Registration Dossier

Administrative data

Link to relevant study record(s)

Description of key information

For propylene carbonate, no experimental in vivo studies are available where absorption, distribution, metabolism and/or excretion are evaluated. Therefore, a qualitative assessment is performed on the basis of the physicochemical properties of the substance, an in vitro hydrolysis/degradation study (Ehmer, 2015) and the publications of Yang et al., (1998) and Hanley et al. (1989). It can be concluded that propylene carbonate hydrolysis in blood is fast and occurred with maximum degradation rates of 0.68 μmol/(ml x min). Under the incubation conditions used in the study, nearly complete hydrolysis and stoichiometric formation of propylene glycol was observed after 5 min.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential
Absorption rate - oral (%):
50
Absorption rate - dermal (%):
50
Absorption rate - inhalation (%):
100

Additional information

Absorption

Oral absorption:

As propylene carbonate is a small molecule (MW 102 g/mol), it will be taken up easily. Moreover, the substance may pass through aqueous pores or be carried through the epithelial barrier by the bulk passage of water. The water-soluble liquid (200 g/L) will readily dissolve into the gastrointestinal fluids. Also the moderate log Kow value is favourable for absorption by passive diffusion. An oral absorption of 50 % is expected. 

Respiratory absorption:

As the substance is liquid at room temperature, with a high boiling point (242 °C) and a low vapour pressure (0.06 hPA), no or only a limited number of airborne particles are expected. The substance is water soluble and will be readily soluble in blood. When the substance is airborne, a high amount will be absorbed per breath. Since the substance has a moderate Log KoW (-0.41) absorption might occur. When exposure occurs, 100% respiratory absorption is proposed as a worst case. 

Dermal absorption:

The substance is liquid, highly water soluble and relatively small. Moreover, propylene carbonate has a low vapour pressure. These parameters favour dermal uptake. On the other hand, the substance might be too hydrophillic to cross the lipid rich environment of the stratum corneum. Similar to the oral route, an absorption of 50% is expected.

 

Distribution/Accumulation

Wide distribution throughout the body is expected as the substance is relatively small and water-soluble. It is likely to diffuse through aqueous channels and pores. Based on the results of the (eco)toxicological studies included in this dossier, no bioaccumulation is expected.

 

Metabolism

In order to demonstrate the metabolism of propylene carbonate, an in vitro hydrolysis study is performed in 2015 (Ehmer B, 2015). The results of the pre-test (Pharmacelsus, 2015) indicate that the hydrolysis of propylene carbonate in rat blood is even faster as compared with ethylene carbonate. Considering that ethylene carbonate was metabolized in vivo to form ethylene glycol and considering that Yang et al. (1998) (here below) showed that alkyl carbonates are hydrolyzed to form CO2and the respective alkyl glycol, it can be concluded that propylene carbonate is hydrolyzed to form propylene glycol.

In the in vitro hydrolysis study, propylene carbonate was incubated in Wistar rat blood over a time span of 30 minutes. There was 5.5 % of the start concentration remaining after 5 minutes of incubation. After 30 minutes 2 out of 3 samples showed quantification results below the limit of quantification. The hydrolysis product propylene glycol was formed simultaneously from the reference item at concentrations that corresponded to its turnover/hydrolysis. The calculated half-life value for propylene carbonate was 0.734 minutes. This corresponds to a turnover of 0.68 μmol/(ml x min). The positive control item ethylene carbonate was also incubated in Wistar rat blood over a time span of 30 minutes. 35.5 % of the start concentration remained after 5 minutes of incubation. After 30 minutes 15.5% of the start concentration was observed. The hydrolysis product ethylene glycol was formed simultaneously from the reference item at concentrations that corresponded to its turnover/hydrolysis. The calculated half-life value for ethylene carbonate was 3.533 minutes. This corresponds to a turnover of 0.14 μmol/(ml x min). These finding indicate that the hydrolysis occurs faster with the propylene carbonate as compared to the positive control. For both compounds the formation of the corresponding glycols was observed simultaneously.

Earlier studies support the abovementioned findings. Hanley et al. (1989) conducted a toxicokinetic study using ethylene carbonate, a structural analogue to propylene carbonate, and demonstrated that the half-life of ethylene carbonate in vivo in rat blood is very short (estimated at 0.25h).

Yang et al. (1998) investigated the biotransformation of certain cyclic alkylene carbonates and demonstrated that these carbonates are hydrolysed to CO2 and the respective alkylene glycol. They tested the hydrolysis of three cyclic carbonates: ethylene carbonate, vinylene carbonate and propylene carbonate. It was confirmed that all three substrates are hydrolysed to CO2 and the respective glycols.

In order to demonstrate the metabolism of propylene carbonate further, an in vitro hydrolysis study is planned. The results of the pre-test (Pharmacelsus, 2015) indicate that the hydrolysis of propylene carbonate in rat blood is even faster as compared with ethylene carbonate. Considering that ethylene carbonate was metabolized in vivo to form ethylene glycol and considering that Yang et al showed that alkyl carbonates are hydrolyzed to form CO2 and the respective alkyl glycol, it can be concluded that propylene carbonate is hydrolyzed to form propylene glycol.

In conclusion, absorbed propylene carbonate is assumed to be metabolised and converted to CO2 and propylene glycol.

 

Excretion

Based on the physicochemical characteristics of propylene carbonate, excretion via urine is expected, as the substance is relatively small and water soluble.

Hanley et al. (1989) conducted a toxicokinetic study using ethylene carbonate, a structural analogue to propylene carbonate, and demonstrated that ethylene carbonate is primarily excreted via exhalation as carbon dioxide (57%), to a lower amount via the urine (27%) and only marginally via feces (2%).