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    TRAGACANTH GUM

    EXPLANATION

         The Joint FAO/WHO Expert Committee on Food Additives has reviewed
    this substance many times in the past (Annex 1, references 19, 32, 44,
    53, & 62). Toxicological monographs were prepared twice previously
    (Annex 1, references 20 & 33).

         Since the previous evaluation, additional data have become
    available and are summarized and discussed here. Material from the
    earlier monographs is incorporated into this evaluation.

    BIOLOGICAL DATA

    Biochemical aspects

         In a comparative study of the hypocholesterolemic activity of
    various mucilaginous polysaccharides, tragacanth gum fed at a level of
    3% along with 3% cholesterol in the diet of cockerels inhibited the
    development of hypercholesterolemia (Riccardi & Fahrenback, 1965).

         Tragacanth gum administered i.p., s.c., or per os 24 hours before
    hexobarbital had no effect on the hexobarbital sleeping time of mice.
    The effect of phenobarbital and urethan pretreatment to induce a
    shortening of hexobarbital sleeping time was blocked by i.p. injection
    of tragacanth gum, thus suggesting the presence of a hepatic effect of
    tragacanth gum (Fujimoto, 1965).

         The influence of a number of hydrocolloids on the transit time of
    digesta, stool weight, and colour of stools was investigated in rats.
    Groups of 23 male rats were fed for 2 weeks the basal diet mixed
    with 2 or 20% of a thickening agent added at the expense of the
    entire diet. Tragacanth gum accelerated the digesta passage. All
    hydrocolloids tested gave the stools a lighter colour and increased
    their size and water content (Gohl & Gohl, 1977).

         Ten Bacteroides species and several strains of anaerobic
    bacteria found in the human colon were surveyed for their ability to
    ferment 21 different complex polysaccharides. Many of the
    Bacteroides strains and a strain of Bifidobacterium (B. longum)
    fermented tragacanth gum (Salyers et al., 1977a & 1977b).

         Fermentation of 20 polysaccharides by species of the family
    Enterobacteriaceae were examined. Species of Klebsiella,
    Serratia, and Yersinia fermented tragacanth gum. As a food
    additive, tragacanth gum may lose some of its properties when exposed
    in various ways to enteric organisms (Ochuba & von Riesen, 1980).

         Female rats were dosed twice-daily with aqueous solutions of
    tragacanth gum at doses of 20, 40, and 80 mg/kg b.w. over a period of
    4 weeks. All doses caused uncoupling of oxidative phosphorylation in
    liver and heart mitochondria and partial inhibition of mixed function
    oxidases of liver endoplasmic reticulum. The uncoupling was reversible
    in the case of heart mitochondria while it was progressive in liver
    mitochondria. Tragacanth gum did not have any adverse effect on the
    hepatic mixed-function oxidases at the 2 lower doses, while a 20%
    inhibition developed after 30 doses with 2 × 40 mg/kg (Bachmann
    et al., 1978).

         Male albino Wistar rats were fed diets containing 0, 0.5, 1.5,
    2.5, and 3.5 (w/w) tragacanth gum for 91 days. Microsomal protein and
    PL-480 content of the liver were measured. No compound-related effects
    were observed. Electron microscopy of liver and heart muscle from the
    treated rats showed no abnormalities in any of the test animals
    (Anderson et al., 1984).

    Toxicological studies

    Special studies on mutagenicity

         Tragacanth gum was evaluated for genetic activity in the
    following in vitro microbial assays, with and without activation:
    Salmonella typhimurium (strains TA1535, TA1537, TA1538, TA98, and
    TA100) and Saccharomyces cerevisiae strain D4. No mutagenic
    activity was observed in any of these assays (Litton Bionetics, 1977).

         Tragacanth gum was not mutagenic in a number of tests using
    mammalian systems. These included: (a) Host Mediated Assay in vivo
    in rats and mice using Salmonella typhimurium strain TA1530 and G46
    or mitotic recombination frequency in S. cerevisiae D3, (b) a
    cytogenic study in vivo of rat bone-marrow cells, and (c) an
    in vitro study with human lung cells (wt. 38) in tissue culture
    (Litton Bionetics, 1972).

    Special studies on teratogenicity

         I.p. injection of 1 ml 1% aqueous mucilage of Persian tragacanth
    gum (single dose or 5 doses of 0.2 ml each) into mice between days 11
    and 15 of gestation caused the death of all foetuses. Oral or s.c.
    administration had no effect. All samples were found to be
    contaminated with Enterobacter spp. and the embryotoxic effects were
    attributed to bacterial metabolites (Frohberg et al., 1969).

         Tragacanth gum showed no evidence of maternal toxicity or
    teratogenicity after oral administration (as a suspension in corn oil)
    at levels up to 1200 mg/kg b.w./day to pregnant mice (days 6-16 of
    gestation) or to pregnant hamsters at dose levels up to 900 mg/kg
    b.w./day (days 6-10 of gestation). Similar studies with pregnant rats

    at dose levels up to 1200 mg/kg b.w. (days 6-15 of gestation) and with
    pregnant rabbits at dose levels up to 700 mg/kg b.w. (days 6-18 of
    gestation) resulted in significant maternal mortality in rats at the
    1200 mg/kg b.w. dose level and in rabbits at dose levels of 150 and
    700 mg/kg b.w. At autopsy, the gross pathological finding was marked
    haemorrhage in the mucosa of the small intestine. Offspring from
    animals surviving in the high-dose group as well as those in other
    test groups showed no compound-related abnormalities in the soft or
    skeletal tissues (FDRL, 1972).

         A study was done using a chick embryo test system. Tragacanth
    gum dissolved in 0.12 N HCl was injected either into the air sac or
    the yolk of fertile chicken eggs at dose levels up to 7 mg/kg. The
    administration of tragacanth gum did not result in a significant
    increase in mortality. All hatched chicks appeared normal.
    Abnormalities observed in eggs that failed to hatch were 22% test, 14%
    solvent-control, and 3.41% flock background (Bodder, 1974).

    Special studies on sensitization

         Although there are only a few reports on sensitization to
    tragacanth gum, the available information indicates that tragacanth
    gum is a powerful allergen capable of causing extremely severe
    reactions. Allergic reactions may occur as a result of inhalation or
    oral ingestion (Gelfand, 1943; 1949).

