N-[3-(trimethoxysilyl)propylcyclohexylamine]

Endpoint summary

Description of key information

No studies are available. Based on molecular structure, molecular weight, water solubility, vapour pressure and octanol-water partition coefficient it can be expected that the substance is likely to be absorbed via the inhalation, dermal and oral route.

Hydrolysis is expected to occur rapidly, and based on the physico-chemical parameters of the silanol containing degradation product, absorption via the gastrointestinal tract, the dermal and inhalation route are expected.

Due to the high water solubility, the hydrolysis product is expected to be widely distributed in the body. Excretion via the renal route is considered favoured. Thus, no bioaccumulation is 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 N-[3-(trimethoxysilyl)propylcyclohexylamine] (CAS 3068-78-8) 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.  

N-[3-(trimethoxysilyl)propylcyclohexylamine] hydrolyses rapidly in contact with water (predicted half-life 4.1 minutes at pH 7 and 2.6 minutes at pH 4 and 20-25°C), generating methanol and N-[3-(trihydroxysilyl)propylcyclohexylamine. This suggests that systemic exposure to both the parent and to the hydrolysis products is possible. Hence, this toxicokinetic behaviour assessment will try to predict the behaviour of these substances. The toxicokinetics of methanol is discussed elsewhere and is not included in this summary.

The molecular weight of N-[3-(trimethoxysilyl)propylcyclohexylamine] is 261.43 g/mol. In contrast, the molecular weight of the hydrolysis product N-[3-(trihydroxysilyl)propylcyclohexylamine is 219.1 g/mol. The hydrolysis product is slightly smaller in size and is more water soluble (1.0E+06 mg/L) than the parent substance (8030 mg/L) and, thereby suggests that it will have greater potential to be absorbed through biological membranes than the parent substance.Also, the predicted log Kow values of 3.0 (QSAR) for the parent substance and -0.1 (QSAR) for the silicon-containing hydrolysis product indicate that both substances are lipophilic enough to efficiently pass through biological membranes by passive diffusion.

Absorption 

Oral:

In an acute toxicity study performed according to OECD TG 401 with the registered substance N-[3-(trimethoxysilyl)propylcyclohexylamine] (CAS 3068-78-8) no signs of systemic toxicity were observed and an acute oral LD50 value of >2000 mg/kg bw was derived, thus no prediction of systemic availability 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 log Kow of 3.0 for the parent substance N-[3-(trimethoxysilyl)propylcyclohexylamine] (CAS 3068-78-8) and -0.1 for the hydrolysis product N-[3-(trihydroxysilyl)propylcyclohexylamine indicate that these substances are lipophilic and would therefore suggest that systemic absorption post oral intake is possible.

 Inhalation:    

The vapour pressure of the parent substance (0.54 Pa) and the boiling point (273.6°C) indicate that inhalation of the registered substance as a vapour is unlikely. However, as an aerosol systemic absorption seems possible as observed in the available acute inhalation toxicity study with the registered substance. In this study, mortality occurred and the following clinical signs were observed: Animals exposed with 0.89 mg/L air of the test material showed fitful and cracking breathing, ataxic/staggering movements, reddish rhinorrhea, sneezing and piloerection. Animals exposed to higher concentrations of the registered substance additionally showed clinical signs such as crouch/abdominal position, tremor, reduced activity, crusty noses and alopecia. Gross pathology of animals which died during the study revealed discoloured lungs and liver, spotted lungs, inflated intestine and foam withdrawal from dissected lungs. 

Dermal

The log Kow (3.0 and -0.1), the high water solubility (8030 and 1.0E+06 mg/L) and the molecular weights (261.43 and 219.1 g/mol) of N-[3-(trimethoxysilyl)propylcyclohexylamine] and its silicon-containing hydrolysis product N-[3-(trihydroxysilyl)propylcyclohexylamine suggest that absorption via the dermal route would be high. QSAR based dermal permeability prediction (DERMWIN V2.02.2012) using molecular weight, log Kow and water solubility, calculated a dermal penetration rate of 41.8 µg/cm²/h for the parent substance -[3-(trimethoxysilyl)propylcyclohexylamine] and 80.7 µg/cm²/h for its silicon-containing hydrolysis product N-[3-(trihydroxysilyl)propylcyclohexylamine, respectively. This shows that dermal penetration would be high (80%) for both the parent substance and its silicon-containing hydrolysis product.

 

Metabolism

No data are available on the metabolism of N-[3-(trimethoxysilyl)propylcyclohexylamine]. However, 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 N-[3-(trihydroxysilyl)propylcyclohexylamine. There are no data regarding the enzymatic metabolism of N-[3-(trimethoxysilyl)propylcyclohexylamine]or its silicon-containing hydrolysis product. Genetic toxicity tests in vitro showed no observable difference in effects with and without metabolic activation for N-[3-(trimethoxysilyl)propylcyclohexylamine].

 

Distribution

The distribution of the parent substance within the body in unlikely given its rapid hydrolysis rate (half-life is 4.1 min at pH 7 and 20-25°C). The smaller size of the silicon-containing hydrolysis product suggests a wide distribution. Since the silicon-containing hydrolysis product is small in size (219.1 g/mol) and highly water-soluble (1E+06 mg/L, respectively), it can be assumed that it will have the potential diffuse through aqueous channels and pores. Since the log Pow is -0.1 for the hydrolysis product, it is likely that it will distribute into cells and the intracellular concentration may be higher than the extracellular concentration particularly in fatty tissues. Based on the physico-chemical properties of the parent substance and the silicon-containing hydrolysis product no bioaccumulation potential is expected.

 

Excretion

N-[3-(trimethoxysilyl)propylcyclohexylamine] is known to undergo hydrolysis rapidly. The hydrolysis product N-[3-(trihydroxysilyl)propylcyclohexylamine is far more water soluble than the parent substance and has a molecular weight lower than 500 g/mol. Therefore, the silicon-containing hydrolysis product is expected to be excreted predominantly via the renal route.