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Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information
The test compound Aluminum, tris(5-amino-4-hydroxy-3-(2-phenyldiazenyl)-2,7-naphthalenedisulfonato(2-))di- (CAS no 68475-50-3) 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
Reference:
Composition 0
Qualifier:
according to
Guideline:
other:
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
Test material information:
Composition 1
Target gene:
No data
Species / strain:
S. typhimurium TA 100
Details on mammalian cell lines (if applicable):
Not applicable
Additional strain characteristics:
not specified
Metabolic activation:
with
Metabolic activation system:
S9 metabolic activation system
Test concentrations with justification for top dose:
No data
Vehicle:
No data
Negative controls:
not specified
Solvent controls:
not specified
True negative controls:
not specified
Positive controls:
not specified
Positive control substance:
not specified
Remarks:
No data
Details on test system and conditions:
No data
Evaluation criteria:
No data
Statistics:
No data
Species / strain:
S. typhimurium TA 100
Metabolic activation:
with
Genotoxicity:
negative
Cytotoxicity:
not specified
Vehicle controls valid:
not specified
Negative controls valid:
not specified
Positive controls valid:
not specified
Remarks on result:
other: strain/cell type:
Remarks:
Migrated from field 'Test system'.
Additional information on results:
No data

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" )  and ("f" and ( not "g") )  )  and ("h" and ( not "i") )  )  and "j" )  and "k" )  and ("l" and ( not "m") )  )  and "n" )  and "o" )  and ("p" and ( not "q") )  )  and ("r" and "s" )  )

Domain logical expression index: "a"

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

Domain logical expression index: "b"

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

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Aniline AND Aryl AND Azo AND Fused carbocyclic aromatic AND Naphtalene AND Overlapping groups AND Phenol AND Sulfonic acid 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 Nitrogen, one aromatic attach [-N] AND Aromatic Carbon [C] AND Azo [-N=N-] AND Hydroxy, aromatic attach [-OH] AND Hydroxy, sulfur attach [-OH] AND Miscellaneous sulfide (=S) or oxide (=O) AND Olefinic carbon [=CH- or =C<] AND Oxygen, one aromatic attach [-O-] AND Suflur {v+4} or {v+6} AND Sulfinic acid [-S(=O)OH] AND Sulfonate, aromatic attach [-SO2-O] by Organic functional groups (US EPA)

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Amine AND Aromatic compound AND Azo compound AND Hydroxy compound AND Phenol AND Primary amine AND Primary aromatic amine AND Sulfonic acid AND Sulfonic acid derivative by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "f"

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

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Michael addition OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Alkyl phenols OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Arenes OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Hydroquinones OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Polycyclic (PAHs) and heterocyclic (HACs) aromatic hydrocarbons-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated ketones OR Michael addition >> Quinones and Quinone-type Chemicals OR Michael addition >> Quinones and Quinone-type Chemicals >> Quinones OR SN1 OR SN1 >> Carbenium Ion Formation OR SN1 >> Carbenium Ion Formation >> Hydrazine OR SN1 >> Carbenium Ion Formation >> Polycyclic (PAHs) and heterocyclic (HACs) aromatic hydrocarbons-SN1 OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Aromatic azo OR SN1 >> Nitrenium Ion formation >> Aromatic nitro OR SN1 >> Nitrenium Ion formation >> Aromatic phenylureas OR SN1 >> Nitrenium Ion formation >> Primary aromatic amine OR SN1 >> Nitrenium Ion formation >> Secondary aromatic amine OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine by DNA binding by OECD

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as AN2 AND AN2 >> Michael-type addition to quinoid structures  AND AN2 >> Michael-type addition to quinoid structures  >> Substituted Anilines by Protein binding by OASIS v1.4

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Acylation involving an activated (glucuronidated) carboxamide group OR Acylation >> Acylation involving an activated (glucuronidated) carboxamide group >> Carboxylic Acid Amides OR Acylation >> Direct acylation involving a leaving group OR Acylation >> Direct acylation involving a leaving group >> Carboxylic Acid Amides OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Amides OR AN2 >> Michael-type addition to quinoid structures  >> Carboxylic Acid Amides OR AN2 >> Michael-type addition to quinoid structures  >> N-Substituted Aromatic Amines OR Michael addition OR Michael addition >> Michae addition on quinoide type compounds OR Michael addition >> Michae addition on quinoide type compounds >> Quinone methide(s)/imines; Quinoide oxime structure; Nitroquinones, Naphthoquinone(s)/imines  OR No alert found OR Schiff base formation OR Schiff base formation >> Schiff base formation with carbonyl compounds OR Schiff base formation >> Schiff base formation with carbonyl compounds >> Aromatic carbonyl compounds by Protein binding by OASIS v1.4

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as No superfragment by Superfragments ONLY

Domain logical expression index: "k"

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

Domain logical expression index: "l"

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

Domain logical expression index: "m"

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

Domain logical expression index: "n"

Similarity boundary:Target: Nc1cc(S(O)(=O)=O)cc2cc(S(O)(=O)=O)c(N=Nc3ccccc3)c(O)c12
Threshold=10%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "o"

Similarity boundary:Target: Nc1cc(S(O)(=O)=O)cc2cc(S(O)(=O)=O)c(N=Nc3ccccc3)c(O)c12
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Aromatic diazo AND H-acceptor-path3-H-acceptor by in vivo mutagenicity (Micronucleus) alerts by ISS

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as No alert found OR Primary aromatic amine, hydroxyl amine and its derived esters OR Quinones by in vivo mutagenicity (Micronucleus) alerts by ISS

Domain logical expression index: "r"

Parametric boundary:The target chemical should have a value of log Kow which is >= -0.864

Domain logical expression index: "s"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.75

