CAROB BEAN GUM* (Locust Bean Gum) Explanation This substance was evaluated for acceptable daily intake for man by the Joint FAO/WHO Expert Committee on Food Additives in 1969, 1973 and 1975 (see Annex I, Refs. 19, 32 and 37). Toxicological monographs were issued in 1969, 1973 and 1975 (see Annex I, Refs. 20, 33 and 38). Since the previous evaluation, additional data have become available and are summarized and discussed in the following monograph. The previously issued monographs have been expanded and are reproduced in their entirety below. BIOLOGICAL DATA BIOCHEMICAL ASPECTS In a bioavailable calorie assay, groups of 10 male weanling rats (Sprague-Dawley) were given 5 g basal diet or basal diet plus 0.5, 1, 2 g sucrose or 0.5, 1, 2 g gum for 10 days. Comparison of the carcass weight gain showed that carob bean gum was not a source of bioavailable calories (Robaislek, 1974). Fifteen controls and 18 male test rats, after three days on normal diet followed by a 12 hour fast, received two-and-one-half days in their diet either 67% cocoa butter with wheat flour or 67% cocoa butter with 33% carob bean gum. Glycogen accumulated in the liver but far less efficiently than with wheat flour (Krantz et al., 1948). A digestibility study in groups of five male and five female rats (Purdue strain) on a mannose-free diet showed that 85-100% of mannose fed as 1% carob bean gum in the diet for 18 hours was excreted in the faeces over a total of 30 hours. Some decrease in chain length of galactomannan may have occurred, probably through the action of the microflora as mammals are not known to possess mannosidase. Liberation of galactose units was not determined (Tsai & Whistler, 1975). * Carob bean gum (also called locust bean gum) is the material separated and variously refined from the endosperm of the seed of the carob tree, Ceratonia siliqua, a large leguminous evergreen that is widely cultivated in the Mediterranean area. The carbohydrate component of carob bean gum is considered to be a neutral galactomannan polymer consisting of a main chain of 1,4- linked D-mannose units with a side chain of D-galactose on every fourth or fifth unit, attached through 1,6-glycosidic linkages to the polymannose chain. (FASEB/LSRO/SCOGS-3) 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 hydrolysed carob bean gum in vitro (Towle & Schranz, 1975) after conditioning to 1% carob bean gum in the diet for three weeks. Groups each of eight male Holtzman rats were maintained on a purified synthetic diet, or the diet plus 1% cholesterol, or the diet + 1% cholesterol + 10% carob bean gum for 28 days. The increased liver cholesterol and liver total lipid induced by cholesterol feeding was largely counteracted by concurrent feeding of carob bean gum (Ershoff & Wells, 1962). Groups each of 12 chicks, one day old were fed a casein sucrose basel diet supplement with 3% cholesterol and either 10%, 6%, 3%, 2%, 1.5% or 1.0% locust bean gum for 27 days. At the end of the test period, plasma cholesterol was determined. At the 10% level, there was a 35% reduction of plasma cholesterol, no significant effect in body weight or food consumption. At the 6% level, there was a moderate reduction in cholesterol level. There was a wide variation in the hypocholesterolemic activity of the carob bean gums tested with some preparation being totally inactive (Fahrenbach et al., 1966). The effect of carob or locust bean gum on nitrogen (N) balance and dry matter digestibility was studied in rats. Seventy-two weanling male Sprague-Dawley rats were divided into a control and five experimental groups of 12 animals each. Various gums including locust bean gum were fed at the 10% level in a casein-saccharose-corn starch diet. Following a three-day adaptation period, feed remnants, urine and faeces were collected during an eight-day balance period. Trypsin inhibitory activity was measured in each diet. Carob bean gum caused a significant rise in faecal N loss, resulting in a marked reduction of apparent protein digestibility from 87.8% in the controls to 75%. Urinary N was significantly lower than controls. Faecal dry matter was also significantly increased by carob bean gum. There was only slight trypsin inhibition caused by carob bean gum (Harmuth-Hoene & Schwerdtfeger, 1979). Carob bean gum has been noted to contain tannins, which depress appetite and growth and trypsin inhibitors, which are also growth inhibitory (LSRO/FASEB/SCOGS-3, 1972). TOXICOLOGICAL STUDIES Special studies on teratogenicity Teratogenical experiments with four species of animals (rats, mice, hamsters and rabbits) did not indicate that the test material was a teratogen to mice at 280 mg/kg bw and 1300 mg/kg, although 5/21 dams died at the latter dose. Up to 1300 mg/kg in rats, up to 1000 mg/kg in hamsters and at 196 mg/kg in rabbits no teratological effects were seen. At 910 mg/kg in rabbits, most of