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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:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
2009-12-08 to 2009-12-17
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The study was conducted according to the appropriate OECD test guideline, and in compliance with GLP. The original study was considered reliability 1. Read-across to the registered substance is considered scientifically justified and is reliability 2.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.10 (Mutagenicity - In Vitro Mammalian Chromosome Aberration Test)
Deviations:
no
GLP compliance:
yes
Type of assay:
in vitro mammalian chromosome aberration test

Test material

Reference
Name:
Unnamed
Type:
Constituent

Method

Species / strain
Species / strain / cell type:
lymphocytes: human, from screened donor
Metabolic activation:
with and without
Metabolic activation system:
phenobarbitone (80 mg/kg) and β-naphthoflavone (100 mg/kg) induced rat liver S9
Test concentrations with justification for top dose:
44.06 to 1410 μg/ml
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: minimal essential medium- Justification for choice of solvent/vehicle: none given in report
Controlsopen allclose all
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
mitomycin C
Remarks:
without activation
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
cyclophosphamide
Remarks:
with activation
Details on test system and experimental conditions:
- Final concentration of S9: 2%- Cofactors: standardMETHOD OF APPLICATION: in mediumDURATION- Preincubation period: none- Exposure duration: 4 hours (with and without activation); 24 hours (without activation)- Expression time (cells in growth medium): 24 hours- Selection time (if incubation with a selection agent): none- Fixation time (start of exposure up to fixation or harvest of cells): 24 hoursSPINDLE INHIBITOR (cytogenetic assays): Colcemid (0.1 μg/ml) 2 hours before harvestSTAIN (for cytogenetic assays): GiesmaNUMBER OF REPLICATIONS: duplicate culturesNUMBER OF CELLS EVALUATED: 100 per culture, unless 30% cells with aberrations observed, when only 50 cells were evaluatedDETERMINATION OF CYTOTOXICITY - Method: mitotic indexOTHER EXAMINATIONS: - Determination of polyploidy: - Determination of endoreplication: - Other: OTHER:
Evaluation criteria:
A positive response was recorded for a particular treatment if the % cells with aberrations, excluding gaps, markedly exceeded that seen in the concurrent control, either with or without a clear dose-relationship. For modest increases in aberration frequency a dose response relationship is generally required and appropriate statistical tests may be applied in order to record a positive response.
Statistics:
The frequency of cells with aberrations excluding gaps and the frequency of polyploid cells was compared, where necessary, with the concurrent vehicle control value using Fisher's Exact test.

Results and discussion

Test results
Species / strain:
lymphocytes: human
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
705 μg/ml
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Additional information on results:
TEST-SPECIFIC CONFOUNDING FACTORS- Effects of pH: no significant change in pH- Effects of osmolality: did not increase by more than 50 mOsm- Precipitation: an oily precipitate was observedRANGE-FINDING/SCREENING STUDIES: Doses were based on the results of a range-finding studyCOMPARISON WITH HISTORICAL CONTROL DATA: results were within expected range
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

No increase in the number of polyploid cells was detected at any concentration with and without activation (4 and 24 hour treatment)

Table 1 Results of Chromosome Aberration Test – 4(20)-Hours Without Metabolic Activation (S9)

Treatment Group  Mitotic index % No. of cells scored  Frequency of aberrations with gaps (%)  Frequency of aberrations (without gaps 
Vehicle control  100  200  2 (1)  2 (1) 
352.5 μg/ml    80  200  2 (1)  1 (0.5)
 705  μg/ml  89  200  0  0
 1040 μg/ml  70  200  1 (0.5)  1 (0.5)
 Positive control  10  100  53 (53.0  52 (52.0)

Table 2 Results of Chromosome Aberration Test – 4(20)-Hours With Metabolic Activation (S9)

Treatment group  Mitotic index %  No. of cells scored  Frequency of aberrations with gaps (%)  Frequency of aberrations without gaps (%)
Vehicle control   100  200  4 (2.0)  1 (0.5)
 176.25 μg/ml  94  200  1 (0.5)  0
 352.5 μg/ml  91  200  2 (1.0)  2 (1.0)
 705 μg/ml  89  200  3 (1.5)  2 (1.0)
 1410 μg/ml  115  200  0  0
 Positive control CP 5 μg/ml  12  100  38 (38)  31 (31)

Table 3 Results of Chromosome Aberration Test – 24-Hours Without Metabolic Activation (S9)

Treatment  Mitotic index %  No of cells scored  Total number of aberrations with gaps (%)  Total number of aberration without gaps (%) 
Vehicle control   100  200  1 (0.5)  1 (0.5)
88.03 μg/ml    114  200  7 (3.5)  3 (1.5)
 176.25 μg/ml  81  200  2 (1.0)  2 (1.0)
 352 μg/ml  64  200  4 (2.0)  2 (1.0)
 705 μg/ml  34  200  6 (3.0)  2 (1.0)
 Positive control MMC 0.2 μg/ml  15  100  76 (76.0)  74 (74.0)

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):negative with and without activationDichloro(methyl)(vinyl)silane has been tested in a valid and reliable in vitro chromosome aberration assay according to OECD TG 473 and under GLP. No increase in the frequency of aberrations resulting from treatment with the test substance was detected. The expected results were obtained with vehicle and positive controls. It is concluded that the test substance is negative for the induction of chromosome aberrations in mammalian cells under the conditions of the test.