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    DEXTRINS

    Explanation

         This substance was evaluated previously for an ADI for man by the
    Joint FAO/WHO Expert Committee on Food Additives in 1969 and 1974 (see
    Annex I, Refs. 19 and 29). Toxicological monographs were published in
    1969 and 1974 (see Annex I, Refs. 20 and 30).

         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.

    Introduction

         White dextrins are prepared by heating dry starch in the presence
    of an acid at a temperature generally below 150°C. White dextrins may
    also be obtained by further continuing the acid process for making
    thin boiling starches. Because of the nature of the application as
    well as their flavour, their use in food is restricted. Dextrins are a
    stage in the normal digestion of starch occurring in the human
    gastrointestinal tract. They represent a broad range of products with
    considerably smaller molecular size than native starch.

         Yellow dextrins are prepared in a similar manner but at a higher
    temperature and using less acid. Apart from depolymerization, a good
    deal of internal rearrangement occurs with formation of highly
    branched molecules. These materials are used in foods in limited
    quantities as adjuvants in flavour encapsulation and similar minor
    uses.

    BIOLOGICAL DATA

    BIOCHEMICAL ASPECTS

    Absorption and metabolism

         Dextrins and their parent starches were fed to groups of 6
    weanling male rats (strain unspecified), initial weight 45-60 g, at a
    level of 60 g/kg bw for 21 to 28 days. Diets contained 18.8% casein.
    The digestibility of wheat dextrin was somewhat lower than that of
    wheat starch. The potato dextrin gave a higher body weight gain and
    digestibility coefficient than the parent starch (Booher et al.,
    1951).

         In a study on the effect of type of dietary carbohydrate on
    B-vitamin synthesis in the digestive tracts of rats, groups of 17 to
    44 male and female rats (strain unspecified), 21 days of age were
    placed on test diets containing 18% protein (casein), 71%

    carbohydrate, and 3% butterfat, cod-liver oil and salt mixture. The
    carbohydrate sources used included cornstarch, corn dextrin, glucose,
    lactose and sucrose. Animals on all diets, without supplemental
    B-vitamins but with access to their faeces, showed low or declining
    growth rates after 2 weeks except for the group fed the dextrin diet.
    Growth rates in all groups were increased after receiving faeces of
    the dextrin-fed group. Rats receiving the dextrin diet had enlarged
    caeca at the conclusion of the study. Caecectomized rats with access
    to their faeces lost weight when fed a dextrin diet; supplementation
    with baker's yeast resulted in weight gain. It was concluded that the
    peculiar property of corn dextrin was not due to retained B-vitamins,
    but rather to the formation of these vitamins in the lower part of the
    digestive tract of the rat as a result of incomplete digestion of this
    particular carbohydrate (Guerrant et al., 1935).

         Fournier (1959) studied the effect of various dietary
    carbohydrate sources on calcium retention, serum calcium levels,
    and caecal size in the rat. Wistar rats (sex unspecified) weighing
    62-74 g, were fed a low calcium diet (50 mg Ca/100 g diet) for 18 days
    after which groups of 6 rats were placed on diets containing 15%
    casein, 1.5% calcium carbonate and 45-70% experimental carbohydrate
    (starch, dextrin, caramel or glucose) plus cereal grain to bring total
    carbohydrate to about 70%. Rats received an estimate of 46 g dextrin
    per kg body weight. Calcium balance was determined during the third to
    fifth day; after 10 days the rats were sacrificed and serum calcium
    determined. Caecal enlargement observations were made after 2 weeks of
    feeding a diet containing 75% of the experimental carbohydrate
    source, 12% casein, 8% peanut oil and 3% salts. Calcium intake was
    approximately the same for all diets, but calcium retention for the
    dextrin and caramel diets was nearly double that for the starch and
    glucose diets. Serum calcium levels also were greater for the dextrin
    and caramel diets. Dry caecal weights of rats fed dextrin and caramel
    were more than double those fed the starch and glucose diets. The
    author postulated that dextrin and caramel were less easily
    metabolized than their parent substances, starch and glucose, and that
    this property contributed to the effects observed.

