2-(diethylamino)ethyl methacrylate

Endpoint summary

Description of key information

Repeated-dose oral studies provide evidence for bioavailability of the test substance.
Intracellular concentration is likely to be higher than extracellular due to the moderate lipophilicity of the test substance. 
Based on the physicochemical properties and the calculated BCF values the test substance is not considered to be bioaccumulative. Excretion may mainly occur via the urine due to the small molecular weight of the test substance.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

2-Propenoic acid, 2-methyl-, 2-(diethylamino)ethyl ester is a clear colourless liquid with a molecular weight of 185.27 g/mol. At standard ambient pressure the melting point is -65.5 °C while the boiling point could not be determined due to limited stability of the substance. The vapour pressure was determined to be 14 Pa at 25 °C. The substance is soluble in water as indicated by the high water solubility value of 100 g/L (25 °C). The log Pow value for the chemical was determined to be 1.67 at 25 °C (shake flask method). The BCF value was calculated to be 9.049 L/kg.

Absorption

Solely based on the substance’s molecular weight and log Pow, absorption through the walls of the gastrointestinal (GI) tract via mechanisms of passive diffusion is possible. Additionally the substance has a very good water solubility leading to good dissolution in the gastro intestinal fluid and hence make contact with the mucosal surface.

A single oral dose of the test substance diluted in olive oil administered to rats led to a LD50 value of > 300 < 2000mg/kg bw. In a second acute oral toxicity assay the structural analogue 2-(DimethyIamino)ethyl methacrylate (CAS No 2867-47-2) lead to a LD50 value of above 2000 mg/kg bw.

Repeated administration of the 2-(DiethyIamino)ethyl methacrylate in a combined repeated dose toxicity study with the reproduction/developmental toxicity screening indicated that the compound became bioavailable.

Dermal uptake may be possible due to the log Pow value, the high water solubility and the physical state. It is generally accepted that if a compound’s water solubility falls between 100-10000 mg/L, absorption can be anticipated to be moderate to high. Moreover, for substances with a log Pow between 1 and 4, both penetration into stratum corneum and partition into the epidermis are likely to occur. Furthermore the test substance caused skin corrosion, which may enhance penetration.

Distribution

Assuming that the test substance is resorbed into the body following oral uptake it may be distributed into interior parts of the cells due to its moderate lipophilic properties and the intracellular concentration may be higher than the extracellular concentration particularly in fat tissues. The results from the combined repeated dose toxicity study with the reproduction/developmental toxicity screening test indicate an effect on the hematological system as well as the kidney in male rats. Penetration through the placenta is not likely to occur as the combined repeated dose toxicity study with the reproduction/developmental toxicity screening indicates no effects on reproduction. Based on the BCF value, the test substance has no potential to bioaccumulate in the human body.

Metabolism

Based on the chemical structure, 2-(DiethyIamino) ethyl methacrylate may be metabolized by Phase I enzymes while undergoing functionalisation reactions aiming to further increase the hydrophilicity. More specifically, based on the structure one or two hydroxyl groups are likely to be introduced by cytochrome P450 mediated oxidative de-alkylation. Furthermore, Phase II conjugation reactions may covalently link an endogenous substrate to the adsorbed test substance itself or the respective Phase I metabolites in order to ultimately facilitate excretion. The substance is most likely not enzymatically activated during metabolism. This assumption is supported by results of in vitro genotoxicity assays in which cytotoxicity of the parent substance was not higher as compared to metabolic activated test substance. Based on the structure a catalytic decomposition by carboxyl esterases into diethylaminoethanol and methacrylic acid cannot be excluded as part of the metabolism.

Excretion

Renal excretion is assumed to be the major route of elimination as the test substance has a low molecular weight and is soluble in water. It is highly unlikely that bioaccumulation within the body will occur according to the estimated BCF values.