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
Geneva
1974
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.
ESTERS OF GLYCEROL AND THERMALLY OXIDIZED SOYBEAN FATTY ACIDS
Explanation
These substances have been evaluated for acceptable daily intake
by the Joint FAO/WHO Expert Committee on Food Additives (see Annex 1,
Ref. No. 27) in 1971.
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.
BIOLOGICAL DATA*
BIOCHEMICAL ASPECTS
Groups of five male and five female rats received in their diet
either 20% soybean oil or thermally oxidized material. Highly modified
material reduced the absorption of dietary fat in proportion to the
degree of modification introduced. Modified material delays absorption
of oil from the gastrointestinal tract as measured by residuals found
in the gut. Similar delaying effects have been demonstrated on the
presence of chylomicrons and fat in the intestinal lymph fluid. The
passage of intestinal contents is delayed if modified oil is
administered. Compared with normal oil there is an early increase
followed by only slight decrease in bile flow following oral
administration of modified oil. Intraperitoneal administration of
modified oil increases the diuretic effect of normal soybean oil when
given intraperitoneally. Study of the liver function after eight weeks
feeding of modified oil showed retention of the bromosulphophthalein
used as indicator compared with normal oil (Kieckebusch et al., 1962).
The in vitro effect of modified oil on the kinetics of various
cellular enzyme systems showed generally no inhibition of oxidative
metabolism (Kieckebusch et al., 1962).
TOXICOLOGICAL STUDIES
Acute toxicity
None available.
* It should be noted that some of the studies refer to the
unesterified thermally oxidized oils.
Short-term studies
Rat
Groups of 20 male and 20 female rats received over 12 to 16 weeks
in their diet either 20% untreated soybean oil of 5% variously
modified soybean oil plus 15% olive oil or 2.5% modified oil plus
17.5% olive oil. Only highly modified oils showed significant
reduction in growth, food intake and increased mortality. No definite
effect was noted at the 2.5% level. Motor activity of animals on high
doses of highly modified oil was increased compared with controls. The
weights of major organs were similarly increased for the groups on the
more highly modified oils. Gross and histopathology showed some
pathological changes in the thyroid and kidney of the group receiving
the most highly modified material (Kieckebusch et al., 1962).
Three groups each of six rats were treated for 17 weeks with an
esterified product at 0, 0.084 and 0.84% of their basic diet. There
was no significant effect on weight gain and macroscopic appearance.
Liver and stomach were examined histologically and found to be normal
(Dam, 1952).
Two groups of nine male rats received for 36 weeks feeds
containing margarine made with an esterified product at 0.3 and 3%
levels. No controls were used. No weight differences or gross
pathological changes were noted. The histology of kidneys, liver and
small intestine was normal (Aaes-Jorgensen et al., 1954).
Pig
Four groups of four female pigs received an esterified product
for 98 days at dietary levels of 0, 0.4, 2 and 10%. No significant
effects were discovered on growth rate, food consumption, blood
picture, liver and kidney function, serum chemistry, organ weights,
gross and histopathology due to administration of the test compound
(Gyrd-Hansen & Rasmussen, 1968).
Long-term studies
Rat
A three generation study was performed using an average level
of 15% esterified product in the diet. The P generation (57 females,
15 males) was observed for at least 24 months. Growth, body weight
gain and appearance were similar to controls (seven male, seven
female) receiving 15% soybean oil. Five animals in the test group
developed tumours but none in the control group. There were 16
survivors in the test group and two in the control group.
The F1 generation (37 male, 37 female) was also observed for 24
months. Thirty-seven males and females received soybean oil as
controls. Twenty-four test and 10 control animals survived two years.
Two test-animals and three controls developed tumours. The F2
generation (57 female, 27 male) was observed for over two years.
Seventy males and females acted as controls on soybean oil. Four test
and 19 control animals survived 24 months. No animal in the test group
but three in the control group developed tumours. Both the F1 and F2
generation showed no significant differences from controls as regards
growth, body weight gain, gross and histopathology.
In another experiment an esterified product was fed orally at the
rate of 3 g/day and injected s.c. to 29 rats at 1 ml weekly for five
months and 2 ml bi-weekly for a further three months. Animals were
observed for 27 months. No tumours developed. A control series of 30
rats treated similarly with oral esterified product and injected s.c.
with refined soybean oil showed four tumours after 24 months
observation, none at the site of injection. The F1 test generation
(nine male, nine female) received 3 g esterified product orally and
1 ml i.p. for eight weeks, followed by a further 1 ml i.p. for four
months. After 11 months six survived without any tumours being noted.
The control group (14 male, four female) received 1 ml soybean oil
s.c. for five months and 2 ml s.c. for three months. During 29 months
observation, one rat developed a tumour at the site of injection
(Harmsen, 1959, 1960, 1961).
Rats fed with 20% of thermally oxidized soybean oil in the diet
had a significantly longer life-span (807 ± 32 days) than those fed
with 20% of fresh soybean oil (673 ± 42 (mean ± S.E.)): a similar
difference was observed between other oxidized and fresh fats and oils
(Kaunitz et al., 1966).
Comments:
No adequate specification has been provided for this material. It
has not been possible to relate the available toxicological
information to the materials in commercial use.
EVALUATION
Not possible on the data provided.
* Previously allocated ADI is withdrawn.
REFERENCES
Aaes-Jorgensen, E. et al. (1954) Unpublished report supplied by
Grindstedvaerket Laboratoriet
Dam, H. (1952) Unpublished report submitted by Grindstedvaerket
Laboratoriet
Gyrd-Hansen, N. & Rasmussen, F. (1968) Fd. Cosmet. Toxicol., 6, 163
Harmsen, H. (1959) Unpublished report submitted by Grindstedvaerket
Laboratoriet
Harmsen, H. (1960) Unpublished report submitted by Grindstedvaerket
Laboratoriet
Harmsen, H. (1961) Unpublished report submitted by Grindstedvaerket
Laboratoriet
Kaunitz, H., Johnson, R. E. & Pegus, L. (1966) Proc. Soc. exptl. Biol.
Med., 123, 204
Kieckebusch, K. et al. (1962) Fette, Seifen, Anstrichmittel, 64, 1154