Registration Dossier

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:
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 findings from reports summarised in the dataset.

Test material

Reference
Name:
Unnamed
Type:
Constituent

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:
Given the vapour pressure and water solubility of the commercial NLP polyol, it is likely that some absorption of the lower molecular weight material will occur in the lung. Absorption of propoxylated nitrilotriethanol is likely when administered orally. Nitrilotriethanol is absorbed, probably by passive diffusion rather than active transport. Propane-1,2-diol and [(methylethylene)bis(oxy)]dipropanol (and, presumably, oxydipropanol) are also absorbed, probably by passive diffusion, when administered orally. Thus it is probable that oligomers may be absorbed, probably by passive diffusion.
Nitrilotriethanol is also absorbed when administered dermally, thus it is possible that propoxylated nitrilotriethanol may also be absorbed by the
dermal route.
Details on distribution in tissues:
Given the logP values, it is likely that any absorbed oligomers of propoxylated nitrilotriethanol will be widely distributed in body water and 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. The material most likely to be absorbed is likely to be hydrolysed and the products appear in urine, except when the end point of metabolism is carbon dioxide. Carbon dioxide will be exhaled. If the hydrolysis is taken to completion, the nitrilotriethanol is likely to be excreted in urine, probably without further metabolism.

Metabolite characterisation studies

Details on metabolites:
Based on information from the propane-1,2-diol and trimer [(Methylethylene)bis(oxy)]dipropanol, if absorbed, the propane-1,2-diol moiety
of the propoxylated nitrilotriethanol could be further conjugated (with glucuronic acid or sulphate) or stepwise hydrolysed. Propane-1,2-diol is also
further metabolised, entering intermediary metabolism via lactic acid/pyruvic acid, and eventually being eliminated as carbon dioxide. If nitrilotriethanol is released, it is unlikely to be further metabolised.

Any other information on results incl. tables

There are no experimental studies on the toxicokinetics of propoxylated nitrilotriethanol. The toxicokinetics of propoxylated nitrilotriethanol is inferred from the core substance and propane-1,2-diol, oxydipropanol and [(methylethylene)bis(oxy)]dipropanol. Nitrilotriethanol has three hydroxy groups, thus NLP polyols are likely to consist predominantly of chains of between one and two propoxyl groups, with some chains containing three.

Applicant's summary and conclusion