alpha- and ß-IONONE Explanation alpha-ionone was evaluated for the acceptable daily intake for man by the Joint FAO/WHO Expert Committee on Food Additives in 1967 (ADI = 0-0.1 mg/kg) and in 1979, 1980, 1982 (ADI = 0-0.05 mg/kg) (Annex I, Ref. 15, 50, 51, 53, and 59). Toxicological monographs were issued in 1967 and 1979 (Annex I, Ref. 15 and 51). BIOLOGICAL DATA BIOCHEMICAL ASPECTS Following oral administration, alpha-ionone undergoes biochemical oxidation in the rabbit and is excreted in the urine, principally, as 5-oxo-cis-tetrahydro-ionone, indicating in vivo oxidation of carbon atom 5 in the ionone structure (Prelog & Wursch, 1951). TOXICOLOGICAL STUDIES Acute toxicity Animal Route LD50 References mg/kg bw. 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% B-ionone. Special studies on mutagenicity The genotoxicity of a alpha-ionone was studied by a bacterial mutation test in the Salmonella/microsome system (with the Salmonella typhimurium histidine (-) mutants, TA 98 and TA 100) and by a chromosome test in Chinese hamster (CH) cells. In the mutation test alpha-ionone (at various dose levels from 0.01 to 50 µg/pl) did not exhibit significant induction of his + revertants in Salmonella, either with or without rat liver microsome metabolic activating system. In the chromosome test, alpha-ionone at the concentration of 25 nM, induced slight chromosome aberrations in the treated CH cells. Short-term studies Rat In a 90-day study on groups of 15 males and 15 females given either 0 or 11.5 mg/kg body weight per day, no adverse effects were observed (Oser et al., 1965). Another study on groups of 10 males and 10 females used a mixture of 60 per cent alpha- and 40 per cent ß-ionone at 0, 0.1, 0.25 and 1.0 per cent of the diet for 17 weeks. A dose-dependent moderate swelling of liver parenchyma was noted which occurred to a very slight degree at the lowest level. No other adverse effects were seen (Hagan et al., 1967). Rat 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 body weight). No adverse effects were observed on growth, appearance, food intake, haematology, final body weight, 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). ß-ionone was fed to Sprague-Dawley strain rats in the diet at levels to provide intakes of approximately 10 or 100 mg/kg body weight per day for 90 days. The study consisted of two test groups each of fifteen rats of each sex and one control group of thirty rats of each sex. Renal function and haematological studies were performed mid-way through the treatment period and at the end of the study. The effects were limited to the 100 mg/kg groups and were a reduced weight gain, and food consumption and serum glucose concentrations, increased water intakes and mild renal functional changes. No histological changes were evident in the kidneys or livers. It was concluded that the no-untoward effect level from this study was 10 mg/kg per day (Ford et al., 1983). Comments Mutagenicity studies carried out with alpha-ionone indicated that there were not mutagenic effects on two strains of Salmonella typhimurium with and without liver enzyme induction but the compound induced light chromosome aberrations. In short-term study on rats with alpha-ionone it was shown that the compound does not produce adverse effects at dose of 10 mg/kg body weight. EVALUATION Estimate of acceptable daily intake for man 0-0.1 mg/kg bw. (group ADI for alpha-ionone and ß-ionone, singly or in combination). REFERENCES FORD, G.P., BUTLER, W.H., HOOSON, S., GAUNT, I.F., HAWKINS, R.I. (1983) The short-term (90-days) toxicity of alpha- and beta-ionones in rats. Unpublished report from the British Industrial Biological Research Association. Submitted to the World Health Organization by the International Organization of the Flavour Industry, Geneva. 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 and chronic toxicity. Food Cosmet. Toxicol., 2: 327-343. KASAMAKI, A., TAKAMASHI, H., TSUMURA, N., NIWA, S., FUJITA, T., & URASAWA, S. (1982) Genotoxicity of flavouring agents. Mutation Res., 105: 387. OSER, B.L., CARSON, S., & OSER, M. (1965) Food Cosmet. Toxicol., 3: 563. PRELOG, V. & WUERSCH, J. (1951) Organ extracts and urine. 21. The biochemical oxidation of alpha-ionone in the animal body. Helv. Chim. Acta, 34(3): 859-861 (in German). SPORN, A. et al. (1963) The toxicity of butyl acetate, methyl naphtylketone, and ionone. Igiena (Bucarest), 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