(3-chloropropyl)diethoxymethylsilane

Endpoint summary

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 in contact with water, 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 can be expected.

Key value for chemical safety assessment

Bioaccumulation potential:

high bioaccumulation potential

Additional information

There are no studies available in which the toxicokinetic properties of (3-chloropropyl) diethoxymethylsilane (CAS: 13501-76-3) 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 structural analogue read-across substance (3-Chloropropyl)trimethoxysilane (CAS: 2530-87-2).

 

(3-chloropropyl)diethoxymethylsilane hydrolyses in contact with water (half-life ca.20-30 hour at pH 7 and 20°C, based on read-across from related alkoxysilanes), generating ethanol and (3-chloropropyl)methylsilanediol. This suggests that systemic exposure to both the parent, (3-chloropropyl)diethoxymethylsilane, and to the hydrolysis product, (3-chloropropyl)methylsilanediol, is possible. Therefore, this toxicokinetic behaviour assessment will try to predict the behaviour of both these substances. The toxicokinetics of ethanol is discussed elsewhere and is not included in this summary.

 

The molecular weight and the predicted water solubility of (3-chloropropyl) diethoxymethylsilane are 210.77 g/mol and 36 mg/l, respectively. In contrast, the molecular weight and predicted water solubility of the hydrolysis product, (3-chloropropyl)methylsilanediol, are 154.66 g/mol and 6E+04 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 greater potential to be absorbed through biological membranes than the parent substance. Furthermore, the predicted log Kow of 4.2 for the parent substance and 0.8 for the hydrolysis product indicates that both substances are lipophilic enough to efficiently pass through biological membranes by passive diffusion.

 

Absorption

 

Oral: An acute oral toxicity study with (3-chloropropyl)diethoxymethylsilane showed no signs of systemic toxicity at the limit dose of 2000 mg/kg bw, therefore, showing the substance to be off low toxicity and/or having low potential to be absorbed by the oral route. If ingestion occurs, the hydrolysis of the parent substance in the low pH of the stomach will be rapid, so 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 (36 mg/l) of the parent and the hydrolysis product (6E+04 mg/l) suggests that the hydrolysis product will more readily dissolve in the gastrointestinal fluids than the parent. Also, the low molecular weight (154.66 g/mol) of the hydrolysis product suggests it will have greater potential to pass though aqueous pores or be carried through the epithelial barrier by the bulk passage of water than the parent. Furthermore, the log Kow of 4.2 for the parent and 0.8 for the hydrolysis product suggest they are both lipophilic enough to be absorbed by passive diffusion. If hydrolysis occurs in the gastrointestinal tract, absorption of the hydrolysis product by passive diffusion is likely to be slower compared to that of the parent substance (log Kow 4.2).

 

Inhalation: The vapour pressure of the parent substance (6.8 Pa) indicates that inhalation of the registered substance as a vapour could occur. The predicted water solubility and log Kow of the parent substance and of the hydrolysis product suggest that absorption from the respiratory tract epithelium by passive diffusion is likely. Any particles deposited on the mucociliary blanket will be elevated into the laryngeal region and ultimately be swallowed (ingestion). In a repeated-dose inhalation (vapour) study with the read across substance (3-chloropropyl)trimethoxysilane (CAS: 2530-87-2) no sign of systemic toxicity was seen even at the top dose of 100 ppm, therefore, showing the substance to be of low toxicity and/or having low potential to be absorbed by the inhalation route.

 

Dermal: The water solubility (36 mg/l), log Kow (4.2) and molecular weight (210.77 g/mol) of the parent substance suggest that absorption via the dermal route will be low. However, for the hydrolysis product, (3-chloropropyl)methylsilanediol, the moderate water solubility (6E+04 mg/l), log Kow (0.8) and molecular weight (154.66 g/mol) suggest that absorption via the dermal route will be higher than for 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 0.00341 mg/cm²/h for (3-chloropropyl)diethoxymethylsilane and 0.03241 mg/cm²/h for (3-chloropropyl)methylsilanediol, respectively. This shows that if hydrolysis occurs dermal penetration of the hydrolysis product will be moderate when compared to the parent substance which is expected to be very low.

 

Distribution

 

The low molecular weight (154.66 g/mol) and high water solubility of the hydrolysis product suggest that it will diffuse through aqueous channels, pores and will be widely distributed. Also, the log Kow of 0.8 indicates that it is likely to be distributed into cells and therefore the intracellular concentration will be higher than the extracellular concentration. However, the parent substance with the low/moderate water solubility (36 mg/l), molecular weight of 210.77 g/mol and high Log Kow (4.2) will be less widely distributed than the hydrolysis product, however, it is more likely to distribute into cells and the intracellular concentration should be higher than extracellular concentration. Furthermore, the high log Kow value of 4.2 for the parent substance suggests it will have the potential to accumulate in the body. It is generally the case that substances with high log Kow (≥4) values have long biological half-lives. On this basis, daily exposure to (3-chloropropyl)diethoxymethylsilane could result in a build up in the body.

 

Metabolism

 

(3-chloropropyl)diethoxymethylsilane hydrolyses in contact with water (half-life ca.20-30 hour at pH 7 and 20°C, based on read-across from related alkoxysilanes), generating ethanol and (3-chloropropyl)methylsilanediol. There are no data regarding the enzymatic metabolism of (3-chloropropyl)diethoxymethylsilane or (3-chloropropyl)methylsilanediol.

 

Excretion

 

The low molecular weight and good water solubility of the parent and hydrolysis product suggests that they are likely to be excreted by the kidneys into urine.