the pregnant dams died (Morgareidge, 1972). In one study, carob bean gum was injected via the air cell and yolk or albumen routes into fertile eggs prior to and after 96 hours of incubation. Eggs were candied at 48-hour intervals and dead embryos were examined for stage of development and defects. At hatching, all chicks were examined for gross defects and samples were taken for gross skeletal staining and histopathological examination. Although the authors do not state levels of carob bean gum injected, they note anophthalmia, phocomelia, micromelia and torticollis occurring with carob bean gum (Naber & Smothers, 1975). Special studies on mutagenicity Mutagenic tests on rats and mice using three different methods gave negative results. There was no measurable mutagenic response in recombination frequency for Sacc. cerev. in host-mediated assay at 5 g/kg or in vitro. No adverse effects were seen on chromosomes in rat bone marrow or human lung cell cultures. The dominant lethal test in rats was negative (Maxwell & Newell, 1972). Carob (locust) bean gum was evaluated for genetic activity in microbial assays with and without the addition of mammalian metabolic activation preparations. Indicator organisms used were Saccharomyces cerevisiae and Salmonella typhimurium, strains TA-1535, TA-1537 and TA-1538. Mammalian metabolic activation preparations were from mouse (ICR adult), rat (Sprague-Dawley adult) and monkey (Macaca mulatta adult). Carob (locust) bean gum did not exhibit genetic activity in any of the assays employed (Brusick, 1975). Acute toxicity LD50 Species Route mg/kg bw Reference Rat Oral >5000 Maxwell & Newell, 1972 Short-term studies Rat Groups of 10 males and 10 females were fed in their diet carob bean gum at levels of 0%, 1%, 2% or 5% for 90 days. General condition, behaviour, survival, growth, food intake, haematology, blood biochemistry and urinalysis showed no treatment-related differences between test and control groups at any dietary level except that the last glucose level was slightly increased in the 5% group. Gross and microscopic examination did not reveal any pathological changes attributable to ingestion of the gum. The increase in the relative weight of the caecum at the 2% level is not considered to be of toxicological importance (Til et al., 1974). Groups each of newly weaned Sprague-Dawley rats (10/group) were fed a soybean-corn meal diet containing 2% locust (carob) bean gum for 36 days. Locust bean gum had no effect in the digestibility of the diet, nor was there any significant effect on growth (Vohra et al., 1979). Dog Four groups of five male and five female Beagles were fed 0%, 1% 5% or 10% of a precooked mixture of carob bean and guar gum (proportions unknown) for 30 weeks. Only at the 10% level were hypermotility and soft, bulky stools observed, probably of not 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). Chicken Groups of 20-day-old chickens were fed diets containing 0.25%, 0.52%, 12% and 22% carob bean gum for three weeks. Growth depression was dose related and marked at the 2% level of intake (Kratzer et al., 1967; Vohra & Kratzer, 1964). Groups of day-old broiler chickens (seven per group, breed not specified) were fed a soybean protein-corn based diet containing 2% carob (locust) bean gum for 24 days. The dietary intake of the chickens was measured daily for the last week of the experimental period; digestibility of the test diet was calculated from the dry weights of the feed and excreta. The average body weight of chickens and the digestibility of the diet was reduced significantly by the inclusion of locust (carob) bean gum in the diet (Vohra et al., 1979). Japanese quail Groups of day-old Japanese quail (10 per group) were fed a soybean-meal-corn based diet containing 2% locust (carob) bean gum for either 35 or 37 days. The dietary intake of the quail was measured daily for the last week of their experimental period; the digestibility of the diet was calculated from the day weights of the feed and excreta. Average body weight and digestibility of the diet was significantly reduced by inclusion of locust (carob) bean gum in the diet (Vohra et al., 1979). Long-term studies None available. OBSERVATIONS IN MAN A clinical study of a commercial preparation of carob bean grain as a laxative in doses of "two heaping teaspoonfuls" in 56 patients, some of whom took the preparation regularly for two years, resulted in no untoward effects related to the gastrointestinal tract, and no allergenic reaction (Holbrook, 1951). Eight infants between the ages of 2.5-5 months were fed meals of sugared milk or sugared milk plus a 1% powder extract from carob bean. Addition of the carob supplement did not alter the duration of the gastrointestinal transit time of the meal. Physiological aerophagy was markedly suppressed by the supplement (Rivier, 1952). In patients with renal