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    TARA GUM

    EXPLANATION

         This substance was evaluated for acceptable daily intake for man
    at the eighteenth, nineteenth, twenty-fourth, twenty-fifth, and
    twenty-eighth meetings of the Joint FAO/WHO Expert Committee on Food
    Additives (Annex 1, references 35, 38, 53, 56, and 66). Toxicological
    monographs were issued after the nineteenth and twenty-fifth meetings
    (Annex 1, references 39 and 57). A temporary ADI of 0-12.5 mg/kg b.w.
    was allocated at the twenty-fifth meeting, which was extended at the
    twenty-eighth meeting. 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

         The principal component of this gum is a galactomannan with a
    linear chain of (1->4) linked ß-D-mannopyranose units with
    alpha-D-glactopyranose units attached by (1->6) linkages to every 
    third mannose unit on average. In a bioavailability calorie assay,
    groups of 10 male weanling Sprague-Dawley rats were given 5 g tara
    gum for 10 days. Weight-gain comparisons showed that tara gum was
    not a source of bioavailable calories (Robaislek, 1974).

         A digestibility study in groups of 5 male and 5 female Purdue
    strain rats on a mannose-free diet showed that 88-100% of the mannose
    fed as 1% tara 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
    microflora, as mammals are not known to possess mannosidase.
    Liberation of galactose units was not determined (Tsai & Whistler,
    1975).

         Incubation of solutions or suspensions of tara gum with human
    gastric juice, duodenal juice + bile, pancreatic juice, or succus
    entericus (with or without added rabbit small intestine membrane
    enzymes) produced no evidence of hydrolysis (Semenza, 1975).

         Rat large intestine microflora partially hydrolysed tara gum
    in vitro after conditioning to 1% tara gum in the diet for 3 weeks
    (Towle & Schranz, 1975).

    Toxicological studies

    Special studies on carcinogenicity

    Mice

         Diets containing 0, 2.5, or 5% tara gum were fed to groups of 50
    male and 50 female B6C3F1 mice for 103 weeks. There were no
    significant differences in survival between mice fed tara gum and the
    control group. Depressions in body-weight gain greater than 10% were
    observed in both sexes fed diets containing 5% tara gum. There were no
    histopathological effects associated with the administration of tara
    gum. Under the conditions of the experiment, tara gum was not
    carcinogenic for B6C3F1 mice (Melnick et al., 1983).

    Rats

         Groups of 50 male and 50 female F344 rats were fed diets
    containing 0, 2.5, or 5% tara gum for 103 weeks. All animals were
    observed twice daily for morbidity and mortality. Body weights,
    clinical signs, and feed consumption were recorded monthly. At the end
    of the study the animals were killed, autopsied, and examined for
    grossly-visible lesions. All organs were examined microscopically.
    There were no histopathological effects associated with the
    administration of the test material. Under the conditions of the
    experiment tara gum was not carcinogenic for F344 rats of either sex
    (Melnick et al., 1983).

    Special study on embryotoxicity

    Rats

         Four groups of 25 Wistar female rats were fed diets containing 0,
    1.25, 2.5, or 5.0% tara gum from day 6 to day 16 of pregnancy. On day
    21 all females were sacrificed and the fetuses removed. There was no
    evidence of embryonic and/or teratogenic effects caused by the tara
    gum in any of the dose groups. No maternal toxicity was observed
    (Becker, 1986).

    Special study on reproduction

    Rats

         A three-generation reproduction study was carried out in CD
    strain Charles River albino rats. Groups of 10 male and 20 female
    animals were fed a diet containing 5% alpha-cellulose (control) or 5%
    tara gum. The same dose and animal numbers were employed for
    successive generations throughout the study. In each generation the
    parental animals received the test diets for 11 weeks prior to mating
    and then through mating, gestation, and weaning. The females of the
    F0 and F2 generations were mated to produce 2 litters. Females of
    the F1 generation produced 3 litters. Ten males and 20 females were
    retained at weaning from the second litter of each dietary group for
    use as parental animals for the next generation. Ten weanlings per sex
    per dietary group from the F3b litters were selected for
    histopathologic examination of 12 tissues and organs; organ-weight
    values were also obtained. All other animals were subjected to gross
    necropsy.

