1-(vinyloxy)octadecane

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

other: Expert statement

Adequacy of study:

key study

Study period:

2013-02-07

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Expert statement in the absence of toxicokinetic studies.

Data source

Reference

Reference Type:

other: Expert statement

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Objective of study:

toxicokinetics

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Expert statement

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

1-(vinyloxy)octadecane

EC Number:

213-208-3

EC Name:

1-(vinyloxy)octadecane

Cas Number:

930-02-9

Molecular formula:

C20H40O

IUPAC Name:

1-(ethenyloxy)octadecane

Test material form:

other: liquid

Test animals

Species:

other: Expert statement

Strain:

other: Expert statement

Details on test animals or test system and environmental conditions:

Not applicable.

Administration / exposure

Route of administration:

other: Expert statement

Vehicle:

other: Expert statement

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

Preliminary studies:

Not applicable.

Toxicokinetic / pharmacokinetic studies

Details on absorption:

Generally, absorption of 1-(vinyloxy)octadecane is limited by its high lipophilicity (log Pow >8) and its low water solubility. However, pathological and histopathological findings in the liver after repeated oral administration indicate that the compound becomes bioavailable to a certain extend. Both, passive diffusion and/or active transport through the cell membrane are considered to be possible mechanisms of absorption from the gastrointestinal tract.
The test item is solidified at room temperature and the vapour pressure of the test item at 25 °C is estimated to be low. Therefore, inhalation of dust or vapour is unlikely. However, if the test item becomes available for inhalation, the test item might be taken up by micellular solubilisation to a certain extend.
Both, uptake of 1-(vinyloxy)octadecane into the stratum corneum and partition from the stratum corneum into the epidermis is limited by the high log Pow value and the low water solubility, respectively. Thus, absorption across the skin is estimated to be low. However, since the available LLNA revealed a skin sensitising effect, the substance has to penetrate the skin to a certain extend. These results indicate skin penetration after dermal application.

Details on distribution in tissues:

The test substance might distribute into the cells and intracellular concentration might be higher than extracellular concentration particularly in fatty tissues due to the high log Pow value. In the available repeated dose toxicity studies the liver was identified as a target organ.
Based on the high log Pow value bioaccumulation of the test substance cannot be excluded but is expected to be limited due to the presumed metabolism.

Details on excretion:

Potential metabolites of 1-(vinyloxy)octadecane described above are estimated to be oxidised to carbon dioxide within the TCA pathway and are therefore expected to be excreted via exhalation. In case of the unchanged test substance biliary excretion is expected due to the molecular weight (~ 300 g/mol) and the low water solubility.

Metabolite characterisation studies

Details on metabolites:

The test substance might be hydrolysed by formation of acetaldehyde and octadecanol. Further oxidation could result in acetic acid and octadecanal, subsequently oxidised to octadecanoic acid which in turn may enter the mitochondrial β-oxidation pathway followed by the citric acid cycle (TCA) pathway.
There are no indications of genotoxicity of the test item and its metabolites from the present Ames and cytogenetic test (BASF, 1989, 2012), and several mutation assays in mammalian cells with three different structure analogues of the test substance (BASF, 1992, 1998, 2010). Thus, 1-(vinyloxy)octadecane and its metabolites are expected not to be genotoxic and metabolic activation is unlikely to occur.

Bioaccessibility (or Bioavailability)

Bioaccessibility (or Bioavailability) testing results:

Based on the results of acute and repeated dose toxicity studies as well as on the structure, the molecular weight and the phys./chem. properties, the test substance can be considered to be bioavailable via oral, dermal and possibly also via inhalation route.