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    QUILLAIA EXTRACTS

    Explanation

         This compound has not previously been reviewed by the Joint
    FAO/WHO Expert Committee on Food Additives.

         Quillaia (synonyns; soapbark, soap tree bark, murillo bark,
    quillaia, Panama bark, Panama wood, and China bark) is the dried inner
    bark derived of cork of Quillaia saponaria Molina and other species
    of Quillaia (Rosaceae). This plant is a large evergreen tree with
    shiny, leathery leaves and thick bark, which is native to China and
    Peru and cultivated in southern California (Leung, 1980).

         Quillaia extract is the aqueous extract of the above bark and
    contains 3 or possibly 4 triterpenoid saponins (2 major, 1 minor, 1
    trace) constituting about 10% of the extract. The sugars, glucose,
    galactose, arabinose, xylose, rhamnose and 2 further unidentified
    sugars, are also present. The extract also contains tannin and about
    11% calcium oxalate. The 2 major saponins are quillaia sapogenin and
    quillaic acid (Commission of the European Communities, 1978).

    BIOLOGICAL DATA

    TOXICOLOGICAL STUDIES

    General biological activity

         Saponins vary widely in the kind and intensity of biological
    activity. Some of the more important reported activities include
    haemolytic, local irritant, inflammatory (especially on intestine),
    cytotoxic and antimicrobial.

         Powdered quillaia bark or saponin concentrate has highly local
    irritant and stimulatory properties. It also possesses expectorant
    properties as well as depressant activity on the heart and
    respiration. Severe toxic effects due to large oral doses have been
    reported to be liver damage, respiratory failure, gastric pain,
    diarrhoea, haemolysis of red blood corpuscles, convulsions and coma
    (Leung, 1980).

    Special studies on pharmacological effects

         Saponins extracted with alcohol from soapbark trees, administered
    orally to rabbits with experimental atherosclerosis, resulted in
    increased plasma lecithin to cholesterol ratio, normalized blood
    cholesterol levels, and decreased elevated blood pressure.
    Subcutaneous injection of the saponin extract did not affect
    atherosclerotic symptoms (Efimova et al., 1966).

         Groups of 12 Swiss mice (strain and sex undefined) were injected
    in the footpad with aliquots of 7 different 5% extracts of Quillaia
    saponica bark. Animals surviving after 24 hours and control animals
    were sacrificed. Degree of oedema was measured in the mice. Haemolysis
    of rabbit erythrocytes was also measured using the same quillaia
    extracts. The adjuvant strength of the various quillaia extracts in
    stimulating immunity to staphylococcal toxin was also measured. The
    samples of quillaia showed no relationship between their inflammatory
    effect on mice, their haemolytic effect for rabbit erythrocytes, their
    toxicity for Swiss mice and their antistaphylococcal immunity-
    stimulation effect for rabbits (Richou et al., 1965).

    Acute toxicity (Saponins extracted from the soapbark tree)
                                                                

                               LD50
    Species      Route      (mg/kg bw)         Reference
                                                                

    Mouse        Oral         1 625        Efimova et al., 1966
                 s.c.           650        Efimova et al., 1966
                 i.p.           275        Efimova et al., 1966
                 i.v.           275        Efimova et al., 1966
                                                                

    Short-term studies

    Rat

         Groups of 15 male and 15 female weanling rats of the CFE strain
    were housed 5 per cage and fed on diets containing 0 (control), 0.6,
    2.0 or 4.0% quillaia extract for 13 weeks. Groups of 5 male and 5
    female rats from the same lot of animals were fed on diets containing
    0 (control), 2.0% or 4.0% quillaia extract for 2 or 6 weeks.

         Animal weights and food intake were measured at the beginning of
    the experiment and weekly throughout the study. Urine analysis was
    carried out during the final week of the study. At sacrifice, absolute
    and relative organ weights were determined, and a histological
    examination was made of tissue and organs from the 4% group.
    Haematological studies and serum chemistry were carried out for all
    groups.

         No abnormalities of behaviour or condition were seen in the rats
    receiving quillaia extract. Body weights of rats fed the highest level
    of quillaia extract (4%) were significantly lower than controls up to
    day 78 in males, but only for the first 2 weeks in females. Food and
    water consumption was reduced in both sexes at all dietary levels, but
    by the end of the study the weights of the treated rats did not differ
    significantly from those of the controls. The feeding of quillaia

    saponin did not affect the results of haematological examinations,
    serum and urine analyses, renal concentrating ability or urinary cell
    excretion. The relative liver weight was reduced in males given 2% or
    4% quillaia extract, and the relative stomach weight was increased in
    both sexes at the same levels. No histopathological effects
    attributable to treatment were found. The no-effect level in this
    study was 0.6% of the diet equivalent to an intake of approximately
    400 mg/kg bw per day (Gaunt, Grasso & Gangolli, 1974).

