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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 [μ-[[7,7'-iminobis[4-hydroxy-3-[[2-hydroxy-5-sulphamoylphenyl]azo]naphthalene-2-sulphonato]](6-)]]dicuprate(2-)(6798-03-4). 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 [μ-[[7,7'-iminobis[4-hydroxy-3-[[2-hydroxy-5-sulphamoylphenyl]azo]naphthalene-2-sulphonato]](6-)]]dicuprate(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. Based on the predicted result it can be concluded that the substance is considered to not toxic as per the criteria mentioned in CLP regulation.

Link to relevant study records
Reference
Endpoint:
in vitro gene mutation study in bacteria
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, but not (completely) falling into its applicability domain, with adequate and reliable documentation / justification
Justification for type of information:
Data is from OECD QSAR Toolbox version 3.3 and the supporting QMRF report has been attached.
Reference:
Composition 0
Qualifier:
according to
Guideline:
other: As mention below
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
Test material information:
Composition 1
Specific details on test material used for the study:
Name: disodium [μ-[[7,7'-iminobis[4-hydroxy-3-[[2-hydroxy-5-sulphamoylphenyl]azo]naphthalene-2-sulphonato]](6-)]]dicuprate(2-)
InChI:1S/C32H25N7O14S4.2Cu.2Na/c33-54(44,45)19-3-7-25(40)23(13-19)36-38-29-27(56(48,49)50)11-15-9-17(1-5-21(15)31(29)42)35-18-2-6-22-16(10-18)12-28(57(51,52)53)30(32(22)43)39-37-24-14-20(55(34,46)47)4-8-26(24)41;;;;/h1-14,35,40-43H,(H2,33,44,45)(H2,34,46,47)(H,48,49,50)(H,51,52,53);;;;/q;2*+2;2*+1/p-6/b38-36+,39-37+;;;;
SMILES:NS(=O)(=O)c1ccc(O{-}.[Na]{+})c(N=Nc2c3cc4cc(ccc4c2O{-}.[Na]{+})Nc2ccc4c(c2)cc(c2c4O{-}.[Cu]{2+}.O{-}c4ccc(S(N)(=O)=O)cc4N=N2)S(=O)(=O)O{-}.[Cu]{2+}.O{-}S3(=O)=O)c1
Mol. formula: C32H19Cu2N7Na2O14S4
Molecular Weight: 1026.87 g/mole
Target gene:
Histidine
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102
Details on mammalian cell lines (if applicable):
Not applicable
Additional strain characteristics:
not specified
Cytokinesis block (if used):
not specified
Metabolic activation:
with
Metabolic activation system:
S9 metabolic activation
Test concentrations with justification for top dose:
not specified
Vehicle:
not specified
Negative controls:
not specified
Solvent controls:
not specified
True negative controls:
not specified
Positive controls:
not specified
Details on test system and conditions:
not specified
Rationale for test conditions:
not specified
Evaluation criteria:
Prediction was done considering a dose dependent increase in the number of revertants/plate.
Statistics:
not specified
Species / strain:
other: TA 1535, TA 1537, TA 98, TA 100 and TA 102
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: No mutagenic effect were observed

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

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Amine OR Anion OR Aromatic compound OR Azo compound OR Cation OR Secondary amine OR Secondary aromatic amine OR Sulfonamide OR Sulfonic acid derivative by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Aliphatic Nitrogen, one aromatic attach [-N] OR Aliphatic Nitrogen, two aromatic attach [-N-] OR Aromatic Carbon [C] OR Azo [-N=N-] OR Miscellaneous metal [Ni, Cu, Zr, Be] OR Miscellaneous sulfide (=S) or oxide (=O) OR Nitrogen, two or tree olefinic attach [>N-] OR Olefinic carbon [=CH- or =C<] OR Oxygen, one aromatic attach [-O-] OR Suflur {v+4} or {v+6} OR Sulfamide, aromatic attach [-SO2-N] OR Sulfonate, aromatic attach [-SO2-O] OR Sulfonyl amide, aromatic attach [-S(=O)N-] OR Sulfur, nitrogen attach [-S-] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Aromatic amine OR Aryl OR Azo OR Fused carbocyclic aromatic OR Overlapping groups OR Phenol OR Sulfonamide OR Sulfonic acid by Organic Functional groups (nested) ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Aromatic amine OR Aryl OR Azo OR Fused carbocyclic aromatic OR Naphtalene OR Phenol OR Sulfonamide OR Sulfonic acid by Organic Functional groups ONLY

Domain logical expression index: "e"

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

Domain logical expression index: "f"

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

Domain logical expression index: "g"

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

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Moderate binder, OH grooup OR Non binder, impaired OH or NH2 group OR Non binder, non cyclic structure OR Non binder, without OH or NH2 group OR Strong binder, OH group OR Very strong binder, OH group OR Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "i"

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

Domain logical expression index: "j"

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

Domain logical expression index: "k"

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

Domain logical expression index: "l"

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

Domain logical expression index: "m"

Parametric boundary:The target chemical should have a value of log Kow which is >= -5.11

