WORLD HEALTH ORGANIZATION FOOD AND AGRICULTURE
ORGANIZATION
ORGANISATION MONDIALE DE LA SANTE ORGANISATION POUR L'ALIMENTATION
ET L'AGRICULTURE
VBC/DS/75.6 (Rev.1)
ORIGINAL: ENGLISH
DATA SHEETS ON PESTICIDES No. 6 Rev.1
PARATHION
CLASSIFICATION:
Primary use: Insecticide
Secondary use: Acaricide, avicide
Chemical Group: Organophosphorus compound
Data sheet No. 6 Rev.1 (8/78)
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.
1. GENERAL-INFORMATION
1.1 COMMON NAME: Parathion (ISO)
1.1.1 Identity: O,O-diethyl O-(4-nitrophenyl) phosphorothioate
1.1.2 Synonyms: OMS 19
E 605 - Belgium
Thiophos - USSR
SNP - France
Local synonyms:
1.2 SYNOPSIS - An organophosphorus pesticide of very high mammalian
toxicity. It may be absorbed through the skin, by inhalation and
via the gastrointestinal tract. It is active upon metabolism.
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.
R 683
The issue of this document does not constitute formal publication.
It should not be reviewed, abstracted or quoted without the
agreement of the Food and Agriculture Organization of the
United Nations or of the World Health Organization.
Ce document ne constitue pas une publication. Il ne doit faire l'objet
d'aucun compte rendu ou résumé ni d'aucune citation sans l'autorisation
de l'Organisation des Nations Unies pour l'Alimentation et
l'Agriculture ou de l'Organisation Mondiale de la Santé.
1.3 SELECTED PROPERTIES
1.3.1 Physical characteristics - When pure a colourless almost
odourless liquid m.p. 6.1°C, b.p. 157-162°C at 0.6 torr. The
technical material is a yellow to dark brown liquid with a
pungent garlic-like odour.
1.3.2 Solubility - Water at 25°C, very slightly soluble (24 mg/l).
Miscible with most organic solvents, slightly soluble in
petroleum oils.
1.3.3 Stability - Fairly stable at neutral or slightly acid pH. At pH
5-6, 1% is hydrolyzed in 62 days at 25°C. Rapidly hydrolyzed in
alkali. Isomerizes on heating to the O,S-diethyl isomer.
Darkens on exposure to sunlight.
1.3.4 Vapour pressure (volatility) 3.78 x 10-5 torr at 20°C.
1.4 AGRICULTURE, HORTICULTURE AND FORESTRY
1.4.1 Common formulations - Dispersible powders, 150 and 250 g/kg;
dusts, 5, 10, 20, 50 and 100 g/kg; granules 100 g/kg,
emulsifiable concentrates and solutions; aerosols 100 g/l. There
are FAO specifications for the technical product, powders, dusts,
oncentrates and solutions.
1.4.2 Susceptible pests - Effective against most insects and mites as
contact and stomach poison. Some fumigant action. Has been used
for the control of nuisance birds.
1.4.3 Use pattern - Used as pre-harvest soil and foliage treatment on a
wide variety of crops, outdoor and in glasshouses. The pre-
harvest interval, depending on crop is usually 7-15 days after
last application, but twice as long in glasshouses. Uses include
tree and berry fruits, nuts, cotton, maize, small grains except
rye, root and leafy vegetables, legumes, tomatoes, grasses,
tobacco, ornamentals. Used as mosquito larvicide on rice fields,
non-crop areas, pastures, and range lands. Usual application
rates are 0.2-1 kg/ha.
Not used on stored crops.
1.4.4 Unintended effects - Not generally phytotoxic, but can, at high
concentrations, injure cucumbers, tomatoes and some ornamentals,
and under certain weather conditions, pears and McIntosh and
related apples.
1.5 PUBLIC HEALTH PROGRAMMES - Use limited to larvicide against
mosquitos in developed countries.
1.6 HOUSEHOLD USE - Parathion is too toxic for household use.
2. TOXICOLOGY AND RISKS
2.1 TOXICOLOGY - MAMMALS
2.1.1 Absorption route - Absorbed by the intact skin as well as by
inhalation and from the gastrointestinal tract.
2.1.2 Mode of action - Cholinesterase inhibition after conversion to
the oxygen analogue paraoxon.
