INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY WORLD HEALTH ORGANIZATION SUMMARY OF TOXICOLOGICAL DATA OF CERTAIN FOOD ADDITIVES WHO FOOD ADDITIVES SERIES NO. 12 The data contained in this document were examined by the Joint FAO/WHO Expert Committee on Food Additives* Geneva, 18-27 April 1977 Food and Agriculture Organization of the United Nations World Health Organization * Twenty-first Report of the Joint FAO/WHO Expert Committee on Food Additives, Geneva, 1977, WHO Technical Report Series No. 617 ORANGE GGN EVALUATION FOR ACCEPTABLE DAILY INTAKE BIOLOGICAL DATA BIOCHEMICAL ASPECTS Excretion The colour was injected intravenously into rats. The bile was collected for six hours and analysed. The recovery of the colour was an average of 23% (10-40%) of the administered quantity (Ryan and Wright, 1961). Effect on enzymes After a prolonged administration to two generations of rats with a daily dose of 50 mg/rat the vitamin A content of the liver showed a three-to four-fold decrease. The glutathione content of the spleen was increased in the first generation, not in the second (Galea et al., 1963). At 6.66 mg dye/ml succinic acid dehydrase was inhibited and xanthine oxidase was weakly inhibited (Schormüller and Schulz, 1958). The products of air-oxidation or reduction and subsequent air-oxidation of Orange GGN inhibited lactic acid fermentation of milk (Eisenbrand and Lang, 1960; Lang, 1967). TOXICOLOGICAL STUDIES Special studies on carcinogenicity A group of 10 male rats was fed 1-(m-sulfophenylazo)-2-naphthol- 6-sulfonic acid, disodium salt at 0.02-0.1% in food (10 mg/kg body weight per day) to assess carcinogenicity. After at least 410 days, there were nine survivors but no tumours were observed. There was no increase in Heinz bodies (Hecht and Wingler, 1952). Five male and five female rats were given in their drinking water 0% or 1.0% of the colour for 266 days. The average daily intake was 0.75 g/kg body weight. Total intake was 50 g/animal. Observation period was 545 days. No tumours were found (Deutsche Forsch., 1957). Five male and five female rats were given this colour at a level of 0% or 1% in the drinking water for 262 days. The average daily intake was 0.9 g/kg body weight. The total intake of the colour was 52 g/animal. The animals were kept under observation for 832 days. Two of the animals died before the end of the experiment. No tumours were observed (Deutsche Forsch., 1957). Ten rats were fed at a level of 0.1% in the diet for a period of 410 days. The average daily dose was 0.06 g/kg. The total intake 6 g/animal. The animals were kept under observation for 761 days. One animal died before the end of the experiment. No tumours were observed (Deutsche Forsch., 1957; Hecht and Wingler, 1952). Two groups of 10 rats were subjected to subcutaneous injections of 0.5 ml of a 1% solution of the colour twice weekly for respectively 364 and 365 days. Total intake in both groups of rats was 0.5 g/animal. The animals were kept under observation for 521 and 839 days. Two animals died before the end of the experiment. In one animal a poly-morphocellular tumour in the lung and in another rat a fibromyoma at the site of injection was observed (Deutsche Forsch., 1957). Other 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 and Rickerl, 1960). Five rats were given 1.4 g of colour per kg body weight for 22 days. No Heinz bodies were found in the blood of the animals (Deutsche Forsch., 1957). In experiments with guinea-pigs it was found that this colour has no sensitization activity (Bär and Griepentrog, 1960). A negative test for Heinz bodies was obtained on a cat given 0.1 g/kg orally for seven days (Deutsche Forsch., 1957; Hecht and Wingler, 1952). In another test in cats given 200 mg/kg orally for six days no Heinz bodies were found (Wingler, 1953). Acute toxicity Animal Route LD50 per kg References body weight Mouse oral >5.0 g Deutsche Forsch, 1957 Rat i.p. >2.0 g Deutsche Forsch, 1957 >1.0 g A.B. Shporn et al., 1958 Rat i.v. Approx. 2.5 g Deutsche Forsch, 1957 Long-term studies Mouse, rat Mice and rats were treated with Orange GGN to assess chronic toxicity. No effects on haematology, clycaemia, or protein synthesis were observed (Sporn and Heilpern, 1958). Rat Rats were treated with Orange GGN to assess chronic toxicity at about 125 mg/kg daily. After prolonged administration, vitamin A content of liver decreased three- to four-fold with parallel decrease in glutathione in liver and spleen (Galea et al., 1962). See also special studies on carcinogenicity. REFERENCES Bär F. and Griepentrog, F. (1960) Die Allergenwirkung von Fremden Stoffen in den Lebensmitteln, Med. u. Ernähr., 1, 99-104 Deutsche Forschungsgemeinschaft (1957) Bad Godesberg, Federal Republic of Germany, Farbstoff Kommission, Mitteilung, 6, 32 Eisenbrand, J. and Lang, E. (1960) Influence of azo dyes on acid production of lactic acid bacteria. V. Action of cleavage and air- oxidation products of Brilliant Black BN, Chrysoin, S., Echtgelb Extra, Yellow 27175 N, Yellow Orange S, Orange GGN and Tartrzine, Z. Lebensm.-Untersuch. u.-Forsch., 113, 48-52 Galea, V., Ariesan, Maria and Luputiu, Georgeta (1962) Biochemical alterations in the liver of white rats under the influence of synthetic organic dyes, Orange GGN and Amaranth, Farmacia (Bucharest), 10, 531-533 Hecht, G. and Wingler, A. (1952) Biological study and suitable chemical constitution of some azo dyes for food colouring, Arzneimittel-Forsch., 2, 192-196 Lang, E. (1967) Cleavage products of the azo dyes, Brilliant Black BN, Yellow Orange S, Orange GGN and their effect on acid production by lactic acid bacteria, Z. Lebensm.-Unters. Forsch., 132, 363-367 Lück, H. and Rickerl, E. (1960) Lebensmittelzusatzstoffe und mutagene Wirkung, Z. Lebensmitt.-Untersuch. u.-Forsch., 112, 157-174 Ryan, A. J. and Wright, S. E. (1961) The excretion of some azo dyes in rat bile, J. Pharm. Pharmac., 13, 492-495 Schormüller, J. and Schulz, W. B. (1958) Action of food colour on the succinic acid dehydrase and xanthine oxidase in vitro, Z. Lebensm. -Untersuch. u.-Forsch., 108, 9-17 Shporn, A. B., Peretsiana, Zh. M. and Gal'perin, S. (1958) Studies on the toxicity of chemicals added to food, Voprosy Pitaniya, 17, No. 4, 48-53 Sporn, A. and Heilpern, J. (1958) The toxicity of the Orange GGN food colouring, Igiena, 7, 235-243 Wingler, A. (1953) Über Farbstoffe zur Lebensmittelfärbung. Zur Frage der Krebsgefährdung, Z. Krebsforschung., 59, 134-155
See Also: Toxicological Abbreviations ORANGE GGN (JECFA Evaluation)