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There are no in vivo data on the toxicokinetics of tetrapropyl orthosilicate.

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 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 other where appropriate, known or predicted physicochemical properties of tetrapropyl orthosilicate or its hydrolysis products, reasonable predictions or statements may be made about their potential absorption, distribution, metabolism and excretion (ADME) properties.

Tetrapropyl orthosilicate hydrolyses in water, with a half-life of 6.7 h at pH 7. The hydrolysis products are propanol and silicic acid, which rapidly precipitates to insoluble silica (SiO2) when the concentration is sufficiently high. The toxicokinetics of propanol have been studied previously and therefore will not be discussed further in this summary.

Human exposure can occur via the inhalation or dermal routes.



Significant oral exposure is not expected for this substance.

Tetrapropyl orthosilicate is likely to be rapidly hydrolysed to silicic acid in the stomach, so minimising absorption of tetrapropyl orthosilicate following ingestion. Silicic acid may be absorbed from the gut before it is precipitated out to insoluble silica. Acute oral studies on tetrapropyl orthosilicate did not show any signs of toxicity and therefore no evidence of absorption was observed. However, although the related substance tetraethyl orthosilicate (TEOS) also showed no evidence of systemic toxicity in an acute oral toxicity study, effects on the kidneys (tubular nephropathy) were observed following repeated oral exposures.


The fat solubility and therefore potential dermal penetration of a substance can be estimated by using the water solubility and log Kowvalues. 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.

Tetrapropyl orthosilicate has water solubility (predicted 78 mg/l) and log Kow (predicted 3.4) values that favour dermal absorption, and it is therefore expected to be absorbed prior to hydrolysis. 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 tetrapropyl orthosilicate has a low vapour pressure (predicted 0.26 Pa) evaporation is not likely to be a factor.

Absorption of the silicic acid and silica precipitate across the skin is unlikely.

There are no dermal data to check for signs of toxicity/absorption.



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 (Koct:air) as independent variables.

Using these values for tetrapropyl orthosilicate results in a blood:air partition coefficient of approximately 1350:1 meaning that, if lung exposure occurred there would be uptake in to the systemic circulation.

Following hydrolysis the silicic acid may be retained within the mucous of the lungs and thus absorption will be limited. Hydrolysis to silica might lead to some precipitate being retained in the lining of the respiratory tract. In a repeated-dose inhalation toxicity test with the related substance, TEOS, effects including tubulo-interstitial nephritis and haematological changes were observed, indicating systemic uptake.


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 (Kow) is described. Using this value for tetrapropyl orthosilicate predicts that, should systemic exposure occur, distribution would primarily be into fat, with potential distribution into liver, muscle, brain and kidney but to a much lesser extent.

Table 1: Tissue:blood partition coefficients


Log Kow







tetrapropyl orthosilicate









There are no repeated dose toxicity studies on tetrapropyl orthosilicate; however, in studies on the structurally-related substance, TEOS, the kidney appears to be a target organ following inhalation and oral exposure, therefore it is assumed that tetrapropyl orthosilicate will be similarly distributed to the kidney.


Besides the already mentioned hydrolysis, there is no information on the potential metabolism of tetrapropyl orthosilicate. Silicic acid is not metabolised, but forms a precipitate, as previously described. Genetic toxicity tests in vitro showed no observable differences in effects with and without metabolic activation.


A determinant of the extent of urinary excretion is the soluble fraction in blood. QPSR’s as developed by De Jonghet al. (1997) using log Kow 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 the algorithm, the soluble fraction of tetrapropyl orthosilicate in blood is approximately 5%. Therefore significant elimination via the kidneys in urine is unlikely.