Pyrrolidine

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

other: theoretical assessment

Adequacy of study:

key study

Study period:

2013

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: A theoretical assessment, non-GLP, based on the REACH guidance IR CSA, R.7, has been performed.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Principles of method if other than guideline:

Expert statement based on the (physico-chemical) properties of the substance.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Pyrrolidine

EC Number:

204-648-7

EC Name:

Pyrrolidine

Cas Number:

123-75-1

Molecular formula:

C4H9N

IUPAC Name:

pyrrolidine

Test material form:

other: liquid

Results and discussion

Main ADME results

Type:

absorption

Results:

For risk assessment purposes an oral, dermal and inhalatory absorption of 100% for all exposure routes was derived.

Any other information on results incl. tables

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 oral 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% dermal absorption of pyrrolidine is proposed for risk assessment purposes.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): other: Based on its physical/chemical properties, absorption factors for pyrrolidine are derived to be 100% (oral), 100% (inhalation) and 100% (dermal) for risk assessment purposes. The bioaccumulation potential is expected to be low.
Based on its physical/chemical properties, absorption factors for pyrrolidine are derived to be 100% (oral), 100% (inhalation) and 100% (dermal) for risk assessment purposes. The bioaccumulation potential is expected to be low.

Executive summary:

Based on its physical/chemical properties, absorption factors for pyrrolidine are derived to be

100% (oral), 100% (inhalation) and 100% (dermal) for risk assessment purposes. The

bioaccumulation potential is expected to be low.