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    WHO/Food Add./24.65
    FAO Nutrition Meetings
    Report Series No. 38A




    SPECIFICATIONS FOR IDENTITY AND 
    PURITY AND TOXICOLOGICAL EVALUATION 
    OF SOME ANTIMICROBIALS AND 
    ANTIOXIDANTS





    The content of this document is the result of the deliberations of the
    Joint FAO/WHO Expert Committee on Food Additives which met 8-17
    December 1964a





                   

    a Eighth Report of the Joint FAO/WHO Expert Committee on Food
    Additives, Wld Hlth Org. techn. Rep. Ser., 1965, 309; FAO
    Nutrition Meetings Report Series 1965, 38.


    PHOSPHORIC ACID

    CHEMICAL NAMES        Phosphoric acid; orthophosphoric acid

    EMPIRICAL FORMULA     H3PO4

    MOLECULAR WEIGHT      98.0

    DEFINITION            Phosphoric acid contains not less than 85% of
                          H3PO4

    DESCRIPTION           Clear, colourless, odourless liquid of syrupy
                          consistency.  Miscible with water and ethanol.

    NATURAL OCCURRENCE    Phosphorus-containing substances occur very
                          widely in natural foods usually as free
                          phosphoric acid or as the potassium, sodium or
                          calcium salts.  Phosphate is found in highest
                          concentrations (0.1-0.5% or more, in terms of
                          phosphorus) in such foods as milk, cheese,
                          nuts, fish, meat, poultry, eggs (yolk), and
                          certain cereals.

    USE                   As a sequestrant, an antioxidant and a
                          "synergist" for other antioxidants; also as an
                          acidulant and flavour in beverages and fruit
                          products.

    Biological Data

    Biochemical aspects

    Phosphoric acid is an essential constituent of the human organism, not
    only in the bones and teeth, but also in many enzyme systems.
    Phosphorus plays an important role in carbohydrate, fat and protein
    metabolism.

    The daily intake of phosphate necessary for man lies between 1 and 
    2 g.  Insufficient supply of phosphate produces deficiency in the
    bones. Since the phosphate concentration of serum and tissues is
    maintained by physiological regulations, the intestinal absorption
    depends on requirements and is therefore limited.  Doses of 2 to 4 g
    act as weak saline cathartics.  Excretion takes place mainly in the
    faeces as calcium phosphate, so that the continuous use of excessive
    amounts of sodium phosphate and phosphoric acid may cause a loss of
    calcium.

    There have been a great many publications on phosphorus metabolism,1
    on the interrelationships of calcium and phosphorus in foods and
    nutrition,2 and on the impact thereon of the use of phosphate as a
    food additive.3

    Short-term studies

    Rat.  Pathological effects in the parathyroids, kidneys and bones
    have been observed in mature male rats fed a diet containing an
    excessively high level (8%) of sodium orthophosphate for 7 months or
    until the animals succumbed.4  Histological and histochemical changes
    in the kidneys have been found in rats fed for 24 to 72 hours on a
    diet containing an excess of inorganic phosphate (10% disodium acid
    phosphate).5

    There are many other reports of adverse effects produced in rats and
    other laboratory animals by an excessive intake of inorganic
    phosphate.6,7,8,9,10

    Three groups of 12 rats each were fed diets containing added dibasic
    potassium phosphate so that the calcium and phosphorus concentrations
    in the experimental diets were as follows:

                                                        

           Diet                Calcium       Phosphorus
                                 %               %
                                                        

    Control                     0.56            0.42
    "Normal orthophosphate"     0.47            0.43
    "High orthophosphate"       0.50            1.30
                                                        

    The experiment was conducted in three stages, with experimental
    observations made when animals had consumed the test diets for 50, 60
    and 150 days.  No adverse physiological effects were observed
    clinically, at autopsy or on histological examination.  All the data
    obtained from this study indicated that there was probably adequate
    absorption and utilization of calcium, phosphorus and iron with both
    high and normal levels of orthophosphate.11

