IPCS INCHEM Home

    ACETYLATED DISTARCH PHOSPHATE

    Explanation

         This substance was evaluated for acceptable daily intake for man
    (ADI) by the Joint FAO/WHO Expert Committee on Food Additives in 1969
    and 1971 (see Annex I, Refs. 20 and 27). A toxicological monograph was
    issued in 1974 (see Annex I, Ref. 33).

         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

         Modification is usually performed by the use of up to 0.1% of
    phosphorus oxychloride and 5% acetic anhydride. Vinyl acetate may be
    used as an alternative acetylating agent. Maximum acetylation amounts
    usually to 2.5% acetyl groups.

    BIOLOGICAL DATA

    BIOCHEMICAL ASPECTS

         The digestibilities in vitro by pancreatin and porcine mucosal
    enzymes of acetylated distarch phosphates, modified to 1.6% and 2.3%
    acetyl content, were found to be 93% and 31%, respectively of that of
    unmodified starch (Leegwater, 1971).

    TOXICOLOGICAL STUDIES

    Special studies on kidney lesions associated with dietary modified
    starches

    Rat

         Groups of 25 female Sprague-Dawley rats were fed diets containing
    either 30% acetylated distarch phosphate or 30% unmodified starch
    (control) in a 1-year study with weanling rats (Experiment I) and a
    separate 9-month study utilizing 9-month-old rats (Experiment II). The
    Ca concentration in the diet was c. 1%, P concentration c. 0.8% and Mg
    c. 0.15%. Urinary calcium concentration and total daily output were
    significantly increased in animals on the test diet (Experiments I and
    II), but only minor differences occurred in phosphorus, oxalate,
    magnesium and creatinine excretion. No significant effects were
    observed on body weight, food consumption, urine volume, urine pH and
    crystal content or faecal mineral content in animals on the test diet.
    At autopsy, caecal enlargement was present in treated animals, but no
    other treatment-related effects on relative organ weights were

    observed. No treatment-related histopathological effects were observed
    in the uterus or lower urinary tract, liver, parathyroid, caecum or
    ovaries in either experiment. Histological examination of kidney
    sections demonstrated the presence of treatment-related pelvic
    nephrocalcinosis. An apparent correlation was observed between the
    increased incidence of pelvic nephrocalcinosis, increased accumulation
    of calcium in the kidney, and increased urinary excretion of calcium.
    Residues of calcium in kidney tissue were significantly higher in test
    groups than in control (Hodgkinson et al., 1981).

         Roe (1979) has conducted an extensive review 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).

    Special studies on reproduction

    Rat

         A 3-generation study was performed using groups of 10 males and
    20 females of the P, F1 and F2 generations to produce 2 successive
    litters in each generation by mating at weeks 12 and 20 after weaning.
    Ten males and 10 females of the F1b generation were kept for 3 weeks
    after weaning and then sacrificed for histopathological studies. The
    P, F1b and F2b parents were used for determination of implantation
    sites. The test material fed at 10% of the diet consisted of a starch
    modified with 8% acetic anhydride and 0.02% phosphorus oxychloride
    (D.S. of 0.093) and another starch modified with 4.5% vinyl acetate
    and 1.2% phosphorus oxychloride (D.S. of 0.064, 0.043% phosphorus
    introduced). No adverse effects were noted with respect to health,
    behaviour, mortality, growth, fertility, litter size, resorption
    quotient, weaning weight or mortality of young. Caecal weight of
    parent rats fed the modified starches was not increased. Gross
    pathology revealed a slightly decreased thyroid weight and a slightly
    increased caecum weight in F3a rats fed the starch treated with
    acetic anhydride and phosphorus oxychloride. Histopathology failed to
    reveal any treatment-related changes (De Groot et al., 1974).

         Weanling Wistar-derived rats were segregated by sex into groups
    of 10 males and 20 females and fed a test diet consisting of 10%
    acetylated distarch phosphate + 20% unmodified starch and a control
    diet of 30% unmodified starch throughout the pre-mating, gestation and
    lactation periods. Control animals received equivalent levels of
    unmodified starch in their diet. At weeks 12 and 20, all rats were
    mated in groups of 5 males and 10 females to produce 2 successive
    litters (F1a and F1b). Litters were randomly culled on day 1 to 8
    pups when required. Ten male and 20 female weanlings were randomly
    selected from the F1b litter and the above procedure repeated to