         At several weeks during the study, there were instances of
    statistically-lower body weights of the tara gum F2 parental males
    and the F0 and F1 parental females than of the controls. There was
    a statistically-significant reduction in the number of pups viable at
    lactation days 12 and 21 in the tara gum group and pup weights were
    significantly lower than those of the controls in the tara gum groups

    at days 4, 12, and 21 of the F1 generation and days 1, 4, 12, and 21
    of the F3 generation. There were no other significant differences in
    reproductive performance. No significant differences were noted in
    parental premating food consumption, mortality, or gross microscopic
    pathology. The following statistically-significant differences in
    organ weights and organ-weight ratios were observed for the tara gum
    group as opposed to the control group: lower absolute liver and brain
    weights and higher kidney, testes, heart, and brain-to-body-weight
    ratios. These differences were ascribed to the lower body weights of
    the tara gum F2 weanlings, from whom the values were obtained
    (Domanski et al., 1980).

    Acute toxicity

         No information available.

    Short-term studies

    Mice

         Groups of 10 male and female mice were fed diets containing 0,
    0.31, 0.63, 1.2, 2.5, or 5.0% tara gum for 13 weeks. At the end of the
    study all animals were killed and subjected to complete gross
    microscopy. Histopathological examination was carried out on tissues
    from all animals in the control and highest-dose groups. None of the
    mice died and no compound-related effects were detected (NTP, 1982).

    Rats

         Groups of 10 rats of each sex were fed diets containing 0, 0.31,
    0.63, 1.2, 2.5, or 5% tara gum for 13 weeks. No deaths occurred during
    the study. All animals were subjected to complete gross necroscopy.
    Mistopathologic examination was carried out on tissues from all
    animals in the control and highest-dose groups. During
    histopathological examination, fewer mature spermatozoa were found in
    the testes of 4/10 male rats receiving 5.0% tara gum than in the
    controls. No other compound-related effects were observed (NTP, 1982).

         A 90-day feeding study was carried out on groups of 10 male and
    10 female rats at dietary levels of 0, 1, 2, or 5% tara gum. No
    abnormalities were observed in general appearance, behaviour, or
    survival in any of the groups. Growth, food intake, and food
    efficiency were slightly decreased at the 5% dietary level in both
    sexes. A relative body-weight decrease was found in males in the 2%
    group; no effects on food intake or efficiency were observed.
    Haematology and urinalysis showed no treatment-related differences. A
    significant increase in blood urea nitrogen was observed in males at
    the 5% dietary level. At the 2% and 5% levels, an increase was found
    in the relative weight of the caecum. An increase in the relative
    weight of the thyroids at the 2% and 5% levels and a slight increase

    in the relative weight of the kidneys at the 5% level were observed in
    males only. No lesions were found on gross or histopathological
    examination that could be attributable to the ingestion of tara gum
    (Til et al., 1974).

    Dogs

         Three groups of 3 male and 3 female beagle dogs received 0, 1, or
    5% tara gum in their diet for 90 days. No abnormalities were noted
    with regard to behaviour, mortality, haematology, urinalysis, clinical
    chemistry, organ weights or gross histopathology examination
    (Oshita et al., 1975).

    Long-term study

    Rats

         Groups of 50 male and 50 female Charles River albino rats were
    fed diets containing 5% alpha-cellulose (control) or 5% tara gum for
    up to two years. An interim sacrifice of 10 animals/sex/group was
    carried out after 12 months. Statistically-significant lower body
    weight and body-weight changes were noted at a number of weeks in both
    male and female animals in the tara gum group. There were also
    statistically-significant reductions in food consumption by both males
    and females in the tara gum group at a number of weeks. This may have
    been due to the physical characteristics of the control diet, of which
    there may have been greater spillage and therefore greater apparent
    food consumption in the control animals. Some changes in
    haematological measurements were noted in rats in the tara gum groups.
    These included statistically-significant differences in haematocrit
    values at 12 months in male rats, in total erythrocyte and leukocyte
    counts in male rats at 99 weeks, in monocyte counts in female rats at
    12 months, in reticulocyte counts in female rats at 18 months, and in
    haemoglobin concentration at 99 weeks. With respect to clinical
    chemistry, statistically-significant increases in animals given tara
    gum were noted for the following measurements; SGPT activity in males
    at 12 months, fasting serum glucose, BUN at 12 months in females, and
    SGOT activity in females at 3 months. A significant decrease was noted
    in total cholesterol levels at 6 and 12 months in females given tara
    gum. At the 12-month interim sacrifice the following statistically-
    significant changes were noted in males fed 5% tara gum: significantly-
    greater brain to body-weight, testes to body-weight, and heart to
    body-weight ratios and significantly lower liver to brain-weight
    ratio. At final sacrifice the following statistically-significant
    changes were noted in animals given tara gum: higher adrenal gland to
    body-weight ratio in males and lower absolute brain weight in females.
    No significant differences were reported between the tara gum and
    control groups with respect to gross or microscopic pathology (Carlson
    & Domanski, 1980).

