7-[[2-[(aminocarbonyl)amino]-4-[[4-chloro-6-[[4-[vinylsulphonyl]phenyl]amino]-1,3,5-triazin-2-yl]amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid, sodium salt

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

The test compound 7-[[2-[(aminocarbonyl)amino]-4-[[4 -chloro-6-[[4-[vinylsulphonyl]phenyl]amino]-1,3,5-triazin-2-yl]amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid, sodium salt is not likely to be a gene mutant 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)

Rationale for reliability incl. deficiencies:

other: Data is from prediction database

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

Qualifier:

according to guideline

Guideline:

other: as mentioned below

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

Target gene:

No data

Species / strain / cell type:

S. typhimurium TA 100

Details on mammalian cell type (if applicable):

Not applicable

Additional strain / cell type characteristics:

not specified

Metabolic activation:

with

Metabolic activation system:

S9 mix

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

Evaluation criteria:

Increase in the number of revertants were noted

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:

No data

Remarks on result:

other: all strains/cell types tested

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 5 nearest neighbours
Domain  logical expression:Result: In Domain

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

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Moderate reactive AND Moderate reactive >> Activated 1,3,5-triazine derivatives AND Not possible to classify according to these rules by DPRA Cysteine peptide depletion

Domain logical expression index: "b"

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

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Moderate reactive AND Moderate reactive >> Activated 1,3,5-triazine derivatives by DPRA Cysteine peptide depletion

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as High reactive AND High reactive >> Activated 1,3,5-triazine derivatives by DPRA Lysine peptide depletion

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Michael addition AND Michael addition >> Michael addition on polarised Alkenes AND Michael addition >> Michael addition on polarised Alkenes >> Polarised Alkenes - sulfones  AND SNAr AND SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds AND SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds >> Activated aryl and heteroaryl compounds by Protein binding by OASIS v1.4

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Michael addition AND Michael addition >> Polarised Alkenes AND Michael addition >> Polarised Alkenes >> Polarised alkene - sulfinyl AND Michael addition >> Polarised Alkenes >> Polarised alkene - sulfone AND SNAr AND SNAr >> Nucleophilic aromatic substitution AND SNAr >> Nucleophilic aromatic substitution >> Halo-triazines by Protein binding by OECD

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Highly reactive (GSH) AND Highly reactive (GSH) >> Phenyl vinyl sulfone (MA) by Protein binding potency

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.4

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as AN2 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 Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide and Aminoalkylamine Side Chain OR Radical OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Geminal Polyhaloalkane Derivatives OR SN2 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 >> Direct acting epoxides formed after metabolic activation OR SN2 >> Direct acting epoxides formed after metabolic activation >> Quinoline Derivatives 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 by DNA binding by OASIS v.1.4

Domain logical expression index: "j"

Similarity boundary:Target: C=CS(=O)(=O)c1ccc(Nc2nc(Nc3ccc(N=Nc4cc5c(cc4S(O)(=O)=O)cc(S(O)(=O)=O)cc5S(O)(=O)=O)c(NC(N)=O)c3)nc(Cl)n2)cc1
Threshold=30%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "k"

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

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Hydroxyazo form - 1,5-H shift by Tautomers unstable

Domain logical expression index: "m"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.407

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.14

Conclusions:

Interpretation of results:
negative with metabolic activation

The test result for 7-[[2-[(aminocarbonyl)amino]-4-[[4-chloro-6-[[4-[vinylsulphonyl]phenyl]amino]-1,3,5-triazin-2-yl]amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid, sodium salt was estimated to be negative (with) in S. typhimurium TA 100.

Executive summary:

Gene mutation toxicity study was performed for the test compound using SSS QSAR prediction database, 2016. The study assumed the use of S. typhiurium strain TA100 with metabolic actovation system. The test result for 7-[[2-[(aminocarbonyl)amino]-4-[[4 -chloro-6-[[4-[vinylsulphonyl]phenyl]amino]-1,3,5-triazin-2-yl]amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid, sodium salt was estimated to be negative (with) in S. typhimurium TA 100.

