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    KARAYA GUM

    Explanation

         This substance has been evaluated for acceptable daily intake by
    the Joint FAO/WHO Expert Committee on Food Additives in 1969, 1973,
    1977 and 1980 (see Annex I, Refs. 19, 32, 43 and 54). Toxicological
    monographs were issued in 1969 and 1973 (see Annex I, Refs. 20 and
    33).

         Since the previous evaluation, additional data have become
    available and are summarized and discussed in the following monograph.
    The previously published monograph has been expanded and is reproduced
    in its entirety below.

    BIOLOGICAL DATA

    BIOCHEMICAL ASPECTS

    Absorption and metabolism

         Karaya gum does not disintegrate or decompose appreciably in the
    alimentary tract. In a study of 10 dogs, 95% of the orally
    administered gum was recovered in the faeces. It absorbs a large
    quantity of water and therefore acts as a mechanical laxative. It
    tends to increase faecal nitrogen excretion, does not affect starch
    digestion in the dog and does not inhibit the utilization of vitamin A
    in rats (Ivy & Isaacs, 1938).

         The caloric value was determined in groups of 10 rats fed for one
    week 5 g basal diet with either 1 g and 3 g corn starch or 1 g and 3 g
    karaya gum supplements. At the i g level, karaya gum only had 30% of
    the caloric value of corn starch. At the 2 g level growth was very
    depressed. The intestine was enlarged in all rats on gum (Anon.,
    1964).

         The action of 10 species of Bacteroides found in the human colon
    on dietary fibre has been studied. Karaya gum is not utilized by these
    bacteria and remains unchanged (Salyers et al., 1977).

         Fermentations of 10 polysaccharides by species of the family of
    Enterobacteriaceae were examined. Karaya gum was not fermented by any
    of the strains tested. As food additive, karaya gum seems safe from
    destruction by facultative fermenters (Ochuba &von Riesen, 1980).

         Two groups of four male rats (365-459 g) were fed pelleted diet
    containing 5% (w/w) karaya gum over a 24-hour period. Urine and faeces
    from each animal were collected and weighed after 24, 48 and 72 hours.
    Faeces were examined, after methanolysis, by GC-MS and the quantity
    and monosaccharide composition of the faecal polysaccharides were

    compared with the dose and original composition of the gum
    polysaccharides. It was estimated that 95% of the gum consumed was
    recovered as faecaI polysaccharide. Rhamnose was not detected in the
    urine. The absence of this component demonstrates that it is not
    liberated from karaya gum during its transit through the intestine.
    These two findings indicate that extensive degradation involving
    chains and chain terminations did not occur. The study has not
    produced any evidence suggesting metabolic modification of karaya gum
    in the intestinal tract of the rat when the gum is added to a normal
    rat diet (Brown et al., 1982).

    TOXICOLOGICAL STUDIES

    Special studies on mutagenicity

         The host-mediated assay of karaya gum did not produce any
    measurable mutagenic response or alteration in the recombination
    frequency of Saccharomyces cerevisiae in either host-mediated assay
    or the associated in vitro tests. The cytogenetic assay of karaya
    gum exhibited no adverse effect on either metaphase chromosomes from
    rat bone marrow or anaphase chromosomes from in vitro cultures of
    human embryonic lung cells at any of the dose levels or time periods
    tested. No consistent responses Occurred in the dominant lethal gum
    test to suggest that karaya gum is mutagenic to the rat as a result of
    this experimental procedure (Newell & Maxwell, 1972, available in
    summary only).

    Acute toxicity

         The acute oral LD50 of 12 food-grade gums (sodium and calcium
    carragheenate, tragacanth, ghatti, locust bean, arabic, guar, karaya,
    propylene glycol, alginate, furcellaran, agar-agar and Na
    carboxymethylcellulose) was studied. Each material was administered by
    gavage to five groups of 10 rats, with five males and five females in
    each group. Vehicles utilized were water, mineral oil, corn oil and
    soybean oil. The animals were fasted 18 hours prior to dosing with
    food and water available ad libitum during the 14-day observation
    period. LD50 values observed ranged from 2.6 to 18.0 g/kg with most
    values in the 5-10 g/kg range. Generally, the rabbit was the most
    sensitive species and the rat and mouse the least sensitive (Bailey et
    al., 1976, available in summary only).

