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 GUAR GUM Explanation This substance was evaluated for acceptable daily intake for man by the Joint FAO/WHO Expert Committee on Food Additives (see Annex 1, Refs No. 20 and No. 33) in 1969 and 1973. Since the previous evaluation, additional data have become available and are summarized and discussed in the following monograph. The previously published monographs have been expanded and are reproduced in their entirety below. BIOLOGICAL DATA BIOCHEMICAL ASPECTS The principal component of this gum is a galactomannan with a linear chain of (1 -> 4) linked ß-D-mannopyranose units with alpha-D-galactopyranose units attached by (1 -> 6) linkages to every alternate mannose. The caloric value was determined in groups of 10 rats fed for one week a 5 g basal diet supplemented with either 1 g or 3 g corn starch or 1 g and 3 g guar gum. At 1 g level guar gum was equivalent to corn starch but at the 3 g level there was a lower equivalence. All animals had large intestines but normal faeces (Anonymous, 1964). In a further bioavailable calorie assay groups of 10 male weanling rats (Sprague-Dawley) were given 5 g basal diet or plus 0.5, 1, 2 g sucrose or 0.5, 1, 2 g guar gum for 10 days. Comparison of the carcass weight gain showed that guar gum was not a source of bioavailable calories (Robaislek, 1974). The rat can use guar flour as a precursor for liver glycogen but at a much reduced efficiency as shown by 15 controls receiving cocoa butter alone (<0.1% glycogen), or cocoa butter + 30% wheat flour (2.6% glycogen) and 18 test animals receiving cocoa butter + 30% guar flour (0.8% glycogen) for two days (Krantz et al., 1948). The digestibility of guar gum in rats fed 0.4 g/day was estimated to be 76% (Booth et al., 1963). However another digestibility study in groups of five male and five female rats (Purdue strain) on a mannose-free diet showed that 83-100% of mannose fed as 1% guar gum in the diet for 18 hours was excreted in the faeces over a total of 30 hours. Some decrease in chain length of galactomannans may have occurred probably through the action of the microflora as mammals are not known to possess mannosidase. Liberation of galactose was not determined (Tsai & Whistler, 1975). Incubation of solutions or suspensions with human gastric juice, duodenal juice + bile, pancreatic juice and succus entericus with or without added rabbit small gut membrane enzymes produced no evidence of hydrolysis (Semenza, 1975). Rat large gut microflora partially hydrolyzed guar gum in vitro (Towle & Schranz, 1975). Feeding chicks for four weeks on a diet containing 3% cholesterol, 3% guar gum and 3% cholesterol + 3% guar gum reduced the serum cholesterol level especially if both cholesterol and guar gum were ingested. Liver cholesterol was only depressed if cholesterol and guar gum were fed (Couch et al., 1966). Groups each of eight male Holtzman rats were maintained on a purified synthetic diet, or the diet plus 1% cholesterol, or the diet plus 1% cholesterol and 10% guar gum for 28 days. The increased liver cholesterol and liver total lipid induced by cholesterol feeding was largely counteracted by concurrent feeding of guar gum (Ershoff & Wells, 1962). Ten per cent. but not 5% guar gum added concurrently to a casein/sucrose diet with 1% cholesterol and 10% corn oil significantly reduced serum and liver cholesterol. Five per cent. guar gum reduced only the liver cholesterol when only 5% corn oil was used with a commercial diet (Riccardi & Fahrenbach, 1967). TOXICOLOGICAL STUDIES Special studies on teratogenicity Teratological experiments with three species of animals (mice, rats and hamsters) did not indicate that the test material was a teratogen in mice at 170 mg/kg and 800 mg/kg although 6/29 dams died at the highest level tested. Similar negative findings were seen in rats up to 900 mg/kg and up to 600 mg/kg in hamsters (Anonymous, 1972). Acute toxicity Eighteen rats given guar gum in cocoa butter at 30% of