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    PECTINS AND AMIDATED PECTINS

    Explanation

         This substance was evaluated for acceptable daily intake for man
    (ADI) by the Joint FAO/WHO Expert Committee on Food Additives in 1973
    (see Annex, Ref. 33). A toxicological monograph was issued in 1975
    (see Annex, Ref. 35).

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

    BIOLOGICAL DATA

    TOXICOLOGICAL STUDIES

    Special studies on reproduction

         A three-generation reproduction study of amidated pectin was
    carried out using groups of eight male and 16 female Charles River
    CD strain mice. The test groups were fed 2% or 5% amidated pectin.
    Similar groups of animals fed 2% or 5% non-amidated pectin were
    utilized as controls. The study design called for two litters to be
    raised per generation with the second (b) litter utilized to produce
    the next generation. In general, there were no dose-related effects on
    mortality, body weight, food consumption, reproductive or survival
    indices or incidence of gross or histopathologic lesions. Mating of
    the 2% non-amidated pectin group to produce the F2b litter resulted
    in only five females becoming pregnant, two died during pregnancy and
    none of the pups survived to day 21. Since the occurrence was limited
    to the second litter of one generation and did not occur at a higher
    dose (5%) the effect is not considered to be related to administration
    of non-amidated pectin. There was some mortality among the other
    groups and generations as well, evidently due to respiratory
    infections (Industrial Biotest, 1979b).*

         Groups of one male and five female Wistar rats were utilized in
    carrying out a two-generation reproduction study of amidated pectin
    fed at a level of 16.6% in the diet. One set of litters were produced
    per generation. Five males and five females per generation were
    subjected to gross and histopathologic examination. No abnormalities
    were reported to occur in any of the offspring and the results of the

              

    *    This study was validated by an independent audit (see memo of 13
         November 1979, International Verband de Pektinprodunzenter -
         submitted to WHO).

    gross and histopathologic examination were said to be normal. Data
    such as reproductive and survival indices, body weight changes, etc.
    were not presented in the report (Mosinger, 1976).

    Special studies on teratology

         Groups of 20 or 22 pregnant females Charles River albino rats
    were fed a diet containing 2 or 5% amidated pectin on gestation days 6
    through 15. Similar groups fed diets containing 2 or 5% non-amidated
    pectin were used as concurrent controls. Dams were sacrificed on day
    20 and foetuses were examined externally. Two-thirds of the foetuses
    were processed for skeletal examination and one-third for soft tissue
    examination. There was no mortality among the dams during the study
    and body weights and food consumption were comparable between groups.
    Data on corpora lutea, implantation sites, resorption sites, foetal
    viability, foetal weight and sex ratio were comparable between all the
    groups. No intergroup differences were reported with respect to
    skeletal or soft tissue anomalies (Industrial Biotest, 1976).*

    Short-term studies

    Rat

         Four groups of 10 male and 10 female rats were fed diets
    containing 0%, 5%, 10% or 15% pectin (21% amidated) for 90 days. No
    adverse effects were noted on general condition, behaviour and
    survival. Growth was slightly decreased at the 15% level and this
    finding was also noted in a range finding test using 20% pectin in the
    diet. Some decrease in growth occurred inconsistently also at the 10%
    dietary level. Food intake and food efficiency were not affected at
    any level. Haematological parameters showed no significant treatment-
    related changes. Total serum protein and albumin were reduced at the
    15% level but the other clinical biochemical parameters and urinalysis
    were essentially normal. Caecal weights were increased at all levels
    but in a dose-related manner. These findings are reminiscent of what
    is seen when high amounts of starch, modified starch or certain other
    carbohydrates are fed. Gross histopathology were normal but a slight
    degree of hyperkeratosis of the forestomach in some males was seen at
    the 10% and 15% level but is probably not of toxicological
    significance (Til et al., 1972).

              

    *    This study was validated by an independent audit (see memo of 13
         November 1979, International Verband de Pektinprodunzenter -
         submitted to WHO).

