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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

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:
2007

Materials and methods

Principles of method if other than guideline:
Review of reports summarised in the dataset

Test material

Constituent 1
Chemical structure
Reference substance name:
Propane-1,2-diol, propoxylated
EC Number:
500-039-8
EC Name:
Propane-1,2-diol, propoxylated
Cas Number:
25322-69-4
Molecular formula:
(C3 H6 O)n H2 O n= >1 - <4.5
IUPAC Name:
propane-1,2-diol, propoxylated

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:
Given the low vapour pressure, it is unlikely that inhalation of the vapour will occur.
Propane-1, 2-diol, propoxylated, 1-4.5 mol (the NLP polyol) contains very little material of the molecular size that may result in significant lymphatic
absorption. Thus the principal mechanism of absorption for these NLP polyols is passive diffusion. Given that the trimer (propane-1,2-diol + 2PO) iswell absorbed, the molecule representing the mean toxicity is probably also absorbed when administered orally.
Given the logP and the fact that propane-1,2-diol can be absorbed when coadministered with oleic acid it is likely that the oligomers are absorbed dermally.
Details on distribution in tissues:
Given the logP values, it is likely that oligomers of propane-1,2-diol will be widely distributed in body water and it is unlikely that they will accumulate in tissues.
Details on excretion:
In rat, some higher molecular weight material may be excreted in bile. In rat the molecular weight threshold for biliary excretion is around 350 Daltons and some material from the highest no longer polymers may just exceed this threshold. In humans the threshold is about 500 (Illing, 1989), thus it would be expected that little, if any, of the NLP polymer would be excreted in human bile. Once the material has been hydrolysed, the products below the appropriate threshold will appear in urine, except when the end point of the product is carbon dioxide. Carbon dioxide will be exhaled.

Metabolite characterisation studies

Details on metabolites:
Based on the information on the repeating unit and trimer, it is likely that the oligomers will be stepwise hydrolysed across the ether linkage and the three carbon elements metabolised to lactic acid/pyruvic acid and taken into intermediary metabolism.

Any other information on results incl. tables

Propane-1, 2-diol is both a core substance (initiator) and a repeating unit. For this particular polyol toxicokinetic information is available for one of the low molecular weight oligomers as well as the core substance/repeating unit. The information on the toxicokinetics of propane-1, 2-diol, propoxylated, 1-4.5 mol (the NLP polyol) is based on the information for propane-1,2-diol and its dimer (1 mol propoxylated propane-1,2-diol) and trimer (2 mol propoxylated propane-1,2-diol). Propane-1,2-diol has two hydroxy groups, thus oligomers are considered to be core substances with chains of between one and three repeating units. Commercial material contains a range of propoxylated propanediols.

At the molecular weight range of the NLP polyol (and up to the pentamer) the postulated mechanism for absorption is passive diffusion. At Mn >400 the facilitated diffusion mechanism probably applies, thus the calculated value for bioavailability of the hexamer, based on passive diffusion, is probably low. It would be inappropriate to calculate values for higher oligomers.

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 58 Daltons. The combined effect of these changes is to reduce the bioavailability by a factor of 1.53 (calculated using the Potts and Guy equation). The substitution of a hydroxyl group on a core compound by an ethoxyl- group decreases its logP value by 0.083 units and increases its molecular weight by 44 Daltons. The effect of these changes is to reduce the bioavailability by a factor of about 2.12. Thus the molecular weight changes are more significant than the logP changes in determining the bioavailability.

Applicant's summary and conclusion