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    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