Reaction products of fatty acids, tall oil and fatty acids, C18 unsaturated, trimers and fatty acids, C18 unsaturated, dimers with (9Z)-octadec-9-en-1-amine

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Fatty acids, C18 -unstad., trimers (CAS 68937 -90 -6), fatty acids, tall-oil

Several studies exist, which compared absorption of monomeric and dimeric fatty acids and their oxidized forms. Nonpolar fatty acid monomers (from olive oil) show high digestibility (94.8% on average). Oxidized fatty acid monomers from heated olive oil have an apparent average absorption of 76.7%. Nonpolar dimers have the lowest average digestibility (10.9%), while oxidized dimers and polymers have higher apparent absorbability, ranging from 22.7% to 49.6% ( Márquez-Ruiz, G. et al., The journal of the American Oil Chemists' Society, 69(9):930-934 (1992)). So relatively low oral uptake is also expected for fatty acids, C18 -unsatdt., trimers. The main component of fatty acids, tall-oil is oleic acid, which is also contained to app. 70% in the above tested fatty acid monomers generated from olive oil. Thus it will be almost completely absorbed.

In studies comparing dermal absorption depending on fatty acid chain length, absorption decreased with increasing chain length. For C16 and C18 monomers a maximum of 0.3% was detected (see REACH registration dossier for CAS 68937 -90 -6). This result fits to the high molecular weight (app. 800g/mol) of the fatty acid, C18 unsatd., trimers, and that both fatty acids are insoluble in water.

Fatty acids are generally ingested as triglycerides, which cannot be absorbed by the small intestine. When ingested, monoglycerides are readily absorbed through the duodenal mucosa and converted to triglycerides. In the small intestine, most triglycerides are split by pancreatic lipases into monoglycerides, free fatty acids, and glycerol, which can be absorbed by the intestinal mucosa. A small fraction of triglycerides are absorbed as free glycerol and as diglycerides. Once across the intestinal barrier, triglycerides are reformed. These resynthesized triglycerides collect into globules along with cholesterol and phospholipids and are encased in a protein coat as chylomicrons. Chylomicrons are transported in the lymph to the thoracic duct and eventually to the venous system. The chylomicrons are removed from the blood as they pass through the capillaries of adipose tissue. Fat is stored in adipose cells until it is transported to other tissues as free fatty acids which are used for cellular energy or incorporated into cell membranes.

Oleylamine (CAS 112 -90 -3)

No data exist on the oral absorption of primary alky amines. Due to the high log PoW value (7 -8), the substance will be taken up by micellular solubilisation into the lymphoid system, which might limit gastro-intestinal uptake. Based on the toxicity observed after oral exposure, 100% absorption is assumed as a worst case approach, even though local irritation might account for most of the effects.

In a study with a related compound, 1 -dodecyl amine, dermal absorption of 28% to 57% (using a concentration of 5% and 0.5%, respectively) was measured. This is considered a worst case estimate, since absorption was probably increased due to skin damage.

In vivo, aliphatic amines are expected to be oxidized by the monoamine oxidase to the corresponding aldehyde, which undergoes subsequent oxidization to the carboxylic acid. Ultimately, carbon dioxide is formed via ß-oxidation (Blaschko, 1952). This is confirmed by data for two other primary amines, octanamine and decanamine. In mice, 95% of the radioactive labelled octanamine was present in blood as non-amine metabolites already five minutes after injection into the tail vein. 25% of these metabolites were identified as carbon dioxide. Almost half of the generated carbon dioxide was exhaled in the first 20 minutes. Metabolism of decanamine was comparable, but slower. Data were similar for rabbits and humans. It is thus assumed that all primary alkylamines including oleylamine are efficiently transformed into ammonia and carbon dioxide.

Reaction mass of Fatty acids, tall-oil, compds. with oleylamine and Fatty acids, C18-unsatd., trimers, compds. with oleylamine

Based on the data above and some effects on the gastro-intestinal tract after acute oral exposure, oral absorption is assumed to be 100%, except for the non-hazardous fatty acid, C18 -unsatd., trimers component. Because the test substance is very lipophilic (log Pow >4.9) and has a high molecular weight of app. 1650g/mol, dermal absorption is expected to be low. In addition, dermal absorption was already very limited for the components mentioned above, for which skin damage probably played an essential part in the absorption observed. Because the reaction mass of fatty acids, tall-oil, compds. with oleylamine and fatty acids, C18 -unsatd., trimers, compds. with oleylamine is only irritant to the skin, absorption will be increased to a lesser extent as was the case for the corrosive primary alkyl amines.Thus 25% absorption through the skin was assumed. Due to the very low vapour pressure of 0.0001Pa, exposure via inhalation is not considered relevant.

Blaschko, H. (1952). Amine oxidase and amine metabolism.Pharmacol. Rev. 4, S. 415 - 458