Bis(trimethoxysilylpropyl)amine

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 dermal and inhalation routes, and only to a minor degree via the oral route. Hydrolysis is expected to occur rapidly, and toxicity data via the oral route indicate that the silanol containing degradation product forms a hard mass, further limiting the absorption potential. However, based on the high water solubility of the hydrolysis product, the traces absorbed are likely to be distributed 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 the registerd substance were investigated.

Bis(trimethoxysilylpropyl)amine (molecular weight of 341.55 g/mol) is a liquid, which is highly soluble in water (measured water solubility: 3.4E+04 mg/l). The log Pow is 0.2. Since the target substance is an alkoxysilane, it will hydrolyse with a half-life of approximately 7 h at 20-25 °C and pH 7 under formation of six equivalents methanol and one equivalent bis(trihydroxysilylpropyl)amine. Acid environments are known to catalyse this abiotic and enzyme-independent reaction and enhance the reaction rate, which is further increased by the body temperature of approximately 37 °C present in mammals. Thus, the predicted half-lives at pH 4, 5, and 9 are 0.3, 0.4, and 0.1 h at 20-25 °C, and at pH 2 at 37.5 °C, which is the condition found in the stomach, bis(trimethoxysilylpropyl)amine is predicted to hydrolyse within 5 s. The silanol-containing hydrolysis product bis(trihydroxysilylpropyl)amine is very soluble in water (measured water solubility: 1E+06 mg/l). The log Pow is -4.0, indicating that fast excretion of the hydrolysis product via the renal route is expected and a general accumulation is unlikely.

Absorption

In an acute oral toxicity study rats were administered the target substance by gavage. No exact LD50 for male rats was reported (>4200 =8400 mg/kg bw); however, for females a LD50 of 3780 mg/kg bw was determined.The predominant clinical signs detected were sluggishness; unsteady gait; prostration; red, crusty discolouration on mouth and nose area; gasping; salivation; and wheezing. Moreover, gross pathology revealed for animals found dead stomachs filled with hard mass; dark red lungs; or lungs with maroon patchy discolouration. One animal found dead showed a dark red liver. No histopathology was performed to clarify the discolouration of these tissues. Nevertheless, the authors reported that the test item reacted very quickly with water to form a hard mass. Since a hard mass in stomachs was noted at necropsy, which was assumed to be reacted sample material, the deaths were concluded to be most likely due to obstruction of the stomach and intestine. Hence, it can be assumed that only traces of the parent compound were adsorbed through the gastrointestinal tract. Taking this into account and considering the high LD50 values and the coloured tissues, bioavailability of bis(trimethoxysilylpropyl)amine after oral administration can be concluded to be likely, even though poor.

A further repeated dose toxicity study (28-day) with bis(trimethoxysilylpropyl)amine (CAS 82985-35-1) is available and was performed according to OECD TG 407. Groups of 5 Crl:CD rats of each sex were administered the test material at doses of 100, 300 and 1000 mg/kg bw/day or vehicle alone (olive oil) via oral gavage for 28 days on 7 consecutive days per week. Five additional animals per sex per dose were included as recovery group for analysis of possible post-exposure reversibility of intoxication symptoms. Gross and histopathological examinations revealed edema (submucosal layer), slight hyperplasia of the surface epithelial cells (fundic mucosa) and slight necrosis (pyloric mucosa) in 1/5 males of the 1000 mg/kg bw/day group. In the recovery group, slight hyperplasia of the surface of epithelial cells in the pyloric mucosa and slight focal necrosis of the fundic mucosa related to the macroscopic findings in the glandular stomach were also observed in 1/5 male animals of the 1000 mg/kg bw/day dose group. Slight hyperplasia of the surface epithelial cells in the pyloric mucosa in the glandular stomach was observed in 1/5 females of the 1000 mg/kg bw/day dose group. Additionally, these effects were also noted in 1/5 females of the 1000 mg/kg bw/day dose group of the recovery group. Taken together, as no adverse effects were observed with respect to general/detailed clinical observations, haematological/clinical chemistry/neurobehaviour examination, body weights, organ measurements or urinalysis, the NOAEL (systemic) was considered to be 1000 mg/kg bw/day. Nevertheless, local adverse effects on gross pathology and histopathological examination following treatment with the test material at 1000 mg/kg bw/day were recorded in 1 male and female animal each (including 1 animal of each sex of the recovery group). Therefore, a NOAEL (local) of 300 mg/kg bw/day was derived.

QSAR based dermal permeability regarding molecular weight, log Pow and water solubility, calculated a low dermal absorption of 0.893 µg/cm²/h (DERMWIN). This value is considered as indicator for a dermal absorption of 20% (medium low). In an acute dermal toxicity study the undiluted test material was occlusively administered to rabbits for 24 h. The LD50 was determined to be 16 800 mg/kg bw (males) and 11 865 mg/kg bw (females). The predominant clinical signs detected were unsteady gait and prostration, as well as local effects, such as oedema, erythema, and desquamation. Gross pathology revealed red tracheae, lungs deep maroon, lungs mottled with tan caseous nodules, and heart with white film like appearance on pericardial sac (histopathology revealed bronchopneumonia, pleuritis, pericarditis). Based on the colouration of the tissues, which were already observed for the oral route, it can be concluded that bis(trimethoxysilylpropyl)amine silane may be absorbed through the skin. In contrast, in a subacute dermal repeated dose toxicity study the test item was occlusively administered at doses of 0.5, 1, and 5% in paraffin oil to the dorsal trunk of rabbits for 6 h/day and 5 days/week for 4 weeks. Mild to moderate skin irritation in the low dose group and mild to marked irritation in mid and high dose groups were observed throughout the study. Since some effects were observed in the solvent controls, irritations seen in test groups may partly have been caused by the solvent. Pathological examination revealed above all local effects on the treated skin such as hyperkeratosis. However, degenerative effects on the treated skin were not observed. Moreover, discolouration of organs comparable to the findings of the acute toxicity study was neither observed. Hence, dermal absorption can be concluded to be dependent on skin damaging effects such as those observed in the acute dermal toxicity study. Absorption via intact skin is therefore not expected.

Bis(trimethoxysilylpropyl)amine has a comparably low vapour pressure of 0.013 Pa. Therefore, inhalation of the vaporised target substance is quite unlikely. No reliable data is available for acute toxicity via inhalation. Nevertheless, supporting data derived from a summary report is available. Rats were exposed to substantially saturated vapour for 6 h. Since no deaths occurred, the LC50 was concluded to be > vapour saturation at 23 °C. Ataxia and slow righting reflex were observed on removal. Nevertheless, gross pathology revealed no remarkable findings. Hence, absorption of bis(trimethoxysilylpropyl)amine through the respiratory tract is considered to be unlikely.

Metabolism

No data are available describing the metabolism of bis(trimethoxysilylpropyl)amine. 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 bis(trihydroxysilylpropyl)amine. It cannot be excluded, that amine containing compounds underlie multiple metabolic reactions such as N-oxidation or N-dealkylation, but this is considered to be insignificant and would only enhance renal excretion.

Excretion

Bis(trimethoxysilylpropyl)amine is known to undergo hydrolysis rapidly. 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.