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 DICHLORIDE Compound Ethylene dichloride Chemical name Ethylene chloride Synonyms 1,2-dichloroethane; ethylene dichloride; glycoldichloride Emperical formula C2H4Cl2 Structural formulaRelevant physical and chemical properties Physical state (atmospheric pressure, 20°C): colourless liquid Boiling-point: 83.5°C Odour: chloroform-like odour Lowest concentration in air which is detectable by odour: 50 ppm Flash point: ca 12°C (open cup) Flammability limits in air: 6.2 to 15.9% by volume Solubility: Water: insoluble Organic solvents: soluble in most common organic solvents Specific gravity (liquid): 1.26 Specific gravity (gas): 3.42 Uses Ethylene dichloride, being flammable, is rarely used alone. When mixed with carbon tetrachloride it is extensively used as a liquid grain fumigant for bulk storage in bins or on floors. The mixture generally used is in the proportion of 3:1 by volume of ethylene dichloride and carbon tetrachloride, this being the smallest proportion of the latter which renders the mixture non-flammable. A small proportion of ethylene dibromide (e.g. 2.5 to 5% by volume) is occaaionaliy added to these or to other mixtures of ethylene dichloride and carbon tetrachloride to improve surface treatment. Rates of dosage of these mixtures for grain are usually between 1 gallon for 5 tons and 1 gallon for 10 tons in a 7-day exposure period. The 3:1 mixture is also used for fumigating a variety of commodities in bags including grain, pulses and animal feeding stuffs usually on a fairly small scale in gas-tight chambers or other types of sealed containers but in some tropical countries large stacks of bagged grain have been treated under a covering of gasproof sheets. Residues During fumigation of cereal grains with ethylene dichloride or its mixtures with other halogenated hydrocarbons, relatively heavy and continuous sorption of the fumigant takes place (Winteringham, 1944). The amount sorbed is higher at lower temperatures. The adsorbed fumigant airs off slowly from whole grains over a period of months. During handling, cleaning or milling processes the amount of adsorbed fumigant is progressively reduced (Lynn and Vorkes, 1957). After milling, a greater proportion of ethylene dichloride is found in the bran than in the whole grain before milling (Conroy et al., 1957). When treated at 9 gallons/1000 bushels with 3:1 ethylene dichloride carbon tetrachloride mixture, triple the dose recommended by the United States Department of Agriculture, showed a maximum of 140 ppm ethylene dichloride three days after application of fumigant (ibid). Loss of fumigant during tempering and cleaning processes was up to 70% and the maximum residue found in flour made from this batch was 5 ppm. When amounts of ethylene dichloride up to 10 times the residue found in the flour from the previous study were added to flour which was then made into loaves, no unchanged fumigant was found in the baked bread (Munsey et al., 1957). (Sensitivity of method 2 ppm.) When added to grain fed to cows, at levels up to 1000 ppm an average of less than 0.25 ppm ethylene dichloride was found in the milk. There appears to be no direct correlation between amounts of ethylene dichloride added to the grain and that found in the milk (Sykes and Klein, 1957). When a 140-lb bag of 85% extraction wheat flour was fumigated for 48 hours in a 17.5 ft3 chamber at 25°C with 300 g of ethylene dichloride applied as vapour (equivalent to 11.1 lb per ton of flour) the following amounts of residual ethylene dichloride in ppm were found after different periods of airing of the bag in still air (Pest Infestation Laboratory, 1943). 1 hour 2 days 7 days Surface of bag 1060 210 22 Centre of bag 1030 350 46 Baking tests carried out after seven days of airing showed no detectable damage to baking quality and no taint of the fumigant was left in the finished bread. Effect of fumigant on treated crop There appears to be no reaction between ethylene dichloride and the constituents of grain. Ethylene dichloride added to grain can be recovered intact by steam distillation with a solvent extraction procedure (Heuser, 1964, personal communication). BIOLOGICAL DATA Biochemical aspects In rabbits ethylene dichloride is mainly exhaled unchanged and no metabolites have been described (Williams, 