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    INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY

    WORLD HEALTH ORGANIZATION



    TOXICOLOGICAL EVALUATION OF SOME
    FOOD COLOURS, ENZYMES, FLAVOUR
    ENHANCERS, THICKENING AGENTS, AND
    CERTAIN FOOD ADDITIVES



    WHO FOOD ADDITIVES SERIES 6







    The evaluations contained in this publication were prepared by the
    Joint FAO/WHO Expert Committee on Food Additives which met in Rome,
    4-13 June 19741


    World Health Organization     Geneva     1975






              

    1  Eighteenth Report of the Joint FAO/WHO Expert Committee on
    Food Additives, Wld Hlth Org. techn. Rep. Ser., 1974, No. 557.
    FAO Nutrition Meetings Report Series, 1974, No. 54.

    MICROBIAL RENNET* (Endothia parasitica)

    Explanation

         This enzyme preparation has been evaluated for acceptable daily
    intake by the Joint FAO/WHO Expert Committee on Food Additives (see
    Annex 1, Ref. No. 27) in 1971.

         Since the previous evaluation additional data have become
    available and are summarized and discussed in the following monograph.
    The previously published monograph has been expanded and is reproduced
    in its entirety below.

    BIOLOGICAL DATA

    BIOCHEMICAL ASPECTS

         No information available.

    TOXICOLOGICAL STUDIES

    Acute toxicity

         Data are available for some commercial preparations.
                                                                

                        LD50
    Animal    Route     (mg/kg bw)     Reference
                                                                

    Mouse     Oral      >5 000         Delahunt & Stebbins, 1965

              i.v.         820         Delahunt & Stebbins, 1965

    Rat       Oral      >2 000         Delahunt & Stebbins, 1965

              i.v.         544         Delahunt & Stebbins, 1965
                                                                

              

    *    This preparation is prepared from the species Endothia
    parasitica.

    Short-term studies

    Rat

         Four groups of 10 male and 10 female rats received daily in their 
    diet for one year either 0, 8, 16 or 40 mg/kg bw of microbial rennet. 
    No adverse effects compared with controls were noted with regard to 
    survival, appearance, growth rate, food consumption, haematology, 
    urinalysis, serum chemistry, liver triglycerides, organ weights, 
    gross and histopathology (Delahunt & Stebbins, 1965).

    Dog

         Four groups of three male and three female beagles received daily
    for one year an oral capsule with 0, 8, 16 or 40 mg/kg bw of microbial
    rennet. There was no difference between controls and test groups
    related to the administration of the test compound as regards
    survival, appearance, behaviour, body weight, haematology, urinalysis,
    serum chemistry, serum electrophoresis, neurological and
    ophthalmological examination, organ weights, gross and histopathology
    (Delahunt & Stebbins, 1965).

    Long-term studies

    Rat

         Microbial rennet was fed to groups of 20 male and 20 female rats
    at a single level of 100 mg/kg bw in their diet for two years. No
    contemporary controls were used. A style first generation was produced
    as well. Neither the long-term study nor the multigeneration study
    revealed any compound-related abnormalities (Mosinger, 1972).

    Comments:

         The studies extending over one year in the rat and dog are
    available for evaluation and do not reveal any adverse effects at
    levels up to 40 mg/kg bw. A two-year single level study in rats did
    not reveal any deleterious effects. This meets the requirements laid
    down by the Committee. Chemical analysis for known microbial
    metabolites in the final product failed to detect their presence.

    EVALUATION

         Acceptable daily intake not specified.*

    REFERENCES

    Delahunt, C. S. & Stebbins (1965) Unpublished report

    Mosinger, M. (1972) Report submitted to WHO

              

    *    The statement "ADI not specified" means that, on the basis of the
    available data (toxicological, biochemical, and other), the total
    daily intake of the substance, arising from its use or uses at the
    levels necessary to achieve the desired effect and from its acceptable
    background in food, does not, in the opinion of the Committee,
    represent a hazard to health. For this reason, and for the reasons
    stated in individual evaluations, the establishment of any acceptable
    daily intake (ADI) in mg per kg of body weight is not deemed
    necessary.


    See Also:
       Toxicological Abbreviations