Disodium 4-hydroxynaphthalene-2,7-disulphonate

Endpoint summary

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 2,7-Naphthalenedisulfonic acid, 4-hydroxy-, sodium salt (1:2). 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. 2,7-Naphthalenedisulfonic acid, 4-hydroxy-, sodium salt (1:2) 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 be 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 3.4 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 doen using OECD QSAR Toolbox version 3.4, 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: 2,7-Naphthalenedisulfonic acid, 4-hydroxy-, sodium salt (1:2)
- IUPAC name: 2,7-Naphthalenedisulfonic acid, 4-hydroxy-, sodium salt (1:2)
- Molecular formula: C10H8O7S2.2Na
- Molecular weight: 348.2624 g/mol
- Substance type: Organic
- Smiles: c1cc2c(cc1S(=O)(=O)[O-])cc(cc2O)S(=O)(=O)[O-].[Na+].[Na+]

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:

without

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 11 nearest neighbours
Domain  logical expression:Result: In Domain

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

Domain logical expression index: "a"

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

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Acid moiety AND Phenols AND Salt by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "c"

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

Domain logical expression index: "d"

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 Acylation >> Ring Opening Acylation OR Acylation >> Ring Opening Acylation >> alpha-Lactams OR Michael addition OR Michael addition >> Polarised Alkenes OR Michael addition >> Polarised Alkenes >> Polarised alkene - esters OR Michael addition >> Polarised Alkenes >> Polarised alkene - ketones OR Michael addition >> Polarised Alkenes >> Polarised alkene - nitro 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 >> Epoxides and Related Chemicals OR SN2 >> Epoxides and Related Chemicals >> Epoxides OR SN2 >> SN2 reaction at a sulphur atom OR SN2 >> SN2 reaction at a sulphur atom >> Disulfides OR SN2 >> SN2 reaction at a sulphur atom >> Thiols OR SN2 >> SN2 reaction at sp3 carbon atom OR SN2 >> SN2 reaction at sp3 carbon atom >> Alkyl halides OR SN2 >> SN2 reaction at sp3 carbon atom >> Allyl acetates and related chemicals OR SNAr OR SNAr >> Nucleophilic aromatic substitution OR SNAr >> Nucleophilic aromatic substitution >> Activated halo-benzenes by Protein binding by OECD

Domain logical expression index: "e"

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: "f"

Referential boundary: The target chemical should be classified as 9,10-dihydrophenanthrenes OR Aliphatic halogens OR Alkyl and aryl N-nitroso groups OR Alkyl hydroperoxides OR alpha,beta-unsaturated carbonyls OR 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 OR Xanthones, Thioxanthones, Acridones by in vitro mutagenicity (Ames test) alerts by ISS

Domain logical expression index: "g"

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

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as 1,3-dialkoxy-benzene OR 1-phenoxy-benzene OR Alkyl carbamate and thiocarbamate OR H-acceptor-path3-H-acceptor OR Nitro-aromatic OR Oxolane by in vivo mutagenicity (Micronucleus) alerts by ISS

Domain logical expression index: "i"

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

Domain logical expression index: "j"

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

Domain logical expression index: "k"

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

Domain logical expression index: "l"

Similarity boundary:Target: Oc1cc(S(=O)(=O)O{-}.[Na]{+})cc2cc(S(=O)(=O)O{-}.[Na]{+})ccc12
Threshold=10%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "m"

Similarity boundary:Target: Oc1cc(S(=O)(=O)O{-}.[Na]{+})cc2cc(S(=O)(=O)O{-}.[Na]{+})ccc12
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "n"

Similarity boundary:Target: Oc1cc(S(=O)(=O)O{-}.[Na]{+})cc2cc(S(=O)(=O)O{-}.[Na]{+})ccc12
Threshold=30%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log Kow which is >= -6.34

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of log Kow which is <= -0.464

Conclusions:

2,7-Naphthalenedisulfonic acid, 4-hydroxy-, sodium salt (1:2) 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 for 2,7-Naphthalenedisulfonic acid, 4-hydroxy-, sodium salt (1:2). 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. 2,7-Naphthalenedisulfonic acid, 4-hydroxy-, sodium salt (1:2) 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 be 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 mutation in vitro:

Prediction model based estimation and data from read across chemicals have been reviewed to determine the mutagenic nature of 2,7-Naphthalenedisulfonic acid, 4-hydroxy-, sodium salt (1:2). 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 2,7-Naphthalenedisulfonic acid, 4-hydroxy-, sodium salt (1:2). 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. 2,7-Naphthalenedisulfonic acid, 4-hydroxy-, sodium salt (1:2) 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.

Gene mutation toxicity was predicted for 2,7-Naphthalenedisulfonic acid, 4-hydroxy-, sodium salt (1:2) using the battery approach from Danish QSAR database (2017). The study assumed the use of Salmonella typhimurium bacteria in the Ames test. The end point for gene mutation 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. Gene mutation toxicity study as predicted by Danish QSAR for(2,7-Naphthalenedisulfonic acid, 4-hydroxy-, sodium salt (1:2)is negative and hence the chemical is predicted to not classify as a gene mutant in vitro.

The ability of 2,7-Naphthalenedisulfonic acid, 4-hydroxy-, sodium salt (1:2) to induce chromosomal aberration was predicted using Chinese hamster ovary (CHO) cells 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. 2,7-Naphthalenedisulfonic acid, 4-hydroxy-, sodium salt (1:2) does notinduce chromosome aberrations in Chinese hamster ovary (CHO) cells and hence is predicted to not classify as a gene mutant in vitro.

In a study for read across chemical, Gene mutation toxicity study was performed by Chung et al (Applied and Environmental Microbiology, 1981) to determine the mutagenic nature 90 -100% structurally and functionally similar read across chemical of R salt (RA CAS no 135 -51 -3, IUPAC name: disodium 3-hydroxynaphthalene-2,7-disulfonate). The study was performed by the standard plate incorporation assay and the preincubation method using Salmonella typhimurium strains TA1535, TA1537, TA1538, TA98, and TA100 with and without S9 metabolic activation system. Also, the liquid preincubation assays were timed for 30 min at 37°C in a Dri-block. The test chemical was dissolved in DMSO and upto a maximum nontoxic dose of 5000 µg/plate for plate incorporation assay and 1000 µg/plate for preincubation assay. Concurrent solvent and positive controls were also included in the study.R salt did not induce gene mutation in Salmonella typhimurium strains TA1535, TA1537, TA1538, TA98, and TA100 in the presence and absence of S9 metabolic activation system and hence it is not likely to classify as a gene mutant in vitro.

Acid orange 10 (RA CAS no 1936 -15 -8; IUPAC name: 7-hydroxy-8-(phenyldiazenyl)naphthalene-1,3-disulfonate) was studied by Zeiger et al (Environmental and Molecular Mutagenesis, 1988) for its ability to induce mutations in strains of Salmonella typhimurium. The test compound was dissolved in water and was tested at concentration of 0, 100, 333, 1000, 3333, 10000 µg/plate using Salmonella typhimurium TA100, TA1535, 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. Acid orange 10 is not mutagenic to the Salmonella typhimurium TA100, TA1535, TA97 and TA98 in the presence and absence of rat and hamster liver S9 metabolic activation system.

Based on the data available for the target chemical and its read across, 2,7-Naphthalenedisulfonic acid, 4-hydroxy-, sodium salt (1:2) does not exhibit gene mutation in vitro. Hence the test chemical is not likely to classify as a gene mutant as per the criteria mentioned in CLP regulation.

Justification for classification or non-classification

Based on the data available for the target chemical and its read across, 2,7-Naphthalenedisulfonic acid, 4-hydroxy-, sodium salt (1:2) (CAS no 20349 -39 -7) does not exhibit gene mutation in vitro. Hence the test chemical is not likely to classify as a gene mutant as per the criteria mentioned in CLP regulation.