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
See Also: Toxicological Abbreviations