         The immunogenicity of tragacanth gum was demonstrated in an
    in vivo test using a foot pad swelling test in mice. Purification of
    the gum led to a marked reduction of the immune response (Strobel
    et al., 1982).

    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 sodium
    carboxymethyl cellulose) were studied. Each gum was administered by
    gavage to 5 groups of 10 animals, with 5 males and 5 females in each
    group. Vehicles utilized were water, mineral oil, corn oil, and
    soybean oil. The animals were fasted 18 hours prier 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 to 10 g/kg range. Generally, the rabbit was the most
    sensitive species and the rat and mouse the least sensitive (Bailey,
    personal communication to WHO, 1976).

    Short-term studies

    Rats

         Groups of newly-weaned rats (10 per group) were fed a soybean-
    corn meal diet containing 2% tragacanth gum for 37 days. Tragacanth
    gum had no effect on the digestibility of the diet, nor was there any
    significant effect on growth (Vohra et al., 1979).

         Tragacanth gum was used in a 6-7 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 growth rates due to lower energy intakes. None of
    the polysaccharides fed, however, decreased energy utilization.
    Similarly, all polysaccharides increased small intestine weights by up
    to about 30% without grossly altering mucosal protein or DNA per unit
    of length. Concerning the effect on the large intestine, tragacanth
    gum had a pronounced effect on caecum weight, which increased by
    factors of 1.8, 2.0, and 4.2 for additions of 10, 20, and 40%,
    respectively. The degree of the observed changes was determined mainly
    by the dietary concentration of the polysaccharide and its
    accessibility to bacterial degradation within the intestinal tract
    (Elsenhaus et al., 1981).

         Groups of 50 male and 50 female Osborne-Mendel rats
    (approximately 21 days of age) were maintained on diets containing 0,
    0.006, 0.06, 0.6, or 6.0% ppm tragacanth gum. After 13 weeks on the
    test diets, the rats were bred to produce an F1 generation. The
    offspring were weaned at day 21 and placed on their respective diets.
    The animals in the F0 generation were maintained on the test diets
    for a total period of 27 weeks. Groups of 50 male and 50 female rats
    of the F1 generation were maintained on the test diets for
    approximately 20 weeks. During the course of the study, body weights
    and food intake were measured. Reproduction data included the
    fertility index, total number of progeny, average litter size of
    pregnant females, total number of liveborn, viability index, survivors
    to days 4 and 21, weaning index at birth, and weaning weights. At
    termination of the study, haematological and clinical chemistry
    studies were carried out. Organ weights were determined, and a
    complete histological study was made of the principal tissues and
    organs. Special studies were carried out on liver composition (DNA,
    RNA, and protein levels), liver DNA synthesis, and intermediary
    metabolism.

         Both males and females in the 6% group showed significantly lower
    body weights, as well as decreased food efficiency, than the controls.
    Lower body weights were also observed in the F1 generation,
    particularly in the males. Haematological measurements showed no
    compound-related effects. Only minor effects were noted in the various

    clinical chemistry parameters. Reproduction data were comparable for
    test and control animals. Histological studies did not show any
    compound-related effects. Enlarged livers were noted in the 6% group,
    but the enlargement was not associated with any significant change in
    liver composition or with histological changes. The ATP/ADP ratio in
    liver preparations for F0 animals was markedly decreased, but this
    effect was not observed in F1 animals (Graham et al., 1985).

    Chickens

         Groups of day-old broiler chickens (7 per group) were fed a
    soybean-corn diet containing 2% tragacanth gum for 24 days. The
    dietary intake of 10 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. Body weights and the
    digestibility of the diet were reduced significantly by the inclusion
    of tragacanth gum in the diet (Vohra et al., 1979).

    Quail

         Groups of day-old Japanese quail (10 per group) were fed a
    soybean-corn diet containing 2% tragacanth gum for 36 days. Tragacanth
    gum did not affect significantly the growth of the quail or the
    digestibility of the diet (Vohra et al., 1979).

    Long-term studies

         No information available.

    Observations in man

         Following a 7-day control period, 5 healthy men ingested 9.9 g
    tragacanth gum daily (3 × 3.3 g-portion gelled in 200 ml water) for 32
    days. The following measurements were made during the control period
    and at the end of the test period: blood glucose, insulin, serum lipid
    estimations of cholesterol and HDL cholesterol, phospholipids,
    triglycerides, haematological indices, and biochemical analyses.
    Twenty-four-hour urine samples were collected and tested for sugar,
    protein, and blood. Five-day faecal collections were made during days
    2-6 of the control period and during days 16-20 of the treatment
    period. The tragacanth gum was well-tolerated and no adverse effects
    were reported in any of the volunteers. Tragacanth gum had no
    significant effect on any of the parameters measured with the
    exception that intestinal transit time decreased, and faecal wet- and
    dry-weights were increased in all subjects at the end of the test
    period. Four subjects also showed an increase in faecal fat
    concentration (Eastwood, et al., 1984).

    Comments

         Tragacanth gum is fermented by several strains of bacteria found
    in the human colon.

         An earlier study showed changes in liver microsomal enzyme
    activity and in the oxidative phosphorylation function of heart and
    liver mitochondria isolated from rats fed tragacanth gum. However, a
    recent study showed no detectable ultrastructural abnormalities in rat
    heart or liver and no changes in microsomal protein or P-450 content
    of the liver that could be attributable to tragacanth gum.

         Tragacanth gum was not mutagenic in bacterial or mammalian
    systems. No teratogenic effects were observed in studies in mice,
    rats, guinea-pigs, or rabbits. Maternal toxicity observed in rats and
    rabbits, at the highest levels tested, may have been due to the mode
    of administration (suspended in corn oil), rather than to any innate
    toxicity of the gum.

         Tragacanth gum fed to rats at dietary levels up to 6% had no
    effect on reproductive performance nor on post-partum development of
    the pups. The only effects observed in both the F0 and F1
    generations were lower body weights and decreased feed-efficiency at
    the 6% level. Since these effects were not accompanied by any
    compound-related histological changes in any tissues or organs, the
    effects may be due to the bulking effect of this non-nutritive
    substance, rather than any innate toxicity. The highest level tested
    in this study exceeds the maximum level (5%) recommended for non-
    nutrients.

         Relatively high levels of tragacanth gum were well-tolerated by
    man. However, possible allergic effects need to be considered.

