WORLD HEALTH ORGANIZATION FOOD AND AGRICULTURE
ORGANIZATION
ORGANISATION MONDIALE DE LA SANTE ORGANISATION POUR L'ALIMENTATION
ET L'AGRICULTURE
WHO/VBC/DS/88.75
ORIGINAL: ENGLISH
Distr.: Limited
DATA SHEETS ON PESTICIDES No. 75
1988
PHORATE
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: Insecticide
Secondary use: Acaricide, nematocide
Chemical group: Organophosphorus
compound
Date Issued: July 1988
1.0 GENERAL INFORMATION
1.1 COMMON NAME
phorate (E-ISO, F-ISO, BSI ANSI, ESA), timet (U.S.S.R.)
1.1.1 Identity
IUPAC: O,O-diethyl S-ethylthiomethyl phosphorodithioate
CAS: O,O-diethyl S-[(ethylthio)methyl] phosphorodithioate
CAS Reg. No.: 298-02-2
Molecular formula: C7H17O2PS3
Relative molecular mass: 260.4
Structural formula:
1.1.2 Synonyms
AC 3911, AgrimetR, CL 35024, EI 3911, ENT 24 042, foraat,
GeometR, GranutoxR, L 11/6, phorat, RampartR, ThimenoxR,
ThimetR, timet, Vergfru ForatoxR.
1.2 SYNOPSIS
Phorate is a broad spectrum, non-biocumulative organophosphorus
insecticide and acaricide, an indirect inhibitor of cholinesterase
with good contact, stomach and fumigant action against target
organisms. It is extremely toxic to mammals and other non-target
organisms. It is a plant systemic with no residual action. Granular
formulations are most commonly used. The sulphone metabolite may
persist in soil, and relatively long pre-harvest intervals are
recommended
1.3 SELECTED PROPERTIES
1.3.1 Physical characteristics
Phorate is a clear, pale yellow mobile liquid. It has a boiling
point of 118-120 °C (107 Pa), and a freezing point of -42.9 °C; a
density (d25) of 1.167. The technical material is over 90% pure.
1.3.2 Solubility
Water, 50 mg/L at 25 °C; miscible with carbon tetrachloride,
dioxane, vegetable oils, xylene, alcohols, ethers and esters.
1.3.3 Stability
Phorate is stable for at least two years at room temperature in
media between pH 5 and 7. In very acidic (pH <2) or very alkaline
(pH >9) media, hydrolysis occurs at rates dependent upon pH and
temperature.
1.3.4 Vapour pressure
85 mPa (25 °C)
1.4 AGRICULTURE, HORTICULTURE AND FORESTRY
1.4.1 Common formulations
Emulsifiable concentrates of various concentrations including
960 g tech./L and 250 g a.i./L are still available, however,
granular formulations containing 50, 100, 150, 200 g a.i./kg are
almost universally used.
1.4.2 Susceptible pests
Mites, aphids, greenbugs, thrips, leafhoppers, sorghum
shootfly, leafminers, corn rootworms, psyllids, cutworms, Hessian
fly, foliar nematodes, wireworms, flea beetles, whiteflies, pine tip
moth, and others.
1.4.3 Use pattern
Phorate may be used in foliar or soil treatments on alfalfa,
barley, beans, brassicas, coffee, corn, cotton, grapes, hops,
lettuce, oats, peanuts, potatoes, rice, sorghum, soybeans, sugar
cane, sugar beets, tomatoes, watermelon, wheat and on ornamentals
and pine nursery stock.
Soil applications may be applied as a band treatment on each
side of the seed row or incorporated into the soil as a side dress,
irrigation should follow as soon as possible. Care should be taken
to avoid contact with seed in the furrow. In foliar treatments apply
under dry conditions into plant crowns as insects appear.
1.4.4 Unintended effects
Phorate is toxic to many seeds and to many non-target
organisms, including bees and fish. Contamination of standing water
and waterways must be avoided. Good agricultural practices and the
use of granular formulations diminish these adverse effects.
