Domain logical expression index: "g"

Referential boundary:The target chemical should be classified as Moderate binder, NH2 group OR Moderate binder, OH grooup OR Non binder, impaired OH or NH2 group OR Non binder, MW>500 OR Non binder, non cyclic structure OR Non binder, without OH or NH2 group OR Strong binder, OH group OR Very strong binder, OH group OR Weak binder, NH2 group OR Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "h"

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

Domain logical expression index: "i"

Referential boundary:The target chemical should be classified as Aniline AND Aryl AND Sulfonic acid by Organic Functional groups

Domain logical expression index: "j"

Referential boundary:The target chemical should be classified as Aniline AND Aryl AND Overlapping groups AND Sulfonic acid by Organic Functional groups (nested)

Domain logical expression index: "k"

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

Domain logical expression index: "l"

Referential boundary:The target chemical should be classified as Amine AND Aromatic compound AND Primary amine AND Primary aromatic amine AND Secondary amine AND Secondary aromatic amine 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 AN2 AND AN2 >> Michael-type addition to quinoid structures  AND AN2 >> Michael-type addition to quinoid structures  >> N-Substituted Aromatic Amines AND AN2 >> Michael-type addition to quinoid structures  >> Substituted Anilines by Protein binding by OASIS v1.4

Domain logical expression index: "n"

