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    FAO Meeting Report No. PL/1965/10/2
    WHO/Food Add/28.65

    EVALUATION OF THE HAZARDS TO CONSUMERS RESULTING FROM THE USE OF
    FUMIGANTS IN THE PROTECTION OF FOOD

    The content of this document is the result of the deliberations of the
    Joint Meeting of the FAO Committee on Pesticides in Agriculture and
    the WHO Expert Committee on Pesticide Residues, which met 15-22 March
    19651

    Food and Agriculture Organization of the United Nations
    World Health Organization
    1965

             
    1 Report of the second joint meeting of the FAO Committee on
    Pesticides in Agriculture and the WHO Expert Committee on Pesticide
    Residues, FAO Meeting Report No. PL/1965/10; WHO/Food Add./26.65.

    ETHYLENE DIBROMIDE

    Compound

         Ethylene dibromide

    Chemical name

         Ethylene bromide

    Synonym

         1,2-dibromoethane, ethylene dibromide, glycol dibromide

    Empirical formula

         C2H4Br2

    Structural formula

    CHEMICAL STRUCTURE 

    Relevant physical and chemical properties

    Physical state (atmospheric pressure, 20C): colourless liquid

    Boiling-point: 131.6C

    Odour: characteristic chlorororm-like odour

    Lowest concentration in air which is detectable by odour: 25 ppm

    Flash point: non-flammable

    Solubility:

         Water: 0.431 g/100 ml

         Organic solvents: soluble in most common organic solvents

    Specific gravity (liquid): 2.17

    Specific gravity (gas): 6.49

    Uses

         Ethylene dibromide is frequently used for the fumigation of fresh
    fruit and stored cereals, millets and pulses and as a soil fumigant.

    It is also used in combination with other fumigants like ethylene
    dichloride, carbon tetrachloride and methyl bromide.

    Residues

         Ethylene dibromide has poor powers of penetration into bulked
    foodstuffs. It is physically absorbed and can be largely dispersed by
    aeration if sufficient time is allowed. Fruits with thick skins and
    some cereals are likely to retain small amounts of the fumigant almost
    indefinitely although except for avocados, pears and bananas, only
    insignificant amounts are to be found in the flesh. A portion of the
    compound may be converted into other forms of bromide, probably
    inorganic (Monro, 1961).

         Upon treating grain or cereal meal with ethylene dibromide only a
    small portion of the fumigant undergoes reaction, mainly with the
    protein, leading to the formation of inorganic bromide. The greater
    part of it remains unchanged, and being absorbed largely in the fat
    and to some extent in the starch, is slow to volatilize and disperse
    (Olomucki and Bondi, 1955).

         On wheat and wheat products, ethylene bromide is strongly
    absorbed, remains unchanged at ordinary temperatures and is very
    resistant to dispersion by airing, residues of the unaltered compound
    thus persisting. On heating, however, as in baking, most of the
    fumigant is lost by volatilization, but some breaks down to ethylene
    glycol which may react with the -SCH3 of the methionine in the wheat
    protein, while some is converted to hydrogen bromide which can cause
    splitting of the starch granule sheaths (Bridges, 1956). Analytical
    methods for determining these residues have been devised (Houser,
    1961).

         When wheat, whole or ground, was subjected artificially to
    fumigation with ethylene dibromide at 0.5 lb and 1.0 lb per 1000 ft3
    for 24 hours, more than 95% of unchanged ethylene dibromide could be
    recovered after 10 days, most of it being retained in the bran. Very
    little of it was converted to ionized bromide. The residues in whole
    grain after 10 days' aeration were 5.8 ppm and in the milled samples
    after 35 days' aeration were 4.5 ppm ethylene dibromide (Sinclair et
    al., 1962).

    Effect of fumigant on treated crop

         In addition to the residues of unchanged ethylene dibromide and
    of some inorganic bromide there may be a very slight change in the
    nature of the foodstuff protein, probably because of interaction with
    its methionine component (Olomucki and Bondi, 1955).

    BIOLOGICAL DATA

    Biochemical aspects

         The fate of ethylene dibromide absorbed from the mammalian
    alimentary tract has apparently not been determined. After uptake by
    the pulmonary route, however, some of the compound is excreted through
    the lungs and some of it is changed in the body with the formation of
    organic bromides (von Oettingen, 1955).

    Toxicological studies

    1. The fumigant

    Acute toxicity
                                                                   
    Animal           Route        LD50 mg/kg      Reference
                                  body weight
                                                                   

    Mouse, female    oral          420            Rowe et al., 1952

    Rat, male         "            146                  "

    Rat, female       "            117                  "

    Chick             "             79                  "

    Guinea-pig        "            110                  "

    Rabbit, female    "             55                  "
                                                                   

         A 43-year-old woman who took a single dose of ethylene dibromide
    amounting to 4.5 ml died 54 hours later after symptoms of vomiting,
    diarrhoea and anuria. At autopsy there was massive centro-lobular
    necrosis of the liver and proximal tubular damage in the kidney
    (Olmstead, 1960).

