Silicon tetrachloride

Endpoint summary

Additional information

There are no in vivo or in vitro data on the toxicokinetics of silicon tetrachloride.

The following summary has therefore been prepared based on the physicochemical properties of the substance itself and its hydrolysis products and using this data in algorithms that are the basis of many computer-based physiologically based pharmacokinetic or toxicokinetic (PBTK) prediction models. 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 silicon tetrachloride or its hydrolysis products, reasonable predictions or statements may be made about their potential absorption, distribution, metabolism and excretion (ADME) properties.

Silicon tetrachloride is a moisture-sensitive, volatile liquid that hydrolyses very rapidly in contact with water (half-life approximately 5 seconds at pH 7), generating HCl and silicic acid; hydrogen gas is a further by-product of the hydrolysis reaction. At concentrations above about 100 -150 mg/l (measured as SiO2 equivalents), condensation products of monosilicic acid can also form. At concentrations >100 -150 mg/l of SiO2, monomeric monosilicic acid condenses into insoluble colloidal particles of polysilicic acid (silica sol) or a highly cross-linked network (silica gel). These forms of polysilicic acid are equivalent to synthetic amorphous silica. Most, if not all, hydrolysis will have occurred before absorption into the body, therefore relevant systemic exposure is limited to the hydrolysis products.

Human exposure can occur via the inhalation or dermal routes. Relevant inhalation exposure would be to the hydrolysis products (hydrolysis would occur rapidly when inhaled, even if a mixture of parent and hydrolysis products were present in air). The substance would also hydrolyse rapidly in contact with moist skin. The resulting HCl hydrolysis product would be severely irritating or corrosive.

Potential systemic exposure to hydrochloric acid is not discussed.

Absorption

Oral

Significant oral exposure is not expected for this corrosive substance.

However, oral exposure to humans via the environment may be relevant for the hydrolysis product, silicic acid and then silica. When oral exposure takes place, it is necessary to assume that except for the most extreme of insoluble substances, that uptake through intestinal walls into the blood takes place. Uptake from intestines can be assumed to be possible for all substances that have appreciable solubility in water or lipid. Other mechanisms by which substances can be absorbed in the gastrointestinal tract include the passage of small water-soluble molecules (molecular weight up to around 200) through aqueous pores or carriage of such molecules across membranes with the bulk passage of water (Renwick, 1993).

As silica is water soluble (approximately 100 - 150 mg SiO2/l with condensation occurring at higher concentrations) and has a molecular weight of approximately 60.08 g/mol it meets both of these criteria, so should oral exposure occur it is reasonable to assume systemic exposure will occur also. Gastrointestinal 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. Due to the very rapid hydrolysis silicon tetrachloride on contact with skin, systemic exposure via this route is predicted to be minimal. After or during deposition of a liquid on the skin, evaporation of the substance and dermal absorption occur simultaneously so the vapour pressure of a substance is also relevant and because silicon tetrachloride is volatile this would further limit the potential for absorption.

Silicon tetrachloride hydrolyses rapidly on the skin, thus producing silicic acid and HCl. The molecular weights of the hydrolysis products favour absorption across the skin. However, silica is water soluble (approximately 100 - 150 mg SiO2/l with condensation occurring at higher concentrations), which suggests that it is too hydrophilic to cross the lipid rich stratum corneum. Since the other hydrolysis product, HCl is corrosive to the skin, damage to the skin might increase penetration. Absorption of the insoluble condensation products is not expected.

Available dermal studies did not show evidence of systemic availability, as effects (such as those on body weights) are generally thought to be secondary to corrosion of the skin.

Inhalation

Inhalation exposure would be to the hydrolysis products as silicon tetrachloride would hydrolyse rapidly when inhaled, even if a mixture of parent and hydrolysis products were present in air. Once hydrolysis has occurred, significant uptake would be expected into the systemic circulation, as the silicic acid hydrolysis product is highly soluble (approximately 100 - 150 mg SiO2/l with condensation occurring at higher concentrations). Due to the hydrophilic nature of silicic acid, it is likely that some will be retained within the mucous of the lungs and thus absorption will be limited. Condensation to silica might lead to some precipitate being retained in the lining of the respiratory tract, although this cannot be confirmed from results of the only reliable experimental animal study available.

As with dermal exposure, damage to membranes caused by the corrosive nature of the hydrochloric acid hydrolysis product might enhance the uptake. In the available acute inhalation toxicity studies, the only adverse effects appeared to be secondary to corrosive effects of the test substance.

Distribution

All absorbed material is likely to be in the form of the hydrolysis products, HCl and silicic acid, which rapidly precipitates to insoluble silica (SiO2) when the concentration is sufficiently high. Silicic acid is a small molecule, and therefore has potential to be widely distributed, but its hydrophilic nature  will limit its diffusion across membranes (including the blood-brain and blood-testes barriers) and its accumulation in fatty tissues. Human blood contains 1 mg SiO2/l of monosilicic acid (Iler RK, 1979).  Hydrogen and chloride ions will enter the body’s natural homeostatic processes.

Metabolism

Silicon tetrachloride is rapidly hydrolysed to HCl and silicic acid, which rapidly precipitates to insoluble silica (SiO2) when the concentration is sufficiently high. Most if not all of this will have occurred before absorption into the body. Silicic acid is not metabolised, but forms a precipitate, as previously described. Silicon is an essential trace element participating in the normal metabolism of higher animals. It is required in bone, cartilage and connective tissue formation as well as participating in other important metabolic processes. The silicon is present almost entirely as free soluble monosilicic acid (Carlisle, 1986). Genetic toxicity tests in vitro showed no observable differences in effects with and without metabolic activation.

Excretion

A determinant of the extent of urinary excretion is the soluble fraction in blood. Given the hydrophilic nature of the hydrolysis product, silicic acid, the soluble fraction of silicic acid in blood is extremely high suggesting it is likely to be effectively eliminated via the kidneys in urine and accumulation is very unlikely.

Following oral ingestion precipitated silica will be eliminated in faeces. The low molecular weight and high water solubility of silicic acid suggest that it is likely to be rapidly eliminated via the kidneys in urine. There is therefore no evidence to suggest that this substance will accumulate in the body.

References

Renwick A. G. (1993) Data-derived safety factors for the evaluation of food additives and environmental contaminants. Fd. Addit. Contam. 10: 275-305.

Iler, Ralph K. (1979) The Chemistry of Silica: Solubility, Polymerization, Colloid and Surface Properties and Biochemistry of Silica, Wiley, p. 13.

Carlisle EM. Silicon as an essential trace element in animal nutrition. Ciba Found Symp. 1986;121:123-39.