2.1.3 Excretion products - In mammals parathion is converted into its
oxygen analogue, paraoxon which is the active form. Parathion
and paraoxon are broken down and excreted as p-nitrophenol and
ethyl and diethyl esters of phosphoric and/or thiophosphoric
acid.
2.1.4 Toxicity, single dose
Oral: LD50 rat (M): 13 mg/kg
rat (F): 3.6 mg/kg
Dermal: LD50 rat (M): 21 mg/kg
rat (F): 6.8 mg/kg
Most susceptible species: Dog - lethal dose 3-5 mg/kg.
(An oral dose of 3-5 mg/kg is reported to be usually fatal to
man.)
2.1.5 Toxicity, repeated doses
Oral: See dietary studies.
Dermal: No information.
Inhalation: No information.
Cumulation of compound: Parathion does not accumulate in body
tissue.
Cumulation of effect: Repeated exposure to sub-lethal amounts may
reduce cholinesterase activity to hazard levels.
2.1.6 Dietary studies
Short-term: In rats which were fed 0.05, 0.5 or 5.0 mg/kg diet
(0.0025, 0.025 or 0.25 (mg/kg)/day) of parathion for 12 weeks the
no-effect level with respect to inhibition of blood
cholinesterases was 0.5 mg/kg (0.025 (mg/kg)/day).
Long-term: In a two-year study groups of rats were maintained
on diets containing 10.25 and 100 mg/kg (0.5, 1.25, 5
(mg/kg)/day) of parathion. No morbid anatomical effects were
seen at any level. There is no information on cholinesterase
activity levels in this study.
2.1.7 Supplementary studies of toxicity
Mutagenicity: Parathion in the diet of mice at three dosage
levels for seven weeks did not induce any dominant lethal
effects. No mutagenic tendency was demonstrated in four
microbial assay systems. In a three generation reproduction
study on rats, the no-effect level was 10 mg/kg diet (0.5
(mg/kg)/day). Information on cholinesterase levels is, however,
not available.
2.1.8 Modifications of toxicity: The acute toxicity of parathion was
increased by a factor of 7.6 when rats were fed a low protein
diet.
2.2 TOXICOLOGY - MAN
2.2.1 Absorption - See 2.1.1. Both the oral and dermal routes have been
responsible for many instances of poisoning.
Dangerous doses
Single: In a number of fatal cases of human poisoning the dosage
which the victims received orally was exactly 900 mg. In another
case death resulted from 120 mg. Children five to six years old
have been killed by ingestion of 2 mg of parathion (about 0.1
mg/kg).
Repeated: See "observations on volunteers".
2.2.3 Observations on occupational exposed workers - Several operators
have died after rather extensive skin contact with diluted
agricultural sprays or dusts.
2.2.4 Observations on exposure of the general population - Total diet
studies in one country have demonstrated a daily intake of 0.001
mg Of parathion per person (0.00002 mg/kg) which is well below
the no-effect level in animal studies.
2.2.5 Observations on volunteers - A daily oral dose of 7.2 mg produced
a 33% reduction in whole blood cholinesterase activity in adult
volunteers in 42 days.
Parathion, given to groups of five subjects in doses of 6
mg/day for 43 days produced 10-15% reduction in plasma and
erythrocyte cholinesterase activity. The inhibition of plasma
cholinesterase persisted for two weeks after discontinuation of
feeding parathion whereas erythrocyte cholinesterase was
inhibited for 43 days. There was no effect from 3 mg and 4.5
mg/day doses given for 28 days.
In another study subjects were fed 0.003, 0.010, 0.025 and 0.050
mg/kg of parathion for successive periods, each of three weeks.
A significant increase in the plasma cholinesterase activity
occurred early in the feeding programme but the level declined to
control values when doses of 0.05 mg/kg were reached. No change
in the erythrocyte cholinesterase activity occurred.
2.2.6 Reported mishaps - There are probably more reported cases of
poisoning with parathion than with any pesticide currently in
frequent use. There have been a number of cases where
intoxication and death have resulted from ingestion of foodstuffs
that have been grossly contaminated with parathion. The list of
outbreaks below is not complete.
