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


    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


    Synonyms                     Disodium EDTA; Disodium Edetate

    Chemical names               Disodium dihydrogen
                                 Disodium dihydrogen (ethylenedinitrilo)

    Empirical formula            C10H14N2Na2O8.2H2O

    Structural formula


    Molecular weight             372.24

    Definition                   Disodium ethylenediaminetetraacetate
                                 contains not less than 99.0 per cent. of

    Description                  Disodium ethylenediaminetetraacetate
                                 occurs as white, odourless crystalline
                                 granules or as a white to nearly white

    Use                          As a sequestrant.

    Biological Data

    Biochemical aspects

    See calcium disodium ethylenediaminetetraacetate.

    Special studies

         Disodium EDTA injected at levels of 3.4, 1.7 and 0.35 mg,/egg,
    gave 40, 50 and 85 per cent. hatch, respectively. At the highest
    level, some embryos which failed to hatch showed anomalies (McLaughlin
    & Scott, 1964).

    Acute toxicity


    Animal   Route     LD50                 References

    Rat      oral      2 000-2 200          Yang, 1964
    Rabbit   oral      2 300                Shibata, 1956
                       471                  Shibate, 1956

    1 Dose depending on the rate of infusion.

    Short-term studies

         Rat. Rats were fed for 44-52 weeks on a diet containing 0.5 per
    cent. disodium EDTA without any deleterious effect on weight gain,
    appetite, activity and appearance (Krum, 1948). In another experiment
    3 groups of 10-13 males and females were fed a low-mineral diet (0.54
    per cent. Ca and 0.013 per cent. Fe) with the addition of 0, 0.5 and 1
    per cent. disodium EDTA for 205 days. At the 1 per cent. level some
    abnormal symptoms were observed: growth retardation of the males,
    lowered erythrocyte and leucocyte counts, a prolonged blood
    coagulation time, slightly but significantly raised blood calcium
    level, a significantly lower ash content of the bone, considerable
    erosion of the molars and diarrhoea. Gross and histological
    examination of the major organs revealed nothing abnormal. Rats fed
    for 220 days on an adequate mineral diet containing 1 per cent.
    disodium EDTA showed no evidence of dental erosion (Chan, 1964).

         Groups of 6 rats ware maintained for 12 weeks on diets containing
    0.5, 1 and 5 per cent. disodium EDTA. No deaths occurred and there
    were no toxic symptoms except diarrhoea and lowered food consumption
    at the 5 per cent. level. Mating in each group was carried out when
    the animals were 100 days old. Mating was repeated 10 days after
    weaning the first litters. Parent generation rats of 0, 0.5 and 1 per
    cent. levels gave birth to normal first and second litters. The
    animals given 5 per cent. failed to produce litters (Yang, 1964). To
    elucidate possible teratogenic effects, daily doses of 20-40 mg/rat
    EDTA were injected intramuscularly into pregnant rats at days 6-9,
    10-15 and 16 to the end of pregnancy. A dose of 40 mg was lethal
    within 4 days but 20 mg was well tolerated, allowing normal foetal
    development; 40 mg, injected during days 6-8 or 10-15 produced some
    dead or malformed foetuses, especially polydactyl, double tail,
    generalised oedema or circumscribed head oedema (Tuchmann-Duplessis &
    Mercier-Parot, 1956).

         Groups of 5 male rats were given 250, 400 or 500 mg/kg
    body-weight disodium EDTA i.p. daily for 3-31 days; some groups were
    observed for another 2 weeks. At the 500 mg level all rats became
    lethargic and died within 9 days, the kidneys being pale and swollen,
    with moderate dilatation of bowl and subserosal haemorrhages.
    Histological examination of a number of organs showed lesions only in
    the kidneys. Animals at the 400 mg level died within 14 days, kidney
    and bowel symptoms being similar to the 500 mg level. One rat at the
    250 mg dose level showed haemorrhage of the thymus. All 3 groups
    showed varying degrees of hydropic necrosis of the renal proximal
    convoluted tubules with epithelial sloughing: recovery occurred in all
    groups after withdrawal of disodium EDTA (Reuber & Schmieler, 1962).

         Rabbit. Eight groups of 3 rabbits ware given either 0.1, 1, 10
    or 20 mg/kg body-weight disodium EDTA i.v., or 50, 100, 500 or 1000
    mg/kg body-weight orally for 1 month. All animals on the highest oral
    test level exhibited severe diarrhoea and died. In the other groups
    body-weight, haemogram, urinary nitrogen and urobilinogen were
    unaffected. Histopathological examination of a number of organs showed
    degenerative changes in the liver, kidney, parathyroid and endocrine
    organs and oedema in muscle, brain and heart at all levels of
    treatment (Shibata, 1956).

    Long-term studies

         Rat. In a 2-year study 5 groups totalling 33 rats were fed 0,
    0.5, 1 and 5 per cent. disodium EDTA. The 5 per cent. group showed
    diarrhoea and consumed less food than the rats in other groups. No
    significant effects on weight gain ware noted nor were blood
    coagulation time, red blood cell counts or bone ash adversely
    affected. The mortality of the animals could not be correlated with
    the level of disodium EDTA. The highest mortality rate occurred in the
    control group. Gross and microscopic examination of various organs
    revealed no significant differences between the groups (Yang, 1964).


         The long-term studies on rats are difficult to assess because of
    the small number of animals and the high mortality rate even in the
    control group. Metabolic studies and feeding, experiments demonstrate
    that the use of calcium disodium EDTA is preferable to that of
    disodium EDTA.


         Because of its effect on calcium, the use of disodium EDTA as a
    food additive is not recommended. Under certain circumstances,
    necessitating an accurate complexing of calcium, it may be used
    provided no excess of disodium EDTA remains and the only compound
    finally present is calcium disodium EDTA.


    Chan, M. S. (1964) Food Cosmet. Toxicol., 2, 763

    Krum  J. K. (1948) Thesis University, of Massachusetts

    McLaughlin, J. jr, & Scott, W. F. (1964) Fed. Proc., 23, 406

    Reuber, M. D. & Schmieller, G. C. (1962) Arch. environ. Health, 5,

    Shibata, S. (1956) Folio pharmacol. Jap., 52, 113

    Tuchmann-Duplessis, H. & Mercier-Parot L. (1956) C.R. Acad.
    Sci.,243, 1064

    Yang, Shou-Shih, (1964) Food Cosmet. Toxicol., 2, 763

    See Also:
       Toxicological Abbreviations