Toxicological evaluation of some food
    additives including anticaking agents,
    antimicrobials, antioxidants, emulsifiers
    and thickening agents


    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).


    Special studies


         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).

    Short-term studies


         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).

    Long-term studies


         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).


         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

         Not limited.*


    *    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
         Chemical Corp.

    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

    See Also:
       Toxicological Abbreviations
       Starch acetate  (FAO Nutrition Meetings Report Series 46a)
       Starch acetate (WHO Food Additives Series 1)
       Starch acetate (WHO Food Additives Series 17)
       STARCH ACETATE (JECFA Evaluation)