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 for the target chemical and data from read across have been has been used to determine the mutagenic potential of the test compound. The summary is as mentioned below:

Gene mutation toxicity study was performed for the test compound CAS no 94158 -80 -2 using SSS QSAR prediction database, 2016. The study assumed the use of S. typhiurium strain TA100 with metabolic actovation system. The test result for 7-[[2-[(aminocarbonyl)amino]-4-[[4 -chloro-6-[[4-[vinylsulphonyl]phenyl]amino]-1,3,5-triazin-2-yl]amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid, sodium salt was estimated to be negative (with) in S. typhimurium TA 100.

Gene mutation toxicity study was performed for the test compound CAS no 94158 -80 -2 using SSS QSAR prediction database, 2016. The study assumed the use of S. typhiurium strain TA1535 without metabolic activation system. The test result for 7-[[2-[(aminocarbonyl)amino]-4-[[4 -chloro-6-[[4-[vinylsulphonyl]phenyl]amino]-1,3,5-triazin-2-yl]amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid, sodium salt was estimated to be negative (with) in S. typhimurium TA 1535.

Based on the QSAR prediction done using the Danish (Q)SAR Database, 2016, the genetic toxicity was estimated to be negative on S. typhimurium TA 1535, TA 1537, TA 98 and TA 100 for 7-[[2-[(aminocarbonyl)amino]-4-[[4-chloro-6-[[4-[vinylsulphonyl]phenyl]amino]-1,3,5-triazin-2-yl] amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid, sodium salt (CAS no 94158 -80 -2) in an Ames test.

Based on the QSAR prediction done using the Danish (Q)SAR Database, the genetic toxicity by chromosome aberration was estimated to be negative on Chinese hamster Ovary (CHO) for 7-[[2-[(aminocarbonyl)amino]-4-[[4-chloro-6-[[4-[vinylsulphonyl]phenyl]amino]-1,3,5-triazin-2-yl] amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid, sodium salt (CAS no 94158 -80 -2).

Ames mutagenicity test was conducted by Seifried et al (2006) for chemical C. I. direct red 80 (RA CAS no 2610 -10 -8) to evaluate its genetoxic effects when exposed to Salmonella typhimurium strains TA98, TA100, TA1535, TA1537, and TA1538 with dose concentration of 333-10000 µg/plate in plate incorporation assay. Based on the preliminary study conducted, the test compound was used at a five dose level from 333- 10000 µg/plate. The test compound C. I. direct red 80 failed to induce mutation in theSalmonella typhirium TA98, TA100, TA1535, TA1537, and TA1538 both in the presence and absence of S9 activation system and hence is not likely to be a gene mutant..

In the same study by Seifried et al (2006), The gene mutation study was conducted according to L5178Y TK+/-Mouse Lymphoma Mutagenicity Assay to determine the mutagenic nature of the test compound C.I. direct red 80 (RA CAS no 2610 -10 -8). The Cells at a concentration of 6 X 10⁵/mL (6 X10⁶cells total) were exposed for 4 h to a range of concentrations from2429-5000µg/mL. The cells were then washed, resuspended in growth medium, and incubated at 37°C for 48 h. The rate of cell growth was determined for each of the treated cultures and compared to the rate of growth of the solvent controls.Results were interpreted using a doubling of the mutant frequency over the concurrent solvent-treated control value as an indication of a positive effect, together with evidence of a dose-related increase. The test chemical C.I. direct red 80 failed to induce a doubling of the mutant frequency both in the presence and absence of S9 activation system and hence is not likely to be gene mutant in vitro

Based on the weight of evidence data summarized, the test chemical

7-[[2-[(aminocarbonyl)amino]-4-[[4-chloro-6-[[4-[vinylsulphonyl]phenyl]amino]-1,3,5-triazin-2-yl] amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid, sodium salt is not likely to be 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, the test chemical

7-[[2-[(aminocarbonyl)amino]-4-[[4-chloro-6-[[4-[vinylsulphonyl]phenyl]amino]-1,3,5-triazin-2-yl] amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid, sodium salt is not likely to be a gene mutant in vitro.