Registration Dossier

Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Gene mutation (Bacterial reverse mutation assay / Ames test): negative with and without metabolic activation in strains TA98, TA100, TA1535 and TA1537 Escherichia coli WP2 (OECD TG 471) (BioReliance 2004a).


Cytogenicity in mammalian cells: positive with metabolic activation in CHO cells (OECD TG 473) (BioReliance 2004b).
Mutagenicity in mammalian cells: positive with metabolic activation in L5178Y mouse lymphoma cells (OECD TG 476) (TNO 2002a).

The selected key studies were chosen because they are the most reliable and recent available studies for the registered substance. They were conducted according to appropriate OECD guidelines and in compliance with GLP.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (positive)

Genetic toxicity in vivo

Description of key information

In vivo Mammalian Alkaline Comet Assay (inhalation): Negative (OECD 489) (Charles River, 2017).

Mouse micronucleus assay (oral gavage): Negative (OECD TG 474) (RTC 2002).

The selected key studies were chosen because they are the most reliable and recent available studies for the registered substance. They were conducted according to appropriate OECD guidelines and in compliance with GLP.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Additional information

Trimethoxy(methyl)silane has been tested for mutagenicity to bacteria in a study which was conducted according to OECD TG 471 and in compliance with GLP (BioReliance 2004a). No evidence of a test substance related increase in the number of revertants was observed with or without activation in the initial or the repeat experiments using S. typhimurium TA 1535, TA 1537, TA 98 and TA 100 and E. coli WP2 uvrA. Appropriate positive and solvent controls were included and gave expected results. It is concluded that the test substance is negative for mutagenicity to bacteria under the conditions of the test. Additional information on mutagenicity to bacteria is provided by two other studies (Dow Corning Corporation, 1977, TNO 2002b). No evidence for genetic toxicity was observed in either of these studies.

Trimethoxy(methyl)silane has been tested for cytogenicity in mammalian cells in a study conducted according to OECD 473 and in compliance with GLP (BioReliance 2004b). A statistically significant dose related increase in the number of structural aberrations in the presence of activation was evident, which was not seen in the absence of metabolic activation. It is concluded that the test substance is positive for the induction of chromosome aberrations in the presence of activation under the conditions of the study.

Trimethoxy(methyl)silane has been tested for mutagenicity in mammalian cells in a study conducted according to OECD 476 and in compliance with GLP (TNO 2002a). A dose-related increase in the mutant frequency was observed with metabolic activation in L5178Y mouse lymphoma cells. The study is concluded to be positive for mutagenicity to mammalian cells under the conditions of the test.

Trimethoxy(methyl)silane has been tested in a mouse micronucleus study, which was conducted according to OECD 474 and under GLP (RTC 2002). No increase in the indicence of micronucleated PCE was observed following exposure to the test substance by oral gavage, administered up to limit concentrations. It is concluded that the test substance is negative for the induction of micronuclei under the conditions of the test. Clinical signs of toxicity were observed that suggested systemic availability, though no toxicity to target tissue was observed.

A dose-range finding study was conducted to determine the maximum tolerated dose (MTD) for a Comet assay (Charles River, 2017). The objective of this study was to establish the MTD to be used in the in vivo Comet assay and to identify any sex-specific difference in toxicity. Trimethoxy(methyl)silane was administered as a vapour by nose only inhalation for 4 hours on three consecutive days to one group of three male and three female Wistar rats. Clinical signs and body weights were recorded during the observation period. On the last day of exposure the animals were sacrificed and macroscopic examination was performed. No mortality was observed during the observation period. Shallow breathing was observed during exposure, but no significant clinical signs were noted in any of the animals post exposure. Reduced body weight gain was noted for all males and one female and body weight loss was noted for two females. These changes were considered to be within the range expected for rats of this strain and age. A small increase in lung/body weight ratio was seen in males, while in females, individual increases and decreases were seen. Overall, it was considered that the changes were not indicative for evident toxicity. No relevant changes were noted for total cell count and cell differentiation of the bronchial alveolar fluid. The maximum tolerated dose value of trimethoxy(methyl)silane was established to be 20 mg/L. No sex-specific toxicity was observed.

Trimethoxy(methyl)silane has been tested in an in vivo mammalian alkaline comet assay conducted according to OECD TG 489 and in compliance with GLP (Charles River, 2017). The test substance was administered by the inhalation route. The study was conducted in two sessions:

Session 1: A test item concentration of 20 mg/L was tested including a negative control (control air) and a positive control (EMS 200 mg/kg, administered orally).

