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.
Esterification is achieved by using either acetic anhydride (up
to 8%) or vinyl acetate (up to 7.5%). A maximum of 2.5% acetyl groups
is introduced corresponding to a maximum degree of substitution of
The digestibility of acetylated starches was measured by the
biochemical oxygen demand of incubated samples. As the acetyl contents
increased so the BOD values decreased and, in parallel, the
digestibility. Starch acetates containing 2.5% acetyl groups are only
93.7% as digestible as native starch (Turner, 1961). Digestibility by
fungal amyloglucosidase was shown to be 68-81% of that of native
starch (Turner, 1961; Kruger, 1970). The digestibility of starch
acetate (containing 1.98% acetyl) groups by pancreatin and procine
mucosal enzymes was found to be 90% of that of the unmodified starch
(Leegwater, 1971). Caloric value was determined in groups of 10 male
rats fed for four weeks a diet supplemented with graded doses of 0,
1.5 g, 3.0 g, 4.5 g and 6.0 g dextrose (equivalent to 0, 6, 12, 18 and
24 calories). The dose response curve was used to estimate the caloric
value of supplements of 3 g and 4.5 g of acetylated (1.8% acetyl) or
native starch. No significant difference was found between the starch
samples with regard to caloric value (Oser, 1961).
Groups of 10 male and 10 female rats were given 25% and 50% of
starch acetate (acetylated to 1.98%) in a low residue diet for seven
days. Thereafter 4% cellulose was added for a further three days. Body
weights were slightly reduced in both sexes at the 50% level after
seven days. Faecal dry matter was increased in all test groups but not
in a dose-related manner. Slight diarrhoea occurred only at the 50%
level in both sexes and this was unaffected by the feeding of
additional cellulose in the diet. No loss of hair was noted (de Greet
& Spanjers, 1970).
Special studies on reproduction
A three-generation study was performed using groups of 10 males
and 20 females to produce successive generations by mating at week 12
and 20 after weaning. The F3b generation was kept for three weeks
after weaning and then sacrificed for histopathological study. The P,
F1b and F2b parents were used for determination of implantation
sites. The test material, fed at 10% of the diet consisted of starch
modified with 5% acetic anhydride (degree of substitutions 0.079). No
adverse effects were noted regarding health, behaviour, mortality,
body weights, fertility, litter size, resorption quotient, weaning
weight of pups or mortality of young. Caecal weights were increased.
Gross and microscopic examination of the F3b generation failed to
reveal any deleterious effects (Til et al., 1971b).
Groups of 10 male rats were fed for 28 days diets containing 60%
of various starch acetates (the degree of acetylation varied from 0,
1.24, 2, 2.56 to 3.25%. Weight gain was reduced in groups receiving
starch acetates with more than 2% acetylation but feed efficiency
remained unaffected. Diarrhoea occurred at 2% and higher degrees of
acetylation and there was noticeable caecal enlargement at the same
levels. No tissue damage or inflammation was noted in association with
the diarrhoea (Turner, 1961).
In another experiment potato starch acetate (acetylated to 1.36%)
was fed for 13 weeks to groups of 10 male and 10 female rats at levels
of 5, 15 and 45% of the diet. The 5% level was fed for only four
weeks. No animal died. Growth rates and haematological findings were
not significantly affected. The relative weights of liver, kidney,
adrenal, pituitary and thyroid showed some significant differences
compared with controls, being generally lower except for male
thyroids. Male caecal weights were higher than controls and distended
caeca were seen at the 15 and 45% dietary levels. No histopathological
changes due to starch acetate were seen (Feron et al., 1967).
In a further experiment starch acetate (acetylated to 1.98%) was
fed to groups of 10 male and 10 female rats for eight weeks at dietary
levels of 25 and 50%. No effects were noted on growth and body weight.
Water content of faeces and faecal production, as measured by dry
matter content, showed no consistent effects but there vas a tendency
towards increased faecal dry matter at the 50% dietary level in both
sexes. No diarrhoea was observed at any dietary level. Caecal weight
and caecal enlargement occurred in a dose-related manner in all
treatment groups. However, histological examination revealed no
abnormality of the caeca examined (de Groot & Spanjers, 1970).
Groups of 30 male and 30 female weanling rats were fed on diets
containing 0, 5, 10 and 30% of starch acetate (acetylated to 1.98%)
for two years. No significant differences were observed with respect
to behaviour, general health and mortality. Growth and food
consumption were essentially similar to those of the controls.
Production of faeces during weeks 11 and 12 showed no dose-related
differences among the various groups. Haematology, serum chemistry and
serum enzymes as well as urinalysis showed no effects related to the
administration of the test material. Among organ weights only the
caecal weight of male rats showed a dose-related increase at 10% and
higher levels and the caecal weight of female rats was increased at
the 30% level compared with controls. Ne other significant changes
were noted which could be ascribed to the test substance. Upon
microscopic examination no changes were found in the enlarged caeca.
The incidence of nephrocalcinosis accompanied by focal hyperplasia of
the pelvic epithelium, was slightly higher in male test animals than
in controls. Distinct pathological changes attributable to the test
compound were not observed (Til et al., 1971a).
OBSERVATIONS IN MAN
Twelve volunteers consumed on each of four consecutive days 60 g
starch acetate with 1.98% acetyl content. No effect was noted on
frequency and amount of faeces, faecal water or lactic acid content.
No other adverse effects were noticed (Pieters et al., 1971).
The feeding studies with rats did not reveal any deleterious
effects. The available evidence for the modified starches as a group
suggest that caecal enlargement without associated histopathological
changes is without toxicological significance. Several short-term
studies, a two-year study and a reproduction study in rats are now
available for evaluation.
Estimate of acceptable daily intake for man
* See relevant paragraph in the seventeenth report, pp. 10-11.
Feron, V. J., Til, H. P. & de Groot, A. P. (1967) Report No. R 2329 by
Centraal Instituut voor Voedingsonderzoek
de Groot, A. P. & Spanjers, M. Th. (1970) Report No. R 3096 by
Centraal Instituut voor Voedingsonderzoek
Kruger, L. (1970) Unpublished reports Nos. 405 & 406 submitted by
National Starch and Chemical Corp.
Leegwater, D. C. (1971) Unpublished report No. R 3431 by Centraal
Instituut voor Voedingsonderzoek
Oser, M. (1961) Unpublished report No. 79868 b and c by Food and Drug
Research Laboratories Inc., submitted by National Starch and
Pieters, J. J. L., van Staveren, W. A. & Brinkhuis, B. G. A. M. (1971)
Unpublished report No. R 3433 by Centraal Instituut voor
Til, H. P. et al. (1971a) Report No. R 3363 by Centraal Instituut voor
Til, H. P., Spanjers, M. Th. & de Groot, A. P. (1971b) Report No. R
3403 of Centraal Instituut voor Voedingsonderzoek
Turner, A. W. (1961) Unpublished report of Avebe. Submitted by Assoc.
Amidonneries de Mais