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There are no data on the toxicokinetics of [2-(perfluorohexyl)ethyl]trichlorosilane.

The following summary has therefore been prepared based on predicted and measured 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. Although these algorithms provide quantitative outputs, for the purposes of this summary only qualitative statements or predictions will be made.

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 [2-(perfluorohexyl)ethyl]trichlorosilane or its hydrolysis products, reasonable predictions or statements may be made about their potential absorption, distribution, metabolism and excretion (ADME) properties.

[2-(Perfluorohexyl)ethyl]trichlorosilane hydrolyses very rapidly in contact with water (half-life approximately 5 seconds at 25°C and pH 4, 7 and 9 (by read-across)) producing [2‑(perfluorohexyl)ethyl]silanetriol and hydrogen chloride. Relevant human exposure would be 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 hydrogen chloride hydrolysis product would be severely irritating or corrosive and this results in the parent substance being corrosive and this is the critical health effect for the registered substance.

Potential systemic exposure to hydrogen chloride is not discussed.

Absorption

Oral

Significant oral exposure is not expected for the corrosive parent substance, [2‑(perfluorohexyl)ethyl]trichlorosilane. However, oral exposure to the hydrolysis product [2‑(perfluorohexyl)ethyl]silanetriol 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 the 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, [2-(perfluorohexyl)ethyl]silanetriol with a predicted water solubility of 0.58 mg/l at 20°C (QSAR) and a molecular weight of 426.21 does not meet these criteria so systemic exposure is unlikely.

Dermal

The fat solubility and therefore 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. The predicted water solubility (0.58 mg/l) of [2-(perfluorohexyl)ethyl]silanetriol is unfavourable for absorption across the skin but the log Kow of 2.7 is in the favourable range. Therefore, absorption across the skin may occur as the substance is likely to be sufficiently hydrophilic to cross the lipid-rich environment of the stratum corneum.

Since [2-(perfluorohexyl)ethyl]trichlorosilane is corrosive to the skin, damage to the skin may increase penetration of the hydrolysis product.

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

Using these values for [2-(perfluorohexyl)ethyl]silanetriol results in a blood:air partition coefficient of approximately 233:1 meaning that if lung exposure occurred uptake into the circulatory system would be likely. The low water solubility of [2‑(perfluorohexyl)ethyl]silanetriol suggests that it is unlikely be dissolved in the mucous of the respiratory tract lining, so passive absorption from the mucous is unlikely.

As with dermal exposure, damage to membranes caused by the corrosive nature of the hydrogen chloride hydrolysis product may increase the uptake.

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 (Kow) is described. Using this value for [2-(perfluorohexyl)ethyl]silanetriol predicts that, should systemic exposure occur, potential distribution into the main body compartments would be predominately to the fat.

Table 1: Tissue:blood partition coefficients

 

Log Kow

Kow

Liver

Muscle

Fat

Brain

Kidney

[2‑(perfluorohexyl)ethyl]silanetriol

2.7

501

4.9

3.2

92.2

3.1

2.3

Metabolism

[2-(Perfluorohexyl)ethyl]trichlorosilane is rapidly hydrolysed in the presence of moisture to [2‑(perfluorohexyl)ethyl]silanetriol and hydrogen chloride. Most if not all of this will have occurred before absorption into the body. There is no data regarding the metabolism of [2‑(perfluorohexyl)ethyl]silanetriol. Genetic toxicity tests in vitro with the analogue substances, [2-(perfluorohexyl)ethyl]dichloro(methyl)silane and dichloromethyl(3,3,3-trifluoropropyl)silane, 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 DeJongh 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 the algorithm, the soluble fraction of [2-(perfluorohexyl)ethyl]silanetriol in blood is 22% meaning that once absorbed there is some potential for the substance to be 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.