2-isocyanatoethyl methacrylate

Endpoint summary

Description of key information

No studies are available. Based on molecular structure, molecular weight, water solubility, octanol-water partition

coefficient, and available toxicity data, it can be expected that the registered substance is likely to be absorbed via the oral and dermal routes, but not via inhalation. Hydrolysis occurs rapidly, and exposure is expected to the parent substance, as well as to its degradation products. Based on the water solubility, the registered substance and its degradation products are likely to be distributed in the body, and excretion via the renal pathway can be expected. Bioaccumulation is not expected.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

There are no studies available in which the toxicokinetic properties of 2-isocyanatoethyl methacrylate have been investigated. Therefore, the toxicokinetic behaviour assessment of the substance and its hydrolysis products was estimated by its physico-chemical properties and the available toxicology studies on the substance itself.

The test substance hydrolyses rapidly in contact with water (half-lives less than 10 min at pH 4, 7 and 9 at 50°C), generating 2-aminoethyl methacrylate and in a further step the condensation product N,N'-[2-(2-Methyl-2-propenoic acid) ethyl ester] urea (Shibuya, 2011; Weber, 2012). This suggests that systemic exposure can occur to the parent substance, as well as and to the hydrolysis product and the condensation product. Hence, this toxicokinetic behaviour assessment will try to predict the behaviour of all these substances.

 

The molecular weight of 2-isocyanatoethyl methacrylate is 155.15 g/mol. In contrast, the molecular weight of the hydrolysis product 2-aminoethyl methacrylate is 129.16 g/mol and 284.31 g/mol for the condensation product N,N'-[2-(2-Methyl-2-propenoic acid) ethyl ester] urea, respectively. The calculated water solubilities at 25 °C for 2-isocyanatoethyl methacrylate, 2-aminoethyl methacrylate, and N,N'-[2-(2-Methyl-2-propenoic acid) ethyl ester] urea are 4214.15 mg/L, 494.130 g/L, and 6.2175 g/L, respectively (Hopp, 2012; Hopp, 2012). Thus, the hydrolysis product is smaller in size and highly water soluble, suggesting that it will have a greater potential to be absorbed through biological membranes than the parent compound. In contrast, the condensation product is also very water soluble, but bigger in size, suggesting that it will have a smaller potential to be absorbed through biological membranes. However, the moderate log Kow of the parent substance (1.72 (Shibuya, 2012)), the hydrolysis product (0.3 (Hopp 2012)), and the condensation product (1.24 (Hopp, 2012)) indicate that all these substances are lipophilic enough to efficiently pass through biological membranes by passive diffusion.

 

Absorption

Oral: In acute oral toxicity studies (SafePharm Laboratories, 1991a; SafePharm Laboratories, 1991b) with the registered substance signs of systemic toxicity were observed observed in both rats and mice, thus systemic availability is expected. If ingestion occurs, the hydrolysis of the parent substance at the low pH of the stomach will be rapid, so any absorption of the parent substance is expected to be minimal and it is more likely to be the degradation products that are absorbed.

 

Inhalation: The vapour pressure of the liquid parent substance (18 Pa at 20°C (Showa Denko K.K., Nishimura, Japan, 2016)) indicates that inhalation of the registered substance as a vapour is unlikely. No data are available for the hydrolysis product or the condensation product; however, based on the structure of these degradation products, the vapour pressure can be expected lower rather than higher.

Acute toxicity data indicate that the test material is highly toxic via inhalation (Dow Chemical U.S.A., 1978). Predominant signs of toxicity were attributed to respiratory irritation rather than systemic toxicity. Additionally, a 90-day repeated inhalation toxicity study (The Dow Chemical Company, 1980) did not show any signs of systemic toxicity even at doses, which were still lightly irritant to the respiratory tract. In conclusion, absorption via the inhalation route is not expected and the main hazard for this route of exposure is attributed to the corrosivity of the test material.

 

Dermal: The moderate log Kow and molecular weights of the parent substance and its two degradation products suggest that absorption via the dermal route is possible. The corrosive properties are expected to enhance dermal absorption and therefore systemic availability.

 

Metabolism

The registered substance hydrolyses rapidly in contact with water (half-life <10 min), generating 2-aminoethyl methacrylate and in a further step the condensation product N,N'-[2-(2-Methyl-2-propenoic acid) ethyl ester] urea. There are no data regarding the enzymatic metabolism of the parent compound and its degradation products.

 

Distribution

Due to the moderate log Kow and molecular weights of the parent substance and its two degradation products distribution through the body can be expected. Furthermore, they are likely to distribute into cells and the intracellular concentration may be higher than the extracellular concentration particularly in fatty tissues.

 

Accumulation

Due to the moderate log Kow of the parent substance and its two degradation products, accumulation in adipose tissue is not expected.

 

Excretion

Based on the molecular weight and the water solubility of the parent and the degradation products, excretion via the renal pathway is likely.