In one Asian country there were 828 cases of poisoning with 106
deaths due to flour, sugar and other foodstuffs becoming
contaminated because parathion was transported in the same ship's
hold as the foodstuff. In another Asian country barley became
contaminated with parathion. There were 38 cases of poisoning
with nine deaths.
In a country in the Americas there were 559 cases of poisoning
and 16 deaths when sacks of sugar and possibly flour absorbed
parathion from the floor of a truck. In another country in the
Americas there were 165 known and 445 more suspected cases of
poisoning with 63 deaths when parathion from broken containers
contaminated sacks of flour during transportation in a truck. In
a Caribbean country there were 27 known and 8-13 more suspected
cases of poisoning with 21 deaths when foodstuffs were
contaminated when placed in paper sacks which had previously been
used to package insecticides. Parathion was the predominant
pesticide but malathion and a chlorinated hydrocarbon were also
involved. In a European country there were 26 cases of poisoning
but no deaths when flour became contaminated because of
transportation in a wagon which was previously used for the
transportation of parathion. In a Caribbean country an outbreak
of poisoning - 79 cases including 17 deaths - occurred due to
contamination of cotton sacks containing flour. The
contamination was believed to have occurred in a European
warehouse.
2.3 TOXICITY TO NON-MAMMALIAN SPECIES
The entries in these sections are intended to draw attention to
special risks and to give warnings of any needs for special
presentation.
2.3.1 Fish - Toxic to fish. Toxicity varies fairly widely in different
species (LC50 0.05 ppm for bluegills, 2 ppm for trout).
2.3.2 Birds - Very toxic to birds and has been used, applied to seed
bait, for the control of nuisance birds.
2.3.3 Other species - Toxic to bees. Toxic to wildlife and domestic
animals generally.
3. FOR REGULATORY AUTHORITIES - RECOMMENDATIONS ON REGULATION OF
COMPOUND
3.1 RECOMMENDED RESTRICTIONS ON AVAILABILITY
(for definition of categories, see introduction)
All formulations Category 3, 4
3.2 TRANSPORTATION AND STORAGE
All formulations - UN classification 6.1 No. 1668
Should be transported or stored in clearly labelled rigid and
leakproof containers and away from containers of food and drink.
Storage should be under lock and key and secure from access by
unauthorized persons and children.
3.3 HANDLING
All formulations - Full protective clothing (see part 4) should
be used for all handling of the compound. Adequate washing
facilities should be available at all times during handling and
should be close to the 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
All formulations - Containers must either be burned or 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
necessary. Workers suffering from active hepatic or renal
disease should be excluded from contact. Pre-employment and
periodic cholinesterase test for workers desirable. A urinary p-
nitrophenol test periodically may be used as an alternative.
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 - Pilots and loaders should have special
training in application methods and early symptoms of poisoning,
and must wear a suitable respirator. Use of flagmen not
recommended. Flagmen, if used, should wear protective clothing
and be located well away from the dropping zone.
3.7 LABELLING
All formulations - "POISON" (skull-and-cross-bones insignia)
"Parathion is an organophosphorus compound which inhibits
cholinesterase. It is a very toxic substance. Contact with the
skin, inhalation of dust or spray, or swallowing may be fatal.
Wear protective gloves, clean protective clothing, and a
respirator of the organic-vapour type 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 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 and pralidoxime
are specific antidotes and repeated doses may be necessary.
Artificial respiration may be needed."
3.8 RESIDUES IN FOOD
3.8.1 Maximum residue levels - The Joint FAO/WHO Meeting on Pesticide
Residues has recommended maximum residue levels.
4. PREVENTION OF POISONING IN MAN AND EMERGENCY AID
4.1 PRECAUTIONS IN USE
4.1.1 General - Parathion is a highly toxic organophosphorus pesticide.
It penetrates the intact skin and is also absorbed by inhalation
and via the gastrointestinal tract. Most formulations should be
handled by trained personnel wearing protective clothing.
4.1.2 Manufacture and formulation
T.L.V.: 0.1 mg/m3 (ACGIH); 0.05 mg/m3 (USSR). Closed systems
and forced ventilation may be required to reduce as much as
possible the exposure of workers to the chemical. Formulation
should not be attempted without advice from the manufacturer.
