This modified starch was previously evaluated for an ADI for man
by the Joint FAO/WHO Expert Committee on Food Additives in 1969, 1971
and 1973 (see Annex I, Refs. 19, 26 and 29). Toxicological monographs
were published in 1969, 1972 and 1974 (see Annex I, Refs. 20, 27 and
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.
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
The Life Sciences Research office of the Federation of American
Societies for Experimental Biology has recently completed an
exhaustive review of the health aspects of modified starches (FASEB,
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 porcine
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 4 weeks a diet supplemented with graded doses of 0, 1.5,
3.0, 4.5 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).
Special studies on reproduction
A 3-generation study was performed using groups of 10 males and
20 females to produce successive generations by mating at weeks 12 and
20 after weaning. The F3b generation was kept for 3 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, weanling
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; de Groot et al.,
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 7 days.
Thereafter, 4% cellulose was added for a further 3 days. Body weights
were slightly reduced in both sexes at the 50% level after 7 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 Groot & Spanjers,
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 4
weeks. No animals died. Growth rates and haematological findings were
not significantly affected. The relative weights of 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
In a further experiment, starch acetate (acetylated to 1.98%) was
fed to groups of 10 male and 10 female rats for 8 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 was a
tendency towards increased faecal dry matter at the 50% dietary level
in both sexes. No diarrhoea was observed in 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 75 male and 75 female Swiss albino SPF mice were fed a
diet containing 55% acetylated potato starch or a control diet
containing 55% pregelatinized potato starch for 89 weeks. Other groups
were maintained on diets containing 55% lactose, 55% hydroxypropyl
distarch phosphate, or 25% sodium alginate (Feron et al., 1978).
Observations were made on growth and appearance, haematology, blood
biochemistry, urine composition, organ weights, mortality, and gross
and microscopic pathology with special attention being given to the
kidney and bladder. In week 80, 10 mice/sex/group were killed and
necropsied. A thorough necropsy was also performed on those animals
found dead or moribund. After 89 weeks, all survivors were killed and
subjected to necropsy.
In both the acetylated starch and control groups loose stools
were observed with similar frequency. Other abnormalities in
appearance were randomly distributed. The death rate was normal for
the starch acetate test group but was elevated in the control males
between weeks 39-65 (haemorrhagic myocarditis). Body weights were
generally comparable although there were significant decreases
(Student t-test) at weeks 16, 20, 40 and 72 in males and in females at
week 84. The starch-acetate-fed animals exhibited a 50-100% increase
in water consumption over controls. Haemoglobin (P < 0.01) and
haematocrit (P < 0.05) were significantly decreased in treated
animals at week 40 (Wilcoxon test), but were within normal limits by
Male test animals had a distinctly higher incidence of amorphous
material in the urine. Analysis of the urine sediment showed 95%
protein with the remainder phosphates, carbohydrates, and possibly
some silica. At week 82, there was an increase in Ca content in the
urine of males over that of control males (38 versus 7 mg%), a
decrease in Mg (36 versus 152 mg%), and a decrease in P content
(990 versus 2840 mg%). In females (versus controls), the Ca was also
increased (97 versus 12 mg%), the Mg content remained level (44 versus
42 mg%), and the P decreased (1150 versus 3080 mg%). The caecum and
colon were statistically heavier in the starch-acetate group than in
the control group. The starch-acetate-fed females also had a slight
but statistically significant increase in kidney weight.
In males of the starch-acetate group, the incidence of thickened
urinary bladder epithelium (occasionally accompanied by a thickened
submucosa) was slightly higher than in controls. One urinary stone was
found in a male of the starch-acetate group and another male had a
considerable amount of a gritty (calcareous?) material in its bladder.
Calcareous deposits were found in the renal pelvis of males in the
test group (9/74) but none in the controls (0/73). The incidence of
intratubular calcareous deposits was significantly greater in test
group males (25/49) than in controls (5/28). The authors concluded
that these renal and urinary changes were of no toxicological
significance (Feron et al., 1978).