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
Phorate may be absorbed from the gastrointestinal tract,
through the intact skin and by inhalation of spray mists or fine
dust.
2.1.2 Mode of action
Several metabolites of phorate inhibit the activity of both
acetylcholinesterase and pseudocholinesterase.
2.1.3 Metabolism and excretion products
Phorate is metabolized in animals to yield phorate sulphoxide
and phorate sulphone and the oxygentated analogues (phoratoxon,
phoratoxone sulphoxide and phoratoxone sulphone) which are excreted
as diethyl phosphoric acid, O-O-diethyl phosphorothioic and O-O-
diethylphosphorodithioic acid.
Oral administration of a single dose of 2 mg/kg of labelled
phorate to rats resulted in 35% of material being excreted in urine
and 3.5% in the faeces, within six days.
Six daily doses of 1 mg/kg/day of phorate to rats resulted in
12% and 6% being excreted in the urine and faeces respectively
within seven days. At necropsy brain, liver and kidney tissue
contained unidentified and largely unextractable residues.
2.1.4 Toxicity, single dose (technical material)
Oral LD50:
Rat (M) 2.3-3.2 mg/kg b.w.
Rat (F) 1.1-1.6 mg/kg b.w.
Mouse (M,F) 3.5-6.5 mg/kg b.w.
Dermal LD50:
Rat (M) 5.7-9.3 mg/kg b.w.
Rat (F) 2.5-3.9 mg/kg b.w.
Rabbit 5.2 mg/kg b.w.
Inhalation LC50:
Rat (M) 60 mg/m3 (1 hour)
Rat (F) 11 mg/m3 (1 hour
I.V. LD50:
Rat (M) 2.2 mg/kg b.w.
Rat (F) 1.2 mg/kg b.w.
I.P. LD50:
Rat 1.98 mg/kg b.w.
Mouse 3.0 mg/kg b.w.
2.1.5 Toxicity, repeated doses
Oral: Mongrel dogs given 0.05 mg/kg/day for 15 weeks had
significantly depressed plasma and erythrocyte cholinesterase
activity. At 2.5 mg/kg two dogs died following a single dose.
2.1.6 Dietary studies
Short term: The plasma, erythrocyte and brain cholinesterase
activity of rats fed on a diet containing phorate at levels greater
than 0.66 ppm was depressed. In rats fed on a diet containing up to
6 ppm of phorate no effect on growth, food consumption, or
histopathology was noticed.
Long term: In a two year rat dietary study at dose levels of
1, 3 or 6 ppm, growth was depressed at the highest dose level, among
females only, and only 36% of animals in this group survived
terminally. Erythrocyte cholinesterase activity was not affected at
any dose level whereas plasma cholinesterase activity was depressed
at 6 ppm in males and at 3 and 6 ppm in females.
In an 18 month study in mice fed on a diet containing phorate
1, 3 or 6 ppm, growth was retarded in females at 6 ppm. However, in
all dose groups food aversion was observed for both sexes. There
were no observed compound related adverse effects other than
clinical signs of cholinesterase inhibition.
2.1.7 Supplementary studies of toxicity
Carcinogenicity: Results of rat and mouse chronic toxicity
studies have not demonstrated any carcinogenic potential for
phorate.
Mutagenicity: Phorate was not mutagenic in a dominant lethal
test in mice and in several microbial systems including Salmonella
typhimurium (reverse mutation), Saccharomyces cerevisiae
(mitotic recombination) and in several Ames tests with E. coli and
B. subtilis.
Teratogenicity: In a rat study phorate was not observed to be
teratogenic at oral doses up to 0.25 mg/kg/day. At 0.5 mg/kg/da
(high dose level), an increased incidence of hypertrophy of the
heart was observed. In another rat study, exposure to phorate by
inhalation at the dose of 1.94 mg/m3/day, during the seventh
through fourteenth day of gestation, caused increased foetal
mortality and decreased foetal weight gain but teratogenic effects
were not observed.