4.1.3 Mixers and applicators - When opening the container and when
mixing, protective impermeable boots, clean overalls, gloves and
respirator should be worn. Beware of possible positive pressure
build-up especially with liquid formulations in metal containers
with inverted pour spout. Mixing, if not mechanical, should
always be carried out with a paddle of appropriate length. When
spraying tall crops or during aerial application a respirator
should be worn as well as an impermeable hood, 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 the 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 parathion 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 agricultural
practice subject to 4.2 below, other populations should not be
exposed to hazardous amounts of parathion.
4.2 ENTRY OF PERSON INTO TREATED AREAS - There have been reports of
workers having been poisoned because they entered fields too soon
after they had been treated with parathion. Unprotected persons
should be kept out of treated areas for considerable periods: a
minimum of 14 days has been suggested and 21 days after the
spraying of peaches, nectarines and grapes.
4.3 SAFE DISPOSAL OF CONTAINERS AND SPILLAGE - Residues in containers
should be emptied in a diluted form into a deep pit taking care
to avoid contamination of ground waters. Decontamination of
containers in order to use them for other purposes must not be
permitted. Spillage of parathion and its formulations should be
removed by washing with 5% sodium hydroxide solution and then
rinsing with large quantities of water.
4.4 EMERGENCY AID
4.4.1 Early symptoms of poisoning - Early symptoms of poisoning may
include excessive sweating, headache, weakness, giddiness,
nausea, vomiting, stomach pains, blurred vision, slurred speech,
and muscle twitching. Later there may be 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 water and soap, if available, and flush the area with
large quantities of water. If swallowed, vomiting should be
induced if the person is conscious. In the event of collapse,
artificial respiration should be given, bearing in mind that if
mouth-to-mouth resuscitation is used vomit may contain toxic
amounts of parathion.
5. FOR MEDICAL AND LABORATORY PERSONNEL
5.1 MEDICAL DIAGNOSIS AND TREATMENT OF CASES OF POISONING
5.1.1 General information - An organophosphorus pesticide of very high
acute toxicity which is easily absorbed through the intact skin
as well as by inhalation and via the gastrointestinal tract. It
is converted in vivo to the oxygen analogue paraoxon which then
inhibits acetyl cholinesterase. Continued exposure to low amounts
may inhibit blood cholinesterase to dangerous levels.
5.1.2 Symptoms and signs - Initial symptoms of poisoning may include
excessive sweating, headache, weakness, giddiness, nausea,
vomiting, stomach 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 laboratory finding is reduction
in activity of blood cholinesterases. Other findings are raised
urinary levels of 2-nitrophenol.
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. For skin contact, the
skin should be washed with soap and water. If the compound has
entered the eyes, they should be washed with isotonic saline.
Persons without signs of respiratory inefficiency but with
manifest peripheral symptoms should be treated with 2-4 mg of
atropine sulfate and additionally with 1000-2000 mg of
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 given
atropine and a reactivator. In such severe cases 4-8 mg of
atropine sulfate should be given initially followed by repeated
doses of 2 mg at 5-10 minute intervals. The patient's condition,
including respiration, blood pressure, pulse frequency,
salivation and convulsions should be carefully observed as a
guide to further adminis-tration of atropine. If the patient is
cyanotic, artificial respiration should be given at the same time
as atropine.
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, barbiturates, phenothiazine
tranquillizers and central stimulants of all kinds.
5.1.5 Prognosis - If the acute toxic effect is survived and adequate
artificial respiration has been given if needed the chances of
complete recovery are good. However, in very severe cases,
particularly if artificial respiration has been inadequate,
prolonged hypoxia may give rise to permanent brain damage.
5.1.6 References of previously reported cases - Case histories and
general methods for treatment are given in: Hayes, W. J., jr,
Clinical handbook on economic poisons, United States Public
Health Service, No. 476, revised 1963.
See also "Safe use of pesticides in public health" (1967) Wld
Hlth Org. techn. Ser., No. 356, pp. 58-59.
For reports of individual cases of poisoning see: Namba, T. &
Hiraki, K. (1968) J. Amer. med. Ass., 166, 1834 and
Kanagartnam, K., Boon, W. H. & Hoh, J. K. (1960) Lancet,
1, 538-542. A recent outbreak of poisoning is described by
Diggory, H. J. P. et al., Amer. J. Epidemiol., 106(2),
145-153 (1977).
