2-(diethylamino)ethyl methacrylate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

other: Expert statement

Adequacy of study:

key study

Study period:

2014-09-19

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Expert statement, no study available.

Data source

Reference

Reference Type:

other: Expert statement

Title:

Unnamed

Year:

2014

Report date:

2014

Materials and methods

Principles of method if other than guideline:

Expert statement based on toxicological data provided in IUCLID section 7.

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2-(diethylamino)ethyl methacrylate

EC Number:

203-275-7

EC Name:

2-(diethylamino)ethyl methacrylate

Cas Number:

105-16-8

Molecular formula:

C10H19NO2

IUPAC Name:

2-(diethylamino)ethyl methacrylate

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on 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.

Similarly based on the physico-chemical properties of the test substance, 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.

Details on distribution in tissues:

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.

Details on 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.

Metabolite characterisation studies

Details on metabolites:

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.