This substance has been evaluated for acceptable daily intake
    by the Joint FAO/WHO Expert Committee on Food Additives in 1969,
    1973, 1977, 1980, 1983, 1986 and 1987 (Annex 1, references 19, 32,
    44, 50, 62, 70 and 73). Toxicological monographs were issued in
    1969, 1973 and 1983 (Annex 1, references 20, 33 and 63). A temporary
    ADI of 0-20 mg/kg bw was established in 1983 and the Committee
    required submission of the results of a short term feeding study in
    a non-rodent species by 1985. The 1985 Committee extended the
    temporary ADI of 0-20 mg/kg bw and requested submission of more
    detailed information on the submitted feeding study by 1986. At the
    1986 meeting another report of the study was submitted to the
    Committee for review, but it still lacked the detailed information
    needed for a proper evaluation. However, the Committee was informed
    that a feeding study in monkeys was in progress. The Committee
    therefore agreed to extend the existing temporary ADI of 0-20 mg/kg
    bw and requested the submission of detailed information by 1988.
    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.


    Biochemical studies

    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 dogs 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 1 g level, karaya gum only
    had 30% of the caloric value of corn starch. At the 2 g level
    growth was depressed. The intestine was enlarged in all rats on gum
    (Wisconsin Alumni Research Foundation, 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, 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 quality 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 faecal 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 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.,

         A finely powdered (passing 150 mesh) gum karaya (GK) was added
    to the basic diet (Spratts' No. 1 powder) at the 7% (w/w) level.
    This dose level was selected so as to exceed, slightly, the
    no-effect level established from 90-day dietary studies, e.g. 5%. This
    supplemented diet was ingested by a group (unspecified number) of

    Albino Wistar rats for 45 days, during which time their initial body
    weights, range 99-120 g, increased an average by 233 g (controls) and
    229 g (GK). The study indicates that the ingestion of GK for 45 days
    does not cause abnormalities in the organelles within the cells of rat
    jejunum, ileum and caecum. Neither inclusions nor other ultra-
    structural or pathological differences between the control animals
    and experimental animals fed diets supplemented with karaya gum
    were detected (Anderson et al., 1986).

    Toxicological Studies

    Special studies on teratogenicity

         The administration of up to 170 mg/kg bw of the test material
    to pregnant mice for 10 consecutive days had no clearly discernable
    effect on nidation nor on maternal or foetal survival. The number
    of abnormalities seen in either soft or skeletal tissues of the
    test groups did not differ from the number occurring spontaneously
    in the controls. In a concurrent group of mice dosed at a level of
    800 mg/kg bw, a significant number of maternal deaths (9 out of 28)
    occurred. The surviving dams appeared to be completely normal and
    bore normal foetuses with no effect on the rate of nidation or
    survival of live pups  in utero. It was concluded that the test
    material was not a teratogen in mice (US FDA, 1972; US FDA, 1973).

         In further studies 1% and 10% aqueous suspensions were given
    orally and a 1% suspension was given intraperitoneally to pregnant
    mice in the 11th to 15th days of gestation. In these tests, GK had
    no influence on fetal development (Frohberg et al., 1969).

    Special studies on immunoresponse

         Female CBA mice, 6 to 8 per group, aged 6 weeks, were used.
    They were immunized by injection of 0.1 mg gum in a volume of
    0.05 ml, in complete Freund's adjuvant, into the left hind footpad.
    Twenty one days after primary immunization, the presence of
    delayed-type hypersensitivity was measured by a skin test. Gum
    karaya (0.1 mg) dissolved in 0.15 M saline in a volume of 0.05 ml
    was injected intradermally into the plantar side of the right
    footpad. Footpad thickness was measured in triplicate immediately
    before the intradermal injection, and 24h later. Gum karaya is
    capable of eliciting an immune response which is comparable to the
    specific immune responses elicited by a protein antigen, hen's egg
    ovalbumin (Strobel et al., 1982).

