الد يا زينون

WORLD HEALTH ORGANIZATION FOOD AND AGRICULTURE
ORGANIZATION
ORGANISATION MONDIALE DE LA SANTE ORGANISATION POUR L'ALIMENTATION
ET L'AGRICULTURE

VBC/DS/79.45
ORIGINAL: ENGLISH


DIAZINON





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 uses: Ectoparaiticide
Namaticide

Chemical group: Organophosphorus compound

Date issued: April 1979

1. GENERAL INFORMATION

1.1 COMMON NAME: Diazinon (ISO)

1.1.1 Identity: O,O-diethyl 0-[6-methyl-2-(1-methylethyl)-4-pyrimidinyl]
phosphorothioate




1.1.2 Synonyms: G.24480
BasudinR
DianonR
KayazinonR
Necidol/NucidolR

Local synonyms:

1.2 SYNOPSIS - An organophosphorus pesticide of moderate mammalian
toxicity. It may be absorbed by all routes of exposure; it is
active upon metabolism and not cumulative in body tissues.

1.3 SELECTED PROPERTIES

1.3.1 Physical characteristics - When pure, it is a colourless oil of
b.p. 83°-84°C at 0.002 torr. The technical product is a pale to
dark brown liquid of at least 95% purity.

1.3.2 Solubility - Its solubility in water at room temperature is 40
mg/l. It is miscible with ethanol, acetone, zylene and is
soluble in petroleum oils.

1.3.3 Stability - Diazinon decomposes above 120°C and is susceptible to
oxidation. It is stable in alkaline media, but is slowly
hydrolysed by water and by dilute acids. The presence of traces
of water promotes hydrolysis on storage to highly toxic
tetraethyl monothiopyrophosphate.

1.3.4 Vapour pressure (volatility) - low: 1.4 x 10-4 torr at 20°C.

1.4 AGRICULTURE, HORTICULTURE AND FORESTRY

1.4.1 Common formulations - ULV concentrates, wettable powders 40%;
emulsifiable concentrates 60%, 40% and 25%; dusts 2-4%;
granules 3-14%, aerosols 20%.

1.4.2 Susceptible pests - House-flies, ticks on cattle, blowflies and
mites on sheep, wide range of sucking and leaf eating insects
on crops; diptera in glasshouses.

1.4.3 Use pattern - Main applications are in rice, fruit, vineyards,
sugar-cane, corn, tobacco, potatoes, horticultural crops,
animal dips and sprays.

1.4.4 Unintended effects - Can damage maidenhair fern, cucumber and
tomatoes if applied before mid May.

1.5 PUBLIC HEALTH PROGRAMME

1.6 HOUSEHOLD USE: Used by trained pest control operators in

households and outbuildings to control cockroaches, ants,
silverfish, spiders, carpet beetles and scorpions.

2. TOXICOLOGY AND RISKS

2.1 TOXICOLOGY - MAMMALS

2.1.1 Absorption routes - May be 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 diazoxon.

2.1.3 Excretion products - After an oral dose, rats excrete diazinon
and its metabolites mainly in the urine; 95-98% of an oral dose
is excreted in 168 hours.

2.1.4 Toxicity, single dose

Oral: LD50 rats: 300-850mg/kg - varies with stability of
product. Lower value adopted for classification purposes.

Dermal: LD50 rats: 2150 mg/kg
Most susceptible species: No infomation.

2.1.5 Toxicity, repeated doses

Oral: See 2.1.6, dietary studies, short-term.

Cumulation of compound: Diazinon and its metabolites are
rapidly excreted from the body, mainly in urine.

Cumulation of effect: Repeated exposures to diazinon may have
a cumulative effect on cholinesterase levels.

2.1.6 Dietary studies

Short-term: Rats fed diazinon in the diet at 100 and 1000
mg/kg diet for four weeks exhibited no toxic symptoms except
a slight inhibition of growth, a distinct inhibition of
erythrocyte cholinesterase and some inhibition of brain
cholinesterase at 1000 mg/kg. No significant inhibition of
plasma cholinesterase was found at either concentration.
Dogs and pigs were orally administered diazinon by capsule
daily for periods of up to eight months. Doses for pigs were
0, 1.25, 2.5, 5 and 10 mg/kg bw; for dogs 0, 2.5, 5, 10 and
20 mg/kg bw. In pigs mortality and cholinergic signs of
poisoning were evident at 2.5 mg/kg per day and above, and in
dogs, above 10 mg/kg.


