Thiazolidine-2,4-dione

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

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:

Peer reviewed journal research article

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

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Refer below principle

Principles of method if other than guideline:

The mutagenicity potential of the Rhodanine was studied by conducting experiment in Salmonella typhimurium strains TA100, TA1535, TA1537, TA98.

GLP compliance:

no

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

2-thioxo-1,3-thiazolidin-4-one

Cas Number:

141-84-4

Molecular formula:

C3H3NOS2

IUPAC Name:

2-thioxo-1,3-thiazolidin-4-one

Details on test material:

- Name of test material: Rhodanine
- Molecular formula: C3H3NOS2
- Molecular weight: 133.1947 g/mol
- Substance type: Organic

Specific details on test material used for the study:

- Name of test material: Rhodanine
- Molecular formula: C3H3NOS2
- Molecular weight: 133.1947 g/mol
- Substance type: Organic
- Physical state: No data
- Purity: 97%
- Impurities (identity and concentrations): 3%

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):

No data

Additional strain / cell type characteristics:

not specified

Cytokinesis block (if used):

No data

Metabolic activation:

with and without

Metabolic activation system:

S9 fractions of Aroclor 1254-induced, male Sprague-Dawley rat and male Syrian hamster livers.

Test concentrations with justification for top dose:

0, 10, 33, 100, 333, 1000 µg/Plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: Solubility of test substance in solvent

Controls

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

9-aminoacridine

sodium azide

other: 4-nitro-o-phenylenediamine: TA98 (Without metabolic activation). 2-Aminoanthracene: TA100, TA1535, TA1537, TA98 (With metabolic activation).

Details on test system and experimental conditions:

METHOD OF APPLICATION: Preincubation

DURATION
- Preincubation period: 20 min
- Exposure duration: 2 days
- Expression time: 2 days
- Selection time: No data
- Fixation time: No data

SELECTION AGENT: No data
SPINDLE INHIBITOR: No data
STAIN: No data

NUMBER OF REPLICATIONS: 3

NUMBER OF CELLS EVALUATED: No data

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

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

- Other:

OTHER:

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 (+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 distinctions between a weak mutagenic response and a mutagenic response, or between a weak mutagenic response and a questionable mutagenic response are highly subjective.

A 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. A 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. The chemicals were decoded by the chemical repository only after a determination had been made regarding their mutagenicity or no mutagenicity.

Statistics:

MEAN, SEM

Results and discussion

Test results

Species / strain:

S. typhimurium, other: TA100, TA1535, TA1537, TA98

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:

No data

Any other information on results incl. tables

Results for Rhodanine

Dose	TA100
	NA (-)		10% HLI (-)		10 % RLI (-)
µg/plate	MEAN	SEM	MEAN	SEM	MEAN	SEM
0	126	18.3	208	15.1	177	13.9
10	153	2.1	221	14.4	201	13
33	141	3.2	204	8	193	17.4
100	147	5.6	202	13.6	194	11.1
333	131	11.4	187	20.1	175	8.2
1000	103	5.7	168	12	168	11
POS	525	8.1	806	48.4	376	16.6

Dose	TA1535
	NA (-)		10% HLI (-)		10 % RLI (-)
µg/plate	MEAN	SEM	MEAN	SEM	MEAN	SEM
0	5	0.6	5	0.0	6	0.6
10	4	0.3	6	0.7	8	0.6
33	5	0.7	5	0.6	7	0.6
100	3	0.3	5	0.6	6	0.6
333	5	1.8	4	0.0	7	1.2
1000	5	2.1	3	0.3	4	0.7
POS	536	47.1	35	3.8	27	0.7

Dose	TA98
	NA (-)		10% HLI (-)		10 % RLI (-)
µg/plate	MEAN	SEM	MEAN	SEM	MEAN	SEM
0	14	0.3	25	2.6	21	2.1
10	19	4.0	25	4.6	24	2.0
33	14	1.5	30	1.8	27	3.5
100	12	0.0	24	2.9	24	1.8
333	12	0.3	20	3.2	22	4.5
1000	10	1.2	18	1.8	15	3.2
POS	411	32.2	650	34.0	244	9.6

Abbreviations:                     

NA: Not activated

RLI: Aroclor 1254-induced rat liver S-9;

HLI: Aroclor 1254-induced hamster liver

POS: Positive control

Applicant's summary and conclusion

Conclusions:

The mutagenic potential of Rhodanine was evaluated by performing experiment in Salmonella typhimurium strains TA100, TA1535, TA1537, TA98 with and without metabolic activation, test chemical not induce mutation in bacterial tester strains. Therefore, Rhodanine was considered to be not mutagenic In vitro.

Executive summary:

The mutagenicity effect of Rhodanine was evaluated by performing mutagenic assay in Salmonella typhimurium. Salmonella typhimurium strainsTA100, TA1535, TA1537, TA98 involved in the study. Mutagenic assay was performed by preincubation method with and without metabolic activation i.e. S9 fractions of Aroclor 1254 -induced, male Sprague-Dawley rat and male Syrian hamster livers. Test chemical in concentrations 0, 10, 33, 100, 333, 1000 µg/Plate were tested. The test chemical, Salmonella culture, and S9 mix were incubated at 37°C without shaking for 20 min. The top agar was added, and the contents of the tubes were mixed and poured onto the surface of petri dishes that contained Vogel-Bonner medium [Vogel and Bonner. The histidine-revertant (his+) colonies arising on these plates were counted following 2 days incubation at 37°C. The plates were hand counted when precipitated was present, otherwise automatic colony counters were used. All doses of test chemical were tested in triplicate. Concurrent solvent and positive controls were run with each trials. The positive control substance without metabolic activation were Sodium azide (TA100, TA1535), 9-aminoacridine (TA1537) and 4-nitro-o-phenylenediamine (TA98). Positive control for metabolic activation was 2-aminoanthracene for all strains.

The number of revertants for test chemical with and without metabolic activation not more than solvent control, hence test chemical was not induce mutation. Therefore Rhodanine was considered to be not mutagenic In vitro.