         14C-labelled beta-cyclodextrin homogenized in aqueous dextran
    was administered to 5 Wistar plus Long Evans F1 hybrid male rats
    weighing about 200 g each. Individual animals received doses
    corresponding to their body weight through an oesophageal cannula.
    Three control animals received 14C-labelled glucose. Blood levels of
    the compounds were measured at intervals up to 97 hours from tail vein
    samples. At 7, 12 and 24 hours after administration, selected animals
    were decapitated, and radioactivity was measured in stomach, small
    intestine and colon. In the case of the cyclodextrin, a maximum of
    only 5% of the administered activity could be found in blood even
    after 10 hours; after 96 hours the same residual radioactivity was
    found in the blood with both glucose and ß-cyclodextrin. This study

    suggests that ß-cyclodextrin cannot be absorbed either from the
    stomach or the small intestine; only the labelled open-chain dextrins
    and glucose formed from cyclodextrin by amylase action were absorbed
    (Szejtli et al., 1980).

    TOXICOLOGICAL STUDIES

    Special studies on nephrosis in the rat kidney due to alpha- and
    beta-cyclodextrin

         Groups of 5 male and 5 female Sprague-Dawley rats weighing 150 to
    160 g were administered cyclodextrins intravenously. The i.v. LD50
    for rats was determined to be 0.79-1.0 g/kg bw with a close
    relationship between the acute toxicity and the nephrotoxic dose
    (Frank et al., 1976).

         Groups of 4 100-124 g Sprague-Dawley rats received single s.c.
    doses of cyclodextrins of 0.225, 0.45 or 0.90 g/kg and were killed 12,
    24, 48 or 96 hours later. Controls received saline injections. Kidneys
    were sectioned for light microscopy and histopathological observations
    (Frank et al., 1976).

         In another experiment, groups of 4 100-125 g Sprague-Dawley rats
    were given 1, 2, 3, 4 or 7 daily s.c. injections of cyclodextrins at
    0.225, 0.45, 0.675, 0.90, 0.1 or 1.0 g/kg bw. Controls received saline
    injections. Rats were killed 24 hours after the last injection and
    kidneys were sectioned for histopathological observations (Frank et
    al., 1976).

         Renal toxicity due to the cyclodextrins was shown to result from
    a series of alterations in the vacuolar organelles of the proximal
    convoluted tubules. Intracellular concentration of toxin via the
    lysosomal pathway resulted in a change of the physiological function
    of the proximal tubule which ultimately leads to cell death (Frank et
    al., 1976).

    Short-term studies

    Rat

         Groups of 10 male Wistar rats received diets with 6 or 15%
    protein from casein and 77 or 66% carbohydrate (75 and 65 g
    carbohydrate/kg bw). After 28 days, protein efficiency and weight
    gain/g of dry food were significantly lower for corn dextrin than for
    cornstarch, but were greater or equal to values for dextrose. Corn
    dextrin diets caused no unusual effect on liver weight or liver fat
    content; however, rats receiving corn dextrin exhibited a slight
    diarrhoea and caecal enlargement to about twice that in rats fed
    unmodified cornstarch (Reussner et al., (1963).

         Groups of 6 Sprague-Dawley male weanling rats (initial weight
    40-50 g), were fed for periods of 2-12 weeks on diets containing
    approximately 80 g dextrin/kg bw; diets contained 81% carbohydrate, 9%
    casein and 5% corn oil. Rates of gain with the dextrins over a 4-week
    period were about 15% less than that for autoclaved cornstarch; the
    latter weight was about double when the carbohydrate source was
    glucose or sucrose. Liver fat deposition was less for one of the
    dextrins, cornstarch or glucose, than for sucrose as the carbohydrate
    source. Liver fat deposition values were not reported for the other
    dextrin (Harper et al., 1953).

