-Ionone was reviewed at the eleventh meeting of the Joint
    FAO/WHO Expert Committee on Food Additives, specifications were
    prepared, and a conditional acceptable daily intake for man (ADI) of
    0-0.1 mg/kg body weight was established (FAO/WHO, 1967; FAO/WHO,

         Since this previous review, new data have become available and
    are included in this monograph.



         The following products have been isolated and identified in
    rabbit urine subsequent to the oral administration of -ionone: 3-oxo-
    -ionone, 3-oxo--ionol, dihydro-3-oxo--ionol, 3-hydroxy--ionol, and
    unchanged -ionone. In addition to the above excretory products, two
    glucuronides of -ionol metabolites have been detected (Ide & Toki,
    1970). This relatively recent work confirms, in many respects, the
    earlier studies on the metabolism of -ionone (Fischer & Bielig, 1940;
    Bielig & Hayasida, 1940; Prelog & Meier, 1950). A recent article has
    also been published (Fujji et al., 1972).


    Acute toxicity


                             LD50               References
    Animal     Route    mg/kg body weight

    Mouse      i.p.           2 277           (Sporn et al., 1963)
    Mouse      s.c.           2 605           (Wenzel & Ross, 1957)
    Rat        Oral           4 590a          (Jenner et al., 1964)

    a  Test material identified as 60% alpha-ionone and 40% -ionone.

    Short-term studies


         Groups of 15 male and 15 female rats were maintained for 90 days
    on diets containing -ionone at levels which provided an average daily
    intake of 11.6 mg/kg bw for the males and 13.1 mg/kg for the females.
    No adverse effects were observed as judged (in comparison with 

    controls) by appearance, growth, haematological and blood chemical
    determinations, terminal body weight, organ weights, or gross and
    microscopic examination of major organs (Oser et al., 1965).

         Groups of 10 male and 10 female rats were maintained for 17 weeks
    on diets containing "Ionone Standard" (60% alpha-ionone and 40%
    -ionone) at levels of 0, 1000, 2500, and 10 000 ppm (approximately
    equivalent to 50, 125, and 500 mg/kg bw). No adverse effects were
    observed on growth, appearance, food intake, haematology, final body
    weights, organ weights, or macroscopic appearance of organs of rats on
    all levels of "Ionone Standard" in the diet. However, microscopic
    examination revealed swelling of the hepatic parenchymal cells at all
    dietary levels. This "swelling of parenchymal cells" was dose-
    dependent, being "slight to moderate" at the highest dietary level
    (10 000 ppm), "slight" at the intermediate level (2500 ppm), and "very
    slight" at the lowest level (1000 ppm) (Hagan et al., 1967).


         The evaluation of -ionone is based on the report of the eleventh
    Expert Committee, supplemented by some further information on
    metabolism. Pending new data from a short-term study, the Committee
    converted its previous conditional ADI of 0-0.1 to a temporary ADI of
    0-0.05 mg/kg bw.


    Estimate of temporary acceptable daily intake for man

    0.0-05 mg/kg bw


    Required by 1980

         A short-term toxicity study (90 days) on a well-characterized
    sample of -ionone with one dietary level comparable to those at which
    minimal effects were previously observed.


    Bielig, H. J. & Hyasida (1940) Behavior of beta-ionone in animals,
         Hoppe-Seyler's Z. Physiol. Chem., 266(1/3), 99-111 (German)

    FAO/WHO (1967) Toxicological evaluation of some flavouring substances
         and non-nutritive sweetening agents, FAO Nutrition Meetings
         Report, Series No. 44a; WHO/Food Add./68.33

    FAO/WHO (1968) Specifications for the identity and purity of food
         additives and their toxicological evaluation: some flavouring
         substances and non-nutritive sweetening agents. Eleventh Report
         of the Joint FAO/WHO Expert Committee on Food Additives, FAO
         Nutrition Meetings Report, Series No. 44; Wld Hlth Org. techn.
         Rep. Ser. No. 383

    F.E.M.A. (1976) Scientific literature review of alicyclic compounds of
         carbon, hydrogen and oxygen in flavor usage, published by the
         National Information Services under contract with the Food and
         Drug Administration

    Fischer, F. G. & Bielig, H. J. (1940) Biochemical hydrogenations. VII.
         Hydrogenation of unsaturated compounds in the animal body, Z.
         Physiol. Chem., 266, 73-98 (in German)

    Fujji, T. et al. (1972) Analgesic and anti-inflammatory effects of
         vipratox (methyl salicylate-camphor-snake venom embrocation),
         Oyo Yakuri, 6(4), 821-830

    Hagan, E. C. et al. (1967) Food flavourings and compounds of related
         structure: II. Subacute and chronic toxicity, Food Cosmet.
         Toxicol., 5, 141-157

    Jenner, P. M. et al. (1964) Food flavourings and compounds of related
         structure: I. Acute oral toxicity, Food Cosmet. Toxicol., 2,

    Oser, B. L., Carson, S. & Oser, M. (1965) Toxicological tests on
         flavouring matters, Food Cosmet. Toxicol., 3(4), 563-569

    Prelog, V. & Meier, H. L. (1950) Organ extracts and urine. 18. The
         biochemical oxidation of beta-ionone in the animal body, Helv.
         Chim. Acta, 33(5), 1276-1285 (in German)

    Sporn, A. et al. (1963) The toxicity of butyl acetate, methyl
         naphthyl ketone, and Ionone, Igiena (Bucharest), 12(5), 437-446

    Wenzel, D. G. & Ross, C. R. (1957) Central stimulating properties of
         some terpenones, J. Am. Pharm. Assoc., 46, 77-82

    See Also:
       Toxicological Abbreviations
       Ionone, beta- (FAO Nutrition Meetings Report Series 44a)