INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY

    WORLD HEALTH ORGANIZATION



    TOXICOLOGICAL EVALUATION OF SOME
    FOOD COLOURS, EMULSIFIERS, STABILIZERS,
    ANTI-CAKING AGENTS AND CERTAIN
    OTHER SUBSTANCES



    FAO Nutrition Meetings Report Series 
    No. 46A WHO/FOOD ADD/70.36




    The content of this document is the result of the deliberations of the
    Joint FAO/WHO Expert Committee on Food Additives which met in Rome,
    27 May - 4 June 19691





    Food and Agriculture Organization of the United Nations

    World Health Organization



                   
    1 Thirteenth report of the Joint FAO/WHO Expert Committee on Food
    Additives, FAO Nutrition Meetings Report Series, in press;
    Wld Hlth Org. techn.  Rep. Ser., in press.


    ACETYLATED DISTARCH ADIPATE

    Modification is carried out by the use of five per cent acetic
    anhydride and a maximum of 0.12 per cent. adipic acid, the latter
    acting as cross-linking agent. The maximum number of acetyl groups
    introduced is 2.5 per cent. The number of adipic cross-links does not
    exceed more than one in about 1000 anhydroglucose units, or not more
    than 0.09 per cent, adipyl groups introduced on the starch.

    Biological Data

    Biochemical aspects

    In vitro studies with pancreatin have shown that only the acetate
    ester bond splits easily while the adipic acid ester linkages are not
    attached. No free adipic acid could be demonstrated in the hydrolysate
    (Morgareidge, 1959a). The metabolic fate of adipate-modified starches
    was therefore investigated in male rats in vivo using
    adipate-modified labelled at C1 and C6 with C14. The rate of
    appearance of 14CO2 was compared between starch modified with 1, 6
    -C14 adipic acid and a physical mixture of untreated starch and
    equivalent amounts of 1, 6 - C14 adipic acid. Starch adipate is
    absorbed and/or metabolised more slowly as shown by the delayed
    appearance of 14 CO2 in the respired air. Almost all the C14
    activity of the free adipic acid was recovered in the respired air;
    only a small amount appeared in the urine while none was detected in
    the faeces, in the gastro-intestinal tract or in the carcass. More
    than half of the C14 activity of the etserified adipic acid appeared
    in the respired air and a proportionate amount in the urine, the rest
    was found in the faeces. No activity appeared in the carcass
    (Morgareidge, 1959b). The caloric equivalent of the modified starch
    was determined in groups of 10 male rats fed for 28 days on a basal
    diet containing either 1.5 or 3.0 g of starch supplements. The
    modified starch had been treated with 0.2 per cent. adipic anhydride
    and 5.5 per cent. acetic anhydride. Native starch was used as control.
    Caloric values were determined from a dose/response curve obtained by
    the use of 0, 0.75 g, 1.5 g, 3.0 g and 4.5 g of sucrose supplements
    equivalent to 0, 3, 6, 12 and 18 calories per day. There was no
    difference in caloric value as between the modified and unmodified
    starches (Oser, 1961).

    Acute toxicity

    None available.

    Short-term studies

    Rat. A 90-day feeding study was carried out in groups of 15 male and
    15 female rats at a dietary level of 50 per cent. modified or
    unmodified starch. The growth rate of males was significantly lower in
    the test group and the full and empty caecal weights of both sexes
    were significantly greater in rats fed the treated starch. All rats
    survived the test period and no differences were observed between the
    groups in respect of liver and kidney weights, haematology, blood
    chemistry, urinalysis, gross and histopathology. The modified starch
    used had been treated with 0.12 per cent. adipic acid and 10.5 per
    cent. acetic anhydride resulting in 3.1 per cent. of acetyl groups
    being present (Oser, 1964).

    Long-term studies

    None available.

    Comments

    The metabolic studies show that adipate cross-linking interferes with
    enzymatic breakdown and possibly delays absorption. A study with the
    C14 labelled material showed that the moiety containing the adipic
    acid was metabolized normally more slowly. No retention of label was
    found in the carcass. The available 90-day studies were only done at
    one dose level and do not establish a no-effect level although the
    pathological findings appear to be related only to the acetylation.
    Estimation of the acceptable daily intake may be based on the
    no-effect level for rats for acetylated starch.

    EVALUATION

    Levels showing no toxicological effect in the rat (for starch acetate)

    Five per cent. (= 50 000 ppm) in the diet equivalent to 2500 mg/kg
    body weight/day.

    Estimate of acceptable daily intake for man

    Temporary acceptance                    mg/kg body weight

                                                 0 - 12.5

    Further work required by June 1974

    Adequate 90-day studies in two species (one a non-rodent mammal).

    REFERENCES

    Morgareidge, K. (1959a) Unpublished report No. 78522 by Food and Drugs
    Research Laboratories Inc., 30th November 1959 submitted by National
    Starch and Chemical Corporation

    Morgareidge, K. (1959b) Unpublished report No. 79408 by Food and Drugs
    Research Laboratories Inc., 28th October 1959 submitted by National
    Starch and Chemical Corporation

    Oser, M. (1961) Report No. 81776 by Food and Drugs Research
    Laboratories Inc., Ist June 1961 submitted by National Starch and
    Chemical Corporation

    Oser, B. L. (1964) Report No. 85555 by Food and Drugs Research
    Laboratories Inc., 16th October 1964 submitted by National Starch and
    Chemical Corporation
    

    See Also:
       Toxicological Abbreviations
       Acetylated distarch adipate (WHO Food Additives Series 1)
       Acetylated distarch adipate (WHO Food Additives Series 5)
       Acetylated distarch adipate (WHO Food Additives Series 17)
       ACETYLATED DISTARCH ADIPATE (JECFA Evaluation)