Aluminium, 2-(1,3-dihydro-3-oxo-5-sulfo-2H-indol-2-ylidene)-2,3-dihydro-3-oxo-1H-indole-5-sulfonic acid complex

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

FD and C blue no.2 was estimated to be non mutagenic in bacterial reverse mutation assay

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 QSAR Toolbox version 3.3

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

Qualifier:

according to guideline

Guideline:

other: Prediction is done using QSAR Toolbox version 3.3

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:

Salmonella typhimurium

Species / strain / cell type:

other: TA1535,TA 1537

Details on mammalian cell type (if applicable):

Not applicable

Additional strain / cell type characteristics:

not specified

Metabolic activation:

with and without

Metabolic activation system:

No data

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

Remarks:

Nodeatils available

Details on test system and experimental conditions:

No data

Evaluation criteria:

No data

Statistics:

No data

Species / strain:

other: TA 1535,TA 1537

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" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as (!Undefined)Aluminum Compounds AND Neutral Organics by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as (!Undefined)Aluminum Compounds OR Neutral Organics by US-EPA New Chemical Categories

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Aryl AND Cycloketone AND Diketone AND Fused carbocyclic aromatic AND Fused saturated heterocycles AND Indoline AND No functional group found AND Sulfonic acid by Organic Functional groups

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Diketone AND Fused carbocyclic aromatic AND Fused saturated heterocycles AND Indoline AND No functional group found AND Overlapping groups AND Sulfonic acid by Organic Functional groups (nested)

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Aliphatic Nitrogen, one aromatic attach [-N] AND Alpha,beta-unsaturated carbonyl compound [C=C(N)C(=O)] AND Aluminium [Al] AND Aromatic Carbon [C] AND Carbonyl, olefinic attach [-C(=O)-] AND Carbonyl, one aromatic attach [-C(=O)-] AND Hydroxy, sulfur attach [-OH] AND Ketone in a ring, olefinic aromatic attach AND Miscellaneous sulfide (=S) or oxide (=O) AND Nitrogen, two or tree olefinic attach [>N-] AND Olefinic carbon [=CH- or =C<] 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: "f"

Referential boundary: The target chemical should be classified as Aromatic compound AND Cation AND Heterocyclic compound AND Sulfonic acid AND Sulfonic acid derivative by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as No alert found by Protein binding by OASIS v1.3

