Dichloro(chloromethyl)methylsilane

Genetic toxicity: in vitro

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: OECD guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

Report date:

2002

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Dichloro(chloromethyl)methylsilane

EC Number:

216-319-5

EC Name:

Dichloro(chloromethyl)methylsilane

Cas Number:

1558-33-4

Molecular formula:

C2H5Cl3Si

IUPAC Name:

dichloro(chloromethyl)methylsilane

Details on test material:

Designation Chlormethyl-methyl-dichlorsilan
CAS No. 1558-33-4
Date of receipt March 6th, 2002
Aggregate state under storage conditions liquid at + 20°C
Storage conditions at room temperature, dark, in original container tightly closed
Colour colourless
Solvent abs. ethylene glycol dimethylether
Stability in solvent at +4°C in the dark: > 1 day
Expiry date March 2003

Method

Species / strain

Species / strain 1

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Additional strain / cell type characteristics:

not applicable

Species / strain 2

Species / strain / cell type:

S. typhimurium TA 102

Additional strain / cell type characteristics:

not applicable

Metabolic activation:

with and without

Metabolic activation system:

S9 mix

Test concentrations with justification for top dose:

10, 31.6, 100, 316 and 1000 µg/plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: Ethylene glycol dimethylether
- Justification for choice of solvent/vehicle: solubility

Controls

Controls 1

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

sodium azide

Remarks:

strains TA 1535, TA 100 without metabolic activation

Controls 2

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

2-nitrofluorene

Remarks:

strain TA 98 without metabolic activation

Controls 3

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

9-aminoacridine

Remarks:

strain TA 1537 without metabolic activation

Controls 4

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

methylmethanesulfonate

Remarks:

strain TA 102 without metabolic activation

Controls 5

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2-anthracene amide

Remarks:

strains TA 98, TA 102, TA 1537 with metabolic activation

Controls 6

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

cyclophosphamide

Remarks:

strains TA 100, TA 1535 with metabolic activation

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation) for 1st experiment, preincubation for second experiment

DURATION
- Preincubation period: 60 min
- Exposure duration: 48 h


NUMBER OF REPLICATIONS:

Evaluation criteria:

The statisIn the test laboratory, a test chemical is considered to show a positive response if the number of revertants is significantly increased (p <= 0.05, U-test according to MANN and WHITNEY, compared with the solvent control to at least 2-fold of the solvent control for TA 98, TA 100 and TA 102 and 3-fold of the solvent control for TA 1535 and TA 1537 in both independent experiments; in addition, a significant (p <= 0.05) concentration (log value)-related effect 5pearman's rank correlation coefficient, is observed; positive results have to be reproducible and the histidine independence of the revertants has to be confirmed by streaking random samples on histidine-free agar plates.

Results and discussion

Test results

Test results 1

Species / strain:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Test results 2

Species / strain:

S. typhimurium TA 102

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative

No mutagenic effect (no increase in revertant colony numbers as compared with control counts) was observed for Chlormethyl-methyl-dichlorsilan tested up to a concentration of 1000 Jµg/plate in any of the 5 test strains in two independent experiments without and with metabolic activation (plate incorporation or preincubation test).

Executive summary:

Chlormethyl-methyl-dichlorsilan was examined in the 5 Sa/monella typhimurium strains TA 98, TA 100, TA 102, TA 1535 and TA 1537 in two independent experiments, each carried out without and with metabolic activation (a microsomal preparation derived from Aroclor 1254-induced rat liver). The first experiment was carried out as a plate incorporation test and the second as a preincubation test.

Preliminary test

Chlormethyl-methyl-dichlorsilan was examined in a preliminary cytotoxicity test without metabolic activation in test strain TA 100. Ten concentrations of Chlormethylmethyl- dichlorsilan ranging from 0.316 to 5000 µg/plate were examined in the preliminary test using strain TA 100. Cytotoxicity (scarce background lawn) was noted at the concentrations of 1000 up to 5000 µg/plate. Hence, 1000 µg/plate was chosen as the top concentration for the main study.

Main study

Five (5) concentrations ranging from 10 to 1000 µg Chlormethyl-methyl-dichlorsilan/ plate were employed in two independent experiments each carried out without and with metabolic activation.

Cytotoxicity

In the plate incorporation test without and with metabolic activation cytotoxicity (scarce background lawn) was noted at the top concentration of 1000 µg Chlormethyl-methyldichlorsilan/ plate in all test strains. In the preincubation test without and with metabolic activation cytotoxicity (scarce background lawn) was noted at the concentration of 1000 µg Chlormethyl-methyldichlorsilan/ plate in all test strains. Pronounced cytotoxicity (reduction of the number of revertants by more than 50%) was noted at the concentration of 1000 µg/plate in test strains TA 1535 and TA 1537.

Mutagenicity

No mutagenic effect (no increase in revertant colony numbers as compared with control counts) was observed for Chlormethyl-methyl-dichlorsilan tested up to 1000 µg Chlormethyl-methyl-dichlorsilan/plate in any of the 5 test strains in two independent experiments without and with metabolic activation (plate incorporation or preincubation test).

In conclusion, under the present test conditions Chlormethyl-methyl-dichlorsilan tested up to cytotoxic concentrations caused no mutagenic effect in the Salmonella typhimurium strains TA 98, TA 100, TA 102, TA 1535 and TA 1537 neither in the plate incorporation test nor in the preincubation test each carried out without and with metabolic activation.