Chlorodimethylvinylsilane

Endpoint summary

Additional information

There are no in vivo data on the toxicokinetics of chloro(dimethyl)vinylsilane.

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 K_ow so by using this, and other where appropriate, known or predicted physicochemical properties of chloro(dimethyl)vinylsilane or its hydrolysis product, reasonable predictions or statements may be made about their potential ADME properties.

Chloro(dimethyl)vinylsilane is a moisture-sensitive liquid that hydrolyses very rapidly in contact with water (based on read-across from related substance: Half-life < 1 min at 25°C and pH 4, 7 and 9), generating hydrochloric acid and dimethyl(vinyl)silanol. 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.

Therefore, due to the very rapid hydrolysis of chloro(dimethyl)vinylsilane, systemic exposure to this parent substance is not expected. Potential systemic exposure to the hydrolysis product, dimethyl(vinyl)silanol is discussed below. Potential systemic exposure to the other hydrolysis product, hydrochloric acid, is not discussed.

Chloro(dimethyl)vinylsilane undergoes condensation reactions in aqueous solution to give siloxane dimers (1,1,3,3 -tetramethyl-1,3 -divinyldisiloxane, CAS 2627 -95 -4). The overall rate and extent of condensation is dependent on nominal loading, temperature and pH of the system, as well as what else is present in the solution. Dimer formation is expected to be significant at concentrations above around 250 mg/l. This concentration is expected to have been exceeded in the gut in the available toxicity studies. Therefore, exposure to 1,1,3,3 -tetramethyl-1,3 -divinyldisiloxane could have occurred.

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, dimethyl(vinyl)silanol. 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 dimethyl(vinyl)silanol, with a predicted water solubility of 3700 mg/l and a molecular weight of 102.21, meets both of these criteria, 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_ow values. 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 of chloro(dimethyl)vinylsilane on contact with skin, systemic exposure via this route is predicted to be minimal. However, the predicted water solubility (3700 mg/l) and predicted log K_ow (1.5) of the hydrolysis product, dimethyl(vinyl)silanol, are favourable for absorption across the skin so systemic exposure via this route is likely. 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. Dimethyl(vinyl)silanol has a high predicted vapour pressure (250 Pa) so evaporation may affect the potential for dermal absorption.

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

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.

The low Henry coefficient of the hydrolysis product, dimethyl(vinyl)silanol, results in a very high 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 water solubility of dimethyl(vinyl)silanol 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.

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 reliable studies on the silanol hydrolysis product to check for signs of inhalation toxicity.

Distribution

For blood:tissue partitioning a QSPR algorithm has been developed by De Jonghet 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, dimethyl(vinyl)silanol, predicts that it will distribute approximately equally to liver, muscle, brain and kidney and about 20-fold higher to fat.

Table 1: tissue:blood partition coefficients

	Log Kow	Kow	Liver	Muscle	Fat	Brain	Kidney
Dimethyl(vinyl)silanol	1.5	31.62	1.5	1.2	22.4	1.4	1.1

 

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

Metabolism

There are no data regarding the metabolism of dimethyl(vinyl)silanol. Major metabolism of dimethyl(vinyl)silanol is not expected due to its high water solubility. Genetic toxicity tests in vitro showed no observable differences in effects with and without metabolic activation for chloro(dimethyl)vinylsilane.

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 dimethyl(vinyl)silanol in blood is approximately 82% suggesting it is likely to be effectively eliminated via the kidneys in urine.

 

Renwick A. G. (1993) Data-derived safety factors for the evaluation of food additives and environmental contaminants.Fd. Addit. Contam.10: 275-305.

Meulenberg, C.J. and H.P. Vijverberg, Empirical relations predicting human and rat tissue:air partition coefficients of volatile organic compounds. Toxicol Appl Pharmacol, 2000. 165(3): p. 206-16.

DeJongh, J., H.J. Verhaar, and J.L. Hermens, A quantitative property-property relationship (QPPR) approach to estimate in vitro tissue-blood partition coefficients of organic chemicals in rats and humans. Arch Toxicol, 1997.72(1): p. 17-25.