Chlorodimethyloctylsilane

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

In vitro gene mutation: Bacterial reverse mutation assay (Ames test / OECD 471): negative

Link to relevant study records

Reference

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Version / remarks:

21st July, 1997

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)

Version / remarks:

May 30, 2008

Qualifier:

according to guideline

Guideline:

EPA OTS 798.5100 (Escherichia coli WP2 and WP2 UVRA Reverse Mutation Test)

Version / remarks:

August 1998

GLP compliance:

yes (incl. QA statement)

Remarks:

Bayerisches Landesamt für Gesundheit und Lebensmittelsicherheit

Type of assay:

bacterial reverse mutation assay

Target gene:

His operon

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102

Metabolic activation:

with and without

Metabolic activation system:

cofactor supplemented post-mitochondrial fraction (S9 mix), prepared from the livers of rats treated with phenobarbital and β-naphthoflavone

Test concentrations with justification for top dose:

Experiment I: 0.0316, 0.100, 0.316, 1.0, 2.5 and 5.0 µL/plate
Experiment II: 0.0158, 0.050, 0.158, 0.5, 1.58 and 5.0 µL/plate

Doses were selected based on the results of a preliminary toxicity test.

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: ethanol
- Justification for choice of solvent/vehicle: The test item was dissolved in ethanol and diluted prior to treatment. The solvent was compatible with the survival of the bacteria and the S9 activity. The pH-value detected with the test item (100 µL stock solution + 500 µL S9 mix substitution buffer) and was within the physiological range (pH 7.5).

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Remarks:

A. dest.

True negative controls:

no

Positive controls:

yes

Positive control substance:

sodium azide

methylmethanesulfonate

other: 4-nitro-o-phenylene-diamine (4-NOPD) and 2-aminoanthracene (2-AA)

Details on test system and experimental conditions:

METHOD OF APPLICATION: iin agar (plate incorporation)

DURATION
- Exposure duration: at least 48 h

NUMBER OF REPLICATIONS: 3

DETERMINATION OF CYTOTOXICITY
- Method: Cytotoxicity can be detected by a clearing or rather diminution of the background lawn or a reduction in the number of revertants down to a mutation factor of approximately ≤ 0.5 in relation to the solvent control.

Evaluation criteria:

A test was considered acceptable if for each strain:
- the bacteria demonstrated their typical responses to ampicillin (TA98, TA100, TA102)
- the negative control plates (A. dest.) with and without S9 mix are within the following ranges:

- S9 + S9
min max min max
TA 98 11 58 15 59
TA 100 49 155 62 160
TA 1535 4 41 3 38
TA 1537 3 35 3 36
TA 102 141 472 157 586

- corresponding background growth on negative control, solvent control and test plates was observed
- the positive controls showed a distinct enhancement of revertant rates over the control plate
- at least five different concentrations of each tester strain were analysable.

A test item was considered as mutagenic if:
- a clear and dose-related increase in the number of revertants occurs and/or
- a biologically relevant positive response for at least one of the dose groups occurs in at least one tester strain with or without metabolic activation.

A biologically relevant increase was described as follows:
- if in tester strains TA98, TA100 and TA102 the number of reversions was at least twice as high
- if in tester strains TA 1535 and TA 1537 the number of reversions was at least three times higher than the reversion rate of the solvent control.

Statistics:

Not reported

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

cytotoxic effects at 5.0 µL/plate, -S9

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Species / strain:

S. typhimurium TA 102

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation: No precipitation of the test item was observed in any tester strain used in experiment I and II (with and without metabolic activation).

RANGE-FINDING/SCREENING STUDIES: In the preliminary experiment, no mutagenicity was observed in either strain, TA98 or TA100, ±S9. Reduced background lawn was observed in TA98 at 5 µL/plate (the high dose), -S9. No other toxicity was observed.

ADDITIONAL INFORMATION ON CYTOTOXICITY:
- Measurement of cytotoxicity used: Toxicity was detected by a clearing or rather diminution of the background lawn or a reduction in the number of revertants down to a mutation factor of approximately ≤ 0.5 in relation to the solvent control.
- Other observations when applicable: No toxic effects of the test item were noted in any of the five tester strains used up to the highest dose group evaluated (with and without metabolic activation) in experiment I and II with one exception: In experiment I toxic effects of the test item were observed in tester strain TA 98 at a concentration of 5.0 µL/plate (without metabolic activation).

Conclusions:

In conclusion, it can be stated that during the described mutagenicity test and under the experimental conditions reported, chloro(dimethyl)octylsilane did not cause gene mutations by base pair changes or frameshifts in the genome of the tester strains used.
Therefore, chloro(dimethyl)octylsilane is considered to be non-mutagenic in this bacterial reverse mutation assay.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

A reliable bacterial gene mutation study (Ames test) performed according to OECD TG 471 and in compliance with GLP with chloro(dimethyl)octylsilane is available (Eurofins 2018). In order to investigate the potential of chloro(dimethyl)octylsilane for its ability to induce gene mutations the plate incorporation test (experiment I and II) was performed with the Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537 and TA 102. In two independent experiments several concentrations (0.0158 to 5 µL/plate) of the test item were used. Each assay was conducted with and without metabolic activation. The concentrations, including the controls, were tested in triplicate. No precipitation of the test item was observed in any tester strain used in experiment I and II (with and without metabolic activation). No toxic effects of the test item were noted in any of the five tester strains used up to the highest dose group evaluated (with and without metabolic activation) in experiment I and II with one exception: In experiment I toxic effects of the test item were observed in tester strain TA 98 at a concentration of 5.0 µL/plate (without metabolic activation). No biologically relevant increases in revertant colony numbers of any of the five tester strains were observed following treatment with chloro(dimethyl)octylsilane at any concentration level, neither in the presence nor absence of metabolic activation in experiment I and II.

In conclusion, it can be stated that during the described mutagenicity test and under the experimental conditions reported, chloro(dimethyl)octylsilane did not cause gene mutations by base pair changes or frameshifts in the genome of the tester strains used.Therefore, chloro(dimethyl)octylsilane is considered to be non-mutagenic in this bacterial reverse mutation assay.

Justification for classification or non-classification

Based on the available data on genetic toxicity, there is no indication that chlorodimethyloctylsilane induces genetic toxicity in bacteria. However, no final decision on classification for genetic toxicity according to Regulation (EC) 1272/2008 can be made, as no information on chromosomal aberration and mutagenicity in mammalian cells/in vivo is available.