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    GLUCOSE ISOMERASE (IMMOBILIZED) FROM STREPTOMYCES OLIVACEUS

    EXPLANATION

         This enzyme preparation has not previously been evaluated by the
    Joint FAO/WHO Expert Committee on Food Additives.

    BIOLOGICAL DATA

    Biochemical aspects

         No information available.

    Toxicological studies

    Special study on reproduction

    Rats

         Groups of 10 male and 10 female Charles-River CD rats were fed
    diets containing 0, 1.5, 3.0, or 6.0% immobilized glucose isomerase
    for 100 days, at which time they were mated on a one-to-one basis.
    Groups of 15 males and 15 females (F1 generation) that resulted from
    the mating were fed the same diets for 90 days; the animals were then
    sacrificed for gross and microscopic pathology studies. No compound-
    related effects were reported with respect to fertility indices, body
    weights, food consumption, ophthalmoscopy, haematology, clinical
    chemistry, urinalysis, or gross or microscopic pathology (Geil
    et al., 1975).

    Acute toxicity
                                                                                         

                                                       LD50
    Species   Material tested      Route            (mg/kg b.w.)   Reference
                                                                                     

    Rat       S. olivaceus         oral (gavage)    2500           Hartnagel, 1970
              cells

    Rat       S. olivaceus         oral (gavage)    50             Porter &
              fermenter beer                        ml/kg          Hartnagel, 1974

    Rat       non-immobilized      oral (gavage)    3330           Hartnagel, 1971
              glucose isomerase

    Rat       immobilized          oral (gavage)    3330           Hartnagel, 1971
              glucose isomerase
                                                                                     
    
    Short-term studies

    Rats

         Groups of 15 male and 15 female Charles-River CD rats were fed
    diets containing 0, 1.5, 3.0, or 6.0% immobilized glucose isomerase
    for 90 days. Haematology, clinical chemistry, and urinalysis
    measurements were conducted on 5 rats/sex/dose at 90 days, and on 5
    male and 5 female control and high-dose animals at 30 and 60 days.
    Gross pathology studies were conducted on all animals and microscopic
    pathology was conducted on 5 males and 5 females from the high-dose
    groups and controls. Total leucocyte counts were elevated in the high-
    and mid-dose animals at 90 days. There were no reported compound-
    related changes with respect to body-weight gain, food consumption,
    ophthalmoscopy, clinical chemistry, urinalysis, organ weights, or
    gross or microscopic pathology (Benson et al., 1975).

    Dogs

         Groups of 4 male and 4 female beagle dogs were fed diets
    containing 0, 1.5, 3.0, or 6.0% immobilized glucose isomerase in the
    diet for 90 days. One female control dog died during the study; the
    likely cause of death was pneumonia. Other dogs on test also developed
    acute pneumonia, possibly related to rooting and sniffing in the
    powdered diet. The pathology report indicated that acute exudative
    (lung) lesions noted in control and all treatment groups likely
    resulted from secondary bacterial infection in areas of the lung
    previously damaged by lung worms (Cookson et al., 1975).

         Because of the lung pathology noted above in the first dog study,
    a new study was undertaken. Groups of 4 male and 4 female beagle dogs
    were fed diets containing 0, 1.5, 3.0, or 6.0% immobilized glucose
    isomerase for 90 days. No compound-related changes occurred with
    respect to body-weight gain, food consumption, ophthalmoscopy,
    haematology, clinical chemistry, urinalysis, organ weights, or gross
    or microscopic pathology. Lung lesions occurred at a high incidence in
    all dose groups and the controls and may have been due to infection
    with parasitic larvae in the lungs (Harris & Teeter, 1976).

    Long-term studies

         No information available.

    Observation in man

         No information available.

    Comments

         No compound-related adverse effects were reported when dietary
    levels of up to 6% of immobilized glucose isomerase were fed to rats
    in reproduction and subchronic toxicity studies and to dogs in
    subchronic toxicity studies.

    EVALUATION

    Level causing no toxicological effect

    Rat: 6% (60,000 ppm) in the diet, equivalent to 6000 mg/kg b.w./day.

    Estimate of Acceptable Daily Intake for Man

    Acceptable for use in food processing when used as a component in an
    immobilized system.

    REFERENCES

    Benson, B.W., Geil, R.G., Keller, W.F., & Blanchard, G.L. (1975).
         Subchronic studies of the toxicity of glucose isomerase enzyme;
         II. Ninety day feeding study in rats. Unpublished study of the
         International Research and Development Corporation. Submitted to
         the World Health Organization by Miles Laboratories, Inc.

    Cookson, K.M., Geil, R.G., & Keller, W.F. (1975). Subchronic studies
         of the toxicity of glucose isomerase enzyme: I. Ninety day
         feeding study in dogs. Unpublished study of the International
         Research and Development Corporation. Submitted to the World
         Health Organization by Miles Laboratories, Inc.

    Geil, R.G., Benson, B.W., Harris, S.B., & Keller, W.F. (1975).
         Subchronic studies of the toxicity of glucose isomerase enzyme:
         III. Two generation feeding study in rats. Unpublished study of
         the International Research and Development Corporation. Submitted
         to the World Health Organization by Miles Laboratories, Inc.

    Harris, D.L. & Teeter, C.L. (1976). Subchronic studies of the toxicity
         of glucose isomerase enzyme; IV. Ninety day feeding study in
         dogs. Unpublished study of the WARF Institute Inc. Submitted to
         the World Health Organization by Miles Laboratories, Inc.

    Hartnagel, R.E. (1970). The acute oral toxicity of a strain of glucose
         isomerase-producing S. olivaceus cells. Unpublished study of
         Miles Laboratories, Inc. Submitted to the World Health
         Organization by Miles Laboratories, Inc.

    Hartnagel, R.E. (1971). The acute oral toxicity of fixed and non-fixed
         glucose isomerase and isomerized syrup. Unpublished study of
         Miles Laboratories Inc. Submitted to the World Health
         Organization by Miles Laboratories, Inc.

    Porter, M.C. & Hartnagel, R.E. (1974). Study of the acute oral
         toxicity of glucose isomerase fermentor beer in the rat.
         Unpublished study of Miles Laboratories, Inc. Submitted to the
         World Health Organization by Miles Laboratories, Inc.
    


    See Also:
       Toxicological Abbreviations