Hydrogen bis[3-[[1-(3-chlorophenyl)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-4-yl]azo]-4-hydroxy-N-methylbenzenesulphonamidato(2-)]cobaltate(1-)

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Genetic mutation in vitro;

The read across substances share high similarity in structure and functional group .Therefore, it is acceptable to derive information on mutation from the analogue substance for test substance. Experimental data from read across chemical have been reviewed to determine the mutagenic nature of Hydrogen bis[3-[[1-(3-chlorophenyl -4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-4-yl]azo]-4-hydroxy-N-methylbenzenesulphonamidato(2-)]cobaltate(1-) (85959-75-7) .The studies are as mentioned below

The read across substances share high similarity in functional group .Therefore, it is acceptable to derive information on mutation from the analogue substance for test substance. Gene mutation study was conducted to evaluate the mutagenic nature of test chemical. The study was performed using the Preincubation protocol using Salmonella typhimurium TA98, TA1538 and TA1535 both in the presence and absence of S9 metabolic activation system.10 µg of the dye partially or completely dissolved in 0.01 ml of dimethyl sulfoxide (DMSO) was added to 0.9 ml of the reagents in the liquid phase and incubated 30 min at 37°C with shaking before plating 0.1 ml onto minimal plates. Test chemical did not induce mutation in the Salmonella typhimurium TA98, TA1538 and TA1535 in the presence and absence of S9 metabolic activation system and hence is negative for gene mutation in vitro.

The read across substances share high similarity in functional group .Therefore, it is acceptable to derive information on mutation from the analogue substance for target substance. Salmonella/microsome test in the absence of exogenous metabolic activation and in the presence of liver S-9 from Aroclor-induced male Sprague-Dawley rats and Syrian hamsters was performed to evaluate the mutagenic nature of test chemical using S. typhimurium tester strains TA1535, TA1537, TA98 and TA100. The study was performed as per the preincubation assay and the preincubation time was 20 mins and the plates were incubated for 48 hrs. The test compound was dissolved in DMSO and was used at a dosage level of 0, 100, 333, 1000, 3333 or 10000 µg/plate in the preincubation assay of 48 hrs. Concurrent solvent and positive control chemicals were included in the study. Test chemical did not induce a reproducible, dose-related increase in his+revertants over the corresponding solvent in the S. typhimurium tester strains TA100, TA1537, TA1535 and TA98 in the presence and absence of S9 metabolic activation system and hence it is not likely to classify as a gene mutant in vitro.  

 

Link to relevant study records

Reference

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

Data for the target chemical is summarized based on the structurally similar read across chemicals

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

other: As mention below

Principles of method if other than guideline:

WoE derived based on the experimental data from structurally and functionally similar read across chemicals for the target chemical.

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Specific details on test material used for the study:

- Name of test material : Hydrogen bis[3-[[1-(3-chlorophenyl)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-4-yl]azo]-4-hydroxy-N-methylbenzenesulphonamidato(2-)]cobaltate(1-)
- Molecular formula : C34H28Cl2CoN10O8S2.H
- Molecular weight : 899.6361 g/mol
- Smiles notation : CC1C(N=Nc2cc3ccc2O[Co]{-}2(N(C)S3(=O)=O)Oc3ccc(S(=O)(=O)NC)cc3N=NC3=C(N(c4cccc(Cl)c4)N=C3C)O2)C(=O)N(c2cccc(Cl)c2)N=1
- InChl : 1S/C17H16ClN5O4S.C17H15ClN5O4S.Co/c2*1-10-16(17(25)23(22-10)12-5-3-4-11(18)8-12)21-20-14-9-13(6-7-15(14)24)28(26,27)19-2;/h3-9,19,24-25H,1-2H3;3-9,16H,1-2H3,(H,21,24);/q;-1;+3/p-2/b21-20+;;
- Substance type : Organic
- Physical state : Solid

Target gene:

Histidine

Species / strain / cell type:

S. typhimurium, other: TA98, TA1538 and TA1535

Details on mammalian cell type (if applicable):

Not applicable

Additional strain / cell type characteristics:

not specified

Species / strain / cell type:

S. typhimurium, other: TA98, TA100, TA1535, and TA97

Details on mammalian cell type (if applicable):

Not applicable

Additional strain / cell type characteristics:

not specified

Cytokinesis block (if used):

not specified

Metabolic activation:

with and without

Metabolic activation system:

Microsomal detoxifying enzymes using a 9000 Xg homogenate prepared from Aroclor 1254- induced male Swiss Webster mice.

