Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Study period:
not applicable
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The metabolism of fatty acids and their methyl esters are well documented in the scientific literature

Data source

Reference
Reference Type:
grey literature
Title:
Summary of fatty acid methyl ester metabolism
Author:
Strother DE
Year:
2012
Bibliographic source:
unpublished

Materials and methods

Principles of method if other than guideline:
Summary of fatty acid methyl ester metabolism

Test material

Reference
Name:
Unnamed
Type:
Constituent

Results and discussion

Any other information on results incl. tables

Metabolism of short chain fatty acid methyl esters

Hydrolysis

Esters of methanol and fatty acids have a common metabolic fate that begins with hydrolysis (both enzymatic and non-enzymatic), resulting in the carboxylic (e.g. fatty) acids and methanol.

Metabolism of methanol

Methanol is polar/hydrophilic (log P < -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 to formaldehyde, which itself is oxidized very rapidly by the aldehyde dehydrogenase and other enzymes to formic acid. Finally, formic acid is metabolized to CO2and H2Oby means of a folate-dependent one-carbon pool pathway.The rate of formate oxidation is regulated by the hepatic concentrations of tetrahydrofolate.CO2and H2O are excreted via exhalation and urinary excretion; urinary excretion of formaldehyde and formic acid is possible to a limited extent.

The rate of methanol metabolism is independent of the plasma concentration, is slow, and is approximately one-seventh that of ethanol. Complete oxidation and excretion of methanol can require several days.

Metabolism of fatty acids

Fatty acids are an important source of energy and adenosine triphosphate (ATP) for many cellular organisms. Linear fatty 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 that it contains an additional step for rearrangement of the double bond (isomerisation cis → trans) leading to the correct trans-intermediate for β-Oxidation.

Fatty acid metabolism involves three major steps:

1.     

2.     

3.     

 

Fatty acids are transported across the outer mitochondrial membrane by carnitine-palmitoyl transferase I (CPT-I), and then couriered across the inner mitochondrial membrane by carnitine. Once inside the mitochondrial matrix, the fatty acyl-carnitine reacts with coenzyme A to release the fatty acid and produce acetyl-CoA. CPT-I is believed to be the rate-limiting step in fatty acid oxidation.

 

Once inside the mitochondrial matrix, fatty acids undergo β-oxidation. During this process, two-carbon molecules acetyl-CoA are repeatedly cleaved from the fatty acid. Acetyl-CoA can then enter the citric acid cycle, which produces NADH and FADH2. NADH and FADH2 are subsequently used in the electron transport chain to produce ATP, the energy currency of the cell.

 

Besides β-oxidation, other oxidative pathways are sometimes employed. The smooth ER of the liver can perform ω-oxidation, which is primarily for detoxification but can become much more prevalent in cases of defective β-oxidation. Fatty acids with very long chains (20 or more carbons) are first broken down to a manageable size in peroxisomes.

Applicant's summary and conclusion

Conclusions:
No bioaccumulation potential based on study results
Executive summary:

9-decenoic acid, methyl ester is a fatty acid methyl ester. Metabolism of short chain fatty acid methyl esters begins with hydrolysis of the ester, resulting inthe carboxylic (e.g. fatty) acids and methanol. Methanol is oxidized to formaldehyde, which itself is oxidized to formic acid. Finally, formic acid is metabolized to CO2and H2O. Fatty acids are an important source of energy and adenosine triphosphate (ATP) for many cellular organisms.Fatty acids undergo β-oxidation, and the products enterphysiological pathways like the citric acid cycle, sugar synthesis, and lipid synthesis.