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. PONCEAU 4R Biological Data Biochemical aspects Rats were injected i.v. and the bile collected for six hours. The recovery of the colour was approximately 34 per cent. (30-45 per cent.) of the administered quantity (Ryan & Wright, 1961). Acute Toxicity Animal Route LD50 Reference mg/kg body-weight mouse oral 8000 Gaunt et al., 1967 i.p. >1750 approx. Gaunt et al., 1967 rat oral >8000 Gaunt et al., 1967 i.p. 2000 approx. DFG, 1957 female i.p. 2600 Gaunt et al., 1967 male i.p. 600 Gaunt et al., 1967 i.v. 1000 DFG, 1957 In experiments with guinea-pigs it was found that this colour had no sensitization activity (Bär & Griepentrog, 1960). A negative test for Heinz bodies was obtained after administering this colour in a five per cent. aqueous solution by stomach tube to four cats (DFG, 1957). Special studies This colour was tested for mutagenic effect in a concentration of 0.5 g/100 ml in cultures of Escherichia coli. No mutagenic effect was found (Lück & Rickerl, 1960). Short-term studies Groups of 16 male and 16 female rats were fed diets containing 0, 0.5 per cent., 1 per cent. and 2 per cent. dye for 90 days. No adverse effects were seen in appearance, behaviour, growth, food consumption, haematological indices, SGPT and SGOT serum levels except at two per cent. level, when females had slightly lowered transammiase values, red cell counts and haemoglobin concentration. Renal function tests and organ weights were normal. Gross and histopathology showed no difference between the test groups (Gaunt et al., 1967). Eleven rats were given 1.0 per cent. of the colour in their drinking water for 216 days and observed for 791 days. Two animals died during the experiment, one had a sarcoma of the liver (DFG, 1957). Rat. Ten rats were given 0.2 per cent. of the colour in their diet for 417 days. The total intake was 11g/animal. Observation extended for 101 days. One rat died. No tumours were found (DFG, 1957). Four groups of 10 male and 10 female rats were given diets containing 0, 0.03 per cent., 0.3 per cent. and 3.0 per cent. of the colour for 64 weeks. No effect was noted on mortality. Females at the highest level had a lower food consumption throughout the experiment than the controls with a significant decrease in body-weight at 16 and 64 weeks. In females the relative weights of heart, liver and kidney were increased. No effects were found on histopathology and as regard haemoglobin levels (Allmark et al., 1957). Seventy-five rats were fed the colour at a level of 0.1 per cent. of the diet. No tumours were observed. Similar results were obtained with 10 rats fed at 0.2 per cent. of the diet. Feeding extended for life-span. Thirteen rats were given twice weekly s.c. injections of 0.5 ml of 1.0 per cent. of the colour for 365 days. Observation extended for 857 days. Five animals died during the experiment. No tumours were found (DFG, 1957). Comments Several long-term studies have been performed in the rat. There is no information on the metabolism of the colour. A short-term study in pigs is in progress. EVALUATION Level causing no toxicological effect in the rat 0.3 per cent. (= 3000 ppm) in the diet equivalent to 150 mg body-weight/day. Estimate of acceptable daily intake in man Temporary acceptance mg/kg body-weight 0 - 0.75 Further work required by June 1974 Metabolic studies in several species preferably including man and a two-year study in a non-rodent mammalian species. REFERENCES Allmark, M, G., Mannell, W. A. & Grice, H. C. (1957) J. Pharm. Pharmacol., 9, 622 Bär, F. & Griepentrog, F. (1960) Med. u. Ernähr., 1, 99 Deutsche Forschungsgemeinschaft, Farbstoff Kommission (1957) Mitteilung 6 Gaunt, I. F. et al. (1967) Fd. Cosmet. Toxicol., 5, 187 Lück, H. & Rickerl, E. (1960) Z. Lebensmitt.-Untersuch., 112, 157 Ryan, A. J. & Wright, S. E. (1961) J. Pharm. Pharmacol., 13, 492
See Also: Toxicological Abbreviations Ponceau 4R (WHO Food Additives Series 6) Ponceau 4R (WHO Food Additives Series 13) Ponceau 4R (WHO Food Additives Series 18) PONCEAU 4R (JECFA Evaluation)