Fatty acids, C16-18, esters with pentaerythritol

Endpoint summary

Additional information

Absorption, Distribution, Biotransformation and Excretion:

There are no quantitative data on the uptake of Fatty Acid Polyol Esters. Low amounts can be absorbed via oral, respiratory, and dermal routes of exposure. Due to the uses stated in chapter 3, dermal as well as inhalative exposure is possible for workers as well as for the general public during certain industrial, professional and consumer applications. The inhalative and dermal availability is limited by the physicochemical properties of fatty acid polyols, which generally have a poor water solubility, a log K_ow>4 and a relatively high molecular weight. The inhalative availability is furthermore reduced by the low vapour pressure of <0.01 Pa. The formation of vapour can therefore be excluded but nevertheless, due to spray-applications, aerosol-formation is possible.

The absorbability of esterified alcohols containing one to eight ester groups given orally have been studied and there was little difference for polyol esters up to four ester groups. Esters of polyols (pentaerythritol, dipentaerythritol and 1,1,1-trimethylolpropane) have a common metabolic fate that involves stepwise hydrolysis to the carboxylic (e.g. fatty) acids and their polyols (pentaerythritol, dipentaerythritol or trimethylolpropane), respectively. This is supported by the action of ubiquitously distributed unspecific esterases and by site-specific and non-specific gastrointestinal lipases so only low and transient exposure to the parent compound is expected.

Straight-chain fatty acids are normal dietary constituents and ubiquitous substrates for energy production by physiological pathways like the citric acid cycle, sugar synthesis, and lipid synthesis. Medium-chain fatty acids (MCFA) are readily absorbed from the small intestine directly into the bloodstream and transported to the liver for hepatic metabolism, while long-chain fatty acids (LCFA) are less readily absorbed, are incorporated into chylomicrons and enter the lymphatic system. It has been noted by several investigators that increasing fatty acid chain length slightly decreased their digestibility. MCFA are readily broken down to carbon dioxide and two-carbon fragments, while LCFA are re-esterified to triacylglycerols and either metabolized for energy or stored in adipose tissue. The natural occurence of fatty acids and their specific metabolic fate imply that the exposure to small amounts is not a risk factor for human beings.

The polyols are very polar (log Kow<-2) and do not accumulate in the body but are readily excreted via urine. Alternatively, one or several hydroxyl groups can be oxidized to a carboxylic acid moiety prior to urinary excretion.

There are sufficient toxicity data for both the resulting fatty acids and the alcohol component, showing that the metabolites have little or no potential to cause toxic effects.