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    FAO Nutrition Meetings
    Report Series No. 40A,B,C
    WHO/Food Add./67.29




    TOXICOLOGICAL EVALUATION OF SOME
    ANTIMICROBIALS, ANTIOXIDANTS, EMULSIFIERS,
    STABILIZERS, FLOUR-TREATMENT AGENTS, ACIDS AND BASES





    The content of this document is the result of the deliberations of the
    Joint FAO/WHO Expert Committee on Food Additives which met at Rome,
    13-20 December, 19651 Geneva, 11-18 October, 19662




                   

    1 Ninth Report of the Joint FAO/WHO Expert Committee on Food
    Additives, FAO Nutrition Meetings Report Series, 1966 No. 40; 
    Wld Hlth Org. techn. Rep. Ser., 1966, 339

    2 Tenth Report of the Joint FAO/WHO Expert Committee on Food
    Additives, FAO Nutrition Meetings Report Series, 1967, in press; 


    Food and Agriculture Organization of the United Nations
    World Health Organization
    1967


    CALCIUM SORBATE

    Chemical name                Calcium sorbate, Calcium salt of
                                 trans,trans-2,4- hexadienoic acid

    Empirical formula            C12H14Cao4

    Structural formula

    MOLECULAR STRUCTURE 13

    Molecular weight             262.32

    Definition                   Calcium sorbate contains not less than
                                 98 per cent. and not more than the
                                 equivalent of 102 per cent. of C12H14CaO4
                                 after drying.

    Description                  Calcium sorbate occurs as a fine white
                                 crystalline powder.

    Uses                         As an antimicrobial and fungistatic
                                 agent.

    Biological Data

    (See Potassium Sorbate)

    POTASSIUM SORBATE

    Chemical names               Potassium sorbate; Potassium salt of
                                 trans,trans-2,4- hexadienoic acid

    Empirical formula            C6H7O2K

    Structural formula

    MOLECULAR STRUCTURE 14

    Molecular weight             150.22

    Definition                   Potassium sorbate contains not less than
                                 98 per cent. and not more than the
                                 equivalent of 102 per cent. of
                                 C6H7O2K. 

    Description               Potassium sorbate occurs as white or yellowish-
                              white crystals or crystalline powder.

    Uses                      As an antimicrobial and fungistatic agent.

    Biological Data

    Biochemical aspects

          The studies on the metabolism of 14C-labelled sorbic acid were
    performed by using either sorbic acid neutralized with sodium
    hydroxide (Fingerhut et al., 1962) or the potassium salt (Westöö,
    1964).

    Acute toxicity

                                                                                              

    Substance             Animal    Route     LD50               References
                                              (mg/kg 
                                              body-weight)
                                                                                          

    Sodium sorbate        rat       oral      7 160              Smyth & Carpenter, 1948
    Sodium sorbate        rat       oral      4 000 and 5 940    Deuel et al., 1954
    Potassium sorbate     rat       oral      4 920              Mellon Institute, 1954
    (solid isomer)
    Potassium sorbate     rat       oral      6 170              Mellon Institute, 1954
    (mixed isomer)
    Sodium sorbate        mouse     i.p.      2 500              Rhône-Poulenc, 1965
    Potassium sorbate     mouse     i.p.      1 300              Rhône-Poulenc, 1965
                                                                                          
    
    Short-term studies

          Rat. Groups of 10 rats (5 male and 5 female) were fed potassium
    sorbate (solid or mixed isomers) at levels of 0, 1, 2, 5 and 10 per
    cent. of the diet for 3 months. Body-weight gain was initially
    depressed at 10 per cent., and, to a lesser degree, in the 5 per cent.
    female group. There are no figures given for the food consumption
    during this time. At the end of the experiment, the weights of the
    rats receiving 10 per cent. of either isomer were slightly depressed,
    but the food consumption of these animals was smaller. The food
    efficiency (weight gain/g food) was practically the same as in the

    control group. Relative liver weights were the same in all groups.
    Kidney weights were increased at the 10 per cent. level, probably due
    to the high potassium load. This was also noted to a lesser degree at
    the 5 per cent. level. Gross pathological examination showed no
    abnormalities, even in the 10 per cent. level groups (Mellon
    Institute, 1954).

          Dog.  Eight dogs received 1 per cent. and 8 dogs 2 per cent. of
    the solid or mixed isomers of potassium sorbate in the diet for 3
    months; 4 dogs were used as controls. There were no differences in
    weight gain. Gross examination on autopsy showed no evidence of a
    deleterious affect attributable to the sorbates (Mellon Institute,
    1954).

    Comments

          The level of 10 per cent. and even per cent. potassium sorbate
    causes a very high potassium intake. The food consumption of 15
    g/rat/day results in a daily intake of 12 meq. K for the 10 per cent.
    level group. The normal daily allowance for the mature rat is 1.5 meq.
    K.

          When considering the results of the short-term studies,
    allowance, has been made for the adverse effects of high potassium
    intake. Accordingly it was concluded that the same no-effect level
    could be accepted for evaluation of sorbic acid and its Ca and K
    salts.

          It is desirable that long-term studies be carried out on animals
    and metabolic investigations in man using the Ca or K salts.

    Evaluation

    Level causing no toxicological effect

          Rat. 50 000 ppm in the diet, equivalent to 2500 mg/k
    body-weight/day.

    Estimate of acceptable daily intakes for man

                                           mg/kg body-weight1

       Unconditional acceptance                  0-12.5
       Conditional acceptance                    12.5-25



                   

    1 As the sum of sorbic acid and Ca and K sorbates (calculated as
    sorbic acid).

    REFERENCES

    Deuel, H. J. jr et al. (1954)Food Res., 19, 1

    Fingerhut, M., Schmidt, B. & Lang, K. (1962) Biochem. Z., 366, 118

    Mellon Institute (1954) Unpublished report

    Rhône-Poulenc (1965) Unpublished report

    Smyth, H. F. jr & Carpenter, C. P. (1948) J industr. Hyg. Toxicol.,
    30, 63

    Westöö, E. (1964) Acta chem. scand., 18, 1373

    


    See Also:
       Toxicological Abbreviations