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EC number: 221-338-7 | CAS number: 3069-40-7
There are no in vitro or in vivo data on the toxicokinetics of trimethoxy(octyl)silane.
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. 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 trimethoxy(octyl)silane, reasonable predictions or statements may be made about its potential ADME properties.
Trimethoxy(octyl)silane is a low volatility, moisture-sensitive liquid that hydrolyses in contact with water (half-life 4 hours at pH 7; predicted), generating methanol and octylsilanetriol. Human exposure can occur via the inhalation or dermal routes. The toxicokinetics of methanol have been reviewed in other major reviews and are not considered further here.
Based on the known use pattern, significant oral exposure is not expected for the parent substance. Oral exposure to humans via the environment may be relevant for the hydrolysis product, octylsilanetriol. 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 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).
As octylsilanetriol, with a water solubility of 59000 mg/L and a molecular weight of 192.33 g/mol, meets both of these criteria, should oral exposure occur it is reasonable to assume systemic exposure will occur also. Repeated dose oral studies with the read-across substance, triethoxy(octyl)silane, from which octylsilanetriol would also be generated as a hydrolysis product, have shown effects resulting from systemic exposure, thus indicating systemic uptake has taken place.
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. With a log Kow of 3.9 and water solubility of 13.3 mg/L, absorption of trimethoxy(octyl)silane across the skin is likely to be moderate. The predicted water solubility (59000 mg/L) and predicted log Kow (1.1) of the hydrolysis product, octylsilanetriol, are favourable for absorption across the skin so systemic exposure via this route is likely. Therefore once hydrolysis has occurred on the skin, absorption is likely to be increased. The available reliable skin irritation study did not report systemic effects.
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. Trimethoxy(octyl)silane is considered to be moderately volatile while the hydrolysis product, octylsilanetriol with a significantly lower vapour pressure is much less so. Therefore, once dermal exposure to trimethoxy(octyl)silane occurs, subsequent systemic exposure is far more likely to be to the hydrolysis product, octylsilanetriol.
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 trimethoxyoctylsilane results in a blood:air coefficient of 13:1 meaning that, as it is moderately volatile, once in the lungs there would be uptake in to the systemic circulation. The high-water solubility of the hydrolysis product, octylsilanetriol, results in a markedly higher blood:air partition coefficient 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 octylsilanetriol 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.
For blood:tissue partitioning a QSPR algorithm has been developed by DeJongh 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 trimethoxy(octyl)silane predicts that it will distribute into the main body compartments (see Table 5.1.1) as follows: fat >> liver > brain > muscle ≈ kidney with tissue:blood partition coefficients of 112.4 for fat and 4.9 to 8.2 for the remaining tissues. For the hydrolysis product, approximately the same proportion would distribute to liver, muscle, brain and kidney, whereas distribution would be 10-fold higher to fat.
Table 5.1.1Tissue:blood partition coefficients
There are no data regarding the metabolism of trimethoxy(octyl)silane. Genetic toxicity tests in vitros howed no observable differences in effects with and without metabolic activation for trimethoxy(octyl)silane. In a 28-day ready biodegradation test there was no evidence for biodegradation other than could be accounted for by biodegradation of the non-silanol hydrolysis product, ethanol, which is readily biodegradable (see Section 4). This suggests that the substance and its silanol hydrolysis product are not recognised by biological systems containing all the mammalian enzymes and metabolic systems.
A determinant of the extent of urinary excretion is the soluble fraction in blood. QPSRs as developed by DeJongh et 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 this algorithm, the soluble fraction of octylsilanetriol in blood is approximately 92% while the equivalent figure for trimethoxy(octyl)silane is 2%. Therefore, these figures taken together with the low molecular weight and high water solubility of the hydrolysis product, octylsilanetriol, suggest that it is likely to be effectively eliminated via the kidneys in urine. The parent substance however, with a lower water solubility and higher log Kow would be predicted to not be as readily eliminated from the body. However, as the parent is hydrolysed, the silanol hydrolysis product will be excreted via urine, and accumulation is therefore unlikely.
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