Test concentrations with justification for top dose:

1,10µg
2,0, 100, 333, 1000, 3333 or 10000 µg/plate

Vehicle / solvent:

1,DMSO
2,DMSO

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

other: 2-aminofluorine, dimethylnitrosamine

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

9-aminoacridine

sodium azide

other: +S(92-Aminoanthracene (2-AA) for all strain

Details on test system and experimental conditions:

1,Details on test system and conditions
METHOD OF APPLICATION: Preincubation

DURATION
- Preincubation period: 30 min
- Exposure duration: No data available
- Expression time (cells in growth medium): No data available
- Selection time (if incubation with a selection agent): No data available
- Fixation time (start of exposure up to fixation or harvest of cells): No data available

SELECTION AGENT (mutation assays): No data available
SPINDLE INHIBITOR (cytogenetic assays): No data available
STAIN (for cytogenetic assays): No data available

NUMBER OF REPLICATIONS: No data available

NUMBER OF CELLS EVALUATED: No data available

DETERMINATION OF CYTOTOXICITY
- Method: mitotic index; cloning efficiency; relative total growth; other: No data available

OTHER EXAMINATIONS:
- Determination of polyploidy: No data available
- Determination of endoreplication: No data available
- Other: No data available

OTHER: No data available

2,Details on test system and conditions
METHOD OF APPLICATION: preincubation

DURATION
- Preincubation period: 20 mins
- Exposure duration: 48 hrs
- Expression time (cells in growth medium): 48 hrs
- Selection time (if incubation with a selection agent): No data available
- Fixation time (start of exposure up to fixation or harvest of cells): No data available

SELECTION AGENT (mutation assays): No data available
SPINDLE INHIBITOR (cytogenetic assays): No data available
STAIN (for cytogenetic assays): No data available

NUMBER OF REPLICATIONS: Triplicate

NUMBER OF CELLS EVALUATED: No data available

DETERMINATION OF CYTOTOXICITY
- Method: mitotic index; cloning efficiency; relative total growth; other: No data available

OTHER EXAMINATIONS:
- Determination of polyploidy: No data available
- Determination of endoreplication: No data available
- Other:

OTHER: No data available

2

Rationale for test conditions:

Not specified

Evaluation criteria:

1,An increase in the number of revertants was noted.
2,An individual trial was judged mutagenic (+) if a dose-related increase over the corresponding solvent control was seen, and it was judged weakly mutagenic C+W) if a low-level dose response was seen. A trial was considered questionable (?) if a dose-related increase was judged insufficiently high to justify a call of "+W," if only a single dose was elevated over the control, or if a non-dose-related increase was seen.
The chemical was judged to be mutagenic (+), or weakly mutagenic (+W), if it produced a reproducible, dose-related increase in his+ revertants over the corresponding solvent controls in replicate trials.

It chemical was considered to be questionable (?) if a reproducible increase of his+ revertants did not meet the criteria for either a " + " or " + W," or if only single doses produced an increase in his+ revertants in repeat trials.

Statistics:

1,Yes ,Mean was observed.
2, Yes ,Mean was observed.

Species / strain:

S. typhimurium, other: TA98, TA1538 and TA1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Species / strain:

S. typhimurium, other: TA98, TA1535, TA100, TA97

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Remarks on result:

other: No mutagenic effect were observed

Conclusions:

Gene mutation toxicity study for Hydrogen bis[3-[[1-(3-chlorophenyl)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-4-yl]azo]-4-hydroxy-N-methylbenzenesulphonamidato(2-)]cobaltate(1-) (85959-75-7)as predicted using data from read across chemicals for Salmonella typhimurium bacterial strains in the presence and absence of S9 metabolic activation system is negative and hence the chemical is not likely to classify as a gene mutant in vitro.

Executive summary:

Genetic mutation in vitro;

The read across substances share high similarity in structure and functional group .Therefore, it is acceptable to derive information on mutation from the analogue substance for test substance. Experimental data from read across chemical have been reviewed to determine the mutagenic nature of Hydrogen bis[3-[[1-(3-chlorophenyl -4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-4-yl]azo]-4-hydroxy-N-methylbenzenesulphonamidato(2-)]cobaltate(1-) (85959-75-7) .The studies are as mentioned below

The read across substances share high similarity in functional group .Therefore, it is acceptable to derive information on mutation from the analogue substance for test substance. Gene mutation study was conducted to evaluate the mutagenic nature of test chemical. The study was performed using the Preincubation protocol using Salmonella typhimurium TA98, TA1538 and TA1535 both in the presence and absence of S9 metabolic activation system.10 µg of the dye partially or completely dissolved in 0.01 ml of dimethyl sulfoxide (DMSO) was added to 0.9 ml of the reagents in the liquid phase and incubated 30 min at 37°C with shaking before plating 0.1 ml onto minimal plates. Test chemical did not induce mutation in the Salmonella typhimurium TA98, TA1538 and TA1535 in the presence and absence of S9 metabolic activation system and hence is negative for gene mutation in vitro.