1959). Toxicological studies 1. The fumigant Maximum permissible concentration in the atmosphere recommended for industrial hygiene in the United States is 50 ppm (200 mg/m3) (Anon, 1964). Other maximum allowable concentrations are 3.0 mg/m3 (Ryazonov, 1959) and 4.0 mg/m3 (Borisova, 1960). In experimental animals corneal lesions have been produced by both subcutaneous and oral routes of administration (Hubbs and Prusmack, 1955). Acute toxicity Animal Route LD50 mg/kg Reference body-weight Mouse oral 910 Smyth et al., 1936 Rat " 680 McCollister et al., 1956 Rat " 770 Smyth et al., 1936 Rabbit " 910 Smyth et al., 1936 Animals fatally poisoned by ethylene dichloride (inhalation) showed hyperaemia and oedema of the lungs, degenerative kidney changes, damage to liver and adrenals (von Oettingen, 1955). Short- and long-term studies Groups of 4-6 female rats were exposed to single doses of varying concentrations of ethylene dichloride vapour for different lengths of time and an estimate of single doses having no observable adverse effects was made. For 12 000 ppm, 3000 ppm, 1000 ppm, 300 ppm and 200 ppm the maximum time was 0.1, 0.3, 1.5, 3.0 and 7.0 hours respectively. Intermittent exposure of animals to various concentrations of ethylene dichloride vapour for 7 hours showed the following no-effect levels (full histopathological examination and clinical biochemical tests were reported): rat (15 male, 15 female) 151 exposures in 212 days, 200 ppm; guinea-pigs (8 male) 121 exposures in 170 days, 1000 ppm; guinea-pigs (8 female) 162 exposures in 226 days, 1000 ppm; rabbits (2 male) 165 exposures in 232 days, 400 ppm and monkeys (2 male) 140 exposures in 212 days, 100 ppm (Spencer et al., 1951). 2. The fumigated foodstuff Chickens fed for five days, pigs for 12 days and cattle for 7.5 days with grain freshly treated with a fumigant containing 29.2% (by weight) of ethylene dichloride appeared unaffected. The level of ethylene dichloride in the grain was not stated and no histopathological examinations were made (Rowe et al., 1956). Comments on the experimental studies reported 1. Quite high levels of ethylene dichloride may remain in whole grain after fumigation. 2. These high residues fall markedly when the grain is processed and flour contains measurable but very low residues. 3. There is no evidence that ethylene dichloride combines chemically with food constituents. Evaluation On the available toxicological evidence it is impossible to calculate an acceptable daily intake for ethylene dichloride. It should be used as a fumigant under conditions which will result in the lowest possible residues in the foodstuffs as consumed. Further work required 1. Further investigation of the amount of the residual ethylene dichloride remaining in the food after treatment and the effect on this of processing and cooking. 2. Feeding studies should be carried out on two mammalian species to determine the effect of the long-term feeding of ethylene dichloride with particular reference to reproduction. REFERENCES Anon. (1964) Threshold limit values for 1964, Arch. environm. Hlth, 9, 545 Borisova, M. K. (1960) Predel' no Dopustimye Kontsentratsii Atmosfern. Zagryazneii, 4, 61 Conroy, H. W., Walkden, H. H. & Farrell, E. (1957) J. Assoc. Off. Agric. Chem., 40, 163 Hubbs, R. A. & Prusmack, J. J. (1955) J. Amer. med. Ass., 159, 673 Lynn, G. E. & Vorkes, F. A. (1957) J. Assoc. Off. Agric. Chem., 40, 163 McCollister, D. D., Hollingsworth, R. L., Oyen, F. & Rowe, V. K. (1956) Arch. industr. Hlth, 13, 1 Munsey, V. E., Mills, P. A. & Klein, A. K. (1957) J. Assoc. Off. Agric. Chem., 40, 201 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 Pest Infestation Laboratory (1943) Pest Infestation Research Report, 87 (Unpublished document) Rowe, V. K., Hollingsworth, R. L. & McCollister, D. D. (1956) J. Agric. Food Chem., 2, 1318 Ryazonov, V. A. (1959) Proc. Int. Clean Air Conf., Nat. Soc. for clean air, London Smyth, H. F., Smyth, H. F., jr & Carpenter, C. P. (1936) J. industr. Hyg., 18, 277 Spencer, H. C. et al. (1951) Arch. industr. Hyg., 4, 482 Sykes, J. F. & Klein, A. K. (1957) J. Assoc. Off. Agric. Chem., 40, 203 Williams, R. T. (1959) Detoxication mechanisms, London, Chapman & Hall Ltd Winteringham, F. P. W. (1944) J. Soc. chem. Ind. (Lond.), 63, 144
See Also: Toxicological Abbreviations Ethylene dichloride (FAO/PL:1967/M/11/1)