N-methyl-N-vinylacetamide

Endpoint summary

Link to relevant study record(s)

Reference

Endpoint:

basic toxicokinetics, other

Remarks:

Expert statement

Type of information:

other: Expert statement

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Expert statement, no study available

Principles of method if other than guideline:

Expert statement

GLP compliance:

no

Details on test animals or test system and environmental conditions:

not applicable

Details on exposure:

not applicable

Duration and frequency of treatment / exposure:

not applicable

Remarks:

not applicable

No. of animals per sex per dose / concentration:

not applicable

Positive control reference chemical:

not applicable

Details on study design:

not applicable

Details on dosing and sampling:

not applicable

Statistics:

not applicable

Details on absorption:

Generally, oral absorption is favoured for molecular weights below 500 g/mol. The miscibility with water at any ratio enables the substance to dissolve in the gastrointestinal fluids. In combination with the low molecular weight of less than 200 g/mol the test substance can pass through aqueous pores or can be carried through the epithelial barrier by the bulk passage of water. The low log Pow value is also favourable for passive diffusion. Taken together, the physiochemical properties indicate that the test substance becomes bioavailable following the oral route. This assumption is confirmed by the results of the acute oral toxicity study. These results did lead to classification of the substance for acute oral toxicity (category 4) as mortality was observed and the oral LD50 was established to be 1760 mg/kg bw.

Due to the vapour pressure of 1.73 hPa the test substance may be available as a vapour. If it is the case absorption via inhalation route might be possible due to the water solubility and the low log Pow value, enabling uptake directly across the respiratory tract epithelium by passive diffusion. This is neither supported not contradicted by the observations after single inhalative exposure of rats to the substance as no mortality was detected. Local effects in the epithelium of the nasal cavity after repeated inhalative exposure indicate an adsorption in at least the outmost layer of epithelial cells. As no systemic effects were detected, adsorption through the complete epithelium is neither established nor disproved.

Dermal absorption will also take place, favoured by the water solubility and the log Pow value, and also by the size of the molecule. The occurrence of dermal absorption is confirmed by the results of the acute dermal toxicity study with the test substance. The observed mortality lead to classification (category 4) and the LD50 was established to be 1354 mg/kg bw.

Details on distribution in tissues:

The physicochemical properties of the test substance favour systemic absorption following oral, inhalative and dermal uptake.

Direct transport through aqueous pores is likely to be an entry route to the systemic circulation. After being absorbed into the body, the test substance is most likely distributed into the interior part of cells due to its slightly lipophilic properties (log Pow 0.5) and in turn the intracellular concentration may be higher than extracellular concentration particularly in adipose tissues.

The logPow of the test substance indicates no bioaccumulation potential. It is well below 3 and the most likely uptake mechanism into cells is passive diffusion, therefore the test substance is not considered to be bioaccumulative.

Details on excretion:

The test substance will be excreted most likely in its metabolised form.
The likely excretion pathway of the test substance is via urine. As substances with a molecular weight below 300 g/mol are prone for this pathway and the substance’s molecular weight is 99.1311 g/mol.

Details on metabolites:

The genotoxicity studies indicated no differences in regard to genotoxicity and cytotoxicity in the presence or absence of metabolic activation systems. Generally it is likely that common protein interaction such as cytochrome P450 oxidases interaction during Phase I metabolism introduce a reactive or polar group in the test substance. Those might be further processed into polar compounds during the metabolism in Phase II.

Description of key information

Based on physicochemical characteristics, particularly water solubility and octanol-water partition coefficient, absorption by the dermal, oral and inhalation route is expected. This assumption is further supported by the results of the oral, inhalation and dermal acute toxicity studies, revealing toxic effects. Bioaccumulation of the test substance is not to be expected after continuous exposure. Phase I and II metabolism within liver cells is likely and excretion will presumably occur after renal passage via urine.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

Toxicokinetic Assessment

The test substance is a colourless liquid at room temperature with a molecular weight of 99.1311 g/mol. The substance is miscible with water at any ratio. The log Pow was determined to be 0.5. The test substance has a vapour pressure of 1.73 hPa at 20 °C.

 

Absorption

Generally, oral absorption is favoured for molecular weights below 500 g/mol. The miscibility with water at any ratio enables the substance to dissolve in the gastrointestinal fluids. In combination with the low molecular weight of less than 200 g/mol the test substance can pass through aqueous pores or can be carried through the epithelial barrier by the bulk passage of water. The low log Pow value is also favourable for passive diffusion. Taken together, the physiochemical properties indicate that the test substance becomes bioavailable following the oral route. This assumption is confirmed by the results of the acute oral toxicity study. These results did lead to classification of the substance for acute oral toxicity (category 4) as mortality was observed and the oral LD50 was established to be between 1760 mg/kg bw.

Due to the vapour pressure of 1.73 hPa the test substance may be available as a vapour. If it is the case absorption via inhalation route might be possible due to the water solubility and the low log Pow value, enabling uptake directly across the respiratory tract epithelium by passive diffusion. This is neither supported not contradicted by the observations after single inhalative exposure of rats to the substance as no mortality was detected. Local effects in the epithelium of the nasal cavity after repeated inhalative exposure indicate an adsorption in at least the outmost layer of epithelial cells. As no systemic effects were detected, adsorption through the complete epithelium is neither established nor disproved.

Dermal absorption will also take place, favoured by the water solubility and the log Pow value, and also by the size of the molecule. The occurrence of dermal absorption is confirmed by the results of the acute dermal toxicity study with the test substance. The observed mortality lead to classification (category 4) and the LD50 was established to be 1354 mg/kg bw. 

 

Distribution

The physicochemical properties of the test substance favour systemic absorption following oral, inhalative and dermal uptake.

Direct transport through aqueous pores is likely to be an entry route to the systemic circulation. After being absorbed into the body, the test substance is most likely distributed into the interior part of cells due to its slightly lipophilic properties (log Pow 0.5) and in turn the intracellular concentration may be higher than extracellular concentration particularly in adipose tissues.

The logPow of the test substance indicates no bioaccumulation potential. It is well below 3 and the most likely uptake mechanism into cells is passive diffusion, therefore the test substance is not considered to be bioaccumulative. 

 

Metabolism

The genotoxicity studies indicated no differences in regard to genotoxicity and cytotoxicity in the presence or absence of metabolic activation systems. Generally it is likely that common protein interaction such as cytochrome P450 oxidases interaction during Phase I metabolism introduce a reactive or polar group in the test substance. Those might be further processed into polar compounds during the metabolism in Phase II.

 

Excretion

The test substance will be excreted most likely in its metabolised form.

The likely excretion pathway of the test substance is via urine. As substances with a molecular weight below 300 g/mol are prone for this pathway and the substance’s molecular weight is 99.1311 g/mol.