         Two preparations of gum karaya (Sterculia spp.) have been used
    to investigate the immunogenicity and specific irritant properties
    of the gum. Sample KA was completely characterized chemically and
    conforms to the current EEC (E416) and JECFA specifications. Sample
    B, a white powder of Sudanese origin (Sterculia setigera) also

    conformed to the above specifications. The animals used were groups
    of six to eight mice (C57BL/6J  DBA/2)F1 (BDF1). The time course
    of the experiments was as follows: day 0 immunization with 0.2 mg gum
    or saline in complete Freund's adjuvant, intradermally into one hind
    footpad; day 21 skin test with 0.1 mg antigen into the other
    footpad; day 22 measure footpad swelling; day 28 bleed out under
    general anesthesia and measure antibody levels. Serum antibody
    levels were measured by an ELISA technique and delayed hyper-
    sensitivity responses by a footpad swelling test. Antigenic
    cross-reactivity within each gum species was tested in a crossover
    fashion. All gum preparations elicited systemic immune responses
    after immunization. Further processing reduced immunogenicity,
    although there was no evidence that systemic immunity to these
    complex polysaccharide antigens responses could be completely
    abolished by processing or purification. The ethanolic extract of
    gum karaya caused considerable footpad swelling when injected
    intradermally (Strobel et al., 1986).

    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 culture of human embryonic lung cells at any of the dose
    levels or time periods tested. No consistent responses were
    reported in the dominant lethal 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 24-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. The rabbit was
    reported to be the most sensitive species and the rat and mouse the
    least sensitive (Bailey et al., 1976, available in summary only).

    Short-term studies


         Groups each of 16 mice, equally divided by sex were fed
    diets containing 0, 2, 10, 20 or 40% Gum Karaya, for 3 weeks.
    Histological examination of all important organs showed no compound
    related effect. In another study groups of 20 weanling mice were
    fed diets containing 0, 20 or 30% gum karaya for 3 months.
    Histopathological examination of all organs at the termination of
    the study showed no compound related effects (Balakrishan, 1984a).


         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.,

         Karaya gum 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-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).

         Groups each of 16 rats (Wistar strain) equally divided by sex,
    were maintained on diets containing 0, 0.5, 2 or 4% gum karaya for
    90 days. Body weight, pattern and food intake was comparable for
    all groups. At the termination of the study, creatine phosphate,
    glutamic-oxaloacetic transaminase, glutamic pyruvic transaminase,
    and protein was measured in serum and liver. Histopathology was
    also carried out on the principle organs and tissues. No compound
    related effects were observed (Dikshith et al., 1984).


         Three dogs were fed 5 g unprocessed karaya gum daily for 30
    days. Faecal bulk and moisture were increased but there was no
    obvious gastro-intestinal irritation (Ivy & Isaacs, 1938).

    Long-term studies


         Five rats were fed karaya gum in the diet for two years. Three
    developed enlarged colons and ulcerations (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).

    Guinea pigs

         Groups of Guinea pigs, distributed as 10 males and 8 females
    in the test group, and 5 males and 5 females in the control group
    were fed stock diet in which increasing amounts of the powdered gum
    were incorporated, starting from 1 g level in the diet. The
    increment of gum in the diet was continued up to obtaining 16.6%
    level of gum (for the first 4 weeks). There after the 16.6% level
    of gum in the stock diet was continued up to the termination of the
    experiment at 52 weeks. Parameters investigated included growth,
    excretion levels of N in urine, haematological values, organs
    weight. At the end of treatment, organs such as heart, liver,
    spleen, kidneys, adrenals were weighed and preserved for
    histopathological observations. No compound related effects were
    observed (Balakrishan, 1984b, National Institute of Nutrition
    (India), 1985).

    Rhesus monkeys

         Four adult female rhesus monkeys  (Macaca mulatta) were fed
    diets containing gum karaya. Levels were progressively increased
    over the course of one month, from 10 g to 25 g in a daily diet of
    250 g (16.6%), and then maintained at this dietary level for 16
    months. A control group of four female rhesus monkeys received
    stock diet. Body weights, hematological data and liver function
    tests were similar for test and control animals (Balakrishnan,
    1984b, National Institute of Nutrition (India), 1985).

