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Introduction

There are no in vivo data or reliable in vitro data on the toxicokinetics of trimethoxysilane.

The following summary has therefore been prepared based on validated predictions of the physicochemical properties of the substance itself and its hydrolysis products and using these data in algorithms that are the basis of many computer-based physiologically based pharmacokinetic or toxicokinetic (PBTK) prediction models. Although these algorithms provide a numerical value, for the purposes of this summary only qualitative statements or comparisons will be made.

The main input variable for the majority of these algorithms is log Kow so by using this, and where appropriate, other known or predicted physicochemical properties of trimethoxysilane reasonable predictions or statements may be made about its potential absorption, distribution, metabolism and excretion (ADME) properties.

Trimethoxysilane is a volatile liquid that hydrolyses very rapidly in contact with water (measured half-life = 0.2 minutes at pH 4 and pH 9, =0.3 minutes at pH 7 and 2°C) generating methanol (CAS 67-56-1) and (poly)silicic acid (CAS 10193-36-9) with silanetriol (CAS 14044-95-2) as an intermediate hydrolysis product.

Exposure may occur via the inhalation or dermal routes.

Relevant inhalation exposure is likely to be a mixture of parent and hydrolysis products as the substance will rapidly hydrolyse in the lungs. The substance would also hydrolyse rapidly in contact with moist skin, therefore relevant dermal exposure will also be a mixture of parent and hydrolysis products. The toxicokinetic behaviour of methanol has been extensively reported in the literature and is not discussed further in this summary.

(Poly)silicic acid is a mixture of monosilicic acid, its oligomers and amorphous polysilicic acid in dynamic equilibrium. It is a naturally occurring inorganic substance that will enter the natural biochemical cycle for silicon

Absorption

Oral

Based on the known use pattern, significant oral exposure is not expected for this corrosive substance.

However, following oral intake silicic acid might be absorbed from the gut before it is precipitated out to insoluble silica; absorption of insoluble silica will be insignificant as compared to the absorption of the soluble species (Carlisle, 1986).

Dermal

The fat solubility and therefore potential dermal penetration of a substance can be estimated by using the water solubility and log Kow values. Substances with log Kow values between 1 and 4 favour dermal absorption (values between 2 and 3 are optimal) particularly if water solubility is high.

The relatively low molecular weights of the parent and hydrolysis products would generally favour dermal absorption.

The predicted high water solubility (170 000 mg/L at 20°C) and predicted partition coefficient (0.2 at 20°C and pH 7) of the parent substance suggest that dermal absorption is possible. Acute dermal toxicity studies using trimethoxysilane show signs of systemic toxicity (including effects on the lungs and liver), and therefore also indicate the occurrence of dermal absorption. Since this substance is corrosive to the skin, damage to the skin might increase penetration. However, dermal penetration will be limited by rapid evaporation from the skin.

However, the very high water solubility (100 0000 mg/L at 20°C) and very low partition coefficient (-2.9 at 20°C) of silanetriol suggest that it might be too hydrophilic to cross the lipid rich stratum corneum. Therefore, dermal uptake is likely to be low for the hydrolysis product.

Inhalation

Trimethoxysilane will rapidly hydrolyse in the lungs. The hydrophilic hydrolysis product, silanetriol, with its very high water solubility is likely to be dissolved in the mucous of the respiratory tract lining, but would likely be retained in the mucous and inhibited from penetrating the lung epithelium. Any remaining parent substance is more likely to be absorbed passively across the respiratory tract epithelium. Damage caused due to the corrosive nature of trimethoxysilane could lead to increased absorption following inhalation.

Distribution

The absorbed material is likely to be in the form of the parent and hydrolysis products, but predominantly as the parent. However, the parent substance, trimethoxysilane, once absorbed, will completely hydrolyse in the blood. Since the hydrolysis product is a small molecule, it is likely to be widely distributed, but its hydrophilic nature will limit its diffusion across membranes (including the blood-brain and blood-testes barriers), and therefore its accumulation in fatty tissues.

Metabolism

Trimethoxysilane is expected to rapidly hydrolyse to methanol and silanetriol in the blood, once absorbed into the body. There are no further data that can be used to characterise the metabolic profile of this substance. Genetic toxicity tests in vitro showed no observable differences in effects with and without metabolic activation.

Excretion

The high water solubility, and low molecular weight (below 300) indicate that the substance is likely to be rapidly eliminated via the kidneys into the urine. There is therefore no evidence to suggest that this substance will accumulate in the body.