2-Propenoic acid, 2-[2-(ethenyloxy)ethoxy]ethyl ester

Endpoint summary

Description of key information

See discussion.

Key value for chemical safety assessment

Bioaccumulation potential:

low bioaccumulation potential

Additional information

The test material is an ether with the functional groups of alkene and ester. The test material is a colourless liquid with vapour pressure value that suggests it is not volatile. It is soluble in water (18.4 g/l at 20 °C) and not readily fat soluble (Log Pow 1.7 at 20°C).

The test material is not expected to undergo significant hydrolysis under physiological conditions. As a result, exposure to degradants, following oral ingestion, is not expected. Good water solubility, small molecular weight and moderate log oil/water partition coefficient of the test material suggests that it is expected to cross biological membranes and some limited accumulation in body fat may potentially take place.

The substance causes a mild irritant in the eyes in rabbits and skin sensitiser in female mice. It has effects on liver metabolism in rats. LD50 (oral) in SD rats is 2026 mg/kg for male and 1790 mg/kg for female. In Wister rats, LD50 (oral) is between 300 – 2000 mg/kg bw. It has high cytotoxicity.

Absorption

The results of the acute repeated oral toxicity study in the rat show significant systemic toxicity, which indicates that the substance is probably absorbed in gastrointestinal tract. This is supported by the relatively low molecular weight, lack of ionisation of the molecule, moderately high log oil/water partition coefficient and good water solubility. The test material may even directly across the respiratory tract epithelium. This may also be the case with other routes of absorption such as through the skin due to the physical state of the substance. The penetration of the substance may be enhanced by the mild irritancy of the substance. The results of the local lymph node assay in the mouse indicate that the substance is a sensitizer which suggests that dermal absorption of the test material can take place. This is supported by the treatment-related anemia observed in repeated-dose study. Inhalation could be a significant route of exposure due to the particle size of the substance, with the evidence of mortality in inhalation study. The effects in inhalation exposure study suggest the substance is likely absorbed in respiratory tract.

Distribution:

The distribution of the substance may be relatively wider due to small molecular weight. There is evidence in the repeated dose study to show that the test material is distributed systemically following oral ingestion. The positive skin sensitisation response suggests that the test material can bind to carrier proteins in blood. The high water solubility of the test material will allow it to disperse into the water compartment of blood for distribution. These characteristics may contribute to the anemia observed in the repeated dose toxicity study. The moderate log oil/water partition coefficient value suggests that some test material can accumulate in body fat but not in significantly high proportions.

Metabolism:

There is no evidence to indicate that there is significant hepatic metabolism of the test material unless it is via non-microsomal systems. Although the results of two in vitro genotoxicity assays showed both positive and negative results, genotoxicity was neither enhanced nor diminished in the presence of S9 metabolising system in both studies. The high water solubility and small molecular weight suggest that metabolism may not be necessary to facilitate excretion.

Excretion:

There is no evidence to indicate the route of excretion of the test material. However, it is likely that the kidney will be a significant route of excretion for a product with high water solubility and relatively small molecular weight. In addition, it may be possible that the substance may be excreted in the bile. There is no evidence to confirm or refuse the potential for enterohepatic circulation.