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.