FAO Nutrition Meetings
Report Series No. 40A,B,C
WHO/Food Add./67.29
TOXICOLOGICAL EVALUATION OF SOME
ANTIMICROBIALS, ANTIOXIDANTS, EMULSIFIERS,
STABILIZERS, FLOUR-TREATMENT AGENTS, ACIDS AND BASES
The content of this document is the result of the deliberations of the
Joint FAO/WHO Expert Committee on Food Additives which met at Rome,
13-20 December, 19651 Geneva, 11-18 October, 19662
1 Ninth Report of the Joint FAO/WHO Expert Committee on Food
Additives, FAO Nutrition Meetings Report Series, 1966 No. 40;
Wld Hlth Org. techn. Rep. Ser., 1966, 339
2 Tenth Report of the Joint FAO/WHO Expert Committee on Food
Additives, FAO Nutrition Meetings Report Series, 1967, in press;
Food and Agriculture Organization of the United Nations
World Health Organization
1967
POLYGLYCEROL ESTERS OF FATTY ACIDS
Synonyms Polyglycerol fatty acid esters; Glyceran
fatty acid esters
Chemical description Mixtures of polyglycerol esters of fatty
acids of food fats.
Structural formula
OR
'
R-(OCH2-CH-CH2O)n-R
Where the average value of n is no more
than 3 and R is partly a fatty acid
moiety or partly hydrogen radical.
Definition Polyglycerol esters of fatty acids are
mixtures of the esters of these fatty
acids with the polyglycerol mixture.
The commercial products will contain
mono- and diglycerides when fats are
used for transesterification with
polyglycerol mixtures.
Description Oleaginous substances, of a consistency
depending on the fatty acids.
Uses As emulsifiers.
Biological Data
Biochemical aspects
The polyglycerol esters of fatty acids include large group of
closely related compounds of complex composition. However, the
individual components are found as normal constituents of the human
diet, i.e. glycerol, glycerol mono-, di- and tri-fatty acid esters and
individual fatty acids, with the exceptions of the artificially
produced polymers of glycerol, polymers of certain fatty acids and the
actual separate esters between these polymers. These latter compounds
represent the toxicologically important constituents.
In vitro experiments on lipase digestion of polyglycerol esters
showed a slower rate of digestion than that of olive oil and the ester
did not affect the lipase digestion of olive oil (Unilever Research
Laboratory, 1966).
Digestibility or caloric utilisation have been used to
demonstrate metabolic conversion; 16 male and female rats were fed a
diet containing 1 per cent. ground-nut oil and 9 per cent.
polyglycerol ester or 10 per cent. ground-nut oil (as control) for 6
and 12 weeks. Polyglycerol ester as an energy source was almost
equivalent to ground-nut oil, as measured by growth rate.
Digestibility was calculated as 92 per cent. In another experiment
rats were kept on a restricted food intake (18 calories/day) for 17
days. After realimentation with 9 per cent. polyglycerol ester and 1
per cent. ground-nut oil, no adverse effect was noted on the animals'
ability to gain weight. Rats fed polyglycerol ester for 54 days as 9
per cent. of the diet showed no difference in composition of carcass
fat, liver fat, liver free fatty, acids and liver phosphorus when
compared with groups fed 1 per cent. or 10 per cent. ground-nut oil in
the diet. Liver vitamin A levels were unaffected. A polyglycerol ester
was shown to be absorbed by intestinal lymphatics, and chylomicron
counts showed normal lipaemia. Suspensions in water were more slowly
absorbed and reduced the rate of gastric emptying compared with
ground-nut oil. The serum cholesterol level of rats was unaffected by
the presence of 10 per cent. polyglycerol ester in a 42 per cent. fat
diet (Unilever Research Laboratory, 1966).
Acute toxicity
Rat. Rats given single doses of 7, 14 and 29 g/kg body-weight
of a polyglycerol eater by intubation showed no signs of any toxic
effect. Repeated deals, with 10 g/kg body-weight daily over 5 days
caused no deaths. Rats, injected i.p. with 1, 3 and 7 g/kg
body-weight, showed no adverse effects; single doses of 10 g/kg
body-weight caused some peritoneal reaction but no deaths (Unilever
Research Laboratory, 1966).