    Long-term studies

         Groups of 20 male weanling Wistar rats were fed diets of purina
    laboratory meal to which was added low molecular pectin (approximately
    18% amidated) or non-amidated pectin at 10% of the diet. Control diets
    contained 10% alphacellulose (alphacel). The rats were fed for
    two years. The diets were made isocaloric by supplementing the
    alphacel with dextrose assuming a caloric equivalent for pectin of
    0.6187 cal/g. Mortality did not vary significantly between groups.
    Body weights for the pectin fed groups were similar but significantly
    less than those of the control animals. A comparison of grams of
    diet/kg body weight showed a slightly greater food utilization for the
    pectin fed groups. The controls, however, consumed more food and
    gained more weight. There was no significant difference in average
    organ to body weight ratios for adrenal, heart, kidney, liver and
    spleen. The testes/body-weight ratio of the pectin fed groups did not
    differ from each other but both were significantly larger than those
    of the control group. Blood chemistry, SGOT and SPGT done at sacrifice
    showed no abnormalities in the pectin groups. Gross examination at
    necropsy showed no unusual findings. Two tumours were noted in the
    control group and one in the amidated pectin group. All gross lesions
    and adrenal, heart, kidney, liver, lung, spleen and testes were
    examined histologically. No compound related effects were observed
    (Palmer & Jones, 1974; Abdul & Palmer, 1974).

         Groups of 50 male and 50 female Charles River strain albino rats
    were fed amidated pectin at dietary levels of 2% and 5% for two years.
    Similar groups of rats were fed non-amidated pectin at 2% or 5% of the
    diet. Initially an untreated control group receiving chow diet only
    was included in the study, however, this group was sacrificed and
    discarded at week 36 of the study. The group fed non-amidated pectin
    served as the control for the amidated pectin groups. An interim
    sacrifice of 10 animals per group per sex was carried out after three
    months of testing. Body weight tended to be lower in the males fed 5%
    of amidated or non-amidated pectin as compared to the males fed 2%
    amidated or non-amidated pectin. The difference was statistically
    significant at a number of weeks during the study. The total weight
    gain at 13 weeks was significantly lower in the males given 5%
    non-amidated pectin than that of the non-amidated 2% group. No
    significant changes were noted in food consumption or mortality. Small
    statistically significant differences between the high dose amidated
    and non-amidated group occurred with respect to leucocyte and
    reticulocyte counts at the three-month repeat blood collection,
    otherwise no significant haematological changes were noted. The 2%
    amidated pectin females had a large increase (about 3x) in serum
    glutamin pyruvate levels at the three-month and three-month repeat
    blood collections. There were other scattered instances of small
    statistically significant between group differences with respect to
    other clinical chemistry parameters. No significant changes were noted

    upon urinalysis. There were scattered instances of small but
    statistically significant between group differences in absolute organ
    and relative organ weights.

         The absolute and relative adrenal glands weight in the low dose
    amidated pectin group was high compared to the other groups, although
    evidently there was not a statistically significant between group
    difference. The adrenal weights were not increased in the high dose
    females.

         In general, the incidence of neoplastic and non-neoplastic
    lesions was similar in all the groups. The incidence of chronic
    inflammation of the liver was 4/37 in the females given 2% non-
    amidated pectin, 3/40 in the females given 5% non-amidated pectin,
    14/39 in the females fed 2% amidated pectin and 13/49 in the females
    given 5% amidated pectin. Although the incidence of this lesion was
    increased in the females given amidated pectin, there was no dose
    response, the incidence being slightly reduced in the 5% amidated
    pectin group as compared to the 2% group (Industrial Biotest, 1979a).*

         A group of 20 male and 20 female Wistar rats were fed a diet
    containing 16.6% amidated pectin for two years. Growth, final body
    weight and incidence of neoplastic and non-neoplastic lesions were
    stated to be comparable to a group of 4000 historical control animals
    maintained in the performing laboratory. Pathology observations for
    each animal were provided, but body weight other than at termination,
    and food consumption data were not reported (Mosinger, 1976).

