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Description of key information

Sucroglyceride C16-18 is a complex reaction product of partial esters of glycerol, propane-1,2-diol and sucrose with fatty acids and unreacted glycerol, fatty acids and sucrose.  Hence, this UVCB substance shows a high level of complexity and a high variability in its physico-chemical properties and the resulting toxicokinetic and metabolic behaviour. 
The major part of the unreacted constituents and the esters formed as reaction products are naturally occurring substances, to a large amount present in food. They are of no particular concern for chemical hazard and they undergo the various biochemical pathways in the organism relevant for the respective chemical class.
Major emphasis for the discussion of toxicokinetics and metabolism is put on the esters of glycerol and fatty acids. Some aspects are also discused for the esters of sucrose with fatty acids.
The available data indicate that glycerides might be completely hydrolysed in the intestinal lumen of the rat, be absorbed at a high rate as fatty acids and then resynthesised in the intestinal wall.
Upon absorption, the fatty acids or glycerides will enter the normal biochemical pathways which fatty acids, their degradation products or their derivatives are part of.
Monoesters of sucrose with fatty acids are extensively hydrolysed in the gastrointestinal tract into the constituent fatty acids and sucrose prior to absorption and then undergo the routine metabolic fate of these nutrients.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential
Absorption rate - oral (%):
100
Absorption rate - dermal (%):
10
Absorption rate - inhalation (%):
10

Additional information

Sucroglyceride C16-18 is a complex reaction product of partial esters of glycerol, propane-1,2-diol and sucrose with fatty acids and unreacted glycerol, fatty acids and sucrose. Hence, this UVCB substance shows a high level of complexity and a high variability in its physico-chemical properties.

Its unreacted constituents are Sucrose, Glycerol and fatty acids, mainly C16 and C18.

 

For all unreacted constituents of Sucroglyceride C16 -18 and for some of the reaction products, the REACH regulation itself states that they are of no concern. This lack of concern is warranted for all substances listed in Annex IV and V of the REACH Regulation:

 

Annex V - exemption from registration according with article 2(7)(b)

Constituents: Substances obtained from natural sources, among which glycerol and fatty acids from C6 to C24 (and their potassium, sodium, calcium and magnesium salts)

 

Annex IV – substances considered to cause minimum risk because of their intrinsic properties according with article 2(7)(a)

Constituents:

Annex IV includes Sucrose, the pure fatty acids Palmitic (C16), Stearic acid (C18), several fatty acids with mixed chain lengths in the range relevant for Sucroglyceride C16 -18

Reaction products:

Also in Annex IV, some substances, in particular glycerides, are listed which are present in the reaction mass of Sucroglyceride C16 -18, for example Glycerol stearate and Glycerides C16-18, C18unsatd.

 

The one type of reaction products which is not immediately exempt from registration due to the lack of concern according to the REACH regulation are the esters of sucrose with fatty acids. However, some of those have a wide application as food additives.

There are no data available directly on Sucrose esters with fatty acids C16 -18. However, information on a read-across substance, a structural analogue containing a fatty acid moiety (Isostearic acid) and a sugar moiety (Methyl α-D-glucoside) is available and was evaluated.

 

Regarding Toxicokinetic, metabolism and distribution, the major part of the available information regards glycerides and fatty acids. Furthermore, an expert statement is available on Isostearic acid, esters with methyl α-D-glucoside

 

Glycerides and fatty acids

 

Absorption

The mechanism of the intestinal fat absorption has been studied with 14C-labelled fat (combinations of corn oil and palmitic acid) in rats with the intestinal lymph duct cannulated (Borgstrom, 1951). The recoveries in the lymph of the fat fed varied widely. Diarrhoea occurred in some animals especially after feeding hydrolysed corn oil. In all three groups of experiments maximum recoveries were found after 24 hours, i. e. 80.9, 85.0 and 87.5% of the activity given. These results indicate that most of the absorbed fat is transported via the lymphatic channels to the systemic circulation whether fed as glycerides or free fatty acids. The proportions of neutral fat and phospholipids in the lymph were in all three cases about the same. 90% of the fatty acids were present in the neutral fat and the remaining 10% in phospholipids. The neutral fat consisted chiefly of triglycerides; cholesterol and cholesterol esters representing only a minor part of this fraction. No free fatty acids or soaps appeared in the lymph. The results indicated that glycerides might be completely hydrolysed in the intestinal lumen of the rat and then resynthesised in the intestinal wall.

 

In another study with soybean oil the oral absorption in rats when fed at 17% of the diet was found to be 95 -98% (Nolen, 1972).

