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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:
1978-01-18 to 1979-11-15
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 acceptable restrictions. It was not compliant with GLP. The restrictions are that only 100 cells were analysed per concentration. Read-across to the registered substance is considered scientifically justified.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1979
Report Date:
1979

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
Deviations:
yes
Remarks:
only 100 cells were analysed per concentration
GLP compliance:
not specified
Type of assay:
in vitro mammalian chromosome aberration test

Test material

Reference
Name:
Unnamed
Type:
Constituent

Method

Species / strain
Species / strain / cell type:
mouse lymphoma L5178Y cells
Metabolic activation:
with and without
Metabolic activation system:
Aroclor induced rat liver S9
Test concentrations with justification for top dose:
0.125-2.0 µl/m
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 for its solubility properties and relative non-toxicity to bacteria
Controls
Untreated negative controls:
yes
Remarks:
Media
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
ethylmethanesulphonate
Details on test system and experimental conditions:
METHOD OF APPLICATION: in medium

DURATION

- Exposure duration: 4 hours

- Expression time (cells in growth medium): 24 hours

- Fixation time (start of exposure up to fixation or harvest of cells): 25 hours

SPINDLE INHIBITOR (cytogenetic assays): Colcemid

STAIN (for cytogenetic assays): 10 % Giemsa

NUMBER OF REPLICATIONS: 1

NUMBER OF CELLS EVALUATED: 100 cells per test conc.

DETERMINATION OF CYTOTOXICITY
- Method: Toxicity was measured as loss in growth potential of the cells induced by a 4-hour exposure to the test article followed by a 24-hour expression period in growth medium


Evaluation criteria:
The test substance is clastogenic if a statistically significant dose related increase in aberrations is shown.
Statistics:
A two-tailed t-test (Finney 1971) was used to determine statistical significance of results. Clearly positive results indicated by p < 0.01

Results and discussion

Test results
Species / strain:
mouse lymphoma L5178Y cells
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: strain/cell type: mouse lymphoma L5178Y cells
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

Table 2: Results of chromosome analysis Experiment 1 without activation (per 100 cells scored)

 

Solvent

Control

Negative Control

Positive

Control

0.125 μl/ml

0.25 μl/ml

0.5 μl/ml

1 μl/ml

2 μl/ml

Cytotoxicity

No

No

Yes

No

No

No

No

No

 

Chromatid aberrations

gaps

0

0

0

0

0

0

0

0

breaks

0

0

4

0

0

0

0

0

interchanges

0

0

0

0

0

0

0

0

deletion

0

0

0

0

0

0

0

0

Chromosome aberrations

gaps

0

0

0

0

0

0

0

0

breaks

0

0

0

0

0

0

0

0

interchanges

0

0

0

0

2

0

0

0

acentric fragment

4

3

18

1

11

5

2

1

pulverised Cells

0

0

0

0

0

0

0

0

pulverised chromosome

0

0

0

0

0

0

0

0

triradial

0

0

11

0

1

0

0

1

quadriradial

0

0

10

0

0

0

0

0

ring

1

0

0

0

1

1

0

0

fragment

2

0

5

4

2

6

1

0

deletion

0

0

0

1

0

0

0

0

diacentric chromosome

0

0

0

0

0

0

0

0

minute chromosome

0

0

0

0

0

1

0

1

complex rearrangement

0

0

0

0

0

0

0

0

Mitotic index (%)

7

7.4

4.4

6.8

7.4

6.8

5.8

5.6

Polyploidy (% mean freq.)

0

0

0

0

0

0

0

0

Endo reduplication

NR

NR

NR

NR

NR

NR

NR

NR

 Solvent control with Ethanol

NR not reported

Table 3: Results of chromosome analysis Experiment 1 with activation (per 100 cells scored)

 

Solvent

Control

Negative Control

Positive

Control

0.125 μl/ml

0.250 μl/ml

0.5 μl/ml

1 μl/ml

2 μl/ml

Cytotoxicity

No

No

Yes

No

No

No

No

No

 

Chromatid aberrations

gaps

0

0

0

0

0

1

0

0

breaks

0

0

3

0

0

0

0

0

interchanges

0

0

0

0

0

0

0

0

deletion

0

0

0

0

0

1

0

0

Chromosome aberrations

gaps

0

0

0

0

0

0

0

0

breaks

0

0

0

0

0

0

0

0

interchanges

0

0

3

0

0

0

0

0

acentric fragment

2

4

3

6

7

5

10

4

pulverised Cells

0

0

27

0

0

1

0

0

pulverised chromosome

0

0

4

0

0

0

0

0

triradial

2

0

2

0

0

2

3

1

quadriradial

0

0

1

0

0

0

0

0

ring

0

0

1

0

0

1

1

0

fragment

4

0

2

4

4

9

8

3

deletion

0

0

0

0

2

0

0

0

diacentric chromosome

0

0

0

0

0

0

0

0

minute chromosome

0

0

0

0

0

1

1

0

complex rearrangement

0

0

1

0

0

0

0

0

Mitotic index (%)

6.8

6.4

0.8

7.8

6.6

10.8

8.6

5.4

Polyploidy (% mean freq.)

0

0

0

0

0

0

0

0

Endo reduplication

NR

NR

NR

NR

NR

NR

NR

NR

 Solvent control with Ethanol

NR not reported

Applicant's summary and conclusion

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

Triethoxy(methyl)silane has been tested according to a protocol that is similar to OECD 473. The test substance did not cause a statistically significant, dose related increase in chromosome aberrations. The test substance was considered non-clastogenic in mouse lymphoma L5178Y cells under the conditions of the test.