         Wistar rats of the Centre for Investigation and Medical Research
    at Marseille strain were administered 100 mg/kg bw of 18.4% amidated
    pectin, daily in the synthetic diet of Lacassagne MABI. Feeding was
    ad lib. Groups of 20 males and 20 females housed five to a cage were
    used. Controls consisted of an identical group of rats fed the basic
    synthetic diet. At this level of pectin in the diet there appeared to
    be no effects on growth and body weights of fed animals as compared to
    historic controls. Also, there appeared to be no effects on the serum
    of fed rats. Since many of the experimental details are lacking it is
    difficult to reconstruct the complete design of the study. It is
    clear, however, that tissues from 20 males and 20 females sacrificed
    at 24 months were studied histologically. Rats dying prior to
    termination of the study were also said to have been examined
    microscopically. However, no mention of such animals is made in the
    detailed pathology. The histopathology revealed no adverse effects on
    the stomachs or testes of fed males. It should be noted that these

              

    *    This study was validated by an independent audit (see memo of 13
         November 1979, International Verband de Pektinprodunzenter -
         submitted to WHO).

    were very small rats. Only one male reached 640 g, the remainder
    ranged from 210 to 420 g with seven of the rats weighing 270 g or
    less. The weight of the females at sacrifice was similar to the males.
    A first generation produced by mating five animals produced a total of
    99 offspring and a second generation produced by mating five animals
    resulted in only 43 offspring (Mosinger, 1974).

    Comments

         Non-amidated pectins and their salts as specified are normal
    constituents of the human diet and have also been administered
    intravenously at high levels to man without acute toxic effects. The
    available short-term tests show that even at 5% dietary levels, no
    adverse effects are seen. The caecal enlargement without any
    accompanying histological changes is probably related to the presence
    of large amounts of a polysaccharide in the diet.

         Amidated pectins produced mild growth depression at a lower level
    (10%) than was seen with non-amidated pectins in a 90-day test as well
    as in a two-year study in rats. The available short-term study in rats
    revealed caecal enlargement but not associated with any histological
    abnormality.

         A three-generation reproduction study and a teratogenicity study,
    and a two-year feeding study in rats fed diets containing 2% and 5%
    amidated pectin or non-amidated pectin showed no significant
    toxicological differences between animals fed amidated and non-
    amidated pectin.

    EVALUATION

    ADI 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

    Abdul, H. & Palmer, G. H. (1974) Twp-year pectin feeding study:
         histopathological studies. Unpublished report from Sunkist
         Growers, Inc. submitted to the World Health Organization by
         Sunkist Growers, Inc.

    Industrial Biotest (1976) Teratologic study on amidated pectin.
         Unpublished report submitted to the International Pectin
         Producers Association

    Industrial Biotest (1979a) Two-year study on amidated pectin.
         Unpublished report submitted to the International Pectin
         Producers Association

    Industrial Biotest (1979b) Three generation reproduction study on
         amidated pectin. Unpublished report submitted to the
         International Pectin Producers Association

    Mosinger, M. (1974) Experimentation d'epreuve concernant les effets de
         l'administration orale prolongée du produit pectine L.H. NST de
         la Société Unipectine SA. Unpublished report from the "Central
         d'explorations et de recherches médicales", Marseille, submitted
         to the World Health Organization by the International Pectin
         Producers Association

    Mosinger, M. (1976) Two-year chronic feeding study and multi
         generation reproductive-teratology study with amidated pectin.
         Unpublished report submitted to the International Pectin
         Producers Association

    Palmer, G. H. & Jones, T. R. (1974) Two-year pectin feeding study.
         Unpublished report from Sunkist Growers, Inc. submitted to the
         World Health Organization by Sunkist Growers, Inc.

    Til, H. P., Seinen, W. & De Groot, A. P. (1972) Sub-chronic (90-day)
         toxicity study with two samples of pectin (Melange A2 and C2)
         in rats. Unpublished CIVO Report No. 3843 studied August 1972,
         Submitted to the World Health Organization by the Inst. Eur. des
         Ind. de la Pectine
    


    See Also:
       Toxicological Abbreviations