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 >> Azlactones and unsaturated lactone derivatives  OR Acylation >> Direct acylation involving a leaving group >> Carbamates  OR Acylation >> Direct acylation involving a leaving group >> N-Acylsulfonamides  OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Amides OR Michael Addition OR Michael Addition >> alpha,beta-Unsaturated carbonyl compounds OR Michael Addition >> alpha,beta-Unsaturated carbonyl compounds >> Lactones OR Michael Addition >> Michael addition on conjugated systems with electron withdrawing group OR Michael Addition >> Michael addition on conjugated systems with electron withdrawing group >> Activated electrophilic ethenylarenes  OR Michael Addition >> Michael addition on conjugated systems with electron withdrawing group >> alpha,beta-Carbonyl compounds with polarized double bonds  OR Michael Addition >> Michael addition on conjugated systems with electron withdrawing group >> Cyanoalkenes OR Michael Addition >> Michael addition on conjugated systems with electron withdrawing group >> Nitroalkenes OR Michael Addition >> Michael type addition on azoxy compounds OR Michael Addition >> Michael type addition on azoxy compounds >> Azoxy compounds  OR Michael Addition >> Quinoide type compounds OR Michael Addition >> Quinoide type compounds >> Quinone methide(s)/imines; Quinoide oxime structure; Nitroquinones, Naphthoquinone(s)/imines  OR Nucleophilic addition OR Nucleophilic addition >> Addition to carbon-hetero double bonds OR Nucleophilic addition >> Addition to carbon-hetero double bonds >> Ketones OR Nucleophilic addition >> Nucleophilic addition reaction at polarized N-functional double bond OR Nucleophilic addition >> Nucleophilic addition reaction at polarized N-functional double bond >> C-Nitroso compounds  OR Schiff base formation OR Schiff base formation >> Direct acting Schiff base formers OR Schiff base formation >> Direct acting Schiff base formers >> 1,2-Dicarbonyls and 1,3-Dicarbonyls  OR Schiff base formation >> Pyrazolones and Pyrazolidinones derivatives OR Schiff base formation >> Pyrazolones and Pyrazolidinones derivatives >> Pyrazolones and Pyrazolidinones  OR SN1 OR SN1 >> Nucleophilic substitution (SN1) on alkyl (aryl) mercury cations OR SN1 >> Nucleophilic substitution (SN1) on alkyl (aryl) mercury cations >> Mercury compounds  OR SN2 OR SN2 >> Interchange reaction with sulphur containing compounds OR SN2 >> Interchange reaction with sulphur containing compounds >> Thiols and disulfide compounds  OR SN2 >> Nucleophilic substitution at a Nitrogen atom OR SN2 >> Nucleophilic substitution at a Nitrogen atom >> N-Nitroso compounds  OR SN2 >> Nucleophilic substitution at a Nitrogen atom >> N-Oxicarbonyl amides, N-Acyloxy-N-alkoxyamides  OR SN2 >> Nucleophilic substitution at sp3 carbon atom OR SN2 >> Nucleophilic substitution at sp3 carbon atom >> (Thio)Phosphates  OR SN2 >> Nucleophilic substitution at sp3 carbon atom >> Alkyl halides  OR SN2 >> Nucleophilic substitution at sp3 carbon atom >> alpha-Activated haloalkanes  OR SN2 >> Nucleophilic substitution at sp3 carbon atom >> N-Nitroso compounds  OR SN2 >> Nucleophilic substitution at the central carbon atom of N-nitroso compounds OR SN2 >> Nucleophilic substitution at the central carbon atom of N-nitroso compounds >> N-Nitroso_compounds  OR SN2 >> Nucleophilic substitution on benzilyc carbon atom OR SN2 >> Nucleophilic substitution on benzilyc carbon atom >> alpha-Activated benzyls  OR SN2 >> Ring opening SN2 reaction OR SN2 >> Ring opening SN2 reaction >> Epoxides, Aziridines and Sulfuranes  OR SN2 >> SN2 Reaction at a sp3 carbon atom OR SN2 >> SN2 Reaction at a sp3 carbon atom >> alpha- or beta-Halo ether  OR SNAr OR SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds OR SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds >> Activated aryl and heteroaryl compounds OR SNVinyl OR SNVinyl >> SNVinyl at a vinylic (sp2) carbon atom OR SNVinyl >> SNVinyl at a vinylic (sp2) carbon atom >> Vinyl type compounds with electron withdrawing groups  by Protein binding by OASIS v1.3

Domain logical expression index: "i"

Similarity boundary:Target: OS(=O)(=O)c1ccc2c(c1)C(=O)C(=C1C(=O)c3cc(S(O)(=O)=O)ccc3N1)N2
Threshold=30%,
Dice(Atom pairs)
Atom type; Count H attached; Hybridization

Domain logical expression index: "j"

Parametric boundary:The target chemical should have a value of log Kow which is >= -3.57

Domain logical expression index: "k"

Parametric boundary:The target chemical should have a value of log Kow which is <= -0.107

Conclusions:

Interpretation of results (migrated information):negativeThe substance fd & c blue no. 2 is estimated to be non mutagenic in an in vitro bacterial reverse mutation assay

Executive summary:

Genetoxicity of fd & c blue no. 2 is predicted using QSAR toolbox version 3.3.

