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تاريخ التسجيل : 22/12/2009
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مُساهمةموضوع: كلورو بيريفوس ميثيل   الأربعاء ديسمبر 23, 2009 2:19 pm

WORLD HEALTH ORGANIZATION FOOD AND AGRICULTURE

ORGANIZATION
ORGANISATION MONDIALE DE LA SANTE ORGANISATION POUR L'ALIMENTATION
ET L'AGRICULTURE

VBC/DS/78.33

ORIGINAL: ENGLISH






DATA SHEETS ON PESTICIDES No. 33

CHLORPYRIFOS-METHYL







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:

Chemical Group: Organophosphorus compound

Date issued:

1. GENERAL INFORMATION

1.1 COMMON NAME:

Chlorpyrifos-methyl

1.1.1 Identity:

O,O-dimethyl O-(3,5,6-trichloro-2-pyridinyl) phosphorothioate



1.1.2 Synonyms:

DOWCO 214
ENT 27520
OMS-1155
Reldan
Zertell

Local synonyms:

1.2 SYNOPSIS

An organophosphorus insecticide of low mammalian toxicity.

1.3 SELECTED PROPERTIES

1.3.1 Physical characteristics

White crystalline solid with a mild mercaptan odour melting point
45.5-46.5°C.

1.3.2 Solubility

Poorly soluble in water (4 mg/l). Moderately soluble in hexane and
alcohols, and readily soluble in other organic solvents such as
acetone, benzene and chloroform.

1.3.3 Stability

Stable under normal storage conditions. Half-life in water at pH 8
is less than nine days at 25°C and three days at 35°C. It is
hydrolysed more rapidly at higher pH. Undergoes rapid
photodecomposition in UV light.

1.3.4 Vapour pressure

(volatility) - 4.2 x 10-5 mm Hg at 25°C, 1.8 x 10-4 mm Hg at
35°C.

1.4 AGRICULTURE, HORTICULTURE AND FORESTRY

1.4.1 Common formulations

25% emulsifiable concentrate: 25% wettable powder: granules 3%, 5%
and 10%: dusts 3%; microfine granules 3%.

1.4.2 Pests mainly controlled

Effective against rice stem borer, aphids, cutworms, plant and leaf
hoppers, mole crickets and some moths; stored grain pests.

1.4.3 Use pattern

Up to four applications per season depending on formulation and pest
on rice, cotton, tobacco and on vegetables up to 2 kg a.i./ha.

1.4.4 Unintended effects

Not phytotoxic at recommended rates.

1.5 PUBLIC HEALTH PROGRAMMES:

Considered as a larvicide for onchocerciasis control and as a
general mosquito larvicide for outdoor surface water that is liable
to be used for human and animal consumption.

1.6 HOUSEHOLD USE:

Not used at present.

2. TOXICOLOGY AND RISKS

2.1 TOXICOLOGY - MAMMALS

2.1.1 Absorption route

Absorbed from the gastrointestinal tract and to a lesser extent
through intact skin.

2.1.2 Mode of action

Cholinesterase inhibition.

2.1.3 Excretion

Principal excretory route for unchanged chlorpyrifos-methyl is by
way of faeces. The metabolite, 3,5,6-trichloro-2-pyridinol is
excreted mainly in the urine as its glucoronide conjugate.

2.1.4 Toxicity, single dose

Oral: LD50 rat (M) about 2000 mg/kg
(F) about 3000 mg/kg
mouse (M) greater than 1000 mg/kg
guinea pig (M) 2250 mg/kg

Dermal: LD50 rabbits > 2000 mg/kg
rats (M,F) > 3700 mg/kg

Most susceptible species: No appreciable species variation.

2.1.5 Toxicity, repeated doses

Oral: Rat - 14 daily doses of 20, 100 and 500 mg/kg body weight by
gavage produced no mortality. At 500 mg/kg/day a slight body weight
decrease, some hypertrophy of the liver and a tendency for cardiac
hypertrophy occurred. In another study, rats were dosed 0.2, 1.0 or
5.0 mg/kg daily for six weeks. Only effect at the highest dose level
was a trend for reduced erythrocyte cholinesterase activity. The
no-effect level for plasma and erythrocyte cholinesterase activity
was 1.0 mg/kg/day.

Mouse - 14 daily doses of 150, 250, 500 and 1000 mg/kg/day: at
1000 mg/kg all mice were dead after four doses; at 500 mg/kg, 40%
mortality occurred in 14 days and there was a noticeable decrease in
body weight of survivors. No mortality or significant changes in
body weight were seen at lower doses.

