WORLD HEALTH ORGANIZATION FOOD AND AGRICULTURE
ORGANIZATION
ORGANISATION MONDIALE DE LA SANTE ORGANISATION POUR L'ALIMENTATION
ET L'AGRICULTURE
WHO/VBC/DS/88.70
ORIGINAL: ENGLISH
Distr.: LIMITED
DATA SHEETS ON PESTICIDES No. 70
1988
ETHOPROPHOS
It must be noted that the issue of a Data Sheet for a
particular pesticide does not imply endorsement of the pesticide by
WHO or FAO for any particular use, or exclude its use for other
purposes not stated. While the information provided is believed to
be accurate according to data available at the time when the sheet
was compiled, neither WHO nor FAO are responsible for any errors or
omissions, or any consequences therefrom.
The issue of this document does Ce document ne constitue pas une
not constitute formal publication. Il ne doit faire
publication. It should not be l'objet d'aucun compte rendu ou
reviewed, abstracted or quoted résumé ni d'aucune citation sans
without the agreement of the l'autorisation de l'Organisation
Food and Agriculture des Nations Unies pour
Organization of the United l'Alimentation et l'Agriculture
Nations or of the World Health ou de l'Organisation Mondiale de
Organization. la Santé.
CLASSIFICATION:
Primary use: Nematicide
Secondary use: Insecticide
Chemical group: Organophosphorus
compound
Date issued: July 1988
1.0 GENERAL INFORMATION
1.1 COMMON NAME
ethoprophos (E-ISO, F-ISO, BSI) ethoprop (ANSI, ES)
1.1.1 Identity
IUPAC and CAS No. 1: O-ethyl S,S-dipropyl phosphorodithioate
CAS Reg. No.: 13194-48-4
Molecular formula: C8H19O2PS2
Relative molecular mass: 242.3
Structural formula:
1.1.2 Synonyms: ENT 27 318, Ethoprop, JoltR, MocapR, ProphosR,
VC9-104.
1.2 SYNOPSIS
Ethrophos is a broad spectrum, non-cumulative and non-systemic
organophosphorus pesticide that is extremely toxic to mammals. It is
a direct cholinesterase inhibitor, with excellent contact action. It
has moderate residual activity and is not phytotoxic.
1.3 SELECTED PROPERTIES
1.3.1 Physical characteristics
Ethoprophos is a clear, pale yellow liquid having a boiling
point of 86-91 °C (27.7 Pa) density (d 20) of 1.094.
4
1.3.2 Solubility
In water, 750 mg/L (at 25 °C) very soluble in organic solvents.
1.3.3 Stability
Ethoprophos is very stable in acid aqueous medium up to 100 °C,
but is rapidly hydrolysed in alkaline media at 25 °C and above.
1.3.4 Vapour pressure
46.7 Pa at 26 °C.
1.4 AGRICULTURE, HORTICULTURE AND FORESTRY
1.4.1 Common formulations
Ethoprophos is available in an emulsifiable concentrate, 700 g
a.i./L and in granular preparations, 60-150 g/kg.
1.4.2 Susceptible pests
These include wire worms, nematodes and corn rootworms and soil
inhabiting arthropods.
1.4.3 Use pattern
It is almost exclusively recommended as a pre-plant, soil
application for tobacco, sweet potatoes, bananas, plantains,
cabbage, corn, pineapple, sugar cane, soybeans, peanuts, cucumber,
snap and lima beans, potatoes and commercial turf.
1.4.4 Unintended effects
It is not phytotoxic when used as directed.
1.5 PUBLIC HEALTH USE
No recommended use.
1.6 HOUSEHOLD USE
No recommended use
2.0 TOXICOLOGY AND RISKS
2.1 TOXICOLOGY - MAMMALS
2.1.1 Absorption route
Ethoprophos may be absorbed from the gastrointestinal tract,
through the intact skin, and by inhalation of spray mist and dusts.