5.2 SURVEILLANCE TESTS
Test Normal Action Symptomatic
level level level
Plasma cholinesterase 100%* 50% variable
Erythrocyte cholinesterase 100% 70% usually < 40%.
It has been reported that absorption of parathion is tolerated
without illness and with little or no reduction in cholinesterase
activity so long as the concentration of the metabolite p-
nitrophenol in the urine does not rise much above 2.0 mg/l. Both
determination of the activities of blood cholinesterase and.2-
nitrophenol in the urine (see 5.3.2 below) should be used in
cases of suspected poisoning.
5.3 LABORATORY METHODS
References are given only.
5.3.1 Detection and assay of compound - lt is unlikely that unchanged
parathion will be detectable in human tissue after exposure.
Determination of levels of blood cholinesterase and urinary p-
nitrophenol (see 5.3.2 below) should be used in cases of
suspected poisoning.
Parathion and other p-nitrophenyl esters such as
parathion-methyl and EPN can be determined in foodstuffs by the
colorimetric method of Averell & Norris (1948) or a later
modification (Sutherland & Miskus, 1964).
Parathion can be determined separately by gas chromatography, e.g.
Abbott et al. (1970) and Storherr et al. (1971). Identity can be
confirmed by thin-layer chromatography (Abbott et al., 1965 and
Gardner, 1971).
5.3.2 Other tests in cases of poisoning
Levels of cholinesterase in the blood, particularly plasma
provide the most useful diagnosis of poisoning, see: Michel, N.
0. (1949) J. Lab. Clin. Med., 34, 1564-1568 and Ellman, G.
L., Courtney, K. D., Andres, V., jr & Featherstone, R. M. (1961)
Biochem. Pharmacol., 7, 88-95.
Urinary levels of p-nitrophenol or diethyl phosphate and
phosphorothioate are also indexes of poisoning: p-nitrophenol
may be determined colorimetrically (Elliott et al., 1960) or gas-
chromatographically (Crammer, 1970), and diethyl phosphate by the
method of Shafik & Enos (1969) as modified by Shafik et al.
(1970).
-------------
* Percentage of pre-exposure activity by any test.
REFERENCES
Abbott, D. C., Crisp, S., Tarrant, K. R. & Tatton, J. O'G. (1970)
Pesticide residues in the total diet in England and Wales, 1966-
1967. III. Organophosphorus pesticide residues in the total
diet, Pestic. Sci., 1, 10
Abbott, D. C., Crosby, N. T. & Thompson, J. (1965) Use of thin-layer
and semi-preparative gas liquid chromatography in the detection,
determination and identification of organophosphorus pesticide
residues, Proc. Soc. anal. Chem. Conf., Nottingham, p. 121
Averell, P. R. & Norris, M. V. (1948) Estimation of small amounts of
O,O-diethyl O,p-nitrophenyl thiophosphate, Anal. Chem.,
20, 753
Crammer, M. (1970) Determination of p-nitrophenol in human urine,
Bull. environm. Contamin. Toxicol., 5, 329
Elliott, J. W., Walker, K. C., Penick, A. E. & Durham, W. F. (1960) A
sensitive procedure for urinary.E-nitrophenol determination as a
measure of exposure to parathion, J. Agric. Fd. Chem., 8, 111
Gardner, A. M. (1971) Confirmation of organophosphorus pesticide
residues at nanogram levels by two-dimensional thin-layer
chromatography, J. Assoc. Offic. Anal. Chem., 54, 517
Shafik, M. T., Bradway, D., Biros, F. J. & Enos, H. F. (1970)
Characterization of alkylation products of diethyl
phosphorothioate, J. Agric. Fd. Chem., 18, 1174
Shafik, M. T. & Enos, H. F. (1969) Determination of metabolic and
hydrolytic products of organophosphorus pesticide chemicals in
human blood and urine, J. Agric. Fd. Chem., 17, 1186
Storherr, R. W., Ott, P. & Watts, R. R. (1971) A general method for
organophosphorus pesticide residues in non-fatty foods,
J. Assoc. Offic. Anal. Chem., 54, 513
Sutherland, G. L. & Miskus, R. (1964) In: Zweig, G. (ed.) Analytical
methods for pesticides, plant growth regulators and food
additives. Vol. II. Academic Press, New York and London, p.
327