failure, ingestion of 25 g of locust bean gum/day had a laxative effect, decreased high blood pressure, and caused a fall in serum urea, creatinine, and phosphorus by the second week of treatment (Yatzidis et al., 1979). Comments In vitro tests with human enzyme preparations show little utilization by the gut. Carob bean gut was not teratogenic in several mammalian species although it did produce terata in the chick embryo assay. The available short-term studies in the rat and dog showed no evidence of adverse effects at the 5% level. The effects noted in feeding trials are those expected of a non-metabolized polymeric substance acting as a bulking agent. Carob bean gum is used in pharmaceutical preparations. The previously requested long-term feeding and reproduction studies are not yet available. EVALUATION Estimate of acceptable daily intake for man Acceptable daily intake not specified.*,** FURTHER WORK OR INFORMATION Required by 1984 (1) An adequate long-term study in a rodent species. (2) Reproduction studies. * 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. ** Temporary. REFERENCES Brusick, D. Mutagenic evaluation of compound FDA 71-14 PM9000-40-2. Locust bean gum. Unpublished report from Litton Bionetics, Inc. Submitted to the World Health Organization by the US Food and Drug Administration, 1975 Cox, G. E., Baily, D. E. & Morgareidge, K. Subacute feeding in dogs with a precooked gum blend. Unpublished report from the Food and Drugs Labs, Inc., submitted to the World Health Organization by Hercules B. V., 1974 Ershoff, B. H. & Wells, A. G. 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, 1962 Fahrenbach, M. J., Riccardi, B. A. & Grant, W. E. Hypocholesterolemic activity of mucilaginous polysaccharides in White Leghorn cockerels. Proc. Soc. exp. Biol. Med., 13(2), 321-6, 1966 Harmuth-Hoene, A. & Schwerdtfeger, E. Effect of indigestible polysaccharrides on protein digestibility and nitrogen retention in growing rats. Nut. Metab., 23, 399-407, 1979 Holbrook, A. A. The behaviour of carob bean in the gastrointestinal tract of man. A. J. Dig. Dis., 18, 24-28, 1951 Krantz, J. C., Jr., Carr, C. J. & de Farson, C. B. Guar polysaccharide as a precursor of glycogen. J. Amer. diet. Ass., 24, 212, 1948 Kratzer, F. H., Rajaguru, R. W. A. S. B. & Vohra, P. The effect of polysaccharides on energy utilization, nitrogen retention and fat absorption in chickens. Poultry Sci., 48, 1489-1493, 1967 LRSO/FASEB. Evaluation of the health aspects of carob bean gum as a food - SCOGS-3, 1972 Maxwell, W. A. & Newell, G. W. Study of the mutagenic effects of FDA 71-14 (Locust bean gum). Unpublished report from the Stanford Research Institute submitted to the World Health Organization by Hercules B. V., 1972 Morgareidge, K. Teratological evaluation of FDA-71-14 (Locust bean gum). Unpublished report from the Food and Drug Research Labs, Inc. submitted to the World Health Organization by Hercules B. V., 1972 Naber, E. C. & Smothers, S. E. Patterns of toxicity and teratogenicity in the chick embryo resulting from the administration of certain nutrients and food additives. Poultry Sci., 54(5), 1806, 1975 Rivier, C. Recherches sur le mode d'action du Nestargel. Schweiz. Mediz., 82, 256, 1952 Robaislek, E. Bioavailable calorie assay of Guar gum. Unpublished report from WARF Institute, Inc. submitted to the World Health Organization by Institut Europeen des Industries de la Gomme de Caroube, 1974 Semenza, G. 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 Eidgenossische Technische Hochschule Zurich submitted to the World Health Organization by the Institut Europeen des Industries de la Gomme de Caroube, 1975 Til, H. P., Spanjers, M. Th. & de Groot, A. P. Subchronic toxicity study with locust bean gum in rats. Unpublished report from Centraal Instituut voor Voedingsonderzoek TNO submitted to the World Health Organization by Hercules B.V. and Institut Europeen des Industries de la Gomme de Caroube, 1974 Towle, G. A. & Schranz, R. E. 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, 1975 Tsai, L. B. & Whistler, R. L. Digestibility of galactomannans. Unpublished report submitted to the World Health Organization by Professor H. Neukom, Chairman of the Technical Committee of Institut Europeen des Industries de la Gomme de Caroube, 1975 Vohra, P. & Kratzer, F. H. Growth inhibitory effects of certain polysaccharides for chickens. Poultry Sci., 43, 1164-1170, 1964 Vohra, P., Shariff, G. & Kratzer, F. H. Growth inhibitory effect of some gums and pectin for Tribolium castaneum larvae, chickens and Japanese quail. Nutr. Rep. Internatl., 19(4), 463-469, 1979 Yatzidis, H., Koutsicos, D. & Digenis, P. Newer oral sorbents in uremia. Clin. Nephrol., 11(2), 105-106, 1979
See Also: Toxicological Abbreviations Carob bean gum (FAO Nutrition Meetings Report Series 46a) Carob bean gum (WHO Food Additives Series 5) CAROB BEAN GUM (JECFA Evaluation)