    Man.  Studies on 15 students, who drank 2000-4000 mg of phosphoric
    acid in fruit juices every day for 10 days, and on 2 males who
    received 3900 mg of phosphoric acid every day for 14 days, revealed no
    observable change in urine composition indicative of a disturbed
    metabolism.12

    Long-term studies

    Rat.  Three successive generations of rats were fed diets containing
    0.4% and 0.75% of phosphoric acid for 90 weeks.  No harmful effect on
    growth or reproduction could be observed.  No significant differences
    were noted in the blood picture in comparison with control rats and
    there was no other pathological finding which was attributable to the
    diets.  There was no acidosis, nor any change in the calcium
    metabolism.  The dental attrition was somewhat more marked than that
    in the control rats.13

    Comment on experimental studies reported

    Phosphoric acid is a material that should not be evaluated solely on
    the basis of toxicological studies in animals.

    There are strong indications that phosphoric acid should not be used
    in such a manner as to result in excessively high phosphorus levels in
    the total diet, adverse alterations in the mineral balance of the diet
    (i.e. Ca/P ratio), or an appreciable increase in the total mineral
    content of the diet as a whole.  This is discussed in greater detail
    in the Seventh Report of the FAO/WHO Expert Committee on Food
    Additives (page 31), where an estimate of the total acceptable dietary
    intake of phosphorus from both foods and food additives is made.

    However, there is ample evidence to support the safety of the addition
    of small quantities of phosphoric acid to food.  Thus, the use of
    0.01-0.02% as a sequestrant, an antioxidant or "synergist" in
    antioxidant mixtures should present no health hazards whatsoever.

    Moreover, the use of phosphoric acid to compensate for deficiency of
    fruit acidity, as a flavour component, and in other ways, essentially
    within the "normal" concentration of phosphates naturally occurring in
    foods, should present no problem.

    Evaluation

    Level causing no significant toxicological effect in the rat

    0.75% (=7500 ppm) in the diet, equivalent to 375 mg/kg body-weight per
    day.

    Estimate of acceptable daily intakes for man

                                         mg/kg body-weight

             Unconditional acceptance           0-5
             Conditional acceptance             5-15

    The total dietary intake of phosphorus from both foods and food
    additives should not exceed:

                                         mg/kg body-weight

             Unconditional acceptance         up to 30
             Conditional acceptance             30-70

    References

    1.  McElroy, W. D. & Glass. B., eds. (1952) Phosphorus metabolism - a
    symposium on the role of phosphorus in the metabolism of plants and
    animals, Baltimore, Johns HopkIns Press, vol. 2

    2.  Sherman, H. C. (1947) Calclium and phosphorus in food and
    nutrition, New York, Columbia University Press

    3.  Lang, K. (1959) Z. Lebensmitt.-Untersuch., 11O, 450

    4.  Saxton, J. A., jr & Ellis, G. M. (1941) Amer. J. Path., 17, 590

    5.  Craig, J. M. (1957) Amer. J. Path., 33, 621

    6.  House, W. B. & Hogan, A. G. (1955) J. Nutr., 55, 507

    7.  Maynard, L. A., Boggs, D., Fisk, G. & Seguin, D. (1957) J. Nutr.,
    64, 85

    8.  Selye, H. & Bois, P. (1956) Amer. J. Physiol., 187, 41

    9.  MacKay, E. M. & Oliver, J. (1935) J. exp. Med., 61, 319

    10. Behrens, B. & Seelkopf, K. (1932) Arch. exp. Path., 169, 238

    11. Dymsza, H.A., Reussner, G., jr & Thiessen, R., jr (1959) J. Nutr.,
    69, 419

    12. Laurens, F. (1953) Z. Lebensmitt.-Untersuch., 96, 418

    13. Bonting, S. L. & Jansen, B. C. (1956) Voeding, 17, 137
    


    See Also:
       Toxicological Abbreviations
       Phosphoric acid (ICSC)
       PHOSPHORIC ACID (JECFA Evaluation)
       Phosphoric acid (UKPID)