    Short- and long-term studies

         A total of 19 rats and guinea-pigs was fed ethylene dibromide in
    oil or 50% alcohol for about 4 months and there were no abnormal signs
    in those receiving about 40-50 mg per kg per day, but no pathological
    tests or autopsy examinations appear to have been undertaken (Aman et
    al., 1946).

         An experiment was also carried out in which fumigants in solution
    were administered directly into the crops of adult hens, the solvent
    being a mixture of equal parts of water and ethyl alcohol.
    Individually caged birds in groups of 10 were fed a standard ration

    ad libitum and were given, respectively, 1 mg, 2 mg, 4 mg and 20 mg
    ethylene dibromide per bird per day for 8 weeks. The controls received
    solvent only. At 8 and 20 mg per day both egg production rate and eggg
    size were diminished and at 2 and 4 mg per day egg size alone was
    depressed. At 1 mg per day there was no apparent difference from
    controls (Fuller and Morris, 1962).

         When the experiment was extended to groups of 24 pullets which
    were treated for 12 weeks, rested for 8 weeks and treated again for 12
    weeks it was found that levels of 21 mg and 8 mg per day of ethylene
    dibromide affected egg production and the lowest intake studied,
    namely, 0.5 mg per day, depressed egg size. At autopsy, the birds
    receiving 8 mg ethylene dibromide per day and showing lowered
    productivity were found to have an excessive number of incompletely
    developed ovarian follicles, but no abnormality in the brain, liver
    and kidneys (Fuller and Morris, 1962).

         Two-week-old chicks, in groups of 24, were fed for two weeks on a
    ration to which ethylene dibromide in ethanol and olive oil had been
    added at the rates of 20, 40 and 80 ppm. Estimates made from chemical
    analyses suggested that these amounts would be reduced by evaporation
    and by conversion to inorganic bromide to somewhat less than 10, 20
    and 40 ppm by the time the ration was consumed. At 10 and 20 ppm no
    change was observed in the chicks over the two weeks, but at 40 ppm
    there was retardation of growth rate, even when a correction was made
    for food intake (Morris and Fuller, 1963).

         Six-month-old pullets in groups of 10 were given ethylene
    dibromide either directly by injection into the crop, or indirectly in
    the diet after fumigation, daily intakes being 0.5, 1, 2, 4 and 8 mg
    per day. At 8 mg per day by both routes of administration, egg
    production was depressed, while egg weight was reduced at all levels
    down to 0.5 mg per bird, whether by crop or diet (Fuller and Morris,
    1963).

    2. The fumigated foodstuff

         When chickens were fed for five days, pigs for 12 days and
    heifers for one week on grain previously fumigated with a gaseous
    mixture containing 7.2% ethylene dibromide none of them showed any
    deleterious effects (Rowe et al., 1954).

         Twenty-five adult hens, in groups of five, were given a ration
    made up of 50% sorghum. In those groups receiving grain containing
    sorbed ethylene dibromide in amounts ranging from 50 to 320 ppm, there
    was a decrease in egg weight proportional to the level of the
    fumigant. Moreover, in those receiving the highest amount, egg laying
    ceased completely in six and a half weeks and, in those receiving 200
    ppm, it ceased within eight weeks. Even as little as 50 ppm had a
    depressive effect on egg size within three weeks. Further, those hens
    in which laying was arrested failed to resume when returned to a
    normal ration (Bondi et al., 1955).

         In another experiment with six-month-old hens in groups of 24 the
    sorghum, making up 50% of the grain fed, contained 10-15 ppm ethylene
    dibromide and 20 ppm residual bromide, 20-30 ppm ethylene dibromide
    and 50 ppm residual bromide and no free ethylene dibromide but 120 ppm
    residual bromide. The fourth group was a control. Over 16 weeks the
    group receiving only the residual bromide behaved the same as the
    controls, but those receiving ethylene dibromide showed a decrease in
    egg size proportional to dose. But when these birds were returned to a
    normal diet the egg size was regained (Bondi et al., 1955).

         In an experiment carried out with two groups each of five hens,
    all of which were laying small eggs (40% below normal) by being fed
    grain containing ethylene dibromide, the administration to one group
    of follicle stimulating hormone intravenously led to a partial
    recovery in egg size. Moreover, there was no reaction between ethylene
    dibromide and follicle stimulating hormone in sorghum. It is therefore
    postulated that the ethylene dibromide acts on the formation or
    release of pituitary follicle stimulating hormone (Olomucki, 1957).

         A group of laying hens that was fed for 23 days with oats
    fumigated with ethylene dibromide several months previously showed
    some diminution of egg size compared with controls and when the grain
    had been treated the day before with Dowfume EB5 (containing 63.6%
    carbon tetrachloride, 29.2% ethylene dichloride and 7.2% ethylene
    dibromide by weight) at 10 times the recommended dose, egg output and
    size declined rapidly in 10 days (Bierer and Vickers, 1959).

