Colchicoside

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:

key study

Study period:

2010

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Version / remarks:

and Commission regulation EC 440/2008 and EPA 712-C-98-247

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Colchicoside

EC Number:

207-513-0

EC Name:

Colchicoside

Cas Number:

477-29-2

Molecular formula:

C27H33NO11

IUPAC Name:

N-[1,2,10-trimethoxy-9-oxo-3-[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-6,7-dihydro-5H-benzo[d]heptalen-7-yl]acetamide

Method

Target gene:

Bacterial reverse mutation assay use amino acid requiring strains of Salmonella typhimurium to detect point mutations, which involve substitution, addition or deletion of one or a few DNA base pairs. The principle of these bacterial reversion assay is that they detect mutations which functionally reverse mutations present in the tester strains and restore the capability to synthesise an essential amino acid. The purpose of this study is to establish the potential of the test item to induce gene mutations in bacteria by means of two independent S. typhimurium reverse mutation assay.

Species / strain

Species / strain 1

Species / strain / cell type:

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

Species / strain 2

Species / strain / cell type:

S. typhimurium TA 102

Metabolic activation:

with and without

Metabolic activation system:

S9 mix

Test concentrations with justification for top dose:

31.6, 100, 316, 1000, 2500 and 5000 microg/plate

Vehicle / solvent:

Distilled water and DMSO

Results and discussion

Test results

Test results 1

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:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 2

Species / strain:

S. typhimurium TA 102

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

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

In order to investigate the potential of COLCHICOSIDE for its ability to induce gene mutations the plate incorporation test and the pre-incubation test were performed with the Salmonella typhimurium strains. In two independent experiments several concentrations of the test item were used. Each assay was conducted with and without metabolic activation. The concentrations, including the controls, were tested in triplicate. No toxic effects of the test item were noted in any of the five tester strains used up to the highest dose group evaluated. No biologically relevant increases in revertant colony number of any of the five concentration level, neither in the presence nor absence of metabolic activation. The reference mutagens induced a distinct increase of revertant colonies indicating the validity of the experiments.

n order to investigate the potential of COLCHICOSIDE for its ability to induce gene mutations the plate incorporation test and the pre-incubation test were performed with the Salmonella typhimurium strains. In two independent experiments several concentrations of the test item were used. Each assay was conducted with and without metabolic activation. The concentrations, including the controls, were tested in triplicate. No toxic effects of the test item were noted in any of the five tester strains used up to the highest dose group evaluated. No biologically relevant increases in revertant colony number of any of the five concentration level, neither in the presence nor absence of metabolic activation. The reference mutagens induced a distinct increase of revertant colonies indicating the validity of the experiments.

In order to investigate the potential of COLCHICOSIDE for its ability to induce gene mutations the plate incorporation test and the pre-incubation test were performed with the Salmonella typhimurium strains. In two independent experiments several concentrations of the test item were used. Each assay was conducted with and without metabolic activation. The concentrations, including the controls, were tested in triplicate. No toxic effects of the test item were noted in any of the five tester strains used up to the highest dose group evaluated. No biologically relevant increases in revertant colony number of any of the five concentration level, neither in the presence nor absence of metabolic activation. The reference mutagens induced a distinct increase of revertant colonies indicating the validity of the experiments.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative with metabolic activation
negative without metabolic activation

It is concluded that the test item Colchicoside did not cause gene mutations by base pair changes or frameshifts in the genome of Salmonella typhimurium strains used.
Therefore, Colchicoside is considered to be non-mutagenic in this bacterial reverse mutation assay.