2-(2-ethoxyethoxy)-2-methylpropane

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

other: Expert statement

Adequacy of study:

key study

Study period:

2014-11-19

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

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2-(2-ethoxyethoxy)-2-methylpropane

EC Number:

257-196-8

EC Name:

2-(2-ethoxyethoxy)-2-methylpropane

Cas Number:

51422-54-9

Molecular formula:

C8H18O2

IUPAC Name:

2-(2-ethoxyethoxy)-2-methylpropane

Test material form:

other: liquid

Test animals

Details on test animals or test system and environmental conditions:

not applicable

Administration / exposure

Details on exposure:

not applicable

Duration and frequency of treatment / exposure:

not applicable

Doses / concentrations

Remarks:

Doses / Concentrations:
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

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

Substances with a molecular weight below 500 g/mol are favoured for oral absorption. This characteristic combined with the moderate lipophilic log Kow value and high water solubility allow dissolution of 2-(2-ethoxyethoxy)-2-methylpropane in the gastro-intestinal fluids and contact with the mucosal surface. In one oral toxicity study a LD50 of 3600 mg/kg bw was determined.

Additionally, readily absorption through the GIT epithelium is assumed after oral intake due to the low log Kow value of the test substance. Furthermore, the low molecular weight (below 200 g/mol) combined with the high water solubility (> 10 g/L) may allow the direct uptake into the systemic circulation through aqueous pores or via carriage of the molecules across the membrane with the bulk passage of water.

Based on the vapour pressure of approximately 36.96 hPa the test substance may reach the respiratory system. If the substance would reach the lungs in its vapour or gaseous state, absorption directly across the respiratory tract epithelium by passive diffusion is likely to occur due to its log Kow value and water solubility. An acute inhalation toxicity study performed on rats with the test substance in its aerosol form revealed a LC50 of 10500 mg/m3.

Similarly, based on physico–chemical properties of the test substance, it may be able to penetrate skin as the log Kow value and water solubility allow dermal penetration. As the compound´s water solubility is very high with 37 g/L and the log Kow is 2.2 absorption can be anticipated to be moderate to high. Moreover, for substances with a log Kow between 1 and 4, both penetration into stratum corneum and partition into the epidermis are likely to occur. In addition, the test substance caused slight skin irritation, which may enhance penetration.

Details on distribution in tissues:

Assuming that the test substance is absorbed into the body following oral, dermal or inhalation intake, it may be distributed into the interior part of cells due to its moderate lipophilic properties and in turn the intracellular concentration may be higher than extracellular concentration particularly in adipose tissues. As mentioned above, the physico-chemical properties, especially the lower molecular weight and relatively high water solubility, favour systemic absorption. Direct transport through aqueous pores is likely to be an entry route to the systemic circulation. Based on the relatively low log Kow and the log Koc values, it can be expected that the test substance has no potential to bioaccumulate in the human body.

Details on excretion:

As the molecule has a low molecular weight (146.2273 g/mol) and is miscible in water renal excretion may be the major route of elimination. The compound may either directly excreted by urine or further metabolised by Phase II enzymes before excretion.

Metabolite characterisation studies

Details on metabolites:

Based on the structure of the molecule it may be metabolized by Phase I enzymes while undergoing functionalization reactions aiming to increase the compound’s hydrophilicity. The substance is most likely not enzymatically activated (toxified) during metabolism. This assumption is supported by the result of an Ames test as well as an in vitro micronucleus assay in V79 Cells in which cytotoxicity of the parent substance was not higher as compared to metabolic activated test substance.
Furthermore, Phase II conjugation reactions may covalently link an endogenous substrate to the parent compound or the Phase I metabolite in order to ultimately facilitate excretion.