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Administrative data

Link to relevant study record(s)

Description of key information

No studies are available. Based on molecular structure, molecular weight, water solibility, and octanol-water partition coefficient it can be expected that the submission substance is likely to be absorbed via the oral, dermal, and inhalation routes. Hydrolysis occurs rapidly, and systemic exposure is expected to both the parent substance and the hydrolysis product. Based on the water solubility, the registered substance and its silanol-containig hydrolysis product are likely to be distributed in the body, and excretion via the renal pathway can be expected. Bioaccumulation is not expected.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information

There are no studies available in which the toxicokinetic properties of trimethoxyphenylsilane have been investigated. Therefore, the toxicokinetic behaviour assessment of the substance and its hydrolysis product was estimated by its physico-chemical properties and the available toxicology studies on the substance itself.  

 

Trimethoxyphenylsilane hydrolyses rapidly in contact with water (half-life 0.4 hour at pH 7 and 20°C), generating methanol and phenylsilanetriol. This suggests that systemic exposure to both the parent, trimethoxyphenylsilane, and to the hydrolysis product, phenylsilanetriol is possible. Hence, this toxicokinetic behaviour assessment will try to predict the behaviour of both these substances. The toxicokinetics of methanol is discussed elsewhere and is not included in this summary.

 

The molecular weight and the predicted water solubility of trimethoxyphenylsilane are 198.29 g/mol and 1700 mg/l, respectively. In contrast, the molecular weight and predicted water solubility of the hydrolysis product, phenylsilanetriol, are 156.21 g/mol and 1E+06 mg/l, respectively. The hydrolysis product is smaller in size and is 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 0.55 for the parent substance and -0.021 for the hydrolysis product indicate that these substances are lipophilic enough to efficiently pass through biological membranes by passive diffusion.

 

 Absorption

 

Oral: An acute and a repeated-dose oral toxicity study with trimethoxyphenylsilane showed signs of systemic toxicity, therefore, indicating that absorption via the oral route is possible. If ingestion occurs, the hydrolysis of the parent substance in the low pH of the stomach will be rapid, so any absorption of the parent substance is expected to be minimal and it is more likely to be the hydrolysis product that is absorbed.

 

The predicted water solubility of the parent (1700 mg/l) and hydrolysis product (1E+06 mg/l) suggest that both substances will readily dissolve in the gastrointestinal fluids. Also, the low molecular weight (≤ 198.29 g/mol) of the substances suggests they will have the potential to pass through aqueous pores or be carried through the epithelial barrier by the bulk passage of water. Furthermore, the moderate log Kow of 0.55 for the parent and -0.021 for the hydrolysis product suggest that both these substances are lipophilic enough to be absorbed by passive diffusion.

 

Inhalation: The vapour pressure of the parent substance (18.2 Pa) indicates that inhalation of the registered substance as a vapour could occur. The predicted moderate water solubility (1700 mg/l) and log Kow (0.55) of the parent substance suggest that absorption from the respiratory tract epithelium by passive diffusion is likely. However, the very high water solubility (1E+06 mg/l) and moderate log Kow (-0.021) of the hydrolysis product, phenylsilanetriol, 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 moderate water solubility (1700 mg/l), log Kow (0.55) and molecular weight (198.29 g/mol) of the parent substance suggest that absorption via the dermal route is possible. Also for the hydrolysis product, phenylsilanetriol, the water solubility of 1E+06 mg/l, log Kow value of -0.021 and molecular weight of 156.21 g/mol suggest that absorption via the dermal route is also possible. QSAR based dermal permeability prediction (DERWIN V2.00.2009) using molecular weight, log Kowand water solubility, calculated a dermal penetration rate of 0.004 mg/cm²/h for trimethoxyphenylsilane and 0.032 mg/cm²/h for phenylsilanetriol, respectively. This shows that dermal penetration of the hydrolysis product will be moderate compared to that of the parent substance which is expected to be low. Therefore, once hydrolysis has occurred, absorption is likely to increase.

 

Distribution

 

The low molecular weight (156.21 g/mol) and very high water solubility of the hydrolysis product suggest it will diffuse through aqueous channels, pores and will be widely distributed. The log Kowof -0.021 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 moderate water solubility (1700 mg/l) and log Kow (0.55) is 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

 

Trimethoxypropylsilane hydrolyses rapidly in contact with water (half-life 0.4 hour at pH 7 and 20°C), generating methanol and phenylsilanetriol. There are no data regarding the enzymatic metabolism of trimethoxyphenylsilane or phenylsilanetriol.

 

Excretion

 

The low molecular weight and moderate water solubility of the parent and hydrolysis product suggest that they are likely to be excreted by the kidneys into urine. This is further compounded by the repeated-dose oral toxicity study with trimethoxyphenylsilane, where effects on the urinary bladder were reported at the lowest test concentration.