INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY
WORLD HEALTH ORGANIZATION
TOXICOLOGICAL EVALUATION OF SOME
FOOD COLOURS, EMULSIFIERS, STABILIZERS,
ANTI-CAKING AGENTS AND CERTAIN
OTHER SUBSTANCES
FAO Nutrition Meetings Report Series
No. 46A WHO/FOOD ADD/70.36
The content of this document is the result of the deliberations of the
Joint FAO/WHO Expert Committee on Food Additives which met in Rome,
27 May - 4 June 19691
Food and Agriculture Organization of the United Nations
World Health Organization
1 Thirteenth report of the Joint FAO/WHO Expert Committee on Food
Additives, FAO Nutrition Meetings Report Series, in press;
Wld Hlth Org. techn. Rep. Ser., in press.
ORANGE I
Biological Data
Biochemical aspects
In dog it was found that 6-41 per cent. of the administered colour was
excreted in the faeces. No colour was found in the urine. Incubating
the colour with a dog's fresh intestinal content destroyed 80 per
cent. of the colour in one hour (DFG Dye Commission, 1957; Vos et al.,
1953).
Acute toxicity
Animal Route LD50 Reference
mg/kg body-weight
Rat i.p. 1 000 DFG, 1957
Short-term studies
Rat. Ten rats were fed this colour at a level of four per cent. in
the diet. The animals lived only a few months. Gross staining of the
glandular stomach and the small intestine, and granular deposits in
the stomach and small intestine were observed (Willheim & Ivy, 1953).
Weanling male rats were fed diets containing 1, 2 or 5 per cent. of
the colour for 16 weeks. The animals with the 2 and 5 per cent. died
all within the first two weeks of the feeding period. A mortality of
80 per cent. occurred in the rats fed one per cent. and the growth
rate of the surviving animals in this group was markedly retarded. The
inclusion of the colour in the diet caused severe diarrhoea,
enlargement of the spleen and an anaemia (Hallesy & Doull, 1956).
Dog. This colour had a significant cathartic effect when 100 to 200
mg were given to groups of five dogs (Vos et al., 1953)
Man. This colour induces also a cathartic action in man (80 mg). The
intact molecule appears to be the active cathartic agent (Radomski &
Deichmann, 1956).
Human volunteers who ate candy containing 0.07 per cent. of this
colour exhibited diarrhoea upon ingestion of one to eight pieces of
the candy (US FDA, 1955).
Skin tests with this colour showed no reaction in patients sensitive
to paraphenylene diamine (Baer et al., 1948).
Long-term toxicity
Mouse. Twenty mice were fed 15-20 mg per week of this colour for
periods up to 409 days five days a week. No tumours were observed
which could be attributed to the colour (Cook et al., 1940).
Rat. This colour was fed to 85 rats at a level of 0.1 per cent. in
the diet. The daily intake varied from 10 to 15 mg for a period of 400
days. No tumours were observed (DFG, 1957).
Groups of 24 weanling rats, equally divided by sex, were fed the
colour at 0, 0.5, 1.0 and 2.0 per cent. in the diet. No rats fed at
2.0 per cent. survived beyond the fifth week, observations are
confined to 0, 0.5 and 1.0 per cent. levels. Body-weight and food
intake were recorded weekly for two years; blood counts were taken
four times. Gross findings at 1.0 per cent. were marked increase of
mortality, enlargement of spleens, leukocytosis and anaemia,
diarrhoea, and growth depression. At 0.5 per cent. kidneys of test
rats showed more chronic congestion than those of controls and there
was some splenic enlargement. Microscopically, spleens showed
uniformly chronic congestion and less often slight hyperplasia and
increased pigmentation. Kidneys showed nephritis of the type common in
older rats with no difference among the groups except in incidence
(Bourke et al., 1956; US FDA, 1963).
Eighteen young rats were given subcutaneous injections, 20 mg of the
colour per week (two per cent. aqueous solution) for two years. In six
cases fibresarcomas were found. The controls did not get tumours
(Nelson & Davidow, 1967).
Dog. The colour was given to 14 dogs at four levels in daily
quantities by capsule ranging from about 0.02 per cent. to 1.0 per
cent. in the diet. The dogs on the lowest level survived for five
years without showing any effect. At higher levels (0.2 per cent. or
more of the diet) effects were variable; some dogs survived only for
short periods, others showed little or no effect for long periods.
Pathological changes were generally non-specific; some animals were
found dead with little to explain the death; others were emaciated and
showed organ changes chiefly of inanition (Bourke et al., 1956; US
FDA, 1963).
Comments
None of the long-term studies except the study carried out in dogs
revealed a satisfactory no-effect level. Further metabolic studies in
several species, preferably including man, are required as well as
long-term studies in a rodent species to establish a no-effect level.
EVALUATION
Not possible on the data available.
REFERENCES
Baer, R. L., Leider, M. & Mayer, R. L. (1948) Proc Soc. exp. Biol.,
67, 489
Bourke, A. R., Nelson, A. A. & Fitzhugh, O. G. (1956) Fed Proc., 15,
404
Cook, J. W., Hewett, C. L., Kennaway, E. L. & Hennaway, N. M. (1940)
Amer. J. Cancer, 40, 62
Deutsche Forschungsgemeinschaft, Farbstoff Kommission (1957)
Mitteilung 6
Hallesy, D. W. & Doull, J. (1956) J. Pharmacol. exp. Ther., 116, 26
Nelson, A. A, & Davidow, B. (1957) Fed. Proc., 16, 367
Radomski, J. L. & Deichmann, H. B. (1956) J. Pharmacol. exp. Ther.,
118, 322
United States Food and Drug Administration (1955) Title 21, Food and
Drugs, Part 135, Federal Register, 20, 8492
United States Food and Drug Administration (1963) Unpublished report
Vos, B. J., Radomski, J. L. & Fuyat, H. N. (1953) Fed. Proc., 12,
376
Willheim, R. & Ivy, A. C. (1953) Gastroenterology, 23, 1