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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.

    HYDROXYPROPYL DISTARCH PHOSPHATE*

    Explanation

         This compound has 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

         Digestibility was tested in groups of five rats fed for seven
    days on basal diet supplemented by 0, 1 and 3 g modified or control
    starch. No difference in weight gain was observed (Prier, 1961).

         In a caloric utilization study groups of 10 male rats were fed
    for 10 days either unmodified starch or starch modified with 3%,
    6% or 8% propylene oxide as well as 0.0123% phosphorus oxychloride
    equivalent to a DS ranging from 0.085 to 0.23. There was a slight
    decrease in caloric utilization with increasing degree of
    modification. Diarrhoea occurred whenever 4 mg modified starch was
    included in the daily ration but also at the 2 mg/day level with the
    more highly modified starches. The relative organ weight of the empty
    caecum was always increased at the 4 mg/day level but also at the
    2 g/day level with the two highly modified starches. Histological
    examination of the heart, liver, spleen, kidney and caecum revealed no
    obvious abnormalities related to treatment. Similar data were obtained
    in a series of tests using starches modified in the intermediate range
    of DS by the use of propylene oxide and phosphorus oxychloride
    (Porter, ]971).

              

    *    Modification is carried out with 0.1% phosphorus oxychloride and
    8-10% of propylene oxide. Cross-linkage would be no greater than is
    experienced on modification with phosphorus oxychloride alone and
    either linkages would probably not exceed 20 per 100 anhydroglucose
    units.

         Groups of six weanling rats (Holtzman strain) were maintained on
    a semi-purified diet containing 35% unmodified starch or hydroxypropyl
    distarch phosphate from tapioca for 30 and 180 days. The starches used
    in the study were either unprocessed or processed (gelatinized at pH 4
    and pH 7 and then freeze-dried). The food efficiency was similar in
    all groups with the exception of the group fed modified unprocessed
    starch which had a food efficiency lower than the other groups.
    Autopsy of the animals at the end of the test period showed no
    abnormalities other than caecal enlargement in all animals fed
    unprocessed or processed modified starch. Test animals fed diets
    containing unmodified starch did not have enlarged caeca. No
    histopathological abnormalities were observed (Hood, 1974).

         Male weanling rats (Holtzman) were fed semi-purified diets
    containing 15 or 35% of either hydroxypropyl distarch phosphate or
    unmodified starch for 28 days. At the 35% level, mean weight gains,
    food consumption and PER's (3.00  0.13/2.74  0.42, modified/
    unmodified) were similar. Diarrhoea, caecal enlargement and depression
    of caecal pH from 7.2 to 5.0 was observed in the animals fed the
    modified starch. Aerobic microorganisms were 10 to 1000-fold greater
    in the faeces from animals on the modified starch than those on
    unmodified starch. The changes were more marked in animals fed the 35%
    diet. After 180 days, all streptococci disappeared from the caecal
    microflora; coliforms declined from 107 to 104/g faeces, while
    lactobacilli remained constant (Bruns & Hood, 1973).

         Studies on the "in vitro" digestibility of hydroxypropyl
    distareh phosphate (tapioca) with pancreatic or fungal amylase, showed
    that the extent of hydrolysis depended on gelatinization conditions
    (time, temperature and pH), and retrogradation of the starch (Hood,
    1973).

    TOXICOLOGICAL STUDIES

    Short-term studies

    Rat

         Groups of 10 male rats were fed diets containing 17%, 34%, 51% or
    68% modified starch for 28 days. Growth and body weights were reduced
    compared with controls at the highest levels tested. The relative
    liver weights were slightly increased for those same levels compared
    with controls fed food grade unmodified starch. The relative organ
    weights of empty caeca was raised at all levels tested. No
    histological abnormalities were seen in heart, liver, spleen, kidney
    and caecum (Porter, 1971).

