Registration Dossier

Administrative data

Link to relevant study record(s)

Description of key information

The available experimental data in animals support limited oral absorption and systemic distribution of the test substance and/or its metabolites or degradation products since only minor effects were reported in the kidneys following repeated oral exposure in rodents.  Owing to the low vapour pressure of the main constituents compared to that of water, it can be considered that the absorption resulting from potential exposure by the inhalation route is considered limited. No systemic effects were observed when the test substance was dermally applied in the acute dermal toxicity study. There was no obvious indication on the test substance metabolism or excretion from the toxicity studies.

Key value for chemical safety assessment

Additional information

No specific toxicokinetic studies are available on Reaction mass of methacrylic acid and N-[2-(2-oxoimidazolidin-1-yl)ethyl]methacrylamide. A toxicokinetic assessment was made based on the physico-chemical properties of the test substance and the results of toxicity studies (acute dermal toxicity, skin irritation, skin sensitisation, in vitro genotoxicity and repeat dose toxicity studies).

Physico-chemical properties:

Molecular Weight: 119 g/mol for the substance as registered (including the water necessary for its stability)

Partition coefficient in octanol/water: <0.3 to 0.79 (at 25°C)

Vapour pressure: 3055 Pa (at 25°C) for the substance as registered (including the water necessary for its stability) ; 0.0000219 Pa for N-[2-(2-oxoimidazolidin-1-yl)ethyl]methacrylamide; 130 Pa for methacrylic acid.

Boiling point: 101.95 ± 0.2°C (at 101 kPa)

Density: 1.11 (at 20°C)

 

Absorption and distribution:

Inhalation:

No data are available for inhalation route of exposure. However, the test substance is a liquid with a low volatility, as evidenced by the low vapour pressure of the main constituents (N-[2-(2-oxoimidazolidin-1-yl)ethyl]methacrylamide and methacrylic acid) compared to that of water. Therefore it can be considered that the absorption resulting from potential exposure by the inhalation route is limited.

Oral route:

In the repeated oral dose toxicity study (OECD 407), macroscopic and microscopic changes were observed mainly in the digestive and respiratory tracts and were most likely due to irritant properties of the test item. The alterations in the respiratory system are likely the results of aspiration of test item after regurgitation at dosing. The minor microscopic and organ weight changes observed in the kidneys of a few animals are consistent with a limited absorption and systemic distribution of the test substance and/or its metabolites or degradation products.

Dermal route:

There was no evidence of systemic toxicity in the acute dermal toxicity study in rats at the dose of 2000 mg/kg bw. There were neither any signs of toxicity or sensitisation after cutaneous exposure on the mouse ears in the LLNA assay. In addition, although the test substance has good water solubility and its molecular weight is relatively small (119 g/mol), the partition coefficient in octanol/water below 1 tends to support a limited capacity for absorption through the skin.

 

Metabolism:

Two in vitro studies assessed the potential genotoxicity of the Reaction mass of methacrylic acid and N-[2-(2-oxoimidazolidin-1-yl)ethyl]methacrylamide. The Ames test showed no mutagenic effects in the presence or in the absence of exogenous mammalian metabolic activation system. In contrast, the chromosome aberration test in Chinese Hamster Lung Fibroblast cells was positive in the absence of metabolic activation and negative in the presence of metabolic activation. This suggests a possible detoxification of the test substance by metabolizing enzymes. However, in the absence of specific metabolism studies, it is not possible to conclude on the metabolisation potential of the test substance.

 

Elimination:

There is no indication of a preferred route of excretion for the Reaction mass of methacrylic acid and N-[2-(2-oxoimidazolidin-1-yl)ethyl]methacrylamide but its good water solubility and low molecular weight indicate that excretion of unchanged parent substance and/or metabolites could occur by the renal route and that bioaccumulation is unlikely. Elimination of the main components via the lungs in expired air is unlikely owing to their low volatility.