    produce F2a and F2b litters. In similar fashion, male and female
    weanlings from the F2b generation were mated to produce F3a and F3b
    litters. After weaning their second litter, dams were sacrificed and
    the uterus examined for implantation sites. Ten male and 20 female
    weanlings were selected from the F3b litters and continued on their
    diets for 3 more weeks before sacrifice. No treatment-related
    differences in mortality or fertility were observed between the test
    groups and controls. The growth rate of the pups in all groups given
    acetylated distarch phosphate was comparable with that in the
    controls, and mortality in utero (resorption quotient) and preweaning
    mortality were low in all groups. The rats from the F3b generation,
    sacrificed 3-4 weeks after weaning, showed no treatment-related gross
    or histological changes (de Groot et al., 1974).

    Special studies

         Groups of 10 male and 10 female rats were fed 0, 25 or 50% of 2
    different modified starches (acetic anhydride and vinyl acetate
    modified) in a low residue diet for 7 days followed by the additional
    feeding of 4% cellulose for 3 days. The body weights of animals fed
    50% modified starch were somewhat lower than those of the controls.
    Production of faecal dry matter was increased in the higher groups and
    less so at the 25% level. Diarrhoea occurred at the higher level with
    both modified starches. The addition of 4% cellulose had no effect on
    the severity or frequency of the diarrhoea. At the higher level, there
    was also some loss of hair in both sexes (de Groot & Spanjers, 1970).

    Short-term studies

    Hamster

         Groups of 10 male and 10 female Syrian Golden hamsters, weighing
    30-40 g, were fed a diet containing either 30% acetylated distarch
    phosphate or 30% untreated starch for 30 days. Hamsters fed the test
    diet exhibited a reduction in average daily weight gain, compared to
    control animals, but the average daily test diet intake was also
    reduced. Comparison of feed consumption to corresponding weight gain
    did not indicate a significant difference in efficiency of utilization
    of the test and control diets. No treatment-related differences were
    noted in haematology, clinical chemistry or urinalysis data. No
    treatment-related lesions were evident in histological sections from
    liver and kidney (Newberne & Buttolph, 1977).

    Rat

         Groups of 10 male and 10 female rats were fed 0, 25 and 50% of 2
    different modified starches (acetic anhydride and vinyl acetate
    modified) in their diet for 8 weeks. Body weights of animals on the
    higher test levels were somewhat lower than at the 25% levels and also
    lower than controls in both sexes. However, the differences were not

    statistically significant. The faecal water content was variable and
    could not be related to dietary dosage levels. Production of faecal
    dry matter was increased in both sexes at the higher level tested and
    slightly so at the 25% dietary level. The incidence of diarrhoea was
    insignificant. A dose-related increase in caecal weight occurred in
    both sexes. No histological abnormalities of the enlarged caeca were
    noted (de Groot & Spanjers, 1970).

    Pig

         Groups of 4 male and 4 female pigs were given 0, 35 or 70% of
    modified starch in their diet over 14-1/2 weeks. Growth rate and food
    consumption were satisfactory. Haematology, blood chemistry and
    urinalysis revealed no treatment-related abnormalities. Ophthalmoscopy
    showed no abnormalities associated with the test substance. Organ
    weight, gross and histopathology revealed no abnormalities in test or
    control groups. Three pigs in the higher test group died suddenly at
    various intervals during the test without any evidence pointing to the
    cause of their death. One pig in the higher test group and another in
    the 35% group showed evidence of neurological malfunction. The animal
    on 70% test substance died, that on the lower dietary level recovered.
    No histological evidence of nervous system involvement was noted in
    these 2 or in any other animal (Shillam et al., 1971).

         A further pig study in which groups of 8 pigs were fed 0, 5, 15
    and 25% modified starch in the diet for 14 weeks, showed no effect on
    growth, food consumption, haematology or biochemistry. One pig died of
    unknown cause. No significant abnormalities were found at post mortem
    but histology was not performed except in the animal which died
    (Shillam et al., 1973).

    Long-term studies

    Rat

         Groups of 30 male and 30 female rats were fed 2 different
    modified starches (acetic anhydride and vinyl acetate modified) at
    levels of 0, 5, 10 and 30% in their diet for 104 weeks. Appearance,
    behaviour, food consumption and mortality were not adversely affected
    nor was diarrhoea observed at any level with either modified starch.
    Haematology, serum chemistry and urinalysis revealed no effects
    related to treatment in any group. There was a dose-related increase
    in the caecal weight in both sexes at the 30% level but in males only
    at the 10% level. All other organ weights showed no treatment-related
    changes. No gross or microscopic pathological abnormalities were noted
    which could be related to the test substances or which would point to
    any carcinogenic effects or to any compound-related effects. The caeca
    appeared remarkably normal (Til et al., 1971a).