    Short-term studies

    Rat

         Examination of the intestine of rats fed 1 g karaya gum per day
    for 91 days showed no gross abnormalities. There was no interference
    with normal growth (Ivy & Isaacs, 1938).

         Karaya gum was used in a six- to seven-week feeding study to
    evaluate the effect on adaptive responses of nutritionally controlled
    parameters in rats by feeding a fibre-free diet containing increasing
    additions of polysaccharides (0, 10, 20 and 40%). In general, the
    supplements reduced weight increases due to lower energy intakes. None
    of the polysaccharides fed, however, decreased energy utilization.
    Similarly, all polysaccharides increased small intestine length up to
    about 30% without grossly altering mucosal protein and DNA per unit of
    length. Concerning the effect on the large intestine, the addition of
    karaya gum at 10, 20 and 40% level caused average increases of the
    weight of the colon by a factor of 1.4, 1.9 and 2.9 respectively
    (Elsenhaus et al., 1981).

         Karaya gum was given to groups of 15 rats of each sex at levels
    of 0 (control), 0.2, 1.0 and 5.0% (w/w) in the diet for 13 weeks (5%
    is the top level recommended for substances that are not absorbed). An
    increase in faecal bulk was seen in all treated groups throughout the
    experiment. There was a decrease in weight gain at the highest dietary
    level (significant only in the females) which was associated with a
    marginal reduction in food conversion efficiency. Males given 1 or 5%
    gum drank more than the controls and a transient increase in water
    intake was seen in females given the highest level. The no-untoward-
    effect level from this study was 5% of the diet, providing a mean
    intake of approximately 4 g karaya gum/kg bw per day (Taupin &
    Anderson, 1982).

    Dog

         Three dogs were fed 5 g unprocessed karaya gum daily for 30 days.
    Defaecations were not frequent, faecal bulk and moisture were
    increased but there was no obvious gastrointestinal irritation (Ivy &
    Isaacs, 1938).

    Long-term studies

         Five rats were fed karaya gum in the diet for two years. Three
    developed enlarged colon and ulceration (Hoelzel et al., 1941).

         In another experiment, groups of three rats were fed karaya gum
    at first at 10%, gradually increasing to 25% in the diet over their
    life span. Controls of five and seven animals received low residue
    diets. No caecal ulceration was found in this experiment (Carlson &
    Hoelzel, 1948).

    OBSERVATIONS IN MAN

         Forty-six female and 46 male subjects took karaya gum granules
    for one week at levels equivalent to 7 g/day. Seven subjects had
    abdominal discomfort (Ivy & Isaacs, 1938). Ingestion or inhalation was

    reported to have caused allergy. Sixteen cases of allergic sensitivity
    to inhalation of the gum used as a wave set and to oral ingestion as a
    laxative were reported. Symptoms included hay fever, asthma,
    dermatitis and gastrointestinal distress (Figley, 1940). In a
    comparison with carob bean gum as a laxative in 10 human subjects,
    karaya gum was found to be transformed to a gelatinous state at a
    higher level in the intestine and to be transported more rapidly
    through the intestinal tract (Holbrook, 1951). A case of allergic
    respiratory symptoms (nasal congestion, coughing and wheezing)
    following exposure to karaya gum powder has been reported in a
    27-year-old female nurse employed for three years as an enterostomal
    therapist (Wagner, 1980).

         The administration of karaya gum to human subjects and the
    effects on glucose absorption, caecal and colonic function and routine
    haematological and biochemical measurements were studied. Karaya gum
    was administered to five fit male volunteers (aged 30-56 years), free
    of gastrointestinal disease and symptoms, over a 21-day period. The
    dose of 10.5 g was well tolerated. Karaya gum had no significant
    effect on wet and dry stool weight, faecal constituents or transit
    time. Also, there was no increase in bacterial metabolic activity. It
    would appear that the molecule is not significantly degraded during
    its passage through the human colon. Karaya gum appears to have little
    metabolic effect upon the host: glucose tolerance is not significantly
    altered after its ingestion and haematological and biochemical indices
    remain unchanged (Eastwood et al., 1982).

