Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Ames test according to OECD TG 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
Study period:
2018-01-25 to 2018-04-24
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
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
Bayrisches 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 and TA 100
Additional strain / cell type characteristics:
other: The tester strains TA98, TA100 and TA102 contain the R-factor plasmid, pkM101
Species / strain / cell type:
S. typhimurium TA 102
Additional strain / cell type characteristics:
other: The tester strains TA98, TA100 and TA102 contain the R-factor plasmid, pkM101
Metabolic activation:
with and without
Metabolic activation system:
S9 liver microsomal fraction from phenobarbital / β naphthoflavone-induced male rats
Test concentrations with justification for top dose:
0.0100, 0.0316, 0.100, 0.316, 1.0, 2.5 and 5.0 µL/plate

Concentrations were selected based on the results of a preliminary experiment.
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: DMSO was selected based on the solubility of the test material.
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
sodium azide
methylmethanesulfonate
other: 4-nitro-o-phenylene-diamine (4-NOPD); 2-aminoanthracene (2AA)
Details on test system and experimental conditions:
METHOD OF APPLICATION: in agar for plate incorporation test (experiment I) and the pre-incubation test (experiment II)

DURATION
- Preincubation period: 60 min
- Exposure duration: 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 were within the historical control data range
- 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 occurred and/or
- a biologically relevant positive response for at least one of the dose groups occurred in at least one tester strain with or without metabolic activation.

A biologically relevant increase was described as follows:
- if in tester strains TA 98, TA 100 and TA 102 the number of reversions was at least twice as high
- if in tester strains TA 1535 and TA 1537 the number of reversions ws 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
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:
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:
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:
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 nor precipitates, but tested up to recommended limit concentrations
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: The toxicity of the test item was determined with tester strains TA 98 and TA 100 in a pre-experiment. Eight concentrations (0.00316, 0.0100, 0.0316, 0.100, 0.316, 1.0, 2.5 and 5.0 µL/plate) were tested for toxicity and induction of mutations with three plates each. No toxicity was observed in the pre-experiment.

HISTORICAL CONTROL DATA (with ranges, means and standard deviation and confidence interval (e.g. 95%)
- Positive historical control data:
- Negative (solvent/vehicle) historical control data:

ADDITIONAL INFORMATION ON CYTOTOXICITY:
- Measurement of cytotoxicity used: In experiment I toxic effects of the test item were observed in tester strain TA 98 at concentrations of 1.0 µL/plate and higher (without metabolic activation) and in tester strain 1537 at a concentration of 5.0 µL/plate (with metabolic activation).

In experiment II toxic effects of the test item were noted in tester strains TA 98 and TA 100 at a concentration of 5.0 µL/plate (without metabolic activation) and at concentrations of 2.5 µL/plate and higher (with metabolic activation). In tester strain TA 1535 toxic effects of the test item were noted at concentrations of 2.5 µL/plate and higher (without metabolic activation) and at concentrations of 1.0 µL/plate and higher (with metabolic activation). In tester strain TA 1537 toxic effects of the test item were observed at a concentration of 5.0 µL/plate (with and without metabolic activation).

- Other observations when applicable: The reduction in the number of revertants down to a mutation factor of ≤ 0.5 found in experiment I in tester strain TA 100 at a concentration of 2.5 µL/plate (without metabolic activation) was regarded as not biologically relevant due to lack of a dose-response relationship.
Conclusions:
In conclusion, it can be stated that during the described mutagenicity test and under the experimental conditions reported, hexyltrimethoxysilane did not cause gene mutations by base pair changes or frameshifts in the genome of the tester strains used. Therefore, hexyltrimethoxysilane 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 key bacterial mutagenicity study according to OECD TG 471 and GLP is available for hexyl(trimethoxy)silane (CAS 3069-19-0). In general, no evidence for a test-substance related increase in the number of revertants was observed in any of the Salmonella typhimurium strains (TA 1535, TA1537, TA98, TA100 and TA102) in two independent experiments without and with metabolic activation. There was a reduction in the number of revertants down to a mutation factor of ≤ 0.5 in experiment I in tester strain TA 100 at a concentration of 2.5 µL/plate (without metabolic activation); however, this effect was regarded as not biologically relevant due to lack of a dose-response relationship. Additionally, cytoxicity effects were noted in both experiments. In experiment I toxic effects of the test item were observed in tester strain TA98 at concentrations of 1.0 µL/plate and higher (without metabolic activation) and in tester strain TA1537 at a concentration of 5.0 µL/plate (with metabolic activation). In experiment II toxic effects of the test item were noted in tester strains TA98 and TA100 at a concentration of 5.0 µL/plate (without metabolic activation) and at concentrations of 2.5 µL/plate and higher (with metabolic activation). In tester strain TA1535 toxic effects of the test item were noted at concentrations of 2.5 µL/plate and higher (without metabolic activation) and at concentrations of 1.0 µL/plate and higher (with metabolic activation). In tester strain TA1537 toxic effects of the test item were observed at a concentration of 5.0 µL/plate (with and without metabolic activation). Appropriate positive and solvent controls were included and gave expected results. Under the conditions of this study, the registered substance was concluded to be non-mutagenic in the strains tested (Eurofins, 2018).

No bacterial mutagenicity potential is also considered for the target substance CAS 3069-19-0.

Justification for classification or non-classification

Hexyltrimethoxysilane is considered to be non-mutagenic in this bacterial reverse mutation assay. However, no final decision on classification for genetic toxicity according to Regulation (EC) 1272/2008 can be made, as any information on chromosomal aberration and mutagenicity in mammalian cells/in vivo is available.