N-[3-(trimethoxysilyl)propyl]butylamine

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 unlikely to be absorbed via the oral and the inhalation routes. However, due to its skin sensitising properties, dermal uptake of the submission substance is likely. Hydrolysis is expected to occur rapidly, and toxicity data via the oral route indicate that the silanol containing degradation  product is absorbed via the gastro intestinal tract. However, hydrolysis after dermal and inhalation exposure is not expected and therefore, absorption of the silanol -containing hydrolysis product is considered negligible. Based on the high water solubility of the parent substance and its hydrolysis product, distribution in the body and a fast excretion via the renal route 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 registered substance were investigated.

 

N-[3-(trimethoxysilyl)propyl]butylamine (molecular weight of 235.4 g/mol) is a liquid, which is very soluble in water (QSAR calculated water solubility: 13 000 mg/l at 20°C. The log Kow is 2.2 at 20°C. Since the target substance is an alkoxysilane, it will hydrolyse with a half-life of approximately 2.2 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, further increased by the body temperature of approximately 37 °C present in mammals. The hydrolysis product 3-(N-butylamino)propylsilanetriol is even more water soluble (QSAR calculated water solubility: 1 000 000 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

Oral: In an acute oral toxicity study, male rats were administered the target substance by gavage. The LD50 reported was 12 825 mg/kg bw; signs of toxicity observed were salivation, diarrhoea, unsteady gait, and sluggishness. Due to the defence reactions of the organism (salivation and diarrhoea), it is assumed that only very little of the test material was absorbed through the gastro intestinal tract. However, clinical signs such as unsteady gait and sluggishness indicate systemic availability. Since the target substance is known to underlie a fast hydrolysis, it can be assumed that the effects observed were contributed to the hydrolysis product rather than the parent substance. The hydrolysis product is assumed to be rapidly excreted via the renal route. Hence, only minor bioavailability of N-[3-(trimethoxysilyl)propyl]butylamine after oral administration is indicated.

 

Dermal: An acute dermal toxicity study with rabbits reveals strong skin damaging effects of the test material at the doses applied. The dermal LD50 reported was 15 200 mg/kg bw, and clinical signs were limited to local effects. However, gross pathology revealed discolouration of lungs, kidneys, spleens, and stomach, indicating systemic availability of the test material. It can be assumed that the potential to cross the skin is based on the skin irritating properties of the submission substance. Hydrolysis is considered to be of minor importance due to the low presence of water on the skin surface. In conclusion, dermal uptake of N-[3-(trimethoxysilyl)propyl]butylamine in humans is considered possible and has to be taken into account for hazard assessment.

 

Inhalation: N-[3-(trimethoxysilyl)propyl]butylamine has a low vapour pressure of 0.76 Pa at 25°C. Therefore, inhalation of the vaporised target substance is quite unlikely. Nevertheless, an acute inhalation toxicity study in rats was carried out, using a test atmosphere containing substantially saturated vapour of the test item. Following 6 hours of exposure no deaths occurred, and no signs of toxicity were observed. Moreover, gross pathology revealed no remarkable findings. Thus, a low hazard potential of the substance via the inhalative route can be estimated. 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 N-[3-(trimethoxysilyl)propyl]butylamine. 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 3-(N-butylamino)propylsilanetriol. 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.

 

Excretion

N-[3-(trimethoxysilyl)propyl]butylamine is known to undergo hydrolysis with a half-life ofapproximately 2.2 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.