m-(4,5-dihydro-5-imino-3-methyl-1H-pyrazol-1-yl)benzenesulphonic acid

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

Data is from peer reviewed publication

Data source

Reference

Reference Type:

publication

Title:

Salmonella Mutagenicity Tests: III. Results from the Testing of 255 Chemicals

Author:

Errol Zeiger, Beth Anderson, Steve Haworth, Timothy Lawlor, Kristien Mortelmans, and William Speck

Year:

1987

Bibliographic source:

Environmental Mutagenesis Volume 9, Supplement 9: 1-110, 1987

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Refer below principle

Principles of method if other than guideline:

Bacterial reverse mutation assay was performed to evaluate the mutagenic nature of the test compound (Phenyl Methyl Pyrazolone)

GLP compliance:

not specified

Type of assay:

bacterial gene mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

3-methyl-1-phenyl-5-pyrazolone

EC Number:

201-891-0

EC Name:

3-methyl-1-phenyl-5-pyrazolone

Cas Number:

89-25-8

IUPAC Name:

5-methyl-2-phenyl-2,4-dihydro-3H-pyrazol-3-one

Constituent 2

Reference substance name:

Phenyl Methyl Pyrazolone

IUPAC Name:

Phenyl Methyl Pyrazolone

Details on test material:

- Name of test material (as cited in study report): 1-Phenyl-3-methyl-5-pyrazolone (PMP)
- Molecular formula (if other than submission substance): C10H10N2O
- Molecular weight (if other than submission substance): 174.202 g/mol
- Substance type: Organic
- Physical state: No data available
Purity No data available
- Impurities (identity and concentrations): No data available

Specific details on test material used for the study:

- Name of test material: 1-Phenyl-3-methyl-5-pyrazolone (PMP)
- Molecular formula: C10H10N2O
- Molecular weight: 174.202 g/mol
- Substance type: Organic
- Physical state: No data available
- Purity No data available
- Impurities (identity and concentrations): No data available

Method

Target gene:

Histidine

Species / strain

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Details on mammalian cell type (if applicable):

Not applicable

Additional strain / cell type characteristics:

not specified

Metabolic activation:

with and without

Metabolic activation system:

The S-9 fractions of Aroclor 1254-induced, male Sprague-Dawley rat and male Syrian hamster livers were prepared

Test concentrations with justification for top dose:

0, 100, 333, 1000, 3333.0, 6666.0, 10000.0 µg/plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: The chemical was soluble and stable in DMSO

Controls

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: 2-Aminoanthracene (2-AA), 4-Nitro-o-phenylenediamine (NOPD)

Details on test system and experimental 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

Rationale for test conditions:

No data

Evaluation criteria:

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:

No data available

Results and discussion

Test results

Species / strain:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

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:

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: The chemical was tested initially in a toxicity assay to determine the appropriate dose range. The toxicity assay was performed by using TA100 or the system developed by Waleh et a1 [1982]. Toxic concentrations were those at which a decrease in the number of his+ colonies was seen or at which there was a clearing in the
density of the background lawn

COMPARISON WITH HISTORICAL CONTROL DATA: No data available

ADDITIONAL INFORMATION ON CYTOTOXICITY: No data available

Remarks on result:

other: No mutagenic potential

Any other information on results incl. tables

Table: Mutagenicity for 1-Phenyl-3- Methyl-5- Pyrazolone

Dose (µg/plate)	TA100
	-S9		-S9		10% HLI		10% HLI		10% RLI		10% RLI
0	137	5.5	101	5.9	152	3.3	130	8.2	160	6.0	132	7.2
100	123	10.7			118	15.5			148	13.5
333	119	12.7	119	7.8	131	9.5	113	8.7	137	10.6	126	20.8
1000	115	3.7	105	6.8	134	9.7	140	7.0	155	8.2	117	10.4
3333	135	3.2	110	1.9	138	12.4	138p	7.7	192	7.4	136	7.2
6666			150	0.9			143p	11.0			138p	4.4
10000	146p	10.8	161p	3.0	154	18.7	128p	3.3	5.8	126p	9.3
Positive control	259	14.4	337	11.3	1148	58.8	1186	32.2	567	27.7	609	12.2

 

Dose (µg/plate)	TA1535
	-S9		-S9		10% HLI		10% HLI		10% RLI		10% RLI
0	25	3.0	9	2.0	13	0.6	7	0.9	18	1.0	12	1.7
100	17	1.2			5	1.5			11	2.8
333	23	2.6	12	3.2	8	2.1	8	4.1	8	0.3	5	1.2
1000	16	2.1	16	2.0	11	2.9	8	3.3	13	2.3	8	1.9
3333	13	3.5	14	4.7	7	1.2	9	2.6	16	1.5	7	3.7
6666			13	2.3			5	0.9			6	0.7
10000	13p	1.8	19p	1.7	7	0.6	7p	1.7	6p	0.9	6p	0.3
Positive control	284	2.3	139	4.6	389	2.5	362	21.2	144	9.4	200	7.4

 

Dose (µg/plate)	TA1537
	-S9		10% HLI		10% RLI
0	6	0.7	6	1.7	7	0.9
100
333	4	1.2	5	1.5	7	1.2
1000	4	0.7	7	0.9	5	1.0
3333	6	0.3	5	0.6	7	0.3
6666	5	0.6	6	0.3	8	1.2
10000	9p	0.3	8p	1.5	7p	1.9
Positive control	247	32.6	619	10.4	233	16.0

 

Dose (µg/plate)	TA98
	-S9		10% HLI		10% RLI
0	22	2.3	26	2.8	23	2.3
100
333	18	6.0	38	1.2	29	5.5
1000	15	1.8	31	3.8	36	1.9
3333	9	2.9	22	2.4	33	4.4
6666	9	0.3	23p	6.0	29	2.3
10000	13p	0.3	29p	5.1	31p	2.6
Positive control	849	44.7	1054	43.7	405	10.2

 

P: precipitation

Applicant's summary and conclusion

Conclusions:

1-Phenyl-3- Methyl-5- Pyrazolone did not induce gene mutation in the S. typhimurium tester strains TA 1535, TA 1537, TA 98 and TA 100 ii n the presence and absence of S9 metabolic activation system and hence it is negative for gene mutation in vitro.

Executive summary:

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 the test compound 1-Phenyl-3- Methyl-5- Pyrazolone. The test compound was dissolved in DMSO and used at a dosage level of 0, 100, 333, 1000, 3333.0, 6666.0, 10000 µg/plate in the preincubation assay of 48 hrs. Concurrent solvent abd positive control chemicals were also included in the study. 1-Phenyl-3- Methyl-5- Pyrazolone did not induce gene mutation in the S. typhimurium tester strains TA 1535, TA 1537, TA 98 and TA 100 in the presence and absence of S9 metabolic activation system and hence it is negative for gene mutation in vitro.