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 2 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. No 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; de Groot et al., 1974). Roe (1979)
has conducted an extensive review of this type of mineral deposition
in the renal pelvis of rats and concluded that pelvic
nephrocalcinosis, corticomedullary nephrocalcinosis, acute tubular
nephropathy, and calculus formation are manifestations of mineral
imbalance and are of relatively common occurrence in untreated
laboratory rats (particularly older animals).
OBSERVATIONS IN MAN
Twelve volunteers consumed on each of 4 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 noted (Pieters et al., 1971).
The short-term feeding studies with rats did not reveal any
deleterious effects. The available evidence for the modified starches
as a group suggests that caecal enlargement without associated
histopathological changes is without toxicological significance.
Several short-term studies and a reproduction study in rats showed no
compound-related effects. Long-term studies in mice and rats showed no
compound-related effects, with the exception of decreased weight gain,
increased caecal weight and increase in the occurrence of renal
lesions, particularly in the males. The renal lesions are considered
to be associated with an imbalance of Ca/P and Mg in the diet.
Estimate of acceptable daily intake for man
* The statement "ADI not specified" means that, on the basis of the
available data (toxicological, biochemical, and other), the total
daily intake of the substance, arising from its use or uses at
the levels necessary to achieve the desired effect and from its
acceptable background in food, does not, in the opinion of the
Committee, represent a hazard to health. For this reason, and for
the reasons stated in individual evaluations, the establishment
of an acceptable daily intake (ADI) in mg/kg bw is not deemed
Feron, V. J. (1975) Letter to Paul Newberne in attachment M, Vol. III
of Corn Refiners Association, Inc. Submission dated 15 September
1976 to Federation of American Societies for Experimental
Biology, Bethesda, Md.
Feron, V. J., Til, H. P. & de Groot, A. P. (1967) Report No. R 2329 by
Centraal Instituut voor Voedingsonderzoek, Zeist, Holland.
Submitted to WHO
Feron, V. J., Til, H. P. & Immel, H. R. (1978) Chronic (89-week)
feeding study with hydroxypropyl distarch phosphate, starch
acetate, lactose and sodium alginate in mice. Report No. R 5690.
Centraal Instituut voor Voedingsonderzoek, Zeist, Holland
de Groot, A. P. & Spanjers, M. Th. (1970) Observations in rats fed on
diets containing five different chemically modified starches.
Report No. R 3096 by Centraal Instituut voor Voedingsonderzoek,
de Groot, A. P. et al. (1974) Two-year feeding and multigeneration
studies in rats on five chemically modified starches, Fd.
Cosmet. Toxicol., 12, 651-664
Federation of American Societies for Experimental Biology (1979)
Evaluation of the health aspects of starch and modified starches
as food ingredients. Prepared for US Food and Drug Administration
under DHEW contract No. FDA 223-75-2004, Bethesda, Md. Submitted
by the FDA to WHO, 1982
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, Zeist, Holland
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
Voedingsonderzoek, Zeist, Holland. Submitted to WHO
Roe, F. J. C. (1979) Mineral deposition in the renal pelvis of rats:
A brief review, unpublished report. Submitted to WHO
Til, H. P. et al. (1971a) Chronic (two-year) feeding study in rats
with two chemically modified starches (starch acetate and
hydroxypropyl distarch glycerol). Report No. R 3363 by Centraal
Instituut voor Voedingsonderzoek, Zeist, Holland
Til, H. P., Spanjers, M. Th. & de Groot, A. P. (1971b) Report
No. R 3403 of Centraal Instituut voor Voedingsonderzoek, Zeist,
Holland. Submitted to WHO
Turner, A. W. (1961) The safety evaluation of Mira-cleer and other
acetylated types of starch. A. E. Staley Manufacturing Company,