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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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The study was conducted according to a test protocol that is comparable to the appropriate OECD test guideline, with restrictions. The restrictions are that only 100 cells evaluated and the reporting differed from the current guideline. It was not compliant with GLP. It is considered that read across to the registered substance is scientifically justified.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1978
Report date:
1978

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
Deviations:
yes
Remarks:
only 50 cells scored for aberrations, reporting has less detail than current guideline
Principles of method if other than guideline:
Litton Bionetics standard procedure: Screening Program for the Identification of Potential Mutagens and Carcinogens. Protocol Number: DMT 100
GLP compliance:
no
Type of assay:
in vitro mammalian chromosome aberration test

Test material

Constituent 1
Reference substance name:
Trichloro(methyl)silane
EC Number:
200-902-6
EC Name:
Trichloro(methyl)silane
Cas Number:
75-79-6
IUPAC Name:
trichloro(methyl)silane

Method

Species / strain
Species / strain / cell type:
mouse lymphoma L5178Y cells
Metabolic activation:
with and without
Metabolic activation system:
mouse liver S9
Test concentrations with justification for top dose:
0.02, 0.04, 0.08, 0.16, and 0.32 µl/ml, equivalent to approximately 20, 40, 80, and 160 µg/ml
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: ethanol

- Justification for choice of solvent/vehicle: It is assumed by the reviewer that the solvent was chosen based on solubility properties and relative non-toxicity to bacteria
Controlsopen allclose all
Untreated negative controls:
yes
Remarks:
Medium
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
ethylmethanesulphonate
Remarks:
(without activation)
Untreated negative controls:
yes
Remarks:
Medium
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
N-dimethylnitrosamine
Remarks:
(with activation)
Details on test system and experimental conditions:
METHOD OF APPLICATION: in medium

DURATION
- Exposure time: 4 hours

- Expression time (cells in growth medium): 20 hours

NUMBER OF REPLICATIONS: 1 plates for each test concentration

NUMBER OF CELLS EVALUATED: 50 per plate

DETERMINATION OF CYTOTOXICITY

- Method: mitotic index

Results and discussion

Test results
Species / strain:
mouse lymphoma L5178Y cells
Metabolic activation:
with and without
Genotoxicity:
ambiguous
Cytotoxicity / choice of top concentrations:
other: >= 0.16 µl/ml (equivalent to approximately 160 µg/ml)
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

Table 2: Cytogenetic analysis (without activation)

Concentration

µg/ml*

Total No.

Of Cells

Type / Frequency

Aberrations per Cell (%)

No. Of Cells with 2+

Aberrations (%)

Mitotic

Index (%)

Negative Control

50

1tb

0

2.2

Solvent Control

50

0

0

13.8

Positive Control

50

6tb, 1f, 1t, 6qr, 5tr, 1min

4

7.4

10

50

1qr

0

7.4

20

50

0

0

4.6

40

50

1f

0

5.2

80

50

1af, 1tb

0

8.4

160

50

0

0

5.4

 * Concentrations given in report as µl/ml - converted by reviewer

Table 3: Cytogenetic analysis (with activation)

Compound and

Concentration

µg/ml*

Total No.

Of Cells

Type / Frequency

Aberrations per Cell (%)

No. Of Cells with 2+

Aberrations (%)

Mitotic

Index (%)

Negative Control

50

1tb, 1>

0

4

Solvent Control

50

0

0

9

Positive Control

50

6tb, 1f, 2t, 1tr, 1qr

1

4.4

20

50

1tb

0

4.4

40

50

2t, 1tr

1

10.8

80

50

1tb, 3f, 1tr

2

8

160

50

1tb, 1f, 1af, 1t

1

7.8

320

50

0

0

10.4

 * Concentrations given in report as µl/ml - converted by reviewer

Key to type of aberration

tb

Chromatidbreak

f

Fragment

qr

Quadriradial

tr

Triradial

min

Minute chromosome

af

Acentricfragment

t

Translocation

 

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
positive with metabolic activation not dose related
negative without metabolic activation

Trichloro(methyl)silane has been tested in a reliable assay according to a protocol that is similar to OECD TG 476. Appropriate concurrent negative and positive controls were included and the expected responses were observed. The number of cells with 2 or more aberrations increased very slightly under activation conditions, and no increase was observed at the highest dose tested. Trimethylchlorosilane was considered by the authors of the study to have weak clastogenic activity that may be related to the cytotoxic properties of the test substance. It is concluded by the reviewer that the study does not demonstrate a biologically relevant effect.