3-(triethoxysilyl)propiononitrile

Endpoint summary

Additional information

There are no in vitro or in vivo data on the toxicokinetics of 3-(triethoxysilyl)propiononitrile.

The following summary has therefore been prepared based on validated predictions of the physicochemical properties of the substance itself and its hydrolysis products. 3-(Triethoxysilyl)propiononitrile is a low volatile liquid that hydrolyses rapidly in contact with water (half-life 6.5 hours at 20°C and pH 7), generating ethanol (CAS 64-17-5) and 3-(trihydroxysilyl)propiononitrile (CAS 182156-21-4). Human exposure can occur via the inhalation and dermal routes. The toxicokinetics of ethanol have been reviewed in other major reviews and are not considered further here. 

Absorption

 

Oral:

Based on the known use pattern, significant oral exposure is not expected for this substance.

 

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. Both the molecular weights of the parent 3-(triethoxysilyl)propiononitrile and the silanol hydrolysis product 3-(trihydroxysilyl)propiononitrile are not ideal for dermal absorption (as being > 100 g/mol), but they would not preclude it. The predicted water solubility (4000 mg/l) and predicted log Kow (1.7) of 3-(triethoxysilyl)propiononitrile suggest that this parent substance will be absorbed effectively through the skin. Conversely, the silanol hydrolysis product has a very high water solubility (1.0E+6 mg/l), but with a log Kow of -2.85 it is not likely to be sufficiently lipophilic to cross the lipid rich environment of the stratum corneum and therefore dermal uptake 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 with the parent substance there was evidence of systemic toxicity following administration of very high doses, providing evidence of some absorption.

 

Inhalation:

Releases to air are negligible given the low vapour pressure of the parent substance (1.9 Pa at 20°C). Furthermore, the parent substance hydrolyses relatively rapidly in presence of water, including atmospheric moisture, to give ethanol and the silanol hydrolysis product 3-(trihydroxysilyl)propiononitrile. However, the high water solubility (1000000 mg/l) and negligible fugacity (vapour pressure = 7 x 10-5 Pa) of the silanol hydrolysis product 3-(trihydroxysilyl)propiononitrile indicate that releases to air are also likely to be low.

If inhaled, the water solubility and log Kow of the parent 3-(triethoxysilyl)propiononitrile 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 absorbed from the mucous by passive diffusion. The hydrolysis product with its very high water solubility is also likely to be dissolved in mucous, but may likely be retained within the mucous as it would be too hydrophilic to be absorbed. There are no reliable inhalation studies to check for signs of systemic toxicity.

 

Distribution

 

The absorbed material is likely to be in the form of the parent and hydrolysis products, but predominantly as the parent, which will then hydrolyse rapidly. 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. Toxicity studies provide evidence for distribution to various organs, but specifically the kidneys in which adverse effects were observed.

 

Metabolism

 

There are no data regarding the metabolism of 3-(triethoxysilyl)propiononitrile. However, it will hydrolyse rapidly to form ethanol and 3-(trihydroxysilyl)propiononitrile 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-(triethoxysilyl)propiononitrile will likely penetrate the viable epidermis and therefore may not be sloughed off with skin cells. The high water solubility and relatively low molecular weights of the parent and hydrolysis products mean that, once absorbed, they are likely to be excreted by the kidneys into urine. This prediction is supported by the repeated dose toxicity studies, in which adverse effects in the kidneys were observed.