GLUCOSE ISOMERASE (IMMOBILIZED) FROM ACTINOPLANES MISSOURIENSIS

    EXPLANATION

         This enzyme preparation has not been previously 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 20 male and 20 female Sprague-Dawley rats were fed
    diets containing 0 or 1% whole, non-viable Actinoplanes
    missouriensis in the diet. After 60 days on test, males and females
    were mated on a 1-to-1 basis. The males were sacrificed after 90 days
    on test for organ-weight analysis and gross and microscopic pathology
    evaluation. The females were allowed to litter and nurse their young
    until weaning at 21 days. Body weights tended to be lower in male rats
    given the test compound but did not differ significantly from
    controls. Right gonad weights tended to be slightly higher in treated
    males and females. No compound-related changes were observed in
    haematology, urinalysis, clinical chemistry, or gross or microscopic
    pathology, nor were there any effects on reproductive performance of
    the offspring (Tisdel & Harris, 1974a).

    Acute toxicity
                                                               

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

    Rat (male)     Oral (dietary)   40,000        Regel, 1973

    Mouse (male)   i.v.             1,250         Regel, 1973

    Mouse (male)   i.v.             875-1,250     Regel, 1973

    Rabbit         s.c.             1,250         Regel, 1973
                                                               

    Short-term study

    Dogs

         Groups of 2 male and 2 female beagle dogs were fed for 90 days
    diets containing 0 or 1% whole, non-viable cells of Actinoplanes
    missouriensis. Body-weight gains and food consumption were less for
    the test dogs than controls, but remained in the normal range for dogs
    of their age during the course of the study. Results of haematology
    and urinalysis were normal for all animals and no compound-related
    effects on organ weights or gross and microscopic pathology were
    reported (Tisdel & Harris, 1974b).

    Long-term studies

         No information available.

    Observations in man

         No information available.

    Comments

         A well-conducted short-term study in rats, which included a
    1-generation reproduction study, showed no significant toxicological
    effects. A short-term study in dogs provides additional information on
    the lack of toxicity of the preparation.

         The studies on the non-immobilized enzyme were considered by the
    Committee to be appropriate for evaluating the immobilized form
    because the use of gelatin as an entrapping agent does not present a
    toxicological problem. The release of free glutaraldehyde from the
    enzyme preparation is controlled by the specifications for the
    preparation established by the Committee.

    EVALUATION

    Level causing no toxicological effect

    Rat: 1% (10,000 ppm) in the diet, equivalent to 1,000 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

    Regel, L. (1973). Untitled report on acute toxicity studies.
         Unpublished study of the Warf Institute, Inc., Madison, WI, USA.
         Submitted to the World Health Organization by Gist-Brocades.

    Tisdel, M. & Harris, D. (1974a). 90-Day subacute and reproduction
         study - Rat. Unpublished study of the Warf Institute, Inc.,
         Madison, WI, USA. Submitted to the World Health Organization by
         Gist-Brocades.

    Tisdel, M. & Harris, D. (1974b). 90-Day subacute and reproduction
         study - Dog. Unpublished study of the Warf Institute, Inc.,
         Madison, WI, USA. Submitted to the World Health Organization by
         Gist-Brocades.
    

    See Also:
       Toxicological Abbreviations