Reproduction: In a three generation study in mice, with
phorate levels in diet up to 3 ppm, no compound related effects on
the fertility, gestation, viability or lactation indices were
observed.
Neurotoxicity: Phorate produced no adverse effects on nerve
fibres or the myelin sheath in hens fed dietary levels of 40 ppm for
four weeks. In a separate study no delayed neurotoxicity was noted
in hens given phorate as a single dose of 14.2 mg/kg.
2.1.8 Modification of toxicity
No potentiation of toxicity was observed in male rats treated
with equitoxic portions of phorate and each of 10 other pesticides.
2.2 TOXICOLOGY - MAN
2.2.1 Absorption route
Phorate may be absorbed from the gastrointestinal tract,
through the intact skin, or by inhalation of dust.
Single: 5 mg/kg b.w.
Repeated: Not known
2.2.3 Observations in occupationally exposed workers
There have been no reports of fatalities associated with the
use of phorate. A 16 year old youth became ill after working with
phorate treated cotton seed. Symptoms included coma, undetectable
blood pressure, pinpoint pupils, blood tinged frothy sputum and
occasional convulsions. One day after onset, erythrocyte and plasma
cholinesterase activities were 21% and 49% of normal respectively.
Two illnesses occurred in the same formulating plant where phorate
concentrations in the air were measured at 0.07-14.60 mg/m3. In
another incident, a formulator experienced neurological symptoms
following exposure to phorate while cleaning a mixing tank. This was
accompanied by a 50% reduction in plasma and erythrocyte
cholinesterase and increased urinary levels of diethyl phosphate, a
metabolite of phorate
2.2.4 Observations on exposures of the general population
No published information available. However, when recommended
agricultural practices are followed no adverse effects are expected.
2.2.5 Observations on volunteers
No published information available.
2.2.6 Reported mishaps
No published information available.
2.3 TOXICOLOGY TO NON MAMMALIAN SPECIES
2.3.1 Birds
Oral LD50 (technical material):
Mallard (F) 0.62-2.55 mg/kg b.w.
Pheasant (F) 7.12 mg/kg b.w.
Chukar (F) 12.8 mg/kg b.w.
Red-winged blackbird 1.00 mg/kg b.w.
Starlings 7.5 mg/kg b.w.
Grackles 1.30 mg/kg b.w.
Dermal LD50 (technical material):
Mallard (F) 203 mg/kg b.w.
Dietary LD50 (5 day):
Bobwhile quail 373 ppm
Japanese quail 200 ppm
Ring-necked pheasant 441 ppm
Mallard 248 ppm
2.3.2 Fish
Highly toxic to fish
Bluegill TLM 5.5 µg/L (48 hour) technical material
Rainbow trout LC50 13.0 µg/L (96 hour) technical material
Channel catfish LC50 280.0 µg/L (96 hour) technical material
2.3.3 Other species
Highly toxic to bees
Oral LD50:
Bullfrog (F) 85.2 mg/kg b.w. (technical material)
3.0 FOR REGULATORY AUTHORITIES - RECOMMENDATIONS ON REGULATION OF
COMPOUND
3.1 RECOMMENDED RESTRICTIONS ON AVAILABILITY
(For definition of categories see the Introduction to Data Sheets.)
Liquid formulation of 10% and over, Category 1.
Other liquid formulations, Category 2.
Solid formulations of 40% and over, Category 1.
Other solid formulations, 4-40%, Category 2, less than 4%,
Category 3.
3.2 TRANSPORTATION AND STORAGE
All formulations: Phorate should be transported and stored in
clearly labelled impermeable containers under lock and key, secure
from access by children and other unauthorized persons. 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 the site of handling. Eating, drinking and smoking should
be prohibited during handling and prior to washing after handling.
3.4 DISPOSAL AND/OR DECONTAMINATION OF CONTAINERS
All formulations: Container must first 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
disease should be excluded from contact. Pre-employment and periodic
blood cholinesterase tests for workers is desirable. Special account
should be taken of the worker's 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: Not recommended for aerial application.
