Diethoxy(methyl)silane

Endpoint summary

Description of key information

No studies are available. Based on molecular structure, molecular weight, water solubility, and octanol-water partition coefficient it can be expected that the submission substance is likely to be absorbed via the inhalation route rather than the oral and dermal routes. Hydrolysis occurs rapidly, and the physico-chemical parameters of the hydrolysis product suggest that absorption is likely to be decreased afterwards. However, if absorption occurs, systemic exposure is expected to both the parent substance and the hydrolysis product. Based on the water solubility, the registered substance and its silanol-containig hydrolysis product are likely to be distributed in the body, and excretion via the renal pathway can be expected. Bioaccumulation is not expected.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

There are no studies available in which the toxicokinetic properties of diethoxy(methyl)silane have been investigated. Therefore, the toxicokinetic behaviour assessment of the substance and its hydrolysis product was assessed from its physico-chemical properties, the available toxicology studies on the substance itself and the read-across substances triethoxy(methyl)silane (CAS 2031-67-6) and diethoxy(dimethyl)silane (CAS 78-62-6). 

Diethoxy(methyl)silane hydrolyses in contact with water (half-life is < 2 min at pH 7 and 20 -25 °C), generating methylsilanediol, which is further oxidised to methylsilanetriol. Ethanol is generated as the non-silanol containing hydrolysis product. An acid environment is hereby known to catalyse this abiotic and enzyme-independent reaction and enhance the reaction rate, further increased by the body temperature of approximately 37 °C present in mammals (predicted half-life < 5 s at pH2 and 37.5 °C). This suggests that systemic exposure to both the parent, diethoxy(methyl)silane, and to the silicon-containing hydrolysis product, methylsilanediol, is possible. Hence, this toxicokinetic behaviour assessment will try to predict the behaviour of both these substances. The toxicokinetics of ethanol is discussed elsewhere and is not included in this summary.

The molecular weight and the predicted water solubility of diethoxy(methyl)silane are 134 g/mol and 1820 mg/L, respectively. In contrast, the molecular weight and predicted water solubility of the hydrolysis product, methylsilanediol and its oxidised product methylsilanetriol are 78 g/mol and 1E+06 mg/L, and 94 g/mol and 1E+06 mg/L at 20 °C, respectively. This shows that methylsilanediol and methylsilanetriol are smaller in size and are more water soluble and, thereby, suggests that they will have higher potential to be absorbed through biological membranes than the parent substance. Furthermore, the predicted moderate log Kow of 1.7 for the parent substance and -1 for methylsilanediol indicate that these substances are lipophilic enough to pass through biological membranes by passive diffusion efficiently. However, methylsilanetriol is less lipophilic (log Kow of -2.4) and therefore, passing of biological membranes by passive diffusion is less likely, but due to its low molecular weight, it still has the potential to pass through aqueous pores or be carried through the epithelial barrier by the bulk passage of water.

 

Absorption

Oral: Acute oral toxicity studies in rats with diethoxy(methyl)silane (CAS 2031-62-1) did not show any signs of systemic toxicity at the limit dose of 2000 mg/kg body weight (BSL Bioservice, 2007), therefore, showing the substance to be of low toxicity and/or having low potential to be absorbed by the oral route. If ingestion occurs, the hydrolysis of the parent substance in the low pH of the stomach will be rapid, so any absorption of the parent substance is expected to be minimal and it is more likely to be the hydrolysis product that is absorbed.

The predicted water solubility (1820 mg/L) of the parent and the hydrolysis products (1E+06 mg/L) suggests that these substances will readily dissolve in the gastrointestinal fluids. Also, the low molecular weight (≤ 134 g/mol) of the substances suggests they will have the potential to pass through aqueous pores or be carried through the epithelial barrier by the bulk passage of water. However, the moderate log Kow value of 1.7 for the parent and -1 for methylsilanediol versus -2.4 for methylsilanetriol suggests that the parent substance is more likely to be absorbed by passive diffusion than the hydrolysis products. Therefore, once hydrolysis has occurred, the level of absorption is expected to decrease.

Inhalation: An acute inhalation study with diethoxy(methyl)silane showed signs of systemic toxicity; therefore, indicating that absorption via the inhalation route is possible for the registered substance. Also, the predicted vapour pressure of the parent substance (840 Pa) is indicative that inhalation of the registered substance as a vapour could occur. 

The predicted moderate water solubility (1820 mg/L) and log Kow (1.7) of the parent substance suggest that absorption from the respiratory tract epithelium by passive diffusion is likely. However, the high water solubility (1E+06 mg/L) and low log Kow (-1 and -2.4) of the hydrolysis products, methylsilanediol and methylsilanetriol, suggest that it will be retained in the mucous of the lungs. Once hydrolysis has occurred, the level of absorption is likely to decrease. Particles deposited on the mucociliary blanket will be elevated into the laryngeal region and ultimately be swallowed (ingestion).

Dermal: An acute dermal toxicity study in rats with diethoxy(methyl)silane (CAS 2031-62-1) did not show any signs of systemic toxicity at the limit dose of 2000 mg/kg body weight (WIL Research Laboratories, Inc, 1996). Therefore, the registered substance can be concluded to be of low toxicity and/or has low potential to be absorbed by the dermal route. The molecular weight of 134 g/mol and the moderate water solubility (1820 mg/L) and log Kow (1.7) of the parent substance suggest that absorption via the dermal route is possible. For the hydrolysis product, methylsilanediol and its hydrolysis product methylsilanetriol, the high water solubility (1E+06 mg/L, respectively) and the low log Kow value (-1 and -2.4, respectively) suggest that the substances may be too hydrophilic to cross the lipid-rich environment of the stratum corneum; however, the molecular weight of less than 100 g/mol may favour some dermal uptake. QSAR-based dermal permeability prediction (DERMWIN V2.02, 2015) using molecular weight, log Kow and water solubility, calculated a dermal penetration rate of 6.79 µg/cm²/h for diethoxy(methyl)silane, 126.8 for methylsilanediol and 12.29 µg/cm²/h for methylsilanetriol, respectively. This shows that dermal penetration of the parent substance and the hydrolysis products will be medium and high, respectively.

 

Distribution

The distribution of the parent substance within the body in unlikely given its rapid hydrolysis rate (half-life is < 2 min hour at pH 7 and 20-25°C). The small size of the hydrolysis products suggests a wide distribution. Since the hydrolysis products are small in size (78 - 94 g/mol) and water-soluble (1E+06 mg/L, respectively), it can be assumed that they will have the potential diffuse through aqueous channels and pores. Since the log Pow is below 0 for both hydrolysis products, it is likely that they will distribute into cells and the intracellular concentration may be higher than the extracellular concentration particularly in fatty tissues. Based on the physico-chemical properties of the parent substance and the hydrolysis products no bioaccumulation potential is expected.

Metabolism

Diethoxy(methyl)silane hydrolyses rapidly in contact with water (half-life is < 2 min at pH 7 and 20-25°C), generating ethanol and ultimately methylsilanetriol. There are no data regarding the enzymatic metabolism of diethoxy(methyl)silane or methylsilanetriol. Genetic toxicity tests in vitro showed no observable difference in effects with and without metabolic activation for triethoxy(methyl)silane.

 

Excretion

The low molecular weight and high water solubility of the parent and hydrolysis product suggest that they are likely to be excreted by the kidneys into the urine.