Toxicological evaluation of some food
additives including anticaking agents,
antimicrobials, antioxidants, emulsifiers
and thickening agents
WHO FOOD ADDITIVES SERIES NO. 5
The evaluations contained in this publication
were prepared by the Joint FAO/WHO Expert
Committee on Food Additives which met in Geneva,
25 June - 4 July 19731
World Health Organization
1 Seventeenth Report of the Joint FAO/WHO Expert Committee on
Food Additives, Wld Hlth Org. techn. Rep. Ser., 1974, No. 539;
FAO Nutrition Meetings Report Series, 1974, No. 53.
MONO- AND DIGLYCERIDES
These substances have been evaluated for acceptable daily intake
by the Joint FAO/WHO Expert Committee on Food Additives (See Annex 1,
Ref. No. 7) in 1963.
Since the previous evaluation, additional data have become
available and are summarized and discussed in the following monograph.
The previously published monograph has been expanded and is reproduced
in its entirety below.
Food fats are in the main triglycerides. However, many of them
have been shown to contain small amounts of diglycerides and
monoglycerides. The amount present is commonly in the region of 1%.
There is some evidence also that further amounts of these partial
glycerides may be formed during the preparation of certain foods.
Therefore, apart from any addition of these substances to food for
technological purposes, they will always be present in the food as
consumed (National Academy of Sciences, 1960).
In the body, the triglycerides undergo digestion in the
gastrointestinal lumen. They are broken down mainly by pancreatic
lipase with the formation of mono- and diglycerides. Pancreatic lipase
removes fatty acids from the 1 and 3 positions preferentially, so that
1,2-diglycerides and 2-monoglycerides are the immediate products.
Mono- and diglycerides are absorbed into the intestinal cells. In
their passage through the intestinal mucosa they are largely converted
back into triglycerides. These pass into the body as a fine emulsion
and give rise to the milky appearance of the chyle and the blood
plasma. Under certain circumstances, these fat particles can be broken
down by another fat-splitting enzyme in the blood-stream. When this
occurs, the formation of mono- and diglycerides can be demonstrated.
It is not certain what part this enzyme plays in normal fat
metabolism. Transesterification and isomerizatlon can occur under
biological conditions. Diglycerides are readily converted in
appropriate tissues either to triglycerides or to mono-glycerides.
Monoglycerides can form diglycerides and triglycerides, but they are
not always easily broken down to fatty acids and glycerol, although
intestinal enzymes that rapidly bring this about have been described.
There is no evidence that the presence of monoglycerides or
diglycerides of food fats has any deleterious effect on cells or
The various fatty acids that may be present in preparations of
di- and monoglycerides used as food additives are not necessarily
absorbed and metabolized in the same way as those of the natural food
fats and their nutritional significance may also differ. Thus,
saturated long-chain fatty acids have a lower digestibility than
unsaturated fatty acids if fed alone, or in large quantities, and
administration of many polyunsaturated fatty acids causes depression
of the blood cholesterol level whereas the ingestion of saturated
fatty acids tends to increase it (Frazer, 1962).
Monoglycerides and diglycerides have no acute toxic effects at
practicable dosage levels.
Glyceryl monostearate was fed to groups of five male hamsters at
a level of 5% and to 10 at a level of 15% of the diet for 22 to 28
weeks. Weight gain was somewhat less in the 15% group, but in a second
experiment was improved by the addition of agar. The livers were
enlarged in this group but no significant histopathological changes
were evident (Orten & Dajani, 1957).
Glyceryl monostearate was fed at levels of 15% and 25% as the
sole source of fat in the diet to groups of 10 male and 10 female rats
over three generations. Studies carried out during the rapid growth
period in each generation showed no adverse effect on weight gain.
Reproductive performance and lactation were also normal. In another
study, 25% of the glyceryl monostearate was fed to groups of 12 male
and 12 female rats for up to two years. Weight gain and survival were
normal. There was a significant increase in liver weight and some
renal calcification (Ames et. al., 1951).
A mixture of lauric acid glycerides (40% monolaurin, 45%
dilaurin, 15% trilaurin) was fed to rats over a two-year period in a
concentration of 25% of the diet of a nutritionally adequate
laboratory chow. There was no histopathological evidence of toxicity
attributable to the lauric glycerides (Fitzhugh et al., 1960).
Glyceryl monostearate was fed to rats at a level of 14% of the
diet (Briski, 1969).
OBSERVATIONS IN MAN
Mono- and diglycerides are consumed every day in any normal mixed
diet and they are also formed from triglycerides during the digestion
and absorption of every meal containing fat. No harmful effects have
been specifically associated with mono- or diglycerides.
The mono- and diglycerides most likely to cause unwanted effects
are those containing long-chain saturated fatty acids, especially
stearic acid. Such compounds have been investigated in long-term
animal studies. (The increase in liver weight reported in these
studies is commonly seen in animals receiving a high fat intake; it is
not regarded as having any toxicological significance.) These studies
provide useful additional information to the wide experience with
glycerides which are a normal constituent of the human diet.
Estimate of acceptable daily intake for man
Ames, S. R. et al. (1951) J. Amer. Oil Chem. Soc., 28, 31
Briski, B. (1969) Farm. Glas., 25, 143-155
Fitzhugh, O. G., Schonboe, P. J. & Nelson, A. A. (1960)
Toxicol. appl. Pharmacol., 2, 59
Frazer, A. C. (1962) Chem. and Ind., p. 1438
National Academy of Sciences (1960) The safety of mono- and
diglycerides for use as intentional additives in food (N.A.S.)
Publication No. 251)
Orten. J. M, & Dajani, R. N. (1957) Food Res., 22, 529
* See relevant paragraph in the seventeenth report, pages 10-11.