4-[(3-aminobenzoyl)amino]-5-hydroxynaphthalene-1,7-disulphonic acid

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Gene toxicity in vitro: Oral

Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, gene mutation was predicted for 4-[(3-aminobenzoyl)amino]-5-hydroxynaphthalene-1,7-disulfonic acid . 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. 4-[(3-aminobenzoyl)amino] -5-hydroxynaphthalene -1,7- disulfonic acid 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.

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)

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 3.3 and the spporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: Refer below principle

Principles of method if other than guideline:

Prediction is done using OECD QSAR Toolbox version 3.3, 2017

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Specific details on test material used for the study:

- Name of the test material: 4-[(3-aminobenzoyl)amino]-5-hydroxynaphthalene-1,7-disulfonic acid
- IUPAC name: 4-[(3-aminobenzoyl)amino]-5-hydroxynaphthalene-1,7-disulfonic acid
- Molecular formula: C17H14N2O8S2
- Molecular weight: 438.4356 g/mol
- Substance type: Organic

Target gene:

Histidine

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102

Details on mammalian cell type (if applicable):

Not applicable

Additional strain / cell type characteristics:

not specified

Cytokinesis block (if used):

No data

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

Details on test system and experimental conditions:

No data

Rationale for test conditions:

No data

Evaluation criteria:

Prediction is done considering a dose dependent increase in the number of revertants/plate

Statistics:

No data

Species / strain:

S. typhimurium, other: TA 1535, TA 1537, TA 98, TA 100 and TA 102

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:

No data

Remarks on result:

no mutagenic potential (based on QSAR/QSPR prediction)

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" or "f" or "g" or "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 ( not "t") )  )  and ("u" and ( not "v") )  )  and ("w" and "x" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Naphthalene sulfonic acids, condensates by OECD HPV Chemical Categories

Domain logical expression index: "b"

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

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Non-covalent interaction AND Non-covalent interaction >> DNA intercalation AND Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide Side Chain by DNA binding by OASIS v.1.3

Domain logical expression index: "d"

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

Domain logical expression index: "e"

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

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Ester aminolysis AND Acylation >> Ester aminolysis >> Amides by Protein binding by OASIS v1.3

Domain logical expression index: "g"

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 by Protein binding by OECD

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Acid moiety AND Amides AND Anilines (Unhindered) AND Phenol Amines AND Phenols by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Non-covalent interaction AND Non-covalent interaction >> DNA intercalation AND Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide Side Chain by DNA binding by OASIS v.1.3

Domain logical expression index: "j"

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 OR AN2 >> Carbamoylation after isocyanate formation OR AN2 >> Carbamoylation after isocyanate formation >> Hydroxamic Acids 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 to metabolically formed thioketenes OR AN2 >> Nucleophilic addition to metabolically formed thioketenes >> Haloalkene Cysteine S-Conjugates OR AN2 >> Schiff base formation OR AN2 >> Schiff base formation >> Dicarbonyl compounds OR AN2 >> Schiff base formation >> Halofuranones OR AN2 >> Schiff base formation >> Polarized Haloalkene 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 >> Shiff base formation for aldehydes OR AN2 >> Shiff base formation for aldehydes >> Geminal Polyhaloalkane Derivatives OR AN2 >> Thioacylation via nucleophilic addition after cysteine-mediated thioketene formation OR AN2 >> Thioacylation via nucleophilic addition after cysteine-mediated thioketene formation >> Polarized Haloalkene Derivatives OR Michael addition OR Michael addition >> Quinone type compounds OR Michael addition >> Quinone type compounds >> Quinone methides OR No alert found OR Non-covalent interaction >> DNA intercalation >> Acridone, Thioxanthone, Xanthone and Phenazine Derivatives OR Non-covalent interaction >> DNA intercalation >> Amino Anthraquinones OR Non-covalent interaction >> DNA intercalation >> Aminoacridine DNA Intercalators OR Non-covalent interaction >> DNA intercalation >> Coumarins 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 >> 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 >> 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 >> Acridone, Thioxanthone, Xanthone and Phenazine Derivatives OR Radical >> Radical mechanism by ROS formation >> Polynitroarenes OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Amino Anthraquinones 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) >> 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-Hydroxylamines OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitro Azoarenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroaniline Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroarenes with Other Active Groups OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR Radical >> Radical mechanism via ROS formation (indirect) >> p-Aminobiphenyl Analogs OR Radical >> Radical mechanism via ROS formation (indirect) >> p-Substituted Mononitrobenzenes 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 >> DNA bases alkylation by carbenium ion formed OR SN1 >> DNA bases alkylation by carbenium ion formed >> Diazoalkanes 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 diazonium or carbenium ion formation OR SN1 >> Nucleophilic attack after diazonium or carbenium ion formation >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Amino Anthraquinones 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 attack after reduction and nitrenium ion formation >> Fused-Ring Nitroaromatics OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitro Azoarenes OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitroaniline Derivatives OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitroarenes with Other Active Groups 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 >> Polynitroarenes 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 ions OR SN1 >> Nucleophilic substitution on diazonium ions >> Specific Imine and Thione Derivatives OR SN1 >> SN1 reaction at nitrogen-atom bound to a good leaving group or on  nitrenium ion OR SN1 >> SN1 reaction at nitrogen-atom bound to a good leaving group or on  nitrenium ion >> N-Acyloxy(Alkoxy) Arenamides OR SN1 >> SN1 reaction at nitrogen-atom bound to a good leaving group or on  nitrenium ion >> N-Aryl-N-Acetoxy(Benzoyloxy) Acetamides OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> Hydroxamic Acids OR SN2 >> Acylation >> Specific Acetate Esters OR SN2 >> Acylation involving a leaving group  OR SN2 >> Acylation involving a leaving group  >> Geminal Polyhaloalkane Derivatives 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, 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 >> 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 >> DNA alkylation OR SN2 >> DNA alkylation >> Alkylphosphates, Alkylthiophosphates and Alkylphosphonates 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 >> Halofuranones 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 Nitrogen Atom OR SN2 >> SN2 at Nitrogen Atom >> N-acetoxyamines 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 sulfur atom OR SN2 >> SN2 at sulfur atom >> Sulfonyl Halides OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 >> Nitroarenes with Other Active Groups OR SN2 >> SN2 reaction at nitrogen-atom bound to a good leaving group OR SN2 >> SN2 reaction at nitrogen-atom bound to a good leaving group >> N-Acetoxyamines OR SN2 >> SN2 reaction at nitrogen-atom bound to a good leaving group or nitrenium ion OR SN2 >> SN2 reaction at nitrogen-atom bound to a good leaving group or nitrenium ion >> N-Acyloxy(Alkoxy) Arenamides OR SN2 >> SN2 reaction at nitrogen-atom bound to a good leaving group or nitrenium ion >> N-Aryl-N-Acetoxy(Benzoyloxy) Acetamides by DNA binding by OASIS v.1.3

