Dichloromethyl(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]dichloro(methyl)silane.

The following summary has therefore been prepared based on predicted and measured physicochemical properties of the substance itself and its hydrolysis products. The data have been used in algorithms which 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 madebecause of the remaining uncertainties that are characteristic of prediction models.

The main input variable for the majority of these algorithms is log K_owso by using this and, where appropriate, other known or predicted physicochemical properties of[2-(perfluorohexyl)ethyl]trichlorosilaneor its hydrolysis products, reasonable predictions or statements may be made about their potential absorption, distribution, metabolism and excretion (ADME) properties.

[2-(perfluorohexyl)ethyl]dichloro(methyl)silane is a moisture-sensitive liquid that hydrolyses very rapidly in contact with water(based on read-across from related substances: half-life approximately 5 seconds at 25°C and pH 4, 7 and 9), generating [2-(perfluorohexyl)ethyl]silanediol and hydrogen chloride. Human exposure could occur 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.

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 humans via the environment may be relevant for the hydrolysis product[2-(perfluorohexyl)ethyl]silanediol.

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).

The hydrolysis product [2-(perfluorohexyl)ethyl]silanediol has a low predicted water solubility of 0.0048 mg/l at 20°C (QSAR) and a molecular weight (424.2) which is above the favourable range, therefore it is considered that significant systemic exposure to the hydrolysis product following oral exposure is unlikely.However, the surface active properties of [2-(perfluorohexyl)ethyl]silanediol mean that the predictions are not be reliable for this substance. Some systemic effects were reported in the available acute oral toxicity study (OECD 423). Since [2-(perfluorohexyl)ethyl]dichloro(methyl)silane is hydrolytically unstable, it is considered that the animals would have been exposed to the hydrolysis products, [2-(perfluorohexyl)ethyl]methylsilanediol and hydrochloric acid, and that the effects observed reflect the properties of the hydrolysis products. Therefore, the study indicates that absorption following oral exposure does occur.

 

Dermal

The fat solubility and therefore potential dermal penetration of a substance can be estimated by using the water solubility and log K_owvalues. Substances with log K_owvalues between 1 and 4 favour dermal absorption (values between 2 and 3 are optimal) particularly if water solubility is high. The predicted water solubility (0.0048 mg/l) of [2-(perfluorohexyl)ethyl]silanediol is unfavourable for absorption across the skin and the log K_owof 4.6 is above the favourable range. Therefore dermal absorption is unlikely to occur, since the substance is not sufficiently soluble in water to partition from the stratum corneum into the epidermis. However, since[2-(perfluorohexyl)ethyl]dichloro(methyl)silane is corrosive to the skin,dermal absorption could be increased if damage to the skin occurs due to corrosive effects of the substance. As for the oral route of exposure these predictions might not be suitable due to the surface active properties of the parent substance.There are no dermal studies to check for signs of systemic availability.

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]silanediol results in a blood:air partition coefficient of approximately 0.04:1 meaning that if lung exposure occurred uptake into the circulatory system would be unlikely. The low water solubility of [2-(perfluorohexyl)ethyl]silanediol also 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. There are no inhalation studies to check for signs of systemic availability.

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 (K_ow) is described. Using this value for[2-(perfluorohexyl)ethyl]silanediolpredicts 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]silanediol	4.6	39810	8.7	5.4	113.6	11.3	6.5

Metabolism

[2-(perfluorohexyl)ethyl]dichloro(methyl)silane is rapidly hydrolysed in the presence of moisture to [2‑(perfluorohexyl)ethyl]silanediol and hydrogen chloride. Most if not all of this will have occurred before absorption into the body. Genetic toxicity testsin vitrowith the registered substance [2-(perfluorohexyl)ethyl]dichloro(methyl)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 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 the algorithm, the soluble fraction of [2-(perfluorohexyl)ethyl]silanediol in blood is <1% and the substance is therefore unlikely 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.