Ethane- 1,2-diol, propoxylated

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

other: Assessment of the toxicokinetic behaviour as can be derived from the available information.

Adequacy of study:

weight of evidence

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Principles of method if other than guideline:

Review of reports summarised in the dataset

Test material

Test material information

Constituent 1

Reference substance name:

Ethane- 1,2-diol, propoxylated

EC Number:

500-078-0

EC Name:

Ethane- 1,2-diol, propoxylated

Cas Number:

31923-84-9

Molecular formula:

HO(C3H6O)nC2H4(C3H6)nOH sum of n: >1 - <4.5 mol PO

IUPAC Name:

Ethane-1,2-diol, propoxylated

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

"Given the vapour pressure and water solubility of the commercial preparation, it is likely that absorption of some of the lower molecular weight components may occur via the lung.

Ethane1,2-diol, oxydiethanol, 2,2’-(ethylenedioxy)diethanol, propane-1,2-diol, oxydipropanol and [(methylethylene)bis(oxy)]dipropanol are absorbed, probably by passive diffusion, when administered orally. Thus it is probable that low number oligomers will be absorbed. The calculated logP suggests that the component representing the mean toxicity of the commercial preparation is likely to be absorbed orally."

Details on distribution in tissues:

"Given the logP values, it is likely that any absorbed oligomers of propoxylated etahne-1,2-diol or 2,2’-oxydiethanol will be widely distributed in the body. As metabolism is likely, it is unlikely that they will accumulate in tissues."

Details on excretion:

"In the event that higher molecular weight material is absorbed, it is likely to be excreted in bile. Lower molecular weight unmetabolised oligomer is likely to be excreted in urine. In rat the molecular weight threshold for biliary excretion is around 350, in human it is about 500 (Illing, 1989). The material most likely to be absorbed is likely to be hydrolysed and the products appear in urine. Some carbon dioxide might be formed from hydrolysis of the propane-1,2-diol groups and exhaled."

Metabolite characterisation studies

Details on metabolites:

"Based on information from ethane-1,2-diol, oxydiethanol, and (ethylenedioxy)diethanol, propane-1,2-diol, oxydipropanol and [(methylethylene)bis(oxy)]dipropanol it is likely some material may be hydrolysed, some oxidation of one or both of the terminal alcohol groups to the corresponding mono and di-carboxylic acids may occure or, possibly some conjugation of the terminal alcohol groups with glucuronic acid and/or sulphate may also be possible. At low doses some further metabolism to carbon dioxide may occur."

Any other information on results incl. tables

"ETHANE-1,2-DIOL, PROPOXYLATED, 1-4.5 MOL PROPOXYLATED (CAS31923-84-9; EU NLP 500-078-0)AND2,2’-OXYDIETHANOL, PROPOXYLATED, 1-4.5 MOL PROPOXYLATED (CAS9051-51-8; EU NLP 500-031-4)

 

 

These two core substances are so closely related structurally that they are best examined together.

 

There are no experimental studies on the toxicokinetics of propoxylated ethane-1,2-diol or propoxylated 2,2’-oxydiethanol. The toxicokinetics of the core substances and the repeating unit are summarised in Illing and Barratt (2007 revised 2009). Both core substances have two free hydroxy groups, thus NLP polyols are likely to consist predominantly of chains of between one and two repeating units, with some chains containing three repeating units.

 

For the calculations of bioavailability of the commercial NLP polyol, logP values were calculated using the incremental fragment method of Suzuki and Kudo (1990). The propoxy groups have an important effect on the toxicity by modulating any toxicity arising from the core substance. The substitution of a hydroxyl group on a core compound by a propoxy group increases its logP value by 0.24 units and its molecular weight by 58Daltons. The combined effect of these changes is to reduce the bioavailability by a factor of 1.53 (calculated using the Potts and Guy equation). MEG + 3PO indicates the component representing the mean toxicity."