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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 OXIDE

    Compound

         Ethylene oxide

    Chemical name

         Ethylene oxide

    Synonyms

         Oxirane, 1,2-epoxyethane

    Empirical formula

         C2H4O

    Structural formula

    CHEMICAL STRUCTURE 

    Relevant physical and chemical properties

    Physical state (atmospheric pressure, 20°C): gas

    Boiling-point: 10.7°C

    Odour: irritating, mustard-like

    Lowest concentration in air which is detectable by odour: hard to
    detect in low concentrations

    Flash point: < -18°C (open cup)

    Flammability limits in air: 3-80% by volume

    Solubility:

         Water: soluble in all proportions

         Organic solvents: infinitely soluble in alcohol and ether

    Specific gravity (liquid): 0.887

    Specific, gravity (gas). 1.52

    Uses

         Ethylene oxide is used as an insecticide and sterilant for a wide
    variety of foodstuffs. It is used mainly in vacuum fumigation mixed
    with different proportions of carbon dioxide or non-flammable
    halogenated hydrocarbons, such as dichloro-difluoromethane, to provide
    non-explosive conditions. For insect control in foodstuffs fumigated
    under vacuum a usual application rate is 100 g/m3 for three hours at
    temperatures between 20°C and 25°C; for sterilizing foodstuffs 500
    g/m3 for six hours at similar temperatures.

    Residues

         Residues of gaseous ethylene oxide as high as 68 ppm have been
    reported in wheat fumigated by ethylene oxide at atmospheric pressure
    and under vacuum in commercial treatments or in experiments simulating
    practical conditions (Lubatti, 1944; El Nahal, 1954). Residues in raw
    copra fumigated at atmospheric pressure did not exceed 4.5 ppm
    (Benedict, 1957).

    Effect of fumigant on treated crop

         The chemical reactions of ethylene oxide with the ingredients of
    certain foodstuffs have to be considered with the foodstuff as a
    whole.

         When proteins are exposed to ethylene oxide, the -COOH, -NH2,
    -C6H4OH and -SH end groups react with the fumigant to give the
    corresponding hydroxy-ethyl compounds (Bruhin et al., 1961a).

         Fumigation of prunes with ethylene oxide-C14 revealed that the
    major fraction of the fumigant is bound to prune cellulose as
    hydroxyethyl cellulose. The only toxic products derived from ethylene
    oxide were ethylene glycol and diethylene glycol in amounts of 0.002%,
    dry weight (Gordon et al., 1959).

    BIOLOGICAL DATA

    Biochemical aspects

    No information available

    Acute toxicity

                                                                   
    Animal       Route         LD50 mg/kg       Reference
                               body-weight
                                                                   

    Rat          oral            330           Bruhin et al., 1961b

    Guinea-pig    "              270                   "
                                                                   

         Ethylene oxide has a moderate toxicity for rats. At a single oral
    does of 0.1 g/kg all animals survived. Doses of 0.2 g/kg killed all
    animals (Hollingsworth et al., 1956).

    Short-term studies

         Mice. Germ-free inbred albino mice were accidentally placed,
    for 150 days, on ground corn-cob bedding treated with ethylene oxide
    by the manufacturer. All males died with massive hemorrhages in the
    thoracic and abdominal cavities and other sites, failure of the blood
    to clot and jaundice (Reyniers et al., 1964). These findings agree
    with the results in other similar experiments (Allen et al., 1962).

         Rat. Feeding experiments with rats given fumigated diets
    resulted in loss of body-weight of the animals and in early death,
    probably due to thiamine destruction. Gain in weight started after
    oral thiamine supplementation (Hawk and Mickelsen, 1955). In another
    experiment young rats fed fumigated diets showed slight growth
    retardation in the first week; in the second week weight gain was
    normal (Oser and Hall, 1956).

         Four groups of five young female rats were given 0.1 mg/kg (15
    doses in 21 days), 0.03, 0.01 and 0.003 mg/kg (22 doses in 30 days)
    in cold olive oil. There was no mortality due to the experimental
    material. Doses of 0.1 mg/kg caused a marked loss of body-weight,
    gastric irritation and a slight liver damage. The groups doses with
    0.03, 0.01, and 0.003 mg/kg showed no adverse effects attributable
    to ethylene oxide as judged by growth, haemotology, blood urea,
    N-determinations, organ-weights and gross and microscopic examination
    of the tissues (Hollingsworth et al., 1956).

         Man. Thirty-seven industrial workers, engaged in manufacturing
    ethylene oxide, showed no ill effects at 5-10 ppm levels over an
    average service of 10 years with an exposure of eight hours daily
    (Joyner, 1964).

         Thiess (1963) described the symptoms of ethylene oxide poisoning
    derived from 41 cases as follows: after a short time of exposure
    periodical vomiting; irritation of the respiratory passages leading to
    emphysema, bronchitis and pulmonary oedema. Skin application caused
    blisters.

    Long-term studies

         No information available.

    Comments on experimental studies reported

         The feeding studies are not satisfactory because of the small
    number of animals and because only rats have been used.

    Evaluation

         Since no long-term experiments are available, no acceptable daily
    intake for ethylene oxide can be estimated.

    Further work required

         The reaction of ethylene oxide with food should be further
    investigated to determine the identity of the reaction products. The
    nutritional and toxicological aspects of any changes that are detected
    should be evaluated. Long-term experiments with the unchanged fumigant
    should be carried out in two species.

    REFERENCES

    Allen, R. C., Meier, H. & Hoag, W. G. (1962) Nature (Lond.), 193,
    387

    Benedict, J. H. (1957) J. Amer. Oil Chem. Soc., 34, 450

    Bruhin, H., Bühlmann, X., Vischer, W. A. & Lammers, T. (1961a)
    Schweiz. med. Wschr., 91, 607

    Bruhin, H., Bühlmann, X., Vischer, W. A. & Lammers, T. (1961b)
    Schweiz. med. Wschr., 91, 635

    El Nahal, A. K. N. (1954) J. Sci. Food Agric., 5, 205

    Gordon, H. T., Thornburg, W. W. & Werum, L. N. (1959) J. Agric. Food
    Chem., 7, 196

    Hawk, E. A. & Mickelsen, O. (1955) Science, 121, 442

    Hollingsworth, R. L., Rowe, V. K., Oyen, F., McCollister, D. D. &
    Spencer, H. C., (1956) Arch. industr. Hlth, 13, 217

    Joyner, R. E. (1964) Arch. environm. Hlth, 8, 700

    Lubatti, O. F, (1944) J. Soc. Chem. Ind. (Lond.), 63, 353

    Lubatti, O. F. & Harrison (1944) J. Soc. Chem. Ind. (Lond.), 63,
    353

    Oser, B. L. & Hall, L. A. (1956) Food Techn., 10, 175

    Reyniers, J. A., Sachsteder, M. R. & Ashburn, L. L. (1964) J. nat.
    Cancer Inst., 32, 1045

    Thiess, A. M. (1963) Arch. Toxikol., 20, 127
    


    See Also:
       Toxicological Abbreviations
       Ethylene oxide (EHC 55, 1985)
       Ethylene oxide (HSG 16, 1988)
       Ethylene oxide (ICSC)
       ETHYLENE OXIDE (JECFA Evaluation)
       Ethylene oxide (FAO/PL:1968/M/9/1)
       Ethylene oxide (WHO Pesticide Residues Series 1)
       Ethylene oxide (CICADS 54, 2003)
       Ethylene Oxide (IARC Summary & Evaluation, Volume 60, 1994)