Toxicological evaluation of some food
    additives including anticaking agents,
    antimicrobials, antioxidants, emulsifiers
    and thickening agents



    WHO FOOD ADDITIVES SERIES NO. 5







    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
    Geneva
    1974

              

    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.

    ISOPROPYL CITRATE MIXTURE AND MONOISOPROPYL CITRATE

    (monoisopropyl citrate 27%; diisopropyl citrate 9%; triisopropyl
    citrate 2%; mono- and diglycerides 62%)

    Explanation

         These substances have been evaluated for acceptable daily intake
    by the Joint FAO/WHO Expert Committee on Food Additives (see Annex 1,
    Refs Nos 6 and 13) in 1961 and 1966.

         The previously published monographs have been revised and are
    reproduced in their entirety below.

    BIOLOGICAL DATA

    BIOCHEMICAL ASPECTS

         Studies in the rat showed that isopropyl mixture was readily
    absorbed when it was incorporated in the diet up to the 10% level
    (Calbert et al., 1951).

    TOXICOLOGICAL STUDIES

    Acute toxicity
                                                             

                            LD50
    Animal       Route      (mg/kg bw)      Reference
                                                             

    Rat          oral       2 800-3 700     Deuel et al., 1951

    Dog          oral       2 250           Deuel et al., 1951
                                                             

    Short-term studies

    Rat

         A group of rats were fed isopropyl mixture in the diet at the
    rate of 1500-2000 mg/rat per day for six weeks. There was no
    demonstrable effect on growth or mortality, and there were no
    pathological findings (Deuel et al., 1951).

    Rabbit

         A group of rabbits were fed isopropyl mixture at an average
    level of about 3600 mg/rabbit per day for six weeks. There was no 
    demonstrable effect on growth or mortality and there were no abnormal
    findings post mortem (Deuel et al., 1951).

    Dog

         A group of dogs were fed isopropyl mixture in the diet at the
    level of 0.06% for six weeks with no demonstrable effect on growth or
    mortality, and no pathological findings (Deuel et al., 1951).

    Long-term studies

    Rat

         Groups of rats were fed isopropyl mixture in the diet at the
    levels of 0%, 0.28%, 0.56% and 2.8% for a period of two years. No
    deleterious effects were noted in any of the treated groups with
    respect to growth rate, mortality or histopathology of the tissues
    (Deuel et al., 1951).

         Multigeneration studies likewise indicated that isopropyl mixture
    at a level of 2.8% in the diet was innocuous (Deuel et al., 1951).

    Comments:

         No deleterious effects were observed in the short-term studies
    in rats, rabbits and dogs, or in the long-term studies in rats.
    Nevertheless, in view of the known toxicity of isopropyl alcohol,
    it is necessary to set a value for an acceptable daily intake.

    EVALUATION

    Level causing no toxicological effect

         Rat: 28 000 ppm (2.8%) of monoisopropyl citrate in the diet
    equivalent to 1400 mg/kg bw.

    Estimate of acceptable daily intake for man

         0-14 mg/kg bw.*

    REFERENCES

    Calbert, C. E. et al. (1951) Food Res., 16, 294

    Deuel, H. J. et al. (1951) Food Res., 16, 258

              

    *    Calculated as monoisopropyl citrate.

    See Also:
       Toxicological Abbreviations