Referential boundary:The target chemical should be classified as Acylation OR Acylation >> Acylation involving an activated (glucuronidated) carboxamide group OR Acylation >> Acylation involving an activated (glucuronidated) carboxamide group >> Carboxylic Acid Amides OR Acylation >> Acylation involving an activated (glucuronidated) ester group OR Acylation >> Acylation involving an activated (glucuronidated) ester group >> Arenecarboxylic Acid Esters OR Acylation >> Acylation involving an activated (glucuronidated) sulfonamide group OR Acylation >> Acylation involving an activated (glucuronidated) sulfonamide group >> Arenesulfonamides OR Acylation >> Direct acylation involving a leaving group OR Acylation >> Direct acylation involving a leaving group >> Carbamates  OR Acylation >> Direct acylation involving a leaving group >> Carboxylic Acid Amides OR Acylation >> Direct acylation involving a leaving group >> N-Carbonylsulfonamides OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Amides OR Acylation >> Ester aminolysis or thiolysis OR Acylation >> Ester aminolysis or thiolysis >> Activated aryl esters  OR Acylation >> Ester aminolysis or thiolysis >> Carbamates  OR Acylation >> Ring opening acylation OR Acylation >> Ring opening acylation >> beta-Lactams  OR AN2 >> Michael addition to activated double bonds OR AN2 >> Michael addition to activated double bonds >> alpha,beta-Unsaturated Carbonyls and Related Compounds OR AN2 >> Michael addition to activated double bonds in heterocyclic ring systems OR AN2 >> Michael addition to activated double bonds in heterocyclic ring systems >> Pyrazolone and Pyrazolidine Derivatives OR AN2 >> Michael addition to alpha, beta-unsaturated acids and esters OR AN2 >> Michael addition to alpha, beta-unsaturated acids and esters >> alpha,beta-Unsaturated Carboxylic Acids and Esters 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 >> Michael-type addition to activated double bonds in vinyl pyridines OR AN2 >> Michael-type addition to activated double bonds in vinyl pyridines >> Ethenyl Pyridines OR AN2 >> Michael-type addition to quinoid structures  >> Carboxylic Acid Amides OR AN2 >> Michael-type addition to quinoid structures  >> Hydroxylated Phenols OR AN2 >> Michael-type addition to quinoid structures  >> Quinoneimine OR AN2 >> Nucleophilic addition at polarized N-functional double bond OR AN2 >> Nucleophilic addition at polarized N-functional double bond >> Arenesulfonamides OR AN2 >> Nucleophilic addition to alpha, beta - unsaturated carbonyl compounds OR AN2 >> Nucleophilic addition to alpha, beta - unsaturated carbonyl compounds >> Propargyl Alcohol derivatives OR AN2 >> Nucleophilic addition to pyridonimine tautomer of aminopyridoindoles or aminopyridoimidazoles (hypothesized) OR AN2 >> Nucleophilic addition to pyridonimine tautomer of aminopyridoindoles or aminopyridoimidazoles (hypothesized) >> Heterocyclic Aromatic Amines OR AN2 >> Schiff base formation with carbonyl compounds (AN2) OR AN2 >> Schiff base formation with carbonyl compounds (AN2) >> Pyrazolone and Pyrazolidine Derivatives OR AN2 >> Schiff base formation with carbonyl group of pyrimidine and purine bases OR AN2 >> Schiff base formation with carbonyl group of pyrimidine and purine bases >> Pyrimidines and Purines OR AR OR AR >>  Radical-type addition to imino tautomer of aminoacridines OR AR >>  Radical-type addition to imino tautomer of aminoacridines >> Benzoquinoline and Аcridine derivatives OR Michael addition OR Michael addition >> Michae addition on quinoide type compounds OR Michael addition >> Michae addition on quinoide type compounds >> Quinone methide(s)/imines; Quinoide oxime structure; Nitroquinones, Naphthoquinone(s)/imines  OR Michael addition >> Michael addition on azoxy compounds OR Michael addition >> Michael addition on azoxy compounds >> Azoxy compounds  OR Michael addition >> Michael addition on conjugated systems with electron withdrawing group OR Michael addition >> Michael addition on conjugated systems with electron withdrawing group >> Activated electrophilic ethenylarenes  OR Michael addition >> Michael addition on conjugated systems with electron withdrawing group >> Nitroalkenes OR Michael addition >> Michael addition on conjugated systems with electron withdrawing group >> N-Sulfonylazomethynes  OR Michael addition >> Michael addition on polarised Alkenes OR Michael addition >> Michael addition on polarised Alkenes >> Polarised Alkene - alkenyl pyridines, pyrazines, pyrimidines or triazines  OR Michael addition >> Michael addition on polarised Alkenes >> Polarised Alkenes - sulfones  OR Michael addition >> Michael type addition on quinone type chemicals OR Michael addition >> Michael type addition on quinone type chemicals >> Pyranones, Pyridones (and related nitrogen chemicals)  OR No alert found OR Nucleophilic addition OR Nucleophilic addition >> Addition to carbon-hetero double bonds OR Nucleophilic addition >> Addition to carbon-hetero double bonds >> Ketones OR Nucleophilic addition >> Nucleophilic addition reaction at polarized N-functional double bond OR Nucleophilic addition >> Nucleophilic addition reaction at polarized N-functional double bond >> C-Nitroso compounds  OR Radical reactions OR Radical reactions >> Free radical formation OR Radical reactions >> Free radical formation >> Hydroperoxides OR Radical reactions >> ROS generation and direct attack of hydroxyl radical to the C8 position of nucleoside base OR Radical reactions >> ROS generation and direct attack of hydroxyl radical to the C8 position of nucleoside base >> Heterocyclic Aromatic Amines OR Schiff base formation OR Schiff base formation >> Schiff base formation with carbonyl compounds OR Schiff base formation >> Schiff base formation with carbonyl compounds >> Aldehydes OR Schiff base formation >> Schiff base formation with carbonyl compounds >> Aromatic carbonyl compounds OR Schiff base formation >> Schiff base on pyrazolones and pyrazolidinones OR Schiff base formation >> Schiff base on pyrazolones and pyrazolidinones >> Pyrazolones and Pyrazolidinones OR SE reaction (CYP450-activated heterocyclic amines) OR SE reaction (CYP450-activated heterocyclic amines) >> Direct attack of arylnitrenium cation to the C8 position of nucleoside base  OR SE reaction (CYP450-activated heterocyclic amines) >> Direct attack of arylnitrenium cation to the C8 position of nucleoside base  >> Heterocyclic Aromatic Amines OR SN2 OR SN2 >> Interchange reaction with sulphur containing compounds OR SN2 >> Interchange reaction with sulphur containing compounds >> Thiols and disulfide compounds  OR SN2 >> Nucleophilic substitution at sp3 carbon atom OR SN2 >> Nucleophilic substitution at sp3 carbon atom >> (Thio)Phosphates  OR SN2 >> Nucleophilic substitution at sp3 carbon atom >> Alkyl halides  OR SN2 >> Nucleophilic substitution at sp3 carbon atom >> alpha-Activated haloalkanes  OR SN2 >> Nucleophilic substitution at sp3 carbon atom >> Phosphonates OR SN2 >> Nucleophilic substitution on a sulphur atom OR SN2 >> Nucleophilic substitution on a sulphur atom >> Organic thiosulfates  OR SN2 >> Nucleophilic substitution on benzilyc carbon atom OR SN2 >> Nucleophilic substitution on benzilyc carbon atom >> alpha-Activated benzyls  OR SN2 >> Ring opening nucleophilic substitution involving arene oxide derivatives and proteins OR SN2 >> Ring opening nucleophilic substitution involving arene oxide derivatives and proteins >> Benzoquinoline and Аcridine derivatives OR SN2 >> SN2 Reaction at a sp3 carbon atom OR SN2 >> SN2 Reaction at a sp3 carbon atom >> Activated alkyl esters and thioesters  OR SN2 >> SN2 reaction at a sulfur atom OR SN2 >> SN2 reaction at a sulfur atom >> Isothiazolidin-3-ones (sulphur) and Isothiazolone derivatives  OR SN2 >> SN2 reaction at a sulfur atom >> Thiocyanates OR SNAr OR SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds OR SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds >> Activated aryl and heteroaryl compounds OR SNAr >> Nucleophilic substitution on activated Csp2-atoms in quinolines OR SNAr >> Nucleophilic substitution on activated Csp2-atoms in quinolines >> Benzoquinoline and Аcridine derivatives OR SNVinyl OR SNVinyl >> SNVinyl at a vinylic (sp2) carbon atom OR SNVinyl >> SNVinyl at a vinylic (sp2) carbon atom >> Vinyl type compounds with electron withdrawing groups  OR SR reaction (peroxidase-activated heterocyclic amines) OR SR reaction (peroxidase-activated heterocyclic amines) >> Direct attack of arylnitrenium radical to the C8 position of nucleoside base OR SR reaction (peroxidase-activated heterocyclic amines) >> Direct attack of arylnitrenium radical to the C8 position of nucleoside base >> Heterocyclic Aromatic Amines by Protein binding by OASIS v1.4