Rhesus monkeys - were dosed orally daily with either 1.0 or
5.0 mg/kg for six months. No reduction of brain cholinesterase or
changes in many parameters studied were seen. A no-effect level for
plasma and erythrocyte cholinesterase activity was estimated as
0.2 mg/kg.

Cumulation of compound: Metabolized rapidly - not cumulative.

Cumulation of effect: Repeated exposure may produce a cumulative
inhibitory effect on cholinesterase.

2.1.6 Dietary studies

Short-term: Female rats were fed dietary concentrations between 20
and 20 000 mg/kg equivalent to 1.6-2.130 mg/kg/day for 14 days. Two
out of six rats died and significant loss in body weight of the
survivors occurred at the highest dose level. Cholinesterase
activity in plasma erythrocyte was significantly reduced at 80 mg/kg
and in brain at 1250 mg/kg. The no-effect level based on
cholinesterase inhibition was between 80 and 20 mg/kg diet.

Rats - both sexes were fed at doses from 0.08 to 160 mg/kg/day for
90 days. The no-effect level based on plasma cholinesterase activity
was between 8 and 0.8 mg/kg/day, in males and between 0.8 and 0.08
mg/kg/day in females. The no-effect level based on brain
cholinesterase activity was between 40 and 8 mg/kg/day. There was no
significant differences in frequency and rates of lesions between
treated and untreated in the main tissues tested.

Rats - both sexes were fed at levels from 0.5 to 100 mg/kg diet
for six months. Plasma and erythrocyte cholinesterase activity of
the groups given more than 20 mg/kg diet showed statistically
significant decreases after one, three and six months of dosing. The
maximum no-effect level using plasma and erythrocyte cholinesterase
activity as the index, was 10 mg/kg diet.

Mice - both sexes were fed the 5-100 mg/kg diet for six months.
Using cholinesterase activity as the index the maximum no-effect
level corresponded to 5 mg/kg diet.

Dogs were fed from 0.3 to 10 mg/kg diet for 92 days. Brain
cholinesterase was not depressed even at highest level. However,
plasma cholinesterase was significantly depressed at all levels
after 1, 4 and 12 weeks' treatment.

Cows were fed silage corn previously treated with
chlorpyrifos-methyl equivalent to a dietary residue intake of up to
0.054 mg of chlorpyrifos-methyl and 0.01 mg of the pyridinol
respectively. No effect was found on food intake, milk production or
blood cholinesterase activity.

Dietary studies

Long-term: Rats were fed at levels from 0.03 mg/kg/day, in the
diet for two years. Rats receiving 3 mg/kg/day showed depression of
erythrocyte and plasma cholinesterase levels. No-effect level was
0.1 mg/kg/day.

Dogs - were fed from 0.03 to 3.0 mg/kg/day for a period of two
years. Brain cholinesterase levels were not affected but the mean
level of plasma cholinesterase as a percentage of the mean control
level was 63 at 3 mg/kg/day. The no-effect level in dogs is
0.01 mg/kg/day and even at 1 mg/kg/day there was only a slight
decrease in plasma cholinesterase levels.

2.1.7 Supplementary studies of toxicity

Carcinogenicity: Rats were fed 0.1 and 1.0 mg/kg/day for two
years. No spontaneous rumour incidence observed and it was concluded
that chlorpyrifos-methyl is not carcinogenic.

Teratogenicity: Rats were fed dose levels of 50, 100 and
200 mg/kg/day on days 6-15 of gestation. No teratogenic effects were
observed. A study on mice with doses up to 250 mg/kg/day for seven
days on days 7-13 of gestation showed effects at highest dose level
associated with decreased weight growth or maturation of the mouse.

Neurotoxicity: Hens surviving an oral dose of 4455 mg
chlorpyrifos-methyl/kg were given both atropine, 10 mg/kg and PAM,
50 mg/kg intramuscularly as well as a second oral dose of 4555 mg
chlorpyrifos-methyl/kg on the twenty-first day after first dose. The
birds were held for a further 21 days during which no clinical signs
of ataxia were observed.

Reproduction: Prolonged dietary administration of
chlorpyrifos-methyl at levels of 1 or 3 mg/kg/day had no adverse
effect on the reproduction capacity of either male or female rat.

2.1.8 Modification of toxicity

No information

2.2 TOXICOLOGY - MAN

2.2.1 Absorption

Ingestion is likely to be the only significant route of absorption.

2.2.2 Dangerous doses

Single: Not known.

Repeated: Not known.

