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Link to relevant study record(s)

Description of key information

There was only one study available, which showed dealkylation of 1-ethylpiperidine to piperidine, which is N-oxidized to the corresponding N-Hydroxyamine. Based on the low molecular weight, moderate water solubility, and moderate octanol-water partition coefficient absorption after oral administration can be expected. The test item has moderate vapour pressure and volatility and due to moderate water solubility may be retained within the mucus after inhalation followed by local irritation and may pass across the respiratory epithelium. The moderate log P value may favour absorption directly across the respiratory tract epithelium by passive diffusion. However, due to the corrosive potential of the test item mainly local effects have to be expected. Concerning the dermal route, rather local effects leading to destruction of membrane barriers than systemic effects have to be considered. Due to molecular weight and water solubility, excretion is likely to be expected by the kidney.

Key value for chemical safety assessment

Additional information

Assessment of the Toxicokinetic Behaviour

1-Ethylpiperidine (molecular weight of 113.2 g/mol) is a colourless to yellowish liquid with an amine-like odor, pH value of 12.2 at a concentration of 50 g/L and 20 °C, water solubility of 6 g/L at 20 °C (GESTIS 2011, see chapter “water solubility”) and a vapour pressure of 12.76 hPa at 20 °C (BASF 1987, see chapter “vapour pressure”). The log P for the molecule was determined to be 1.49 at 25 °C at a pH of 10.2 to 10.5 (BASF 1988, see chapter “partition coefficient”), indicating no accumulation of the substance.

There was one study available on the cleavage of 1-Ethylpiperidine by the 9000 x g supernatant of mouse and rat liver in vitro (Kimura 1979, Val 4). No other studies were available in which the toxicokinetic properties of 1-Ethylpiperidine were investigated.

 

Absorption

Data on absorption can only be taken from acute (oral, inhalative and dermal) studies.

In an acute oral toxicity study, rats were administered the substance by gavage at doses of 165 to 1322 mg/kg bw., a LD50 of ca. 280 mg/kg bw was determined, clinical signs such as sedate behaviour; spasmodic convulsions; opisthotonus; flexor spasms; tremor; dyspnea; lacrimation; salivation; exophthalmus; chromodakryorrhoe; crouching position; accelerated, irregular respiration; scrubby fur. No abnormalities were noted at necropsy of deceased and sacrificed animals (BASF, XX/36, 1970, see chapter “acute oral toxicity”). Due to the low molecular weight may pass through aqueous pores or be carried through the epithelial barrier by the bulk passage of water. Additionally, the moderate log P may facilitate absorption of the test compound in the gastrointestinal tract by passive diffusion (ECHA Guidance 7c, 2008).

 

The test compound has a moderate vapour pressure and volatility. In an inhalation hazard exposure for 10 min to an atmosphere that had been saturated at 20 degrees centigrade with the volatile parts of the compound all animals died within 10 min (BASF, XX/36, 1970, see chapter “acute inhalative toxicity”). Clinical signs included gasping, strong mucosal irritation, agony, tremor, convulsions and disturbances of equilibrium. These effects at the site of action and mortality are caused primarily by the strong corrosive mode of action of the substance.

In an acute inhalative toxicity study, rats were whole body exposed at concentrations of 1.88 to 6.84 mg/L, a LC50 (male and female rat, 4h) of 2.42 mg/L was determined. Clinical signs were restless behavior, gasping respiration, lid closure, anemic aspect, tremors and convulsions (saltatory spasms), sighing, jerky and irregular respiration, salivation, lateral or abdominal position, reddish discharge from the noses, encrustations and ruffled fur after inhalation of an aerosol for 4 hours (BASF85/207, 1987, see chapter “acute inhalative toxicity”). Due to the moderate water solubility, the test substance may be retained within the mucus after inhalation followed by local irritation and may pass across the respiratory epithelium. Thereby, the moderate log P value may favour absorption directly across the respiratory tract epithelium by passive diffusion. However, due to the corrosive potential of the test substance the main effects are local effects.

In an acute dermal study the LD50 for male and female rabbits was > 200 mg/kg bw. Clinical signs were irritation and formation of necrosis, no systemic effects were observed (BASF 77/515, 1980, see chapter “acute dermal toxicity”). Therefore, the primary action of the test item is the local effect which led to destruction of membrane barriers.

 

Metabolism

In rat and mouse liver in vitro N-C-cleavage was investigated and dealkylation of N-Ethylpiperidine to piperidine was shown (Kimura et al., 1979, Yakugaku Zasshi 99, 228-234 and Kimura et al., 1979, Yakugaku Zasshi 99, 235-239). Piperidine is N-oxidized to the corresponding N-Hydroxylamine. Other metabolites are 2,3,4,5-tetrahydropyridine-1-oxide, 3-hydroxy piperidine, 4-hydroxy piperidine and Piperidone-2 (Wang et al., 1989, Acta Pharmacol. Sin. 10, 252-256 and Okano et al., 1978, Japan. J. Pharmacol. 28: 41-47).

Studies on genotoxicity, in mammalian cells gave indications of a reactivity of the substance or its metabolites under the test conditions as shown by cytotoxicity in treatments with or without metabolic activation. No increased Mutagenicity was observed.

 

Excretion

1-Ethylpiperidine has a molecular weight of 113.2 g/mol and has moderate water solubility and is therefore likely to be excreted predominantly via the urine (ECHA GD 7c, 2008). The metabolite piperidine is excreted by the kidneys, too. Okano et al., 1978 (J. Pharmacol. 28: 41-47) found unchanged piperidine, 3-hydroxypiperidine, 4-hydroxypiperidine, and two unidentified metabolites in urine collected over 72 hours after i.p. injection of rats with [³H]piperidine.