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


    GAMMA-NONALACTONE

    Chemical name                 Gamma-Nonalactone

    Empirical formula             C9H16O2

    Structural formula            CH3(CH2)4CHCH2CH2
                                           '    '
                                           O -- C = O

    Molecular weight              156.23

    Definition                    gamma-Nonalactone contains not less than
                                  97 per cent. C9H16O2.

    Description                   A nearly colourless to yellow liquid
                                  having a strong odour suggestive of
                                  coconut.

    Biological Data

    Biochemical aspects

         This lactone was found to open the ring on incubation with rat
    liver homogenate, and 62-88 per cent. was hydrolysed (Oser, 1967).

    Acute toxicity

                                                                       

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

    Rat            oral       9780              Jenner et al., 1964

    Guinea-pig     oral       3440              Jenner et al., 1964
                                                                       

    Short-term studies

         Rat. In a 12-week feeding study on 15 males and 15 females,
    using mixed lactones, a slight reduction in the growth rate was noted
    at a level of 32.7 mg/kg body-weight/day (Oser, 1967). A 90-day study
    on 15 male and 15 female rats fed 0 or 67.5 mg/kg body-weight/day
    showed no adverse effect (Oser et al., 1965).

    Long-term studies

         Rat.  Groups of 20 male and 20 female rats were fed diets
    containing 0, 0.1 and 0.5 per cent. of nonalactone for 2 years without
    any adverse effects being noted (Baer & Griepentrog, 1967).

    Comments

         The long-term studies in rats compensate for the inadequate
    information on the metabolic fate of this compound, and serve as basis
    for the evaluation. Nevertheless, as only one species has been
    investigated, metabolic studies and studies in other species are
    desirable.

    EVALUATION

    Level causing no toxicological effect

         Rat. 0.5 per cent. (= 5000 ppm) of the diet, equivalent to 250
    mg/kg body-weight/day.

    Estimate of acceptable daily intake for man

                                       mg/kg body-weight

         Unconditional acceptance           0-1.25

    REFERENCES

    Baer, F. & Griepentrog, F. (1967) Med. Ehrnährung, 8, 244

    Jenner, P. M., Hagan, E. C., Taylor, J. M., Cook, E. L. & Fitzhugh, O.
    C. (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
    

    See Also:
       Toxicological Abbreviations