WORLD HEALTH ORGANIZATION
ORGANISATION MONDIALE DE LA SANTE
FOOD AND AGRICULTURE ORGANIZATION
OF THE UNITED NATIONS
ORGANISATION DES NATIONS UNIES POUR
L'ALIMENTATION ET L'AGRICULTURE
Date of issue: February 1994
WHO/FAO DATA SHEET ON PESTICIDES
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
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.
Primary use: Insecticide
Secondary use: Acaricide
Chemical group: Organophosphorus compound
1.0 GENERAL INFORMATION
1.1 COMMON NAME: azinphos-ethyl (ISO, BSI).
IUPAC chemical name: S-(3,4-dihydro-4-oxobenzo[d]-[1,2,3]-
CAS name: O,O-diethyl S-[(4-oxo-1,2,3-
benzotriazin-3(4 H )-yl)methyl]
CAS registry number: 2642-71-9
RTECS number: TD8400000
Molecular formula: C12H16N3O3PS2
Relative molecular mass: 345.4
Synonyms & tradenames: Athyl-GusathionR; azinfosethyl;
AzinosR; Azinophos-aethylR; Azinphos-etileR; Bay 16255;
Bayer 16259; Benzotriazine derivative of ethyl dithiophosphate;
Cotnion-ethylR; CrysthionR; ENT 22,014; Ethyl-azinophosR;
Ethyl-GusathionR; Ethyl-Guthion; GusationR; GusathionR;
Guthion (ethyl); R1513; triazotion.
1.2 SYNOPSIS: Azinphos-ethyl is a broad spectrum,
non-cumulative and non-systemic organophosphorus
insecticide/acaricide with good ovicidal properties and good
contact and stomach action. It has excellent residual activity
and is not phytotoxic. It is very toxic to mammals with a WHO
hazard classification of a technical product in class IB, Highly
1.3 SELECTED PROPERTIES
1.3.1 Physical characteristics: Azinphos-ethyl forms
colourless (clear) crystals melting at 50 °C and boiling at 147
°C. It has a density of 1.284 and a refractive index of 1.5928.
The technical material is 92% pure compound.
1.3.2 Solubility: The compound is virtually insoluble
in water (4-5 mg per litre at 20 °C), it is soluble in most
organic solvents except light petroleum and aliphatic
1.3.3 Stability: Azinphos-ethyl is thermally stable
but is readily hydrolysed in alkaline media.
1.3.4 Vapour pressure: 0.32 mPa at 20 °C.
1.4 AGRICULTURE, HORTICULTURE AND FORESTRY
1.4.1 Common formulations: These include emulsifiable
concentrates, 200 - 400 g a.i./L; wettable powders, 250-400 g
a.i./kg; and, an ULV product, 500 g a.i./L.
1.4.2 Pests controlled: These include susceptible
spider mites, aphids, caterpillars, potato bug, beetles,
bollweevils, whiteflies, bollworms, thrips and other biting and
1.4.3 Use pattern: Azinphos-ethyl is no longer
registered for use in many countries, but it is still widely used
in some countries, especially on fruit and vegetable crops,
cotton, pastures, coffee, cereals, potatoes, hops, grapes,
citrus, rice, tobacco and other crops.
1.4.4 Unintended effects: Considered to be non-
phytotoxic when used as recommended.
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: Azinphos-ethyl is absorbed from
the gastrointestinal tract, through the intact skin, and by
inhalation of fine spray mist and dusts.
2.1.2 Mode of action: Azinphos-ethyl after conversion
to the oxygen analogue is an inhibitor of acetylcholinesterase
thereby causing impairment of nervous transmission.
2.1.3 Excretion products: After oral administration
azinphos-ethyl was almost completely absorbed from the
gastrointestinal tract of the rat. Following intravenous or oral
administration of 0.1 - 6 mg/kg b.w. to rats, 60 - 65% of the
compound was eliminated in urine and 20 - 40% was excreted in
faeces irrespective of route of administration or dose level.
Less than 0.1% of the compound when dosed intravenously or orally
at 2 mg/kg, was eliminated with the exhaled air within 24 hours.
