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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro cytogenicity / chromosome aberration study in mammalian cells
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2004
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP and appropriate guidelines
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2004
Report Date:
2004

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
Qualifier:
according to
Guideline:
EU Method B.10 (Mutagenicity - In Vitro Mammalian Chromosome Aberration Test)
Principles of method if other than guideline:
not relevant
GLP compliance:
yes
Type of assay:
in vitro mammalian chromosome aberration test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Identification: FR-513
Mol. formula: C5H9Br3O
Mol. Weight: 324.92
CAS #: 36483-57-5
Description: White flakes
Batch: 039084 (taken from label)
Composition: Tribromoneopentyl alchohol 97%, Dibromoneopentyl glycol < 0.1%
Storage: At room temperature in the dark
Stability under storage conditions: Stable

Method

Target gene:
not relevant
Species / strain
Species / strain / cell type:
lymphocytes: Peripheral human lymphocytes
Metabolic activation:
with and without
Metabolic activation system:
Aroclor-1254 induced rat liver S9-mix
Test concentrations with justification for top dose:
Range finder test: control: (DMSO), 33, 100, 333, 1000, 3250µg/ml (-S9-mix) (3hr, 24 hr, 48 hr exposure; 24hr, 24hr,48 hr fixation) ; control (DMSO), 33, 100, 333, 1000, 3250µg/ml (+S9-mix) (3hr exposure; 24hr fixation)
Main test 1: control (DMSO), 100, 333, 666, 1000, 1250, 1500, 2000 µg/ml, MMC-C (0.5 µg/ml) (-S9-mix)(3hr exposure, 24 hr fixation); control (DMSO), 100, 333, 666, 1000, 1250, 1500, 2000 µg/ml, CP (15 µg/ml) (+S9-mix)(3hr exposure, 24 hr fixation)
Main test 1A: control (DMSO), 100, 333, 666, 1000, 1050, 1100, 1150, 1200 µg/ml, MMC-C (0.5 µg/ml) (-S9-mix)(3hr exposure, 24 hr fixation); control (DMSO), 100, 333, 666, 1000, 1050, 1100, 1150, 1200 µg/ml, CP (15 µg/ml) (+S9-mix)(3hr exposure, 24 hr fixation)
Main test 1B: control (DMSO), 333, 1000, 1010, 1020, 1030, 1040, 1050 µg/ml, CP (15 µg/ml) (+S9-mix)(3hr exposure, 24 hr fixation)
Main test 1C: control (DMSO), 333, 666, 1000 µg/ml, MMC-C (0.5 µg/ml) (-S9-mix)(3hr exposure, 24 hr fixation); control (DMSO), 333, 666, 1000, 1020, 1050, 1100, 1200 µg/ml, CP (15 µg/ml) (+S9-mix)(3hr exposure, 24 hr fixation)
Main test 1D: control (DMSO), 100, 300, 600, 800, 1000, 1020, 1030, 1050, 1100 µg/ml, CP (15 µg/ml) (+S9-mix)(3hr exposure, 24 hr fixation)
Main test 2: control (DMSO), 17, 66, 100, 126, 150, 200 µg/ml, MMC-C (0.2 µg/ml) (-S9-mix)(24 hr exposure, 24 hr fixation); control (DMSO), 1, 3, 10,17, 66, 100 µg/ml, MMC-C (0.1 µg/ml) (-S9-mix)(48 hr exposure, 48 hr fixation); control (DMSO), 100, 167, 666, 1000, 1250, 1500, 2000 µg/ml, CP (15 µg/ml) (+S9-mix)(3 hr exposure, 3 hr fixation)
Main test 2: control (DMSO), 17, 66, 100, 126, 150, 200 µg/ml, MMC-C (0.2 µg/ml) (-S9-mix)(24 hr exposure, 24 hr fixation); control (DMSO), 1, 3, 10,17, 66, 100 µg/ml, MMC-C (0.1 µg/ml) (-S9-mix)(48 hr exposure, 48 hr fixation)
Main test 2A: see in materials and methods*
Vehicle / solvent:
DMSO
Controls
Untreated negative controls:
yes
Remarks:
DMSO
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
Positive controls:
yes
Remarks:
Mytomycin (MMC-C) (-S9-mix)
Positive control substance:
cyclophosphamide
Remarks:
Migrated to IUCLID6: (CP) + (S9-mix)
Details on test system and experimental conditions:
see attached document on test system and conditions
Evaluation criteria:
see attached document on data evaluation and statistical procedures
Statistics:
see attached document on data evaluation and statistical procedures

Results and discussion

Test resultsopen allclose all
Species / strain:
lymphocytes: Peripheral human lymphocytes
Metabolic activation:
with and without
Genotoxicity:
not determined
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
cell lysis at 3250µg/ml
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Species / strain:
lymphocytes: Peripheral human lymphocytes
Metabolic activation:
without
Genotoxicity:
not determined
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
1000µg/ml
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Species / strain:
lymphocytes: Peripheral human lymphocytes
Metabolic activation:
with
Genotoxicity:
not determined
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
100µg/ml, 1020 µg/ml
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Species / strain:
lymphocytes: Peripheral human lymphocytes
Metabolic activation:
with
Genotoxicity:
not determined
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Species / strain:
lymphocytes: Peripheral human lymphocytes
Metabolic activation:
with
Genotoxicity:
not determined
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
1100 µg/ml
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
see attached document on results
Remarks on result:
other:
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

see attached document on tables

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
positive clastogenic in the presence and in the absence of metabolic activation

FR-513 was found to be clastogenic in the presence of metabolic activation and at the highest test substance concentration (1000 microgram/ml) in the absence of metabolic activation. FR-513 has the potential to disturb mitotic processes and cell cycle progression.
Executive summary:

Evaluation of the ability of FR-513 to induce chromosome aberrations in cultured peripheral human lymphocytes was conducted using appropriate guidelines such as OECD 473. The report describes the effect of FR-513 on the number of chromosome aberrations in cultures perpheral human lymphocytes in the presence and absence of a metabolic activation system. A range finder study was conducted which followed by several main tests.

It is concluded that the test was valid and under the experimental conditions FR-513 was found to be clastogenic in the presence of metabolic activation and at the highest test substance concentration (1000 microgram/ml) in the absence of metabolic activation. FR-513 has the potential to disturb mitotic processes and cell cycle progression.