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Diss Factsheets

Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1977-12-08 to 1977-12-11
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to a test protocol that is comparable to the appropriate OECD test guideline. It was not compliant with GLP.

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 471 (Bacterial Reverse Mutation Assay)
Deviations:
yes
Remarks:
range of strains and no replicates
Principles of method if other than guideline:
Method: other: Litton Bionetics standard procedure: Screening Program for the Identification of Potential Mutagens and Carcinogens. Protocol Number : DMT 100
GLP compliance:
no
Type of assay:
bacterial reverse mutation assay

Test material

Constituent 1
Chemical structure
Reference substance name:
Trichloro(methyl)silane
EC Number:
200-902-6
EC Name:
Trichloro(methyl)silane
Cas Number:
75-79-6
Molecular formula:
CH3Cl3Si
IUPAC Name:
trichloro(methyl)silane

Method

Species / strain
Species / strain / cell type:
other: Salmonella typhimurium: TA 1535, TA 1537, TA 1538, TA 98 and TA100; Saccharomyces cerevisiae D4, and E coli Pol A+/A-
Metabolic activation:
with and without
Metabolic activation system:
Aroclor induced rat liver S9
Test concentrations with justification for top dose:
0.001-5 µl/plate, equivalent to approx 10-5000 µg/plate
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: ethanol

- Justification for choice of solvent/vehicle: no information
Controlsopen allclose all
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: Methylnitrosoguanidine
Remarks:
TA 1535, TA 100, D4 (without activation)
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: Quinicrine Mustard
Remarks:
TA 1537 (without activation)
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
2-nitrofluorene
Remarks:
TA 1535, TA 98 (without activation)
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: 2-anthramine
Remarks:
TA 1535, TA 100, D4 (with activation)
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: 8-aminoquinoline
Remarks:
TA 1537 (with activation)
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: 2-acetylaminofluorene
Remarks:
TA 1538, TA 98 (with activation)
Details on test system and experimental conditions:
METHOD OF APPLICATION: in agar (plate incorporation)

DURATION

- Expression time (cells in growth medium): 48 hours

NUMBER OF REPLICATIONS: 2 plates for each test concentration for strains TA 98 and TA 1537

DETERMINATION OF CYTOTOXICITY

- Method: relative total growth; background lawn
Statistics:
Responses (number of revertants) from the test substance were compared to concurrent negative and positive controls, as well as to historical data.

Results and discussion

Test results
Species / strain:
other: Salmonella typhimurium: TA 1535, TA 1537, TA 1538, TA 98 and TA100; Saccharomyces cerevisiae D4, and E coli Pol A+/A-
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
other: at 5 µg/plate with TA 1535, TA 1537 and TA 1538 and D4 ; and 1 and 5 ug/plate for E.coli
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Additional information on results:
The results of the tests conducted without metabolic activation were all negative. The test with the TA 1535 and TA 1537 strains were repeated due to increased numbers of revertants being observed - these results are not presented in detail in the study report. The repeat tests were negative. The E. coli tests were also repeated to determine if the zone of inhibition was due to an effect on the DNA. The repeat test showed that the inhibition was due to the toxicity of the chemical.

With activation, the test substance exhibited toxicity with strains TA 1535, TA 1537, TA 1538 and D4 at 5 µg/plate. There was also toxicity to the E. coli strains at 1 and 5 µl /plate.

For the Salmonella strains, revertants per plate for the positive control substances ranged from 124 to >1000, depending on the agent and strain.
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

 

Table 2 : Experiment 1 Plate incorporation number of revertants per plate

 

TA 98

TA 100

TA 1535

Conc.
(
µl/ml)

— MA

+ MA

Cytotoxic
(yes/no)

— MA

+ MA

Cytotoxic
(yes/no)

— MA

+ MA

Cytotoxic
(yes/no)

0*

63

49

No

230

217

No

30

29

No

0.001

89

43

No

260

136

No

38

33

No

0.01

87

69

No

220

158

No

28

27

No

0.1

75

77

No

227

148

No

21

30

No

1

74

74

No

203

187

No

15

33

Yes

5

47

19

Yes

106

159

Yes

0

10

Yes

Positive control

636

870

No

672

921

No

681

240

No

*solvent control withEthanol

 

Table 2: Experiment 1 Plate incorporation number of revertants per plate

 

TA 1537

TA 1538

Conc.
(
µl/ml)

— MA

+ MA

Cytotoxic
(yes/no)

— MA

+ MA

Cytotoxic
(yes/no)

0*

9

16

No

13

20

No

0.001

19

18

No

20

20

No

0.01

6

17

No

19

12

No

0.1

12

16

No

24

12

No

1

3

22

Yes

31

11

No

5

4

11

Yes

4

11

Yes

Positive control

724

210

No

593

635

No

*solvent control withEthanol

Applicant's summary and conclusion

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

Trimethylchlorosilane has been tested for mutagenicity to bacteria in a valid assay using a protocol that is similar to OECD 471. Appropriate concurrent negative and positive controls were included, and the expected responses were observed. The test substance, trimethylchlorosilane (CAS No. 75-79-6), exhibited some toxicity to 3 of the Salmonella strains. However there was no reproducible evidence of mutagenic activity in any of the assays conducted, both with and without metabolic activation. In addition, no genotoxic activity was observed in Saccharomyces cerevisiae D4, nor in the E coli Pol A+/A- zone of inhibition assay. The test substance was not considered to be mutagenic under these test conditions.