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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 trimethoxy(propyl)silane have been investigated. Therefore, the toxicokinetic behaviour assessment of the substance and its hydrolysis product was assessed by its physico-chemical properties, the available toxicology studies on the substance itself and the read-across substance trimethoxymethylsilane (CAS 1185-55-3).

 

Trimethoxy(propyl)silane hydrolyses rapidly in contact with water (half-life 2.6 hour at pH 7 and 20°C), generating methanol and propylsilanetriol. This suggests that systemic exposure to both the parent , trimethoxy(propyl)silane, and to the hydrolysis product, propylsilanetriol, 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 trimethoxy(propyl)silane are 164.27 g/mol and 9200 mg/l, respectively. In contrast, the molecular weight and predicted water solubility of the hydrolysis product, propylsilanetriol, are 122.19 g/mol and 1E+06 mg/l, respectively. This shows that the hydrolysis product is smaller in size and is more water soluble and, thereby, suggests that it will have the greater potential to be absorbed through biological membranes than the parent substance. Furthermore, the predicted log Kow of 1.7 for the parent substance and -1.4 for the hydrolysis product indicates that both substances are lipophilic enough to efficiently pass through biological membranes.

 

Absorption

 

Oral:  In an acute oral toxicity study with trimethoxy(propyl)silane, there was evidence of systemic toxicity at 5170 mg/kg bw, therefore showing that the substance has the potential to be absorbed by the oral route. Also, in a repeated dose oral toxicity study with the structural analogue substance trimethoxy(methyl)silane (MTMS), systemic effects were seen at dose levels above 250 mg/kg bw/day, therefore further indicating that absorption via the oral route is possible for the registered substance.e.  

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 is more likely to be the hydrolysis product that is absorbed. The predicted moderate water solubility and log Kow of the parent and hydrolysis product, suggests that both substances will readily dissolve in the gastrointestinal fluids and are likely to be absorbed by passive diffusion. Furthermore, the low molecular weight (≤164.27 g/mol) of the substances suggests they will have the potential to pass though aqueous pores or be carried through the epithelial barrier by the bulk passage of water.

 

Inhalation: An acute inhalation toxicity study with trimethoxy(propyl)silane showed no signs of systemic toxicity at 22.2 g/m³, therefore showing the substance to be of low toxicity and/or having low potential to be absorbed by the inhalation route. However, in a repeated dose inhalation toxicity study with the structural analogue substance trimethoxy(methyl)silane, systemic effects were seen at dose levels above 560 mg/m³, therefore indicating that absorption via the inhalation route is possible for the registered substance. Another possibility is that the systemic toxicity seen could be due to the oral exposure resulting from the transport of mucous out of the respiratory tract and eventually being ingested.

 

The predicted vapour pressure of the parent (293.68 Pa) is indicative that inhalation of the registered substance as a vapour could occur. The predicted moderate water solubility (9200 mg/l) and log Kow (1.7) of the parent substance suggest that absorption from the respiratory tract epithelium by passive diffusion is likely. However, the high water solubility (1E+06 mg/l) and moderate log Kow (-1.4) of the hydrolysis product, propylsilanetriol, suggest that it may be retained in the mucous of the lungs. Therefore, once hydrolysis has occurred, the level of absorption is likely to decrease. Particles deposited on the mucociliary blanket will be elevated into the laryngeal region and ultimately be swallowed (ingestion).

 

Dermal: The moderate water solubility (9200 mg/l) and log Kow (1.7) of the parent substance suggest that absorption via the dermal route is possible, however the molecular weight of 164.27 g/mol indicates that absorption could be low. For the hydrolysis product, propylsilanetriol, the moderate log Kow (-1.4), high water solubility (1E+06 mg/l ) and the low molecular weight (122.195 g/mol) suggest it will have greater potential to be absorbed via the dermal route than the parent substance. QSAR based dermal permeability prediction (DERWIN V2.00.2009) using molecular weight, log Kow and water solubility, calculated a dermal penetration rate of 0.00916 mg/cm²/h for trimethoxy(propyl)silane and 0.0342 mg/cm²/h for propylsilanetriol, respectively. This shows that dermal penetration of the hydrolysis product, propylsilanetriol, will be moderate compared to the parent substance, trimethoxy(propyl)silane, which will be low. 

 

Distribution

 

The low molecular weight (122.195 g/mol) and high water solubility of the hydrolysis product (1E+06 mg/l) suggest it will diffuse through aqueous channels, pores and will be widely distributed; however, the log Kow of -1.4 indicates it is unlikely to be distributed into cells and therefore the extracellular concentration will be higher than the intracellular concentration. Conversely, the parent substance, with the moderate water solubility (9200 mg/l) and log Kow (1.7), is more likely to distribute into cells and the intracellular concentration may be higher than extracellular concentration. The high water solubility and the moderate and low log Kow of both the parent and hydrolysis product suggest that accumulation in the body is not favourable for both substances.

 

Metabolism

 

Trimethoxy(propyl)silane hydrolyses rapidly in contact with water (half-life 2.6 hour at pH 7 and 20°C), generating methanol and propylsilanetriol. There are no data regarding the enzymatic metabolism of trimethoxy(propyl)silane or propylsilanetriol.

 

Excretion

 

The low molecular weight and good 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 histopathological changes in the urinary bladder and effects on the kidney in a repeated inhalation dose study with the read-across substance, trimethoxy(methyl)silane.