Furan, 2-(ethoxymethyl)tetrahydro-

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vitro / ex vivo

Type of information:

calculation (if not (Q)SAR)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

Assessment made on result of testing to support registration of this substance and using test data from key metabolites
See report attached

Data source

Reference

Reference Type:

other company data

Title:

Unnamed

Year:

2021

Report date:

2021

Materials and methods

Objective of study:

absorption

distribution

excretion

metabolism

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Assessment made on result of testing to support registration of this substance and using test data from key metabolites

GLP compliance:

not specified

Test material

Test material information

1

Reference substance name:

-

EC Number:

423-630-1

EC Name:

-

Cas Number:

62435-71-6

Molecular formula:

C7H14O2

IUPAC Name:

2-(ethoxymethyl)oxolane

Test material form:

liquid

Radiolabelling:

no

Test animals

Species:

other: Not applicable

Administration / exposure

Route of administration:

not specified

Results and discussion

Preliminary studies:

The substance is soluble in water and is considered rapidly biodegradable (although along with other ethers and glycols, the results will depend on the type of method performed). A hydrolysis study has been performed and although apparently stable under environmental conditions, ethers will hydrolyse under gastric conditions to corresponding alcohols and aldehydes.

In view of the metabolic route being to tetrahydrofurfuryl alcohol (plus acetylaldehyde) and then on to hydroxybutanoic acid, date from these metabolites can be used to assess the potential toxicity of the ether.

Main ADME results

Main ADME results 1

Type:

absorption

Results:

Yes, oral

Main ADME results 2

Type:

distribution

Results:

Yes, target organs identified

Main ADME results 3

Type:

metabolism

Results:

Yes, key metabolites estimated

Main ADME results 4

Type:

excretion

Results:

No evidence of excretion, but metabolism is to substances found in nature

Toxicokinetic / pharmacokinetic studies

Details on absorption:

There was evidence of systemic effects reported for oral toxicity studies, with the repeat oral study and reproduction toxicity screening tests showing adverse effects at higher dose levels. Effects for both the ethyl ether and the alcohol include effects on liver function and organ weights, including testes.

There is no evidence of absorption following dermal or inhalation exposure, but in view of the low molecular weight, polarity and similarity to other ethers and alcohols, dermal absorption is considered likely.

Details on distribution in tissues:

The impact on organs following oral ingestion and changes in chemistry parameters confirms distribution to key organs, even though some of the reported changes are possibly adaptive (ie metabolic processes) and not toxic adverse effects.

The low molecular weight and solubility in biological media would suggest transport of the substance and primary metabolites.

Details on excretion:

There is limited evidence that furans and linear ethers are directly excreted, but in view of the potentially rapid metabolism to substances found naturally in the body, it is not expected that there will be excretion of the substance itself.

The ultimate metabolisms is to water and carbon dioxide that are excreted as part of natural biological systems.

Metabolite characterisation studies

Metabolites identified:

yes

Details on metabolites:

Furans and linear ethers are well document for metabolic processes in biotic and in acidic media. The route of metabolism is illustrated below.

This route of degradation is the basis for validating the read-across between the ethyl ether and alcohol. Although the impact of acetaldehyde cannot be ignored, the reaction kinetics is thought to result in further degradation to acetate at a sufficiently high rate to ensure low levels of acetaldehyde. However, the slight, but significant, mutagenic potential from in-vitro gene mutation testing is consistent with low levels of acetaldehyde and furan.

In human metabolism, acetaldehyde forms naturally as part of the metabolism of ethanol.

Applicant's summary and conclusion

Conclusions:

Considered to be readily adsorbed and metabolised to alcohols, aldhehydes and acid salts.