Long-term: Two groups of weanling rats (20 males and 20
females) and one group of 20 males were fed for 72 weeks on
diets containipg 10, 100 and 1000 mg/kg diet of diazinon as a
25% wettable powder. At 1000 mg/kg some inhibition of growth
was observed. No macroscopic or histological lesions were
observed at autopsy.

A group of 3 males and 3 female monkeys were given daily oral
doses of 0.05, 0.5 and 5.0 mg/kg bw diazinon for two years.
No significant inhibition of erythrocyte or plasma
cholinesterase was found at the 0.05 mg/kg/day level. This
did occur at higher levels and was dose related.

2.1.7 Supplementary studies of toxicity

Teratogenicity: Oral administration of diazinon in maize oil
at a dose of 0.125 mg/kg bw on day 6, 7 and 8 of gestation and
at 2.25 mg/kg on day 7 or 8 produced no terata in the hamster.
Administration of diazinon to rabbits daily from day 5-15 of
gestation at 7 or 30 mg/kg bw per day, induced no terata or
dose-related embryo toxic effects.

Mutagenicity: In one test in vitro, diazinon applied at high
concentrations, was considered to have a mutagenic effect on
human lymphocytes. However, a dominant lethal test on male
mice given single doses of 15 and 45 mg/kg bw was negative.
In vitro tests on E. coli systems were also negative.

2.1.8 Modification of toxicity - Raising the protein content of feed
from 29% to 81% or lowering it to 4% increased the acute
toxicity of diazinon to rats approximately twofold.

2.2 TOXICOLOGY - MAN

2.2.1 Absorption - Diazinon may be absorbed readily through the intact
skin, from the gastrointestinal tract or by inhalation.

2.2.2 Dangerous doses

Single: Not known. A man swallowed a quantity of 30 mg/kg of
diazinon without any detrimental effect on health. Another
man who took 250 mg/kg recovered after treatment.

Repeated: No information (see 2.2.5 "observations on
volunteers").

2.2.3 Observations of occupationally exposed workers - Slight
asymptomatic reduction in cholinesterase activity has been
found in spraymen as a result of extensive occupational
exposure to diazinon.

2.2.4 Observations on exposure of the general population - With good
agricultural practice, the general population should not be
exposed to hazardous amounts of diazinon.

2.2.5 Observations of volunteers - Volunteers have been given in
separate experiments, oral doses of diazinon at 0.025 mg/kg
bw for 5 days, 0.025-0.03 mg/kg for 32-34 days, 0.05
mg/kg for 5 days, then allowed to recover for 23 days; this
was followed by 0.05 mg/kg for a further 5 days, 0.025
mg/kg for 43 days and 0.02 mg/kg for 37 days. Under none of
these dosing regimens was an effect on haematology, liver
function or urine analysis observed, nor were any symptoms
experienced. Slight reduction of plasma cholinesterase
activity was observed with all dosing schedules, but no
effect was seen on erythrocyte cholinesterase.

2.2.6 Reported mishaps - Contamination of doughnut mix due to spillage
during storage resulted in 20 cases of poisoning with diazinon,
none of which was fatal. Eight children were poisoned in two
separate incidents by eating grain treated with diazinon.

2.3 TOXICITY TO NON-MAMMALIAN SPECIES

2.3.1 Fish - Toxic

2.3.2 Birds - Very highly toxic (mallards and pheasants LD50 2-6
mg/kg)

2.3.3 Other species - Toxic to bees and livestock.

3. FOR REGULATORY AUTHORITIES - RECOMMENDATIONS ON REGULATION OF
COMPOUND

3.1 RECOMMENDED RESTRICTIONS ON AVAILABILITY

(For definition of categories see Introduction to data sheets)

Liquids over 20%; category 3. Other liquids, solids over 50%;
category 4 all other solids: category 5.

3.2 TRANSPORTATION AND STORAGE

Formulations in Categories 3 and 4 should be transported and
stored in clearly labelled rigid and leakproof containers,
away from containers of food and drink. Storage should
be under lock and key and secure from access by unauthorized
persons and children.

Formulations in Category 5 should be transported and stored

in clearly labelled leakproof containers, out of reach of
children, away from food and drink.

3.3 HANDLING

Formulations in Categories 3 and 4 - Protective clothing (see
part 4) should be used by 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.

