[7-hydroxy-8-[(2-methoxyphenyl)azo]-2-naphthyl]trimethylammonium chloride

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

The genetic toxicity potential for [7-hydroxy-8-[(2-methoxyphenyl)azo]-2-naphthyl]trimethylammonium chloride is estimated using OECD QSAR toolbox version 3.3 The substance [7-hydroxy-8-[(2-methoxyphenyl)azo]-2-naphthyl]trimethylammonium chloride is estimated to give negative genetic toxicyt results in an Ames test carried out on S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102 with and without metabolic activation.

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)

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.3

GLP compliance:

no

Type of assay:

bacterial reverse mutation assay

Species / strain / cell type:

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

Additional strain / cell type characteristics:

not specified

Metabolic activation:

with and without

Metabolic activation system:

Rat liver S9

Test concentrations with justification for top dose:

not reported

Vehicle / solvent:

water

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

Species / strain:

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

Metabolic activation:

with and 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

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" )  and ("g" and ( not "h") )  )  and "i" )  and "j" )  and ("k" and "l" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Cationic (quaternary ammonium) surfactants by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Ammonium salt AND Aromatic amine AND Aryl AND Azo AND Ether AND Fused carbocyclic aromatic AND Naphtalene AND Phenol by Organic Functional groups

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Aromatic amine AND Aryl AND Azo AND Ether AND Fused carbocyclic aromatic AND Naphtalene AND Overlapping groups AND Phenol by Organic Functional groups (nested)

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Alcohol, olefinic attach [-OH] AND Aliphatic Carbon [CH] AND Aliphatic Carbon [-CH2-] AND Aliphatic Carbon [-CH3] AND Aliphatic Nitrogen, one aromatic attach [-N] AND Aromatic Carbon [C] AND Azo [-N=N-] AND Hydroxy, aromatic attach [-OH] AND Nitrogen, single bonds  [N{v+5}] AND Olefinic carbon [=CH- or =C<] AND Oxygen, one aromatic attach [-O-] by Organic functional groups (US EPA)

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Alkylarylether AND Anion AND Aromatic compound AND Azo compound AND Cation AND Ether AND Hydroxy compound AND Phenol AND Quaternary ammonium salt by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "f"

Similarity boundary:Target: CN{+}(C)(C)(.Cl{-})c1ccc2ccc(O)c(N=Nc3ccccc3OC)c2c1
Threshold=50%,
Dice(Atom pairs)
Atom type; Count H attached; Hybridization

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.3

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Shiff base formation after aldehyde release OR AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> Fused-Ring Primary Aromatic Amines OR Radical OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Fused-Ring Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitro Azoarenes OR SN1 OR SN1 >> Nucleophilic attack after carbenium ion formation 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 metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Fused-Ring Primary Aromatic Amines OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitro Azoarenes OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> Specific Acetate Esters OR SN2 >> Alkylation, direct acting epoxides and related after cyclization OR SN2 >> Alkylation, direct acting epoxides and related after cyclization >> Nitrogen Mustards OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate Esters by DNA binding by OASIS v.1.3

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 High (Class III) by Toxic hazard classification by Cramer (with extensions) ONLY

Domain logical expression index: "k"

Parametric boundary:The target chemical should have a value of log Kow which is >= 1.3

Domain logical expression index: "l"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.55

Conclusions:

Interpretation of results (migrated information):negativeThe substance [7-hydroxy-8-[(2-methoxyphenyl)azo]-2-naphthyl]trimethylammonium chloride is estimated to give negative genetic toxicyt results in an Ames test carried out on S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102 with and without metabolic activation.

Executive summary:

The genetic toxicity potential for [7-hydroxy-8-[(2-methoxyphenyl)azo]-2-naphthyl]trimethylammonium chloride is estimated using OECD QSAR toolbox version 3.3

The substance [7-hydroxy-8-[(2-methoxyphenyl)azo]-2-naphthyl]trimethylammonium chloride is estimated to give negative genetic toxicyt results in an Ames test carried out on S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102 with and without metabolic activation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

Additional information from genetic toxicity in vitro:

Genetic toxicity in vitro

The genetic toxicity potential for [7-hydroxy-8-[(2-methoxyphenyl)azo]-2-naphthyl]trimethylammonium chloride is estimated using OECD QSAR toolbox version 3.3

The substance [7-hydroxy-8-[(2-methoxyphenyl)azo]-2-naphthyl]trimethylammonium chloride is estimated to give negative genetic toxicyt results in an Ames test carried out on S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102 with and without metabolic activation.

