N-[3-(triethoxysilyl)propyl]ethylenediamine

Endpoint summary

Description of key information

The available information showed some evidence that N-[3-(triethoxysilyl)propyl]ethylenediamine, is expected to be absorbed via the gastro-intestinal and respiratory tract. Once absorbed, the substance may be distributed systemically in the water compartment of the body. The substance is supposed to be excreted via the urine without being further metabolised.

Additional information

ASSESSMENT OF TOXICOKINETIC BEHAVIOUR

SUMMARY

In accordance with Annex VIII, Column 1, Item 8.8.1, of Regulation (EC) 1907/2006 and with Guidance on information requirements and chemical safety assessment Chapter R.7c: Endpoint specific guidance (ECHA, 2017), assessment of the toxicokinetic behaviour of the substance is conducted to the extent that can be derived from the relevant available information. This comprises a qualitative assessment of the available substance specific data on physicochemical and toxicological properties according to the relevant Guidance (ECHA, 2017).There are no studies available in which the toxicokinetic behaviour of N-[3-(triethoxysilyl)propyl]ethylenediamine (CAS 5089-72-5) has been investigated.

N-[3-(triethoxysilyl)propyl]ethylenediamine is a liquid at 20°C and 1013 hPa with a molecular weight of 264 g/mol. N-[3-(triethoxysilyl)propyl]ethylenediamine has a calculated water solubility of 240 g/l (PFA, 2014), a calculated vapour pressure of 0.03 Pa at 25 °C (PFA, 2014), and a log Pow of 1.2 (PFA, 2014). Hydrolysis is supposed to be quite fast, leading to ethanol and N-[3 -(trihydroxysilyl)propyl]ethylenediamine. Hydrolysis half-time is 15 min, 165 min, and 14 min at pH 4, 7, and 9, respectively.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 ethanol is discussed elsewhere and is not included in this summary.

The silanol-containing hydrolysis product has a calculated water solubility of 1000 g/l (PFA, 2014), a calculated vapour pressure of 6.8E-06 Pa at 25 °C (PFA, 2014), and a log Pow of -3.4 (PFA, 2014).

 

Absorption

Absorption is a function of the potential for a substance to diffuse across biological membranes.The most useful parameters providing information on this potential are the molecular weight, the octanol/water partition coefficient (log Pow) value and the water solubility.The log Pow value provides information on the relative solubility of the substance in water and lipids (ECHA, 2014).

 

Absorption, oral

In general, molecular weights below 500 and log Pow values between -1 and 4 are favourable for absorption via the gastrointestinal (GI) tract, provided that the substance is sufficiently water soluble (> 1 mg/l). Lipophilic compounds may be taken up by micellar solubilisation by bile salts, but this mechanism may be of particular importance for highly lipophilic compounds (log Pow > 4), in particular for those that are poorly soluble in water (≤ 1 mg/l) which would otherwise be poorly absorbed (ECHA, 2017).

Based on the PC data absorption of the parent substance and hydrolysis product is expected. The parent substance may be absorbed by passive diffusion, based on the log Pow of 1.2 and the high water solubility. In case of the hydrolysis product passage through aqueous pores or being carried through the epithelial barrier by the bulk passage of water could be possible based on the low molecular weight and the high water solubility.

These assumptions are supported by the results of the acute oral toxicity study in rats where dosage of up to 2000 mg/kg bw test substance provoked mortality and clinical signs of toxicity, showing systemic availability of the substance.

 

Absorption, dermal

The dermal uptake of liquids and substances in solution is higher than that of dry particulates, since dry particulates need to dissolve into the surface moisture of the skin before uptake can begin.Molecular weights below 100 g/mol favour dermal uptake, while for those above 500 g/mol the molecule may be too large. Dermal uptake is anticipated to be low, if the water solubility is < 1 mg/l; low to moderate if it is between 1-100 mg/l; and moderate to high if it is between 100-10000 mg/l. Dermal uptake of substances with a water solubility > 10000 mg/l (and log Pow < 0) will be low, as the substance may be too hydrophilic to cross the stratum corneum. Log Pow values in the range of 1 to 4 (values between 2 and 3 are optimal) are favourable for dermal absorption, in particular if water solubility is high. For substances with a log Pow above 4, the rate of penetration may be limited by the rate of transfer between the stratum corneum and the epidermis, but uptake into the stratum corneum will be high.Log Pow values above 6 reduce the uptake into the stratum corneum and decrease the rate of transfer from the stratum corneum to the epidermis, thus limiting dermal absorption (ECHA, 2017).

The physicochemical properties of the substance and its hydrolysis product suggest a rather low absorption through the skin. The high water solubility may limit the ability of the substance and its hydrolysis product to cross the stratum corneum. If a substance shows skin irritating or corrosive properties, damage to the skin surface may enhance penetration.If the substance is a skin sensitizer then some uptake must have occurred although it may only have been a small fraction of the applied dose (ECHA, 2017). For the test substance itself, effects regarding to skin and eye irritation were observed, which could enhance dermal penetration of the substance.

Overall, taking all available information into account, the dermal absorption potential is considered to be rather low.

 

Absorption, inhalation

N-[3-(triethoxysilyl)propyl]ethylenediamine has a calculated vapour pressure of 0.03 Pa at 25 °C (PFA, 2014). Therefore, under normal use and handling conditions, inhalation exposure and thus availability for respiratory absorption of the substance in the form of vapours and gases is not significant.

However, the substance may be available for respiratory absorption in the lung after inhalation of aerosols, if the substance is sprayed (e.g. as a formulated product). In humans, particles with aerodynamic diameters below 100 μm have the potential to be inhaled.Particles with aerodynamic diameters below 50μm may reach the thoracic region and those below 15μm the alveolar region of the respiratory tract (ECHA, 2017).

As for oral absorption, the molecular weight, log Pow and water solubility indicate that absorption via inhalation is possible.

 

Distribution and accumulation

Distribution of a compound within the body depends on the physicochemical properties of the substance; especially the molecular weight, the lipophilic character and the water solubility. In general, the smaller the molecule, the wider is the distribution.If the molecule is lipophilic, it is likely to distribute into cells and the intracellular concentration may be higher than extracellular concentration, particularly in fatty tissues (ECHA, 2014).

Once absorbed, the substance is likely to be distributed within the water compartment of the body due to the high water solubility.

 

Metabolism

There are no data regarding the metabolism of N-[3-(triethoxysilyl)propyl]ethylenediamine. Genetic toxicity tests in vitro showed no observable differences in effects with and without metabolic activation for the substance N-[3-(triethoxysilyl)propyl]ethylenediamine itself or the analogue substance N-(3-(trimethoxysilyl)propyl)ethylenediamine (CAS 1760-24-3).

 

Excretion

The low molecular weight (below 300 g/mol) and good water solubility of the parent and hydrolysis product suggest that they are likely to be excreted by the kidneys into urine.

 

Conclusion

The available information showed some evidence that N-[3-(triethoxysilyl)propyl]ethylenediamine, is expected to be absorbed via the gastro-intestinal and respiratory tract. Once absorbed, the substance may be distributed systemically in the water compartment of the body. The substance is supposed to be excreted via the urine without being further metabolised.