N-[3-(dimethoxymethylsilyl)-2-methylpropyl]ethylenediamine

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 N-[3-(dimethoxymethylsilyl)-2-methylpropyl]ethylenediamine is likely to be absorbed. However, hydrolysis is expected to occur rapidly, and data from the silanol containing degradation product indicate a less favourable absorption. Due to the high water solubility, distribution in the body is likely, 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:

no bioaccumulation potential

Additional information

Toxicokinetic behaviour assessment for N-[3-(dimethoxymethylsilyl)-2-methylpropyl]ethylenediamine (CAS 23410-40-4)

There are no studies available in which the toxicokinetic properties of N-[3-(dimethoxymethylsilyl)-2-methylpropyl]ethylenediamine (CAS 23410-40-4) have been investigated. Therefore, the toxicokinetic behaviour assessment of the substance and its hydrolysis product was assessed by its physico-chemical properties, the available toxicology studies on the substance itself and the read-across substances N-(3-(trimethoxysilyl)propyl)ethylenediamine (CAS 1760-24-3), N-[3-(dimethoxymethylsilyl)propyl]ethylenediamine (CAS 3069-29-2), and N-[3-(methoxydimethylsilyl)propyl]ethylenediamine (CAS 3069-33-8). The submission substance is a moisture-sensitive liquid that hydrolyses rapidly in contact with water. As no data are available about the exact hydrolysis time a R-A was performed to CAS 3069-29-2 (half-life 15 min at pH 7 and 20 -25 °C), generating methanol and N-[3-(dihydroxymethylsilyl)propyl]ethylenediamine. At pH 4 and 2 the hydrolysis is even faster (<3 min at 20-25 °C), and at pH 2 and 37.5 °C, which corresponds to the acidic conditions in te stomach, hydrolysis is predicted to occur already within 5 s. This therefore suggests that systemic exposure will be to the hydrolysis product rather than the parent substance. However, this toxicokinetic behaviour assessment will try to predict the behaviour of both.The toxicokinetics of methanol are discussed elsewhere and are not included in this summary.

The molecular weight and the predicted water solubility of CAS 23410-40-4 are 220.39 g/mol and 450 g/L, respectively. In contrast, the molecular weight and predicted water solubility of the hydrolysis product are 192.33 g/mol and 1000 g/L, respectively. This shows that the hydrolysis product is smaller in size and is more water soluble; therefore suggesting it has the greater potential to be absorbed than the parent substance. However, the predicted log Kow of 1.4 for the parent substance and -1.0 for the hydrolysis product indicate that both may efficiently pass through biological membranes.

Absorption

Oral: In an acute oral toxicity study with the analogue substance N-[3-(dimethoxymethylsilyl)propyl]ethylenediamine (CAS 3069-29-2), the LD50 determined was in the range of 200-2000 mg/kg bw, thus indicating that absorption via the oral route is possible. If absorption occurs, the hydrolysis of the parent substance in the low pH of the stomach will be rapid, so absorption of the parent substance is expected to be minimal and is more likely to be the hydrolysis product. The predicted water solubility of 450 g/L of the parent and 1000 g/L of the hydrolysis product suggest that both substances will readily dissolve into the gastrointestinal fluids. Also, the low molecular weight (220.39 and 192.33 g/mol) of the substances suggests that they have the potential to pass though aqueous pores or be carried through the epithelial barrier by the bulk passage of water. Furthermore, the predicted log Kow of 1.0 for the parent substance and the log Kow of -1.4 for the hydrolysis product suggest that due to its moderate log Kow the parent substance is favourable to be absorbed by passive diffusion.

 

Inhalation: The predicted water solubility (450 and 1000 g/L) and log Kow (1.4 and -1) of the parent substance and the hydrolysis product indicate that absorption from the respiratory tract epithelium by passive diffusion may be possible, but due to the high water solubility the substances may be retained in the mucus. Particles deposited on the mucociliary blanket will be elevated into the laryngeal region and ultimately be swallowed (ingestion). An acute inhalation toxicity study with the submission substance revealed no signs of systemic toxicity, indicating that systemic availability after inhalation exposure is limited.

Dermal: The predicted water solubility (450 and 1000 g/L) and log Kow (1.4 and -1) of the parent substance and the hydrolysis product suggest that absorption will be low. For the hydrolysis product the water solubility of above 10 000 mg/l and the log Kow value below 0 suggest the substance may be too hydrophilic to cross the lipid rich environment of the stratum corneum. Dermal uptake of the hydrolysis product should be very low.

Distribution

The high water solubility and the moderate and low Log Kow of the parent and hydrolysis products, respectively, suggest that accumulation in the body is not favourable.

Metabolism

There are no data regarding the metabolism of N-[3-(dimethoxymethylsilyl)-2-methylpropyl]ethylenediamine. Genetic toxicity tests in vitro showed no observable differences in effects with and without metabolic activation for the analogue substance N-[3-(methoxydimethylsilyl)propyl]ethylenediamine (CAS 3069-33-8).

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.