Triethoxy(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-containing 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 triethoxy(methyl)silane have been investigated. Therefore, the toxicokinetic behaviour assessment of the substance and its hydrolysis product was assessed from its physico-chemical properties and the available toxicology studies on the substance itself.

 

Triethoxy(methyl)silane hydrolyses in contact with water (half-life is 5.5 hour at pH 7 and 20°C), generating ethanol and methylsilanetriol. This suggests that systemic exposure to both the parent, triethoxy(methyl)silane, and to the hydrolysis product, methylsilanetriol, 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 triethoxy(methyl)silane are 178.30 g/mol and 2900 mg/L, respectively. In contrast, the molecular weight and predicted water solubility of the hydrolysis product, methylsilanetriol, are 94.142 g/mol and 1E+06 mg/L, respectively. This shows that the hydrolysis product is smaller in size and is more water soluble and, thereby, suggests that it will have greater potential to be absorbed through biological membranes than the parent substance. However, the predicted log K_ow values of 2.2 for the parent substance and -2.4 for the hydrolysis product indicate that the hydrolysis product, unlike the parent, is not lipophilic enough to efficiently pass through biological membranes by passive diffusion.

Absorption

Oral: In an acute oral limit test with triethoxy(methyl)silane, there was no mortality or marked systemic effect in rats at 2007 mg/kg bw, 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 (2900 mg/L) of the parent and the hydrolysis product (1E+06 mg/L) suggests that both substances will readily dissolve in the gastrointestinal fluids. Also, the low molecular weight (≤ 178 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 K_ow value of 2.2 for the parent versus -2.4 for the hydrolysis product suggests that the parent substance is more likely to be absorbed by passive diffusion than the hydrolysis product. Therefore, once hydrolysis has occurred, the level of absorption is likely to decrease.

Inhalation: An acute inhalation study with triethoxy(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 (100 Pa) is indicative that inhalation of the registered substance as a vapour could occur. 

The predicted moderate water solubility (2900 mg/L) and log K_ow (2.2) 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 K_ow (-2.4) of the hydrolysis product, 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: The moderate water solubility (2900 mg/L) and log K_ow (2.2) of the parent substance suggest that absorption via the dermal route is possible. For the hydrolysis product, methylsilanetriol, the high water solubility (1E+06 mg/L) and the low log K_ow value (-2.4) suggest that the substance 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 (DERWIN V2.00.2009) using molecular weight, log Kow and water solubility, calculated a dermal penetration rate of 0.00167 mg/cm²/h for triethoxy(methyl) silane and 0.01004 mg/cm²/h for methylsilanetriol, respectively. This shows that dermal penetration of the parent substance and of the hydrolysis product will be very low and low, respectively. The low dermal absorption and/or toxicity potential is also confirmed in an acute dermal limit test with triethoxy(methyl) silane, where no mortality or marked systemic effect in rats were seen at 2007 mg/kg bw.

Distribution

For blood: tissue partitioning a QSPR algorithm has been developed by De Jongh et al. (1997) in which the distribution of compound between blood and human body tissues as a function of water and lipid content of tissues and the n-octanol: water partition coefficient (K_ow) is described. Using this value for triethoxy(methyl)silane predicts that it will distribute into the main body compartments as follows: fat >> liver > brain > muscle > kidney with tissue: blood partition coefficients of 79 for fat and 2.8 to 1.7 for the remaining tissues. For the hydrolysis product, distribution would be approximately equal to liver, muscle, brain and kidney and about 800-fold lower to fat. In comparison to the parent product, distribution would be approximately 5-fold lower into each tissue.

 

Table: Tissue: blood partition coefficients

	Log Kow	Kow	Liver	Muscle	Fat	Brain	Kidney
Triethoxy(methyl)silane	2.2	158.59	2.8	2.1	79	2.4	1.7
Methylsilanetriol	-2.4	3.98E-03	0.5	0.7	-0.1	0.7	0.8

 

Metabolism

 Triethoxy(methyl)silane hydrolyses rapidly in contact with water (half-life is 5.5 hour at pH 7 and 20°C), generating ethanol and methylsilanetriol. There are no data regarding the enzymatic metabolism of triethoxy(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 urine.

Summary

Oral absorption – expected for triethoxy(methyl)silane and methylsilanetriol
Dermal absorption - triethoxy(methyl)silane > methylsilanetriol
Inhaled absorption – triethoxy(methyl)silane > methylsilanetriol

Distribution – triethoxy(methyl)silanefat >> liver > brain > muscle > kidney
Distribution – methylsilanetriol kidney > muscle ≈ brain > liver > fat
Distribution triethoxy(methyl)silane 5- fold greater than methylsilanetriol

Metabolism – no data

Excretion via urine – minimal for triethoxyl(methyl)silane, significant for methylsilanetriol