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log Kow which is <= -1.27

Conclusions:
Disodium [μ-[[7,7'-iminobis[4-hydroxy-3-[[2-hydroxy-5-sulphamoylphenyl]azo]naphthalene-2-sulphonato]](6-)]]dicuprate(2-)(6798-03-4)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 [μ-[[7,7'-iminobis[4-hydroxy-3-[[2-hydroxy-5-sulphamoylphenyl]azo]naphthalene-2-sulphonato]](6-)]]dicuprate(2-)(6798-03-4). 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 [μ-[[7,7'-iminobis[4-hydroxy-3-[[2-hydroxy-5-sulphamoylphenyl]azo]naphthalene-2-sulphonato]](6-)]]dicuprate(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 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

Genetic mutation in vitro;

Prediction model based estimation and data from read across chemical have been reviewed to determine the mutagenic nature of Disodium [μ-[[7,7'-iminobis[4-hydroxy-3-[[2-hydroxy-5-sulphamoylphenyl]azo]naphthalene-2-sulphonato]](6-)]]dicuprate(2-)(6798-03-4). The studies are as mentioned 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 [μ-[[7,7'-iminobis[4-hydroxy-3-[[2-hydroxy-5-sulphamoylphenyl]azo]naphthalene-2-sulphonato]](6-)]]dicuprate(2-)(6798-03-4). 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 [μ-[[7,7'-iminobis[4-hydroxy-3-[[2-hydroxy-5-sulphamoylphenyl]azo]naphthalene-2-sulphonato]](6-)]]dicuprate(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. Based on the predicted result it can be concluded that the substance is considered to not toxic as per the criteria mentioned in CLP regulation.

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, chromosomal aberration was predicted for Disodium [μ-[[7,7'-iminobis[4-hydroxy-3-[[2-hydroxy-5-sulphamoylphenyl] azo]naphthalene-2-sulphonato]](6-)]]dicuprate(2-)(6798-03-4).The study assumed the use of Chinese hamster ovary (CHO) cell line with and without S9 metabolic activation system  for Disodium [μ-[[7,7'-iminobis[4-hydroxy-3-[[2-hydroxy-5-sulphamoylphenyl]azo]naphthalene-2-sulphonato]](6-)]]dicuprate(2-)was predicted to not induce chromosomal aberrations in Chinese hamster ovary (CHO) cell line 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. Based on the predicted result it can be concluded that the substance is considered to not toxic as per the criteria mentioned in CLP regulation.

In a study for structurally and functionally similar read across chemical, Gene mutation toxicity study was performed by Aparajita Das et al.( Int J Hum Genet,2004) to determine the mutagenic nature of Amaranth [Food Red 2]; IUPAC Name; Amaranth dye; trisodium (4E)-3-oxo-4-[(4- sulfonato-1- naphthyl)hydrazono]naphthalene- 2,7-disulfonate; trisodium 3-hydroxy-4-[(4-sulfonato-1-naphthyl)diazenyl]naphthalene-2,7-disulfonate (915-67-3) .The read across substances share high similarity in structure and log kow .Therefore, it is acceptable to derive information on mutation from the analogue substance. Ames mutagenicity assay was performed to evaluate the mutagenic nature of the test compound Amaranth in plate incorporation assay. The test material was tested at a concentration of 10,100,250,500 and 1000 μg /plate. The plates were inverted within an hour and placed in a dark vented incubator at 37⁰C for 48 hours. Positive controls (for TA97a and TA98, 20 μg/plate nitro phenylene diamine and for TA100, 1.5 μg/plate sodium azide) and negative controls were maintained concurrently for all the experiments. Three plates were used for each set. After 48 hours of incubation, the revertant colonies were counted. ANOVA test was performed at 0.05 levels. Amaranth [Food Red 2] was considered to be non - mutagenic under the study conditions.

 

 

 In a study for structurally and functionally similar read across chemical, Gene mutation toxicity study was performed by H. E. Seifried et al.( Chem. Res. Toxicol,2006) to determine the mutagenic nature of Brilliant Black 1; IUPAC name; tetrasodium 4-acetamido-5-hydroxy-6-({7-sulfonato-4-[(4-sulfonatophenyl) diazenyl]-1-naphthyl}diazeny... (2519-30-4). The read across substances share high similarity in structure and log kow .Therefore, it is acceptable to derive information on mutation from the analogue substance. The mutagenic potency of C.I Brilliant black BN( food black 1) was tested by the plate incorporation method usingSalmonella typhimuriumstrainTA98, TA100, TA1535, TA1537, and TA1538. When the test bacterial strain is exposed with the test chemical for 48hrs, no mutagenic response was seen in any of the strains of Salmonella typhimurium(with and without metabolic activation system).

 

Based on the data available for the target chemical and its read across substance and applying weight of evidence of Disodium [μ-[[7,7'-iminobis[4-hydroxy-3-[[2-hydroxy-5-sulphamoylphenyl]azo]naphthalene-2-sulphonato]](6-)]]dicuprate(2-)(6798-03-4) does not exhibit gene mutation in vitro. Hence the test chemical is not likely to classify as a gene mutant in vitro.

Justification for classification or non-classification

 Based on the above annotation and CLP criteria for the target chemical Disodium [μ-[[7,7'-iminobis[4-hydroxy-3-[[2-hydroxy-5-sulphamoylphenyl]azo]naphthalene-2-sulphonato]](6-)]]dicuprate(2-)(6798-03-4) does not exhibit gene mutation in vitro Hence the test chemical is not likely to classify as a gene mutant in vitro.