FAO Nutrition Meetings
Resort Series No. 44A
TOXICOLOGICAL EVALUATION OF SOME
FLAVOURING SUBSTANCES AND
NON-NUTRITIVE SWEETENING AGENTS
Geneva, 21-28 August 1967
The Eleventh Report of the Joint FAO/WHO Expert Committee on Food
Additives is published as FAO Nutrition Meetings Report Series,
1967, No. 44; Wld Hlth Org. techn. Rep. Ser., 1968, 383. This
Report contains general considerations, including the principles
adopted for the evaluation, and a summary of the results of the
evaluations of a number of food additives. Additional information,
such as biological data and a toxicological evaluation, considered at
that meeting, is to be found in this document.
Food and Agriculture Organization of the United Nations
World Health Organization
Chemical name ▀-Ionone
Empirical formula C13H20O
Molecular weight 192.30
Definition ▀-Ionone contains not less than 95 per cent.
of ketones expressed as C13H20O.
Description A slightly yellow liquid having a more
fruity and woody odour than alpha-ionone.
Rabbits were fed 5 g of ▀-ionone per animal daily for 2-3 weeks.
In addition to 4 per cent. benzoic acid and 1.4 per cent. of
m-hydroxybenzoic acid, 42 per cent. of the total dose was recovered
as mostly neutral metabolites from the urine. 35-40 per cent. of the
neutral metabolites, i.e. ▀-ionol, dihydro-▀-ional, hydroxy-▀-ionol,
dihydroxy-▀-ionol and hydroxy-▀-ionone, retained the ionone
trimethylcyclohexene ring (Bielig & Hayasida, 1940). More recent
studies identified 4-oxo-▀-ionone, 4-hydroxy-▀-ionol and probably
4-oxo-▀-ionol (Prelog & Meier, 1950).
Animal Route LD50 References
Mouse i.p. 2277 Sporn et al., 1963
Rat oral 4590 Jenner et al., 1964
Feeding 13-115 mg daily to rats for 5-9 days has been reported to
cause fatty infiltration of liver parenchymal cells (Shillinger,
Rat. In a 90-day feeding study on 15 males and 15 females, no
adverse effects were reported at a level of 228 ppm in the diet (Oser,
1967). In another 90-day study, groups of 15 males and 15 females were
fed 0 or 12.3 mg/kg body-weight/day without adverse effect (Oser et
al., 1965). A 17-week study on groups of 10 male and 10 female rats
used a mixture of 60 per cent. alpha-ionone and 40 per cent. ▀-ionone
at 0, 0.1, 0.25 and 1.0 per cent. of the diet. A dose-related swelling
of the liver parenchyma was noted, but was only very slight at the
lowest level. No other adverse effects were seen (Hagan et al., 1967).
The biochemical information available together with the
short-term studies allows assessment. Further metabolic and long-term
studies are needed.
Level causing no toxicological effect
Rat. 12.3 mg/kg body-weight/day equivalent to 246 ppm in the
Estimate of acceptable daily intake for man
Conditional acceptance 0-0.1
Further work required
Biochemical and metabolic as well as long-term studies, with
special emphasis on effects on the liver.
Bielig, H.-J. & Hayasida, A. (1940) Z. physiol. Chem., 266, 99
Hagan, E. C., Hansen, W. H., Fitzhugh, O. G., Jenner, P. M., Jones, W.
I., Taylor, J. M., Long, E. L., Nelson, A. A., Brouwer, J. B. (1967)
Fd Cosmet. Toxicol., 5(2), 141
Jenner, P. M., Hagan, E. C., Taylor, J. M., Cook, E. L. & Fitzhugh, O.
G. (1964) Fd Cosmet. Toxicol., 2, 327
Oser, B. L., Carson, S. & Oser, M. (1965) Fd Cosmet. Toxicol., 3,
Oser, B. L. (1967) Unpublished report
Prelog, V. & Meier, H. L. (1950) Helv. chim. Acta, 33, 1276
Shillinger, J. I. (1950) Gig. i. San., 3, 37
Sporn, A., Sch÷besch, O., Marin, V., Panaitescu, E. & Runcanu, L.
(1963) Igiena, 12, 437