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.



         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.



         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).


    Special studies

         Groups of 10 male and 10 female rats were fed 0, 25 or 50% of two
    different modified starches (acetic anhydride and vinylacetate
    modified) in a low residue diet for seven days followed by the
    additional feeding of 4% cellulose for three 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).

    Reproduction studies


         A three generation study was performed using groups of 10 males
    and 20 females for the P, F1 and F2 generations to produce two
    successive litters in each generation by mating at week 12 and 20
    after weaning. Ten males and 10 females of the F b generation were
    kept for three weeks after weaning and then sacrificed for
    histopathological studies. The P, F b and F b 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% vinylacetate and 1.2% phosphorus oxychloride (D.S.
    of 0.064, 0.043% phosphorus introduced). No adverse effects were noted

    in respect of health, behaviour, mortality, growth, fertility, litter
    size, resorption quotient, weaning weight or mortality of young.
    Caecal weight of parent rats fed the modified starches were not
    increased. Gross pathology revealed a slightly decreased thyroid
    weight and a slightly increased caecum weight of F3b rats fed the
    starch treated with acetic anhydride and phosphorus oxychloride.
    Histopathology failed to reveal any treatment-related changes (Til et
    al., 1971b).

    Short-term studies


         Groups of 10 male and 10 female rats were fed 0, 25 and 50% of
    two different modified starches (acetic anhydride and vinylacetate
    modified) in their diet for eight weeks. Body weights of animals on
    the higher test level were somewhat lower than at the 25% level 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 abnormality of the enlarged
    caeca was noted (de Greet & Spanjers, 1970).


         Groups of four male and four 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 two nor in any other animal (Shillam et al., 1971).

         A further pig study in which groups of eight 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


         Groups of 30 male and 30 female rats were fed two different
    modified starches (acetic anhydride and vinylacetate 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. Growth was slightly depressed
    at the highest dietary level with both modified starches. 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).


         Twelve volunteers consumed on each of four successive days, 60 g
    acetylated distarch phosphates of either 1.6% 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 noticed (Pieters et al., 1971).


         The feeding studies with rat and pig show that these modified
    starches are well utilized. The long-term and reproduction studies in
    rats reveal only caecal enlargement. It is appropriate to use these
    studies for evaluation.


    Estimate of acceptable daily intake for man

         Not limited.*


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


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

    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

    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. et al. (1971a) Unpublished report No. R 3351 by Centraal
         Instituut voor Voedingsonderzoek

    Til, H. P., Spanjers, M. Th. & de Groot, A. P. (1971b) Report No. 3403
         of Centraal Instituut voor Voedingsonderzoek, 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 17)