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
Relevant physical and chemical properties
Physical state (atmospheric pressure, 20°C): colourless liquid
Boiling-point: 131.6°C
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.
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