    EVALUATION

    Level causing no toxicological effect

    Rat: 6000 ppm tragacanth gum in the diet, equivalent to
         3000 mg/kg b.w./day.

    Estimate of acceptable daily intake for man

    ADI "not specified".

    REFERENCES

    Anderson, D.M.W., Ashby, P., Busuttil, A., Kempson, S.A., & Lawson,
         M.E. (1984). Transmission electron microscopy of heart and liver
         tissues from rats fed with gums arabic and tragacanth.
         Toxicology Letters, 21, 83-89.

    Bachmann, E., Weber, E., Post, M., & Zbinden, G. (1978). Biochemical
         effects of gum arabic, gum tragacanth and carboxymethyl cellulose
         in rat heart and liver. Pharmacology, 17, 39-49.

    Bodder, R. (1974). Evaluation of chemicals for toxic and teratogenic
         effects using the chick embryo as a test system. Unpublished
         report of Warf Institute, Inc. Submitted to WHO by U.S. Food and
         Drug Administration.

    Eastwood, M.A., Brydon, W.G., & Anderson, D.M.W. (1984). The effects
         of dietary gum tragacanth in man. Toxicology Letters, 21,
         73-81.

    Elsenhaus, B., Blume, R., & Caspary, W.F. (1981). Long-term feeding
         of unavailable carboydrate gelling agents. Influence of dietary
         concentration and microbiological degradation on adaptive
         responses in the rat. Am. J. Clin. Nutr., 34, 1837-48.

    FDRL, 1972. Teratology evaluation of gum tragacanth in mice, rats,
         hamsters and rabbits. Unpublished report of Food and Drug
         Research Laboratories, Inc. Submitted to WHO by U.S. Food and
         Drug Administration.

    Frohberg, H., Oettel, H., & Zeller, H. (1969). Concerning the
         mechanisms of the fetal toxic effects of tragacanth. Arch.
         Toxicol., 25, 268-295.

    Fujimoto, J.M. (1965). Effect of gum tragacanth, urethan, and
         phenobarbital on hexobarbital narcosis in mice. Toxicol. Appl.
         Pharmacol., 7, 287-290.

    Gelfand, H.H. (1943). The allergenicity of vegetable gums, a case of
         asthma due to tragacanth. J. Allergy, 14, 203.

    Gelfand, H.H. (1949). Vegetable gums by ingestion in etiology of
         allergic disorders. J. Allergy, 20, 311-321.

    Graham, S.L., Friedman, L., & Garthoff, L. (1985). The subchronic
         effects of gum tragacanth on F0 and F1 generation Osborn-Mendel
         rats. Unpublished report of the Food and Drug Administration.
         Submitted to WHO by U.S. Food and Drug Administration.

    Gohl, B. & Gohl, I. (1977). The effect of viscous substances on the
         transit time of barley digesta in rats. J. Sci. Fd. Agric.,
         28, 911-915.

    Litton Bionetics (1972). Summary of mutagenicity screening studies,
         contract FDA71-268, gum tragacanth host-mediated assay,
         cytogenetics, dominant lethal assay, L.B.I. Project No. 2311.
         Unpublished report of Litton Bionetics Inc. Submitted to WHO by
         U.S. Food and Drug Administration.

    Litton Bionetics (1977). Mutagenicity evaluation of gum tragacanth,
         LBI Project No. 20671. Unpublished report of Litton Bionetics
         Inc. Submitted to WHO by U.S. Food and Drug Administration.

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

    Riccardi, B.A. & Fahrenbach, M.J. (1965). Hypocholestrolemic activity
         of mucilaginous polysaccharides in white leghorn cockerels.
         Fed. Proc., 24, 263-265.

    Salyers, A.A., Vercellotti, J.R., West, S.E.H., & Wilkins, T.D.
         (1977a). Fermentation of mucins and plant polysaccharides by
         strains of Bacteroides from the human colon. Appl. Environ.
         Microbiol., 33, 319-322.

    Salyers, A.A., Vercellotti, J.R., West, S.E.H., & Wilkins, T.D.
         (1977b). Fermentation of mucins and plant polysaccharides by
         anaerobic bacteria from the human colon. Appl. Environ.
         Microbiol., 34, 529-533.

    Strobel, S., Ferguson, A., & Anderson, D.M.W. (1982). Immunogenicity
         of food and food additives - In vivo testing of gums arabic,
         karaya and tragacanth. Toxicology Letters, 14, 247-252.

    Vohra, P., Shariff, G., & Kratzer, F.H. (1979). Growth inhibitory
         effect of some gums and pectin for Tribolium castaneum larvae,
         chickens, and Japanese quail. Nutr. Rep. Int., 19, 463-469.

    ANNEX 1

    REPORTS AND OTHER DOCUMENTS RESULTING FROM MEETINGS OF THE JOINT
    FAO/WHO EXPERT COMMITTEE ON FOOD ADDITIVES

    1.   General principles governing the use of food additives (First
         report of the Joint FAO/WHO Expert Committee on Food Additives).
         FAO Nutrition Meetings Report Series, No. 15, 1958; WHO Technical
         Report Series, No. 129, 1957 (out of print).

    2.   Procedures for the testing of intentional food additives to
         establish their safety for use (Second report of the Joint
         FAO/WHO Expert Committee on Food Additives). FAO Nutrition
         Meetings Report Series, No. 17, 1958; WHO Technical Report
         Series, No. 144, 1958 (out of print).

    3.   Specifications for identity and purity of food additives
         (antimicrobial preservatives and antioxidants) (Third report of
         the Joint FAO/WHO Expert Committee on Food Additives). These
         specifications were subsequently revised and published as
         Specifications for identity and purity of food additives, Vol. I.
         Antimicrobial preservatives and antioxidants, Rome, Food and
         Agriculture Organization of the United Nations, 1962 (out of
         print).

    4.   Specifications for identity and purity of food additives (food
         colours) (Fourth report of the Joint FAO/WHO Expert Committee on
         Food Additives). These specifications were subsequently revised
         and published as Specifications for identity and purity of food
         additives, Vol. II. Food colours, Rome, Food and Agriculture
         Organization of the United Nations, 1963 (out of print).

    5.   Evaluation of the carcinogenic hazards of food additives (Fifth
         report of the Joint FAO/WHO Expert Committee on Food Additives).
         FAO Nutrition Meetings Report Series, No. 29, 1961; WHO Technical
         Report Series, No. 220, 1961 (out of print).