         Groups each of 30 weanling rats (FDRL-Wistar) equally divided by
    sex, were maintained on diets containing 5, 10 or 25% of the starch
    modified with 10% propylene oxide, or 25% unmodified starch, for a
    period of 90 days. Four rats died during the test period, but deaths
    were not treatment-related. At the highest level of intake of the
    modified starch, the faeces were soft and bulky during the first seven
    weeks of test, but normal for the rest of the test period. Growth,
    food intake, and food efficiency of all groups was normal with the
    exception of a slight decrease in feed efficiency in males in the 25%
    modified starch group. Haematologic, biochemical and urine analysis
    were within normal limits. At autopsy, absolute and relative organ
    weight of test and control animals were comparable with exception of
    the caecum. Caecum plus contents showed a treatment-corelated
    response, however, in the case of the empty caeca, significant
    increase in weight was only observed in males on the 25% diet.
    Histological studies showed that about 40% of the rats in the test
    groups had calcerous deposits within the renal pelvis and/or pelvic
    epithelium (5% group, 18/30, 10% group, 20/30, 25% group, 22/30). No
    other compound-related changes were observed with the exception of a
    slight thinning of the caecum, which were cytologically normal (Food
    and Drug Research Laboratories Inc., 1973).

         Groups of 15 male and 15 female rats are fed on diets containing
    0, 5, 10 and 25% of a modified starch prepared by treating corn starch
    with 0.1% phosphorus oxychloride and 5% propylene oxide (hydroxypropyl
    degree of substitution 0.07). The feeding period was 90 days. General
    condition, growth, food intake and efficiency, haematology, serum
    chemistry and urine analyses were not unfavourably affected at any
    dietary level. Diarrhoea did not occur, but the water content of the
    faeces and the amount of faeces dry matter per 100 g food consumed was
    increased at the 10 and 25% feeding level. The caecal weights both
    filled and empty were distinctly increased only in the 25% diet group
    in both sexes. Males of this group also showed slightly decreased
    weights of adrenals and testicles. Macroscopically no compound-related
    differences were observed amongst the various groups. The incidence of
    calcerous deposits in the interocorticomedullary area of the kidneys
    was found to be higher in females of the highest dose group than
    controls (viz., 11/15:2/15). However, although the incidence was
    high compared with test animals, the incidence was comparable with
    that previously observed in control rats in this laboratory. No other
    compound-related effects were observed. Haematologic studies at the
    termination of the study showed slight changes in total serum protein
    and serum albumin in the test groups (Til et al., 1973; Til et al.,
    1974).

    Long-term studies

         None available.

    Comments:

         The available data from several short-term studies show no
    significant adverse effect on feeding up to 35% of modified starch to
    rats for six months. The reports of calcerous deposits in the renal
    pelvis of the rat have been confirmed although the incidence seen was
    comparable with that seen in studies on other phosphate-modified
    starches and may be related to the high phosphate content of the
    starch. The requirements of the Committee have now been met.

    EVALUATION

         Acceptable daily intake not specified.*

    REFERENCES

    Bruns, P. & Hood, L. F. (1973) J. Nutr., 103, XXI (Abstract 20)

    Hood, L. (1974) Personal communication

    Hood, L. (1973) Cereal Science Today, 18, 294

    Food and Drug Research Laboratory Inc. (1973) Unpublished report
         submitted to Corn Refiners Association Inc.

    Porter, M. W. (1971) Report dated 7 May 1971 submitted to WHO by R & D
         Division, A. E. Staley Manufacturing Co., Illinois

    Prier, R. T. (1961) Unpublished report by Wisconsin Alumni Research
         Foundation No. 1031347/8, submitted by Stein, Hall & Co. Inc.

    Til, H. P. et al. (1973) Unpublished report No. R 4082 by Centraal
         Instituut voor Voedingsonderzoek TNO

              

    *    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.


    See Also:
       Toxicological Abbreviations
       Hydroxypropyl distarch phosphate  (FAO Nutrition Meetings Report Series 46a)
       Hydroxypropyl distarch phosphate (WHO Food Additives Series 1)
       Hydroxypropyl distarch phosphate (WHO Food Additives Series 5)
       HYDROXYPROPYL DISTARCH PHOSPHATE (JECFA Evaluation)