Tris(2-methoxyethoxy)vinylsilane

Endpoint summary

Additional information

There are no data on the toxicokinetics of tris(2-methoxyethoxy)vinylsilane.

Therefore, the following summary has been prepared based on the predicted and measured physicochemical properties of the registered substance and its hydrolysis products (see Table 5.1.1 below). The data have been used in algorithms which are the basis of many physiologically based pharmacokinetic and toxicokinetic (PBTK) prediction models. Although these algorithms provide quantitative outputs, for the purposes of this summary only qualitative statements or predictions will be made because of the remaining uncertainties that are characteristic of prediction models.

The main input variable for the majority of the algorithms is the log K_ow. By using this, and where appropriate, other known or predicted physicochemical properties of tris(2-methoxyethoxy)vinylsilane or its hydrolysis products, reasonable predictions or statements may be made about their potential absorption, distribution, metabolism and excretion (ADME) properties.

Tris(2-methoxyethoxy)vinylsilane hydrolyses in contact with water (half-life approximately 1-hour at pH 7 and at 20°C), generating vinylsilanetriol and 2-methoxyethanol. Human exposure may occur via the inhalation, oral or dermal routes and exposure would be to the parent substance and hydrolysis products.

Table5.1.1:Physicochemical properties

Physicochemical properties	Trimethoxy(vinyl)silane	Vinylsilanetriol	2-Methoxyethanol
Water solubility	220 000 mg/l at 20°C	1 000 000 mg/l at 20°C (predicted, in reality concentration in water limited by condensation reactions)	1 000 000 mg/lat 20°C
Vapour pressure	0.43 Pa at 25°C	0.02 Pa at 25°C	1300 Pa at 25°C
Log Kow	0.3 at 20°C	-2.0 at 20°C	-0.77 at 20°C
MW	280.4	106.2	76.09
Half-life	1-hour at pH 7 and at 20°C	N/A	N/A

 

Absorption

Oral

Significant oral exposure is not expected for this substance. However, oral exposure to the hydrolysis products is potentially possible via the environment.

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 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).

Therefore, if oral exposure did occur, the molecular weight of tris(2-methoxyethoxy)vinylsilane (280.4) is above the favourable range but the water solubility (220 mg/ml) suggests the possibility of systemic exposure via the oral route. At pH 2, the parent compound is predicted to hydrolyse into the hydrolysis product vinylsilanetriol within 5 seconds at the temperature of 37.5°C. Vinylsilanetriol and 2-methoxyethanol both have a favourable molecular weight (106.2 and 76.09 respectively) and water solubility (both 1000 mg/ml) values for absorption so systemic exposure to both would also be likely.

Signs of systemic toxicity were evident in the acute toxicity (WIL, 1999a) and repeat dose toxicity (WIL, 2005) oral studies, which indicates exposure to substance-related material.

Dermal

If dermal exposure were to occur, in practice this would be to the parent compound as well as the hydrolysis products.

The fat solubility and the 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.

Although the water solubility of tris(2-methoxyethoxy)vinylsilane (220 mg/ml) is favourable for dermal absorption, the log K_ow (0.3) is not; so although absorption by this route is not impossible, it is not likely. For the hydrolysis products, vinylsilanetriol and 2-methoxyethanol, although they are highly soluble (both 1000 mg/ml), the log K_ow values (-2.0 and -0.77 respectively) indicate they are not likely to be sufficiently lipophilic to cross the stratum corneum and therefore dermal absorption into the blood is likely to be minimal.

There were no adverse systemic effects in an acute (WIL, 1999b) or repeat dose (Carnegie-Mellon, 1975) dermal toxicity studies and therefore, no evidence of absorption.

Inhalation

There is a Quantitative Structure-Property Relationship (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’s Law coefficient and the octanol:air partition coefficient (K_oct:air) as independent variables.

Using these values for tris(2-methoxyethoxy)vinylsilane predicts a blood:air partition coefficient of approximately 2.1E+06:1 meaning that, if lung exposure occurred there would be significant uptake into the systemic circulation. The water solubility of tris(2-methoxyethoxy)vinylsilane also suggests that it could be dissolved in the mucus of the respiratory tract lining, so it may also be passively absorbed from the mucous, further increasing the potential for absorption.

For the hydrolysis products, vinylsilanetriol and 2-methoxyethanol, predicted blood:air partition coefficients are approximately 5E+08:1 and 1.2E+04:1 respectively meaning that there would be significant exposure to both.

Distribution

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 (K_ow) is described. Using this value for tris(2-methoxyethoxy)vinylsilane predicts that, should systemic exposure occur, potential distribution into the main body compartments would be minimal.

Similarly for the hydrolysis products, distribution into the main body compartments is predicted to be minimal.

Table 5.1.2: Tissue: blood partition coefficients

	Log Kow	Kow	Liver	Muscle	Fat	Brain	Kidney
Trimethoxy(methyl)silane	0.3	2	0.7	0.8	1.4	0.8	0.8
Vinylsilanetriol	-2.0	0.01	0.6	0.7	0.0	0.7	0.8
2-Methoxyethanol	-0.77	0.17	0.6	0.7	0.0	0.7	0.8

Metabolism

There are no data on the metabolism of tris(2-methoxyethoxy)vinylsilane. However, it will hydrolyse to form 2-methoxyethanol and vinylsilanetriol 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. QPSRs as developed by DeJonghet 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 the algorithm, the soluble fraction of tris(2-methoxyethoxy)vinylsilanein blood is approximately 99%. Similarly for the hydrolysis products, the figure is >99% meaning that, once absorbed, both the parent substance and hydrolysis product are likely to be eliminated via the kidneys in urine, and accumulation is unlikely.