Multiple genetic toxicity studies are reported in Scientific Committee on Consumer Safety SCCS - OPINION ON Basic Red 76 (2011). They are summarised as below:

 

Basic Red 76 was investigated for the induction of gene mutations in strains ofSalmonella typhimurium (Ames test).

Salmonella typhimurium TA98, TA100, TA102, TA1535 and TA1537 were used for the AMES assay. DMSO was used as a vehicle. The assay was conducted by plate incorporation as well as pre-incubation method.

In the main tests toxic effects evident as clearing of the bacterial background lawn were observed in experiment I in TA98 and TA100 and in experiment II in all strains predominantly at higher concentrations. Toxic effects evident as a reduction in the number of revertants were observed at higher concentrations without and with metabolic activation in nearly all strains tested. A biologically relevant increase in revertant colonies was not observed in any of the strains tested at any dose level in the absence or presence of S9-mix in both experiments.

Under the experimental conditions used, Basic Red 76 was not mutagenic in this gene mutation tests in bacteria both in the absence and the presence of S9 metabolic activation.

 

In another study, Basic Red 76 was assayed for gene mutations at the tk locus of mouse lymphoma cells both in the absence and presence of S9 metabolic activation.

In both experiments in the absence and presence of S9-mix the appropriate level of toxicity (about 10-20% survival after the highest dose) was reached; only in experiment II in one culture treated with the highest concentration of the test chemical, the appropriate level of toxicity was not reached. Both in the absence and presence of metabolic activation, a biologically relevant increase in the mutant frequency due to exposure to the test chemical was not reported.

Under the experimental conditions used, Basic Red 76 was not mutagenic in this mouse lymphoma assay using the tk locus as reporter gene

 

Basic Red 76 has been investigated in the absence and presence of metabolic activation for the induction of micronuclei in V79 cells.

In experiment I in the absence of S9-mix a biologically relevant increase in cells with micronuclei was not observed. With S9-mix a first experiment (IA) did show a biologically relevant and dose dependent increase in cells with micronuclei but a second confirmatory experiment (IB) did not. In experiment II in the absence and presence of S9-mix biologically relevant increases in cells with micronuclei were observed; in the presence of S9-mix the increase in cells with micronuclei was dose dependent.

Under the experimental conditions used C 008 induced an increase in cells with micronuclei and, consequently, is genotoxic (clastogenic and/or aneugenic) in V79 cells.

 

Opinion of the Scientific Committee on Cosmetic Products and Non-Food Products Intended for Consumers Concerning Basic Red 76 (2003) also reports multiple genetic toxicity studies for the test chemical as below:

Basic Red 76 was investigated for the induction of gene mutations in strains TA98, TA100, TA1535, TA1537, TA 1538of Salmonella typhimurium (Ames test).

Basic Red 76 has induced mutation in the strain TA1537 (with metabolic activation) and in the strain 1538 (in the presence and in the absence of metabolic activation).

Under the test conditions, Basic Red 76 was non-mutagenic in the gene mutation tests in strains TA98, TA100, TA1535 both in the absence and the presence of S9 metabolic activation.

 

Basic Red 76 was investigated for the induction of gene mutations in mammalian cell line. Basic Red 76 has did not induce mutation in the Chinese hamster lung cells V79. Under the test conditions, Basic Red 76 was non mutagenic in the gene mutation tests in V79 cell line both in the absence and the presence of S9 metabolic activation.

 

Basic Red 76 was investigated for the induction of chromosomal aberration in mammalian cell line

Under all conditions C8 was found non-clastogenic, except at the 1000 mg/ml dose, in the absence of S9 mix, which produced a slight but significant increase in the frequency of chromosome aberrations, over the control.

Based on the results, the test chemical can be considered non-mutagenic under all conditions up to 500 mg/ml

Justification for selection of genetic toxicity endpoint
The genetic toxicity potential for [7-hydroxy-8-[(2-methoxyphenyl)azo]-2-naphthyl]trimethylammonium chloride is estimated using OECD QSAR toolbox version 3.3
The substance [7-hydroxy-8-[(2-methoxyphenyl)azo]-2-naphthyl]trimethylammonium chloride is estimated to give negative genetic toxicyt results in an Ames test carried out on S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102 with and without metabolic activation.

Justification for classification or non-classification

On the basis of available data, the substance Basic red 76is not likely to exhibit genetic toxicity and can be classified as 'non-hazardous' as per the CLP classification criteria.