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.



         Whatever oxidizing agent is used only minor modifications of the
    starch molecule are achieved in normal manufacturing practice. These
    are equivalent to the introduction of 1% w/w of carboxyl (-COOH) or
    0.5% w/w of keto (-CO) groups or, 3.6 carboxyl and 2.9 carbonyl groups
    per 100 glucopyranose units. No chlorine is introduced into the
    molecule and the final products usually contain only residues of
    sodium chloride, sodium sulfate and sulfur dioxide.



         Early comparative experiments pointed to inhibition of amylolysis
    (Tremolières et al., 1959). In vitro digestibility by pancreatin or
    saliva was used to compare slightly and highly oxidized corn starch
    with unmodified corn starch and a reference starch. Maltose production
    after a fixed interval of enzyme action was taken as a measure of
    digestibility. The oxidized starch was 10-15% less digestible by
    pancreatin than unmodified starch but there was no obvious difference
    as regards salivary digestion (Shuman & Mertz, 1959). The
    digestibility of oxidized wheat starch (conditions not stated) was
    examined in rats by matched-feeding techniques using the modified
    starch as the sole source of carbohydrate at a level of 63.7% (dry
    basis) of the diet. The degree of assimilation by and the general
    effects on groups of six rats over a feeding period of 28 days were
    assessed from consideration of body weight changes, faecal residues,
    digestibility coefficients for starch and postmortem appearance of the
    animals and their gastrointestinal tracts. The digestibility
    coefficients were calculated from the starch content of ingested food
    and residues found in faeces and postmortem gastrointestinal contents.
    Body weight gain and digestibility coefficients were practically
    indistinguishable from those obtained for wheat starch or corn starch.
    Nothing abnormal was noted on postmortem examination (Booher et al.,

         Other studies, in three groups of three rats each, used corn
    starch oxidized with 3.9, 4.5, or 5.5% hypochlorite calculated as
    chlorine. This corresponds to the introduction of 0.57%, (2.04 COOH
    groups per 100 glucopyranose units), 0.8%, (2.86 COOH groups per 100
    glucopyranose units) and 0.9% (3.57 COOH groups per 100 glucopyranose
    units) carboxyl groups. To 5 g basal diet were added 1, 2 or 4 g
    modified or control starch and this diet was fed to rats for 10 days.
    Comparison of digestibilities showed an apparent decrease with
    increasing oxidation but no effect on caloric values. No tissue damage

    was associated with the diarrhoea and caecal enlargements observed in
    groups receiving 2 g or 4 g starch in their feed. Liver, kidney, heart
    and spleen weights were normal. Diarrhoea and caecal enlargement are
    known to occur in rats fed starches of poor digestibility or other
    carbohydrates (White, 1963).

         The digestibility of oxidized starches at levels of 2.5, 6 and
    43.2% calculated as chlorine, equivalent to a carboxyl content of
    0.32% (1.15 COOH per 100 glucopyranose units), 0.9% (3.81 COOH per
    100 glucopyranose units) or 1.46% (5.23 COOH per 100 glucopyranose
    units), was studied in groups of six male and six female rats. The
    animals were kept for seven days on 5 g basal diet and then given
    either 1 g or 2 g starch supplements for 21 days. Poor weight gain
    with diarrhoea were noted only with the highly oxidized material at
    both dietary levels. One rat from each of the high dietary level
    groups was examined. Marked caecal dilatation was seen only in animals
    fed the heavily oxidized starch. It is to be noted that this very
    highly oxidized starch is a commercially unacceptable product
    (Whistler & Belfort, 1961).



         Starch treated at a level of 0.375% chlorine was fed to weanling
    albino rats at 70% of their diet for 10 weeks with corn starch as
    control. Feeding was either unrestricted or by paired-feeding
    technique. No toxic effects were noted. No details of this work,
    carried out in 1944-1945, were available (Garton Sons & Co. Ltd.,

         A corn starch oxidized with 5.5% chlorine using sodium
    hypochlorite (carboxyl content 0.90) was fed to groups of 15 male and
    15 female rats at dietary levels of 0, 5, 10 or 25% for 90 days.
    No adverse effects were noted regarding general health, growth, food
    intake and efficiency, haematology, serum chemistry and urine
    analyses. Diarrhoea was not observed. The amount of faeces dry
    matter/unit food consumed was slightly increased at 25% of the
    oxidized starch in both sexes. In this group the relative weight of
    the caecum was slightly increased, the effect being significant in
    females only. The other organ-to-body weight ratios showed slightly
    increased adrenal weights of females on the test diets, but the
    differences with the controls were not dose-related. No other gross
    changes were observed at autopsy. The histopathological examination
    has not yet been completed (Til et al., 1973).


         The digestibility of hypochlorite-oxidized starch has been
    investigated in vivo and found to be similar to that of unmodified
    starch. The longest of the short-term studies reported extended only
    over 10 weeks and was carried out with an inadequately defined sample.
    Studies with highly oxidized starches (1.4% or more carboxyl groups)
    are not applicable because these products are not acceptable for food
    additive use. Provided the chemical change is limited to the
    introduction of no more than 1 carboxyl group per 25 anhydro-glucose
    units, the biological effects of the modified starch do not appear to
    be deleterious.


    Estimate of acceptable daily intake for man

         Temporarily not limited.*



         Results of histopathological studies by 1974.


    Booher, L. E., Behan, I. & McMeans, E. (1951) J. Nutr., 45, 75

    Garton Sons & Co. Ltd. (1967) Unpublished report

    Shuman, A. C. & Mertz, E. T. (1959) Unpublished report No. 4 of Shuman
         Chemical Lab. Inc. to Corn Industries Research Foundation

    Til, H. P. et al. (1973) Unpublished report No. R 4081 by Centraal
         Instituut voor Voedingsonderzoek TNO

    Tremolières, J., Bernier, J. J. & Lowy, R. (1959) Nutritio et Dieta,
         1, 100

    Whistler, R. L. & Belfort, A. M. (1961) Science, 133, 1599

    White, T. A. (1963) Cereal Science Today, 8, 48


    *    See relevant paragraph in the seventeenth report, pages 10-11.

    See Also:
       Toxicological Abbreviations
       Oxidized starches  (FAO Nutrition Meetings Report Series 46a)
       Oxidized starches (WHO Food Additives Series 1)
       Oxidized starches (WHO Food Additives Series 6)