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Key value for chemical safety assessment

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There are no in vivo data on the toxicokinetics of 3-chloropropyltrimethoxysilane. The following summary has therefore been prepared based on validated predictions of the physicochemical properties of the substance itself and its hydrolysis products. 3 -Chloropropyltrimethoxysilane is a volatile liquid with a hydrolysis half-life of <0.083 hour at pH 4, 3.1 hours at pH 7 and <0.1 hour at pH and 25oC, generating methanol and 3-chloropropylsilanetriol. 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 is discussed elsewhere and is not included in this summary.

Absorption

Oral: Significant oral exposure is not expected for this substance.

Dermal: Dermal exposure would be to the parent and hydrolysis products. The molecular weights of 3-chloropropyltrimethoxysilane and 3-chloropropylsilanetriol are not ideal for dermal absorption, but they would not preclude it. The predicted water solubility (1.1E+3mg/l) and predicted log Kow (1.96) of 3-chloropropyltrimethoxysilane suggest that the parent substance could 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 -1.13 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 no evidence of systemic toxicity, and therefore no evidence of absorption.

Inhalation: The water solubility and log Kow of 3-chloropropyltrimethoxysilane 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 less likely to be absorbed. Repeated dose studies on 3-chloropropyltrimethoxysilane showed signs of systemic toxicity, and therefore were evidence of absorption via the inhalation route. It must also be considered that some of the absorbed effects could be a result of oral exposure resulting from transport of mucous out of the respiratory tract.

Distribution

The absorbed material is likely to be in the form of the parent and hydrolysis products. The log Kow of the parent substance means that it is likely to distribute into cells and 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 provide evidence for distribution to the bladder and kidneys.

Metabolism

There are no data on the metabolism of 3-chloropropyltrimethoxysilane. However, it will hydrolyse to form methanol and 3-chloropropylsilanetriol once absorbed into the body. In vitro mammalian mutagenicity tests gave positive results with metabolic activation, but negative results without metabolic activation. However, there were no observable differences in effects with and without metabolic activation in bacterial mutagenicity tests, which were positive.

Excretion

Following dermal exposure 3-chloropropylsilanetriol 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.