N-(dimethylvinylsilyl)-1,1-dimethyl-1-vinylsilylamine

Endpoint summary

Additional information

There are no in vivo data on the toxicokinetics of N-(dimethylvinylsilyl)-1,1-dimethyl-1-vinylsilylamine.

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 N-(dimethylvinylsilyl)-1,1-dimethyl-1-vinylsilylamineor its hydrolysis products, reasonable predictions or statements may be made about their potential absorption, distribution, metabolism and excretion (ADME) properties.

N-(Dimethylvinylsilyl)-1,1-dimethyl-1-vinylsilylamine is a moisture-sensitive liquid that hydrolyses very rapidly in contact with water, generating ammonia and dimethylvinylsilanol. There are no data for the hydrolysis of N-(dimethylvinylsilyl)-1,1-dimethyl-1-vinylsilylamine, therefore data for the related substance 1,1,1,3,3,3-hexamethyldisilazane (CAS 999-97-3) have been read-across. This read-across substance is fully hydrolysed within less than one minute at pH 4, 7 and 9 and 1.5°C.

For N-(dimethylvinylsilyl)-1,1-dimethyl-1-vinylsilylamine human exposure can occur via the inhalation or dermal routes. Due to the very rapid hydrolysis, relevant dermal and inhalation exposure would be to the hydrolysis products.

The toxicokinetics of ammonia have been reviewed in other major reviews and are not considered further here.

Absorption

Oral

Significant oral exposure is not expected for this substance.

However, oral exposure to humans via the environment may be relevant for the hydrolysis product,dimethylvinylsilanol.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 dimethylvinylsilanol, with a calculated 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_ow values 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 N-(dimethylvinylsilyl)-1,1-dimethyl-1-vinylsilylamineon 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, dimethylvinylsilanol, 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. Dimethylvinylsilanol has a high vapour pressure so evaporation may limit the potential for dermal absorption.

There are no dermal toxicity studies for N-(dimethylvinylsilyl)-1,1-dimethyl-1-vinylsilylamine. Skin irritation studies did not show any signs of systemic toxicity.

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 the hydrolysis product,dimethylvinylsilanol, 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 high water solubility ofdimethylvinylsilanolmay lead to some of it being retained in the mucus of the lungs so once hydrolysis has occurred, absorption is likely to slow down.

There are no inhalation data that could be reviewed for signs of systemic toxicity, and therefore absorption.

Distribution

All absorbed test substance is likely to be in the form of the hydrolysis products.

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 the hydrolysis product,dimethylvinylsilanol, the QSPR algorithm 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
Dimethylvinylsilanol	1.5	31.62	1.5	1.2	22.4	1.4	1.1

 

Metabolism

N-(Dimethylvinylsilyl)-1,1-dimethyl-1-vinylsilylamine is hydrolysed into dimethylvinylsilanol and ammonia before absorption. There are no data regarding the metabolism of dimethylvinylsilanol. Genetic toxicity tests in vitro showed no observable differences in effects with and without metabolic activation for N-(dimethylvinylsilyl)-1,1-dimethyl-1-vinylsilylamine.

Excretion

A determinant of the extent of urinary excretion is the soluble fraction in blood. QPSRs as developed by DeJongh et al. (1997) using log K_owas 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 the hydrolysis productdimethylvinylsilanolin blood is approximately 82% suggesting it is likely to be effectively eliminated via the kidneys in urine.

References:

DeJongh, J., H.J. Verhaar, and J.L. Hermens, A quantitative property-property relationship (QPPR) approach to estimatein vitrotissue-blood partition coefficients of organic chemicals in rats and humans. Arch Toxicol, 1997. 72(1): p. 17-25.

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.

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