    6.   Evaluation of the toxicity of a number of antimicrobials and
         antioxidants (Sixth report of the Joint FAO/WHO Expert Committee
         on Food Additives). FAO Nutrition Meetings Report Series, No. 31,
         1962; WHO Technical Report Series, No. 228, 1962 (out of print).

    7.   Specifications for the identity and purity of food additives and
         their toxicological evaluation: emulsifiers, stabilizers,
         bleaching and maturing agents (Seventh report of the Joint
         FAO/WHO Expert Committee on Food Additives). FAO Nutrition
         Meetings Report Series, no. 35, 1964; WHO Technical Report
         Series, No. 281, 1964 (out of print).

    8.   Specifications for the identity and purity of food additives and
         their toxicological evaluation; food colours and some
         antimicrobials and antioxidants (Eighth report of the Joint
         FAO/WHO Expert Committee on Food Additives). FAO Nutrition
         Meetings Report Series, No. 38, 1965; WHO Technical Report
         Series, No. 309, 1965 (out of print).

    9.   Specifications for identity and purity and toxicological
         evaluation of some antimicrobials and antioxidants. FAO Nutrition
         Meetings Report Series, No. 38A, 1965; WHO/Food/Add/24.65 (out of
         print).

    10.  Specifications for identity and purity and toxicological
         evaluation of food colours. FAO Nutrition Meetings Report Series,
         No. 35B, 1966; WHO/Food Add/66.25.

    11.  Specifications for the identity and purity of food additives
         and their toxicological evaluation: some antimicrobials,
         antioxidants, emulsifiers, stabilizers, flour-treatment agents,
         acids, and bases (Ninth report of the Joint FAO/WHO Expert
         Committee on Food Additives). FAO Nutrition Meetings Report
         Series, No. 40, 1966; WHO Technical Report Series, No. 339, 1966
         (out of print).

    12.  Toxicological evaluation of some antimicrobials, antioxidants,
         emulsifiers, stabilizers, flour-treatment agents, acids, and
         bases. FAO Nutrition Meetings Report Series, No. 40A, B, C;
         WHO/Food Add/67.29.

    13.  Specifications for the identity and purity of food additives and
         their toxicological evaluation: some emulsifiers and stabilizers
         and certain other substances (Tenth report of the Joint FAO/WHO
         Expert Committee on Food Additives). FAO Nutrition Meetings
         Report Series, No. 43, 1967; WHO Technical Report Series, No.
         373, 1967.

    14.  Specifications for the identity and purity of food additives and
         their toxicological evaluation: some flavouring substances and
         non-nutritive sweetening agents (Eleventh report of the Joint
         FAO/WHO Expert Committee on Food Additives). FAO Nutrition
         Meetings Report Series, No. 44, 1968; WHO Technical Report
         Series, No. 383, 1968.

    15.  Toxicological evaluation of some flavouring substances and non-
         nutritive sweetening agents. FAO Nutrition Meetings Report
         Series, No. 44A, 1968; WHO/Food Add/68.33.

    16.  Specifications and criteria for identity and purity of some
         flavouring substances and non-nutritive sweetening agents. FAO
         Nutrition Meetings Report Series, No. 44B, 1969; WHO/Food
         Add/69.31.

    17.  Specifications for the identity and purity of food additives and
         their toxicological evaluation; some antibiotics (Twelfth report
         of the Joint FAO/WHO Expert Committee on Food Additives). FAO
         Nutrition Meetings Report Series, No. 45, 1969; WHO Technical
         Report Series, No. 430, 1969.

    18.  Specifications for the identity and purity of some antibiotics.
         FAO Nutrition Meetings Report Series, No. 45A, 1969; WHO/Food
         Add/69.34.

    19.  Specifications for the identity and purity of food additives and
         their toxicological evaluation; some food colours, emulsifiers,
         stabilizers, anticaking agents, and certain other substances
         (Thirteenth report of the Joint FAO/WHO Expert Committee on Food
         Additives). FAO Nutrition Meetings Report Series, No. 46, 1970;
         WHO Technical Report Series, No. 445, 1970.

    20.  Toxicological evaluation of some food colours, emulsifiers,
         stabilizers, anticaking agents, and certain other substances. FAO
         Nutrition Meetings Report Series, No. 46A, 1970; WHO/Food
         Add/70.36.

    21.  Specifications for the identity and purity of some food colours,
         emulsifiers, stabilizers, anticaking agents, and certain other
         food additives. FAO Nutrition Meetings Report Series, No. 46B,
         1970; WHO/Food Add/70.37.

    22.  Evaluation of food additives; specifications for the identity and
         purity of food additives and their toxicological evaluation; some
         extraction solvents and certain other substances; and a review of
         the technological efficacy of some antimicrobial agents
         (Fourteenth report of the Joint FAO/WHO Expert Committee on Food
         Additives). FAO Nutrition Meetings Report Series, No. 48, 1971;
         WHO Technical Report Series, No. 462, 1971.

    23.  Toxicological evaluation of some extraction solvents and certain
         other substances. FAO Nutrition Meetings Report Series, No. 48A,
         1971; WHO/Food Add/70.39.

    24.  Specifications for the identity and purity of some extraction
         solvents and certain other substances. FAO Nutrition Meetings
         Report Series, No. 48B, 1971; WHO/Food Add/70.40.

    25.  A review of the technological efficacy of some antimicrobial
         agents. FAO Nutrition Meetings Report Series, No. 48C, 1971;
         WHO/Food Add/70.41.

    26.  Evaluation of food additives: some enzymes, modified starches,
         and certain other substances: toxicological evaluations and
         specifications and a review of the technological efficacy of some
         antioxidants (Fifteenth report of the Joint FAO/WHO Expert
         Committee on Food Additives). FAO Nutrition Meetings Report
         Series, No. 50, 1972; WHO Technical Report Series, No. 488, 1972.

    27.  Toxicological evaluation of some enzymes, modified starches, and
         certain other substances. FAO Nutrition Meetings Report Series,
         No. 50A, 1972; WHO Food Additives Series, No. 1, 1972.

    28.  Specifications for the identity and purity of some enzymes and
         certain other substances. FAO Nutrition Meetings Report Series,
         No. 50B, 1972; WHO Food Additives Series, No. 2, 1972.