Formulations in Category 5 - The same facilities required as
those needed for the handling of any chemical.

3.4 DISPOSAL AND/OR DECONTAMINATION OF CONTAINERS

All formulations - Containers may be decontaminated (for
method see paragraph 4.3). Decontaminated containers should
not be used for food and drink. Containers that are not
decontaminated should be burned or crushed and buried below
topsoil. Care must taken to avoid subsequent contamination of
water sources.

3.5 SELECTION, TRAINING AND MEDICAL SUPERVISION OF WORKERS

Formulations in Categories 3 and 4 - Pre-employment medical
examination of workers desirable. Workers suffering from
active hepatic or renal disease should be excluded from
contact. Pre-employment and periodic cholinesterase test for
workers desirable especially for those handling concentrates.
Special account should be taken of the workers' mental
ability to comprehend and follow instructions. Training of
workers in techniques to avoid contact essential.

Formulations in Category 5 - Warning of workers to minimize
contact essential.

3.6 ADDITIONAL REGULATIONS RECOMMENDED IF DISTRIBUTED BY AIRCRAFT

All formulations - Pilot and loaders should have special
training in application methods and early symptoms of
poisoning, and must wear a suitable respirator. Flagmen, if
used, should wear overalls and be located well away from the
dropping zone.

3.7 LABELLING

Formulations in Categories 3 and 4 - Minimum cautionary
statement - Diazinon is an organophosphorus compound that

inhibits cholinesterase. It is poisonous if swallowed. It
may be absorbed through the skin. Avoid skin contact; wear
hand protection, clean protective clothing and a respirator
when handling the material. Wash thoroughly with soap and
water after using. Keep the material out of reach of
children and well away from foodstuffs, animal feed and their
containers. If poisoning occurs, call a physician. Atropine
and pralidoxime are specific antidotes and artificial
respiration may be needed.

Formulations in Category 5 - Minimum cautionary statement -
This formulation contains diazinon which is a toxic
substance. Keep the material out of reach of children and
well away from foodstuffs, animal feeds and their containers.

3.8 RESIDUES IN FOOD

Maximum residue limits have been recommended for diazinon by
the Joint FAO/WHO Meeting on Pesticide Residues. These are
subject to change at annual reviews.

4. PREVENTION OF POISONING IN MAN AND EMERGENCY AID

4.1 PRECAUTIONS IN USE

4.1.1 General - Diazinon is an organophosphorus pesticide of moderate
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
levels.

4.1.2 Manufacture and formulation - TLV: 1 mg/m3 (FRG). 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 tall crops or during aerial
application, 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, or
smoking, hands and other exposed skin should be washed.


4.1.4 Other associated workers (including flagmen in aerial operations)
- Persons exposed to diazinon and associated with its
application should wear protective clothing and observe the
precautions described above in 4.1.3 under "mixers and
applicators".

4.1.5 Other populations likely to be affected - With good application
practice, subject to 4.2 below, other persons should not be
exposed to hazardous amounts of diazinon.

4.2 ENTRY OF PERSONS INTO TREATED AREAS - Unprotected persons
should be kept out of treated citrus, and store fruit areas
and vineyards for five days and out of other treated areas
for at least one day.

4.3 DECONTAMINATION OF SPILLAGE AND CONTAINERS - Residues in
containers should be emptied in a diluted form into a deep
pit, taking care to avoid ground waters. The empty
container may be decontaminated by rinsing two or three times
with water and scrubbing the sides. An additional rinse
should be carried out with 5% sodium hydroxide solution which
should remain in the container overnight. Impermeable
gauntlets should be worn during this work, and a soakage pit
should be provided for the rinsings. Decontaminated
containers should not be used for food and drink.
Spillage of diazinon 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, hypersalivation, stomach pains, blurred
vision, slurred speech and muscle twitching. Later there may
be convulsions, and coma.

4.4.2 Treatment before person is seen by a physician, if these symptoms
appear following exposure - The person should stop work
immediately, remove contaminated clothing and wash the
affected skin with soap and water, if available, 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 toxic amounts of diazinon.

5. FOR MEDICAL AND LABORATORY PERSONNEL

5.1 MEDICAL DIAGNOSIS AND TREATMENT IN CASES OF POISONING

5.1.1 General information - Diazinon is an organophosphorus pesticide
of moderate mammalian toxicity which is active against a variety
of agricultural and public health pests. It is readily
absorbed by the gastrointestinal tract, through the intact
skin and by inhalation. It is converted in vivo to the
oxygen analogue diazixon which then inhibits cholinesterase.
It does not accumulate in body tissues.

