Reaction product with n-butanol of high-boiling stream resulting from the hydroxylation, oxidative cleavage and hydrolysis of vegetable oil saturated and unsaturated C16-C22 triglycerides.

Endpoint summary

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

Basic toxicokinetics

A number of publications are available from the 1950-1960s in which the fat digestion and absorption processes are examined. These publications are added to the FAV-ES dossier as they are carried out using some of the substances identified as source substances for the read-across. The findings of these toxicokinetic experiments are summarized below. They have contributed to the current knowledge of the physiological processes involved in digestion and absorption of lipids. Due to the functional similarity between the constituens of FAV-ES and the examined substances, it can reasonably be assumed that the same metabolic pathways apply to FAV-ES.

 

Metabolism through lipase activity

 

The activity of pancreatic and other lipases towards the hydrolysis of different types of triglycerides has been studied. Cohen et al. compared the properties of gastric lipase with those of duodenal lipases (Cohen, 1971) in an in vitro experiment with human gastric and duodenal juices. The authors demonstrated that the pancreatic (duodenal) lipase was in general more active than the gastric lipase. Furthermore, it was shown that both the gastric and the duodenal (pancreatic) lipase are able to hydrolyse the medium chain triglycerides, whereas the long chain triglycerides are only hydrolysed by the pancreatic lipase.

 

Mattson and Volpenheim studied the in vitro hydrolysis of esters of fatty acids and primary n-alcohols of different chain length (Mattson and Volpenheim, 1969). In this in vitro experiment, the test substrate was added to a digestion mixture containing pancreatic lipase. The substrates involved in the test included inter alia esters of n-butanol with fatty acids with a varying chain length of C3 to C16, and C18:1. Under the conditions of the test, all n-butanol fatty acid esters were found to undergo hydrolysis.

 

Absorption of lipid digestion products

 

In 1951, Borgström examined the mechanism of intestinal fat absorption (Borgström, 1951). It was found that after absorption, the lipids are transported via the lymphatic channels. The lymph does not contain free fatty acids. The author concluded that triglycerides might be completely hydrolysed in the intestinal lumen and then resynthesized in the intestinal wall.

 

In an other experiment, Mattson and Volpenheim compared the composition of administered triglycerides with the composition of the triglycerides that were collected from the lymph fluid of rats (Mattson and Volpenheim, 1961). The study confirmed that the triglycerides were hydrolysed and re-synthesized during the metabolic processes involved in lipid digestion. Furthermore, it was observed that absorption of fatty acids was greater when the rats were dosed with triglycerides, and lower when the animals received the free fatty acid.

Dermal absorption

The main factors determining the extent to which a substance may be absorbed following exposure via the dermal route are the vapour pressure, the log Kow and the water solubility.

 

Substances having a high vapour pressure will evaporate from the skin before absorption occurs. However, the target substances in FAV-ES all have a low vapour pressure, so if exposure to the skin occurs, the product will not be removed due to evaporation.

 

The parameters water solubility and log Kow have to be considered together. Indeed, in order to be absorbed via the skin, a substance needs to be sufficiently lipophilic (log Kow > 4) to enable penetration into the stratum corneum, but at the same time, it needs to have a sufficiently high water solubility (≥1 mg/L) to partition from the stratum corneum into the epidermis. The target substances in FAV-ES all have log Kow values that are sufficiently high to enable the uptake of the substances into the stratum corneum, but as the water solubility of the target substances is very low (10^-1-10^-21mg/L), partitioning from the stratum corneum into the epidermis is hampered.

 

As a consequence, uptake of the FAV-ES constituents following dermal exposure is likely to be low.