    29.  A review of the technological efficacy of some antioxidants and
         synergists. FAO Nutrition Meetings Report Series, No. 50C, 1972;
         WHO Food Additives Series, No. 3, 1972.

    30.  Evaluation of certain food additives and the contaminants
         mercury, lead, and cadmium (Sixteenth report of the Joint FAO/WHO
         Expert Committee on Food Additives). FAO Nutrition Meetings
         Report Series, No. 51, 1972; WHO Technical Report Series, No.
         505, 1972, and corrigendum.

    31.  Evaluation of mercury, lead, cadmium, and the food additives
         amaranth, diethylpyrocarbamate, and octyl gallate. FAO Nutrition
         Meetings Report Series, No. 51A, 1972; WHO Food Additives Series,
         No. 4, 1972.

    32.  Toxicological evaluation of certain food additives with a review
         of general principles and of specifications, (Seventeenth report
         of the Joint FAO/WHO Expert Committee on Food Additives). FAO
         Nutrition Meetings Report Series, No. 53, 1974; WHO Technical
         Report Series, No. 539, 1974, and corrigendum (out of print).

    33.  Toxicological evaluation of certain food additives including
         anticaking agents, antimicrobials, antioxidants, emulsifiers, and
         thickening agents. FAO Nutrition Meetings Report Series, No. 53A,
         1974; WHO Food Additives Series, No. 5, 1974.

    34.  Specifications for identity and purity of thickening agents,
         anticaking agents, antimicrobials, antioxidants and emulsifiers.
         FAO Food and Nutrition Paper, No. 4, 1978.

    35.  Evaluation of certain food additives (Eighteenth report of the
         Joint FAO/WHO Expert Committee on Food Additives). FAO Nutrition
         Meetings Report Series, No. 54, 1974; WHO Technical Report
         Series, No. 557, 1974, and corrigendum.

    36.  Toxicological evaluation of some food colours, enzymes, flavour
         enhancers, thickening agents, and certain other food additives.
         FAO Nutrition Meetings Report Series, No. 54A, 1975; WHO Food
         Additives Series, No. 6, 1975.

    37.  Specifications for the identity and purity of some food colours,
         flavour enhancers, thickening agents, and certain food additives.
         FAO Nutrition Meetings Report Series, No. 54B, 1975; WHO Food
         Additives Series, No. 7, 1975.

    38.  Evaluation of certain food additives: some food colours,
         thickening agents, smoke codensates, and certain other substances
         (Nineteenth report of the Joint FAO/WHO Expert Committee on Food
         Additives). FAO Nutrition Meetings Report Series, No. 55, 1975;
         WHO Technical Report Series, No. 576, 1975.

    39.  Toxicological evaluation of some food colours, thickening agents,
         and certain other substances. FAO Nutrition Meetings Report
         Series, No. 55A, 1975; WHO Food Additives Series, No. 8, 1975.

    40.  Specifications for the identity and purity of certain food
         additives. FAO Nutrition Meetings Report Series, No. 55B, 1976;
         WHO Food Additives Series, No. 9, 1976.

    41.  Evaluation of certain food additives (Twentieth report of the
         Joint FAO/WHO Expert Committee on Food Additives). FAO Food and
         Nutrition Series, No. 1. 1976; WHO Technical Report Series, No.
         599, 1976.

    42.  Toxicological evaluation of certain food additives. WHO Food
         Additives Series, No. 10, 1976.

    43.  Specifications for the identity and purity of some food
         additives. FAO Food and Nutrition Series, No. 1B, 1977; WHO Food
         Additives Series, No. 11, 1977.

    44.  Evaluation of certain food additives (Twenty-first report of the
         Joint FAO/WHO Expert Committee on Food Additives). WHO Technical
         Report Series, No. 617, 1978.

    45.  Summary of toxicological data of certain food additives. WHO Food
         Additives Series, No. 12, 1977.

    46.  Specifications for identity and purity of some food additives,
         including antioxidants, food colours, thickeners, and others. FAO
         Nutrition Meetings Report Series, No. 57, 1977.

    47.  Evaluation of certain food additives and contaminants (Twenty-
         second report of the Joint FAO/WHO Expert Committee on Food
         Additives). WHO Technical Report Series, No. 631, 1978.

    48.  Summary of toxicological data of certain food additives and
         contaminants. WHO Food Additives Series, No. 13, 1978.

    49.  Specifications for the identity and purity of certain food
         additives. FAO Food and Nutrition Paper, No. 7, 1978.

    50.  Evaluation of certain food additives (Twenty-third report of the
         Joint FAO/WHO Expert Committee on Food Additives). WHO Technical
         Report Series, No. 648, 1980, and corrigenda.

    51.  Toxicological evaluation of certain food additives. WHO Food
         Additives Series, No. 14, 1980.

    52.  Specifications for identity and purity of food colours,
         flavouring agents, and other food additives. FAO Food and
         Nutrition Paper, No. 12, 1979.

    53.  Evaluation of certain food additives (Twenty-fourth report of the
         Joint FAO/WHO Expert Committee on Food Additives). WHO Technical
         Report Series, No. 653, 1980.

    54.  Toxicological evaluation of certain food additives. WHO Food
         Additives Series, No. 15, 1980.

    55.  Specifications for identity and purity of food additives
         (sweetening agents, emulsifying agents, and other food
         additives). FAO Food and Nutrition Paper, No. 17, 1980.

    56.  Evaluation of certain food additives (Twenty-fifth report of the
         Joint FAO/WHO Expert Committee on Food Additives). WHO Technical
         Report Series, No. 669, 1981.

    57.  Toxicological evaluation of certain food additives. WHO Food
         Additives Series, No. 16, 1981.

    58.  Specifications for identity and purity of food additives (carrier
         solvents, emulsifiers and stabilizers, enzyme preparations,
         flavouring agents, food colours, sweetening agents, and other
         food additives). FAO Food and Nutrition Paper, No. 19, 1981.

    59.  Evaluation of certain food additives and contaminants (Twenty-
         sixth report of the Joint FAO/WHO Expert Committee on Food
         Additives). WHO Technical Report Series, No. 683, 1982.

    60.  Toxicological evaluation of certain food additives. WHO Food
         Additives Series, No. 17, 1982.

    61.  Specifications for the identity and purity of certain food
         additives. FAO Food and Nutrition paper, No. 25, 1982.

