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    WORLD HEALTH ORGANIZATION

    WHO Food Additives Series 1972, No. 1




    TOXICOLOGICAL EVALUATION OF SOME 
    ENZYMES, MODIFIED STARCHES AND 
    CERTAIN OTHER SUBSTANCES




    The evaluations contained in this publication were prepared by the
    Joint FAO/WHO Expert Committee on Food Additives which met in Rome,
    16-24 June 19711





    World Health Organization

    Geneva

    1972





                   

    1 Fifteenth Report of the Joint FAO/WHO Expert Committee on Food
    Additives, Wld Hlth Org. techn. Rep. Ser., 1972, No. 488; FAO
    Nutrition Meetings Report Series, 1972, No. 50.

    The monographs contained in the present volume are also issued by the
    Food and Agriculture Organization of the United Nations, Rome, as FAO
    Nutrition Meetings Report Series, No. 50A

    (c) FAO and WHO 1972


    DISTARCH PHOSPHATE

    Biological data

    Native starches are known to contain phosphoric acid esters equivalent
    to 0.004 per cent. P and some potato starches up to 0.1 per cent.
    Distarch phosphate is made by the use of sodium trimetaphosphate which
    cross-links starch chains at an approximate rate of one phosphate link
    per 620 glucopyranose units.  The amounts of phosphate introduced are
    at the most 0.04 per cent. P (Graefe, 1964).

    Cross-linking of starch chains may be produced also by the use of
    phosphorus oxychloride.  Although theoretically likely, there is no
    relevant chemical evidence to show that modification by phosphorus
    oxychloride in fact produces distarch phosphate.  Although the
    addition of phosphorus oxychloride to dry material will cause
    chlorination, the processes involved in starch modification always
    proceed in the presence of water and/or alkali.  Under these
    circumstances phosphorus oxychloride hydrolyses rapidly with the
    production of phosphoric and hydrochloric acid and the formation of
    other products than phosphate cross-linkages is very unlikely (Hudson
    and Moss, 1962; Grunze, 1959). The maximum number of phosphate bridges
    could reach one per 100 glucopyranose units.

    Biochemical aspects

    In vitro digestion of a distarch phosphate using trimetaphosphate by
    salivary, pancreatic and intestinal amylase was measured by the
    production rate of reducing sugar.  No deleterious effect was shown on
    enzymic depolymerisation (Rosner, 1960).

    Caloric value and digestibility of a distarch phosphate using
    trimetaphosphate were tested in groups of 10 rats fed for 7 days on 4g
    basal diet with either 0.9 g or 3.6 g starch supplement by observing
    the gain in body-weight and the organ weights of liver, kidney, heart
    and spleen after the feeding period.  No significant differences were
    noted between the modified and the unmodified starches (Hixson, 1960).
    Distarch phosphate using trimetaphosphate was fed to groups of male
    and female rats on 5 g diets as 1 g or 2 g supplements over 21 days.
    Weight gains were comparable for modified and unmodified starches
    tested. Animals appeared normal at autopsy (Whistler and Belfort,
    1961),

    The in vitro digestibility of trimetaphosphate modified starch by
    pancreatic mylase was somewhat reduced compared with normal unmodified
    starch (Kohn and Kay, 1963a).  In vivo digestibility was examined in
    groups of 10 male rats fed for 10 days 5 g basal diet supplemented by
    1 g, 2 g or 4 g unmodified or trimetaphosphate modified starch. 
    Weight gains were identical for both types tested at all three levels
    of supplementation.  No unusual behaviourial reactions were observed
    (Kohn and Kay, 1963a).

    In vitro digestibility by pancreatin of corn or potato starch
    modified with 0.05 or 0.1 per cent. phosphorus oxychloride was found
    to be similar to the unmodified starch.  When 0.5 or 1.5 per cent. of
    phosphorus oxychloride was used, the resulting crosslinkage
    considerably inhibited digestibility in vitro in a manner related to
    the concentration of cross-linking agent used. (Janzen, 1969.) 
    Caloric value was determined for starch treated with 0.06 per cent.
    phosphorus oxychloride in groups of 6 male and 6 female rats receiving
    52 per cent. of distarch phosphate for six weeks as sole carbohydrate
    source in their diet.  No differences were noted between modified and
    unmodified starches (Oser, 1954).  The in vitro digestibility by
    amyloglucosidase of starch modified with 0.035, 0.07 or 0.1 per cent.
    phosphorus oxychloride varied between 96.4 and 98.3 per cent. (Kruger,
    1970).

    Short-term studies

    Rat

    Groups of 10 male and 10 female rats were fed on a diet containing 10
    per cent. rising to 35 per cent. of phosphated distarch phosphate
    (trimetaphosphate) for a total of 60 days.  Female rats showed a
    consistent reduced rate of 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 liver weights of male rats were
    lower for the test group than for controls and the kidney weights 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 per cent. trimetaphosphate 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 groups (Kohn et
    al., 1964).

    Groups of 10 male and 10 female rats received 0, 5, 15 and 45 per
    cent. of two types of distarch phosphate (0.085 per cent. esterified
    and 0.128 per cent. esterified phosphate) in their diet for 90 days.
    No abnormalities compared with controls were seen as regards general
    appearance, behaviour, mortality, food consumption, haematology, serum
    chemistry and urinalysis which could be ascribed to the action of
    either of the test substances.  No diarrhoea or increased caecal
    weights were observed. Gross and histopathology revealed no
    abnormalities attributable to the test substances (Til et al., 1970).

    Long-term studies

    None available.

    Comments

    Although direct chemical evidence is lacking, it is very likely that
    phosphorus oxychloride modification will produce distarch phosphates
    similar to those formed from trimetaphosphate.  The extent of
    phosphate cross-linkage using trimetaphosphate is very small.  The
    metabolic behaviour of the phosphate bridges has not been studied.
    However, the available short-term studies reveal no adverse changes
    with either type of modified starch even at high levels in the diet.
    As these modified starches represent preliminary stages in the
    manufacture of the more highly modified phosphated distarch phosphates
    it is appropriate to use the results of the long-term and reproduction
    studies in rats relating to phosphated distarch phosphate to evaluate
    all phosphate-modified starches.

    EVALUATION

    Temporarily not limited.*

    Further work required

    See phosphated distarch phosphate.

    REFERENCES

    Graefe, G. (1964) "Die Stärke", 16, 158

    Hixson, 0. F. (1960) Unpublished report H-1004 of Rosner-Hixson
    Laboratories

    Industrial Biotest Lab. Inc. (1964) Unpublished report submitted by
    Corn Products Co.

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

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

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


                   

    * Except for good manufacturing practice.

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

    Rosner, L. (1960) Unpublished report H-1004-1 of Rosner-Hixson
    Laboratories

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


    See Also:
       Toxicological Abbreviations
       Distarch phosphate (WHO Food Additives Series 5)
       DISTARCH PHOSPHATE (JECFA Evaluation)