Domain logical expression index: "o"

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

Domain logical expression index: "p"

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 by Protein binding by OECD

Domain logical expression index: "q"

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

Domain logical expression index: "r"

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: "s"

Referential boundary:The target chemical should be classified as AN2 OR AN2 >> Michael addition to the quinoid type structures OR AN2 >> Michael addition to the quinoid type structures >> N-Subsituted Aromatic Amines OR AN2 >> Michael addition to the quinoid type structures >> Substituted Anilines by Protein binding alerts for Chromosomal aberration by OASIS v.1.2

Domain logical expression index: "t"

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: "u"

Referential boundary:The target chemical should be classified as Anthrones OR Aromatic diazo OR Aromatic mono-and dialkylamine OR Heterocyclic Polycyclic Aromatic Hydrocarbons OR Hydrazine OR Nitro-aromatic OR Polycyclic Aromatic Hydrocarbons OR Primary aromatic amine,hydroxyl amine and its derived esters OR Quinones by in vitro mutagenicity (Ames test) alerts by ISS

Domain logical expression index: "v"

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

Domain logical expression index: "w"

Referential boundary:The target chemical should be classified as SN1 OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Primary aromatic amine by DNA binding by OECD

Domain logical expression index: "x"

Parametric boundary:The target chemical should have a value of log Kow which is >= -2.18

Domain logical expression index: "y"

Parametric boundary:The target chemical should have a value of log Kow which is <= -0.889

Conclusions:

5-amino-2-anilinobenzenesulphonic acid failed to induce mutation in Salmonella typhimurium strain TA100 in the presence of S9 metabolic activation system and hence is predicted to not classify as a gene mutant in vitro.