         Five groups, each of 16 pullets six months of age, were fed for
    19 days on:

    (i)  a protein laying ration, plus non-fumigated oats;

    (ii)  a protein laying ration, plus oats fumigated at the rate of 1.1
          ml/kg;

    (iii) a protein laying ration, plus oats fumigated at the rate of 3.3
          ml/kg;

    (iv)  a commercial, all-mash ration, non-fumigated;

    (v)   a commercial, all-mash ration, the corn component of which had
          been fumigated previously at the rate of 1.1 ml/kg.

         The fumigant was a commercial mixture containing carbon
    tetrachloride 64%, ethylene dichloride 29% and ethylene dibromide 7%.
    After fumigation the grain was allowed to air for two weeks.

         In those groups which received fumigated oats, egg size was
    seriously and significantly depressed, more so at the heavy dosage
    (when production was totally arrested) than at the lower dosage. A
    smaller but still significant depression of egg production was

    observed in the birds on the mash ration containing fumigated oats
    subsequently ground (Caylor and Laurent, 1960).

    Comments on the experimental studies reported

    1. When ethylene dibromide is used as a fumigant on food products a
    little of the compound may be converted to inorganic bromides by
    reaction with the foodstuff, but the major part remains absorbed in
    the unchanged form for some time.

    2. As far as can be judged from the experimental studies here
    reported, the quantity of inorganic bromide is usually insufficient to
    be of any serious consequence when food products previously fumigated
    with ethylene dibromide are consumed.

    3. Similarly, there is little reason to believe that the limited
    changes brought about chemically in the foodstuff by the action of
    ethylene dibromide on its components are responsible for any
    significant changes in its food value or for the production of any
    toxic substances.

    4. On the other hand, the deleterious effects observed experimentally
    with the feeding of fumigated rations to animals can be attributed, in
    all probability, to the residue of unchanged etnylene dibromide.

    5. The feeding studies carried out with ethylene dibromide, either fed
    directly or as a residue after fumigation, are principally concerned
    with poultry. This is a species which seems particularly sensitive to
    the compound, for the other experiments on animals, though limited,
    give little indication of toxicity.

    6. This action of ethylene dibromide on poultry may be due to
    interference with the hormonal balance.

    Evaluation

         On the available toxicological evidence ethylene dibromide should
    be used for fumigation of foodstuffs only on condition that no residue
    (the sensitivity of the present analytical method being 1 ppm) of the
    unchanged compound will reach the consumer.

         The small residue of inorganic bromide is unlikely to make any
    significant contribution to the total bromide content of the
    foodstuff.

    Further work required

         Further investigation of the effect of processing and cooking on
    residual ethylene dibromide in food.

         Feeding studies should be carried out on two mammalian species to
    determine the effect of long-term feeding of ethylene dibromide with
    particular reference to reproduction.

    REFERENCES

    Aman, J., Farkas, L. & Ben-Shamai, M. H. (1946) Ann. appl. Biol.,
    33, 389

    Bierer, B. W. & Vickers, C. L. (1959) J. Amer. vet. med. Ass.,
    134, 452

    Bondi, A., Olomucki, E. & Calderon, M. (1955) J. Sci. Food Agric.,
    6, 600

    Bridges, R. G. (1956) J. Sci. Food Agric., 7, 305

    Caylor, J. F. & Laurent, C. K. (1960) Poultry Sci., 39, 216

    Fuller, H. L. & Morris, G. K. (1962) Poultry Sci., 41, 645

    Fuller, H. L. & Morris, G. K. (1963) Poultry Sci., 42, 508

    Heuser, S. G. (1961) J. Sci. Food Agric., 12, 103

    Monro, H. A. U. (1961) Manual of fumigation for insect control, FAO,
    Agric. Studies, 56

    Morris, G. K. & Fuller, H. L. (1963) Poultry Sci., 42, 15

    von Oettingen, W. F. (1955) The halogenated aliphatic, olefinic,
    cyclic, aromatic and aliphatic-aromatic hydrocarbons, including the
    halogenated insecticides, their toxicity and potential dangers,
    Public Health Service Publ. No. 414

    Olmstead, E. V. (1960) Arch. environm. Hlth, 21, 525

    Olomucki, E. (1957) Nature (Lond.), 180, 1358

    Olomucki, E. & Bondi, A. (1955) J. Sci. Food Agric., 6, 592

    Rowe, V. K., Hollingsworth, R. L. & McCollister, D. D. (1954) J.
    Agric. Food Chem., 2, 1318

    Rowe, V. K., Spencer, H. C., McCollister, D. D., Hollingsworth, R. L.
    & Adams, E. M. (1952) Arch. industr. Hyg., 6, 158

    Sinclair, W. B., Lindgren, D. L. & Forbes, R. (1962) J. econ. Ent.,
    55, 836
    


    See Also:
       Toxicological Abbreviations
       Ethylene dibromide (ICSC)
       Ethylene dibromide (FAO/PL:CP/15)
       Ethylene dibromide (FAO/PL:1967/M/11/1)
       Ethylene dibromide (FAO/PL:1968/M/9/1)
       Ethylene Dibromide (IARC Summary & Evaluation, Volume 71, 1999)