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.



         These modified starches are prepared by the combined use of
    sodium tripolyphosphate and sodium trimetaphosphate which results in
    cross-linking and esterification of starch chains. The overall extent
    of modification is small, the residual phosphate being of the order of
    0.4% phosphorus.



         The in vitro digestibility of this modified starch by
    pancreatic amylase (Kohn & Kay, 1963) or by pancreatin and porcine
    intestinal mucosa (Leegwater, 1971) was somewhat reduced compared with
    unmodified starch.


    Special studies

         Groups of 10 male and 10 female rats were given 0, 25, or 50%
    modified starch in a low residue diet for seven days. This was
    followed by three further days on a diet containing additional 4%
    cellulose. The body weights of test animals were slightly reduced in
    both sexes in a dose-related manner but the actual changes were small.
    No diarrhoea was noted although faecal dry matter was somewhat higher
    in test animals compared with controls. The addition of cellulose to
    the diet had no adverse effect. No histological abnormality of the
    enlarged caeca was noted (de Groot & Spanjers, 1970).

    Special studies on reproduction

         Groups of 10 males and 20 females were fed for three generations
    10% of starch modified with sodium trimetaphosphate up to 0.01% P and
    sodium tripolyphosphate up to a total of 0.35% P. Rats were mated (P,
    F1 and F2) at week 12 and 20 after weaning. The second litter
    of each generation was used to produce the next generation. 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 counting implantation sites. No adverse effects were
    noted regarding appearance, behaviour, body weights, fertility, litter
    size, resorption quotient, weights of pups and mortality. Caecal
    weights were not increased except the filled caecum weight of F1
    parent males. The spleen weight of F3b females was increased. Gross
    and macroscopical examination did not reveal pathological changes
    attributable to the ingestion of this starch (Til et al., 1971).

    Short-term studies

         Groups of 10 male and 10 female rats received in their diet 0, 25
    and 50% of modified starch (0.3% P) for eight weeks. There were no
    detectable adverse effects on body weight. Faecal water content
    appeared to be higher in animals fed the 50% test level but the
    results were too variable to allow any definite conclusions.
    Production of faeces appeared to be unaffected by this modification
    when compared with controls. No diarrhoea occurred at any test level.
    Caecal weight was only slightly increased at the 25% level in male
    rats but there was no consistent effect on females at any level tested
    (de Groot & Spanjers, 1970).


         Groups of 10 male and 10 female rats were fed on a diet
    containing 10% rising to 35% of phosphated distarch phosphate for a
    total of 60 days. Female rats showed a consistent reduced weight gain
    throughout the test. Although four test and two control animals died
    during the test these incidents were regarded as unrelated to the test
    substance. All animals behaved normally. Haematological examination
    and urinalysis were normal and comparable in the various groups. The
    absolute liver weights of male rats were lower for the test group than
    for controls and the absolute kidney weight were lower for both sexes
    but these findings were not associated with any gross or
    histopathological changes (Kohn et al., 1964).

         Groups of 25 male and 25 female rats were fed diets containing
    0.2, 1.0 and 5.0% modified or unmodified starch for 90 days. Eleven
    controls and three test animals died from intercurrent disease. There
    were no obvious gross or histopathological changes attributable to the
    test substance. Organ weights and haematological examination (days 45
    and 90) were normal in both groups. Pooled urinalysis was comparable
    for all three groups (Kohn et al., 1964).


         Groups of three male and three female beagles were given daily
    for 90 days gelatine capsules containing 50, 250 and 1250 mg modified
    starch/kg bw. No adverse effects were observed as judged by behaviour,
    body weight changes, mortality, haematological studies, blood
    chemistry, urinalysis, liver function tests, organ weights, gross and
    histopathological findings (Cervenka & Kay, 1963).


         Groups of eight Pitman-Moore miniature pigs were weaned at three
    days of age, and were fed formula diets containing 5.4% unmodified
    starch or 5.6% phosphated distarch phosphate for 25 days. Growth was
    normal during the test period. At termination of the study,

    biochemical analyses of blood (haemoglobin) and serum (cholesterol,
    triglyceride, calcium, phosphorus, alkaline phosphatase, urea
    nitrogen, total protein, albumin and globulin) were similar for test
    and control animals. Relative organ weight as well as carcass
    composition (water, fat, protein, ash, Ca, PO4, Na, Mg) and liver
    composition (water, fat, protein and ash), were similar for test and
    control animals (Anderson et al., 1973).

    Long-term studies


         Groups of 30 male and 30 female rats were fed a modified starch
    at dietary levels of 0, 5, 10 and 30% for 104 weeks. No adverse
    effects were noted on general appearance, behaviour, mortality
    experience or food intake. Growth rate and food efficiency were
    similar to controls. Haematology, serum chemistry and urinalysis
    revealed no consistent changes related to the administration of the
    test substance. Relative organ weights were comparable with controls
    except for significantly decreased spleen weight in males and
    significantly increased spleen and kidney weights in females at the
    highest levels fed. These changes were not associated with any gross
    pathological findings. Caecal weights were normal at all test levels.
    There was no obvious evidence of any carcinogenic effect. The
    histological examination did not reveal any distinct compound-related
    changes. The incidence of nephrocalcinosis accompanied by hyperplasia
    of the pelvic epithelium was slightly higher in test animals than in
    controls (de Knecht-Van Eekelen et al., 1971).


         Twelve volunteers consumed on each of four successive days 60 g
    of a phosphated distarch phosphate with 0.35% introduced P. No adverse
    effects were noticed. No changes occurred as regards frequency and
    amount of faeces of faecal water and lactic acid content (Pieters et
    al., 1971).


         The extent of the modification is small. The metabolic behaviour
    of the phosphate moieties has not been studied. The available short-
    term studies in the rat, dog and pig do not reveal any significant
    adverse effects even at high dietary levels. The available evidence
    for modified starches as a group, indicates that caecal enlargement
    without associated histopathological changes is without toxicological
    significance. The long-term and reproduction studies in the rat did
    not reveal any significant adverse effects and can be used for


    Estimate of acceptable daily intake for man

         Not limited.*


    Anderson, T. A. et al. (1973) Unpublished data submitted to Corn
         Refiners Ass., Inc.

    Cervenka, H. & Kay, J. H. (1963) Unpublished report of Industrial
         Biotest Laboratories submitted by Corn Products Co.

    de Groot, A. P. & Spanjers, M. Th. (1970) Unpublished report No. R
         3096 by Centraal Instituut voor Voedingsonderzoek

    de Knecht-van Eekelen, A. et al. (1971) Unpublished report No. R 3392
         by Centraal Instituut veer Voedingsonderzoek

    Kohn, F. E., Kay, J. H. & Calandra, J. C. (1964) Unpublished report
         submitted by Corn Products Co.

    Kohn, F. E. & Kay, J. H. (1963) Unpublished report by Industrial
         Biotest Laboratories submitted by Corn Products Co.

    Leegwater, D. C. (1971) Unpublished report No. R 3431 by Centraal
         Instituut voor Voedingsonderzoek

    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., Spanjers, M. Th. & de Groot, A. P. (1971) Report No. 3403
         of Centraal Instituut voor Voedingsonderzoek


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

         Includes distarch phosphate prepared using trimetaphosphate or
    phosphated distarch phosphate or the sum of both. Subject to limits of
    phosphorous load.

    See Also:
       Toxicological Abbreviations
       Phosphated distarch phosphate  (FAO Nutrition Meetings Report Series 46a)
       Phosphated distarch phosphate (WHO Food Additives Series 1)
       Phosphated distarch phosphate (WHO Food Additives Series 17)