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    PHOSPHATED DISTARCH PHOSPHATE

    Explanation

         This modified starch was previously evaluated for an ADI for man
    by the Joint FAO/WHO Expert Committee on Food Additives in 1969, 1971
    and 1973 (see Annex I, Refs. 19, 26 and 29). Toxicological monographs
    were published in 1969, 1972 and 1974 (see Annex I, Refs. 20, 27 and
    30).

         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.

    Introduction

         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.

    BIOLOGICAL DATA

    BIOCHEMICAL ASPECTS

         The in vitro digestibility of this modified starch (prepared
    from cornstarch) by pancreatic amylase was somewhat reduced compared
    with unmodified starch (Kohn & Kay, 1963a). In vitro digestibility
    of this modified starch (prepared from potato starch) by pancreatin
    and porcine intestinal amylase was also reduced compared with
    unmodified starch (Leegwater, 1971). However, in vitro digestibility
    and utilization of this modified starch (prepared from milo starch)
    was similar to unmodified starch when measured by weight gain (Kohn &
    Kay, 1963b).

    TOXICOLOGICAL STUDIES

    Special studies on reproduction

         Groups of 10 male and 20 female rats were fed for 3 generations
    10% of starch modified with sodium trimetaphosphate up to 0.01% P and
    sodium tripolyphosphate up to a 0.32% P. Rats were mated (P1, F1 and
    F2) at weeks 12 and 20 after weaning. The second litter of each
    generation was used to produce the next generation. The F3b-
    generation was kept for 3 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 weight, 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; de Groot et al., 1974).

    Special studies

         Groups of 10 male and 10 female rats were given 0, 25, or 50%
    modified starch in a low residue diet for 7 days. This was followed by
    3 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).

    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 8 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).

    Rat

         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 4 test and 2 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 weights were lower for both sexes
    but these findings were not associated with any gross or
    histopathological changes (Kohn et al., 1964a).

         Groups of 25 male and 25 female rats were fed diets containing
    1.0 and 5.0% modified or unmodified starch for 90 days. Eleven
    controls and 3 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 3 groups (Kohn et al., 1964b).

    Dog

         Groups of 3 male and 3 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).

    Pig

         Groups of 8 Pitman-Moore miniature pigs were weaned at 3 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., 1973a, b).

    Long-term studies

    Rat

         Groups of 30 male and 30 female rats were fed this 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.
    Histological examination did not reveal any distinct compound-related
    changes. The study did not reveal any indication of carcinogenicity.
    In comparison with the controls, the males fed the 30% level of the
    modified starch showed a slightly increased degree and incidence of
    focal hyperplasia of the renal papillary and pelvic epithelium,
    accompanied by calcified patches in the underlying tissue. The
    hyperplastic and calcified tissues often protruded into the renal
    pelvis and were localized most often in the papilla near the junction
    of the papillary and pelvic epithelium. This lesion was seen to a

    slight or moderate degree in both sexes at most levels including the
    controls but was more pronounced and of higher occurrence in males at
    the highest dose level (de Knecht-Van Eekelen et al., 1971; de Groot
    et al., 1974).

         Roe (1979) has conducted an extensive review of this type of
    mineral deposition in the renal pelvis of rats and concluded that
    pelvic nephrocalcinosis, corticomedullary nephrocalcinosis, acute
    tubular nephropathy, and calculus formation are manifestations of
    mineral imbalance and are of relatively common occurrence in untreated
    laboratory rats (particularly older animals).

    OBSERVATIONS IN MAN

         Twelve volunteers consumed on each of 4 successive days 60 g of a
    phosphated distarch phosphate. No adverse effects were noted. No
    changes occurred as regards frequency and amount of faeces or faecal
    water and lactic acid content (Pieters et al., 1971).

    Comments

         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 effects, except for a slight increase in
    the incidence of renal focal hyperplasia and mineral deposit. This
    lesion is considered to be associated with imbalances of Ca/P and Mg
    in the diet.

    EVALUATION

    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
         necessary.

         The ADI includes distarch phosphate prepared using
    trimetaphosphate or phosphated distarch phosphate or the sum of both.
    Subject to limits of phosphorus load (see monograph on "Phosphoric
    acid and phosphate salts").

    REFERENCES

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

    Anderson, T. A., Filer, L. J., Fomon, S. J., Andersen, D. W.,
         Jensen, R. L. & Rogers, R. R. (1973b) Effects of waxy corn starch
         modification on growth, serum biochemical values and body
         composition of Pitman-Moore miniature pigs, Fd. Cosmet.
         Toxicol., 11, 747-754

    Cervenka, H. & Kay, J. H. (1963) Subacute oral toxicity of phosphate
         starch code number 4822: beagle dogs. Report of Industrial
         Biotest Laboratories, Inc., Northbrook, Ill. Submitted by Corn
         Products Co., Argo, Ill.

    de Groot, A. P. & Spanjers, M. Th. (1970) Observations in rats fed on
         diets containing five different chemically modified starches.
         Report No. R 3096 by Centraal Instituut voor Voedingsonderzoek,
         Zeist, Holland

    de Groot, A. P., Til, H. P., Feron, V. J., Van der Meullen, H. C. D. &
         Willems, M. I. (1974) Two-year feeding and multigeneration
         studies in rats on five chemically modified starches, Fd.
         Cosmet. Toxicol., 12, 651-664

    de Knecht-van Eekelen, A., Til, H. P., Willems, M. I. & de Groot,
         A. P. (1971) Chronic (2-year) feeding study in albino rats with
         phosphated distarch phosphate (a chemically modified starch).
         Report No. R 3392. Centraal Instituut voor Voedingsonderzoek,
         Zeist, Holland

    Kohn, F. E. & Kay, J. H. (1963a) The digestion of various starches by
         pancreatic amylase. Report of Industrial Biotest Laboratories,
         Inc., Northbrook, Ill. Submitted to Corn Products Company, Argo,
         Ill.

    Kohn, F. E. & Kay, J. H. (1963b) Nutritional assay of starch 4822.
         Report of Industrial Biotest Laboratories, Inc., Northbrook, Ill.
         Submitted to Corn Products Company, Argo, Ill.

    Kohn, F. E., Kay, J. H. & Calandra, J. C. (1964a) 60-day Target organ
         study on phosphate starch, code No. 4822. Report of Industrial
         Biotest Laboratories, Inc., Northbrook, Ill. Submitted to Corn
         Products Company, Argo, Ill.

    Kohn, F. E., Kay, J. H. & Calandra, J. C. (1964b) Subacute oral
         toxicity of phosphate starch code No. 4822. Report of Industrial
         Biotest Laboratory, Inc., Northbrook, Ill. Submitted to Corn
         Products Company, Argo, Ill.

    Leegwater, D. C. (1971) Report No. R 3431 by Centraal Instituut voor
         Voedingsonderzoek, Zeist, Holland. Submitted to WHO

    Pieters, J. J. L., van Staveren, W. A. & Brinkhuis, B. G. A. M. (1971)
         Unpublished report No. 3433 by Centraal Instituut voor
         Voedingsonderzoek, Zeist, Holland. Submitted to WHO

    Roe, F. J. C. (1979) Mineral deposition in the renal pelvis of rats:
         A brief review, unpublished report. Submitted to WHO

    Til, H. P., Spanjers, M. Th. & de Groot, A. P. (1971) Report No. 3403
         of Centraal Instituut voor Voedingsonderzoek, Zeist, Holland.
         Submitted to WHO
    


    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 5)
       PHOSPHATED DISTARCH PHOSPHATE (JECFA Evaluation)