their diet for 48 hours showed no adverse effects (Krantz et al., 1948). Feeding 27% guar gum to rats for seven days caused 7/10 deaths due to probable intestinal blockage (Anonymous, 1964). Short-term studies Rat Five male rats were fed 0 and 6% guar gum for 91 days in their diet. No differences were observed between the two groups in weight gain and food efficiency (Booth et al., 1963). Fifteen rats were fed a diet containing 0.5% guar gum and varying amounts of water for 21 days. Weight gain and protein efficiency increased with higher water content (Keane et al., 1962). Groups of 10 male and 10 female rats were fed in their diet either 0, 1%, 2% or 5% guar flour for 90 days. At the end of the test general behaviour, appearance, survival were not noticeably affected by feeding guar gum. Growth was relatively low in males fed 2% and 5% and food efficiency was slightly diminished in males of the 5% group. Haematology, urinalysis, serum enzyme activities or blood sugar levels showed no effects. Blood urea nitrogen values were slightly increased in males at the 5% level. The relative weight of the caecum was increased at the 2% and 5% levels in both sexes, that of the thyroid only in males. Gross and histopathology revealed no changes attributable to gum ingestion (Til et al., 1974). Chicken Groups of 20 chicks, one-day old, were maintained on diets containing 2% guar gum for 21 days and showed depressed growth, reduced nitrogen retention and fat absorption. Pancreatic weight was significantly increased when diets contained guar gum in a high protein (30%) diet (Kratzer et al., 1967). Dog Four groups of five male and five female beagles were fed 0, 1%, 5% or 10% of a precooked mixture of guar and carob bean gum (proportions not stated) for 30 weeks. Only at the 10% level were gut hypermotility and soft bulky faeces observed, probably of no toxicological significance. Also at the 10% level digestibility was reduced. No adverse haematological, urinary, gross and histopathological and ophthalmological findings were noted (Cox et al., 1974). Monkey Two monkeys received 1 g of guar flour in their diet daily. Wellbeing, growth and haematology (RBC, WBC, Hb, urea) remained normal. One monkey died after 16 months, the other was sacrificed at 24 months. No abnormalities were noted on gross and histopathology (Krantz, 1948). Long-term studies Rat Out of two groups of 15 male and 15 female rats receiving either 0 or 5% guar flour in their diet seven males and eight females survived in each group and were followed up for 24 months. One test animal died after 12, 18, 19 and 22 months, the last surviving test animal was sacrificed after 24 months. Three control rats survived to 24 months. All animals appeared in good health, had similar body weights. Histology of liver, kidney, spleen, gut and bone marrow showed no abnormality (Krantz et al., 1948). OBSERVATIONS IN MAN Five volunteers ingested 1 g of guar flour in capsule per day for 10 days without any apparent effects (Krantz, 1947). Comments: Guar gum is consumed in some parts of the world as a component of guar flour. One study using guar gum at less than 15% of the diet pointed to guar gum being calorically equivalent to corn starch. More recent studies, however, on digestibility and caloric availability in vivo in rats at dietary levels of 1-2% and in vitro studies with human enzyme preparations showed no evidence of hydrolysis by mammalian intestinal enzymes. Rat gut flora in vitro partially hydrolizes guar gum. A recent adequate short-term study in rats revealed no adverse effects apart from caecal enlargement and thyroid enlargement in one sex only. The significance of these findings for human safety evaluation is doubtful. The long-term study, though not adequate by present standards, revealed no adverse effects at the 5% level. EVALUATION Acceptable daily intake not specified.