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Ester aminolysis AND Acylation >> Ester aminolysis >> Amides by Protein binding by OASIS v1.3

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Acylation >> Direct acylation involving a leaving group OR Acylation >> Direct acylation involving a leaving group >> Azlactones and unsaturated lactone derivatives  OR Acylation >> Direct acylation involving a leaving group >> N-Acylsulfonamides  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 SN2 OR SN2 >> SN2 reaction at a sulfur atom OR SN2 >> SN2 reaction at a sulfur atom >> Isothiazolidin-3-ones (sulphur) and Isothiazolone derivatives  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 by Protein binding by OASIS v1.3

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Aniline AND Aryl AND Benzamide AND Fused carbocyclic aromatic AND Naphtalene AND Phenol AND Sulfonic acid by Organic Functional groups

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Thiazole/ Isothiazole OR Urea derivatives by Organic Functional groups

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Aniline AND Aryl AND Benzamide AND Fused carbocyclic aromatic AND Naphtalene AND Phenol AND Sulfonic acid by Organic Functional groups

Domain logical expression index: "p"

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

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Aniline AND Aryl AND Benzamide AND Fused carbocyclic aromatic AND Naphtalene AND Phenol AND Sulfonic acid by Organic Functional groups

Domain logical expression index: "r"

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

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Aniline AND Aryl AND Benzamide AND Fused carbocyclic aromatic AND Naphtalene AND Phenol AND Sulfonic acid by Organic Functional groups

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Hydrazo OR Imide OR Isopropyl by Organic Functional groups

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as Aniline AND Aryl AND Benzamide AND Fused carbocyclic aromatic AND Naphtalene AND Phenol AND Sulfonic acid by Organic Functional groups

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as Ether OR Fluorene by Organic Functional groups

Domain logical expression index: "w"

Parametric boundary:The target chemical should have a value of log Kow which is >= -3.37

Domain logical expression index: "x"

Parametric boundary:The target chemical should have a value of log Kow which is <= 0.384

Conclusions:

4-[(3-aminobenzoyl)amino] -5-hydroxynaphthalene -1,7- disulfonic acid 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 3.3 with log kow as the primary descriptor and considering the five closest read across substances, gene mutation was predicted for 4-[(3-aminobenzoyl)amino]-5-hydroxynaphthalene-1,7-disulfonic acid . 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. 4-[(3-aminobenzoyl)amino] -5-hydroxynaphthalene -1,7- disulfonic acid 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

