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'-CAROTENAL*
Explanation
This compound has 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
After administration to rats as the only dietary carotenoid, some
beta-apo-8'carotenal accumulates in the liver together with Vitamin A
and beta-apo-8'-carotenoic acid (Thommen, 1962; Brubacher et al.,
1960).
Almost all of an excessive dose is excreted in the faeces, only a
small fraction being absorbed ordinarily (Wiss & Thommen, 1963).
Dogs absorb it poorly from the gastrointestinal tract and excrete
it in the urine together with beta-apo-8'-carotenoic acid (Bagdon et
al., 1960).
Hypervitaminosis A has not been seen in these dogs. The body fat
and livers of monkeys show an orange discoloration after oral feeding
of beta-apo-8'-carotenal, and it is stored in the liver together with
an unidentified carotenoic acid. Laying hens excrete some into yolk
(90% as ester, 10% as free beta-apo-8'-carotenoic acid), with
deepening of colour (Tiews, 1963; Thommen, 1962).
Hypercholerolemic activity has been noted (Wood, 1963).
Only 4% of dietary catorenal is converted to Vitamin A in the gut
of Vitamin A-deficient rats, compared with 10% of beta-carotene.
Carotenals are easily oxidized to carotenoic acids and less readily
reduced to alcohols in vivo, pointing to metabolic pathways other
than beta-oxidation (Wiss & Thommen, 1963; Glover, 1960).
* Beta-apo-8'-carotenal is found in abundance in the vegetable
kingdom, e.g. in the pulp and skin of citrus fruits and in various
fodder plants (Wiss & Thommen, 1963; Thommen, 1962).
TOXICOLOGICAL STUDIES
Acute toxicity
LD50
Animal Route mg/kg bw Reference
Mouse Oral > 10 000 Anonymous, 1966
Short-term studies
Rat
Groups of 16 male rats received 0, 100 or 500 mg/kg of carotenal
intragastrically five days per week for 34 weeks. No adverse effects
were seen on body weight gain, general health, survival, liver and
kidney function and organ weights. The testicular weight of the high
level test group was significantly lower than that of the controls.
Microscopic findings were normal except for granular pigment
deposition in the liver and kidneys of test animals. Fertility as
shown by monthly mating of four females, was not affected (Anonymous,
1962; Anonymous, 1966).
Dog
Groups of two to three female and three to four male dogs
received 0, 0.1 or 1.0 g of carotenal daily per animal during 14
weeks. All remained healthy and no significant effect was noted. No
pathological lesions related to the test substance were seen at post-
mortem. Peripheral blood picture, liver function tests, serum enzymes
and blood urea were normal. Vitamin A and carotenal levels of serum,
liver, kidney, adrenal and mesenteric fat were estimated. The kidney
level of Vitamin A was three to five times that of controls. The serum
level of carotenal was elevated in the group receiving 1.0 g and there
was an occasional trace in the group on 0.1 g. Tissue amounts were
variable. The only microscopic finding was pigmentation of the adipose
tissue, kidney and adrenal cortex. Organ weights were normal (Bagdon
et al., 1962).
Long-term studies
Rat
A three-generation study in rats at 0 ppm, 1000 ppm, 2000 ppm and
5000 ppm for two years showed no adverse effect in any generation
(Anonymous, 1966).
Comments:
Beta-apo-8'-carotenal has been adequately tested in rats. The
use of this substance is unlikely to result in an increased level
of vitamin A although the conversion rate for man is not known.
Similarly to beta-carotene, this substance is poorly absorbed from
the gastrointestinal tract when present in large amounts. It 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
Anonymous (1966) Hoffmann-La Roche, Unpublished report
Bagdon, R. E., Impellizzeri, C. & Osadca, M. (1962) Toxic. Appl.
Pharm., 4, 444
Bagdon, R. E., Zbinden, G. & Studer, A. (1960) Toxic. Appl.
Pharm., 2, 223
Brubacher, G., Gloor, U. & Wiss, O. (1960) Chimia, 14, 19
Glover, J. (1960) Vit. Horm., 18, 371
Thommen, H. (1961) Chimin, 15, 433
Thommen, H (1962) Naturw., 49, 517
Tiews, J. (1963) Dtsch. Gesellsch. Ernährung., 9, 236
Wiss, O. & Thommen, H. (1963) Dtsch. Gesellsch. Ernährung., 9, 179
Wood, J. D. (1963) Canad. J. Biochem., 41, 1663
* As sum of the carotenoids: Beta-apo-8'-carotenal
Beta-carotene
Beta-carotenoic acid methyl ester
Beta-carotenoic acid ethyl ester
See Also:
Toxicological Abbreviations