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Description of key information

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information

Since no experimental data are available to assess the absorption and metabolism properties of the test substance, the expected toxickinetic behavior is estimated based on the physicochemical properties. The test substance is a liquid with a low vapour pressure of 0.0032 Pa. The molecular weight varies between app. 316 and 544 g/mol, depending on the number of propoxy and acrylic acid units per molecule. The moderate water solubility of 1.2 g/L matches the LogPoW of 2.52. Hydrolysis in water can occur, but is very slow (half life above 100 days at 30°C) and thus not considered relevant in this context.

 

Absorption:

No toxicity was observed following ingestion of the substance, which is either due to the low toxicity of the substance or due to low GI absorption. Substances with a molecular weight below 1000 g/mol and a moderate logPoW between -1 and 4 are usually readily absorbed in the gastrointestinal tract. Additionally, the water solubility of 1.2 g/L, which allows dissolution in the GI fluids, and the absence of ionisable elements in the structure favour gastric absorption. In summary, the substance will likely be well absorbed after oral exposure.

Based on the water solubility and low lipophilicity, the substance will probably also be absorbed, if it reaches the lung mucosa. On the other hand, exposure is considered negligible due to the very low vapour pressure of only 0.0032 Pa. Thus, even though absorption cannot be excluded, inhalation is not considered a relevant route of exposure unless the substance is sprayed.

As for oral and inhalation absorption, the moderate water solubility and logPoW of 2.52 also favour absorption after dermal exposure, while the molecular weight might hinder dermal uptake, since it is close to 500 g/mol, above which dermal absorption is frequently limited. No toxicity occurred in acute dermal studies, but this might be due to the low toxicity of the substance. The substance causes only very slight skin irritation, but caused skin sensitization in animals. The latter proves that dermal absorption is possible, though no information about the percentage is available. In conclusion, although dermal absorption might be lower than GI absorption, it is definitely possible. Moderate to well absorption is assumed for the risk assessment.

 

Distribution and Metabolism:

Once absorbed the substance is expected to be quickly metabolized by esterases in the liver or other tissues (e.g., the skin after dermal contact) to acrylic acid and the corresponding tri-alcohol. Acrylic acid is first converted to acrylyl-CoA, which is subsequently oxidized to 3-hydroxypropionate. 3-hydroxypropionate is, in turn, metabolized to acetate and carbon dioxide via malonic semialdehyde. The resultant acetate is then incorporated into intermediary metabolism. 

The resulting tri-alcohol is either further metabolized via alcohol – and aldehyde dehydrogenases to the corresponding acid, which is then bound to glutathione prior to excretion, or the tri-alcohol is directly conjugated to glutathione and excreted. Both reactions are believed to be rapid and to compete with one another, so that either way is about equally likely. In any case, the substance will be quickly metabolized and excreted. No accumulation or long half-life is expected. This is also supported by the water solubility of 1.2 g/L, and a logPoW of 2.5.

Parent compound that reaches the blood is likely not metabolized but directly and very rapidly conjugated to glutathione, as was shown for other acrylates by Miller et al. in 1981.

 

Excretion

Glutathione conjugates of the substance and its break down products are expected to be biliary excreted and may undergo enterohepatic recycling while passing through the intestine before finally excreted via faeces. Small, water soluble metabolites are predominantly excreted via urine. Carbon dioxide as a product of acrylic acid metabolism is exhaled.

 

Miller, R. R. (1981). Metabolism of Acrylate Esters in Rat Tissue Homogenates. Fundamental and Applied Toxicology, 1, S. 410-414.

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