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. PATENT BLUE V Biological Data Biochemical aspects After intravenous injection into the rat of 0.5 ml of an aqueous solution containing 5 g per 100 ml the colour is excreted in the urine which is coloured blue during the 12 hours following the injection. Findings are similar in the case of man when the colour is injected subcutaneously for the detection of peripheral lymphatic trunks and nodes for the purpose of lymphography. (Truhaut, 1962). Acute toxicity Animal Route LD50 Reference per kg body-weight Mouse oral > 3.0 g Truhaut, 1962 Mouse i.v. 1.2 g " Rat oral > 5.0 g " Rat i.v. 5.0 g " Special studies The dye (as the Ca salt) had slight surface activity. The Na salt had considerable surface activity. Protein binding and lipophilic activity were negligible for both salts. The authors conclude that the difference in surface activity explains the difference in the local reactions to the two salts (Cangolli et al., 1967). Short-term studies Rat. Subcutaneous injections of 1 ml of 0.8 per cent. aqueous solution twice weekly for five weeks produced only slight tissue reactions (Grasso & Goldberg, 1966). Cat. Three cats were given daily a five per cent. aqueous solution of the colour orally doses of 0.25, 0.50 and 0.75 g. No abnormalities were found (Truhaut, 1962). Long-term studies Rat. Sixty rats, half males and half females, were given in their diet 10 000 ppm of the colour for their life-span. The used colour was pure (no impurities were found by paperchromatography studies). The average life-span of treated animals was 24 months and the last animal died at an age of 37 months, two weeks. The average intake of the colour was approximately 8O g. Forty animals were used as controls.The average life-span of these animals was 22 months, two weeks. For the second experiment 30 rats, half males and half females, were given the same diet with 10 000 ppm and also for 15-19 months once a week a subcutaneous injection of 1 ml of a one per cent. aqueous solution. The average life-span of the animals was 18 months. The last animal died at an age of 30 months. Twenty-six rats were used as controls and were given 1 ml of distilled water subcutaneously for the same period as the treated animals. The average life-span of these animals was 19 months. In both experiments it was found that growth, blood composition, reproduction and the three generations of animals which were bred were not influenced. Also, no abnormal histopathological findings or sarcomas at the site of injection were observed (Truhaut, 1962). Comments Information on the metabolism of the colour is lacking. Long-term and reproduction studies in the rat did not reveal any significant toxicological effects. However, the corresponding sodium salt which is not used as food colour showed evidence of considerable surface activity on subcutaneous injection and for this reason a long-term study in a second species is required. EVALUATION Level causing no toxicological effects in the rat One per cent. (= 10 000 ppm) in the diet equivalent to 500 mg/kg body weight/day. Estimate of daily acceptable intake for man mg/kg body weight Temporary acceptance 0 - 1 Further work required by June 1974 Metabolic studies in several species, preferably including man, two year studies in non-rodent mammalian species and long-term studies in a second species. REFERENCES Gangolli, S. D., Grasso, P. & Go1dberg, L. (1967) Fd. Cosmet. Toxicol., 5, 601 Grasso, P. & Goldberg, L. (1966) Fd. Cosmet. Toxicol., 4, 269 Truhaut, R. (1962) Aliment. et Vie, 50, 77
See Also: Toxicological Abbreviations Patent blue V (WHO Food Additives Series 6) PATENT BLUE V (JECFA Evaluation)