Triethoxy(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)silane

Endpoint summary

Additional information

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

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. Although these algorithms provide a numerical value, 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 K_ow so by using this, and other where appropriate, known or predicted physicochemical properties of [2‑(perfluorohexyl)ethyl]triethoxysilane or its hydrolysis products, reasonable predictions or statements may be made about their potential absorption, distribution, metabolism and excretion (ADME) properties.

[2-(Perfluorohexyl)ethyl]triethoxysilane, hydrolyses at a moderate rate in contact with water, with a hydrolysis half-life of 12.5 h at pH 7 and 20°C (1.44 at pH 4 and 20°C, at pH 9 and 20°C. The products of hydrolysis are [2-(perfluorohexyl)ethyl]silanetriol and ethanol. Relevant human exposure would be to the parent substance and can occur via the oral, inhalation or dermal routes.

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

Absorption

Oral

Significant oral exposure is not expected for this substance.

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).

Therefore, following oral exposure to the parent, the molecular weight of [2‑(perfluorohexyl)ethyl]triethoxysilane (510.37) is above the favourable range and, due to its lipophilicity (log Kow value of 7.2 at 20°C) and low water solubility (6.4E-06 mg/l), the only means by which absorption from the gastrointestinal tract is likely to occur is via micellar solubilisation.

Oral exposure to humans via the environment may be relevant for the hydrolysis product, [2-(perfluorohexyl)ethyl]silanetriol. The hydrolysis product, [2-(perfluorohexyl)ethyl]silanetriol has a low water solubility value (0.58 mg/L) and the molecular weight (426.21) is above the favourable range, therefore it is considered that significant systemic exposure to the parent substance following oral exposure is unlikely.

However, the surface active properties of [2‑(perfluorohexyl)ethyl]triethoxysilane mean that the predictions are not be reliable for this substance. The available oral OECD 422 screening study on this substance confirms that absorption following oral exposure does occur, as extensive adverse systemic effects were observed.

Dermal

If dermal exposure was to occur, in practice this would be to the parent compound.

The fat solubility and the 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.

Both the water solubility andthelog K_owof [2‑(perfluorohexyl)ethyl]triethoxysilane are unfavourable for dermal absorption,therefore absorption by this route unlikely. Although the log K_ow value of hydrolysis product [2-(perfluorohexyl)ethyl]silanetriol is optimal for dermal absorption, the low water solubility and slow hydrolysis of the parent indicate thatdermal absorption of [2-(perfluorohexyl)ethyl]silanetriol into the blood is likely to be minimal.

As for the oral route of exposure these predictions might not be suitable due to the surface active properties of the parent substance. The acute dermal test did not reveal signs of systemic toxicity.

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 (K_oct:air) as independent variables.

Using these values for [2‑(perfluorohexyl)ethyl]triethoxysilane predicts an extremely low blood:air partition coefficient of approximately 1.6E-06:1 meaning that even if lung exposure occurred there would be no uptake into the systemic circulation. 

For the hydrolysis product [2-(perfluorohexyl)ethyl]silanetriol the predicted blood:air partition coefficient is markedly higher at approximately 133:1. Therefore, following hydrolysis, some uptake of the hydrolysis product would be expected into the systemic circulation.

As for the oral route of exposure these predictions might not be suitable due to the surface active properties of the parent substance. The acute inhalation test did not reveal signs of systemic toxicity.

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 (K_ow) is described. Using this value for [2‑(perfluorohexyl)ethyl]triethoxysilane predicts that, should systemic exposure occur, potential distribution into the main body compartments would be mainly to the adipose tissue.

Similarly, for the hydrolysis products, distribution into the main body compartments is predicted to be mainly to the adipose tissue.

Table: Tissue:blood partition coefficients

	Log Kow	Kow	Liver	Muscle	Fat	Brain	Kidney
[2‑(perfluorohexyl)ethyl]triethoxysilane	7.2	1.00E+07	8.9	5.5	113.9	19.5	8.3
[2-(perfluorohexyl)ethyl]silanetriol	2.8	6.31E+02	5.3	3.4	96.1	3.3	2.4

 

Metabolism

There are no data on the metabolism of [2‑(perfluorohexyl)ethyl]triethoxysilane. However, it will hydrolyse at a moderate rate to form ethanol and [2-(perfluorohexyl)ethyl]silanetriol once absorbed into the body. 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. A quantitative property-property relationship (QPPR) approach, as developed by De Jongh et al. (1997) using log K_ow as an input parameter, calculates 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]triethoxysilane in blood is approaching zero, meaning that if the parent substance were absorbed, accumulation is likely. For the hydrolysis product, [2-(perfluorohexyl)ethyl]silanetriol, the figure is 18% meaning that if absorbed, the hydrolysis product is likely to be eliminated via the kidneys in urine and accumulation is 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.