2.1.2 Mode of action
Ethoprophos is a direct inhibitor of cholinesterases through
phosphorylation of the esteratic site of the enzyme. Accumulation of
acetylcholine at the nerve synapses and myoneural junctions causes
toxic effects.
2.1.3 Excretion products
Following oral administration of 14C-labelled ethoprophos to
rats, O-ethyl- S-propyl phosphorothioic acid, O-ethyl-
phosphoric acid and desethyl ethoprophos were the major urinary
metabolites. The urine also contained traces of methyl propyl
sulfide, methyl propyl sulfoxide and methyl propyl sulfone. In
vitro hepatic microsome and supernatant preparations produced
similar degradation products, ethoprophos was de-ethylated in the
presence of glutathione.
2.1.4 Toxicity, single dose:
Oral LD50:
Rat (M) 62 mg/kg b.w.; technical material in corn oil
Rat (F) 33 mg/kg b.w.; technical material in corn oil
Mouse (M,F) 31 mg/kg b.w.; technical material in water
Rabbit (F) 33 mg/kg b.w.; technical material, vehicle
unknown
Dermal LD50:
Rat (M,F) 226 mg/kg b.w.; technical material in water
Rabbit 26 mg/kg b.w.; technical material, vehicle
unknown
Mouse 18 mg/kg b.w.; technical material in acetone
Pig 327 mg/kg b.w.; technical material, no vehicle
Inhalation LC50: (4 hour)
Rat 250 mg/L air
Most susceptible species: Probably mice
2.1.5 Toxicity, repeated doses
No information available.
2.1.6 Dietary studies
Short-term: In a 90 day study in rats, using dose levels of
0.3, 1.0 or 100 ppm in diet a no-effect level could not be
demonstrated since brain cholinesterase activity depression was
recorded at the low-dose level. Growth depression was also observed
at the high-dose level.
In a similar dog study cholinesterase depression was observed
at the lowest dose level, 1.0 ppm in a diet. The incidence of
myocardial lesions was increased at the high-dose level, 100 ppm,
relative to control values, however, the lower dose group was not
examined for this effect.
Long-term: In a rat study test animals (60/sex/group) were
selected from among pups of first generation control and treatment
group litters of a reproduction study (see reproduction section
below). The treatment group pups were first placed on a diet
containing ethoprophos 4.5, 9.0 and 18.0 ppm for 12 weeks, then 49,
98 and 196 ppm for the remainder of the 109 week study. The only
adverse effects observed were plasma and brain cholinesterase
activity depression at all dose levels. However, erythrocyte
cholinesterase activity was not changed at: any dose level.
2.1.7 Supplementary studies of toxicity
Carcinogenicity: After 109 weeks of dietary exposure the
incidence of thyroid C-cell adenoma was significantly increased
among male rats in the high dose group (see 2.1.6).
Teratogenicity: In rats, dose levels of 0.16, 1.6 and 16.0
mg/kg b.w. of ethoprophos administered daily by gavage caused an
increased incidence of incomplete vertebral ossification in 43, 39
and 58 percent of the treatment group litters respectively. An
increased incidence in rudimentary and extra ribs was also observed
at 1.6 mg/kg b.w./day.
In a gavage study in rabbits, an increased total incidence of
skeletal variants, per foetus, was observed at all ethoprophos dose
levels (0.125, 0.5 and 2 mg/kg b.w./day). However, since no single
variant change was observed to be increased, a teratogenic no-effect
level was estimated to be 2.0 mg/kg b.w./day for ethoprophos in
rabbits.
Reproduction: In a three generation study, rats were fed
ethoprophos at dose levels of 60.5, 131 or 262 ppm. The no-adverse
effect level was observed to be 60.5 ppm for parental growt
depression at higher doses in all generations. There were no other
compound related adverse effects which were consistently observed in
all generations.
