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Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information
The target compound Pyrazolne T is not mutagenic 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:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Data is from peer reviewed publication
Qualifier:
according to
Guideline:
other:
Principles of method if other than guideline:
The results of mutagenicity testing of some dyes and their metabolites are determined by using the Salmonella-microsome mutagenicity test ()Plate incorporation method developed by Ames et al.
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay
Target gene:
No data avaialble
Species / strain / cell type:
S. typhimurium, other: TA1535, TA1537, TA1538, TA98, and TA100
Details on mammalian cell type (if applicable):
Not applicable
Additional strain / cell type characteristics:
not specified
Metabolic activation:
with and without
Metabolic activation system:
S9 of male Sprague-Dawley rats stimulated with Aroclor 1254
Test concentrations with justification for top dose:
5 to 5000 µg.
Vehicle / solvent:
DMSO
Untreated negative controls:
not specified
Negative solvent / vehicle controls:
yes
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
9-aminoacridine
2-nitrofluorene
sodium azide
other: 2-aminoanthracene
Details on test system and experimental conditions:
METHOD OF APPLICATION: Plate incorporation

DURATION(for liquid preincubation assays)
- Preincubation period:
- Exposure duration: 30min at 37’c
- Expression time (cells in growth medium):No data
- Selection time (if incubation with a selection agent): No details
- Fixation time (start of exposure up to fixation or harvest of cells): No details
METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- Preincubation period: No data available
- 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
Evaluation criteria:
A compound was considered mutagenic when the number of revertants above background was at least twice the value of the historical control mean or twice the value of the current control mean, whichever was greater, and a dose-response curve could be demonstrated
Statistics:
No data available
Species / strain:
S. typhimurium, other: TA1535, TA1537, TA1538, TA98, and TA100
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
Additional information on results:
Additional information on results
TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: No data available
- Effects of osmolality: No data available
- Evaporation from medium: No data available
- Water solubility: No data available
- Precipitation: No data available
- Other confounding effects: No data available

RANGE-FINDING/SCREENING STUDIES: No data available

COMPARISON WITH HISTORICAL CONTROL DATA: Yes

ADDITIONAL INFORMATION ON CYTOTOXICITY: No data available
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.
Conclusions:
Interpretation of results (migrated information):
negative withand without

The test compound Pyrazolone T failed to induce mutation in the Salmonella typhimurium tester strains TA1535, TA1537, TA1538, TA98, and TA100 with and without S9 activation system and hence is negative for gene mutation in vitro.
Executive summary:

Bacterial gene mutation assay was performed to evaluate the mutagenic nature of the test compound Pyrazolone T by the plate incorporation method. The test was performed using Salmonella typhimurium tester strains TA1535, TA1537, TA1538, TA98, and TA100 with and without S9 activation system. After the treatment , the revertant colonies were counted by using a hand-held tally.

                                                          

The test compound Pyrazolone T failed to induce mutation in theSalmonella typhimurium tester strains TA1535, TA1537, TA1538, TA98, and TA100 with and without S9 activation system and hence is negative for gene mutation in vitro.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Additional information

Additional information from genetic toxicity in vitro:

Gene mutation in vitro:

Data from peer reviewed publication for the target chemical and its read across was assessed to determine the mutagenic nature of he test compound Pyrazolone T. The summary is as mentioned below:

Bacterial gene mutation assay was performed by Chung (1981) to evaluate the mutagenic nature of the test compound Pyrazolone T (CAS no 118 -47 -8) by the liquid preincubation assay and by plate incorporation method. The test was performed using Salmonella typhimurium tester strains TA1535, TA1537, TA1538, TA98, and TA100 with and without S9 activation system. Preincubation was perfomed for 30mins at 37⁰C in a Dri-block. The revertant colonies were counted by using a hand-held tally. The test compound Pyrazolone T failed to induce mutation in the Salmonella typhimurium tester strains TA1535, TA1537, TA1538, TA98, and TA100 with and without S9 activation system and hence is negative for gene mutation in vitro.

Ames mutagenicity assay was performed by Das et al (2004) to evaluate the mutagenic nature of the test compound tartrazine (RA CAS no 1934 -21 -0) in plate incorporation assay. The test material was tested at a concentration of 10,100,250,500 and 1000 μg /plate without metabolic activation system. 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. The test compound tartrazine is not mutagenic in the study conducted using Salmonella typhimurium TA97a, TA98 and TA100 without metabolic activation system.

Tartrazine (RA CAS no 1934 -21 -0) was tested by Tonogai et al (1979) for gene mutation in vitro in the bacterium Bacillus subtilis H17 (Rec+) and M45 (Rec-) in the repair test rec assay performed. Agar plates were streaked with inocula of two strains and paper disk 8 mm of diameter, immersed with 10 µM of dye in DMSO solution, was placed on the surface so as to cover the beginning of the bacterial streaks. After incubation for 24 hrs at 37C, the length of growth inhibition of the bacterial streak was measured. No length of growth inhibition was found in Rec+and Rec-strains. Tartrazine failed to induce gene mutation inBacillus subtilisH17 (Rec+) and M45 (Rec-) in the rec assay.

Bacterial gene mutation assay was also performed by Chung (1981) to evaluate the mutagenic nature of the test compound tartrazine (CAS no 1934 -21 -0) by the liquid preincubation assay and by plate incorporation method. The test was performed using Salmonella typhimurium tester strains TA1535, TA1537, TA1538, TA98, and TA100 with and without S9 activation system. Preincubation was perfomed for 30mins at 37⁰C in a Dri-block. The revertant colonies were counted by using a hand-held tally. The test compound tartrazine failed to induce mutation in the Salmonella typhimurium tester strains TA1535, TA1537, TA1538, TA98, and TA100 with and without S9 activation system and hence is negative for gene mutation in vitro.

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 bu Zeiger et al (1987) to evaluate the mutagenic nature of the test compound Phenyl Methyl Pyrazolone (RA CAS no 89 -25 -8). The test compound was used at a dosage level of 0, 100, 333, 1000, 3333.0, 6666.0, 10000 µg/plate in the preincubation assay of 48 hrs. Phenyl Methyl Pyrazolonefailed to induce mutation in the S. typhimurium tester strains TA 1535, TA 1537, TA 98 and TA 100 and hence is negative for mutation in vitro.

The key study and its supporting data suggests that the chemical is not mutagenic in vitro.

Justification for selection of genetic toxicity endpoint
Data is from peer reviewed publication

Justification for classification or non-classification

Based on the data presented, the test compound Pyrazolone T (118 -47 -8) is found to be negative for gene mutation in vitro.