Thiosemicarbazide

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro DNA damage and/or repair study

Remarks:

Type of genotoxicity: DNA damage and/or repair

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Data is from peer reviewed journal

Data source

Reference

Reference Type:

publication

Title:

Genotoxicity of a Varity of Hydrazine Derivative in the Hepatocyte Primary Culture/DNA repair Test Using Rat and Mouse Hepatocytes

Author:

Hideki Mori, Shigeyuki Sugie, Naoki Yoshimi, Hitishi Iwata, Akiyoshi Nishikawa, Kogen Matsukubo, Hidesuke Shimizu And Iwao Hirono

Year:

1988

Bibliographic source:

Japanese Journal of Cancer Research (Gann), 79, 204-211; February, 1988

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: as below

Principles of method if other than guideline:

The genotoxicity of Thiosemicarbazide was studied in Hepatocyte primary culture/DNA repair test using rat hepatocyte

GLP compliance:

no

Type of assay:

DNA damage and repair assay, unscheduled DNA synthesis in mammalian cells in vitro

Test material

Test material information

Constituent 1

Reference substance name:

Thiosemicarbazide

EC Number:

201-184-7

EC Name:

Thiosemicarbazide

Cas Number:

79-19-6

Molecular formula:

CH5N3S

IUPAC Name:

hydrazinecarbothioamide

Details on test material:

- Name of test material (as cited in study report): Thiosemicarbazide
- Molecular formula (if other than submission substance): C-H5-N3-S (H2NCSHNNH2- as mentioned in publication)
- Molecular weight (if other than submission substance): 91.1375 g/mol
- Substance type: Organic
- Physical state: Solid
- Purity: No data available
- Impurities (identity and concentrations): No data available

Method

Species / strain

Species / strain / cell type:

hepatocytes: ACI/N rats

Details on mammalian cell type (if applicable):

- Type and identity of media: The hepatocytes isolated from the liver of ACI/N rats were allowed to attach for 2 hr to plastic coverslips in primary culture using Williams’ Medium E for further experiment to be performed.
- Properly maintained: No data available
- Periodically checked for Mycoplasma contamination: no data
- Periodically checked for karyotype stability: no data
- Periodically "cleansed" against high spontaneous background: no data

Additional strain / cell type characteristics:

not specified

Metabolic activation:

not specified

Test concentrations with justification for top dose:

10-³,10-⁴,10-⁵M (0.001, 0.0001, 0.00001 M)

Vehicle / solvent:

Distilled water

Controls

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

yes

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

other: N-2-fluorenylacetamide

Details on test system and experimental conditions:

METHOD OF APPLICATION: in medium

DURATION
- Preincubation period: No data
- Exposure duration: 20 hrs
- Expression time (cells in growth medium): No data
- Selection time (if incubation with a selection agent): 14 days
- Fixation time (start of exposure up to fixation or harvest of cells): No data

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

NUMBER OF REPLICATIONS: 2

NUMBER OF CELLS EVALUATED: 50 cells/3 coverslips

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: No data

OTHER:

Evaluation criteria:

The test compound judged positive when the mean nuclear grain count was more than 5 grains or positive cells were more than 33%.

Statistics:

No data available

Results and discussion

Test results

Species / strain:

hepatocytes: ACI/N rats

Metabolic activation:

not specified

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: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

The results of DNA repair test:

Chemical	Dose(M)	UDS grains/nucleus	DNA repair
Thiosemicarbazide	0.001	-1.0 ± 1.5	-
	0.0001	-1.2 ± 1.4	-
	0.00001	-0.8 ± 1.3	-

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative

In the DNA repair test with rat hepatocytes, thiosemicarbazide showed negative response. Therefore, the genotoxicity of thiosemicarbazide is negative in rat hepatocytes.

Executive summary:

The Genotoxicity of thiosemicarbazide was examined in Hepatocyte primary culture/DNA repair test on rat hepatocytes.

 

The test was performed basically in accordance with the methods of Williams et al. Hepatocytes were isolated from the livers of ACI/N rats weighing 200-250g.The isolated hepatocytes were allowed to attach for two hr to plastic coverslips in primary culture using Williams’ Medium E.The culture were washed and exposed to test compound at 10¯³, 10¯⁴, 10¯⁵M (0.001, 0.0001, 0.00001 M) doses.N-2-fluorenylacetamide used as a positive control substance.

 

In the DNA repair test, all the numbers of UDS grains/nucleus of test compound or control were negative value. It means thiosemicarbazide have negative DNA repair response.

 

Therefore, the genotoxicity of thiosemicarbazide is negative in rat hepatocytes.

 

In accordance with the CLP classification, the test material does not classify as an in vitro mutagen.