 

The distribution of the fatty acids in the triglycerides of the lymph was determined upon oral administration of triglycerides of known structure to rat (Mattson and Volpenhein, 1961). The extent of absorption of palmitic acid depended on the form in which it was fed (rates between 52 an 96%). Absorption was greatest when palmitic acid was fed asβ-palmitoyl diolein, and least when it was fed as the free acid.

 

Metabolism

Fatty Acid Glycerides (mono-, di-, and tri-esters of carboxylic acids with glycerol) have a common metabolic fate that involves stepwise hydrolysis to the carboxylic (e. g. fatty) acids and glycerol. Carboxylic acids and glycerol feed into physiological pathways like the citric acid cycle, sugar synthesis, and lipid synthesis. Fatty Acid Glycerides constitute a large part of the human diet. Triglyceride fats are a major source of calories in the human diet.

 

Matulka (2009) summarised that the metabolism of medium chain triglycerides in the canine is a process whereby lipases from the buccal cavity and pancreas release the fatty acids in the gastrointestinal tract where they are absorbed. Unlike long chain triglycerides (LCT), where long chain fatty acids (LCFA) form micelles and are absorbed via the thoracic lymph duct, MCFA are most often transported directly to the liver through the portal vein and do not necessarily form micelles. Also, MCFA do not re-esterify into MCT across the intestinal mucosa. MCFA are transported into the hepatocytes through a carnitine-independent mechanism, and are metabolized into carbon dioxide, acetate, and ketones through boxidation, and the citric acid cycle.

 

Adolph (1999) summarised that lipids are not only structural building blocks of cells and tissues but at the same time suppliers of C-atoms for a number of biosynthetic pathways as well as carriers of essential fatty acids and fat-soluble vitamins. In addition, fatty acids are precursors of prostaglandins and other eicosanoids and therefore have important metabolic functions. Fatty acids can be divided into three groups: saturated, monounsaturated, and polyunsaturated fatty acids.

 

Each class of fatty acids has a preferential specific role. Saturated fatty acids (medium or long-chain) are more devoted to energy supply, but one should not forget their specific structural role. The polyunsaturated fatty acids of the n–3 and n–6 families have very important structural and functional roles and ideally should not be utilized for energy purposes.

 

Excretion (Lipolysis)

Typical dietary lipids from vegetable oils, termed long-chain triacylglycerols (LCT), are degraded by salivary, intestinal and pancreatic lipases into two fatty acids and a monoacyl glycerol; whereas, MCT are degraded by the same enzymes into three fatty acids and the simple glycerol backbone. 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 incorporated into chylomicrons and enter the lymphatic system. 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.

 

 

Isostearic acid, esters with methyl α-D-glucoside

 

Isostearic acid, esters with methyl α-D-glucoside is a composition of 80% Methyl glucoside isostearate esters (mainly di-), 16% Isostearic acid and 4% Methyl glucoside.

 

The water solubility of Isostearic acid, esters with methyl α-D-glucoside is very low ( < 5 x10E-04 g/L). Since in general a substance needs to be dissolved before it can be taken up from the gastrointestinal tract, it is unlikely that there will be a high systemic exposure after oral administration. The absorption will furthermore be lowered by the relatively high molecular weight Iimiting the passage through biological membranes. Its highly Iipophilic character (log Pow > 6.5) indicates that uptake by micellular solubilisation may be of particular importance.

Toxicological data do not provide reasons to deviate from the proposed low oral absorption.

The high molecular weight and the low water solubility of also indicate a low potential for distribution through the human body. Any Isostearic acid, esters with methyl α-D-glucoside absorbed from the gastrointestinal tract might undergo biotransformation. Excretion will be predominantly via the bile (high molecular weight substances).

Uptake via inhalation is anticipated to be low, because of the low vapour pressure and high molecular weight of the paste Isostearic acid, esters with methyl α-D-glucoside. The log Pow (> 6.5) indicates a potential for absorption directly across the respiratory tract epithelium.

Isostearic acid, esters with methyl α-D-glucoside being a paste with a relatively high molecular weight has no real potential for dermal absorption. As the criteria for 10% dermal absorption as given in the TGD (ECB EU Technical Guidance Document on Risk Assessment, 2003) (MW > 500 and log Pow > 4) are met, 10% dermal absorption of Isostearic acid, esters with methyl α-D-glucoside is proposed for risk assessment purposes. The results of the toxicity studies do not provide reasons to deviate from this proposed dermal absorption factor.

Based on the present available data, no additional conclusions can be drawn on the distribution, metabolism and excretion of Isostearic acid, esters with methyl α-D-glucoside after dermal and inhalatory absorption.