[3-(2,3-epoxypropoxy)propyl]triethoxysilane

Endpoint summary

Additional information

There are no reliable in vivo data on the toxicokinetics of [3-(2,3-epoxypropoxy)propyl]triethoxysilane.

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 K_ow so by using this, and other where appropriate, known or predicted physicochemical properties of [3-(2,3-epoxypropoxy)propyl]triethoxysilane, reasonable predictions or statements may be made about its potential absorption, distribution, metabolism and excretion (ADME) properties.

[3-(2,3-Epoxypropoxy)propyl]triethoxysilane is a moisture-sensitive liquid that has a predicted hydrolysis half-life of 12-36 hours at pH 7 and 25°C), generating 2,3-dihydroxypropoxypropylsilanetriol and ethanol. Hydrolysis of the alkoxy and epoxy groups will happen concurrently and at a similar rate. Human exposure can occur via the inhalation or dermal routes. Relevant inhalation and dermal exposure would be predominantly to the parent substance.

The toxicokinetics of ethanol have been reviewed in other major reviews and are not considered further here.

Absorption

Oral

Significant oral exposure is not expected for this substance.

However, oral exposure to humans via the environment may be relevant for the hydrolysis product, 2,3-dihydroxypropoxypropylsilanetriol. When oral exposure takes place it can be assumed, except for the most extreme of insoluble substances, that uptake through intestinal walls into the blood occurs. Uptake from intestines must 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).

2,3 -Dihydroxypropoxypropylsilanetriol is highly water soluble (1E+06 mg/l) but its molecular weight of 242.30 is above the favourable range. However, it is considered that should oral exposure occur it is reasonable to assume that resulting systemic exposure is probable. 

Dermal

The fat solubility and therefore potential dermal penetration of a substance can be estimated by using the water solubility and log K_ow values. Substances with log K_ow values between 1 and 4 favour dermal absorption (values between 2 and 3 are optimal) particularly if water solubility is high. With a log K_ow of 2.0 and water solubility of 3300 mg/l, absorption of [3-(2,3-epoxypropoxy)propyl]triethoxysilane across the skin is likely to occur. 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 but as [3-(2,3-Epoxypropoxy)propyl]triethoxysilane has a low vapour pressure evaporation is not likely to be a factor.

The high water solubility (1E+06 mg/l) of the hydrolysis product, 2,3-dihydroxypropoxypropylsilanetriol, is favourable for absorption across the skin but the log K_ow of -3.8 is not. Therefore absorption across the skin is not likely to occur as the substance is likely to be too hydrophilic to cross the lipid-rich environment of the stratum corneum.

Therefore absorption might be expected to be significantly reduced once hydrolysis has occurred. There are no dermal studies to check for evidence of absorption.

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 parent substance [3-(2,3 -epoxypropoxy)propyl]triethoxysilane, results in a blood:air partition coefficient of approximately 2E+05:1 meaning that if lung exposure occurred there would be uptake into the systemic circulation. The high water solubility of the hydrolysis product, 2,3-dihydroxypropoxypropylsilanetriol, results in a markedly higher blood:air partition coefficient (approximately 2.6E+13:1) 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 of 2,3-dihydroxypropoxypropylsilanetriol may lead to some of it being retained in the mucus of the lungs so once hydrolysis has occurred, absorption is likely to slow down.

There are no inhalation studies to check for evidence of absorption.

Distribution

For blood:tissue partitioning a QSPR algorithm has been developed by De Jongh et 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 [3-(2,3-Epoxypropoxy)propyl]triethoxysilane predicts that, should systemic exposure occur, distribution would primarily be into fat, with potential slight distribution into liver, muscle, brain and kidney.

For the hydrolysis product, distribution into the main body compartments would be minimal with tissue:blood partition coefficients of less than 1 for all major tissues (zero for fat).

Table 1: tissue:blood partition coefficients

	Log Kow	Kow	Liver	Muscle	Fat	Brain	Kidney
[3-(2,3-Epoxypropoxy)propyl] triethoxysilane	2.0	100	2.5	1.8	50.9	1.9	1.4
2,3-dihydroxypropoxy propylsilanetriol	-3.8	0.00016	0.6	0.7	0.0	0.7	0.8

Metabolism

There are no data on the metabolism of [3-(2,3-epoxypropoxy)propyl]triethoxysilane. However, it will hydrolyse to form ethanol and 2,3-dihydroxypropoxypropylsilanetriol once absorbed into the body. 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. QPSR’s as developed by De Jongh et al. (1997) using log K_ow as 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 of [3-(2,3-epoxypropoxy)propyl]triethoxysilane in blood is approximately 59% while the corresponding value for the hydrolysis product, 2,3-dihydroxypropoxypropylsilanetriol, is > 99%. Therefore these figures suggest that both the parent and the hydrolysis product are likely to be effectively eliminated via the kidneys in urine and accumulation is therefore unlikely.