ACETYLATED DISTARCH GLYCEROL
Explanation
This substance was evaluated for acceptable daily intake for man
(ADI) by the Joint FAO/WHO Expert Committee on Food Additives in 1969
and 1971 (see Annex I, Refs. 20 and 27). A toxicological monograph was
issued in 1974 (see Annex I, Ref. 33).
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.
Introduction
Modification is carried out with epichlorohydrin to a maximum of
0.3% and acetic anhydride to a maximum of 8%. The amount of acetyl
groups introduced does not exceed 2.5%. Further treatment, such as
bleaching is often carried out.
BIOLOGICAL DATA
BIOCHEMICAL ASPECTS
The in vitro digestibility of acetylated distarch glycerol
(0.3% epichlorohydrin, 1.2 or 2.5% acetyl content) varies with the
acetyl content but is not affected by cross-linkage. At 1.2%
acetylation, some 82% of the modified starch is digestible, but at
2.5% only 68.5% is hydrolysed enzymatically (Kruger, 1970). The
caloric value was determined by reference to a dose-response curve
established in groups of 10 male rats given a basic diet with graded
supplements of 0, 0.75, 1.5, 3.0 and 4.5 g sucrose equivalent to 0, 3,
6, 12 and 18 calories per day. Starches modified by the use of 0.1%
epichlorohydrin + 5.5% acetic anhydride and 0.3% epichlorohydrin +
5.5% acetic anhydride were tested against native starch at levels of
supplementation of 1.5 g and 3.0 g per day for 28 days. Weight gain on
modified starch supplement was slightly reduced compared with that on
unmodified starch. All rats remained normally active and healthy. The
caloric estimates were similar for both levels of epichlorohydrin
treatment (Oser, 1961).
TOXICOLOGICAL STUDIES
Special studies on reproduction
Rat
Groups of 10 male and 10 female rats, Sprague-Dawley derived,
were selected at random from a concurrent 2-year chronic toxicity
study, and 6 weeks after weaning, mated to produce F1a and F1b
litters. Test animals were maintained on a diet of 62% acetylated
distarch glycerol, while controls received 62% unmodified starch in
their diet. After breeding was complete, parents were returned to the
chronic study while 10 male and 10 female rats from the F1b litter
were bred to produce F2a litters. In each generation, litters from
the first mating were sacrificed at weaning, and from the second
mating, 6 weeks after weaning, except for the 10 males and 10 females
selected for breeding. The percentage of females with litters was
reduced in both litters from second generation rats fed acetylated
distarch glycerol. Pre-weaning deaths were significantly elevated in
offspring from F2b litters for both control and test animals compared
to the previous generations, but were within normal limits for the
strain. The remaining test parameters (litter size, incidence of
stillbirths, sex ratio at weaning and pre-weaning growth) were similar
in treated and control animals. Histological sections taken from
principal organs of F3b rats reportedly did not reveal evidence of
anomalies. No detailed information from the histopathological
examinations was provided (Truhaut et al., 1979).
Short-term studies
Rat
Groups of 15 male and 15 female rats were fed for 90 days on
diets containing 50% either native or modified starch (0.3%
epichlorohydrin + 10.5% acetic anhydride). The growth rate of male
rats was significantly lower compared with controls on unmodified
starch. The full and empty caecal weights of both male and female rats
in the test groups were significantly greater than in controls.
Haematology, blood chemistry, urinalysis, organ weights and gross as
well as histological examination were normal (Oser, 1964).
Pig
Groups of 8 miniature pigs, Pitman-Moore, 3 days old, were fed
diets containing either 6% acetylated distarch glycerol or 6%
hydrochloric acid-treated ("thin-boiling") starch (control) for 25
days. Treated animals experienced a reduction in rate of growth in the
early stages of the study, but grew at a rate comparable to controls
in the last week of the study. The empty caeca of test animals were
significantly heavier in relation to body weight than were the empty
caeca of controls. Animals fed the test diet had a significantly
higher water content and lower protein content than control animals.
