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    WORLD HEALTH ORGANIZATION

    WHO Food Additives Series 1972, No. 1




    TOXICOLOGICAL EVALUATION OF SOME 
    ENZYMES, MODIFIED STARCHES AND 
    CERTAIN OTHER SUBSTANCES




    The evaluations contained in this publication were prepared by the
    Joint FAO/WHO Expert Committee on Food Additives which met in Rome,
    16-24 June 19711





    World Health Organization

    Geneva

    1972





                   

    1 Fifteenth Report of the Joint FAO/WHO Expert Committee on Food
    Additives, Wld Hlth Org. techn. Rep. Ser., 1972, No. 488; FAO
    Nutrition Meetings Report Series, 1972, No. 50.

    The monographs contained in the present volume are also issued by the
    Food and Agriculture Organization of the United Nations, Rome, as FAO
    Nutrition Meetings Report Series, No. 50A

    (c) FAO and WHO 1972




    MICROBIAL CARBOHYDRASE

    Biological data

    Source

    This enzyme preparation is prepared from some varieties of
    Asperigillus niger.

    Acute toxicity

    Data are available for some commercial preparations.

                                                                     

    Animal   Route        LD50             Reference
                     (mg/kg body-weight)
                                                                     

    mouse    oral        >3 200        Hunt & Garvin, 1963
                         >4 000        Hunt & Garvin, 1971
                         >3 200        Willard & Garvin, 1968
                         >4 000        Garvin et al., 1966

    rat      oral        10 000        Gray, 1960
                         31 600        Kay & Calandra, 1962
                         >3 200        Willard & Garvin, 1968
                         >4 000        Garvin et al., 1966
                        >10 000        Gray, 1960

    rabbit   oral        >4 000        Garvin et al., 1966

    dog      oral        >4 000        Garvin et al., 1966
                                                                     

    Short-term studies

    Rat

    Four groups of 10 male rats received in their diet for 30 days enzyme
    at 0, 0.5 and 5 per cent.  There were no adverse effects related to
    treatment regarding growth, appearance, behaviour, survival, food
    consumption, haematology, organ weights and gross pathology (Garvin et
    al., 1966).

    Two groups of 10 male and 10 female rats received daily for 91 days in
    their diet either 0 or 5 per cent. enzyme.  There was no difference
    from controls regarding appearance, behaviour, survival, weight gain,
    haematology, organ weights and gross pathology (Garvin & Merubia,
    1959).

    Long-term studies

    None available.

    Special studies

    Groups of 5 ducklings received in their diet either 0, 1, 5 or 10 per
    cent. of enzyme for 29 days. Growth, feed consumption, survival,
    behaviour and mean liver weights were comparable.  No gross or
    histo-pathological lesions of the liver were seen (F.D.R.L., 1963).

    Groups of 5 ducklings received in their diet either 0, 1, 5 or 10 per
    cent. of enzyme for 29 days. Growth, feed consumption, behaviour and
    development were comparable in all groups.  No gross liver lesions
    were seen at autopsy and mean liver weights were similar to controls.
    Histopathology of the livers was normal.  No toxic element was noted
    (F.D.R.L., 1963).

    Comments

    Aspergillus niger is a contaminant of food. The available
    information appears to indicate that it is not pathogenic to man.
    Duckling tests are available on 2 preparations and 2 inadequate
    short-term studies in rats on another 2 preparations using levels up
    to 5 per cent. in the diet. These give some reassurance that the
    strains used to prepare carbohydrase do not produce aflatoxin or
    related mycotoxins.

    EVALUATION

    Temporarily not limited. *

    Further work required by 1972

    Adequate 90-day study in rats.

    REFERENCES

    F.D.R.L. (1963) Unpublished report No. 84600e submitted by Miles Chem.
    Co.

    F.D.R.L. (1963) Unpublished report No. 84600f submitted by Miles Chem.
    Co.

    Garvin, P. & Merubia, J. (1959) Unpublished report submitted by Baxter
    Laboratories Inc.


                   

    *Except for good manufacturing practice.

    Garvin, P. J., Willard, R., Merubia, J., Huszar, B., Chiu, E. &
    Gilbert, C. (1966) Unpublished report submitted by Baxter Laboratories
    Inc.

    Gray, E. H. (1960) Unpublished report submitted by Miles Laboratories
    Inc.

    Hunt, R. F. & Garvin, P. J. (1963) Unpublished report submitted by
    Baxter Laboratories Inc.

    Hunt, R. F. & Garvin, P. J. (1971) Unpublished report submitted by
    Travenol Laboratories Ltd.

    Kay, J. H. & Calandra, J. C. (1962) Unpublished report submitted by
    Miles Chem. Co.

    Phillips, B. M., Hartnagel, R. E. & Thompson, D. (1967) Unpublished
    report submitted by Miles Chem. Co.

    Willard, R. L. & Garvin, P. J. (1968) Unpublished report submitted by
    Travenol Laboratories Ltd.
    


    See Also:
       Toxicological Abbreviations