ß-IONONE Explanation ß-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, 1968). Since this previous review, new data have become available and are included in this monograph. BIOLOGICAL DATA BIOCHEMICAL ASPECTS The following products have been isolated and identified in rabbit urine subsequent to the oral administration of ß-ionone: 3-oxo- ß-ionone, 3-oxo-ß-ionol, dihydro-3-oxo-ß-ionol, 3-hydroxy-ß-ionol, and unchanged ß-ionone. In addition to the above excretory products, two glucuronides of ß-ionol metabolites have been detected (Ide & Toki, 1970). This relatively recent work confirms, in many respects, the earlier studies on the metabolism of ß-ionone (Fischer & Bielig, 1940; Bielig & Hayasida, 1940; Prelog & Meier, 1950). A recent article has also been published (Fujji et al., 1972). TOXICOLOGICAL STUDIES 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% ß-ionone. Short-term studies Rat Groups of 15 male and 15 female rats were maintained for 90 days on diets containing ß-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% ß-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). Comments The evaluation of ß-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. EVALUATION Estimate of temporary acceptable daily intake for man 0.0-05 mg/kg bw FURTHER WORK OR INFORMATION REQUIRED Required by 1980 A short-term toxicity study (90 days) on a well-characterized sample of ß-ionone with one dietary level comparable to those at which minimal effects were previously observed. REFERENCES 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, 327-343 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)