         Eleven adult rhesus monkeys (5 males and 6 females) were
    divided into two groups. The control group consisted of one male
    and two female monkeys which were fed a basal stock diet. The
    experimental groups consisted of four male and four female monkeys

    which were fed a basal stock diet to which gum karaya at the 5% level 
    was added. The feeding trial was continued for a period of 18 weeks. 
    There was no difference in growth between the control and experimental
    groups. There were some reduction in weight of control and experimental
    male animals; it had no relation to the feeding of gum karaya. No
    significant changes in the hematological parameters were found.
    Absolute and relative weights of the various organs did not show
    any change. The authors concluded that the organs and tissues of
    the animals in the control and experimental groups were essentially
    similar (Bhat et al., 1987).

    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 wave set and to oral ingestion as a laxative were reported.
    Symptoms included hay fever, asthma, dermatitis and gastro-
    intestinal 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 and biochemical measurements were
    studied. Karaya gum was administered to 5 healthy male volunteers
    (aged 30-56 years), free of gastro-intestinal 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
    bactericidal 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., 1983).

         Five male volunteers made 24-h collections prior to, and
    following, the ingestion of 10 g gum karaya for 15 days. Paper
    chromatographic separations, with two solvent systems, were made on
    the fresh urine specimens and also after ten-fold enrichments of

    all urinary constituents. Standard aqueous solutions of rhamnose, 
    and urine to which rhamnose had been added, showed the detection limit
    to be 0.2 g rhamnose. Independent examinations on two laboratories
    failed to detect rhamnose at this level in any of the urine
    specimens. Had 1% of the rhamnose present in 10 g gum karaya
    appeared in the 24-h urine specimens, it would have been detected.
    This confirms previous evidence that dietary gum karaya is neither
    digested nor degraded by enteric bacteria and is not absorbed to
    any significant extent in man (Anderson et al., 1985a).

         Gum karaya (10 g) was added to the normal diet of 5
    participating male volunteers with ages ranging from 21 to 57
    years. A series of urinary, blood and faecal analyses were made
    during an initial control period of 7 days and for a further 7 days
    during the third week of the supplemented diet period. Gum karaya
    had no effect on stool weight, serum cholesterol or hydrogen in
    expired air (Eastwood et al., 1986).

         Eleven men, age 23-62 years (averaging 38 years and 86.0 kg
    bw) consumed a basal diet with a relatively low fiber 4 day
    rotating menu containing 6.33 g neutral detergent fiber per 
    2550 kcal throughout the 20-week study. Four refined fibers, locust 
    bean gum (LBG), karaya gum (KG), carboxymethylcellulose gum (CMC), and
    cellulose, were used as the fiber sources. Each fiber source was
    added to the basal diet in the form of baked muffins or fruit juice
    gel for 4 wk at 7.5 g of refined fiber per 1000 kcal. Refined fiber
    intake ranged from 19.1 g/d to 26.0 g/d depending on caloric
    intake. Food, urine and faecal composites were collected during the
    last 8 d of each feeding period. Bowel transit time was not
    significantly affected; however total dry fecal weight was
    significantly increased after administration of the refined fiber
    diet compared with that after the basal diet. Adding refined fibers
    to the basal diet did not significantly affect apparent mineral
    balance of calcium, magnesium, manganese, iron, copper or zinc,
    with the exception of a negative mineral balance for manganese with
    carboxymethylcellulose. Karaya gum had a mean positive balance for
    all minerals tested (Behall et al., 1987).


         The Committee considered that the data provided additional
    information on the lack of toxicity of karaya gum when fed at high
    dietary levels. The analysis of the gum revealed that there are no
    unusual amino acids present. Karaya gum is not degraded by strains
    of bacteria found in the human colon and does not undergo any
    metabolic modification in the intestinal tract of rats and dogs.
    Studies in both rats and human subjects failed to detect rhamnose
    in the urine of both species, suggesting that the gum is neither
    digested nor degraded by enteric bacteria. A short-term study in
    rats showed no evidence of adverse effects at the 5% level. Dietary
    studies in man indicate that karaya gum is tolerated for 21 days at
    dose levels of 10.5 g/day without any adverse effect.