    62.  Evaluation of certain food additives and contaminants (Twenty-
         seventh report of the Joint FAO/WHO Expert Committee on Food
         Additives). WHO Technical Report Series, No. 696, 1983, and
         corrigenda.

    63.  Toxicological evaluation of certain food additives and
         contaminants. WHO Food Additives Series, no. 18, 1983.

    64.  Specifications for the identity and purity of certain food
         additives. FAO Food and Nutrition Paper, No. 28, 1983.

    65.  Guide to specifications - General notices, general methods,
         identification tests, test solutions, and other reference
         materials. FAO Food and Nutrition Paper, No. 5, Rev. 1, 1983.

    66.  Evaluation of certain food additives and contaminants (Twenty-
         eighth report of the Joint FAO/WHO Expert Committee on Food
         Additives). WHO Technical Report Series, No. 710, 1984.

    67.  Toxicological evaluation of certain food additives and
         contaminants. WHO Food Additives Series, No. 19, 1984.

    68.  Specifications for the identity and purity of certain food
         additives. FAO Food and Nutrition paper, No. 31/1, 1984.

    69.  Specifications for the identity and purity of certain food
         additives. FAO Food and Nutrition Paper, No. 31/2, 1984.

    70.  Evaluation of certain food additives and contaminants (Twenty-
         ninth report of the Joint FAO/WHO Expert Committee on Food
         Additives). WHO Technical Report Series, No. 733, 1986.

    ANNEX 2

    ABBREVIATIONS USED IN THE MONOGRAPHS

    ADI       acceptable daily intake
    BUN       blood urea nitrogen
    b.w.      body weight
    CD50      convulsive dose, median
    CHO       Chinese hampster ovary
    DCI       immobilized glucose isomerase from S. rubiginosis
    FAO       Food and Agriculture Organization of the United Nations
    FFA       free fatty acids
    g         gram
    GOT       see SGOT
    GPM       alpha-D-glucopyranosido-1,6-mannitol
    GPS       alpha-D-glucopyranosido-1,6-sorbitol
    GPT       see SGPT
    Hb        haemoglobin
    HFE       non-immobilized glucose isomerase from S. rubiginosis
    HGS       hydrogenated glucose syrups
    IARC      International Agency for Research on Cancer
    i.m.      intramuscular
    i.p.      intraperitoneal
    IPCS      International Programme on Chemical Safety
    IRI       immunoreactive insulin
    i.v.      intravenous
    JECFA     Joint FAO/WHO Expert Committee on Food Additives
    kg        kilogram
    LD50      lethal dose, median
    LDH       lactate dehydrogenase
    4-MEI     4-methylimidazole
    µg        microgram
    µl        microlitre
    µM        micromolar
    mg        milligram
    ml        millilitre
    mM        millimolar
    MTD       maximum tolerated dose
    NAG       N-acetylglucosaminidase
    nM        nanomolar
    NOEL      no observed effect level
    OCT       ornithine carbamoyl transferase
    PCV       haematocrit
    per os    by mouth
    RBC       red blood cell (erythrocyte count)
    SAP       serum alkaline phosphatase
    s.c.      subcutaneous
    SG        specific gravity
    SGOT      serum glutamate-oxaloacetate transaminase
    SGPT      serum glutamate-pyruvate transaminase

    T3        triiodothyronine
    T4        thyroxine
    TG        triglycerides
    THI       2-acetyl-4(5)-tetrahydroxybutylimidazole
    WBC       white blood cell (total leukocyte count)
    WHO       World Health Organization
    w/w       weight/weight

    ANNEX 3

    JOINT FAO/WHO EXPERT COMMITTEE ON FOOD ADDITIVES
    Geneva, 3-12 June 1985

    Members invited by FAO

    Dr I. Chakravarty, Professor and Head, Department of Biochemistry and
         Nutrition, All India Institute of Hygiene and Public Health,
         Calcutta, India

    Dr W.H.B. Denner, Head, Food Composition and Information Unit, Food
         Sciences Division, Ministry of Agriculture, Fisheries and Food,
         London, England (Vice-Chairman)

    Dr S.W. Gunner, Director General, Food Directorate, Health Protection
         Branch, Health and Welfare Canada, Ottawa, Canada

    Professor K. Kojima, College of Environmental Health, Azabu
         University, Sagamihara-Shi, Kanagawa-Ken, Japan

    Dr W. Kroenert, Head, Food Chemistry Division, Max von Pettenkofer
         Institute, Federal Office of Public Health, Berlin (West)

    Dr R. Mathews, Director, Food Chemicals Codex, National Academy of
         Sciences, Washington, DC, USA

    Dr J.P.M. Modderman, Food Additives Chemistry Evaluation Branch,
         Center for Food Safety and Applied Nutrition, Food and Drug
         Administration, Washington, DC, USA

    Professor F.J. Pellerin, Faculty of Pharmacy, Université de Paris XI,
         Centre hospitalier Corentin-Celton, Issy-les-Moulineaux, France

    Members invited by WHO

    Dr H. Blumenthal, Director, Division of Toxicology, Center for Food
         Safety and Applied Nutrition, Food and Drug Administration,
         Washington, DC, USA

    Dr A.H. El-Sebae, Chairman, Pesticides Division, Faculty of
         Agriculture, Alexandria University, Alexandria, Egypt

    Professor P.E. Fournier, Professor of Clinical Toxicology, Hôpital
         Fernand Widal, Paris, France

    Dr B. MacGibbon, Senior Principal Medical Officer, Division of
         Toxicology and Environmental Protection, Department of Health and
         Social Security, London, England

    Professor K.A. Odusote, Associate Professor of Medicine, College of
         Medicine, University of Lagos, Lagos, Nigeria (Rapporteur)

    Dr P. Pothisiri, Director, Food Control Division, Food and Drug
         Administration, Ministry of Public Health, Bangkok, Thailand

    Professor M.J. Rand, Head, Department of Pharmacology, University of
         Melbourne, Victoria, Australia (Chairman)

    *Dr V.A. Tutelyan, Deputy Director, Institute of Nutrition, Academy of
         Medical Sciences of the USSR, Moscow, USSR

    Secretariat

    Dr J.R.P. Cabral, Scientist, Unit of Mechanisms of Carcinogenesis,
         International Agency for Research on Cancer, Lyons, France