    Comments

         Studies in rats on the in vivo digestibility and caloric
    bioavailability of tara gum show that it is not digested by mammalian
    intestinal enzymes, but it is partially hydrolysed by rat intestinal
    flora. Human intestinal enzymes do not hydrolyse tara gum in vitro.

         Short-term studies in rats and dogs showed no evidence of adverse
    effects at the 5% level. A long-term study in rats demonstrated no
    significant toxicity. Carcinogenicity studies in mice and rats fed
    diets containing up to 5% tara gum were negative. A reproduction study
    reviewed by an earlier Committee indicated a possible effect of 5%
    tara gum on lactation, since pup body weights and viability tended to
    be lower in the tara gum groups than in the controls given cellulose.
    A new study indicated no evidence of embryonic and/or teratogenic
    effects.

    EVALUATION

    Estimate of acceptable daily intake for man

    ADI "not specified".

    REFERENCES

    Becker, B., Schafroth, P., Terrier, C., & Sachsse, K. (1986).
         Embryo-toxicity (including teratogenicity) study with tara gum in
         the rat. Unpublished report No. 53335 from Research & Consulting
         Company AG, Itingen, Switzerland. Submitted to WHO by
         Unipektin AG, Zurich, Switzerland.

    Carlson, W.A. & Domanski, J. (1980). Two-year chronic oral toxicity
         study with tara gum in albino rats. Unpublished report from
         Industrial Bio-Test Laboratories, Inc., Northbrook, IL, USA.

    Domanski, J., Carlson, W., & Frawley, J. (1980). Three generation
         reproduction study with tara gum in albino rats. Unpublished
         report from Industrial Bio-Test Laboratories, Inc.,
         Northbrook, IL, USA.

    Melnick, R.L., Hutt, J., Haseman, J.K., Deter, M.P., Grieshaber, C.K.,
         Wyand, D.S., Russfield, A.B., Murthy, A.S.K., Fleischman, R.W., &
         Lilja, H.S. (1983). Chronic effects of agar, guar gum, gum
         arabic, locust-bean gum, or tara gum in F344 rats and B6C3F1
         mice. Fd. Chem. Toxicol., 21, 305-11.

    NTP (1982). Carcinogenesis bioassay of tara gum in F344 rats and
         B6C3F1 mice (feed study). National Toxicology Program Technical
         Report Series No. 224. Available from National Technical
         Information Service (Publication No. PB82-195546),
         Springfield, VA, USA.

    Oshita, G. et al. (1975). 90-Day subacute oral toxicity study with
         tara gum in beagle dogs. Unpublished report from Industrial
         Bio-Test Laboratories, Inc., Northbrook, IL, USA. Submitted to
         WHO by Hercules Incorporated.

    Robaislek, E. (1974). Bioavailable calorie assay of guar gum.
         Unpublished report from WARF Institute, Inc. Submitted to WHO 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 Swiss Federal Institute of
         Technology, Zurich. Submitted to WHO by Institut Européen des
         Industries de la Gomme de Caroube.

    Til, H.P., Spanjers, M.T., & De Groot, A.P. (1974). Sub-chronic
         toxicity study with tara gum in rats. Unpublished report from
         Centraal Instituut voor Voedingsonderzoek, TNO. Submitted to WHO
         by Hercules Incorporated 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 WHO by Hercules
         Incorporated.

    Tsai, L.B. & Whistler, R.L. (1975). Digestibility of galactomannans.
         Unpublished report submitted to WHO by Institut Européen des
         Industries de la Gomme de Caroube.
    


    See Also:
       Toxicological Abbreviations
       Tara gum (WHO Food Additives Series 16)
       TARA GUM (JECFA Evaluation)