Pyrrolidine

Endpoint summary

Description of key information

A toxicokinetic assessment was performed based on the available data of the substance. Furthermore, a publication (Hawksworth et al 1974) describing metabolism of piperidine is available. Data obtained with piperidine can be read across to pyrrolidine (rationale in Section 13).

Key value for chemical safety assessment

Bioaccumulation potential:

low bioaccumulation potential

Absorption rate - oral (%):

100

Absorption rate - dermal (%):

100

Absorption rate - inhalation (%):

100

Additional information

Hawskworth et al (1974) describe that rats were orally dosed with 500µg piperidine. In 3/6 rats with urinary bladder infection approximately 0.2 µg nitrosopiperidine was found in the urine by GC-MS analysis, which represents a nitrosation of 0.04% of the amine dose. Similar results were obtained when pyrrolidine was used, but no exact data were given on this substance. A justification to read across data from piperidine to pyrrolidine is given in Section 13.

The low molecular weight (71.14) of pyrrolidine favours absorption in the gastro-intestinal tract by passive diffusion. The high water solubility (1000 mg/L) and the low log Pow (0.22) of pyrrolidine also favour absorption in the gastro-intestinal tract by passive diffusion.

Therefore, for risk assessment purposes, the oral absorption of pyrrolidine is set at 100% (1).

The results of the oral toxicity studies with pyrrolidine show severe corrosive effects after oral exposure to pyrrolidine, which may enhance uptake of the substance. These data do not provide reason to deviate from the proposed oral absorption percentage.

Pyrrolidine may be expected to be distributed widely throughout the body based on the small molecular weight. Based on the low lipophilicity and high water solubility of pyrrolidine bioaccumulation is expected to be low. Absorbed pyrrolidine might undergo biotransformation (3), of which the products are expected to be excreted via the urine as they are still low molecular weight compounds with high hydrophilicity.

The low molecular weight favours dermal absorption. Since the log Pow is low (0.22), pyrrolidine may be taken up in the stratum corneum to a limited extent, followed by transfer to the epidermis based on the high water solubility (1000 mg/L). According to the criteria given in the REACH guidance (1): 10% dermal absorption will be considered in case MW>500 and log Pow <-1 and >4, otherwise 100% dermal absorption should be chosen. The two available studies on acute dermal toxicity both report severe corrosive effects. Exposure to pyrrolidine will lead to disturbance of the dermal integrity which will enhance dermal absorption. Therefore, for risk assessment purposes, the dermal absorption of pyrrolidine is set at 100% (2).

The vapour pressure (64.5 hPa at 20 °C) indicates that pyrrolidine might be available for inhalation as a vapour. The high hydrophilicity (1000 mg/L) of pyrrolidine might prevent adsorption via the respiratory tract due to retention in the mucus. However, the moderate log Pow (0.22) allows absorption directly across the respiratory tract epithelium by passive diffusion. After inhalation exposure to pyrrolidine local effects were observed, caused by the corrosive properties of the substance. Taken together, 100% absorption via inhalation of pyrrolidine is proposed for risk assessment purposes.