3-trimethoxysilylpropyl methacrylate

Endpoint summary

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

There are no data on the toxicokinetics of 3-trimethoxysilylpropyl methacrylate.

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 these 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_ow so by using this, and other where appropriate, known or predicted physicochemical properties of 3-trimethoxysilylpropyl methacrylate or its hydrolysis products, reasonable predictions or statements may be made about their potential absorption, distribution, metabolism and excretion (ADME) properties.

3-Trimethoxysilylpropyl methacrylate hydrolyses in contact with water (half-life 0.018 h at pH 4, 1.87 h at pH 7, and 0.068 h at pH 9 and 20°C), generating 3 -(trihydroxysilyl)propyl methacrylate and methanol. Human exposure can occur via the inhalation or dermal routes. Relevant inhalation and dermal exposure would be to the parent substance and hydrolysis products.

The toxicokinetics of methanol have been reviewed 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, if oral exposure did occur, although the molecular weight of 3-trimethoxysilylpropyl methacrylate (248.4) is above the favourable range, the water solubility of 2200 mg/L would favour absorption, so some exposure by this route is probable. The hydrolysis product, 3 -(trihydroxysilyl)propyl methacrylate has favourable molecular weight (206.27) and water solubility values for absorption so exposure to this is also likely.

Dermal

Dermal exposure would be to the parent and hydrolysis products.

The fat solubility and therefore 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.

With a water solubility of 2200 mg/L and log K_ow of 2.1, 3-trimethoxysilylpropyl methacrylate is in the favourable range for dermal absorption, and is therefore expected to be absorbed prior to hydrolysis. After or during deposition on the skin, evaporation of the substance and dermal absorption occur simultaneously so the vapour pressure of a substance is also relevant. With a vapour pressure of 2.3 Pa, evaporation of 3-trimethoxysilylpropyl methacrylate is not likely to be a major factor influencing potential dermal absorption.

For the hydrolysis product, 3-trihydroxysilylpropyl methacrylate, although it is highly soluble (1E+06 mg/L), the log K_ow value (-0.9) 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.

Using these values for 3-trimethoxysilylpropyl methacrylate predicts a blood:air partition coefficient of approximately 4500:1 meaning that, if lung exposure occurred there would be uptake into the systemic circulation. The water solubility of 3-trimethoxysilylpropyl methacrylate also suggests that it could be dissolved in the mucous of the respiratory tract lining, so it may also be passively absorbed from the mucous, further increasing the potential for absorption.

For the hydrolysis product 3 -(trihydroxysilyl)propyl methacrylate the predicted blood:air partition coefficient is approximately 5E+11:1 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.

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 3-trimethoxysilylpropyl methacrylate predicts that, should systemic exposure occur, potential distribution into the main body compartments would primarily be into fatty tissues with similar but much lower proportions into the other tissues.

For the hydrolysis product 3 -(trihydroxysilyl)propyl methacrylate, 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-trimethoxysilylpropyl methacrylate	2.1	126	2.8	2.0	57.6	2.0	1.5
3-(trihydroxysilyl)propyl methacrylate	-0.9	0.13	0.6	0.7	0.0	0.7	0.8

Metabolism

There are no data on the metabolism of 3-(trimethoxysilyl)propyl methacrylate. However, it will hydrolyse to form methanol and 3-trihydroxysilylpropyl methacrylate 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. QPSR’s 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 3-(trimethoxysilyl)propyl methacrylate in blood is approximately 53%. For the hydrolysis product 3 3-trihydroxysilylpropyl methacrylate the figure is >99% meaning that once absorbed the parent substance and hydrolysis product are 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.