Mutagenicity: Ethoprophos was not observed to have any
mutagenic potential in two in vitro studies, an unscheduled DNA
synthesis test in primary rat hepatocytes at (25 µl/ml) and in a
mouse lymphoma specific-locus mutation assay at 0.237 nl/ml, nor in
an in vitro male rat cytogenetic study at 20 mg/kg b.w./day for
five days.
Neurotoxicity: In two studies ethoprophos could not be
evaluated for delayed neurotoxic effects due to study inadequacies.
Primary irritation: Skin and eye irritation effects could not
be adequately evaluated due to high mortality of test animals
following administration of recommended dose levels.
2.1.8 Modification of toxicity
No published information available.
2.2 TOXICOLOGY - MAN
No published information available.
2.3 TOXICITY, NON MAMMALIAN SPECIES
2.3.1 Fish, LC50:
Goldfish 13.6 ppm (96 hours)
Bluegill 2.07 ppm (96 hours)
Rainbow trout 13.8 ppm (96 hours)
2.3.2 Birds
Oral LD50:
Mallard 12.6 mg/kg b.w.; technical material
Pheasant 4.2 mg/kg b.w.; technical material
Chicken 6.1 mg/kg b.w.; technical material
Dermal LD50:
Mallard 10 mg/kg b.w.; technical material
2.3.3 Other species
Not toxic to bees.
3.0 FOR REGULATORY AUTHORITIES - RECOMMENDATIONS OF COMPOUND
3.1 RECOMMENDED RESTRICTIONS ON AVAILABILITY
(For definition of categories see the Introduction to Data Sheets).
Liquid formulations of 70% and over category 2
Other liquid formulations, Category 3
Solid formulations (granules) of 101 and over, Category 3
3.2 TRANSPORTATION AND STORAGE
All formulations: Should be transported and stored in clearly
labelled impermeable containers under lock and key, secure from
access by unauthorized persons and children. No food or drink should
be stored in the same compartment.
3.3 HANDLING
All formulations: Full protective clothing (see 4.3) should
be used by those handling the compound. Adequate washing facilities
should be available at all times during the handling and should be
close to site of handling. Eating, drinking and smoking should be
prohibited during handling and before washing after handling.
3.4 DISPOSAL AND/OR DECONTAMINATION OF CONTAINERS
Container must be decontaminated and then crushed and buried
below topsoil. Care must be taken to avoid subsequent contamination
of water sources. Decontamination of containers in order to use them
for other purposes should not be permitted.
3.5 SELECTION, TRAINING AND MEDICAL SUPERVISION OF WORKERS
All formulations: Pre-employment medical examination of
workers is necessary. Workers suffering from active hepatic or renal
diseases should be excluded from contact with ethoprophos. Pre-
employment and periodic blood cholinesterase tests for workers are
desirable. Special account should be taken of the workers' mental
ability to comprehend and follow instructions. Training of workers
in techniques to avoid contact is essential.
3.6 ADDITIONAL REGULATIONS RECOMMENDED IF DISTRIBUTED BY AIRCRAFT
All formulations: No recommended aerial applications
3.7 LABELLING
All formulations
"DANGER - POISON"
(skull and cross-bones insignia)
Ethoprophos is an organophosphorus compound which inhibits
cholinesterase. It is of very high toxicity. Contact with the skin,
inhalation of dust or spray, or swallowing may be fatal.
Wear protective gloves, clean protective clothing, and a
respirator when handling this material. Bathe immediately after
work. Ensure that containers are stored under lock and key. Empty
containers must be disposed of in such a way as to prevent all
possibility of accidental contact with them. Keep the material out
of reach of children and well away from foodstuffs, animal feed and
food containers.
In case of contact, immediately remove contaminated clothing
and wash the skin thoroughly with soap and water; for eye contact,
flush with water for 15 minutes. If poisoning occurs, call a
physician. Atropine sulfate is a recommended antidote, repeated
doses may be necessary. Artificial resuscitation may also be needed.