         Groups of 30 male and 30 female weanling Wistar-derived rats were
    fed diets containing 0, 5, 10 and 30% acetylated distarch phosphate
    and 30% unmodified starch (control) for 2 years. A slight growth
    retardation was observed at the 30% dietary level, with an increase in
    the relative weight of the caecum. The caecal enlargement was
    attributed to an adaptive response to the presence of indigestible
    material, rather than to a pathological response. Females exhibited an
    apparent dose-related increase in relative adrenal weight. Other
    organs exhibited slightly increased weight at higher dose levels, but
    these findings were, in most cases, considered incidental because
    histological sections revealed no treatment-related effects. The only
    treatment-related effect that was observed histologically was a kidney
    lesion which occurred at a higher incidence in the high dose males.
    The lesion consisted of focal hyperplasia of the renal papillary and
    pelvic epithelium accompanied by calcified patches in the underlying
    tissues. No treatment-related effect was observed on the pattern of
    neoplasm development, or on food intake, survival, haematology or
    clinical chemistry (de Groot et al., 1974).

    OBSERVATIONS IN MAN

         Twelve volunteers consumed on each of 4 successive days, 60 g
    acetylated distarch phosphates of either 1.5% or 2.33% acetyl content.
    No abnormalities were observed as regards frequency and amount of
    faeces as well as faecal water and lactic acid content. No other
    adverse effects were noted (Pieters et al., 1971).

    Comments

         The feeding studies with rats show that the modified starch is
    well utilized. The available evidence for the group of modified
    starches considered suggests that caecal enlargement without
    associated histopathological changes is without toxicological
    significance. The short-term study shows no other significant effects
    related to treatment, the observed growth depression being the obvious
    result of the high dietary level used. A reproduction study in rats
    showed no significant compound-related effects. A long-term feeding
    study in rats showed no compound-related effect, apart from decreased
    weight gain, caecal enlargement, and an increased incidence of renal
    epithelial hyperplasia in female rats. Data derived from special
    studies with a group of modified starches suggest that the latter
    effect is due to an imbalance in dietary Ca/F and Mg.

    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.

    REFERENCES

    De Groot, A. P. & Spanjers, M. Th. (1970) Unpublished 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, 651-663

    Hodgkinson, A., Robertson, W. G., Fourman, J. & Davis, D. (1981) A
         comparison of the effects on mineral metabolism of diets
         containing waxy maize starch, either of two chemically-modified
         waxy maize starches, or lactose. Unpublished report from the
         General Infirmary, and from the Medical School, University of
         Leeds (1981). Submitted by the US Food and Drug Administration to
         the World Health Organization, 1982

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

    Newberne, P. M. & Buttolph, M. L. (1977) A preliminary report of a
         thirty-day study in hamsters fed modified starches. Unpublished
         report from Massachusetts Institute of Technology (1977),
         submitted by the US Food and Drug Administration to the World
         Health Organization, 1982

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

    Roe, F. J. C. (1979) Mineral deposition in the renal pelvis of rats: A
         brief review. Unpublished report submitted to the World Health
         Organization

    Shillam, K. W. G. et al. (1971) Unpublished report No. 3978/71/136
         by Huntingdon Research Centre

    Shillam, K. M. G. et al. (1973) Unpublished report No. CRN5/73254 by
         Huntingdon Research Centre

    Til, H. P., Feron, V. J., Spanjers, M. Th. & de Groot, A. P. (1971a)
         Chronic (two-year) feeding study in rats with two chemically
         modified starches (acetylated distarch phosphate and acetylated
         diamylopectin phosphate). Unpublished report from report No. R
         3351. Centraal Instituut voor Voedingsonderzoek, Zeist, Holland.
         Submitted to WHO

    de Groot, A. O., Til, H. P., Feron, V. J., Dreef-van der Meulen, H. C.
         & Willems, M. I. (1971b) Two-year feeding and multigeneration
         studies in rats on five chemically modified starches. Unpublished
         report from Centraal Instituut voor Voedingsonderzoek, Zeist,
         Holland. Submitted to WHO

    


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