3.7 LABELLING
All formulations
"DANGER - POISON"
(skull and cross-bones insignia
Phorate is an organophosphorus compound which inhibits
cholinesterase. It is extremely toxic. Contact with the skin,
inhalation of dust or spray, or swallowing may he fatal. Wear
protective gloves, clean protective clothing, and a respirator of
the organic-vapour type when handling this material. Wash
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 their containers.
In case of contact, immediately remove contaminated clothing
and wash the skin thoroughly with soap and water; for eyes, flush
with water for 15 minutes.
If poisoning occurs, call a physician. Atropine sulfate is the
principal antidote, repeated doses may be necessary. Pralidoxime
chloride (2-PAM or protopam chloride) may be effective as an adjunct
to atropine treatment. Artificial respiration also may be needed.
3.8 RESIDUES IN FOOD
Maximum residue levels: Maximum residue levels were estimated
by the Joint FAO/WHO Meeting on Pesticide Residues in 1984 for
several commodities as temporary.
4.0 PREVENTION OF POISONING IN MAN AND EMERGENCY AID
4.1 PRECAUTIONS IN USE
General: Phorate is an extremely toxic organophosphorus
pesticide. It penetrates the intact skin and is also absorbed by
inhalation and from the gastrointestinal tract. Repeated exposure
may have a cumulative effect on the cholinesterase activity. Most
formulations should be handled by trained personnel wearing
protective clothing.
4.1.2 Manufacture and formulation - T.L.V.
0.05 mg/m3 (TWA); 0.2 mg/m3 (STEL) for skin absorption.
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 respirator should be
worn. Mixing, if not mechanical, should always be carried out with a
paddle of appropriate length. When spraying all crops a face mask
should be worn, as well as an impermeable hat, clothing, boots and
gloves. The applicator should avoid working in spray mist and avoid
contact with the mouth. Particular care is needed when equipment is
being washed after use. All protective clothing should be washed
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, smoking, hands and
other exposed skin should be washed.
4.1.4 Other associated workers
Persons exposed to the compound 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
Respecting good agricultural practice, subject to 4.2 below,
other persons should not be exposed to hazardous amounts of the
compound.
4.2 ENTRY OF PERSONS INTO TREATED AREA
Unprotected persons should be kept out of tall crops for four
days and out of other crops for 24 hours
4.3 DECONTAMINATION OF SPILLAGE AND CONTAINERS
Residues in containers should be emptied in a diluted form into
a shallow pit, taking care to avoid contamination of ground waters.
The empty container may be decontaminated prior to disposal by
rinsing two or three times with water and scrubbing the sides.
Impermeable gauntlets should be worn during this work, and a soakage
pit should be provided for the rinsings. Decontamination of
containers in order to use them for other purposes including storage
of food and drink should not be permitted. Spillage of the compound
and its formulations should be removed by washing with 5% sodium
hydroxide solution and theft rinsing with large quantities of water
4.4 EMERGENCY AID
4.4.1 Early symptoms of poisoning
Early symptoms of poisoning may include tightness of chest,
non-reactive pinpoint pupils, excessive sweating, headache,
weakness, giddiness, nausea, vomiting, hypersalivation, diarrhoea,
abdominal pains, blurred vision, slurred speech and muscle
twitching. Advanced symptoms are: convulsions, coma, loss of
reflexes and loss of sphincter control.
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 and 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 respiration should be given, bearing in mind
that if mouth-to-mouth respiration is used, vomit may contain
hazardous amounts of the pesticide. Call a physician immediately and
transport the patient to the nearest medical facility if necessary.
5.0 FOR MEDICAL AND LABORATORY PERSONNEL
5.1 MEDICAL DIAGNOSIS AND TREATMENT IN CASES OF POISONING
5.1.1 General information
Phorate, an organophosphorus pesticide, is extremely toxic to
mammals. It is readily absorbed from the gastrointestinal tract,
through the intact skin and by inhalation. It is converted in vivo
to the oxygen analogue which inhibits cholinesterase. It does not
accumulate in body tissues.
