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There are no data on the toxicokinetics of 1,1,1,3,5,5,5-Heptamethyl-3-[(trimethylsilyl)oxy]trisiloxane.

The following summary has therefore been prepared based on the physicochemical properties of 1,1,1,3,5,5,5-heptamethyl-3-[(trimethylsilyl)oxy]trisiloxane itself 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 Kow so by using this, and other where appropriate, known or predicted physicochemical properties of 1,1,1,3,5,5,5-heptamethyl-3-[(trimethylsilyl)oxy]trisiloxane reasonable predictions or statements may be made about its potential absorption, distribution, metabolism and excretion (ADME) properties.

In contact with water, the substance reacts slowly (half-life of approximately 630 hours at pH 7 and 25°C). The hydrolysis products are trimethylsilanol and methylsilanetriol.

Relevant human exposure can occur via the oral, inhalation or dermal routes.

Absorption:

Oral:

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).

The molecular weight of 1,1,1,3,5,5,5-heptamethyl-3-[(trimethylsilyl)oxy]trisiloxane (approximately 311) is above the favourable range for absorption and due to its highly lipophilic nature and low water solubility the only means by which absorption from the gastrointestinal tract is likely to occur is via micellar solubilisation.

Methylsilanetriol and trimethylsilanol are both highly water soluble and have molecular weights below 200. Therefore, favourable characteristics for absorption of these compounds occur why oral exposure to the hydrolysis product (which potentially might occur via the environment) would likely result in systemic exposure.

An acute oral study on 1,1,1,3,5,5,5-heptamethyl-3-[(trimethylsilyl)oxy]trisiloxane did not show any signs of toxicity and therefore, no evidence of absorption was observed.

Dermal:

The fat solubility and 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. Therefore, with a log Kow of 8.2 and water solubility of approximately 0.002 mg/L, dermal absorption is unlikely to occur as 1,1,1,3,5,5,5-heptamethyl-3-[(trimethylsilyl)oxy]trisiloxane is not sufficiently soluble in water to partition from the stratum corneum into the epidermis. Furthermore, 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. 1,1,1,3,5,5,5-heptamethyl-3-[(trimethylsilyl)oxy]trisiloxane is volatile so this would further reduce the potential for dermal absorption.

There are no dermal toxicity studies available on1,1,1,3,5,5,5-heptamethyl-3-[(trimethylsilyl)oxy]trisiloxane to check for signs of dermal absorption although the available skin irritation studies did not report systemic effects.

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's Law coefficient and the octanol:air partition coefficient (Koct: air) as independent variables.

 

Using these values for 1,1,1,3,5,5,5-heptamethyl-3-[(trimethylsilyl)oxy]trisiloxane results in an extremely low blood: air partition coefficient (approximately 3.6E-05:1) so absorption across the respiratory tract epithelium is likely to be restricted to micellar solubilisation. There are no inhalation toxicity studies to check for signs of absorption.

 

Distribution:

For blood: tissue partitioning a QSPR algorithm has been developed by De Jongh 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 for 1,1,1,3,5,5,5-heptamethyl-3-[(trimethylsilyl)oxy]trisiloxane predicts that should systemic exposure occur it will distribute into the main body compartments as follows: fat >> brain > liver ≈ kidney > muscle with tissue: blood partition coefficients of 113.9 for fat and 5.5 to 20.3 for the remaining tissues.

Table 1: tissue:blood partition coefficients

 

 

Log Kow

Kow

Liver

Muscle

Fat

Brain

Kidney

1,1,1,3,5,5,5-heptamethyl-3-[(trimethylsilyl)oxy]trisiloxane

8.2

1.58E+08

8.9

5.5

113.9

20.3

8.4

 

Metabolism:

There are no data regarding the metabolism of 1,1,1,3,5,5,5-heptamethyl-3-[(trimethylsilyl)oxy]trisiloxane. 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. QPSR’s as developed by De Jongh 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 1,1,1,3,5,5,5-heptamethyl-3-[(trimethylsilyl)oxy]trisiloxanein blood is <1E-04%, therefore it would not be eliminated via the urine.