[3-(2,3-epoxypropoxy)propyl]diethoxymethylsilane

Endpoint summary

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

There are no data on the toxicokinetics of [3-(2,3-epoxypropoxy)propyl]diethoxy(methyl)silane (CAS 2897-60-1).

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 comparisons will be made.

The main input variable for the majority of these algorithms is log K_owso by using this, and other where appropriate, known or predicted physicochemical properties of [3-(2,3-epoxypropoxy)propyl]diethoxy(methyl)silane or its hydrolysis products, reasonable predictions or statements may be made about their potential absorption, distribution, metabolism and excretion (ADME) properties.

[3-(2,3-epoxypropoxy)propyl]diethoxy(methyl)silane hydrolyses in contact with water (half-life 0.4 hours at pH 4, 0.5 hours at pH 5, 11.7 hours at pH 7 and 0.2 hours at pH 9 and 25°C), generating [3-(2,3-epoxypropoxy)propyl]methylsilanediol and ethanol.

Human exposure can occur via the oral, inhalation or dermal routes. Relevant oral and dermal exposure would be to the hydrolysis product and the parent substance.

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

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).

In the acidic environment of the stomach, the parent substance hydrolyses very rapidly (hydrolysis at 37.5°C and pH2 is 5 seconds). The hydrolysis product, [3-(2,3-epoxypropoxy)propyl]methylsilanediol has a favourable molecular weight (192.28) and water solubility (1.0E+06 mg/l) for absorption so systemic exposure is likely. The parent substance has a molecular weight which is not favourable for uptake (284.4) but is water soluble (1200 mg/l), so some systemic exposure is possible.

 

Dermal

Dermal exposure would be to the parent and the hydrolysis products, as at pH 5 the hydrolysis rate is 0.5 hours.

The fat solubility and therefore potential dermal penetration of the parent and the hydrolysis product [3-(2,3-epoxypropoxy)propyl]methylsilanediol 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 parent substance has a log K_owvalue in the favourable range (2.7) and is water soluble (1200 mg/l) so dermal absorption is likely. For the hydrolysis product, [3-(2,3-epoxypropoxy)propyl]methylsilanediol, although it is highly soluble (1.0E+06 mg/l), the log K_owvalue (0.7) indicates it is not likely to be sufficiently lipophilic to cross the stratum corneum and therefore dermal absorption into the blood is likely to be minimal. Therefore, absorption of substance-related material will slow down as hydrolysis progresses

 

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.

For the hydrolysis product [3-(2,3-epoxypropoxy)propyl]methylsilanediol the predicted blood:air partition coefficient is approximately 8.1E+08:1 meaning that significant uptake in to the systemic circulation is likely. However, the high water solubility 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. Similarly, for the parent, the blood:air coefficient is approximately 1.1+04:1, and uptake is likely.

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.

For the parent compound, distribution into fat tissue is likely, but distribution to other compartments is likely to be minimal.

For the hydrolysis product [3-(2,3-epoxypropoxy)propyl]methylsilanediol, distribution into the main body compartments is predicted to be minimal.

Table 5.1: Tissue:blood partition coefficients

	Log Kow	Kow	Liver	Muscle	Fat	Brain	Kidney
[3-(2,3-epoxypropoxy)propyl]diethoxy(methyl)silane	2.7	501.19	4.9	3.2	92.2	3.1	2.3
[3-(2,3-epoxypropoxy)propyl]methylsilanediol	0.7	5.01	0.8	0.8	3.9	1	0.9

 

Metabolism

There are no data on the metabolism of [3-(2,3-epoxypropoxy)propyl]diethoxy(methyl)silane. However, it will hydrolyse when in contact with moisture to form ethanol and [3-(2,3-epoxypropoxy)propyl]methylsilanediol. 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 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 the algorithm, the soluble fraction of the parent in blood is 22% but for the hydrolysis product[3-(2,3-epoxypropoxy)propyl]methylsilanediolthe soluble fraction in blood is >96% meaning that once absorbed the hydrolysis product is likely to be eliminated via the kidneys in urine and accumulation is unlikely.

 

References

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.