    Mr A. Feberwee, Chairman, Codex Committee on Food Additives; and
         Deputy Director, Nutrition and Quality Affairs, Ministry of
         Agriculture and Fisheries, The Hague, The Netherlands (Member of
         FAO Secretariat)

    Professor C.L. Galli, Professor of Experimental Toxicology, Institute
         of Pharmacology and Pharmacognosy, University of Milan, Milan,
         Italy (WHO Temporary Adviser)

    Dr W. Grunow, Head, Division of Food Toxicology, Max von Pettenkofer
         Institute, Federal Office of Public Health, Berlin (West) (WHO
         Temporary Adviser)

    Mr R. Haigh, Principal Administrator, Commission of the European
         Communities, Brussels, Belgium (WHO Temporary Adviser)

    Dr Y. Hayashi, Director, Division of Pathology, Biological Safety
         Research Centre, National Institute of Hygienic Sciences, Tokyo,
         Japan (WHO Temporary Adviser)

    Dr J.L. Herrman, Division of Food and Color Additives, Center for Food
         Safety and Applied Nutrition, Food and Drug Administration,
         Washington, DC, USA (WHO Consultant)

    Dr F. Käferstein, Responsible Officer, Food Safety Programme, Division
         of Environmental Health, WHO, Geneva, Switzerland

    Dr N. Rao Maturu, Food Standards Officer, Joint FAO/WHO Food Standards
         Programme, FAO, Rome, Italy

              

    *    Invited but unable to attend

    Dr M. Mercier, Manager, International Programme on Chemical Safety,
         Division of Environmental Health, WHO, Geneva, Switzerland

    Dr A.W. Randell, Nutrition Officer (Food Science), Food Policy and
         Nutrition Division, FAO, Rome, Italy (FAO Joint Secretary)

    Dr S.I. Shibko, Associate Director for Regulatory Evaluation, Division
         of Toxicology, Center for Food Safety and Applied Nutrition, Food
         and Drug Administration, Washington, DC, USA (WHO Temporary
         Adviser)

    Dr P. Shubik, Senior Research Fellow, Green College, Oxford, England
         (WHO Temporary Adviser)

    Professor R. Truhaut, Professor Emeritus of Toxicology, Department of
         Toxicology and Industrial Hygiene, René Descartes University,
         Paris, France (WHO Temporary Adviser)

    Dr G. Vettorazzi, Senior Toxicologist, International Programme on
         Chemical Safety, Division of Environmental Health, WHO, Geneva,
         Switzerland (WHO Joint Secretary)

    Dr R. Walker, Department of Biochemistry, University of Surrey,
         Guildford, Surrey, England (WHO Temporary Adviser)



        ANNEX 4

    ACCEPTABLE DAILY INTAKES, OTHER TOXICOLOGICAL RECOMMENDATIONS AND INFORMATION ON SPECIFICATIONS
                                                                                                          

                                                                       ADI for man
                                                 Specifications1       and other
                                                                       toxicological
                                                                       recommendations
                                                                                                          

    A.  Specific food additives

       Enzyme preparations and enzyme immobilizing agents

       Carbohydrase (alpha-amylase)                      R             ADI not specified2
       from Bacillus licheniformis

       Glucose isomerase (immobilized)                   S             Acceptable3
       from Actinoplanes missouriensis

       Glucose isomerase                                 S             No ADI allocated4
       from Bacillus coagulans

       Glucose isomerase (immobilized)                   S             Acceptable3
       from Bacillus coagulans

       Glucose isomerase (immobilized)                   S             Acceptable3
       from Streptomyces olivaceus

       Glucose isomerase (immobilized)                   S             Acceptable3
       from Streptomyces olivochromogenes

       Glucose isomerase                                 R             No ADI allocated4
       from Streptomyces rubiginosus

       Glucose isomerase (immobilized)                   R             Acceptable3
       from Streptomyces rubiginosus)
                                                                                                          

    ANNEX 4 (Con't)

                                                                                                          

                                                                       ADI for man
                                                 Specifications1       and other
                                                                       toxicological
                                                                       recommendations
                                                                                                          

       Polyethylenimine                                  -             Suitable5

       Flavouring agent
       Benzyl acetate                                    S             0-56 mg/kg b.w.

       Flour treatment agent
       Chlorine                                          S             2.5 g Cl2/kg flour7

       Food acids and their salts
       Aluminium ammonium sulfate                        N             0-0.6 mg/kg b.w. 6,8
       Aluminium, calcium, magnesium,                    O             No ADI allocated9
         potassium, and sodium salts
         of capric, caprylic, lauric
         and oleic acids
       Ammonium succinate                                O             No ADI allocated9
       Calcium adipate                                   O             No ADI allocated9
       Calcium aluminium silicate                        S             ADI "not specified"2, 10
         (previously aluminium
         calcium silicate)
       Calcium fumarate                                  O             No ADI allocated9
       Calcium hydrogen carbonate                        O             No ADI allocated9
       Calcium succinate                                 O             No ADI allocated9
       Dipotassium guanylate                             N             ADI "not specified"2, 12
       Dipotassium inosinate                             N             ADI "not specified"2, 13
       Ferric ammonium citrate                           S             0-0.8 mg/kg b.w.11
       Guanylic acid                                     N             ADI "not specified"2, 12
       Inosinic acid                                     N             ADI "not specified"2, 13
                                                                                                          

    ANNEX 4 (Con't)

                                                                                                          

                                                                       ADI for man
                                                 Specifications1       and other
                                                                       toxicological
                                                                       recommendations
                                                                                                          

       Magnesium acetate                                 O             No ADI allocated9
       Magnesium adipate                                 O             No ADI allocated9
       Magnesium citrate                                 O             No ADI allocated9
       Magnesium succinate                               O             No ADI allocated9
       Monomagnesium phosphate                           O             No ADI allocated9
       Potassium aluminosilicate                         O             No ADI allocated9
       Potassium fumarate                                O             No ADI allocated9
       Potassium succinate                               O             No ADI allocated9
       Potassium sulfate                                 N             ADI "not specified"2
       Potassium sulfite                                 N             0-0.7 mg/kg b.w.14
       Sodium aluminium polyphosphate                    O             No ADI allocated9
       Sodium sorbate                                    O             0-25 mg/kg b.w.15