3.8 RESIDUES IN FOOD
Maximum residue limits - The Joint FAO/WHO Meeting on
Pesticides Residues has been unable, in the absence of an acceptable
daily intake, to recommend maximum residue limits, but has proposed
guidelines for residues in a limited number of foods.
4.0 PREVENTION OF POISONING IN MAN AND EMERGENCY AID
4.1 PRECAUTIONS IN USE
4.1.1 General
Ethoprophos is an organophosphorus pesticide of very high
toxicity. It is absorbed through the intact skin by inhalation of
dust and fine spray mist and from the gastrointestinal tract. Most
formulations should be handled by trained personnel wearing
protective clothing.
4.1.2 Manufacture and formulations - T.L.V.
No information available. Closed systems and forced ventilation
may be required to reduce, as much as possible, the exposure of
workers to the chemical.
4.1.3 Mixers and applicators
When opening the container and when mixing, protective
impermeable boots, clean overalls, gloves and a respirator should be
worn. Mixing, if not mechanical, should always be carried out with a
paddle of appropriate length. The applicator should wear an
impermeable hat, protective clothing, boots and gloves. The
applicator should avoid working in spray mist and avoid contact by
the mouth. Particular care is needed when equipment is being washed
after use. All protective clothing should be washed separately from
other laundry immediately after use, including the insides of
gloves. Splashes must be washed immediately from the skin, or eyes,
with large quantities of water. Before eating, drinking, or smoking,
hands and other exposed skin should be washed.
4.1.4 Other associated workers (including flagmen in aerial
operations)
Persons exposed to ethoprophos and associated with its
application should wear protective clothing and observe the
precautions described above in 4.1.3 under "Mixers and applicators"
4.1.5 Other populations likely to be affected
With good application practice, subject to 4.2 below, other
persons are not likely to be exposed to hazardous amounts of
ethoprophos.
4.2 ENTRY OF PERSONS INTO TREATED AREA
Unprotected persons should be kept out of application sites for
at least one day
4.3 DECONTAMINATION OF SPILLAGE AND CONTAINERS
Residues in containers should be emptied in a diluted form into
a pit, taking care to avoid contamination of ground waters. A
soakage pit should be provided for the rinsings. Decontaminated
containers should not be used for any purpose. Spillage of
ethoprophos and its formulations should be removed by washing with
5% sodium hydroxide solution and then rinsing with large quantities
of water. Impermeable gauntlets should be worn during this work.
4.4 EMERGENCY AID
4.4.1 Early symptoms of poisoning
Early symptoms of poisoning may include excessive sweating,
headache, weakness, giddiness, nausea, vomiting, hypersalivation,
stomach pains, blurred vision, slurred speech and muscle twitching.
Later, there may be convulsions and coma.
4.4.2 Treatment before person is seen by a physician, if these
symptoms appear following exposure
The person should stop work immediately, remove contaminated
clothing, wash the affected skin with soap and water, and flush the
area with large quantities of water. If swallowed, and if the person
is conscious, vomiting should be induced. In the event of collapse,
artificial resuscitation should be given, bearing in mind that if
mouth-to-mouth resuscitation is used, vomit may contain hazardous
amounts of ethoprophos.
5.0 FOR MEDICAL AND LABORATORY PERSONNEL
5.1 MEDICAL DIAGNOSIS AND TREATMENT IN CASES OF POISONING
5.1.1 General information
Ethoprophos is an organophosphorus pesticide of very high
mammalian toxicity. It is readily absorbed from the gastrointestinal
tract, through intact skin, and by inhalation of dust or fine spray
mist.
5.1.2 Symptoms and signs
Initial symptoms of poisoning may include excessive sweating,
headache, weakness, giddiness, nausea, hypersalivation, vomiting,
stomach pains, blurred vision, slurred speech and muscle twitching.
More advanced symptoms of poisoning may include convulsions, coma,
loss of reflexes and loss of sphincter control.
