Trichloro(propyl)silane

Endpoint summary

Additional information

There are no in vivo data on the toxicokinetics of trichloro(propyl)silane.

The following summary has therefore been prepared based on validated predictions of the physicochemical properties of the substance itself and its hydrolysis productsand 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 K_owso by using this, and other where appropriate, known or predicted physicochemical properties of trichloro(propyl)silane or its hydrolysis products, reasonable predictions or statements may be made about their potential absorption, distribution, metabolism and excretion (ADME) properties.

Trichloro(propyl)silane is a moisture-sensitive liquid that hydrolyses very rapidly in contact with water (half-life <1 minute at pH 7; predicted), generating hydrochloric acid and propylsilanetriol. 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 hydrochloric acid 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, propylsilanetriol. 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 propylsilanetriol is very water soluble (1E+06 mg/l) and has a molecular weight of approximately 121 it meets both of these criteria, so should oral exposure occur it is reasonable to assume systemic exposure will occur also. 

Dermal

The fat solubility and therefore potential dermal penetration of a substance can be estimated by using the water solubility and log K_owvalues. Substances with log K_owvalues between 1 and 4 favour dermal absorption (values between 2 and 3 are optimal) particularly if water solubility is high. Due to the likely very rapid hydrolysis oftrichloro(propyl)silaneon 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 becausetrichloro(propyl)silane is volatile this would further limit the potential for absorption.

Although the water solubility (1E+06 mg/l) of the hydrolysis product propylsilanetriol is favourable for absorption, the predictedlog K_owof -1.4 is not, so it is consideredtoo hydrophilic to cross the lipid-rich stratum corneum. Therefore dermal uptake is likely minimal.

Since the other hydrolysis product, hydrochloric acid is corrosive to the skin damage to the skin might increase penetration of either the parent or hydrolysis product. There are no studies to check for signs of dermal toxicity.

Inhalation

There is a QSPR to estimate the blood:air partition coefficient for human subjects as published by Meulenberg and Vijverberg (2000). The resulting algorithm uses the dimensionless Henry coefficient and the octanol:air partition coefficient (K_oct:air) as independent variables.

Using these values for the hydrolysis product,propylsilanetriol, results in a very high blood:air partition coefficient (approximately 2E+09:1) so once hydrolysis has occurred, as it would be expected to in the lungs, then significant uptake would be expected into the systemic circulation. However, the high water solubility ofpropylsilanetriolmay lead to some of it being retained in the mucus of the lungs so once hydrolysis has occurred, absorption is likely to slow down.

As with dermal exposure, damage to membranes caused by the corrosive nature of the hydrochloric acid hydrolysis product might enhance the uptake. There are no studies to check for signs of inhalation toxicity.

Distribution

For blood:tissue partitioning a QSPR algorithm has been developed by DeJonghet al. (1997) in which the distribution of compounds 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 the hydrolysis product, propylsilanetriol, predicts that distribution would be minimal with tissue:blood partition coefficients of less than 1 for all tissues (zero for fat).

Table 1: Tissue:blood partition coefficients

	Log Kow	Kow	Liver	Muscle	Fat	Brain	Kidney
Propylsilanetriol	-1.4	0.04	0.6	0.7	0.0	0.7	0.8

Hydrogen and chloride ions will enter the body's natural homeostatic processes.

Metabolism

Trichloro(propyl)silane is very rapidly hydrolysed to propylsilanetriol and hydrochloric acid in the presence of moisture. Most if not all of this will have occurred before absorption into the body. There are no data regarding the metabolism of propylsilanetriol. Genetic toxicity tests in vitro showed no observable differences in effects with and without metabolic activation for trichloro(propyl)silane.

Excretion

A determinant of the extent of urinary excretion is the soluble fraction in blood. QPSRs as developed by DeJongh et al. (1997) using log K_owas an input parameter, calculate the solubility in blood based on lipid fractions in the blood assuming that human blood contains 0.7% lipids.

Using this algorithm, the soluble fraction ofpropylsilanetriolin blood is >99% suggesting it is likely to be effectively eliminated via the kidneys in urine and accumulation is very unlikely.