INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY
WORLD HEALTH ORGANIZATION
TOXICOLOGICAL EVALUATION OF SOME
FOOD COLOURS, ENZYMES, FLAVOUR
ENHANCERS, THICKENING AGENTS, AND
CERTAIN FOOD ADDITIVES
WHO FOOD ADDITIVES SERIES 6
The evaluations contained in this publication were prepared by the
Joint FAO/WHO Expert Committee on Food Additives which met in Rome,
4-13 June 19741
World Health Organization Geneva 1975
1 Eighteenth Report of the Joint FAO/WHO Expert Committee on
Food Additives, Wld Hlth Org. techn. Rep. Ser., 1974, No. 557.
FAO Nutrition Meetings Report Series, 1974, No. 54.
BETA-APO-8'-CAROTENOIC ACID, ETHYL AND METHYL ESTERS
Explanation
These compounds have been evaluated for acceptable daily intake
by the Joint FAO/WHO Expert Committee on Food Additives (see Annex 1,
Ref. No. 10) in 1966.
Since the previous evaluation additional data have become
available and are summarized and discussed in the following monograph.
The previously published monograph has been expanded and is reproduced
in its entirety below.
BIOLOGICAL DATA
BIOCHEMICAL ASPECTS
The acid as well as the esters are normal metabolites of apo-
carotenal. Only a minor fraction of the methyl ester, if given in
large doses to rats, is absorbed, most being excreted in the faeces
(Wiss & Thommen, 1963). The elimination of ester from the blood of
human infants is proportional to the blood concentration and is very
rapid (Kübler, 1963).
TOXICOLOGICAL STUDIES
Acute toxicity
LD50
Animal Route mg/kg bw Reference
Mouse Oral > 10 000 (Anonymous, 1966)
Short-term studies
Rat
Groups of 16 rats received 0, 100 or 500 mg/kg of methyl ester
daily, five days per week, for 34 weeks. No adverse effects on
mortality or weight gain were noted, but the male rats receiving
500 mg/kg bw showed reduced testicular weights compared with
controls, and granular pigment deposits in the liver and kidney. No
deleterious effect on spermatogenesis was noted and their general
health was satisfactory (Anonymous, 1962; Anonymous, 1966).
Long-term studies
Rat
In a four-generation study, test groups of male and female rats
of 20 to 40 animals each and control groups of 28 to 39 each were fed
diets containing 0, 0.1, 0.2 and 0.5 and 1.0% of methyl ester for
periods of 52 to 104 weeks. No difference was observed between test
and control groups regarding food consumption and general health;
mortality was unrelated to the test substance (Anonymous, 1966).
In another experiment, 15 male rats were fed the ethyl ester at
1% of their diet for two years, with a control group on 7500 IU of
Vitamin A per day per animal and another control group on the basic
diet. Mortality and weight gain were identical in test and control
groups except for the group fed the Vitamin A supplement. Fertility
was similarly unaffected except in the group given Vitamin A. No
adverse effects were noted on general health (Anonymous, 1966).
Comments:
Although the toxicological information on each individual ester
is incomplete, long-term studies have been reported in rats. The use
of these substances is unlikely to result in an increased level of
Vitamin A, although the conversion rate for man is not known.
Similarly to beta-carotene, these substances are poorly absorbed from
the gastrointestinal tract especially when present in large amounts.
They can, therefore, be evaluated on the same basis as beta-carotene.
EVALUATION
Estimate of acceptable daily intake for man
0-5 mg/kg bw*
REFERENCES
Anonymous (1962) Hoffmann-La Roche unpublished report submitted to WHO
Anonymous (1966) Hoffmann-La Roche unpublished report submitted to WHO
Kübler, W. (1963) Wiss. Veröff. Dtsch. Gesellsch. Ernährung., 9, 222
Wiss, O., & Thommen, H. (1963) Dtsch. Gesellsch. Ernährung., 9, 179
* As sum of the carotenoids: beta-carotene, beta-apo-8'carotenoic
acid methylester, beta-apo-8'carotenoic acid ethyl ester, beta-apo-
8'carotenal.