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    INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY

    WORLD HEALTH ORGANIZATION



    TOXICOLOGICAL EVALUATION OF SOME
    FOOD COLOURS, ENZYMES, FLAVOUR
    ENHANCERS, THICKENING AGENTS, AND
    CERTAIN FOOD ADDITIVES



    WHO FOOD ADDITIVES SERIES 6







    The evaluations contained in this publication were prepared by the
    Joint FAO/WHO Expert Committee on Food Additives which met in Rome,
    4-13 June 19741


    World Health Organization     Geneva     1975






              

    1  Eighteenth Report of the Joint FAO/WHO Expert Committee on
    Food Additives, Wld Hlth Org. techn. Rep. Ser., 1974, No. 557.
    FAO Nutrition Meetings Report Series, 1974, No. 54.

    OXIDIZED STARCHES*

    Explanation

         These compounds have been evaluated for acceptable daily intake
    by the Joint FAO/WHO Expert Committee on Food Additives (see Annex 1,
    Refs Nos 20, 27 and 34) in 1969, 1971 and 1973.

         Since the previous evaluation additional data have become
    available and are summarized and discussed in the following monograph.
    The previously published monographs have been expanded and are
    reproduced in their entirety below.

    BIOLOGICAL DATA

    BIOCHEMICAL ASPECTS

         Early comparative experiments pointed to inhibition of amylolysis
    (Tremolieres 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 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, C. C. & Mertz, E. T., 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 post-mortem 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 post-mortem 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 post-mortem examination
    (Booher et al., 1959).

              

    *    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 carbozyl 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.

         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 dilation 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).

    TOXICOLOGICAL STUDIES

    Short-term studies

    Rat

         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,
    1967).

         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. No compound related effects were
    observed. Haematologic studies at week 13 showed no distinct or
    significant differences between tests and control groups (Til et al.,
    1973; Til et al., 1974).

    Long-term studies

         None supplied.

    Comments:

         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 extends over 90 days and
    showed no serious toxic effects at the 25% dietary level, the highest
    level-tested. The full results of this study have now been reported.
    Studies with highly oxidized starches (14% or more carboxyl group) are
    not applicable because these products are not useful as food
    additives. Provided the chemical change is limited to the introduction
    of no more than one carboxyl group per 25 anhydroglucose units, the
    biological effects of the modified starch do not appear to be
    deleterious. The requirements of the Committee have now been met.

    EVALUATION

         Acceptable daily intake 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 any acceptable
    daily intake (ADI) in mg per kg of body weight is not deemed
    necessary.

    REFERENCES

    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 Laboratories Inc. to Corn Industries Research Foundation

    Til, H. P. et al. (1973) Unpublished report No. R4081 by Centraal
         Instituut voor Voedingsonderzoek TNO

    Til, H. P. et al. (1974) Unpublished report NR R4081 by Centraal
         Instituut voor Voedingsonderzack, TNO

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

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

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


    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 5)