2.1.4 Toxicity, single dose (technical product):
Rat 12 mg/kg b.w.
Rat (F) 7.2 mg/kg b.w.
Rat (M) 15.2 mg/kg b.w.
Guinea-pig 17.0 mg/kg b.w.
Rat 72-280 mg/kg b.w.
Rat (M) 545 mg/kg b.w. (24 hour exp.)
Rat (F) 402 mg/kb b.w. (24 hour exp.)
Rat (M) 7.5-9.2 mg/kg b.w.
Rat (F) 4.4 mg/kg b.w.
Mouse 3.8-4.0 mg/kg b.w.
Rat c0.15 mg/L (4 hours exposure)
2.1.5 Toxicity, repeated dose:
Oral: Male rats given 1.0 mg/kg b.w. orally for 28 consecutive
days showed no clinical signs of toxicity and no changes in body
weight gain. Cholinesterase activity was depressed in
erythrocytes by 50% after 2 days, 82% by three days and 90% by 28
days. Normal cholinesterase activity was re-established by 35
days after administration ceased.
Dermal: Male and female rabbits were treated for three weeks with
15 x 7 hour applications of 0.1 - 0.05 mg/kg b.w. The no-effect-
level (NOEL) was 0.05 mg/kg b.w.
Inhalation: Male and female rats were exposed 15 times for 6 hours
to 0, 0.3, 1.8 or 12.7 mg/m3 air over a three week period. The
NOEL was 0.3 mg/m3 air.
Cumulation of compound: Groups of female rats were administered
doses of 0.5, 1, 2, or 3 mg/kg b.w. intraperitoneally for 60
days. Only the two highest dosage levels caused a reduction in
weight gain and an increased mortality. Azinphos-ethyl does not
accumulate in body tissues, but a cumulation of effect was
demonstrated at higher doses.
2.1.6 Dietary studies:
Short term: Groups of 15 male and female rats were fed azinphos-
ethyl at 0, 1, 2, 4 and 8 mg/kg/diet for 90 days. There were no
clinical signs of toxicity, no changes in blood chemistry and no
increases in mortality in any of the treatment groups. After 30
days the erythrocyte cholinesterase activity was depressed in
rats fed on a diet containing 4 mg/kg azinphos-ethyl. In a group
of rats fed 8 mg/kg plasma cholinesterase activity was depressed
and stabilized after one week, while the erythrocyte
cholinesterase activity continued to fall for the first 30 days.
Females were more sensitive than males. There were no treatment
related gross or histological abnormalities found in the organs
or tissues of the treated animals. 2 mg/kg of diet was accepted
as the no-effect level.
In another experiment, groups of 12 male and female rats were fed
diets containing 0, 5, 10 or 50 mg of azinphos-ethyl/kg/diet for
16 weeks. At 50 mg/kg/diet males showed a decrease in body
weight but no clinical signs of toxicity. In this group
cholinesterase activity was depressed in erythrocytes, serum and
brain. At 10 mg/kg/diet only serum and erythrocyte
cholinesterase activities were inhibited. Rats on the 5
mg/kg/diet showed only erythrocyte cholinesterase activity
depression. No gross or histological abnormalities were observed
in any of the treatment group animals.
In a 12 week study, groups of two male and female young dogs were
fed 0, 0.25, 0.5, 1, 2, 3 and 10 mg of azinphos-ethyl/kg/diet.
At dietary levels of 3 and 10 mg/kg the dogs exhibited clinical
signs of poisoning after 6 and 1 weeks respectively. They were
removed from these diets and their cholinesterase activity
returned to normal after 3-4 weeks on normal diet.
Cholinesterase activities were depressed in all other treatment
groups, but they returned to normal in treated animals after 2-3
weeks on normal diet. Only in the group receiving 0.25 mg/kg of
diet did the erythrocyte activity remain unchanged, and this was
accepted as the no-effect-level.
Long term: Male and female Rhesus monkeys were dosed orally with
azinphos-ethyl at 0, 0.02, 0.04 and 0.08 mg/kg b.w./day for 32
months. A NOEL of 0.02 mg/kg b.w. was obtained. At higher doses
depression of plasma cholinesterase activity was observed.