Rabbit. Rabbits dosed orally with 10~29 g/kg body-weight showed
no toxic effects.
Short-term studies
Rats. Thirteen rats maintained on 9 per cent. polyglycerol
ester and 1 per cent. ground-nut oil for 17 weeks showed normal kidney
function (Unilever Research Laboratory, 1966). Rats kept 22 weeks on 9
per cent. PGE + 1 per cent. ground-nut oil showed no difference in
weights of liver, kidney, adrenal, spleen and testes when compared
with controls on 10 per cent. ground-nut oil. Gross autopsy and
histological examination of liver revealed no abnormalities (Unilever
Research Laboratory, 1966).
Man. Thirty-seven volunteers, aged 19-24, were fed 2-20 g
polyglycerol ester per day for 3 weeks in their diet. No abnormalities
were detected in plasma proteins, serum amino-acids, thymol turbidity,
serum bilirubin, total and free serum cholesterol, serum alkaline
phosphatase, SGOT, SGPT, cholinesterase, cholesterol esterase, 24 hour
urine volume, urinary creatinine, urea output, total and split faecal
fat or total faecal nitrogen (Unilever Research Laboratory, 1966).
Long-term studies
Mouse. Groups of 25 male and 25 female mice were fed for 80
weeks on either polyglycerol ester or ground-nut oil at 5 per cent. in
their diet. No adverse effect on body-weight, food consumption,
peripheral blood picture and survival rate were noted. Carcass fat of
the test group showed no polyglycerol residues. The levels of free
fatty acids, unsaponifiable material, fatty acid composition of
carcass fat and organ weights were the same in test and control
groups, except for the liver and kidney weights of female mice which
were significantly higher. Microscopic examination of all major organs
showed nothing remarkable (Unilever Research Laboratory, 1966).
Rat. A test group of 22 rats, with a control group of 28B, were
kept on a diet containing 1.5 per cent. of polyglycerol ester for 3
generations and maintained for over one year without significant
variation in fertility and reproductive performance. Gross and
histological examination of the third generation revealed no
consistent abnormality related to the test substance (Unilever
Research Laboratory, 1966).
In another experiment 28 male and 28 female rats were fed 5 per
cent. polyglycerol ester or ground-nut oil in their diet for 2 years.
No adverse effects on body-weight, food consumption, peripheral blood
picture, and survival rate were noted. Liver function tests and renal
function tests at 59 and 104 weeks were comparable between groups. The
carcass fat contained no polyglycerol and the levels of free fatty
acid, unsaponifiable residue and fatty acid composition of carcass fat
were no different from controls. Organ weights, tumour incidence and
tumour distribution ware similar in control and test groups. Complete
histological examination of major organs showed nothing remarkable
(Unilever Research Laboratory, 1966).
Comments
The toxicological assessment of this group of diverse but related
substances is based an evaluation of satisfactory evidence for one
member and assumes that alterations in the fatty acid distribution or
polyglycerol content of individual members have no toxicological
bearing and only affect the physical and emulsifying properties of
each ester. The metabolic studies point to hydrolysis of these
polyglycerol esters in the gastrointestinal tract and the utilization
and digestibility studies justify the assumption that the fatty acid
moiety is metabolized in the normal manner. Analytical studies have
produced no evidence of cumulation of the polyglycerol moiety in body
tissues. Human studies showed no adverse effects.
It is desirable to have properly conducted biochemical studies on
other members of this group, that do not conform to the specifications
detailed above, to exclude-unforeseen effects.
Evaluation
Level causing no toxicological effect
Rat. 50 000 ppm in the diet, equivalent to 2500 mg/kg
body-weight/day.
Estimate of acceptable daily intakes for man
mg/kg body-weight1
Unconditional acceptance 0-12.5
Conditional acceptance 12.5-25
REFERENCES
Unilever Research Laboratory (1966) Unpublished report
1 Calculated as total polyglycerol ester of palmitic acid.