Gene toxicity in vitro: Oral

Prediction model based estimation for the target chemical and data from read across chemicals have been reviewed to determine the mutagenic nature of 4-[(3-aminobenzoyl)amino]-5-hydroxynaphthalene-1,7-disulfonic acid. The studies are as mentioned below:

Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, gene mutation was predicted for 4-[(3-aminobenzoyl)amino]-5-hydroxynaphthalene-1,7-disulfonic acid . 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. 4-[(3-aminobenzoyl)amino] -5-hydroxynaphthalene -1,7- disulfonic acid 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 prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, chromosomal aberration was predicted for 4-[(3-aminobenzoyl)amino]-5-hydroxynaphthalene-1,7-disulfonic acid. The study assumed the use of Chinese hamster ovary (CHO) cell line with and without S9 metabolic activation system. 4-[(3-aminobenzoyl)amino]-5-hydroxynaphthalene-1,7- disulfonic acid 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.

The ability of 4-[(3-aminobenzoyl)amino]-5-hydroxynaphthalene-1,7-disulfonic acid to induce chromosomal aberration was predicted using Chinese hamster ovary cells (CHO) using Danish QSAR database (2017). The end point for chromosome aberrations has been modeled in the Danish QSAR using the three software systems Leadscope, CASE Ultra and SciQSAR. Based on predictions from these three systems, a fourth and overall battery prediction is made. The battery prediction is made using the so called Battery algorithm. With the battery approach it is in many cases possible to reduce “noise” from the individual model estimates and thereby improve accuracy and/or broaden the applicability domain. 4-[(3-aminobenzoyl)amino]-5-hydroxynaphthalene-1,7-disulfonic acid does notinduce chromosome aberrations inChinese hamster ovary cells (CHO)and hence is predicted to not classify as a gene mutant in vitro.

The predicted data is further supported by the data from read across chemicals as mentioned below:

In a mutagenicity test performed by Haveland-Smith et al (Mutation Research, 1979), the mutagenic effect of 50 -60% strcturally and functionally simlar read across chemical Red 2G (RA CAS no 3734 -67 -6; IUPAC name: disodium 5-acetamido-4-hydroxy-3-(phenyldiazenyl)naphthalene-2,7-disulfonate) was evaluated using Salmonella typhimurium strain TA1538 and E. coli WP2 uvrA by the Fluctuation test. The bacteria were exposed to the test compound at the concentration of 10 mg /ml in presence or absence of metabolic activation for strain TA1538 and 10 mg/L (Without S9) and 1, 5 or 10 mg/L (with S9) for strain WP2 uvrA. At the end of the study, the tubes were scored for turbidity. When dyes such as Red 2G was used in this system, it may be impossible to detect the turbidity in the tubes by eye or to use a growth indicator such as bromothymol blue, due to masking by the color. In this case, the presence of viable prototrophic revertants was verified by streaking loopfuls from each tube onto non-supplemented agar. Red 2G did not induce gene mutation in Salmonella typhimurium strain TA1538 and E. coli WP2 uvrA and hence is considered to be negative for gene mutation in vitro.

Rafii et al (Food and chemical toxicology, 1997) performed a gene toxicity test by the plate incorporation method. Salmonella typhimurium Strain- TA98, TA100 were exposed to 50 -60% structrally and functionally similar read across chemical D & C Red No. 33 (RA CAS no 3567 -66 -6; IUPAC name: disodium 5-amino-4-hydroxy-3-(phenyldiazenyl)naphthalene-2,7-disulfonate) in the concentration of 0, 50 or 200 µg/plate with and without metabolic activation. In addition D & C Red No. 33 metabolites were also prepared by treating with azo reductase - producing bacteria namely Clostridium strain isolated from the human gastrointestinal tract. The results showed that there was no evidence of gene toxicity after treatment with D & C Red No. 33 in Salmonella typhimurium Strain- TA98, TA100. Independently of tested D & C Red No. 33 reduced metabolite in the concentration of 0, 50 or 200 µg/plate showed that there was no evidence of gene toxicity. Based on the results observed, D & C Red No. 33 in the concentration of 0, 50 or 200 µg/plate did not show any evidence of gene toxicity when Salmonella typhimurium Strain-TA 98, TA 100 were exposed to the test chemicals.

Based on the data available for the target chemical and its read across, 4-[(3-aminobenzoyl)amino]-5-hydroxynaphthalene-1,7-disulfonic acid does not exhibit gene mutation vitro. Hence the test chemical is not liekly to classify as a gene mutant in vitro.

Justification for classification or non-classification

Based on the data available for the target chemical and its read across, 4-[(3-aminobenzoyl)amino]-5-hydroxynaphthalene-1,7-disulfonic acid (CAS no 70239 -77 -9) does not exhibit gene mutation vitro. Hence the test chemical is not liekly to classify as a gene mutant in vitro.