3-aminopropyltriethoxysilane

Endpoint summary

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

There are no in vivo data on the toxicokinetics of 3-aminopropyl(triethoxy)silane.

The following summary has therefore been prepared based on validated predictions of the 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 made because of the remaining uncertainties that are characteristic of prediction models.

The main input variable for the majority of these algorithms is log Kow so by using this, and where appropriate, other known or predicted physicochemical properties of 3-aminopropyl(triethoxy)silane or its hydrolysis products, reasonable predictions or statements may be made about their potential absorption, distribution, metabolism and excretion (ADME) properties.

3-Aminopropyl(triethoxy)silane hydrolyses in contact with water (0.8 hours, 8.5 hours and 0.15 hours at pH 4, 7 and 9 and 24.7°C), generating 3-aminopropylsilanetriol and ethanol. Human exposure can occur via the inhalation or dermal routes. Due to the rapid hydrolysis at relevant physiological pH values inhalation and dermal exposure would be to the parent and hydrolysis products.

The ADME properties of ethanol have been reviewed in other major reviews (OECD SIDS, 2004) 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).

The molecular weight of 3-aminopropyl(triethoxy)silane is slightly above the ideal range but the substance is water soluble so should oral exposure occur then systemic exposure is likely. The hydrolysis product 3-aminopropylsilanetriol with a predicted water solubility of 1000 g/L and a molecular weight of 137.21 clearly meets these criteria so should oral exposure occur then systemic exposure is very likely.

Clinical signs and histopathological changes were recorded in the key acute (BRRC, 1989) and repeat dose (WIL, 2001) oral studies indicating systemic exposure of substance-related material had occurred.

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 of 3-aminopropyl(triethoxy)silane (17000 mg/L) is favourable for absorption across the skin, but the predicted log Kow of -1.3 at pH 7 is not. Therefore, absorption across the skin is not likely to occur as the substance is too hydrophilic to cross the lipid-rich environment of the stratum corneum.

Similarly, the predicted water solubility (1000 g/L) of the hydrolysis product, 3-aminopropylsilanetriol, is favourable for absorption across the skin but the log Kow of -4 is not. However, the parent substance, 3-aminopropyl(triethoxy)silane is corrosive to the skin so damage to the skin may increase potential for dermal penetration of the hydrolysis products. Clinical signs and histopathological changes were recorded in the key acute (BRRC, 1989) dermal study indicating systemic exposure of substance-related material had occurred.

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

Using these values for 3-aminopropyl(triethoxy)silane predicts a blood:air partition coefficient of approximately 6000:1 meaning that, if lung exposure occurred there would be significant uptake into the systemic circulation.

The high water solubility of the hydrolysis product, 3-aminopropylsilanetriol, results in a markedly higher blood:air partition coefficient so once hydrolysis has occurred, as it would be expected to in the lungs, then uptake would be expected into the systemic circulation to an even greater extent that the parent. However, the high water solubility of 3-aminopropylsilanetriol may lead to some of it being retained in the mucus of the lungs so once hydrolysis has occurred, absorption is likely to slow down.

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. For both the parent substance, 3-aminopropyl(triethoxy)silane, and the hydrolysis product, 3-aminopropylsilanetriol, distribution into the main body compartments would be minimal with tissue:blood partition coefficients of less than 1 for all major tissues (zero for fat).

Table 5.1.1: Tissue:blood partition coefficients

	Log Kow	Kow	Liver	Muscle	Fat	Brain	Kidney
3 -Amino propyltriethoxysilane	-1.3	0.005	0.6	0.7	0	0.7	0.8
3 -Aminopropylsilanetriol	-4	0.0001	0.6	0.7	0.0	0.7	0.8

Metabolism

There are no data regarding the metabolism of 3-aminopropyl(triethoxy)silane. However, it will hydrolyse to form 3-aminopropylsilanetriol and ethanol 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. 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 fractions of 3-aminopropyl(triethoxy)silane and the hydrolysis product 3-aminopropylsilanetriol in blood are both >99% meaning they are likely to be eliminated via the kidneys in urine and accumulation is unlikely.

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

Meulenberg, C.J. and H.P. Vijverberg (2000) Empirical relations predicting human and rat tissue:air partition coefficients of volatile organic compounds. Toxicol Appl Pharmacol. 165(3): p. 206-16.

OECD (2004) OECD SIDS Initial Assessment Report/Profile on ethanol. https://hpvchemicals.oecd.org/UI/SIDS_Details.aspx?key=82ce88f9-3fa9-4604-ac4a-abbc768da1b6&idx=0

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