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