Livers (wet or fat-free) of test animals were lower in protein content
than controls. The effect appeared to be related to increased water
content in the livers of treated animals. Other composition parameters
(ash, calcium, phosphorus, potassium sodium, magnesium) were
comparable in liver and carcass of treated and control animals. Serum
chemistry values were also similar in test and control groups
(Anderson et al., 1974).
Long-term studies
Rat
Rats, Sprague-Dawley derived, 4-5 weeks old, were distributed in
groups of 30 males and 30 females and fed a test diet containing 62%
acetylated distarch glycerol and a control diet of 62% unmodified
starch for 2 years. Significant reductions in growth occurred in
treated animals, particularly in females. These differences could not
be attributed to reduced food intake, because consumption of modified
starch and control diets was comparable. The 2-year survival rate in
treated animals (60%) was reported to be slightly higher than in
control animals (52%). These figures were considered to be in the
normal range. At autopsy, adipose deposits were much less extensive in
treated rats, which could account for the reduced weights of these
animals compared to controls. Statistically significant treatment-
related variations occurred in absolute organ weights relative to
controls, but not in relative organ/body weights. Because no
treatment-related changes could be detected microscopically, the
variations in organ weight were considered to be incidental.
Haematology and serum biochemistry parameter results were reported to
be normal, with the exception of SGOT in treated animals which
exceeded normal limits. Histological examination of the tissues showed
hyperplasia of the kidney urothelium, sometimes accompanied by
calcification, in both control and test groups, but neither the
incidence nor severity of these effects were considered by the authors
to be treatment-related. However, independent reviewers of the data
concluded that in female rats, the incidence of epithelial hyperplasia
was greater in the rats fed modified starch. Tumour incidence was, in
general, slightly lower in treated females than in controls. However,
treated males showed a slight increase in the incidence of adrenal
tumours (pheochromocytomas and cortical adenomas) and in thyroid
tumours (trabecular adenomas) relative to controls, but this was not
statistically significant (Truhaut et al., 1979).
Comments
The feeding studies with rats show that the modified starch is
well utilized. The available evidence for the group of modified
starches considered suggests that caecal enlargement without
associated histopathological changes is without toxicological
significance. The short-term study shows no other significant effects
related to treatment, the observed growth depression being the obvious
result of the high dietary level used. A multigeneration reproduction
study in rats showed no significant compound-related effects. A 2-year
feeding study in rats showed no compound-related effect, apart from
decreased weight gain, caecal enlargement, and an increased incidence
of epithelial hyperplasia in female rats. Data derived from special
studies with a group of modified starches suggest that the latter
effect is due to an imbalance in dietary Ca/P and Mg.
EVALUATION
Estimate of acceptable daily intake for man
Not specified.*
* 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
necessary.
REFERENCES
Anderson, T. A. et al. (1974) Digestibility of acetylated distarch
glycerol - effect on growth, serum biochemical values and body
composition of Pitman-Moore miniature pigs, Fd. Cosmet.
Toxicol., 12, 201-207
Kruger, L. (1970) Unpublished reports Nos. 405 and 406 submitted
by National Starch and Chemical Corporation
Oser, M. (1961) Unpublished report of Food and Drug Research
Laboratories, Inc. No. 81774, submitted to National Starch and
Chemical Corporation
Oser, B. L. (1964) Unpublished report of Food and Drug Research
Laboratories, Inc. No. 85554, submitted by National Starch and
Chemical Corporation
Truhaut, T., Coquet, B., Fouillet, X., Galland, D., Guyot, D. & Long,
D. (1979) Two-year toxicity and multigeneration studies in rats
on two chemically modified maize starches, Fd. Cosmet.
Toxicol., 17, 11-17
See Also:
Toxicological Abbreviations
Acetylated distarch glycerol (FAO Nutrition Meetings Report Series 46a)
Acetylated distarch glycerol (WHO Food Additives Series 1)
Acetylated distarch glycerol (WHO Food Additives Series 5)
ACETYLATED DISTARCH GLYCEROL (JECFA Evaluation)