In a two-year feeding study male and female dogs were fed
azinphos-ethyl at 0, 0.1, 0.2, 2, 20, 30, 60 and 90 mg/kg/diet.
A NOEL of 0.1 - 0.2 mg/kg/diet was obtained. At doses up to 30
mg/kg/diet only depression of cholinesterase activity in plasma
and erythrocytes was observed.
In a two year feeding study in male and female rats, azinphos-
ethyl was fed at 0, 2, 8 and 32 mg/kg/diet. No carcinogenic
effects were observed up to and including 32 mg/kg/diet.
In a two year feeding study in male and female mice, azinphos-
ethyl was fed at 0, 0.5, 1.4, 4.0 and 11.3 mg/kg/diet. No
carcinogenic effects were observed up to and including 11.3
2.1.7 Supplementary studies of toxicity:
Carcinogenicity: In long term studies in mice and rats
carcinogenicity was not demonstrated at 11.3 and 32 mg/kg/diet
Teratogenicity: Studies in rats and rabbits did not show any
embryotoxic or teratogenic effects.
Mutagenicity: Azinphos-ethyl was not mutagenic in the
Salmonella/Microsome Test (Ames-test), micronucleus-test nor in
the dominant-lethal test. It has no DNA-damaging properties.
Neurotoxicity: No ataxia was observed in hens five weeks after a
single administration of 10 or 25 mg/kg b.w. given orally. There
were no clinical or histological signs in hens fed 75, 150, 300
or 600 mg/kg/diet for 30 days during the treatment period or at 4
weeks after cessation of treatment.
2.1.8 Modification of toxicity: No potentiation
occurred when azinphos-ethyl was used with a variety of
pesticides including parathion, methyl parathion, malathion,
trithion, phosdrin, carbaryl, diazinon, azinphos-methyl,
coumaphos, chlorobenzilate or fenchlorphos. A twofold
potentiation occurred when used with ethion.
2.2 TOXICOLOGY - MAN
2.2.1 Absorption route: Azinphos-ethyl may be absorbed
from the gastrointestinal tract, through the intact skin, and by
inhalation of fine spray mist and dusts.
2.2.2 Dangerous doses: No information available.
2.2.3 Observations on occupationally exposed workers:
No information available.
2.2.4 Observations on exposure of the general population:
No information available.
2.2.5 Observations on volunteers: Six volunteers
received 0.01 or 0.02 mg azinphos-ethyl technical product per day
in gelatine capsules for 28 consecutive days. The volunteers
tolerated the treatment without any effect.
2.2.6 Reported mishaps: None.
2.3 TOXICITY TO NON-MAMMALIAN SPECIES
LC50 (96 h)
Goldfish 0.1 mg/L
Guppies 0.01 - 0.1 mg/L
Oral LD50 Chicks 34 mg/kg b.w.
Oral LD50 Quail (F) 20 mg/kg b.w.
2.3.3 Other species: 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
Liquid formulation of 6.0% and over, Category 2
Other liquid formulations, Category 3
Solid formulations of 25% and over, Category 2
Other solid formulations, Category 3
Azinphos ethyl has been banned or severely restricted in several
3.2 TRANSPORTATION AND STORAGE
All formulations: Should be transported in clearly labelled
impermeable containers and stored under lock and key, secure from
access by unauthorized persons and children. No food or drink
should be stored in the same compartment.
All formulations: Full protective clothing (see 4.3 part 4)
should be used by those handling 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
3.4 DISPOSAL AND/OR DECONTAMINATION OF CONTAINERS
All formulations: Whenever possible containers should be
either returned to the supplier, or safely disposed of in an
approved manner. 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 and periodic medical
examination of workers is necessary and should include blood
cholinesterase activity tests. Special account should be taken
of the workers' ability to comprehend and follow instructions.
Training of workers in techniques to avoid contact 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.
DANGER - POISON
(Skull and cross bones insignia)
Azinphos-ethyl is an organophosphorus compound which inhibits
cholinesterase enzymes. 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 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 sulphate is a pharmacological antidote.
