Trimethoxy(2,4,4-trimethylpentyl)silane

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 likely to be absorbed via the oral and dermal routes rather than by inhalation. 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. The bioaccumulation potential is expected to be low. 

Key value for chemical safety assessment

Bioaccumulation potential:

low bioaccumulation potential

Additional information

There were no studies available in which the toxicokinetic properties of the test item were investigated.

 

Trimethoxy(2,4,4-trimethylpentyl)silane (molecular weight of 234.4 g/mol) is a colourless liquid, which is moderately soluble in water (predicted water solubility: 110 mg/l at 20 °C). The log Kow is 4 at 20 °C. Since the target substance is an alkoxysilane, it will hydrolyse with a half-life of approximately 5.7 hours at 20-25 °C and pH 7 under formation of three equivalents methanol and the respective silanetriol. Acid environment is hereby known to catalyse this abiotic and enzyme-independent reaction and enhance the reaction rate (0.3 h at pH 4 at 20-25 °C), further increased by the body temperature of approximately 37 °C present in mammals (5 s at pH 2 and 37.5 °C). The hydrolysis product (2,4,4-trimethylpentyl)silanetriol is very soluble in water (predicted water solubility: 2.4E+05 mg/l at 20 °C). The log Kow is 0.9 at 20 °C, indicating that fast excretion of the hydrolysis product via the renal route is expected and a general accumulation is unlikely.

 

Absorption

In acute oral toxicity studies, rats were administered the target substance by gavage. No exact levels of the LD50 were reported (> 2000 mg/kg bw); no signs of toxicity were observed. It is assumed that the target substance was hydrolysed in the stomach and only traces of the parent compound were adsorbed through the gastrointestinal tract. The hydrolysis product is assumed to be rapidly excreted via the renal route. Hence, bioavailability of trimethoxy(2,4,4-trimethylpentyl)silane after oral administration is not indicated.

 

Acute dermal toxicity studies are not available. QSAR based dermal permeability regarding molecular weight, log Pow and water solubility, calculated a moderate dermal absorption of 5.39 µg/cm²/h (DERMWIN v1.43, 2009). This value is considered as indicator for a dermal absorption of 50%. Hydrolysis is considered to be of minor importance due to the low presence of water on the skin surface. In conclusion, dermal uptake of trimethoxy(2,4,4-trimethylpentyl)silane in humans is considered possible and has to be taken into account for hazard assessment.

 

Trimethoxy(2,4,4-trimethylpentyl)silane has a comparably low vapour pressure of 8.6 Pa at 25 °C. Therefore, inhalation of the vaporised target substance is quite unlikely. Nevertheless, acute inhalation toxicity studies in rats were carried out, using a test atmosphere containing 11.2 mg/l aerosol of the test item. Following 6 hours of exposure no deaths occurred, but signs of toxicity such as anaesthesia, irritation of the respiratory tract, and signs of discomfort were observed. Repeated exposure of rats to aerosol of the test item for 28 days (6 h/day, 5 days/week) revealed lack of coordination for 2 hours after treatment at 1.54 mg/l air and minimal intense irritation of the alveoli at 2.89 mg/l air. Histopathology, haematology, and clinical chemistry revealed no test material related effects. Taken together, local effects rather than systemic toxicity are considered to be of relevance, indicating a low hazard potential of the substance via the inhalation route. Hydrolysis of the target substance is considered of minor importance due to the quite long half-live of the parent substance at the physiological pH in the respiratory tract.

 

Metabolism

No studies are available determining the metabolism of trimethoxy(2,4,4-trimethylpentyl)silane. Nevertheless, metabolism of the target substance is considered negligible, since abiotic and enzyme independent hydrolysis is the prominent degradation reaction, leading to the highly water soluble products methanol and trimethoxy(2,4,4-trimethylpentyl)silane. It cannot be excluded that further oxidation of the aliphatic group under formation of hydroxyl groups takes place, but this is considered to be insignificant and would only enhance renal excretion.

Studies on genotoxicity (Ames-Test, cytogenicity in mammalian cells in vitro, and micronucleus assay in vivo tested with an structural analogue) were negative, i.e. there is no indication of a reactivity of trimethoxy(2,4,4-trimethylpentyl)silane or its metabolites under the test conditions.

 

Excretion

Trimethoxy(2,4,4-trimethylpentyl)silane is known to undergo hydrolysis with a half-life of approximately 5.7 hours at 20 °C and pH 7. 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.