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.


         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.



         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).


    Special studies on reproduction


         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


         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).


         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


         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).


         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.


    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


    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)