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 not recommended maximum residue levels
neither has it established an Acceptable Daily Intake (ADI).
4.0 PREVENTION OF POISONING IN MAN AND EMERGENCY AID
4.1 PRECAUTIONS IN USE
4.1.1 General: Azinphos-ethyl is an organophosphorus
pesticide of high toxicity. It is readily absorbed through the
intact skin, from the gastrointestinal tract and by inhalation.
Repeated exposure may have a cumulative effect on cholinesterase
activity. Most formulations should be handled by trained
personnel only. Its use is severely restricted in several
4.1.2 Manufacture and formulation: 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, neoprene gloves and respirator should be worn. Mixing,
if not mechanical, should always be carried out with a paddle of
appropriate length. When spraying tall crops or during aerial
application, a face mask should be worn, as well as an
impermeable hood, clothing, boots, and neoprene 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, or 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:
Subject to 4.2 below, persons other than applicators are not
likely to be exposed to hazardous amounts of azinphos-ethyl.
4.2 ENTRY OF PERSONS INTO TREATED AREAS
Unprotected persons should be kept out of treated crops for four
4.3 SAFE DISPOSAL OF CONTAINERS AND SPILLAGE
Residues in containers should be kept to a minimum and emptied in
a diluted form into a deep dry pit (depth over 0.5 m), taking
care to avoid contamination of ground waters. The empty
containers should be disposed of in an approved manner. If not
returned to the producer, re-use of containers should not be
permitted for any purpose.
Spillage of liquid azinphos-ethyl formulations should be
contained with absorbent material. This material or spillage of
dry residues should be collected and burned or buried as
described above. Residues should be removed by scrubbing with
detergent and then rinsing with large quantities of water.
Impermeable gauntlets and protective overalls should be used for
all handling procedures.
4.4 EMERGENCY AID
4.4.1 Early symptoms of poisoning: Early symptoms of
poisoning may include excessive sweating, headache, weakness,
giddiness, nausea, vomiting, increased salivation, stomach pains,
diarrhoea, blurred vision, slurred speech and muscle twitching.
Later there may be shortness of breath, convulsions and coma.
4.4.2 Treatment before person is seen by physician, if
these symptoms appear following exposure:
The person should stop work immediately, remove contaminated
clothing and wash contaminated 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. Artificial
respiration should be given when necessary bearing in mind that
if mouth-to-mouth resuscitation is used, vomit may contain toxic
amounts of pesticide. Call a physician immediately or organize
immediate transport to a physician or hospital.
5.0 FOR MEDICAL AND LABORATORY PERSONNEL
5.1 MEDICAL DIAGNOSIS AND TREATMENT IN CASES OF POISONING
5.1.1 General information: Azinphos-ethyl is an
organophosphorus pesticide of high mammalian toxicity. 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 cholinesterases. It does not
accumulate in body tissues.
5.1.2 Symptoms and signs: Poisoning is due to
excessive stimulation by acetylcholine of all cholinergic
innervation. Thus initial symptoms and signs of poisoning may
include excessive sweating and salivation, headache, weakness,
miosis, dyspnoea, nausea, vomiting and diarrhoea, blurred vision
and muscle fasciculations. More severe poisoning leads to
respiratory failure due to a combination of bronchorrhea,
bronchoconstriction (muscarinic effects), paralysis of
respiratory muscles (nicotinic effects) and respiratory centre
paralysis (central effects). The latter include, in severe
cases, coma and convulsions.
5.1.3 Laboratory: Diagnosis is confirmed by finding
inhibition of erythrocyte or whole blood acetylcholinesterase.
However, treatment must start immediately and cannot be delayed
until confirmation from the laboratory. This test cannot be used
to control the effectiveness of the treatment nor is it of help
5.1.4 Treatment: Patients with respiratory failure
must be given artificial ventilation, then diazepam (10 mg
intravenously) to control convulsions. When vital functions are
controlled, atropine sulfate is given (initial dose is usually 2
mg intravenously) followed by pralidoxime (1000 mg) or toxogonin
(250 mg) by slow intravenous infusion.