The substance fd & c blue no. 2 is estimated to be non mutagenic in an in vitro bacterial reverse mutation assay

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

Additional information from genetic toxicity in vitro:

Gene toxicity in vitro:

The study results for read-across substance (CAS: 483-20-5) are used for toxicity to TA1535,TA 1537. Since the read-across is a major component of the target Aluminium lake substance, the inference can be drawn using the information for the major component. 

On the basis of prediction using QSAR Toolbox by SSS (2016), in vitro gene toxicity of FD and C blue no.2 was estimated to be non mutagenic in bacterial reverse mutation assay.

Peer reviewed articles were reviewed to determine the mutagenic nature of the similar substance, C.I. Acid blue 74 (CAS no 860-22-0). The studies are summarized as below:

Genetic toxicity test was performed by T.P. Cameron et al, 1987 for Standard Plate-incorporation on S typhimurium(Strain TA1535, TA1537, TA1538, TA98 and TA100). All strain was tested at dose 3333, 1000, 6666 and 10000 µg/plate both with and without metabolic activation (Aroclor 1254-induced male Fischer). Positive control and solvent control are used. There is no dose-related increase in the number of revertants above spontaneous solvent controls, with a 2-fold increase for strains TA1535, TA1538, TA98 and TA100, and a 3-fold increase for TA1537.Hence, the substance C.I. Acid blue 74is considered to be not mutagenic in Salmonella typhimurium strain TA1535, TA1537, TA1538, TA98 and TA100 with and without metabolic activation.

Mutagenicity testing of C.I. Acid blue 74, performed by T.P. Cameron et al, 1987 by using the FMN preincubation modification of the Salmonella assay. Salmonella typhimurium strain TA98 and TA100 was exposed to C.I. Acid blue 74 at 33, 100, 333, 1000 and 3333 µg/plate. For metabolic activation Hamster liver $9 (30% V/V), plus cofactors (FMN, NADH, G6PD, G6P) was used and Trypan blue (228 /µg/plate) used as a positive control substance. No positive mutagenic response obtained at any tested concentration. Hence, the substance is considered to be not mutagenic in Salmonella typhimurium strain TA98 and TA100 with metabolic activation.

C.I. Acid blue 74 tested for mutagenicity, performed by T.P. Cameron et al, 1987, in mouse lymphoma TK⁺′⁻assay toxicity of test chemical was determined both with and without S9 prepared from Aroclor-1254-induced male Fischer 344 rats. L5178Y TK +/- mouse lymphoma cells was exposed to Without S9: 971, 971, 1229, 1229, 1486, 1486, 1743, 1743, 2000 and 2000 µg/ml and positive control is Ethyl methanesulfonate at 0.5 µl/ml. With S9: 92, 206, 332, 439, 439, 556 and 556 µg/ml concentration of test chemical and positive control is 3-methylcholanthrene at 5.0 or 10.0 µg/ml. There was no dose-related increase in the mutant frequency above the spontaneous control frequency, no 2-fold increase at more than 1 dose and not relative total growth greater than 10% at any exposed concentration.Hence, the substance is considered to be not mutagenic inL5178Y TK +/- mouse lymphoma cells with and without metabolic activation.

Mutagenicity of FD&C Blue no. 2 was determined by the Angela E. Auletta et al. 1977 with Salmonella typhimurium strain TA1535, TA1537, TA1538, TA98 and TA100. All strain was tested at dose 1, 10, 100, 1000 and 10000 µg/plate both with and without metabolic activation (Aroclor 1254-induced male Fischer). Positive control and solvent control was used. There is no dose-related increase in the number of revertants colonies per plate either with or without metabolic activation with either of these strains. Therefore, the substance FD&C Blue no. 2is considered to be not mutagenic inSalmonella typhimuriumstrain TA1535, TA1537, TA1538, TA98 and TA100 with and without metabolic activation.

