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Description of key information

Key value for chemical safety assessment

Additional information

There are no reliable in vivo data on the toxicokinetics of [3-(2,3-epoxypropoxy)propyl]trimethoxysilane. The following summary has therefore been prepared based on the physicochemical properties of the substance itself and its hydrolysis products. [3-(2,3-Epoxypropoxy)propyl]trimethoxysilane is a moisture-sensitive, volatile liquid that has a hydrolysis half-life of 6.5 hours at pH 7), generating methanol and 3-(2,3-epoxypropoxy)propyl]silanetriol. Information is also included from the structurally related substance 4-[(triethoxysilyl)methyl]morpholine (CAS 21743-27-1) derived from an in vivo bioavailability study in mice (Harlan, 2009). Both [3-(2,3-epoxypropoxy)propyl]trimethoxysilane and 4-[(triethoxysilyl) methyl]morpholine are trialkoxy functional silanes.

Human exposure to the registered substance can occur via the inhalation or dermal routes. Relevant inhalation and dermal exposure would be predominantly to the parent substance.

Absorption

Oral: Significant oral exposure is not expected for the registered substance. Based on the bioavailability study with the related substance, systemic exposure following oral exposure would be expected.

In mice, following an oral dose of 2000 mg/kg the related radiolabelled substance, 4-[(triethoxysilyl)methyl]morpholine (CAS 21743-27-1) was rapidly absorbed and peak concentrations were noted at 1 hour after dosing. Oral bioavailability was approximately 28%.

Dermal: Dermal exposure would be to the parent and hydrolysis products. The molecular weights of [3-(2,3-epoxypropoxy)propyl]trimethoxysilane and 3-(2,3-epoxypropoxy)propyl]silanetriol are not ideal for dermal absorption, but they would not preclude it. The predicted water solubility (3.7E+4 mg/l) and predicted log Kow (0.5) of [3-(2,3-epoxypropoxy)propyl]trimethoxysilane suggest that this parent substance will be absorbed very effectively through the skin. Conversely, the hydrolysis product has a high water solubility (1.0E+6 mg/l), but with a log Kow of -2.6 it is not likely to be sufficiently lipophilic to cross the stratum corneum and therefore dermal absorption into the blood is likely to be low. Therefore absorption of the test substance might be expected to be significantly reduced once hydrolysis has occurred. In an acute dermal toxicity study there was some systemic toxicity, and therefore evidence of absorption.

Inhalation: The water solubility and log Kow of [3-(2,3-epoxypropoxy)propyl]trimethoxysilane suggest that it will be dissolved in the mucous of the respiratory tract lining, but the log Kow is optimal for absorption, so it could be passively absorbed from the mucous. The hydrolysis product is also likely to be dissolved in mucous, but is significantly less likely to be absorbed. Repeated dose studies on [3-(2,3-epoxypropoxy)propyl]trimethoxysilane showed signs of systemic toxicity, and therefore evidence of absorption.

Distribution

The absorbed material is likely to be in the form of both the parent and hydrolysis products. The log Kow of the parent substance means that it is likely to distribute into cells (although with a molecular weight of approximately 236 this could be limited). The intracellular concentration might be higher than the extracellular concentration particularly in fatty tissues. The hydrolysis product is likely to be widely distributed in the blood, but uptake into organs and tissues will be limited by its diffusion across membranes. Toxicity studies do not provide convincing evidence for systemic distribution to any particular organ or tissue.

In mice, following an oral dose of 2000 mg/kg the related radiolabelled substance, 4-[(triethoxysilyl)methyl]morpholine (CAS 21743-27-1) was shown to be present in femur, liver and kidneys.

Metabolism

There are no data on the metabolism of [3-(2,3-epoxypropoxy)propyl]trimethoxysilane. However, it will hydrolyse to form methanol and 3-(2,3-epoxypropoxy)propyl]silanetriol once absorbed into the body. Genetic toxicity tests in vitro showed no observable differences in effects with and without metabolic activation.

Excretion

Following dermal exposure 3-(2,3-epoxypropoxy)propyl]silanetriol is likely to be sloughed off with skin cells. The high water solubility of both the parent and hydrolysis products means that, once absorbed, they are likely to be excreted by the kidneys into urine.

In mice, following an oral dose of 2000 mg/kg the related radiolabelled substance, 4-[(triethoxysilyl)methyl]morpholine (CAS 21743-27-1) approximately 20% was excreted in urine and approximately 64% excreted in faeces within 24 hours.

A toxicokinetic study (Harlan, 2009) for the structurally similar substance (trialkoxy functional silane) 4-[(triethoxysilyl)methyl]morpholine demonstrates the systemic availability of this substance following oral administration. This suggests that [3-(2,3-epoxypropoxy)propyl]trimethoxysilane, which is also a trialkoxy functional silane, is likely to be bioavailable.