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 Observation of volunteers

Human - 28 single daily doses were administered to two groups of
five adult males each at either 0.1 or 0.03 mg/kg/day. These
treatments were without effect and produced no measurable
cholinesterase changes.

Chlorpyrifos-methyl was given orally three times a day to three male
and three female humans at either 0.1 or 0.3 mg/kg/day. At a dose
rate of 0.3 mg/kg/day for 14 days there was no effect on erythrocyte
cholinesterase activity but plasma cholinesterase depression greater
than two standard deviations below the mean pretreatment level was
noted. At the dose rate of 0.1 mg/kg for 21 days there was no change
in plasma or erythrocyte cholinesterase activity. There were no
other changes or adverse clinical symptoms at any dose level.

2.2.6 Reported mishaps

No information.

2.3 TOXICITY TO NON-MAMMALIAN SPECIES

2.3.1 Fish - Toxic to shrimps, crabs and fish.

2.3.2 Birds

Chicken LD50 > 2000 mg/kg
Bob white quail LD50 1835 mg/kg in diet
Japanese quail LC50 > 5000 mg/kg in diet
Mallard duck LC50 2500-5000 mg/kg in diet

2.3.3 Other species

No information.

3. FOR REGULATORY AUTHORITIES - RECOMMENDATIONS ON REGULATIONS OF
COMPOUND

3.1 RECOMMENDED RESTRICTIONS ON AVAILABILITY

(for definition of categories, see introduction)

Liquid formulations 25% and over, category 4. All other
formulations, category 5.

3.2 TRANSPORATION AND STORAGE

All formulations - Should be transported or stored in clearly
labelled leak-proof containers out of reach of children, away from
food or drink.

3.3 HANDLING

Formulations in category 4 - Adequate washing facilities should be
provided at all times during handling and should be close to the
site of the handling. Eating, drinking and smoking should be
prohibited during handling and before washing after handling.

Formulations in category 5 - No facilities other than those needed
for the handling of any chemical may be required.

3.4 DISPOSAL AND/OR DECONTAMINATION OF CONTAINER

Containers may be decontaminated (for method see paragraph 4.3 in
Part 4). Decontaminated containers should not be used for food and
drink. Containers that are not decontaminated should be burned or
should be crushed and buried below topsoil. Care must be taken to
avoid subsequent contamination of water sources.

3.5 SELECTION, TRAINING AND MEDICAL SUPERVISION OF WORKERS

Formulations in category 4 - Pre-employment medical examination
and periodic cholinesterase test for workers desirable. Warning of
workers to avoid contact essential.

3.6 ADDITIONAL REGULATIONS RECOMMENDED IF DISTRIBUTED BY AIRCRAFT

All formulations - No special regulations recommended.

3.7 LABELLING

Formulations in category 4 - Minimum cautionary statement

"Chlorpyrifos-methyl is an organophosphorus compound which inhibits
cholinesterase. It is of low toxicity but may be poisonous if
swallowed. 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 atropine with pralidoxime are
specific antidotes; artificial respiration may be needed."

Formulations in category 5 - Minimum cautionary statement

This formulation contains chlorpyrifos-methyl. Keep the material out
of reach of children and well away from foodstuffs, animal feed and
their containers.

3.8 RESIDUES IN FOOD

Maximum residue limits have been recommended by the Joint FAO/WHO
Meeting on Pesticide Residues.

4. PREVENTION OF POISONING IN MAN AND EMERGENCY AID

4.1 PRECAUTIONS IN USE

4.1.1

Chlorpyrifos-methyl is an organophosphorus insecticide of low
toxicity. It can be absorbed by mouth, and to some extent through
the intact skin. In dilute liquid formulations the vehicle (solvent)
may be more toxic than the insecticide.

4.1.2 Manufacture and formulation

T.L.V. - No information. Although volatility is low, vapour and
dust should be controlled. Protective equipment for skin and
respiratory protection may be desirable.

4.1.3 Mixers and applicators

When opening the container and when mixing, care should be taken to
avoid contact with the mouth and eyes. If necessary a facial visor
and gloves should be worn. Mixing, if not mechanical, should always
be carried out with a paddle of appropriate length.

Splashes should 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 chlorpyrifos-methyl and associated with its
application should 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, other populations should not be
exposed to hazardous amounts of chlorpyrifos-methyl.

4.2 ENTRY OF PERSONS INTO TREATED AREAS

Persons may enter treated areas as soon as the spray has dried
without being exposed to hazardous amounts of chlorpyrifos-methyl.

