Glycerides, C16-18

Endpoint summary

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

‘Glycerides, C16-18 (SDA Reporting Number: 19-001-00)’ is composed mainly of triglycerides containing a glycerol backbone esterified to linear fatty acids with a carbon chain length of C16-18. The other known constituents are mono- and di-glycerides as well as fatty acids. The toxicokinetics of glycerides and fatty acids are well known as a result of their widespread use in nutritional (food and feed), cosmetic and industrial applications for example.

When taken up orally, triglycerides are split in the intestinal lumen into glycerol and fatty acids with the help of lipases and bile secretions (in a process called lipolysis), then move into the cells lining the intestines (absorptive enterocytes). The triglycerides are rebuilt in the enterocytes from their fragments and packaged together with cholesterol and proteins to form chylomicrons. These are excreted from the cells, collected by the lymph system and transported to the large vessels near the heart before entering the blood. Various tissues can capture the chylomicrons, releasing the triglycerides to be used as a source of energy. When the body requires fatty acids as a source of energy, the hormone glucagon signals the breakdown of the triglycerides by hormone-sensitive lipases to release free fatty acids from the adipose cells (fat cells), the major site of triglyceride accumulation. The fatty acids are then broken down by stepwise elimination of C2-units in the mitochondrial β-oxidation. The C2-units are esterified to acetyl-Coenzyme A which directly enters the citric acid cycle where it is converted to carbon dioxide and energy.

In general, the extent of absorption of triglycerides in the gastro-intestinal system varies depending on the chain length of the fatty acids and their degree of saturation. The long-chain fatty acids are lesser absorbed than the short chain counterparts and it further decreases with increasing saturation.

No experimental studies were located for absorption through the dermal route. However,as per Section R.7.12.2.1 of REACH guidance document R7.C (May 2008),the extent of dermal absorption may be predicted based on physico-chemical properties, including:

-        Water solubility

-        Partition coefficient

-        Molecular weight / triglyceride chain length (inversely proportional)

‘Glycerides, C16-18 (SDA Reporting Number: 19-001-00) ’is poorly water soluble (< 10 mg/L), has an estimated log Pow > 6 and a molecular weight range > 500(see Sections 1.3 and 4). As such,uptake into thestratum corneumof skin and further transfer into the epidermis are likely to be low. A default dermal penetration value of 10% can be assumed (REACH guidance document R7.C (May 2008)).

 

Exposure via the inhalation route is not expected given the physical state(solid under environmental conditions)  and low vapour pressure(< 1.33 x 10^-8Pa at 20°C) of ‘glycerides, C16-18 (SDA Reporting Number: 19-001-00)’. In many cases the substance is used in industrial applications and transported and handled in liquid form (heated). If the substance is handled in powder form, sprayed or otherwise finely dispersed in the air, the use of appropriate risk management measures (e.g. filter mask) is recommended.

Weight of evidence from in vivo studies:

The oral absorption of the constituent 'glycerides, C16 -18' (as fully hydrogenated soybean oil) was measured in a 15 d feeding study by analysis of fecal unabsorbed fat. Diet containing 15% of the constituent was fed to 10 Sprague-Dawley rats/sex for 15 d. Control group was fed with 15% soybean oil for same duration. Feces were collected for the final 10 d, and analysed for unabsorbed fat. Low absorption was observed for the test substance (6±4% ) compared to soybean oil (94±2%). Under the test conditions, the constituent was poorly absorbed after dietary administration in rats (Nolen 1981).

The oral absorption of 'glycerides, C16 -18' (as fully hydrogenated soybean oil) was measured in a 91 day oral toxicity study by analysis of unabsorbed fecal fat. Diet containing 7.5% of the test substance (plus 11.5% soybean oil as normal fat source) was fed to 20 Sprague-Dawley rats/sex for 91 days. Control group was fed with 19% soybean oil for same duration. During the 3rd and 11th weeks of study, feces were collected from 10 animals/sex/group for analysis of unabsorbed fat. Low absorption (17%) was observed for the substance in comparison to soybean oil. Under the test conditions, the test substance was poorly absorbed after dietary administration in rats (Nolen, 1981).

The absorption of the constituent 'glycerides, C8-18 and C18-unsatd.' (as coconut oil) was determined in a 47 week repeated dose study in rats. The substance was included at 18.5% level in diets of 15 wistar rats/sex/group for 47 weeks. Additional 2.5% safflower oil was included to ensure adequacy of the essential fatty acids. At intervals during the study, feces were collected daily, pooled in weekly samples, and analyzed for fat content. The net fat absorption was calculated from dietary intakes and fecal excretion. The net fat absorption was 96%. The absorption of the substance can be considered to be similar to this value as 2.5% safflower oil was the only other fat source in diet. Hence, under the test conditions, the constituent was highly absorbed after dietary administration in rats (Harkins, 1968).

The oral absorption of the constituent 'glycerides, C16 -18 and C18 -unsatd.' (as soybean oil) was measured in a 15 d feeding study by analysis of fecal unabsorbed fat. Diet containing 15% of the test substance was fed to 10 male Sprague-Dawley rats for 15 d. For the final 10 d, the feces were collected for unabsorbed fat analysis. The net fat absorption was calculated from dietary intakes and fecal excretion. High (94%) absorption was observed. Under the test conditions, the test substance was highly absorbed after dietary administration in rats (Nolen, 1981).

The absorption of 'glycerides, C16-18 and C18-unsatd.' (as soybean oil) was measured in a 91 day oral toxicity study by analysis of unabsorbed fecal fat.

Diet containing 19% test substance (7.5% experimental fat plus 11.5% as source of norma dietary fat) was fed to 20 Sprague-Dawley rats/sex for 91 days. During 3rd and 11th weeks of study, feces were collected from 10 animals/sex/group for analysis of unabsorbed fat. The net fat absorption was calculated from dietary intakes and fecal excretion. High (96%) absorption was observed. Under the test conditions, the test substance was highly absorbed after dietary administration in rats (Nolen, 1981).