    Comments

         Karaya gum is not degraded by strains of bacteria found in the
    human colon. An especially designed metabolic study in the rat
    demonstrated that karaya gum does not undergo any metabolic
    modification in the intestinal tract.

         The available short-term study in the rat showed no evidence of
    adverse effects at the 5% level. The effects noted in feeding trials
    were those expected of a non-metabolized polymeric substance acting as
    a bulking agent.

         The new data submitted indicate that karaya gum, even ingested in
    a relatively large dose, has no toxic effect and also has little
    metabolic action of consequence.

    EVALUATION

    Level causing no toxicological effect

         Rat: 5% (50 000 ppm) in the diet, equal to 4000 mg/kg bw.

    Estimate of temporary acceptable daily intake for man

         0-20 mg/kg bw.

    FURTHER WORK OR INFORMATION

    Required by 1985

         Submission of the results of a short-term feeding study in a
    non-rodent species.

    REFERENCES

    Anon. (1964) Unpublished report (No. 3110860/1) from the Wisconsin
         Alumni Research Foundation to Stein, Hall & Co.

    Bailey, D. E., Morgareidge, K. & Collins, T. X. (1976) Comparative
         acute oral toxicity of twelve food grade gums in the mouse, rat,
         hamster and rabbit. Food and Drug Res. Labs, Inc., New York; US
         Food and Drug Administration, Washington, D.C. - Abst. 15th
         Annual Meeting of the S.O.T., Toxicol. appl. Pharmacol., 37,
         143

    Brown, P. H., Pringuer, M. A. & Anderson, D. M. W. (1982) A study of
         the fate of gum karaya in the rat, Toxicol. Lett., 13,
         247-251

    Carlson, A. J. & Hoelzel, F. (1948) Prolongation of the life span of
         rats by bulking agents in the diet, J. Nutr., 36, 27-40

    Eastwood, M. A., Brydon, W. G. & Anderson, D. M. W. (1982) The effects
         of gum karaya in man. Unpublished report submitted by INGAR to
         WHO

    Elsenhaus, B., Blume, R. & Caspary, W. F. (1981) Long-term feeding of
         unavailable carbohydrate gelling agents. Influence of dietary
         concentration and microbiological degradation on adaptive
         responses in the rat, Am. J. Clin. Nutr., 34, 1837-1848

    Figley, K. D. (1940) Karaya gum hypersensitivity, J. Am. Med. Ass.,
         114, 747-748

    Hoelzel, F., Costel, E. & Carlson, A. J. (1941) Production of
         intestinal lesions by feeding karaya gum and other materials to
         rats, Am. J. dig. Dis., 8, 266-270

    Holbrook, A. A. (1951) The behaviour of carob gum in the
         gastrointestinal tract of man, Am. J. dig. Dis., 18, 24-28

    Ivy, A. C. & Isaacs, B. L. (1938) Karaya gum as a mechanical laxative.
         An experimental study on animals and man, Am. J. dig. Dis.,
         5, 315-321

    Newell, G. W. & Maxwell, W. A. (1972) Mutagenic effects of sterculia
         gum (karaya). Stanford Res. Inst.; US Nat. Tech. Inf. Ser., PB
         Rep. 1972, No. 221823/8. From Govt. Rep. Announce (US) 1973, 73
         (17) 45; C.A. 80: 10842s, 1974

    Ochuba, G. U. &von Riesen, V. L. (1980) Fermentation of
         polysaccharides by Klebsiellae and other facultative bacilli,
         Appl. Environ. Microbiol., 39, 988-992

    Salyers, A. A. et al. (1977) Fermentation of mucin and plant
         polysaccharides by Bacteroides from the human colon, Appl.
         Environ. Microbiol., 33, 319-322

    Taupin, P. J. Y. & Anderson, D. M. W. (1982) Subchronic toxicity
         study in rats fed gum karaya, Fd Chem. Toxicol., 20, 513-517

    Wagner, W. (1980) Karaya gum hypersensitivity in an enterostomal
         therapist, J.A.M.A., Feb. 1, 243, No. 5, 432
    


    See Also:
       Toxicological Abbreviations
       Karaya gum (FAO Nutrition Meetings Report Series 46a)
       Karaya gum (WHO Food Additives Series 5)
       Karaya gum (WHO Food Additives Series 24)
       KARAYA GUM (JECFA Evaluation)