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Description of key information

Key value for chemical safety assessment

Additional information

Two studies (1940 and 1971; reliability 3) are available for the test substance.

In a non-guideline study conducted in 1940, a human test person who received an oral dose of 5 g of the hydrochlorid form of the test substance excreted 86.2 % (after correction for the normal concentration of N) unchanged test substance in the day urine. Another study dealing with the metabolism of the test substance after ingestion stated that the formation of nitrosamines after reaction with nitrite depends greatly on the basicity of the amines.

 

However, as no valid data are available for the determination of toxicokinetics (absorption, distribution, metabolism, and excretion), this evaluation is based on the physico-chemical properties of the substance.

The test substance is a colourless liquid with a molecular weight of 73.1 g/mol and a vapour pressure of 316 hPa (25°C). It is completely miscible in water (at 25 °C) the log Po/w is 0.58.

Evidence for systemic availability of the test substance comes from acute (oral, dermal, inhalation), subacute and sub-chronic studies.

Absorption

 

Toxic effects have been observed after oral, dermal and inhalative exposure to the test substance. Therefore, an absorption via all three routes is likely.

-oral: The log Po/w value is favourable for absorption by passive diffusion. Moreover, after being dissolved in the gastrointestinal fluids the potential of absorption is high due to the miscibility of the substance with water. Furthermore, the test substance has a low molecular weight which supports the assumption, that a steric hindrance of the passage through aqueous pores or the carriage across membranes with the bulk passage of water is unlikely.

-inhalation: The test substance is highly volatile, thus may be available for inhalation as a vapour. Based on the log Po/w, absorption across the respiratory tract epithelium by passive diffusion is likely after inhalation.

For all exposure routes, local tissue corrosion at the site of entry was observed in animal studies. As already indicated by the acute toxicity data, the existing repeated dose toxicity data (inhalative route of exposure) indicate that the local effects (respiratory tract) are the primary effects of the test substance after inhalation.

- dermal: The dissolution of the substance in skin surface moisture, which is necessary for dermal uptake, is likely due to its miscibility with water. Also, the low molecular weight favours dermal uptake. The available toxicological data characterize the test substance to be skin corrosive.Therefore, a damage of the skin surface may enhance penetration.

 

Distribution

Due to the low molecular weight and the miscibility in water, the test substance is expected to have a wide distribution and to diffuse through aqueous channels and pores. The test substance is not lipophilic and is therefore not likely to distribute into cells.

 

Metabolism

Generally, low molecular weight secondary amines tend to be excreted unchanged but might to a low extent be metabolized to the primary amine via dealkylation.

 

Excretion

The low molecular weight as well as the miscibility in water are indicators for renal excretion. The substance is not expected to accumulate in the human body.