Ethyl decanoate

Endpoint summary

Description of key information

Based on the read across category conducted in order to provide information on the test substance ethyl decanoate, it was stated that the source substances are not considered to be bioaccumulable. Hence, according to similar physico-chemical pattern between source and target substances, ethyl decanoate followed the same toxicokinetic behavior and is considered as not bioaccumulable.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

Similar toxicokinetic behavior

The fatty acid esters of the LCAE C8-C18 category are considered to undergo hydrolysis in the gastrointestinal (GI) tract by ubiquitous expressed GI enzymes (Lehninger, 1970; Mattson and Volpenhein, 1972). The breakdown products of ester hydrolysis are free alcohols and the respective free fatty acids with carbon chain length from C8-C18, mainly satured but also unsatured. Due to their physical-chemical properties, the main route of exposure of the fatty acid esters of the category is via the oral route.

o       Absorption

The absorbed esters undergo stepwise chemical changes in the gastrointestinal fluids as a result of enzymatic hydrolysis. The respective alcohols as well as the fatty acid are formed (Mattson and Volpenhein, 1972). For both cleavage products absorption will occur in the gastrointestinal tract:  The highly lipophilic fatty acid is absorbed by micellar solubilization (Ramirez et al. 2001), soluble alcohol are dissolved in pancreatic juice and the ester can be distributed.

Dermal absorption:

According to the current literature, esterase enzymes were present into the skin of different mammalian species (as human, rodents or minipigs). These enzymes, as carboxylesterase, hydrolyzed different substrates as xenobiotic or different ester as fatty acids esters (C. Jewell, 2007; J.J. Prusakiewicz, 2006). Based on this principle, when applied on skin, the source and the target substances are expected to be substrates of these carboxylesterase. They are hydrolyzed into fatty acids and alcohols. In the case that the products of hydrolysis could across the dermal barrier to reach systemic system, they have the same behavior as oral ingestion. The potential toxicity should be bring by these hydrolyzed products.

o       Distribution

The alcohol components have low molecular weights (46.06 to 131.02 g/mol) and high water solubility (except for hexanol which is insoluble) and will therefore be widely distributed within the body (ECHA, 2008; HSDB, 2011; Amidon GL, 1974 citated in HSDB).

The high log Pow value of the category members implies that they have the potential to accumulate in adipose tissue. However, as they undergo esterase-catalysed hydrolysis, the accumulation of the cleavage products has to be considered. Substances with high water solubility, like the alcohols, do not have the potential to accumulate in adipose tissue due to their low log Pow. In contrast, accumulation of the fatty acids in triglycerides in adipose tissue or the incorporation into cell membranes is possible. Overall, the available information that they were required as energy source, indicates that no significant bioaccumulation in adipose tissue is anticipated.

o       Metabolisation

Esters of fatty acids are hydrolysed to the corresponding alcohol and fatty acid by esterases (Fukami and Yokpo, 2012). Depending on the route of exposure, esterase-catalysed hydrolysis takes place in different places in the organism: after oral ingestion, esters of alcohol and fatty acids undergo enzymatic hydrolysis already in gastro instestinal fluids. In contract, substances that are absorbed through the pulmonary alveolar membrane or through the skin enter the systemic circulation directly before joining the liver where hydrolysis basically takes place. The first cleavage product, the alcohol, is oxidized in several steps by the nonspecific alcohol dehydrogenase and the aldehyde dehydrogenase to the corresponding aldehyde and alcohol. Glucuronidation will also take place at all steps to facilitate urinary excretion (HSDB, 2011). The second cleavage product, the fatty acid, is stepwise degraded by beta-oxydation based on enzymatic removal of C2 units in the matrix of mitochondria in most vertebrate tissues. The C2 units are cleaved as acyl-CoA, the entry molecular of citric acid cycle. The omega- and alpha-oxydation, alternative pathways for oxidation can be found in the liver and the brain, respectively.

Based on the metabolism described, the fatty acids esters and the breakdown products will be metabolised in the body in high extent. The fatty acid components will be metabolized for energy generation or stored as lipid in adipose tissue or used for further physiological properties as incorporation in lipid cell membranes (Lehninger 1970; Stryer 1994).

o       Excretion

The fatty acid component are not expected to be excreted to a significant degree via urine or faeces but excreted via exhaled air as CO2 or stored. The second route of excretion is expected to be by biliary excretion within the faeces. For the alcohol, the main route is renal excretion via the urine due to the low molecular weight and the high water solubility (HSDB, 2011)