5.1.2 Symptoms and signs - Initial symptoms of poisoning may include
excessive sweating, headache, weakness, giddiness, nausea,
hypersalivation, vomiting, stomach pains, blurred vision,
slurred speech and muscle twitching. More advanced symptoms
of poisoning may be convulsions, coma, loss of reflexes and
loss of sphincter control.

5.1.3 Laboratory - The most important laboratory finding is reduction
of activity of blood cholinesterases. Urinary levels of organic
phosphorus containing metabolites may also be used as a
measure for exposure. Neither method is specific for diazinon.

5.1.4 Treatment - If the pesticide has been ingested, 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 large quantities of isotonic saline or
water.

Persons without signs of respiratory inefficiency but with
manifest peripheral symptoms should be treated with 2-4 mg of
atropine sulfate and 1000 mg pralidoxime chloride or 250 mg
of toxogonin (adult dose) by slow intravenous injection.
More atropine may be given as needed. Persons with severe
intoxication with respiratory difficulties, convulsions and
unconsciousness should immediately be given atropine and a
reactivator. In such severe cases 4-6 mg of atropine
sulfate should be given initially followed by repeated doses
of 2 mg at 5-10 min intervals. Diazepam may be given to
control convulsions. The patient's condition including
respiration, blood pressure, pulse frequency, salivation and
convulsions should be carefully observed as a guide to
further administration of atropine.

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, other
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 anoxia may give rise to permanent brain
damage.

5.1.6 References of previously reported cases

Willems, J., Vermeire, P. & Rolly, G. (1971) Arch. Toxikol., 28,
182-191
Namba, T. et al. (1971) Amer. J. Med., 50 (4), 475-492
West, I. (1965) Calif. Hlth, p. 11
Hayes, W. J. (1963) Clinical Handbook on Economic Poisons,
US Department of Health Education and Welfare

5.2 SURVEILLANCE TESTS

Test Normal Action Symptomatic
level* level* level*

Plasma cholinesterase 100% 50% variable

Erythrocyte cholinesterase 100% 70% usually 40%

* Expressed at percentage of pre-exposure activity.


5.3 LABORATORY METHODS

5.3.1 Detection and assay of compound - References are given only,



A method involving conversion of diazinon sulfur to H2S,
which is then reacted with dimethyl-P-phenylenediamine and
FeCl3 to give methylene blue, and is determined
spectrophotometrically at 665 mu is given in:

Analytical methods for pesticides, Plant growth regulators
and food additives, Vol. II Insecticides, Academic Press,
1964.

Diazinon, Section 10, p. 109, Margot, A. & Stammbac, K.

A second spectrophotometric method involves conversion of
diazinon to pyrimidinol and measurement at 272 mu. See:
Blinn, R. C. & Gunther, F. A. (1953) J. Agr. Food Chem.,1
(4), 325.


Methods involving gas liquid chromatography using a
thermionic phosphorus detector are given in: Analytical
methods for pesticides and plant growth regulators, Vol.
VI; Gas chromatographic analysis, edited by Zweig, G.,
Academic Press, 1972, Section 21, p. 345.

5.3.2 Other tests in cases of poisoning

Levels of cholinesterase in the blood, particularly plasma,
provide the most useful diagnosis of poisoning. Michel, N. 0.
(1949) J. Lab. Clin. Med., 34, 1564-1568. Ellman, G. L.
et al. (1961) Biochem. Pharmacol., 7, 88-95.

Measurement of urine metabolites may also be determined in
order to give an indication of exposure for methods. See
section 5.3.1, Detection and assay.





See Also:
Toxicological Abbreviations
Diazinon (EHC 198, 1998)
Diazinon (ICSC)
Diazinon (FAO Meeting Report PL/1965/10/1)
Diazinon (FAO/PL:CP/15)
Diazinon (FAO/PL:1967/M/11/1)
Diazinon (FAO/PL:1968/M/9/1)
Diazinon (AGP:1970/M/12/1)
Diazinon (WHO Pesticide Residues Series 5)
Diazinon (Pesticide residues in food: 1979 evaluations)
Diazinon (Pesticide residues in food: 1993 evaluations Part II Toxicology)
Diazinon (JMPR Evaluations 2001 Part II Toxicological)