WORLD HEALTH ORGANIZATION FOOD AND AGRICULTURE
ORGANIZATION
ORGANISATION MONDIALE DE LA SANTE ORGANISATION POUR L'ALIMENTATION
ET L'AGRICULTURE
WHO/PCS/DS/94.72
Original: ENGLISH
Distr.: LIMITED
Date of issue: February 1994
WHO/FAO DATA SHEET ON PESTICIDES No. 72
AZINPHOS-ETHYL
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
Chemical group: Organophosphorus compound
1.0 GENERAL INFORMATION
1.1 COMMON NAME: azinphos-ethyl (ISO, BSI).
1.1.1 Identity
IUPAC chemical name: S-(3,4-dihydro-4-oxobenzo[d]-[1,2,3]-
triazin-3-ylmethyl) 0,0-diethyl
phosphorodithioate
CAS name: O,O-diethyl S-[(4-oxo-1,2,3-
benzotriazin-3(4 H )-yl)methyl]
phosphorodithioate
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 hazardous.
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 hydrocarbons.
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 sucking insects.
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):
Oral LD50
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.
Dermal LD50
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.)
Intraperitoneal LD50
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.
Inhalation LC50
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 mg/kg/diet.
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
respectively.
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
2.3.1 Fish:
LC50 (96 h)
Goldfish 0.1 mg/L
Guppies 0.01 - 0.1 mg/L
2.3.2 Birds:
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 sheets'].
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
countries.
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.
3.3 HANDLING
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
after handling.
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.
3.7 LABELLING
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 countries.
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
days.
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 for
prognosis.
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 reactivators.
5.1.5 Prognosis: Unless brain hypoxia has occurred,
full recovery is expected.
5.1.6 References to previously reported cases: No
information available.
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 undesirable exposure.
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 basic
references:
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):
p. 517.
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): p. 1094.
5.3.2 Other tests in case of poisoning: Activity of
cholinesterase in the blood provide the most useful diagnosis of
poisoning.
Ellman GL et al (1961), A new and rapid colorimetric determination of
acetylcholinesterase activity, Biochem pharmacol 7: 88-95.
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.
REFERENCES
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 Organization.
3. WHO (1986), Environmental Health Criteria 63; Organophosphorus
Insecticides. A General Introduction; Geneva, World Health
Organization.
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).
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