Session 2: Test item concentrations of 5 and 10 mg/L were tested including a negative control (control air) and a positive control (EMS 200 mg/kg).

After treatment, single cell suspensions from the bone marrow, liver and lung tissue were prepared. Comet slides were prepared and analyzed.

The results revealed that no statistically significant increase in the mean Tail Intensity (%) was observed in bone marrow, liver and lung cells of trimethoxy(methyl)silane treated female animals at 5, 10 and 20 mg/L compared to the vehicle treated animals. The Tail Intensity was 9.13%, 7.03% and 12.29% at 5, 10 and 20 mg/L in bone marrow, 6.80%, 10.06%, and 3.66% at 5, 10 and 20 mg/L in liver, and 4.52%, 6.33% and 8.42% at 5, 10 and 20 mg/L in lung. All these Tail Intensities in bone marrow, liver and lung are within the historical control data range of the negative control of 1.92-17.26% for bone marrow, 0.13-27.12% for liver and 0.69-37.02% for lung.

The assays passed the acceptance criteria:

- The negative control Tail Intensity (%) in bone marrow, liver and lung was within the historical control data range in the two sessions with exception of bone marrow and liver in session 1. The mean Tail Intensity in bone marrow and liver in session 1 were with 18.43% and 35.76% just above the upper limit of the ranges of 17.26% and 27.12%, respectively. Since the values were only just above the upper range of the historical data and the positive control caused severe DNA damage with a Tail Intensity of 87.94% and 95.29% in bone marrow and liver, respectively, the sensitivity of these assays was considered not to be affected and both assays were considered acceptable.

- EMS, the positive control item, induced a statistically significant increase in all assays in all tissues (Students t-test one-sided, p < 0.05).  

 Exposure of the target tissue is supported by evidence of systemic exposure observed in the dose range-finding study. It was therefore concluded that the test substance does not cause DNA damage in lung, liver or bone marrow after inhalation exposure of female Wistar Han rats.

Information is available from reliable studies for all the required in vitro endpoints. Where there was more than one result for an endpoint the most reliable study available was chosen as key study. Where there was more than one reliable study, the most recent study was selected. The results of all the bacterial studies were negative. The results of testing in mammalian cells showed evidence of genetic toxicity in the presence of metabolic activation. There was evidence for clastogenicity (causing chromosomal aberrations) in the presence of metabolic activation in vitro. There was evidence of mutagenicity to mammalian cell in the presence of metabolic activation.

An in vivo micronucleus study did not support the positive result of the in vitro chromosome aberration assay, so it is concluded that the in vitro result does not reflect an ability to cause chromosome aberrations in vivo. Clinical signs of toxicity were observed that suggested systemic availability, although it is noted that the test substance did not affect the NCE/PCE ratio.

At the request of ECHA, further investigation of the ability of trimethoxy(methyl)silane to damage DNA was carried out in an in vivo mammalian alkaline comet assay conducted according to OECD TG 489 (inhalation route). The results of the study were negative and indirect evidence of exposure of the target tissue comes from the dose range-finding and main studies carried out to investigate subchronic inhalation toxicity (Dow Corning Corporation 2007, Dow Corning Corporation 2008). In these studies, mortalities and clinical effects were observed in animals exposed to trimethyoxy(methyl)silane at 22.2 and 44.4 mg/L for 14 days, and at 2.2 and 8.9 mg/L for 90 days. It is therefore concluded that the test substance is not clastogenic or mutagenic in vivo and no further investigation of germ cell mutagenicity is required.

Justification for classification or non-classification

The available information for trimethyoxy(methyl)silane indicates that when tested in vitro, trimethoxy(methyl)silane (CAS number 1185-55-3) does not induce mutations in bacterial cells. The substance does cause chromosomal aberrations in vitro in the presence of metabolic activation. An in vivo mouse micronucleus study and an in vivo Mammalian Alkaline Comet Assay (inhalation) did not confirm the potential for damage to chromosomes or to DNA so it is concluded that trimethoxy(methyl)silane is not clastogenic and does not have DNA damaging potential. Based on the available information trimethoxy(methyl)silane does not require classification for genetic toxicity according to Regulation (EC) No 1272/2008.