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Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information
In the DNA repair tests conducted with rat and mouse hepatocytes, thiosemicarbazide showed negative response. Therefore, the genotoxicity of thiosemicarbazide is negative in rat as well as mouse hepatocytes.
Link to relevant study records
Reference
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
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
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
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
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'.

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

-

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.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Additional information

Additional information from genetic toxicity in vitro:

Studies were reviewed for genetic toxicity from reliable sources having Klimisch rating 2

The summary of the results are presented below:

 Sr.No.

Endpoint

Species/ Strain

Result

Sources

1.     

Genetic toxicity

Rat hepatocytes

Negative

Experimental data for target chemical

2.     

Genetic toxicity

Mouse hepatocytes

Negative

Experimental data for target chemical

Applying weight of evidence approach to the above studies, the substance thiosemicarbazide is not expected to be an in vitro mutagen.


Justification for selection of genetic toxicity endpoint
In the DNA repair test with rat hepatocytes, thiosemicarbazide showed negative response. Therefore, the genotoxicity of thiosemicarbazide is negative in rat hepatocytes.

Justification for classification or non-classification

On the basis of available information, the substanceThiosemicarbazide is not expected to be mutagenic in nature.