Allyltrimethylsilane

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

In vitro gene mutation:

Bacterial reverse mutation assay (similar to OECD 471): negative

In vitro mammalian cell gene mutation assay (similar to OECD 490): negative

Link to relevant study records

Reference

Reference 1

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

The 5th strain is missing either E.coli or TA102

GLP compliance:

not specified

Type of assay:

bacterial forward mutation assay

Target gene:

his operon

Species / strain / cell type:

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

Additional strain / cell type characteristics:

not specified

Species / strain / cell type:

S. typhimurium TA 1538

Additional strain / cell type characteristics:

not specified

Metabolic activation:

with and without

Metabolic activation system:

Aroclor 1254-induced rat liver S9 and induced hamster liver S9 mix

Test concentrations with justification for top dose:

1 to 1000 µg/plate based on a preliminary dose range-finding study using strain TA100.

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: not reported; however, the study states that the appropriate concurrent solvent was used

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

not specified

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation)
- Cell density at seeding: (1-2) X 10^9 cells/mL

DURATION
- Exposure duration: 48 h

NUMBER OF REPLICATIONS: triplicate

Rationale for test conditions:

Not reported

Evaluation criteria:

For the test article to be considered positive, it had to induce at least a doubling (TA98, TA100, and TA1535) in the mean number of revertants per plate of at least one tester strain. This increase inthe mean revertants per plate had to be accompanied by a doseresponse to increasing concentrations of the test chemical. If the study showed a dose response with a less than 3-fold increase onTA1537 or TA1538, the response had to be confirmed in a repeat experiment

Statistics:

Not reported

Key result

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

not specified

Untreated negative controls validity:

not applicable

Positive controls validity:

not specified

Key result

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

not specified

Untreated negative controls validity:

not applicable

Positive controls validity:

not specified

Key result

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

not specified

Untreated negative controls validity:

not applicable

Positive controls validity:

not specified

Key result

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

not specified

Untreated negative controls validity:

not applicable

Positive controls validity:

not specified

Key result

Species / strain:

S. typhimurium TA 1538

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

not specified

Untreated negative controls validity:

not applicable

Positive controls validity:

not specified

Additional information on results:

No additional information

Conclusions:

There was no evidence of a test-substance related increase in the number of revertants with or without activation.

Reference 2

Endpoint:

in vitro gene mutation study in mammalian cells

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 490 (In Vitro Mammalian Cell Gene Mutation Tests Using the Thymidine Kinase Gene)

Deviations:

yes

Remarks:

Cytoxocity not specified; limited details provided

GLP compliance:

not specified

Type of assay:

in vitro mammalian cell gene mutation tests using the thymidine kinase gene

Target gene:

thymidine kinase locus

Species / strain / cell type:

mouse lymphoma L5178Y cells

Details on mammalian cell type (if applicable):

CELLS USED
- Source of cells: Dr. Donald Clive, Burroughs Wellcome Co. (Re-search Triangle Park, NC)

MEDIA USED
- Type and identity of media including CO2 concentration if applicable: Fischer's medium for leukemic cells of mice supplemented with 10% horse serum and 0.02% pluronic F-68
- Periodically checked for Mycoplasma contamination: yes

Additional strain / cell type characteristics:

not specified

Metabolic activation:

with and without

Metabolic activation system:

Aroclor 1254-induced male Sprague-Dawley rats

Test concentrations with justification for top dose:

0.01-0.37 µg/mL

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: none reported

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

3-methylcholanthrene

ethylmethanesulphonate

methylmethanesulfonate

other: dimethylbenz[a]-anthracene

Details on test system and experimental conditions:

METHOD OF APPLICATION: in medium, Fischer's medium
- Cell density at seeding: 3 X 10^5 /mL

DURATION
- Exposure duration: 4 hr
- Expression time (cells in growth medium): 48 hr
- Selection time (if incubation with a selection agent): 10-12 dyas

SELECTION AGENT (mutation assays): trifluorothymidine (TFT)

NUMBER OF REPLICATIONS: duplicate

NUMBER OF CELLS EVALUATED: Only colonies larger than 0.2 mm in diameter were counted.

Rationale for test conditions:

The mutagenicity assay was performed according to the procedure described by Clive and Spector.

Evaluation criteria:

Results from this study were interpreted using a doubling of the mutant frequency over the concurrent solvent-treated control value as an indication of a positive effect, together with evidence of a dose-related increase. Only doses yielding total growth values of 10% were used in the analysis of induced mutant frequency. Doses yielding less than 10% total growth were used in determining dose response.

Statistics:

None reported

Key result

Species / strain:

mouse lymphoma L5178Y cells

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

not applicable

Untreated negative controls validity:

not specified

Positive controls validity:

not specified

Conclusions:

The test material is not considered to be mutagenic in an in vitro mammalian cell gene mutation assay (thymidine kinase locus) in mouse lymphoma L5178Y cells both with and without metabolic activation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Two genetic studies were identified in a published article by Seifried et al., 2006. Assays conducted in this report were not performed according to Guideline but are similar and acceptable for evaluation. For the Ames assay, the main deviation is that the 5th strain is missing either E.coli or TA102. Even though these two studies had some deviations, but both studies showed negative results and thus there is no evidence of mutagenicity potential.

Genetic toxicity (mutagenicity) in bacteria in vitro

In a published study (Seifried et al., 2006), the mutagenicity potential of allyltrimethylsilane was examined in an Ames assay. According to the publication, Salmonella typhimurium strains TA98, TA100, TA1535, TA1537, and TA1538 were evaluated according to the plate incorporation procedure in the absence and presence of a metabolic activation system (Aroclor 1254-induced rat and hamster liver S9-mix). The table in the report suggests that doses of 1 to 1000 µg/plate were examined. No significant increase in the number of revertants was observed in any of the tester strains with and without metabolic activation.

Genetic toxicity (mutagenicity) in mammalian cells in vitro

In a published study (Seifried et al., 2006), an in vitro mammalian cell gene mutation assay (thymidine kinase locus) in mouse lymphoma L5178Y cells both with and without metabolic activation was performed. For the study, mouse lymphoma L5178Y cells were treated with the test substance at concentrations of 0.1 to 0.37 µg/mL for 4 hours in the absence and presence of a metabolic activation system (Aroclor 1254-induced rat liver S9-mix. Based on these results, the test material is not considered to be mutagenic in an in vitro mammalian cell gene mutation assay (thymidine kinase locus) in mouse lymphoma L5178Y cells both with and without metabolic activation.

Justification for classification or non-classification

The available data on genetic toxicity of allyltrimethylsilane do not meet the criteria for classification according to Regulation (EC) No 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.