Executive summary:

Gene mutation toxicity was predicted for the test compound 5-amino-2-anilinobenzenesulphonic acid SSS QSAR prediction database, 2016. The study assumed the use of Salmonella typhimurium strain TA100 with S9 metabolic activation system. 5-amino-2-anilinobenzenesulphonic acid failed to induce mutation in Salmonella typhimurium strain TA100 in the presence of S9 metabolic activation system and hence is predicted to not classify as a gene mutant 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 data from read across chemical have been reviewed abd summarized below to determine the mutagenic nature of the target chemical 5-Amino-2-anilinobenzenesulfonic acid:

Gene mutation toxicity was predicted for the test compound 5-amino-2-anilinobenzenesulphonic acid (CAS no 91 -30 -5) SSS QSAR prediction database, 2016. The study assumed the use of Salmonella typhimurium strain TA100 with S9 metabolic activation system. 5-amino-2-anilinobenzenesulphonic acid failed to induce mutation in Salmonella typhimurium strain TA100 in the presence of S9 metabolic activation system and hence is predicted to not classify as a gene mutant in vitro.

Gene mutation toxicity was predicted for the test compound 5-amino-2-anilinobenzenesulphonic acid (CAS no 91 -30 -5) SSS QSAR prediction database, 2016. The study assumed the use of Salmonella typhimurium strain TA1535 without S9 metabolic activation system. 5-amino-2-anilinobenzenesulphonic acid failed to induce mutation in Salmonella typhimurium strain TA1535 in the abesence of S9 metabolic activation system and hence is predicted to not classify as a gene mutant in vitro.

Gene mutation toxicity study was performed by Chung et al (1981) for sodium 4-aminonaphthalene-1-sulphonate (RA CAS no 130 -13 -2) using the Salmonella typhimurium tester strains TA1535, TA1537, TA1538, TA98 and TA100 with and without male rat Aroclor S9 mix in the plate incorporation assay. The read across chemical was dosed at dose value from 5 - 5000 µg/plate. Concurrent vehicle control and appropriate positive controls were also incorporated on the study. Sodium 4-aminonaphthalene-1-sulphonate failed to induce mutation in the Salmonella typhimurium tester strains TA1535, TA1537, TA1538, TA98,or TA100 with and without male rat Aroclor S9 mix and hence is not likely to classify as a gene mutant in vitro.

Gene toxicity in vitro study was performed by Garner and Nutman (1977) on the Salmonella typhimurium TA1538 strain to evaluate the mutagenic effect of the read across material 4-Amino-1-naphthalene sulphonic acid (RA CAS no 84 -86 -6). 4-Amino-1-naphthalene sulphonic acid was used at a concentration of 50 and 100 µg/ plate in the presence and absence of S9 metabolic activation system. The given test material 4-Amino-1-naphthalene sulphonic acid failed to induce mutation in Salmonella typhimurium TA1538 strain with and without S9 metabolic activation system and hence is not likely to classify as a gene mutant in vitro.

Based on the weight of evidence data summarized, 5-Amino-2-anilinobenzenesulfonic acid (CAS no 91 -30 -5) is not likely to classify as a gene mutant in vitro.

Justification for selection of genetic toxicity endpoint

Data is from prediction database

Justification for classification or non-classification

Based on the weight of evidence data summarized, 5-Amino-2-anilinobenzenesulfonic acid (CAS no 91 -30 -5) is not likely to classify as a gene mutant in vitro.