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Link to relevant study record(s)

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 dimethoxymethylsilane is likely to be absorbed via the oral and inhalation routes, but not dermally. However, hydrolysis is expected to occur rapidly, and data from the silanol containing degradation  product indicate a less favourable absorption. Due to the high water solubility, distribution in the body is likely, and a fast excretion via the renal route can be expected. The bioaccumulation potential is expected to be negligible. 

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information

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

 

Dimethoxymethylsilane hydrolyses in contact with water (half-life 0.3 hours at 20-25 °C), generating methylsilanediol, which is further oxidised to methylsilanetriol. Methanol is generated as the non-silanol containing hydrolysis product. 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 (predicted half-life 0.5 s at pH 2 and 37.5 °C). This suggests that systemic exposure to both the parent, dimethoxymethylsilane, and to the hydrolysis products, methylsilanediol and -triol is possible. Hence, this toxicokinetic behaviour assessment will try to predict the behaviour of all these substances. The toxicokinetic of methanol is discussed elsewhere and is not included in this summary.

 

The molecular weight and the predicted water solubility of dimethoxymethylsilane are 106 g/mol and 17000 mg/l at 20 °C, respectively. In contrast, the molecular weight and predicted water solubility of the hydrolysis products, methylsilanediol and -triol, are 78 g/mol and 1E+06 mg/l and 94 g/mol and 1E+06 mg/L at 20 °C, respectively. The hydrolysis products are smaller in size and are more water soluble and, thereby suggest that they will have greater potential to be absorbed through biological membranes than the parent substance. Furthermore, the predicted moderate log Kow of 1.4 for the parent substance and -1 for methylsilanediol indicate that these substances are lipophilic enough to efficiently pass through biological membranes by passive diffusion. However, the second hydrolysis product methylsilanetriol is less lipophilic (log Kow of -2.4) and therefore, passing of biological membranes by passive diffusion is less likely, but due to its low molecular weight, 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: An acute oral toxicity study in rats with structural analogue substance diethoxymethylsilane (CAS 2031-62-1) did not show any signs of systemic toxicity at the limit dose of 2000 mg/kg body weight. However, an oral repeated-dose study in rats with another structural analogue trimethoxymethylsilane (CAS 1185-55-3) showed signs of systemic toxicity (organ weight and/or histomorphological changes in males (liver, thymus, thyroid, duodenum, jejunum, and red blood cell) and females (liver, thyroid, duodenum, jejunum, and adrenal gland) and increased prothrombin time, therefore, indicating that absorption via the oral route is possible. If ingestion occurs, the parent substance hydrolyses in the low pH of the stomach and absorption of the parent substance is expected to be low. It is more likely to be the hydrolysis products that are absorbed.

 

The predicted water solubility of the parent substance (17000 mg/l) and hydrolysis products (1E+06 mg/l) suggest that all substances will readily dissolve in the gastrointestinal fluids. Additionally, the low molecular weight (≤ 106 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 1.4 for the parent and -1 for the first hydrolysis product suggest that both these substances are lipophilic enough to be absorbed by passive diffusion.

 

Inhalation: The vapour pressure of the parent substance (71 hPa) indicates that inhalation of the registered substance as a vapour is likely. An acute inhalation toxicity limit test (rats, vapour, whole body exposure, LD50 > 4.6 mg/l) however, did not result in any signs of toxicity. The predicted moderate water solubility (17000 mg/l) and log Kow (1.4) 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 (-1 and -2.4) of the hydrolysis products, methylsilanediol and -triol, 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). Since repeated oral exposure did result in systemic toxicity, absorption via the respiratory tract may therefore still be a possibility.

 

Dermal: The moderate water solubility (17 000 mg/l), log Kow (1.4) and molecular weight (106 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 products, methylsilanediol and -triol, the high water solubility of 1E+06 mg/l and a log Kow<0 (-1 and -2.4, respectively) suggest that both substances would be too hydrophilic to cross the lipid rich environment of the stratum corneum. Dermal uptake is therefore expected to be low. A repeated dermal study (9 applications over a period of 11 days, rabbit) did support this conclusion, since this study did primarily show irritating effects on the skin but no systemic toxicity was reported, even though, damage to the skin surface may enhance absorption.

 

Distribution 

The low molecular weight (<94 g/mol) and very high water solubility of the hydrolysis products suggest they will diffuse through aqueous channels, pores and will be widely distributed. The log Kow of -1 and 2.4 indicate 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 (17 000 mg/l) and log Kow (1.4) 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 

Dimethoxymethylsilane hydrolyses in contact with water (predicted half-life 0.3 hours at 20-25 °C), generating ethanol, methylsilanediol and -triol. There are no data regarding the enzymatic metabolism of dimethoxymethylsilane, methylsilanediol or methylsilanetriol. However, data obtained from genotoxicity studies with the structural analogue substance diethoxymethylsilane indicate no observable differences in with or without metabolic activation. Thus, further metabolism the common silanol-containing hydrolysis product can be expected to be negligible.

 

Excretion 

Dimethoxymethylsilane is known to undergo hydrolysis with a half-life of approximately 0.3 hours at 20-25 °C. The hydrolysis products named above are far more water soluble than the parent chemical and have a molecular weight lower than 500 g/mol. Therefore, they are expected to be excreted predominantly via the renal route.