* REFERENCES Anonymous (1964) Evaluation of Jaguar A-20 and Karaya gum. Assay report No. 3110860 and 3110861. Unpublished report from the Wisconsin Alumni Research Foundation submitted to the World Health Organization Anonymous (1972) Teratologic evaluation of FDA 71-16 (guar gum) in mice, rats, hamsters and rabbits. Unpublished report from the Food and Drug Research Labs, Inc. submitted to the World Health Organization by the Food and Drug Administration, United States of America * The statement "ADI not specified" means that, on the basis of the available data (toxicological, biochemical, and other), the total daily intake of the substance, arising from its use or uses at the levels necessary to achieve the desired effect and from its acceptable background in food, does not, in the opinion of the Committee, represent a hazard to health. For this reason, and for the reasons stated in individual evaluations, the establishment of an acceptable daily intake (ADI) in mg/kg bw is not deemed necessary. Booth, A. N., Hendrickson, A. P. and De Eds, F. (1963) Physiologic effects of three microbial polysaccharides on rats, Toxicol. appl. Pharmacol., 5, 478-484 Couch, J. R., Bakshi, Y. K., Fergusson, T. M., Smith, E. B. & Creger, C. R. (1967) The effect of processing on the nutritional value of guar meal for broiler chicks, Brit. Poultry Sci., 8, 243-250 Cox, G. E., Baily, D. E. & Morgareidge, K. (1974) Subacute feeding in dogs with a pre-cooked gum blend. Unpublished report from the Food and Drug Labs, Inc. submitted to the World Health Organization by Hercules BV Ershoff, B. H. & Wells, A. F. (1962) Effects of gum guar, locust bean gum and carrageenan on liver cholesterol of cholesterol-fed rats, Proc. soc. exp. biol. med., 110, (3), 580-582 Keane, K. W., Smutko, C. J., Krieger, C. H. & Denton, A. E. (1962) The addition of water to purified diets and its effect upon growth and protein efficiency ratio in the rat, J. Nutr., 77, 18-22 Krantz, J. C. (1947) Unpublished report from General Mills, Inc. submitted to the World Health Organization Krantz, J. C., jr (1948) The feeding of guar gum to rats (lifespan) and to monkeys. Unpublished report from the University of Maryland, School of Medicine submitted to the World Health Organization by General Mills Chemicals, Inc. Krantz, J. C., jr, Carr, C. J. and de Farson, C. B. (1948) Guar polysaccharide as a precursor of glycogen, J. Amer. Diet. Ass., 24, 212 Krutzer, F. H., Rajaguru, R. W. A. S. B. & Vohra, P. (1967) The effect of polysaccharides on energy utilization, nitrogen retention and fat absorption in chickens, Poultry Sci., 48, 1489-1493 Riccardi, B. A. & Fahrenback, H. J. (1967) Effect of guar gum and pectin N.F. on serum and liver lipids of cholesterol fed rats, Proc. Soc. Exp. Biol. Med., 124, (3), 749-752 Robaislek, E. (1974) Bioavailable calorie assay of guar gum. Unpublished report from WARF Institute, Inc. submitted to the World Health Organization by Institut Européen des Industries de la Gomme de Caroube Semenza, G. (1975) Report on the possible digestion of locust bean gum in the stomach and/or in the small intestine in an in vitro study. Unpublished report from the Eidgenössische Technische Hochschule Zürich submitted to the World Health Organization by the Institut Européen des Industries de la Gomme de Caroube Til, H. P., Spanjers, M. Th. & de Groot, A. P. (1974) Sub-chronic toxicity study with locust bean gum in rats. Unpublished report from Centraal Instituut voor Voedingsonderzoek TNO submitted to the World Health Organization by Hercules BV and Institut Européen des Industries de la Gomme de Caroube Towle, G. A. & Schranz, R. E. (1975) The action of rat microflora on carob bean gum solutions in vitro. Unpublished report from Hercules Research Center submitted to the World Health Organization by Hercules Incorporated Tsai, L. B. & Whistler, R. L. (1975) Digestibility of galactomannans. Unpublished report submitted to the World Health Organization by Professor H. Neukom, Chairman of the Technical Committee of Inst. Europ. des Industries de la Gomme de Caroube
See Also: Toxicological Abbreviations