5.1.3 Laboratory
The most important finding is reduction of activity of blood
cholinesterases. Urinary levels of organic phosphorus containing
metabolites may also be used as a measure of exposure. Neither
method is specific for ethoprophos.
5.1.4 Treatment
If the pesticide has been ingested, unless the patient is
vomiting, rapid gastric lavage should be performed using 5% sodium
bicarbonate. For skin contact, the skin should be washed with soap
and water. If the compound has entered the eyes, they should be
washed with large quantities of isotonic saline or water.
Persons without signs of respiratory insufficiency but with
manifest peripheral symptoms should be treated with 2-4 mg of
atropine sulfate by intravenous injection and 1 000 mg pralidoxime
chloride or 250 mg of toxogonin (adult dose) by slow intravenous
injection. More atropine may be given as needed. Persons with severe
intoxication, with respiratory difficulties, convulsions and
unconsciousness should immediately be provided with ventilatory
support and given atropine and a reactivator. In such severe cases
4-6 mg of atropine sulfate should be given initially followed by
repeated doses of 2 mg at 5-10 minute intervals. Diazepam may be
given to control convulsions. The patient's condition including
respiration, blood pressure, pulse frequency, salivation, and
convulsions should be carefully observed as a guide to further
administration of atropine. If the patient is cyanotic, oxygen
should be given at the same time as atropine sulfate. The airways
should be kept free and artificial resuscitation should be applied
if required, preferably by mechanical means
Contraindications are morphine, barbituates, phenothiazine and
central stimulants of all kinds. Pralidoxime and toxogonin alone are
not regarded as effective antidotes in ethoprophos poisoning.
5.1.5 Prognosis
If the acute toxic effect is survived and adequate artificial
resuscitation has been given as needed, the chances of complete
recovery are good. However, in very severe cases, particularly if
respiratory support has been inadequate, prolonged anoxia may give
rise to permanent brain damage.
5.1.6 References of previously reported cases
No published information.
5.2 SURVEILLANCE TESTS
Test Normal Action Symptomatic
level* level* level*
Plasma cholinesterase 100% 50% variable
Whole blood or 100% 70% usually 40%
erythrocyte
cholinesterase
5.3 LABORATORY METHODS
5.3.1 Detection and assay of compound
Thin layer chromatography and gas-liquid chromatography methods
have been used to analyse ethoprophos in technical products and its
formulations. Analysis of residues in plant and animal tissues may
be performed by gas chromatography and flame photometry methods.
Foster R. L., (1974), Proc. Annu. Ind. Air Pllut. Conf., 4,
66.
Hunt T. W., (1979), Diss. Abst. Int. B., 40, 1 437.
Hunt T. W., Leidy R. B., Sheets T. J., and Duncan H. E. (1981),
Bull. Environ. Contam. Toxicol., 27, 84.
* Expressed as percentage of pre-exposure activity.
Leidy R. B. and Sheets T. J. (1980), Beitr. Tabakforsch.
Int., 10, 127.
Sagredos A. N. N. and Echert, W. R. (1976), Beitr.
Tabakforsch., 8, 447.
5.3.2 Other tests in case of poisoning
Blood cholinesterase activity, particularly erythrocyte provide
the most useful diagnosis of poisoning. Urine metabolites may also
be determined in order to give an indication of exposure. For
methods, see section 5.3.1.
REFERENCES
1. Hartley, D., Kidd, H. (1983) "The Agrochemicals Handbook".
Royal Society of Chemistry. Unwin Bors. Surrey, United
Kingdom
2. Hudson, R. M. "Handbook of Toxicity of Pesticides to Wildlife",
2nd Edition (1985): p. 41
3. FAO/WHO (1985) - 1985 Evaluations of Some Pesticide Residues in
Food. FAO Plant Production and Protection Paper 61.
4. Worthing, C. R. (1987) "The Pesticide Manual. A World
Compendium". British Crop Protection Council, United Kingdom,
Eighth Edition.