         Groups of 5 or 10 male weanling Sprague-Dawley or Osborne-Mendel
    rats, weighing initially 40-50 g, were fed diets containing about 80 g
    carbohydrate/kg bw; diets consisted of 87% carbohydrate, 9% casein, 3%
    gelatin and 3% corn oil. Weight gain over a 4-week period with niacin
    supplementation was the same with either dextrin, starch or glucose as
    carbohydrate source, without niacin supplementation, growth rate
    decreased about 40% for starch and dextrin as the carbohydrate source,
    as compared to 60% decrease with glucose as the carbohydrate source,
    suggesting a lesser niacin requirement with starch and dextrin as
    carbohydrate source (Hundley, 1949).

    Long-term studies

         Groups of 9 male Sprague-Dawley rats (2 months of age) were fed
    diets with different sources of carbohydrate for a 20-month period.
    Diets consisted of rat chow mixed with 20%, by weight, of the various
    carbohydrate sources, including dextrin, sucrose, and dextrose. Rats
    received approximately 10 g experimental carbohydrate/kg bw. Protein
    efficiency ratios calculated after 6 months feeding were nearly equal
    for the dextrin, dextrose and sucrose diets and significantly higher
    than for the basal rat chow diet. Weight gain after 20 months of
    feeding was about 5% less for dextrin than for dextrose or sucrose but
    about 5% more than on the basal rat chow (Cohen et al., 1967).

    Comments

         These substances are regarded as identical to the intermediates
    formed in the normal digestion of starch and normal constituents of
    food.

    EVALUATION

    Estimate of acceptable daily intake for man

    Not specified.*

              

    *    The statement "ADI not specified" means that, on the basis of the
         available data (toxicological, biochemical, and other), the total
         daily intake of the substance, arising from its use or uses at
         the levels necessary to achieve the desired effect and from its
         acceptable background in food, does not, in the opinion of the
         Committee, represent a hazard to health. For this reason, and for
         the reasons stated in individual evaluations, the establishment
         of an acceptable daily intake (ADI) in mg/kg bw is not deemed
         necessary.

    REFERENCES

    Booher, L. E., Behan, I. & McMeans, E. (1951) Biological utilization
         of unmodified and modified food starches, J. Nutr., 45, 75-95

    Cohen, L., Perkin, E. G. & Dobrilovic, L. (1967) The manifold effects
         of different dietary carbohydrates, Progr. Biochem. Pharmacol.,
         2, 182-202

    Fournier, P. (1959) Le caramel et la dextrine préparés par action de
         la chaleur sèche sur le glucose et l'amidon possèdent les
         qualités physiologiques des composés de structure, C. R. Acad.
         Sci., 248, 3744-3746

    Frank, D. W., Gray, J. E. & Weaver, R. N. (1976) Cyclodextrin
         nephrosis in the rat, Am. J. Pathol., 83(2), 367-382

    Guerrant, N. B., Dutcher, R. A. & Tomey, L. F. (1935) The effect of
         the type of carbohydrate on the synthesis of B vitamins in the
         digestive tract of the rat, J. Biol. Chem., 110, 223-243

    Harper, A. E. et al. (1953) Influence of various carbohydrates on the
         utilization of low protein rations by the white rat, J. Nutr.,
         51, 523-537

    Hundley, J. M. (1949) Influence of fructose and other carbohydrates on
         the niacin requirement of the rat, J. Biol. Chem., 181, 1-9

    Reussner, G., Jr, Andros, J. & Thiessen, R., Jr (1963) Studies on the
         utilization of various starches and sugars in the rat,
         J. Nutr., 80, 291-298

    Szejtli, J., Gerl'oczy, A. & F'Onagy, A. (1980) Intestinal absorption
         of the 14C-labelled beta-cyclodextrin in rats, Arzneim.,
         30(5), 808-810
    


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       Toxicological Abbreviations