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
chlorpyrifos-methyl 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 following the ingestion of
chlorpyrifos-methyl may include excessive sweating, headache,
weakness, giddiness, nausea, vomiting, stomach pains, blurred
vision, slurred speech, and muscle twitching. If a massive dose has
been swallowed there may be convulsion, coma, loss of reflexes and
loss of sphincter control. Symptoms of poisoning are unlikely to
occur following dermal contact.

4.4.2 Treatment before person is seen by a physician, if these
symptoms appear following exposure

If swallowed, vomiting should be induced if the person is conscious.
In the event of a collapse, artifical respiration should be given.

5. FOR MEDICAL AND LABORATORY PERSONNEL

5.1 MEDICAL DIAGNOSIS AND TREATMENT OF CASES OF POISONING

5.1.1 General information

An organophosphorus insecticide of low toxicity which can be
absorbed by the mouth and by inhalation. Absorption may occur slowly
through the dermal route. It is a weak inhibitor of acetyl
cholinesterase. It is metabolized and excreted rapidly from the
body. Poisoning in man has not been reported. In dilute liquid
formulations the vehicle may be more toxic than the insecticide.

5.1.2 Symptoms and signs

Based upon studies and upon symptoms of poisoning from other
organophosphorus pesticides, initial symptoms of poisoning may
include excessive sweating, headache, weakness, giddiness, nausea,
vomiting, stomach pains, blurred vision, slurred speech and muscle
twitching. In the event of ingestion of an excessive dose more
advanced symptoms of poisoning may be convulsions, coma, loss of
reflexes and loss of sphincter control.

5.1.3 Laboratory

The most important finding is reduction in activity of blood
cholinesterase. Urinary levels of the main metabolite
3,5,6-trichloro-2-pyridinol could be used as a measure of exposure.

5.1.4 Treatment

If pesticide has been ingested, unless the patient is vomiting,
rapid gastic lavage should be performed using 5% sodium bicarbonate,
if available. In spite of the low dermal toxicity after skin
contact, it is advisable to wash the skin 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 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 4-6 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 administration of atropine. If the patient is
cyanotic, artificial respiration should be given at the same time as
atropine sulfate. The airways should be kept free and artificial
respiration, if necessary, should be applied, preferably by
mechanical means. If necessary intubation should be performed.

Contraindicated are morphine, barbiturates, phenothiazine
tranquillizers and central stimulants of all kinds.

5.1.5 Prognosis

As there have been no reports of poisoning of man with
chlorpyrifos-methyl the prognosis is not known. By analogy with
other moderately toxic organophosphorus compounds it may be assumed
that if the acute toxic effect is survived the chances of complete
recovery are good. In very severe cases following the ingestion of a
massive dose of chlorpyrifos-methyl it is possible that without
adequate artificial respiration prolonged hypoxia could give rise to
permanent brain damage.

5.1.6 References of previously reported cases

None.

5.2 SURVEILLANCE TESTS


Test Normal level Action level Symptomatic level

Plasma cholinesterase 100%* 50% variable

Erythrocyte cholinesterase 100% 70% usually < 40%

*Percentage of pre-exposure activity by any test.


5.3 LABORATORY METHODS

References are given only.

5.3.1 Detection and assay of compound

It is unlikely the unchanged chlorpyriphos-methyl will be measurable
in human tissues after exposure. Determination of the level of blood
cholinesterase is probably the most suitable method in cases of
suspected poisoning. Levels of unchanged chlorpyrifos-methyl and its
major metabolite, 3,5,6-trichloro-2-pyridinol can be measured in
faeces and urine by methods using gas-liquid chromatography.

Johnson, J. C. et al. (1974) J. Dairy Sci., 57(1), 467-73

McKellar, R. L. & Dishburger, H. J. (1970) The Dow Chemical Company
Method ACR 70.19

5.3.2. Other tests of cases of poisoning

Levels of cholinesterase in blood provide the most useful diagnosis
of poisoning.


Michel, N. O. (1949) J. Lab. Clin. Med., 34, 1564-1568

Ellman, G. L., Courtney, K. D., Andreas, V. jr, & Featherstone, R.
M. (1961) Biochem. Pharmacol., 7, 88-95

See Also:
Toxicological Abbreviations
Chlorpyrifos-methyl (WHO Pesticide Residues Series 5)
Chlorpyrifos-methyl (Pesticide residues in food: 1979 evaluations)
Chlorpyrifos-methyl (Pesticide residues in food: 1991 evaluations Part II Toxicology)
Chlorpyrifos-methyl (Pesticide residues in food: 1992 evaluations Part II )
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