Piperidine

Endpoint summary

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

Absorption:

In a secondary source publication (original data not available) piperidine was reported to be absorbed from the respiratory tract, digestive tract, and skin (Gehring, 1983, cited in NAC/AEGL Committee, ACUTE EXPOSURE GUIDELINE LEVELS (AEGLs) for piperidine (CAS No. 110-89-4) 2007).

Accordingly, Zaeva et al. (1968, original publication in Russian, cited in BG Chemie, Toxicological evaluation No 72 Piperidine, 2000) found that after immersion of the tail of mice the test item was well absorbed through the skin and the amount was sufficient to cause death of the animals with a median lethal time of 77 minutes.

Absorption via the respriratory route and the gastrointestinal tract is supported by pronounced oral and inhalative toxicity (see Chapter 7.2.1).

 

Distribution: 

Piperidine was reported to be detected in various organs of mammalian and non-mammalian species (reviewed in Giacobini 1976 and Kasé 1976, see Chapter 7.10.1 and 7.12). It has been identified in muscle, liver, heart, kidney, spleen, testes, small intestine, lung of rats and mice. In healthy humans piperidine was found in heart, kidneys, liver, and cerebrospinal fluid. The highest concentrations were found in the brain.

 

Metabolism: 

Piperidine is a normal human metabolic product. In mammalians piperidine is synthesized in and outside of the brain. Thereby, piperidine is synthesized endogenously from lysine, cadaverine, and pipecolic acid. There are two possible biosynthetic pathways using the amino acid lysine as basic product (reviewed in Giacobini 1976, see Chapter 7.10.1). In the brain, it seems to be obvious that piperidine is derived from lysine, either exogenously or endogenously, by two alternative routes. One pathway via cadaverine, the decarboxylation product of lysine, involving deamination and cycIization of cadaverine. The other pathway from lysine, via pipecolic acid as an intermediate step, and decarboxylation. So homogenates of brain tissue are proved to convert pipecolic acid to piperidine. After intraperitoneal injection of radioactive pipecolic acid, radioactive piperidine is recovered from rat brain.

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 and Okano et al., 1978).

 

Excretion: 

Piperidine is excreted by the kidneys. Okano et al., (1978) 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. Using a colorimetric method, von Euler (1945) investigated the amount of piperidine in the urine of non-smoking human subjects. In total male subjects excreted 8.5 mg and females 7.6 mg in 24-hours.

 

Mechanism of toxicity:

Piperidine is a very strong alkaline agent with a pKb of 2.88 at 25°C. It is therefore severely corrosive to skin and causes burns to the skin after less than 3 min exposure duration (Linch, 1965, see Chapter 7.10.3). Due to the corrosive property, piperidine causes also severe eye damage and is expected to cause irritation to the respiratory tract (see Chapter 7.3). 

Piperidine occurs naturally in the brain and in other tissues of vertebrates and invertebrates. It is proved as a biogenic amine and acts as a neuromodulator (Giacobini, 1976, see Chapter 7.10.1 and 7.12). Thus piperidine effects respiration, blood pressure, contraction of smooth muscle and skeletal muscle (Kasé 1976 see Chapter 7.10.1 and 7.12). Additionally, piperidine acts on the central nervous system and mimics nicotinic effects (reviewed in Giacobini, 1976, see Chapter 7.10.1 and 7.12).