Toxicological evaluation of some food
additives including anticaking agents,
antimicrobials, antioxidants, emulsifiers
and thickening agents
WHO FOOD ADDITIVES SERIES NO. 5
The evaluations contained in this publication
were prepared by the Joint FAO/WHO Expert
Committee on Food Additives which met in Geneva,
25 June - 4 July 19731
World Health Organization
Geneva
1974
1 Seventeenth Report of the Joint FAO/WHO Expert Committee on
Food Additives, Wld Hlth Org. techn. Rep. Ser., 1974, No. 539;
FAO Nutrition Meetings Report Series, 1974, No. 53.
alpha-TOCOPHEROL AND MIXED TOCOPHEROLS CONCENTRATE
Explanation
These substances have been evaluated for acceptable daily intake
by the Joint FAO/WHO Expert Committee on Food Additives (see Annex 1,
Ref. No. 6) in 1961.
The previously published monograph has been revised and is
reproduced in its entirety below.
BIOLOGICAL DATA
BIOCHEMICAL ASPECTS
The metabolic fate of alpha-tocopherol is not fully known. When
rats are given 3.5 mg daily by mouth 3 to 15% appears in the faeces.
With doses larger than this, up to 25% may appear in the faeces. There
is practically no urinary excretion of tocopherols, but from studies
with labelled material it appears that one or more metabolites of
tocopherols are excreted in the urine (Sternberg & Pascoe-Dawson,
1959).
When more than the daily requirement is administered, there is
some storage of tocopherol in the liver (Sebrell & Harris, 1954).
TOXICOLOGICAL STUDIES
Acute toxicity
LD50 values are not known.
Short-term studies
Rat and Mouse
Rats receiving alpha-tocopherol in a dosage of 100 mg/rat per day
for 19 weeks showed an increase in phosphorus metabolism, but no
effect was found when the dose was 10 mg/rat per day (Weissburger &
Harris, 1943).
It has been found that mice will tolerate oral doses of 50 g/kg
and rats 4 g/kg daily for two months (Demole, 1939).
OBSERVATIONS IN MAN
Adult humans have tolerated 1 g per day for months or larger
doses for shorter periods with no undesirable effects.
Therapeutically, daily doses of 20 to 600 mg of alpha-tocopherol or
its acetate are often taken with no toxic effects (Finkler, 1949;
McLaren, 1949; Sebrell & Harris, 1954). The clinical literature
contains references to complaints of gastric distress and other
symptoms in patients receiving much smaller dosages; these symptoms
are probably attributable to fatty substances present in alpha-
tocopherol concentrates or, in some instances, to psychic factors
(Sebrell & Harris, 1954).
Comments:
Though the toxicological studies are less than would normally be
required for foreign substances used as food additives, it is
considered that alpha-tocopherol is a nutrient. The clinical
experience with this vitamin is used as the basis for the evaluation.
EVALUATION
Estimate of acceptable daily intake for man
0-2* mg/kg bw.**
REFERENCES
Demole, V. (1939) Int. Z. Vitaminforsch., 8, 338
Finkler, R. S. (1949) J. clin. Endocr., 9, 89
McLaren, H. C. (1949) Brit. med. J., 2, 1378
Sebrell, W. H. jr & Harris, R. S. (1954) The vitamins, New York,
Academic Press, vol. 3, p. 481
Sternberg, J. & Pascoe-Dawson, E. (1959) Canad. med. Ass. J., 80, 266
Weissburger, L. H. & Harris, P. L. (1943) J. biol. Chem., 151, 543
* Calculated as alpha-tocopherol.
** Total.