Reverse mutation assay was of Food blue 2 (Indigo carmine) y the M. ISHIDATE et al 1984, carried out usingS. typhimuriumstrains TA92, TA1535, TA100, TA1537, TA94 and TA98 by method of Ames, McCann & Yamasaki (1975). Duplicate plates were used for each of six different concentrations of the sample. All strain was tested at dose 3333, 1000, 6666 and 10000 µg/plate both with and without metabolic activation (Aroclor 1254-induced male Fischer). All trains were exposed to six different concentrations of the chemical having 5000 µg/plate (5 mg/plate) is highest concentration. No significant increases in the number of revertant colonies were detected in any S. typhimurium strains at the maximum dose.  Therefore, the substanceFood blue 2 (Indigo carmine)is considered to be not mutagenic inSalmonella typhimurium strain TA92, TA1535, TA100, TA1537, TA94 and TA98 with and without metabolic activation.

Chromosomal aberration tests were performed by M. ISHIDATE et al (1984) carried out on Food blue 2 using a Chinese hamster fibroblast cell line. The cells were exposed to three different concentration having highest concentration is 12000 µg/ml (12 mg/ml). Test substance induced polyploid cells at 48 hr after treatment. On the basis of this, the substance is considered to be mutagenic in Chinese hamster fibroblast cell line without metabolic activation.

Mutagenicity of Food blue 2 (Indigo carmine) performed by Joseph P. Brown et al (1978) was evaluate in S. typhimurium strains TA92, TA1535, TA100, TA1537, TA94 and TA98 by method of by Ames et al. All strain was tested at dose 50, 250 and 1000 µg/plate both with and without metabolic activation). No significant increases in the number of revertant colonies were detected in any S. typhimurium strains with and without metabolic activation. Therefore, the substance Food blue 2 (Indigo carmine)is considered to be not mutagenic in Salmonella typhimurium strain TA92, TA1535, TA100, TA1537, TA94 and TA98 with and without metabolic activation.

 

Mutagenicity test was conducted to observe genetic effect ofC.I. Acid blue 74 by H. E. Seifried (2006) in S.typhimurium strainTA98, TA100, TA1535, TA1537, and TA1538 by plate Incorporation methodology. All strain was tested at dose five doses (100-10000 µg/plate) both with and without metabolic activation (Aroclor 1254-induced male Fischer). Positive control and solvent control was used. There is no dose-related increase in the number of revertants. Hence, the substance C.I. Acid blue 74is considered to be not mutagenic in Salmonella typhimurium/TA98, TA100, TA1535, TA1537, and TA1538with and without metabolic activation.

 

C.I. Acid blue 74 tested for mutagenicity in L5178Y TK+/- 3.7.Cby H. E. Seifried (2006) inmouse lymphoma cells. Toxicity of test chemical was determined both with and without S9 prepared from Aroclor-1254-induced male Fischer 344 rats. L5178Y TK +/- mouse lymphoma cells was exposed to 92-2000 µg/ml concentration of test chemical and positive control for without metabolic activation: ethyl methylsulfonate at 4.7Χ10-6 M (or methyl methanesulfonate at 10-20 µg/ mL), for metabolic activation: 3-methylcholanthrene at 1.86 Χ 10-5 M (or dimethylbenz[a]- anthracene at 0.5-4 µg/mL). There is dose related 2-fold increase in mutant frequency was observed at 92 µg/ml with S9.Hence, the substanceC.I. Acid blue 74is considered to be mutagenic inL5178Y TK +/- mouse lymphoma cells with metabolic activation and, not mutagenic without activation.

 

From the available studies, though there was presence of two positive results but based on the majority of studies reviewed, the test material C.I. Acid blue 74 is not mutagenic in vitro.

Justification for selection of genetic toxicity endpoint
Data is from QSAR tool box of Klimish 2

Justification for classification or non-classification

Gene toxicity in vitro:

Based on the key study used and its relative supporting data, the test materialC.I. Acid blue 74is not mutagenic in vitro.