Conclusions:
Interpretation of results (migrated information):negative with metabolic activationThe test compound Aluminum, tris(5-amino-4-hydroxy-3-(2-phenyldiazenyl)-2,7-naphthalenedisulfonato(2-))di- failed to induce mutation in the Salmonell typhimurium strain TA100 in the presence of S9 metabolic cativation system and hence is not likely to classify as a gene mutant in vitro.
Executive summary:
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Gene mutation toxicity (Ames assay) was predicted for the test compound Aluminum, tris(5-amino-4-hydroxy-3-(2-phenyldiazenyl)- 2,7-naphthalenedisulfonato(2-))di using SSS QSAR prediction database, 2016. The study assumed the use of Salmonell typhimurium strain TA100 in the presence of S9 metabolic cativation system. The test compound Aluminum, tris(5-amino-4-hydroxy-3 -(2-phenyldiazenyl)-2,7-naphthalenedisulfonato(2-))di failed to induce mutation in the Salmonella typhimurium strain TA100 in the presence of S9 metabolic cativation system and hence is not likely to classify as a gene mutant in vitro.

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 and data from read across are used to determine the mutagenic nature of the test compoundAluminum, tris(5-amino-4-hydroxy-3-(2-phenyldiazenyl)-2,7-naphthalenedisulfonato(2-))di-(CAS no 68475-50-3). The summary is as mentioned below:

Gene mutation toxicity (Ames assay) was predicted for the test compound Aluminum, tris(5-amino-4-hydroxy-3-(2-phenyldiazenyl)- 2,7-naphthalenedisulfonato(2-))di (CAS no 68475 -50 -3) using SSS QSAR prediction database, 2016. The study assumed the use of Salmonell typhimurium strain TA100 in the presence of S9 metabolic cativation system. The test compound Aluminum, tris(5-amino-4-hydroxy-3 -(2-phenyldiazenyl)-2,7-naphthalenedisulfonato(2-))di failed to induce mutation in the Salmonella typhimurium strain TA100 in the presence of S9 metabolic cativation system and hence is not likely to classify as a gene mutant in vitro.

Gene mutation toxicity (Ames assay) was predicted for the test compound Aluminum, tris(5-amino-4-hydroxy-3-(2-phenyldiazenyl)- 2,7-naphthalenedisulfonato(2-))di (CAS no 68475 -50 -3) using SSS QSAR prediction database, 2016. The study assumed the use of Salmonell typhimurium strain TA1535 in the absence of S9 metabolic cativation system. The test compound Aluminum, tris(5-amino-4-hydroxy-3 -(2-phenyldiazenyl)-2,7-naphthalenedisulfonato(2-))di failed to induce mutation in the Salmonella typhimurium strain TA1535 in the absence of S9 metabolic cativation system and hence is not likely to classify as a gene mutant in vitro.

In a gene toxicity test, Salmonella typhimurium Strain TA 98 and TA 100 were exposed to D&C Red No. 33 (RA CAS no 3567-66-6) in the concentration of 50 and 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 the concentration of 50 and 200 µg/plate in Salmonella typhimurium Strain TA 98, TA 100. Independently of tested D&C Red No. 33 reduced metabolite in the concentration of 50 and 200 µg/plate showed that there was no evidence of gene toxicity. Therefore, it is considered that D&C Red No. 33 and its reduced metabolites in the concentration of 50 and 200 µg/plate do not cause genetic mutation(s) when Salmonella typhimurium Strain-TA 98 and TA 100 are exposed to the test chemical in the presence and absence of metabolic activation (S9). Hence the test chemical is not likely to be gene mutant in vitro.

 

Gene mutation study was performed by Wuebbles et al (1985) to evaluate the mutagenic nature of the test compound Coumarin 30 (RA CAS no 41044-12-6) using Salmonella typhimurium strain TA1538, TA98 and TA100 with and without S9 metabolic activation system. Bacteria were grown overnight in Oxoid nutrient broth, then refrigerated at 4-5OC for a few hours before use. 0.1 ml of bacterial culture was added to 2 ml of 45°C molten top agar containing 0.01 mg histidine HCI and 0.012 mg biotin/ml, followed by the test sample in ≤0.2 ml DMSO. Finally, 0.5 ml of sodium phosphate buffer, pH 7.4 (no activation), or 0.5 ml of Aroclor-induced rat S9 mixture was added, and the mixture was poured on minimal glucose agar plates. Histidine revertant colonies were counted on a Biotran II automated colony counter after a 2-day incubation at 37°C. A sample was judged mutagenic if it produced greater than twice the spontaneous background colonies at more than one dose or at the highest dose tested. In the above mentioned study, coumarin 30, the test material failed to induce gene mutation in the Salmonella typhimurium strains TA1538, TA98 and TA100 with and without metabolic activation. Hence the given test material, Coumarin 30, is not likely to be a gene mutant in vitro.

Mutagenicity testing of Sodium naphthionate (RA CAS no 130 -13 -2) was performed using the Salmonella-microsome mutagenicity test developed by Ames et al. The test compound was tested at five concentrations from 5 to 5,000 µg. Plate incorporation method was performed to determine the mutagenic effect. The test compound Sodium naphthionate is not mutagenic to the Salmonella typhimurium TA1535, TA1537, TA1538, TA98 and TA100 in the presence and absence of S9 activation system. Thus the chemical is not likely to be classified as a gene mutant.

Based on the weight of evidence data summarized, the test chemical Aluminum, tris(5-amino-4-hydroxy-3-(2-phenyldiazenyl)-2,7-naphthalenedisulfonato(2-))di- 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 Aluminum, tris(5-amino-4-hydroxy-3-(2-phenyldiazenyl)- 2,7-naphthalenedisulfonato(2-))di- is not likely to be a gene mutant in vitro.