If the pesticide has been ingested, gastric lavage might be
needed or vomiting induced. Protection of airways (intubation)
is required if inducing vomiting in unconscious patients.
For skin contact, the skin should be washed with soap and large
amounts of water. Precautions should be taken by medical
personnel during these decontamination procedures to prevent
their own overexposure. If the compound has entered the eyes,
they should be washed with large quantities of saline or water.
Atropine treatment might be required for several days after
poisoning. Only clinical assessment determines atropine dose,
i.e. evident signs of atropinization (dry mouth, tachycardia,
vasodilation, mydriasis) should be maintained. Total amounts of
atropine given to these patients might be extremely high because
they are tolerant to the effects of atropine.
Caution should be taken when doses of atropine are reduced
because reappearance of symptoms might occur, due to
redistribution processes in the body. Cholinesterase
reactivators such as pralidoxime and toxogonin are usually only
effective during the first few days of poisoning, unless the slow
disposal of the chemical within the body suggests that some
acetylcholinesterase is newly inhibited. Indications for the
continuing use of reactivators might derive from measurements of
erythrocyte cholinesterase before and after treatment with such
5.1.5 Prognosis: Unless brain hypoxia has occurred,
full recovery is expected.
5.1.6 References to previously reported cases: No
5.2 SURVEILLANCE TESTS
Any fall in erythrocyte cholinesterase activity to 70% of the
pre-exposure values, requires an investigation of working methods
and hygiene and more frequent cholinesterase tests. Symptoms of
poisoning may appear when the erythrocyte cholinesterase activity
is less than 35% of normal. If erythrocyte cholinesterase
activity is less than 50% of normal, the worker must be suspended
from all contact with organophosphorus or carbamate pesticides
until the level rises above 70% of pre-exposure value.
Pseudocholinesterase activity in the plasma can fall to very low
levels without evidence of symptoms. This only indicates
5.3 LABORATORY METHODS
5.3.1 Detection and assay of compound:
Analysis of the product is by colorimetric measurement of the
complex of the liberated O,O-diethylphosphorodithioate (following
alkaline hydrolysis) and copper (II) ions, extracted and measured
at 420 nm. Residues are measured by GLC. The following are some
CIPAC Handbook, 1070, 1, 18.
Curini M et al (1980), Talanta 27(1): p. 45.
Ferreira JR, & Fernandes A (1980), J Assoc Off Anal Chem 63(3):
Meagher WR et al (1960), J Agric Food Chem 8: p. 282.
Mestres R et al (1977), Anal Falsif Expert Chim, 70(751): p. 177.
Miles JRW (1964), J Assoc Off Agric Chem, 47: p. 882.
Stan HJ et al (1977), Fresentius Z Anal Chem, 287 (4-5): p. 271.
Stein UB & Pitman KA (1976), J Assoc Off Anal Chem 59(5):
5.3.2 Other tests in case of poisoning: Activity of
cholinesterase in the blood provide the most useful diagnosis of
Ellman GL et al (1961), A new and rapid colorimetric
determination of acetylcholinesterase activity, Biochem pharmacol
Wilhelm K & Reiner E (1973), Bull Wld Health Org, 48: 235-238.
Urine metabolites such as dialkylphosphates and
dialkylthiophosphates may also be determined in order to give an
indication of exposure, particularly when exposure is so low as
not to inhibit cholinesterase. For methods see section 5.3.1,
Detection and Assay.
1. The Pesticide Manual, A World Compendium (9th edition 1991),
Worthing CR & Hance RJ, eds., British Crop Protection Council, 20
Bridport Road, Thornton Heath, CR4 7QG, United Kingdom.
2. WHO (1974) 1973 Evaluations of some pesticide residues in food.
WHO Pesticide Residues Series, No. 3, Geneva, World Health
3. WHO (1986), Environmental Health Criteria 63; Organophosphorus
Insecticides. A General Introduction; Geneva, World Health
4. WHO (1994) The WHO Recommended Classification of Pesticides by
Hazard and Guidelines to Classification 1994-1995, Geneva, World
Health Organization mimeographed document (WHO/PCS/94.2).
= = =
Azinphos ethyl (PIM 054)