The read across substances share high similarity in functional group .Therefore, it is acceptable to derive information on mutation from the analogue substance for target substance. Salmonella/microsome test in the absence of exogenous metabolic activation and in the presence of liver S-9 from Aroclor-induced male Sprague-Dawley rats and Syrian hamsters was performed to evaluate the mutagenic nature of test chemical using S. typhimurium tester strains TA1535, TA1537, TA98 and TA100. The study was performed as per the preincubation assay and the preincubation time was 20 mins and the plates were incubated for 48 hrs. The test compound was dissolved in DMSO and was used at a dosage level of 0, 100, 333, 1000, 3333 or 10000 µg/plate in the preincubation assay of 48 hrs. Concurrent solvent and positive control chemicals were included in the study. Test chemical did not induce a reproducible, dose-related increase in his+revertants over the corresponding solvent in the S. typhimurium tester strains TA100, TA1537, TA1535 and TA98 in the presence and absence of S9 metabolic activation system and hence it is not likely to classify as a gene mutant in vitro.  

 The data available for the target chemical based on its read across substance and applying weight of evidence Hydrogen bis[3-[[1-(3-chlorophenyl)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-4-yl]azo]-4-hydroxy-N-methylbenzenesulphonamidato(2-)]cobaltate(1-) (85959-75-7)does not exhibit gene mutation in vitro. Hence the test chemical is not likely to classify as a gene mutant in vitro.

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;

The read across substances share high similarity in structure and functional group .Therefore, it is acceptable to derive information on mutation from the analogue substance for test substance. Experimental data from read across chemical have been reviewed to determine the mutagenic nature of Hydrogen bis[3-[[1-(3-chlorophenyl -4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-4-yl]azo]-4-hydroxy-N-methylbenzenesulphonamidato(2-)]cobaltate(1-) (85959-75-7) .The studies are as mentioned below

The read across substances share high similarity in functional group .Therefore, it is acceptable to derive information on mutation from the analogue substance for test substance. Gene mutation study was conducted to evaluate the mutagenic nature of test chemical. The study was performed using the Preincubation protocol using Salmonella typhimurium TA98, TA1538 and TA1535 both in the presence and absence of S9 metabolic activation system.10 µg of the dye partially or completely dissolved in 0.01 ml of dimethyl sulfoxide (DMSO) was added to 0.9 ml of the reagents in the liquid phase and incubated 30 min at 37°C with shaking before plating 0.1 ml onto minimal plates. Test chemical did not induce mutation in the Salmonella typhimurium TA98, TA1538 and TA1535 in the presence and absence of S9 metabolic activation system and hence is negative for gene mutation in vitro.

The read across substances share high similarity in functional group .Therefore, it is acceptable to derive information on mutation from the analogue substance for target substance. Salmonella/microsome test in the absence of exogenous metabolic activation and in the presence of liver S-9 from Aroclor-induced male Sprague-Dawley rats and Syrian hamsters was performed to evaluate the mutagenic nature of test chemical using S. typhimurium tester strains TA1535, TA1537, TA98 and TA100. The study was performed as per the preincubation assay and the preincubation time was 20 mins and the plates were incubated for 48 hrs. The test compound was dissolved in DMSO and was used at a dosage level of 0, 100, 333, 1000, 3333 or 10000 µg/plate in the preincubation assay of 48 hrs. Concurrent solvent and positive control chemicals were included in the study. Test chemical did not induce a reproducible, dose-related increase in his+revertants over the corresponding solvent in the S. typhimurium tester strains TA100, TA1537, TA1535 and TA98 in the presence and absence of S9 metabolic activation system and hence it is not likely to classify as a gene mutant in vitro.  

 The data available for the target chemical based on its read across substance and applying weight of evidence Hydrogen bis[3-[[1-(3-chlorophenyl)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-4-yl]azo]-4-hydroxy-N-methylbenzenesulphonamidato(2-)]cobaltate(1-) (85959-75-7)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

Thus based on the above annotation and CLP criteria for target substance Hydrogen bis[3-[[1-(3-chlorophenyl)-4,5-dihydro-3-methyl -5-oxo-1H-pyrazol-4-yl]azo] -4-hydroxy-N-methylbenzenesulphonamidato(2-)]cobaltate(1-) (85959-75-7)does not exhibit gene mutation in vitro. Hence the test chemical is not likely to classify as a gene mutant in vitro.