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    FAO Nutrition Meetings
    Resort Series No. 44A
    WHO/Food Add./68.33




    TOXICOLOGICAL EVALUATION OF SOME
    FLAVOURING SUBSTANCES AND
    NON-NUTRITIVE SWEETENING AGENTS





    Geneva, 21-28 August 1967



    The Eleventh Report of the Joint FAO/WHO Expert Committee on Food
    Additives is published as FAO Nutrition Meetings Report Series,
    1967, No. 44; Wld Hlth Org. techn. Rep. Ser., 1968, 383. This
    Report contains general considerations, including the principles
    adopted for the evaluation, and a summary of the results of the
    evaluations of a number of food additives. Additional information,
    such as biological data and a toxicological evaluation, considered at
    that meeting, is to be found in this document.


    Food and Agriculture Organization of the United Nations
    World Health Organization
    1967

 

    ▀-IONONE

    Chemical name            ▀-Ionone

    Empirical formula        C13H20O

    Structural formula

    MOLECULAR STRUCTURE 12

    Molecular weight         192.30

    Definition               ▀-Ionone contains not less than 95 per cent.
                             of ketones expressed as C13H20O.

    Description              A slightly yellow liquid having a more
                             fruity and woody odour than alpha-ionone.

    Biological Data

    Biochemical aspects

         Rabbits were fed 5 g of ▀-ionone per animal daily for 2-3 weeks.
    In addition to 4 per cent. benzoic acid and 1.4 per cent. of
    m-hydroxybenzoic acid, 42 per cent. of the total dose was recovered
    as mostly neutral metabolites from the urine. 35-40 per cent. of the
    neutral metabolites, i.e. ▀-ionol, dihydro-▀-ional, hydroxy-▀-ionol,
    dihydroxy-▀-ionol and hydroxy-▀-ionone, retained the ionone
    trimethylcyclohexene ring (Bielig & Hayasida, 1940). More recent
    studies identified 4-oxo-▀-ionone, 4-hydroxy-▀-ionol and probably
    4-oxo-▀-ionol (Prelog & Meier, 1950).

    Acute toxicity

                                                                       

    Animal       Route       LD50               References
                             (mg/kg 
                             body-weight)
                                                                       

    Mouse        i.p.        2277               Sporn et al., 1963

    Rat          oral        4590               Jenner et al., 1964
                                                                       

    Feeding 13-115 mg daily to rats for 5-9 days has been reported to
    cause fatty infiltration of liver parenchymal cells (Shillinger,
    1950).

    Short-term studies

         Rat. In a 90-day feeding study on 15 males and 15 females, no
    adverse effects were reported at a level of 228 ppm in the diet (Oser,
    1967). In another 90-day study, groups of 15 males and 15 females were
    fed 0 or 12.3 mg/kg body-weight/day without adverse effect (Oser et
    al., 1965). A 17-week study on groups of 10 male and 10 female rats
    used a mixture of 60 per cent. alpha-ionone and 40 per cent. ▀-ionone
    at 0, 0.1, 0.25 and 1.0 per cent. of the diet. A dose-related swelling
    of the liver parenchyma was noted, but was only very slight at the
    lowest level. No other adverse effects were seen (Hagan et al., 1967).

    Long-term studies

         None available.

    Comments

         The biochemical information available together with the
    short-term studies allows assessment. Further metabolic and long-term
    studies are needed.

    EVALUATION

    Level causing no toxicological effect

         Rat. 12.3 mg/kg body-weight/day equivalent to 246 ppm in the
    diet.

    Estimate of acceptable daily intake for man

                                           mg/kg body-weight

         Conditional acceptance                  0-0.1

    Further work required

         Biochemical and metabolic as well as long-term studies, with
    special emphasis on effects on the liver.

    REFERENCES

    Bielig, H.-J. & Hayasida, A. (1940) Z. physiol. Chem., 266, 99

    Hagan, E. C., Hansen, W. H., Fitzhugh, O. G., Jenner, P. M., Jones, W.
    I., Taylor, J. M., Long, E. L., Nelson, A. A., Brouwer, J. B. (1967)
    Fd Cosmet. Toxicol., 5(2), 141

    Jenner, P. M., Hagan, E. C., Taylor, J. M., Cook, E. L. & Fitzhugh, O.
    G. (1964) Fd Cosmet. Toxicol., 2, 327

    Oser, B. L., Carson, S. & Oser, M. (1965) Fd Cosmet. Toxicol., 3,
    563

    Oser, B. L. (1967) Unpublished report

    Prelog, V. & Meier, H. L. (1950) Helv. chim. Acta, 33, 1276

    Shillinger, J. I. (1950) Gig. i. San., 3, 37

    Sporn, A., Sch÷besch, O., Marin, V., Panaitescu, E. & Runcanu, L.
    (1963) Igiena, 12, 437
    


    See Also:
       Toxicological Abbreviations
       Ionone, beta- (WHO Food Additives Series 14)