    Long-term studies

    Mouse

         Groups of 48 male and 48 female TO strain mice were fed diets
    containing 0, 0.1, 0.5 and 1.5% quillaia extract for 84 weeks. The
    mice were observed regularly for abnormalities of condition or
    behaviour, and some males were weighed at intervals. Haematological
    studies were made at weeks 24, 56 and 84. No compound-related effects
    were reported. At the highest dose level, there was a decreased weight
    gain in the male mice. Quillaia at the levels fed had no adverse
    effect on condition, behaviour or death rate. At the termination of
    the study a detailed autopsy and histopathological examination of
    tissues and organs showed no compound-related effects.

         Quillaia extract fed at levels up to 1.5% in the diet (2.2 g/kg
    bw per day) was not carcinogenic; the slightly lower body weight gain
    in the mice on the highest dietary level and some organ weight
    changes, albeit of doubtful significance, indicate a no-effect level
    for quillaia extract of 0.5% in the diet (or 700 mg/kg bw per day)
    (Phillips et al., 1979).

    Rat

         Groups of 48 male and 48 female rats were housed in groups of 4
    and fed on diets containing 0 (control), 0.3, 1.0 or 3.0% quillaia
    extract for 108 weeks. Rats used in the study were a Wistar-derived
    strain from a specified pathogen-free breeding colony. Haematological
    studies were made at weeks 15, 25, 52 and 108 of the study and
    urinalysis at weeks 13, 24 and 78. At the termination of the study a
    complete autopsy was carried out, including histological examination
    of the tissues and organs.

         Male rats fed the highest dietary level had lower body weights
    throughout the experiment than control animals, the differences being
    statistically significant between 10 and 22 months. Females on the
    lowest dietary level had significantly higher body weights than the
    control animals during the first 6 months of the study. The lower body
    weights and reduced incidence of glomerulonephrosis in the male rats
    fed 3% quillaia are considered to be due to reduced food consumption.
    Preference tests run before the start of the 2-year study showed that

    the rats avoided diet containing quillaia extract. Haematological
    parameters and urinalysis showed no compound-related effects and were
    within normal range.

         In general, the incidence of histological findings was similar in
    treated and control animals. The only lesions with incidences greater
    than those of control were fibrosis of the heart and dilatation of the
    glands of the gastric mucosa in females, at the lowest dietary level
    of quallaia. These effects are considered to be fortuitous since there
    was no dose relationship and no similar occurrence in males.

         A variety of benign and malignant tumours were found. The
    incidence of haemangiomas and haemangiosarcomas in the lymh nodes were
    similar in both control and treated animals. The only tumour showing a
    statistical difference from the control incidence was thyroid adenoma,
    which occurred more frequently in females fed 1% quillaia extract in
    the diet. This finding was not considered treatment related, since
    incidence did not increase with level of quillaia extract fed and the
    total incidence of thyroid adenoma in both sexes fed 1% quillaia
    extract was not statistically different from the total control
    incidence (Drake et al., 1982).

    Comments

         A short-term study in the rat showed that even at the highest
    test level (up to 4% of the diet) the only effects observed were some
    decrease in body weight gain, and relative liver weight. In lifetime
    studies in the mouse and rat, at dietary levels up to 1.5%, there were
    minor changes in body weight gain, and some relative organ weights. No
    compound-related histological changes were reported. The no-effect
    level for quillaia extract in the diet of mice was 0.5% and in the rat
    1.0%. No evaluation is possible at this time because specifications
    for quillaia extract are not available.

    EVALUATION

    Estimate of acceptable daily intake for man

    Not allocated.

    REFERENCES

    Commission of the European Communities (1978) Report of the Scientific
         Committee for Food, Emulsifiers, Stabilizers, Thickeners and
         Gelling Agents, Brussels

    Drake, J. J.-P. et al. (1982) Long-term toxicity study of quillaia
         extract in rats, Fd. Cosmet. Toxicol., 20, 15-23

    Efimova, T. G. et al. (1966) The action of soapbark tree Quillaia
         saponaria saponins on blood pressure and cholesterol content in
         animals, Farm. Zh. (Kiev), 21(16), 45-49

    Gaunt, I. F., Grasso, P. & Gangolli, S. D. (1974) Short-term toxicity
         of quillaia extract in rats, Fd. Cosmet. Toxicol., 12,
         641-650

    Leung, A. Y. (1980) Encyclopedia of common natural ingredients used
         in food, drugs, and cosmetics, John Wiley & Sons, NY

    Phillips, J. E. et al. (1979) Long-term toxicity study of quillaia
         extract in mice, Fd. Cosmet. Toxicol., 17, 23-27
    


    See Also:
       Toxicological Abbreviations
       Quillaia extracts (JECFA Food Additives Series 48)
       QUILLAIA EXTRACTS (JECFA Evaluation)