Triethoxyisobutylsilane

Endpoint summary

Additional information

There are no in vivo data on the toxicokinetics of triethoxyisobutylsilane. The following summary has therefore been prepared based on validated predictions of the physicochemical properties of the substance itself and its hydrolysis products. Triethoxyisobutylsilane is a moisture-sensitive liquid that hydrolyses at a moderate rate in contact with water (half-life 22 hours at pH 7; predicted), generating ethanol and isobutylsilanetriol. Human exposure can occur via the inhalation or dermal routes. Relevant inhalation exposure would be to the parent and hydrolysis products.

Absorption

Oral: Significant oral exposure is not expected for this substance.

Dermal: The molecular weights of the parent and hydrolysis products do not negate the possibility of absorption across the skin, although they are not ideal. The measured water solubility (212 mg/l) and predicted log K_ow (3.6) of the parent suggest that absorption across the skin is likely to be moderate to high. The predicted water solubility (miscible in all proportions) and predicted log K_ow (-1.0) of the hydrolysis product, isobutylsilanetriol, are not favourable for absorption across the skin, as the substance is likely to be too hydrophilic to cross the lipid rich environment of the stratum corneum.

Inhalation: The predicted log K_ow of the parent substance is favourable for absorption from the respiratory tract epithelium by passive diffusion. The very high water solubility of the hydrolysis product, isobutylsilanetriol is likely to lead to some of this hydrolysis product being retained in the mucus of the lungs. Therefore, once hydrolysis has occurred, absorption is likely to slow down. No measured data on hydrolysis kinetics in vivo are available. A 90-day repeated dose inhalation study did not provide convincing evidence for systemic availability.

Distribution

Due to the moderate rate of hydrolysis of triethoxyisobutylsilane, and lower absorption of the hydrolysis product, most of the absorbed substance is likely to be in the form of the parent, triethoxyisobutylsilane. Hydrolysis will continue to occur once the substance is in the blood. The lipophilic parent substance is likely to distribute into cells and the intracellular concentration might be higher than the extracellular concentration, particularly in fatty tissues. The hydrolysis product is not likely to distribute into cells due to its very high water solubility and low log K_ow.

Metabolism

There are no data regarding the metabolism of triethoxyisobutylsilane. Genetic toxicity tests in vitro showed no observable differences in effects with and without metabolic activation for triethoxyisobutylsilane.

The hydrolysis product ethanol is rapidly metabolised via well-described pathways. Metabolism of ethanol is described extensively in the open literature and it is outside the scope of the CSR to consider this in detail.

Excretion

The low molecular weight and water solubility of the parent and hydrolysis product suggest that they are likely to be effectively eliminated via the kidneys in urine.