    Estimate of Acceptable Daily Intake for Man

         ADI "not specified".

    Further work or information


         Detailed histopathological information on the monkey studies.


    Anderson, A.W.J., Brydon, W.J., Eastwood, M.A., McDougall, F.J. &
    Anderson, D.M.W. (1985a). The absence of rhamnose in human urine
    following the ingestion of gum karaya  (Sterculia). Food Additives
     and Contaminants, 2, No. 1, 33-36.

    Anderson, D.M.W., Busuttil, A., Kempson, S.A, & Penman, D.W.
    (1966). Transmission electron microscopy of jejunum, ileum and
    caecum tissues from rats fed with gums arabic, karaya and
    tragacanth.  Toxicology, 41, 75-82.

    Anderson, D.M.W., Howlett, J.F. & McNab, C.G.A. (1985b). The amino
    acid composition of the proteinaceous component of gum karaya
    ( Sterculia spp.).  Food additives and Contaminants, 2, No. 3,

    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.

    Balakrishnan, B. (1984a). Unpublished data submitted to the WHO
    from Permanent Mission of India to the United Nations Offices,
    Geneva, Switzerland.

    Balakrishnan, B. (1984b). Unpublished data submitted to the WHO
    from Permanent Mission of India to the United Nations Offices,
    Geneva, Switzerland.

    Behall, K.M., Scholfield, D.J., Lee, K., Powell, A.S. & Moser, P.B.
    (1987). Mineral balance in adult men: effect of four refined
    fibers.  Am. J. Clin. Nutr., 46, 307-314.

    Bhat, R.V., Sesikeran, B., Reddy, C.V.K. & Radhaiah (1987).
    Toxicological evaluation of gum karaya in rhesus monkeys.  J. Food
     Safety, 8, 161-166.

    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.

    Dikshith, T.S.S., Raizada, R.B., Misra, R.B. & Srivastava, K.
    (1984). Toxicological evaluation of karaya gum acute and subacute
    oral toxicity in rats.  J. Biosci., 6, 147-153.

    Eastwood, M.A., Brydon, W.G. & Anderson, D.M.W. (1983). The effects
    of gum karaya in man.  Toxicol. Lett., 17, 153-166.

    Eastwood, M.A., Brydon, W.G. & Anderson, D.M.W. (1986). The effect
    of the polysaccharide composition and structure of dietary fibers
    on fecal fermentation and fecal excretion.  Am. J. Clin. Nutr.,
    44, 51-55.

    Elsenhaus, B., Blume, R. & Caspary, W.F. (1981). Long-term feeding
    of unavailable carbohydrate 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.

    Frohberg, H., Oetterl, H. & Zeller, H. (1969). The mechanisms of
    foetal toxic effects.  Arch. Toxikol., 25, 268-295.

    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 behavior 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.

    National Institute of Nutrition (India) (1985). Unpublished data
    submitted to the WHO from National Institute of Nutrition,
    Hyderabad, India.

    Newell, G.W. & Maxwell, W.A. (1972). Mutagenic effects of sterculia
    gum (karaya). Stanford Res. Inst.; US Natl. 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.
     App. Environ. Microbiol., 39, 988-992.

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

    Strobel, S., Ferguson, A. & Anderson, D.M.W. (1986). Immuno-
    genicity, immunological cross reactivity and non-specific
    irritant properties of the exudate gums, arabic, karaya and
    tragacanth.  Food Additives and Contaminants, 3, No. 1, 47-56.

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

    US FDA (1972). Teratogenic evaluation of gum karaya. NTIS Report

    US FDA (1973). Teratological evaluation of gum karaya. NTIS Report

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

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

    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 18)
       KARAYA GUM (JECFA Evaluation)