WORLD HEALTH ORGANIZATION Toxicological evaluation of some food colours, thickening agents, and certain other substancse WHO FOOD ADDITIVES SERIES NO. 8 The evaluations contained in this publication were prepared by the Joint FAO/WHO Expert Committee on Food Additives which met in Geneva, 14-23 April 19751 World Health Organization, Geneva 1975 1 Nineteenth Report of the Joint FAO/WHO Expert Committee on Food Additives, Wld Hlth Org. techn. Rep. Ser., 1975, No. 576; FAO Nutrition Meetings Report Series, 1975, No. 55. The monographs contained in the present volume are also issued by the Food and Agriculture Organization of the United Nations, Rome, as FAO Nutrition Meetings Report Series, No. 55A ISBN 92 4 166008 2 (C) FAO and WHO 1975 QUINOLINE YELLOW Explanation This compound was evaluated for acceptable daily intake for man by the Joint FAO/WHO Expert Committee on Food Additives (see Annex 1, Refs No. 10, No. 20 and No. 35) in 1966, 1969 and 1974. Since the previous evaluation additional data have become available and are summarized and discussed in the following monograph addendum. It should be noted that there are two types of quinoline yellow, namely one a combination of methylated and non-methylated materials, the second a wholly unmethylated material (see specifications for particulars). In this monograph studies related to the methylated product are indicated by an asterisk. BIOLOGICAL DATA TOXICOLOGICAL STUDIES Special studies on teratogenicity Rat Groups of 20-24 pregnant Long-Evans rats received by gavage from day six to 15 of gestation 0, 15, 50 or 150 mg/kg/day. Three control groups were used and a positive control group of 22 rats was given 30 mg trypan blue/kg/day subcutaneously from days seven to nine. Rats were sacrificed at day 20. No signs of maternal or foetal toxicity or anomalies were seen attributable to the colour. Trypan blue produced the expected abnormalities (Anonymous, 1972a). Rabbit Groups of 15 pregnant rabbits received by gavage from days six to 18 of gestation 0, 15, 50 and 150 mg/kg/day. Three control groups were used and a positive control group of 15 rabbits was given 150 mg/ kg/day thalidomide. Animals were sacrificed on day 29. No significant maternal or foetal abnormalities due to the colour were noted. Thalidomide produced the expected abnormalities (Anonymous, 1972b). Special studies on mutagenicity *This colour was tested for mutagenic effect in a concentration of 0.5 and 1.0 g/100 ml in cultures of Escherichia coli. No mutagenic effect was found (Lück & Rickerl, 1960). Other special studies *In guinea-pigs it was found that this colour had no sensitization activity (Bär & Griepentrog, 1960). Cats received daily doses of 0.1 g/kg colour for seven days. No increase in Heinz bodies in the blood of the test animals was noted (Oettel et al., 1965). Short-term studies Rat *Groups of five male and five female rats were fed diets containing 0, 0.25%, 0.5%, 1.0%, 2.0%, and 5.0% for 90 days. No effect on body weight, food intake, blood cell counts and organ weights were observed (Hansen et al., 1960). *Ten male and 10 female rats were given a total of 55 subcutaneous injections of 1 ml of 2% aqueous solution over a period of seven months, then observed until death. No local tumours developed and total tumour incidence was less than in control groups given similar injections of glucose or salt solution (Oettel et al., 1965). Dogs *Groups of three male and three female dogs were fed diets containing 0.03 and 0.2% of the colour for two years. The control group consisted of 10 animals of each sex. No colour-induced effects were noted in terms of body weight, food consumption, gross and microscopic pathology. Long-term studies Rat *Groups of 20 male and 20 female rats or more were fed diets containing 0 and 1% of the colour for two years. A similar test group was formed from the first filial generation and was fed at 1% level for a similar period of time. No effect of the diet was noted in the test groups and gross and microscopic examination of the animals disclosed no charges attributable to the test diet. There was no significant difference in tumour incidence between the groups (Oettel et al., 1965). *Twenty rats, half males and half females, received twice weekly subcutaneously 1 ml of a 2% aqueous solution into the same site. A total of 55 injections were given for seven months and animals observed for 32 months. Three groups of 20 rats acted as controls. No significant effects on behaviour, growth, mortality, microscopic appearance of principal organs was noted. No tumours appeared at the site of injection of test animals but one sarcoma at the injection site and two tumours of ovary and uterus appeared in controls (Oettel et al., 1965). Groups of 25 male and 25 female rats were fed diets containing 0.0, 0.2 and 0.1% of the colour for up to two years. No colour-induced effects were seen in terms of body weight, food intake, survival, haematology, urinalyses, organ weights, gross and microscopic pathology. Comments: In the manufacture of these colours the impurities are qualitatively the same. Therefore toxicological data obtained on the colour containing the methylated derivative could be used as collateral evidence to assure also the safety of the non-methylated preparation. There is no biological information on either preparation but an adequate long-term study in rats is available. Additional studies on non-rodents have also been evaluated. Multi-generation studies are in progress but embryotoxicity including teratology has already been studied in two species. EVALUATION Level causing no toxicological effect in the rat 0.1% (= 1000 ppm) in the diet equivalent to 50 mg/kg body weight Estimate of acceptable daily intake for man 0-0.5 mg/kg body weight* FURTHER WORK OR INFORMATION Required by 1978 (June). (1) Metabolic studies in several species, preferably including man. (2) Adequate long-term studies in other species. (3) Results of multi-generation study in progress. * Temporary. REFERENCES Anonymous (1972a) Unpublished report from Biodynamics, Inc. submitted to the World Health Organization by the Inter-Industry Color Committee, United States of America Anonymous (1972b) Unpublished report from Biodynamics, Inc. submitted to the World Health Organization by the Inter-Industry Color Committee, United States of America Anonymous (1967a) Unpublished report from Hazleton Labs, Inc. submitted to the World Health Organization Anonymous (1967b) Unpublished report from Hazledon Labs, Inc. submitted to the World Health Organization Bär, F. & Griepentrog, F. (1960) Die Allergenwirkung von Fremden Stoffen in den Lebensmitteln, Med. U. Ernaehr., 1, 99 Hansen, W. H., Wilson, D. C. & Fitzhugh, O. C. (1960) Subacute oral toxicity of ten D & C coal-tar colors, Fed. Proc., 19, 390 Lück, H. & Rickerl, E. (1960) Lebensmittelzusatzstoffe und mutagene Wirkung (Food additives and mutagenic effect). VI. Report, Z. Lebensmitt.-Untersuch., 112, 157 Oettel, H., Frohberg, H., Nothdurft, H. & Wilhelm, G. (1965) Die prüfung einiger synthetischer Farbstoffe auf ihre Eignung zur Lebensmittelfärbung, Arch. Toxicol., 21, 9-29
See Also: Toxicological Abbreviations Quinoline yellow (FAO Nutrition Meetings Report Series 46a) Quinoline yellow (WHO Food Additives Series 6) Quinoline yellow (WHO Food Additives Series 13) Quinoline yellow (WHO Food Additives Series 19) QUINOLINE YELLOW (JECFA Evaluation)