       Food colours
       Brown FK                                          N             0-0.075 mg/kg b.w.6
       Caramel colours
         Class I                                        R,T            ADI "not specified"2
         Class II                                       N,T            No ADI allocated16
         Class III                                      R,T            0-200 mg/kg b.w.
                                                                       (0-150 mg/kg b.w.
                                                                       on solids basis)
                                                                                                          

    ANNEX 4 (Con't)

                                                                                                          

                                                                       ADI for man
                                                 Specifications1       and other
                                                                       toxicological
                                                                       recommendations
                                                                                                          

       Caramel colours (con't)
         Class IV                                       R,T            0-200 mg/kg b.w.
                                                                       (0-150 mg/kg b.w.
                                                                       on solids basis)
       Carthamus yellow                                 R,T            No ADI allocated16
       Fast green FCF                                    R             0-12.5 mg/kg b.w.6
       Saffron                                          R,T            Food ingredient17

       Sweetening agents
       Hydrogenated glucose syrups                       R             ADI "not specified"2
       Isomalt                                           R             ADI "not specified"2
       Mannitol                                          T             0-50 mg/kg b.w.6
       Thaumatin                                         S             ADI "not specified"2

       Thickening agents
       Dammer gum                                       S,T            No ADI allocated16
       Ethylhydroxyethyl cellulose                      R,T            0-25 mg/kg b.w. 6, 18
       Gum ghatti                                        R             No ADI allocated16
       Karaya gum                                        R             0-20 mg/kg b.w.6
       Oat gum                                           O             No ADI allocated16
       Tragacanth gum                                    R             ADI "not specified"2
       Xanthan gum                                       S             0-10 mg/kg b.w.
                                                                                                        

    ANNEX 4 (Con't)

                                                                                                          

                                                                       ADI for man
                                                 Specifications1       and other
                                                                       toxicological
                                                                       recommendations
                                                                                                          

       Miscellaneous food additives
       Bone phosphate                                    R             70 mg/kg b.w.19
       Carbon dioxide                                   R,T            ADI "not specified"2
       Nitrous oxide                                     R             Acceptable20
       Polyvinylpyrrolidone (PVP)                       R,T            0-25 mg/kg b.w.6
       Quillaia extract                                 N,T            0-5 mg/kg b.w.
       Sodium thiocyanate                                S             Decision postponed

    B.  Contaminants

       Ethylenimine                                      -             Provisional acceptance21
                                                                                                        
    

    ANNEX 4 (Con't)
                                                                        

                               Specifications only1
                                                                        

         Acesulfame potassium                                     S
         Ammonium hydrogen carbonate                              R
         Ammonium polyphosphate                                   S,T
         Butylated hydroxyanisole                                 R
         Calcium polyphosphates                                   S
         Calcium, potassium, and sodium                           R
            salts of myristic, palmitic, and
            stearic acids
         Carrageenan                                              R
         Diethyleneglycol monomethylether                         S,T
         Diethyl tartrate                                         R
         Ethyl alcohol (previously ethanol)                       R
         Ethylhydroxymethyl cellulose                             R
         Eugenyl methyl ether                                     R
         Gum arabic                                               R
         Hydrogen peroxide                                        R
         Hydroxypropyl cellulose                                  R
         Hydroxypropylmethyl cellulose                            R
         Insoluble polyvinylpyrrolidone                           R
         Methylethyl cellulose                                    S
         Modified starches:
            Acetylated distarch adipate                           R
            Acetylated distarch phosphate                         R,T
            Hydroxypropyl distarch phosphate                      R
         Pentapotassium triphosphate                              R
         Polydimethylsiloxane                                     R
         Saccharin                                                R
         Sodium aluminium phosphate,                              R
            acidic
         Sorbitan monolaurate                                     R,T
         Sorbitan monooleate                                      R,T
         Sorbitol                                                 R
         Sucrose acetate isobutyrate                              R,T
         Turmeric oleoresin                                       N
                                                                        

    Notes to Annex 4

    1.   N, new specifications prepared; O, specifications not prepared;
         R, existing specifications revised; S, specifications exist,
         revision not considered or not required; and T, the existing, new
         or revised specifications are tentative and comments are invited.

    2.   ADI "not specified" means that, on the basis of the available
         data (chemical, biochemical, toxicological, and other), the total
         daily intake of the substance, arising from its use 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 that reason, and for the
         reasons stated in the individual evaluations, the establishment
         of an acceptable daily intake (ADI) expressed in numerical form
         is not deemed necessary.

    3.   Acceptable for use in food processing.

    4.   No information was available on the food use of this enzyme.

    5.   Polyethylenimine is considered to be a suitable substance for use
         as an immobilizing agent in the production of immobilized
         enzymes. (See also note 21.)

    6.   Temporary acceptance.

    7.   Acceptable level for treatment of flours for cake manufacturing.

    8.   Group ADI for aluminium salts expressed as aluminium.

    9.   No information was available on the food use of these salts.

    10.  Group ADI for silicon dioxide and certain silicates (aluminium,
         calcium, and sodium aluminosilicate); the previous ADI "not
         limited" was changed to ADI "not specified".

    11.  Included in the group maximum tolerable daily intake for iron.

    12.  Group ADI for guanylic acid and its calcium, dipotassium, and
         disodium salts.

    13.  Group ADI for inosinic acid and its calcium, dipotassium, and
         disodium salts.

    14.  Group ADI for sulfur dioxide and sulfites (sodium and potassium
         metabisulfites, sodium sulfite, and sodium hydrogen sulfite
         expressed as sulfur dioxide).

    15.  Group ADI for sorbic acid and its calcium, potassium, and sodium
         salts expressed as sorbic acid.

    16.  Insufficient information available on its toxicology and chemical
         composition.

    17.  This substance is regarded as a food rather than as a food
         additive.

    18.  Group ADI for modified celluloses.

    19.  This figure represents the maximum tolerable daily intake (MTDI)
         of phosphates expressed as phosphorus; it applies to the sum of
         phosphates naturally present in food and the additives listed in
         Annex 4 of the twenty-sixth report (WHO Technical Series, No.
         683, 1982). It also applies to diets that are nutritionally
         adequate in respect of calcium. However, if the calcium intake
         were high, the intake of phosphate could be proportionately
         higher; the reverse relationship would also apply.

    20.  The food use of nitrous oxide as a propellant is acceptable.

    21.  Acceptable on condition that the amount of ethylenimine migrating
         into food is reduced to the lowest technically attainable level.
    


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