Disodium [6-amino-5-[(2-hydroxy-4-nitrophenyl)azo]-N-methylnaphthalene-2-sulphonamidato(2-)][6-amino-5-[(2-hydroxy-4-nitrophenyl)azo]naphthalene-2-sulphonato(3-)]cobaltate(2-)

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 3.3 with log kow as the primary descriptor and considering the five closest read across substances, gene mutation was predicted for Disodium [6-amino-5-[(2-hydroxy-4-nitrophenyl)azo]- N-methylnaphthalene-2-sulphonamidato(2-)] [6-amino-5- [(2-hydroxy-4-nitrophenyl) azo]naphthalene-2-sulphonato(3-)]cobaltate(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. Disodium [6-amino-5-[(2-hydroxy-4-nitrophenyl)azo] -N-methylnaphthalene-2-sulphonamidato (2-)] [6-amino-5- [(2-hydroxy-4-nitrophenyl) azo]naphthalene-2-sulphonato(3-)]cobaltate(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 3.3 and the supporting 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, 2018

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Specific details on test material used for the study:

- Name of test material: Disodium [6-amino-5-[(2-hydroxy-4-nitrophenyl)azo]-N-methylnaphthalene-2-sulphonamidato(2-)] [6-amino-5- [(2-hydroxy-4-nitrophenyl) azo]naphthalene-2-sulphonato(3-)]cobaltate(2-)
- IUPAC name: Disodium [6-amino-5-[(2-hydroxy-4-nitrophenyl)azo]-N-methylnaphthalene-2-sulphonamidato(2-)][6-amino-5-[(2-hydroxy-4-nitrophenyl) azo]naphthalene-2-sulphonato(3-)]cobaltate(2-)
- Molecular formula: C33H22CoN9O11S2. 2 Na
- Molecular weight: 890 g/mol
- Smiles :Cc1cc(N(=O)=O)c2c(c1)N=N1c3c4ccc(S(O)(=O)=O)cc4ccc3N[Co]{2+}113(Nc4ccc5cc(S(=O)(=O)N C)ccc5c4N1=Nc1ccc(N(=O)=O) cc1O{-}.3).O{-}2Na
- Substance type: Organic
- Physical state: Solid

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 and 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:

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 6 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 ( not "j") )  )  and ("k" and "l" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Radical OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Diazenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitro Azoarenes OR SN1 OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitro Azoarenes by DNA binding by OASIS v.1.3 ONLY

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as SN1 OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Aromatic azo OR SN1 >> Nitrenium Ion formation >> Aromatic nitro by DNA binding by OECD ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Aromatic azo AND SN1 >> Nitrenium Ion formation >> Aromatic nitro by DNA binding by OECD

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as No alert found OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine by DNA binding by OECD

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Non binder, MW>500 by Estrogen Receptor Binding

Domain logical expression index: "f"

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, without OH or NH2 group OR Strong binder, 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: "g"

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

Domain logical expression index: "h"

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 - ketones OR Michael addition >> Quinones and Quinone-type Chemicals OR Michael addition >> Quinones and Quinone-type Chemicals >> Quinone-imine OR SN2 OR SN2 >> SN2 reaction at sp3 carbon atom OR SN2 >> SN2 reaction at sp3 carbon atom >> Alkyl diazo by Protein binding by OECD

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Inclusion rules not met by Eye irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Organic sulphonic salts by Eye irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "k"

Parametric boundary:The target chemical should have a value of Molecular weight which is >= 757 Da

Domain logical expression index: "l"

Parametric boundary:The target chemical should have a value of Molecular weight which is <= 931 Da

Conclusions:

