[3-(triethoxysilyl)propyl]urea

Endpoint summary

Description of key information

No studies are available. Based on molecular structure, molecular weight, water solubility, and octanol-water partition coefficient it can be expected that the submission substance is unlikely to be absorbed via the dermal or oral routes, but possibly via the respiratory tract. However, hydrolysis is expected to occur rapidly, and toxicity data via the oral route indicate that the silanol containing degradation  product might be absorbed rather than the parent compound. Inhalation toxicity data do not indicate an absorption potential of the submission substance. Based on the high water solubility of the hydrolysis product, the traces absorbed are likely to be distributed in the body, and a fast excretion via the renal pathway can be expected. The bioaccumulation potential is expected to be low. 

Key value for chemical safety assessment

Bioaccumulation potential:

low bioaccumulation potential

Additional information

There are no studies available in which the toxicokinetic properties of [3-(triethoxysilyl)propyl]urea have been investigated. Therefore, the toxicokinetic behavior assessment of the substance and its hydrolysis product was estimated by its physico-chemical properties and the available toxicology studies on the substance itself.  

 

[3-(triethoxysilyl)propyl]urea hydrolyses in contact with water (predicted half-life 16.4 hours at pH 7), generating [3-(trihydroxysilyl)propyl]urea and ethanol. Acid environment is hereby known to catalyse this abiotic and enzyme-independent reaction and enhance the reaction rate, further increased by the body temperature of approximately 37 °C present in mammals. This suggests that systemic exposure to both the parent, [3-(triethoxysilyl)propyl]urea, and to the hydrolysis product, [3-(trihydroxysilyl)propyl]urea, is possible. Hence, this toxicokinetic behaviour assessment will try to predict the behaviour of both these substances. The toxicokinetic of ethanol is discussed elsewhere and is not included in this summary.

 

The molecular weight and the predicted water solubility of [3-(triethoxysilyl)propyl]urea are 264 g/mol and 7000 mg/l, respectively. In contrast, the molecular weight and predicted water solubility of the hydrolysis product, [3-(trihydroxysilyl)propyl]urea, are 180 g/mol and 1E+06 mg/l. The hydrolysis product is smaller in size and more water soluble, and thereby suggests that it will have greater potential to be absorbed through biological membranes than the parent substance. Furthermore, the predicted moderate log Kow of 1.3 at 20°C for the parent substance indicates that this substance is lipophilic enough to efficiently pass through biological membranes by passive diffusion. However, the hydrolysis product [3-(trihydroxysilyl)propyl]urea is much more hydrophilic (log Kow of -3.3 at 20°C) and therefore, passing of biological membranes by passive diffusion is less likely, but due to its low molecular weight and its high water solubility, it still has the potential to pass through aqueous pores or be carried through the epithelial barrier by the bulk passage of water.

 

Absorption

Oral: A repeated oral toxicity study with the structural analogue ureidopropyltrialkoxysilane (CAS 116912-64-2) in rats for 28 days did not show signs of systemic toxicity (NOAEL=1228 mg/kg body weight), indicating that absorption via the oral route did not occur. It is assumed that the parent substance was hydrolysed in the stomach and only traces of the parent compound were absorbed through the gastrointestinal tract. The hydrolysis product is assumed to be rapidly excreted via the renal route. Hence, bioavailability of the substance after oral administration is not indicated.

 

Inhalation: The vapour pressure of the parent substance is low (3.1E-03 Pa) indicating that inhalation of the registered substance as a vapour is not highly likely. If inhalation of vapour occurs, the predicted water solubility (7000 mg/l) and log Kow (1.3) of the parent substance suggest that absorption from the respiratory tract epithelium by passive diffusion is possible. However, the very high water solubility (1E+06 mg/l) and the high hydrophilicity (log Kow and -3.3) of the hydrolysis product, [3-(trihydroxysilyl)propyl]urea, might cause retention in the mucous of the lungs. Therefore, once hydrolysis has occurred, absorption is likely to slow down. Particles deposited on the mucociliary blanket will be elevated into the laryngeal region and ultimately be swallowed (ingestion).

 

Dermal: The water solubility (7000 mg/l), log Kow (1.3) and molecular weight (264 g/mol) of the parent substance suggest that absorption via the dermal route is possible. Hydrolysis is considered to be of minor importance due to the low presence of water on the skin surface. Additionally, for the hydrolysis product, [3-(trihydroxysilyl)propyl]urea, the high water solubility of 1E+06mg/l and a log Kow < -1 (-3.3) suggest that the substance would be too hydrophilic to cross the lipid rich environment of the stratum corneum. An acute dermal toxicity study using the structural analogue [3-(trimethoxysilyl)propyl]urea (CAS 23843-64-3) did not show any systemic effects in rats. Only minor desquamation was noted at the site of application. In conclusion, dermal uptake of [3-(triethoxysilyl)propyl]urea is not likely.

 

Distribution

The molecular weight (<180 g/mol) and very high water solubility (1E+06 mg/l) of the hydrolysis product suggest it will diffuse through aqueous channels and pores and will be widely distributed. The log Kow of -3.3 indicates it is unlikely to be distributed into cells and therefore the extracellular concentration will be higher than the intracellular concentration. However, the parent substance with the water solubility (7000 mg/l) and log Kow (1.3) is more lipophilic and therefore likely to distribute into cells and the intracellular concentration may be higher than extracellular concentration. Accumulation in the body is not favourable for both substances.

 

Metabolism

[3-(triethoxysilyl)propyl]urea hydrolyses in contact with water (predicted half-life 16.4 hours at pH 7), generating ethanol and [3-(trihydroxysilyl)propyl]urea. There are no data regarding the enzymatic metabolism of [3-(triethoxysilyl)propyl]urea or [3-(trihydroxysilyl)propyl]urea.

 

Excretion

[3-(triethoxysilyl)propyl]urea is known to undergo hydrolysis with a predicted half-life of approximately 16.4 hours. The hydrolysis product named above is far more water soluble than the parent chemical and has a molecular weight lower than 300 g/mol. Therefore, it is expected to be excreted predominantly via the renal route.