Potassium methylsilanetriolate

Endpoint summary

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

There are no data on the toxicokinetics of potassium methylsilanetriolate.

The following summary has therefore been prepared based on validated predictions of the physicochemical properties of the substance itselfand 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 potassium methylsilanetriolate reasonable predictions or statements may be made about its potential absorption, distribution, metabolism and excretion (ADME) properties.

Potassium methylsilanetriolate is a mono-constituent ionic substance of 35-55% w/w potassium methylsilanetriolate in aqueous solution that has a very alkaline pH of >12. Potassium methylsilanetriolate dissociates complete into potassium and methylsilanetriolate ions in aqueous solution. In more dilute aqueous solution the pH of the substance will be reduced dependent on concentration. As the pH is reduced, the concentration of the non-ionised form of methylsilanetriolate (methylsilanetriol) increases. At pH < 9.0, the substance is no longer in the ionised form; methylsilanetriol is the predominant species at low concentrations, with dimers and oligomers of methylsilanetriol forming at higher concentrations. Under comparable conditions of concentration and pH, methylsilanetriolate is equivalent to methylsilanetriol.

Potential human exposure can occur via inhalation, as an aerosol, or dermal routes. However, due to the very high pH of the parent solution, severe irritant or corrosive effects are likely to be the most significant factors when exposure occurs.

Absorption

Oral

Significant oral exposure is not expected for this corrosive substance.

However, should it occur, and excepting the fact that the primary limiting factor will be the corrosive nature of the solution, oral exposure to humans may be relevant for potassium methylsilanetriolate. If oral exposure should occur, at doses which do not cause local corrosion, potassium methylsilanetriolate will be neutralised by the acidity of the stomach and exposure will be to methylsilanetriol. 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 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).

As methylsilanetriol is very water soluble (1E+06 mg/l) and has a molecular weight of approximately 94.14 it meets both of these criteria, so should oral exposure occur it is reasonable to assume systemic exposure will occur also. However, the formation of dimers and oligomers at higher concentrations might reduce systemic uptake.

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.

Although the water solubility (1E+06 mg/l) of methylsilanetriol is favourable for absorption, the predictedlog K_owof -2.4 is not, so it is consideredtoo hydrophilic to cross the lipid-rich stratum corneum. Therefore dermal uptake is likely minimal.

However, since the parent solution with a pH of 13 will be severely corrosive to the skin damage to the skin may result in increased penetration. There are no dermal studies which would indicate if uptake by this route had occurred.

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 methylsilanetriol results in a blood:air partition coefficient (approximately 8.0E+07:1) meaning that uptake would be expected into the systemic circulation. However, the high water solubility of methylsilanetriol may lead to some of it being retained in the mucus of the lungs so this may limit absorption.

As with dermal exposure, damage to membranes caused by the corrosive nature of the parent solution may enhance the uptake. There are no studies 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 methylsilanetriol, predicts that should systemic exposure occur, distribution would be minimal with tissue:blood partition coefficients of less than 1 for all tissues (zero for fat).

Table 1: tissue:blood partition coefficients

	Log Kow	Kow	Liver	Muscle	Fat	Brain	Kidney
methylsilanetriol	-2.36	3.98E-03	0.6	0.7	0.0	0.7	0.8

Potassium ions will enter the body's natural homeostatic processes.

Metabolism

There are no data regarding the metabolism of potassium methylsilanetriolate or methylsilanetriol.Genetic toxicity tests in vitro showed no observable differences in effects with and without metabolic activation whenpotassium methylsilanetriolate or related substances were tested.

Excretion

A determinant of the extent of urinary excretion is the soluble fraction in blood. QPSRs as developed by De Jonghet 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 methylsilanetriol in blood is > 99% suggesting it is likely to be effectively eliminated via the kidneys in urine and accumulation is very unlikely.

 

 

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.