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 formulaRelevant 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)