Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics
Type of information:
other: figure on metabolism
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Figure on metabolism of SCAE methyl esters

Data source

Reference
Reference Type:
other: figure
Title:
Figure on the metabolism of short chain fatty acid methyl esters
Author:
Dr. KNOELL CONSULT GmbH
Year:
2010
Report Date:
2010

Materials and methods

Results and discussion

Any other information on results incl. tables

Metabolism of short chain fatty acid methyl esters:

Figure a) Hydrolysis:

Esters of methanol and fatty acids have a common metabolic fate that involves hydrolysis to the carboxylic (e.g. fatty) acids and methanol.

Figure b) Metabolism of methanol:

Methanol is polar/hydrophilic (log KOW < -0.5) and thus distributed in the aqueous compartments of the organism. However, direct urinary excretion is known to be low (<3% in humans); unchanged methanol is excreted to some extent via exhalation.

Predominating is the metabolism of methanol: initially, methanol is slowly oxidized by the enzyme alcohol dehydrogenase (ADH) to formaldehyde, which itself is oxidized very rapidly by the aldehyde dehydrogenase (ALDH) to formic acid. Finally, formic acid is slowly metabolised to CO2and H2O (metabolism using tetrahydrofolic acid in humans; see Figure 1). These are excreted via exhalation and urinary excretion as predominant excretion way; urinary excretion of formaldehyde and formic acid is possible to a low extent.

Figure c) Metabolism of fatty acids

Linear carboxylic acids feed into physiological pathways like the citric acid cycle, sugar synthesis, and lipid synthesis. The metabolic pathway of unsaturated fatty acids differs from that of saturated fatty acids in an additional step for rearrangement of the double bond (isomerisation cis → trans) leading to the correct trans-intermediate for β-Oxidation.

Applicant's summary and conclusion