INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY WORLD HEALTH ORGANIZATION SUMMARY OF TOXICOLOGICAL DATA OF CERTAIN FOOD ADDITIVES AND CONTAMINANTS WHO FOOD ADDITIVES SERIES NO. 13 The data contained in this document were examined by the Joint FAO/WHO Expert Committee on Food Additives* Rome, 3-12 April 1978 Food and Agriculture Organization of the United Nations World Health Organization * Twenty-second Report of the Joint FAO/WHO Expert Committee on Food Additives, Geneva, 1978, WHO Technical Report Series No. 631 AMARANTH Explanation This colour was evaluated at the Joint FAO/WHO Expert Committee on Food additives in 1964, 1972 and 1975. Since the previous evaluation, additional data have become available and are summarized below. BIOLOGICAL DATA Special studies on teratology Rat A collaborative government-industry study was initiated to evaluate the teratogenic potential of amaranth which involved three laboratories: Food and Drug Administration (FDA), Industrial Bio-Test Laboratories (IBT) and the National Center for Toxicological Research (NCTR). Groups of 20 to 30 pregnant females received 200 mg/kg bw amaranth by gavage during days 0-19, 6-15 or 7-9 of gestation. Another group received amaranth at the same dose level in their drinking-water from day 0 to day 20. Appropriate controls were utilized. The Osborne-Mendel strain of rat was used by FDA while IBT used Charles River and NCTR both strains. The Charles River strain in the IBT and NCTR studies showed a significant increase in litters with two or more resorptions after dams had been given 200 mg/kg by gavage from day 0-19. As well, a significant increase in the percentage resorption/litter was observed in this strain in the NCTR study. A significant increase in resorptions was not observed in the Osborne-Mendel strain. There were no apparent compound-related skeletal or visceral effects (Collins et al., 1976a, 1976b; Keplinger et al., 1976; Holsen et al., 1976a, 1976b). Cat Amaranth was administered daily by gelatin capsule to adult female cats at dose levels of 0, 92, 187 or 264 mg/kg bw extending from 22 days before gestation to day 61 or 62 of gestation. Seven trials commencing at time intervals of 10 to 38 days were conducted. Six trials contained 20 cats each and one contained 11 cats. The cats in each trial were assigned randomly to five groups, three groups were treated with amaranth and the remaining two groups served as controls. The pregnancies were timed by having controlled copulation of females that were in oestrus which occurred spontaneously or was stimulated by gonadotrophin. Caesarian section was performed on day 61 or 62 of gestation. No significant effects which could be related to the ingestion of this colour were observed with respect to total implants, ratio of corpora lutea to total implants, dead foetuses, deciduomas, live foetuses, 24-hour viability of live foetuses in an incubator, mean live foetal weight, sex ratio and foetal abnormalities (Khera et al., 1976). Special studies on mutagenicity Groups of 12 male mice were injected intraperitoneally with a 5% aqueous solution of amaranth at dose levels of 0, 250 or 500 mg/kg bw. Each male was then mated with three untreated females each week for six weeks. Females were killed one week after their removal from breeding cages and were examined for signs of pregnancy. The mating indices and mutation rates gave no indication of a dominant lethal response (Arnold et al., 1976). Short-term studies Rat Groups of weanling rats were fed diets containing amaranth at levels of 0, 1200, 3000, 10 000 or 20 000 ppm for 10 days. The test and control groups contained nine and 12 rats/group respectively. All rats received 30 µg of vitamin A daily. No significant changes were observed in body weight, food consumption, liver weight and vitamin A content of the liver (Truhaut and Ferrando, 1975). Long-term studies Rat Groups of 50 male and 50 female weanling rats were fed amaranth at 0, 0.003, 0.03, 0.3 or 3% (0, 1.5, 15, 150 or 1500 mg/kg bw) in the diet for approximately two-and-a-half years. The rats used in this study were randomly selected from the F2a litters of parents treated with amaranth. During the study certain animals were inadvertently placed in the wrong cages so that a number of animals were shifted among the control and treated animals. A variety of benign and malignant tumours was observed with no apparent differences between the treated and control groups. When the pathological data, however, were subjected to biostatistical analysis, a significant increase in the number of malignant tumours was observed in the female rats maintained at the 1500 mg/kg bw dietary level. There was no significant difference in the total number of tumours, both benign and malignant, between high dose and control animals. No compound-related effects were noted with respect to general condition, survival, body weight gain, haematology, clinical chemistry or relative organ weights (Gordon and Taylor, 1975). REFERENCES Arnold, D. W., Kennedy, G. L., jr, Keplinger, M. L. and Calandra, J. C. (1976) Failure of FD and C Red No. 2 to produce dominant lethal effects in the mouse, Food Cosmet. Toxicol., 14, 163 Collins, T. F. X., Ruggles, D. I., Holson, J. F., jr, Schumacher, H., Gaylor, D. W. and Kennedy, G. L., jr (1976a) Teratological evaluation of FD and C Red No. 2 - a collaborative government-industry study. I. Introduction, Experimental Materials, and Procedures, J. Toxicol. and Environ. Health, 1, 851 Collins, T. F. X., Black, T. N., Ruggles, D. I. and Gray, G. C. (1976b) Teratological evaluation of FD and C Red No. 2. A collaborative government-industry study. II. FDA's study, J. Toxicol. and Environ. Health, 1, 857 Gordon, L. A. and Taylor, J. M. (1975) Chronic feeding study of amaranth in rats, unpublished data from FDA-US Holson, J. F., jr, Schumacher, H. J., Gaylor, D. W. and Gaines, T. B. (1976a) Teratological evaluation of FD and C Red No. 2 - A collaborative government-industry study. IV. NCTR's study, J. Toxicol. and Environ. Health, 1, 867 Holson, J. F., jr, Gaylor, D. W., Schumacher, H. J., Collins, T. F. X., Ruggles, D. I., Keplinger, M. L. and Kennedy, G. L., jr (1976b) Teratological evaluation of FD and C Red No. 2 - A collaborative government-industry study. V. Combined findings and discussion, J. Toxicol. and Environ. Health, 1, 875 Keplinger, M. L., Kinoshita, F. K., Smith, S. H. and Kennedy, G. L., jr (1976) Teratological evaluation of FD and C Red No. 2 - A government-industry study. III. IBT's study, J. Toxicol. and Environ. Health, 1, 863 Khera, K. S., Roberts, G., Trivett, G., Terry, G. and Whalen, C. (1976) A teratogenicity study with amaranth in cats, Toxicol. appl. Pharmacol., 38, 389 Truhaut, R. and Ferrando, R. (1975) Influence de l'administration par voie orale, de differentes doses de deux colorants azoiques, l'Amarante et le Jaune Soleil FCF, sur la mise en réserve de la vitamine A dans le foie du rat, C.R. Acad. Sci., Paris t. 281 (4, 11, 18, 25 août 1975)
See Also: Toxicological Abbreviations Amaranth (WHO Food Additives Series 4) Amaranth (WHO Food Additives Series 8) Amaranth (WHO Food Additives Series 19) AMARANTH (JECFA Evaluation) Amaranth (IARC Summary & Evaluation, Volume 8, 1975)