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    ENZYMES DERIVED FROM ASPERGILLUS ORYZAE

    EXPLANATION

         Enzymes from this source were considered at the fifteenth meeting
    of the Committee (Annex 1, reference 26), at which time a decision on
    the ADI was postponed because of concern that one of the known
    metabolites of A. oryzae is -nitropropionic acid, which was
    suspected of carcinogenic potential. Later, at the eighteenth meeting
    of the Committee, a lipase derived from this organism was considered
    (Annex 1, reference 35). It was determined at that time that there was
    no information to substantiate the concern for the potential
    carcinogenicity of -nitropropionic acid, and that analyses of foods
    have shown that the metabolite is present in very few foods and then
    only in minute amounts. The present Committee was also informed that
    A. oryzae varieties are used in certain parts of the world in the
    preparation of foods.

    alpha-AMYLASE (E.C. 3.2.1)

    BIOLOGICAL DATA

    Biochemical aspects

    No information available.

    Toxicological studies

    Acute toxicity

                                                                        

    Animal                 Route       LD50                Reference
                                                                        

    Mouse (Novo Strain)    Oral        > 20 g/kg b.w.      Novo, 1971a
                                                                        

    Short-term studies

    Rats

         Three groups, each containing 5 male and 5 female SPF Wistar
    rats, were maintained for 3 weeks on diets containing 0, 0,5, or 5% of
    the enzyme preparation. Only minor differences were observed among the
    groups in body-weight change and food intake. At termination of the
    study, haematologic measurements, organ-weights analyses, and gross
    post mortem examinations showed no compound-related effects
    (Novo, 1971b).

         In another study, two groups, each containing 10 male and 10
    female ARS Sprague-Dawley rats, were fed diets containing 5 or 10% of
    the test enzyme (equivalent to 3.5 or 7 g enzyme/kg/b.w./day) for
    90-94 days. A control group of 20 male and 20 female rats was
    maintained on the diet alone. No signs of toxicity were observed
    during the test period. Body-weight gain and food consumption were
    similar among animals in the test and control groups. Differential
    blood counts were within the normal range at weeks 4 and 8 in all
    groups. At the end of the study, haematologic parameters, organ-weight
    analyses, and gross and microscopic pathology showed no
    compound-related effects (Garvin et al., 1972a).

         A similar study was performed with carbohydrases from A. oryzae
    (alpha-amylase and amyloglucosidase), prepared under different culture
    conditions. No compound-related effects were reported
    (Gavin et al., 1972b).

    Long-term studies

    No information available.

    Observations in man

    No information available.

    COMMENTS

         Short-term studies on alpha-amylase from A. oryzae did not
    reveal any adverse effects. Based upon its lack of toxicity and the
    fact that A. oryzae varieties are used in the preparation of foods,
    this enzyme was considered to be acceptable for use in food.

    EVALUATION

    Level causing no toxicological effects

    Rat:      10% in the diet, equivalent to 7 g/kg b.w./day.

    Estimate of acceptable daily intake

         Acceptable for use in food when used according to good
    manufacturing procedures.

    REFERENCES

    Garvin, P.J., Ganote, C.E., Merubia, J., Delahany, E., Bowers, S.,
    Varnado, A., Jordan, L., Hatley, G., DeSmet, C., & Porth, J. (1972a).
    Unpublished report from Travenol Laboratories, Inc., Morton Grove,
    IL, USA. Submitted to WHO by Gist-brocades NV, Delft, Holland.

    Garvin, P.J., Ganote, C.E., Merubia, J., Delahany, E., Varnado, A.,
    Jordan, L., Hatley, G., DeSmet, C., & Porth, J. (1972b). Carbohydrase
    from A. oryzae. Unpublished report from Travenol Laboratories, Inc.,
    Morton Grove, IL, USA. Submitted to WHO by Gist-brocades NV,
    Delft, Holland.

    Novo (1971a). Acute toxicity of fungamyl to mice. Unpublished report
    from Novo Industri A/S, Bagsvaerd, Denmark. Submitted to WHO by Novo
    Industri A/S, Bagsvaerd, Denmark.

    Novo (1971b). Three week oral toxicity study of fungamyl in rats.
    Unpublished report BSi/BS from Novo Industri A/S, Bagsvaerd, Denmark.
    Submitted to WHO by Novo Industri A/S, Bagsvaerd, Denmark.

    PROTEASES (B.C. 3.4.21.14; 3.4.23.6)

    BIOLOGICAL DATA

    Biochemical aspects

    No information available.

    Toxicological studies

    Acute toxicity

    No information available.

    Short-term study

    Rats

         Two groups of 10 male and 10 female ARS Sprague-Dawley rats were
    fed diets containing 5 or 10% of the test enzyme preparation
    (equivalent to 3.5 or 7 g enzyme preparation/kg b.w./day) for 90 to 94
    days. A control group of 20 male and 20 female rats were maintained on
    the diet alone. No signs of toxicity were observed during the test
    period. Body-weight gain and food consumption were similar in animals
    in the test and control groups. Differential blood counts were within
    the normal range at weeks 4 and 8 in all groups. At the end of the
    study serum clinical chemistry parameters, organ weight analyses, and
    gross and microscopic pathology showed no compound-related effects
    (Garvin et al, 1972).

    Long-term studies

    No information available.

    Observations in man

    No information available.

    COMMENTS

         A short-term study in rats on a protease preparation from
    A. oryzae did not reveal any adverse effects. Based on its lack of
    toxicity and the fact that A. oryzae varieties are used in the
    preparation of foods, this enzyme was considered to be acceptable for
    use in food.

    EVALUATION

    Level causing no toxicological effect

    Rat:      10% in the diet, equivalent to 7 g/kg b.w./day.

    Estimate of acceptable daily intake

         Acceptable for use in food when used according to good
    manufacturing procedures.

    REFERENCES

    Garvin, P.J., Ganote, C.E., Merubia, J., Delahany, E., Bowers, S.,
    Varuado, A., Jordan, L., Harley, G., DeSmet, C., & Porth, J. (1972).
    Protease from Aspergillus oryzae. Unpublished report from Travenol
    Laboratories, Inc., Morton Grove, IL, USA. Submitted to WHO by
    Gist-brocades NV, Delft, Holland.
    


    See Also:
       Toxicological Abbreviations