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Diss Factsheets

Administrative data

Endpoint:
in vitro cytogenicity / micronucleus study
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1997
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
publication
Title:
Indication for thresholds of chromosome non-disjunction versus chromosome lagging induced by spindle inhibitors in vitro in human lymphocytes.Mutagenesis, 12, 133-140.
Author:
Elhajouji A, Tibaldi F and Kirsch-Volders M
Year:
1997
Bibliographic source:
Mutagenesis, 12, 133-140.

Materials and methods

Principles of method if other than guideline:
Chromosome non-disjunction was estimated on cytokinesis-blocked binucleated lymphocytes in combination with FISH using chromosome specific centromeric probes (pUC1.77 for chromosome 1 and D17Z1 for chromosome 17). This combination allows accurate evaluation of non-disjunction since artefacts are excluded from the analysis as only binucleates with the correct number of hybridization signals were taken into account. Based on mathematical models, concentrationdependent effect and number of targets necessary for induction of chromosome loss and chromosome non-disjunction were assessed.
GLP compliance:
not specified
Remarks:
No indication about GLP-compliant is reported in the paper
Type of assay:
in vitro mammalian cell micronucleus test

Test material

Constituent 1
Chemical structure
Reference substance name:
Colchicine
EC Number:
200-598-5
EC Name:
Colchicine
Cas Number:
64-86-8
Molecular formula:
C22H25NO6
IUPAC Name:
colchicine
Constituent 2
Reference substance name:
N-[(7S)-1,2,3,10-tetramethoxy-9-oxo-6,7-dihydro-5H-benzo[d]heptalen-7-yl]acetamide
IUPAC Name:
N-[(7S)-1,2,3,10-tetramethoxy-9-oxo-6,7-dihydro-5H-benzo[d]heptalen-7-yl]acetamide

Method

Species / strain
Species / strain / cell type:
lymphocytes: human
Metabolic activation:
without
Test concentrations with justification for top dose:
0.0025-0.1 mcM

Results and discussion

Test results
Species / strain:
mammalian cell line, other:
Metabolic activation:
without
Genotoxicity:
positive
Remarks on result:
other: strain/cell type: lymphocytes
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

In the absence of metabolic activation, there was a dose-related increase in the frequency of micronuclei, chromosome loss and chromosome non-disjunction.

Conc. range: 0,0025 - 0,1 microM

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
positive

Positive. In the absence of metabolic activation, there was a dose-related increase in the frequency of micronuclei, chromosome loss and chromosome non-disjunction.