5.1.2 Symptoms and signs
Initial symptoms of poisoning may include tightness of chest,
non-reactive pinpoint pupils, excessive sweating, headache,
weakness, giddiness, nausea, hypersalivation, vomiting, diarrhoea,
abdominal pains, blurred vision, slurred speech and muscle
twitching. More advanced symptoms of poisoning may be 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 the compound.
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, if available. In case of 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 impairment but with
manifest peripheral symptoms should be treated with 2-4 mg of
atropine sulfate by intravenous or intramuscular injection and 1 000
mg of pralidoxime chloride or 250 mg of toxogonin (adult dose) by
slow intravenous infusion. More atropine may be given as needed.
Persons with severe intoxication, with respiratory difficulties,
convulsions and unconsciousness should immediately be given
ventilatory support followed by 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 which are unresponsive
to atropine and pralidoxime. The patient's condition including
respiration, blood pressure, pulse frequency, salivation and
convulsions should be carefully observed as a guide to furthe
administration of atropine. If the patient is cyanotic artificial
respiration should be given at the same time as atropine sulfate.
The airways should be kept free and artificial respiration should be
applied if required, preferably by mechanical means. If necessary,
intubation should be performed.
Contraindications are morphine, aminophylline, phenothiazines,
reserpine, furosemide or ethacrynic acid.
Pralidoxime and toxogonin alone are not regarded as effective
antidotes organophosphorus poisoning, but may be effective as an
adjunct to atropine.
5.1.5 Prognosis
If the acute poisoning episode is survived and if needed
adequate artificial respiration has been given the chances of
complete recovery are good. However, in very severe cases,
particularly if artificial respiration has been inadequate,
prolonged anoxia may give rise to permanent brain damage.
5.1.6 References of previously reported cases
Phorate has been implicated in a number of cases of pesticide
poisoning.
Brokopp, C.D., Wyatt, J. L and Gabica, J., Dialkyl Phosphates
in Urine Samples from Pesticide Formulators to Disulfoton and
Phorate. (1981), Bull. Environ. Contam. Toxicol., 26,
524-529.
Hayes, W. J. (1982), "Pesticides Studied in Man" p. 360,
Williams and Wilkins, Baltimore, USA
Young, R. J., Jung, F. P. and Ayer H. E., Phorate Intoxication
at an Insecticide Formulating Plant. (1979), Amer. Indust.
Hyg. Assoc. 40, 1 013-1 016.
5.2 SURVEILLANCE TESTS
Test Normal Action Symptomatic
level* level* level*
Plasma cholinesterase 100% 50% variable
Whole blood or 100% 70% usually 40%
erythrocyte
cholinesteras
* Expressed as a percentage of pre-exposure activity.
5.3 LABORATORY METHODS
5.3.1 Detection and assay of compound
Product analysis is by I.R. spectroscopy. Residues of phorate
and its oxidation products may be determined by GLC.
Boshoff, P.R. and Pretorius, V., (1979), J. Agric. Food Chem.
27, 626-630.
Boyd, J.G. (1972), Anal. Methods Pestic. Plant Growth Regul.
Food Addit., 6, 493-510.
Brokopp, C.D., Wyatt, J. L and Gabica, J., (1981), Bull.
Environ. Contam. Toxicol., 26, 524-529.
Carson, L.J. (1981), J. Assoc. Off. Anal. Chem., 64, 714-719.
Mount, M.E. and Oehme F. W. (1981), Vet. Hum. Toxicol., 23,
34-42.
Sans, W.W. (1978), Assoc. Off. Anal. Chem., 61, 837-840.
Stan, A.J., Abraham, B., June, J., Kellert, M., Steinland, K.
(1977), Fresenius Z. Anal. Chem., 287, 271-285.