Disodium [6-amino-5-[(2-hydroxy-4-nitrophenyl)azo] -N-methylnaphthalene-2-sulphonamidato (2-)] [6-amino-5- [(2-hydroxy-4-nitrophenyl) azo]naphthalene-2-sulphonato(3-)]cobaltate(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 3.3 with log kow as the primary descriptor and considering the five closest read across substances, gene mutation was predicted for Disodium [6-amino-5-[(2-hydroxy-4-nitrophenyl)azo]- N-methylnaphthalene-2-sulphonamidato(2-)] [6-amino-5- [(2-hydroxy-4-nitrophenyl) azo]naphthalene-2-sulphonato(3-)]cobaltate(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. Disodium [6-amino-5-[(2-hydroxy-4-nitrophenyl)azo] -N-methylnaphthalene-2-sulphonamidato (2-)] [6-amino-5- [(2-hydroxy-4-nitrophenyl) azo]naphthalene-2-sulphonato(3-)]cobaltate(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 for the target chemical and data from read across chemicals has been reviewed to determine the mutagenic nature of Disodium [6-amino-5-[(2-hydroxy-4-nitrophenyl)azo]- N-methylnaphthalene-2-sulphonamidato(2-)] [6-amino-5- [(2-hydroxy-4-nitrophenyl) azo]naphthalene-2-sulphonato(3-)]cobaltate(2-). The studies are as mentoned 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 Disodium [6-amino-5-[(2-hydroxy-4-nitrophenyl)azo]- N-methylnaphthalene-2-sulphonamidato(2-)] [6-amino-5- [(2-hydroxy-4-nitrophenyl) azo]naphthalene-2-sulphonato(3-)]cobaltate(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. Disodium [6-amino-5-[(2-hydroxy-4-nitrophenyl)azo] -N-methylnaphthalene-2-sulphonamidato (2-)] [6-amino-5- [(2-hydroxy-4-nitrophenyl) azo]naphthalene-2-sulphonato(3-)]cobaltate(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.

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

Gene mutation toxicity study was performed by Muzall and Cook (Mutation Research, 1977) to determine the mutagenic nature of structurally and functionally similar FD and C red no 4 (RA CAS no 25956 -17 -6). The study was performed as per the plate incorporation assay using Salmonella typhimurium strain TA98, TA1537, TA100, TA1535 with and without S9 metabolic activation system. The 2 ml of liquid top agar was cooled to 45°C and 0.1 ml of a broth cultureof microorganism and test substance in volumes of ≤0.4 ml of DMSO was added prior to placing on minimal agar plates. The plates were incubated for 48 h at 37°C and the colonies which reverted to the prototroph were counted and compared to counts on the control plate (containing no test substance) to demonstrate mutagenicity or toxicity. Materials which caused a 2-fold increase of revertants, as compared to the number of spontaneous revertants on the control plates, were denoted as mutagens. Those which reduced the number of revertants were considered inhibitory. FD and C red no 40 did not result in a 2-fold increase in the number of revertants as compared to the number of spontaneous revertants on the control plates in Salmonella typhimurium strain TA98, TA1537, TA100, TA1535 in the presence and absence of S9 metabolic activation system and hence is not likely to classify as a gene mutant in vitro.

In another study by Garner and Nutman (Mutation Research, 1977) gene toxicity in vitro study on Salmonella typhimurium TA 1538 strain to evaluate the mutagenic effect of strcuturally and functionally similar read across chemical Sunset yellow (RA CAS no 2783 -94 -0). The test chemical was dissolved in DMSO and was used at a concentration of 50 and 100 µg/ plate in the presence and absence of S9 metabolic activation system. Concurrent solvent and negative control chemicals were also ncluded in the study. Sunset yellow did not induce gene mutation in Salmonella typhimurium TA 1538 strain with and without S9 metabolic activation system and hence is not likely to classify as a gene mutant in vitro.

Based on the data available for the target chemical and its read across, Disodium [6-amino-5-[(2-hydroxy-4-nitrophenyl)azo]- N-methylnaphthalene-2-sulphonamidato(2-)] [6-amino-5- [(2-hydroxy-4-nitrophenyl) azo]naphthalene-2-sulphonato(3-)]cobaltate(2-) does not exhibit gene mutation in vtro. 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, Disodium [6-amino-5-[(2-hydroxy-4-nitrophenyl)azo]- N-methylnaphthalene-2-sulphonamidato(2-)] [6-amino-5- [(2-hydroxy-4-nitrophenyl) azo]naphthalene-2-sulphonato(3-)]cobaltate(2-) (CAS no 75314 -27 -1) does not exhibit gene mutation in vtro. Hence the test chemical is not likely to classify as a gene mutant as per the criteria mentioned in CLP regulation.