IPCS INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY
Health and Safety Guide No. 79
METHAMIDOPHOS
HEALTH AND SAFETY GUIDE
UNITED NATIONS INTERNATIONAL
ENVIRONMENT PROGRAMME LABOUR ORGANISATION
WORLD HEALTH ORGANIZATION
WORLD HEALTH ORGANIZATION, GENEVA 1993
Published by the World Health Organization for the International
Programme on Chemical Safety (a collaborative programme of the United
Nations Environment Programme, the International Labour Organisation,
and the World Health Organization)
This report contains the collective views of an international group of
experts and does not necessarily represent the decisions or the stated
policy of the United Nations Environment Programme, the International
Labour Organisation, or the World Health Organization
WHO Library Cataloguing in Publication Data
Methamidophos: health and safety guide.
(Health and safety guide ; no. 79)
1.Hazardous substances - standards
2.Insecticides, Organothiophosphate - standards
3.Insecticides, Organothiophosphate - toxicity I.Series
ISBN 92 4 151079 X (NLM Classification: WA 240)
ISSN 0259-7268
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CONTENTS
INTRODUCTION
1. PRODUCT IDENTITY AND USES
1.1. Identity
1.2. Physical and chemical properties
1.3. Analytical methods
1.4. Uses
2. SUMMARY AND EVALUATION
2.1. Exposure
2.2. Kinetics and metabolism
2.3. Effects on experimental animals and in vitro test systems
2.4. Effects on humans
2.5. Effects on the environment
3. CONCLUSIONS AND RECOMMENDATIONS
3.1. Conclusions
3.2. Recommendations
4. HUMAN HEALTH HAZARDS, PREVENTION AND PROTECTION, EMERGENCY ACTION
4.1. Human health hazards, prevention and protection, first aid
4.1.1. Advice to physicians
4.1.1.1 Symptoms of poisoning14
4.1.1.2 Medical treatment14
4.1.2. Health surveillance advice
4.2. Explosion and fire hazards
4.3. Storage
4.4. Transport
4.5. Spillage and disposal
4.5.1. Spillage
4.5.2. Disposal
5. HAZARDS FOR THE ENVIRONMENT AND THEIR PREVENTION
6. CURRENT REGULATIONS, GUIDELINES, AND STANDARDS
6.1. Previous evaluations by international bodies
6.2. Exposure limit values
6.3. Specific restrictions
6.4. Labelling, packaging, and transport
6.5. Waste disposal
BIBLIOGRAPHY
ANNEX Treatment of organophosphate insecticide poisoning in man
INTRODUCTION
This Health and Safety Guide is not based on an existing Environmental
Health Criteria monograph, but on evaluations by the Joint FAO/WHO
Meeting on Pesticide Residues and on critical national reviews.
The first three sections of this Health and Safety Guide present
essential technical information and the hazard evaluation. Section 4
includes advice on preventive and protective measures and emergency
action; health workers should be thoroughly familiar with the medical
information to ensure that they can act efficiently in an emergency.
The section on regulatory information has been extracted from the
legal file of the International Register of Potentially Toxic
Chemicals (IRPTC) and from other United Nations sources.
The target readership includes occupational health services, those in
ministries, governmental agencies, industry, and trade unions who are
involved in the safe use of chemicals and the avoidance of
environmental health hazards, and those wanting more information on
this topic. An attempt has been made to use only terms that will be
familiar to the intended user. However, sections 1 and 2 inevitably
contain some technical terms.
Revision of the information in this Guide will take place in due
course, and the eventual aim is to use standardized terminology.
Comments on any difficulties encountered in using the Guide would be
very helpful and should be addressed to:
The Director
International Programme on Chemical Safety
World Health Organization
1211 Geneva 27
Switzerland
THE INFORMATION IN THIS GUIDE SHOULD BE CONSIDERED AS A STARTING POINT
TO A COMPREHENSIVE HEALTH AND SAFETY PROGRAMME
1. PRODUCT IDENTITY AND USES
1.1 Identity
Chemical structure:
O
"
CH3OPSCH3
'
NH2
Molecular formula: C2H8O2NPS
Common names: Methamidophos, (BSI, E-ISO, F-ISO, ANSI)
IUPAC name: O,S,-dimethyl phosphoramidothioate
CAS chemical name: O,S,-dimethyl phosphoramidothioate
Trade names: Monitor(R), Tamaron(R), Nitosol(R)
CAS registry number: 10265-92-6
RTECS registry number: TB4970000
1.2 Physical and chemical properties
Pure methamidophos is a colourless crystalline solid with a melting
point of 44.5 °C. Technical methamidophos, which is about 73% pure,
is in the form of yellowish to colourless crystals. Some physical
properties are given in Table 1.
Table 1. Physical properties of methamidophos
Relative molecular mass 141.1
Melting point (°C) 44.5 (pure)
37-39 (technical)
Boiling point (°C) thermally unstable
Vapour pressure (30 °C) 40 mPa
Solubility in water (kg/litre) 2
Density (20 °C) 1.31
Half-life in aqueous solution
at pH 2.0 (40 °C) 140 h
at pH 9 (37 °C) 120 h
Methamidophos, which is readily soluble in water (>2 kg/litre),
alcohols, ketones, and aliphatic chlorinated hydrocarbons, is
sparingly soluble in ether and practically insoluble in petroleum
ether. This insecticide is stable at ambient temperatures.
Methamidophos decomposes before its boiling point is reached.
Technical methamidophos and concentrated formulated products are
corrosive to mild steel and copper-containing alloys. This
insecticide is not compatible with alkaline pesticides.
1.3 Analytical methods
The active ingredient contents of the formulated products are
determined using infrared spectrometry or high-pressure liquid
chromatography. Residues can be determined by gas-liquid
chromatography using a flame ionization detector or a flame thermionic
detector after clean-up in silica gel columns.
Recommendations for methods of determination of methamidophos residues
have been made by the Codex Alimentarius Commission (FAO/WHO, 1989).
1.4 Uses
Methamidophos is an acaricide-insecticide with systemic properties.
It has been shown to be effective against a broad range of insect
pests (sucking, biting, and mining insects) on such crops as brassica,
cotton, tobacco, sugar beet, head lettuce, and potatoes. It is used
as a preharvest spray at 0.5-1.5 kg/ha. At these rates, control is
obtained for 7-21 days.
Methamidophos is marketed mainly as the water-soluble concentrate in
various concentrations.
2. SUMMARY AND EVALUATION
The following information is largely based on the evaluations of the
Joint FAO/WHO Meeting on Pesticide Residues (JMPR).
2.1 Exposure
The general population is not generally exposed to methamidophos in
air or water. Use of methamidophos in edible commodities may result
in low-level residues in some that reach the market place. If the
recommended preharvest intervals are observed, there should not be any
health hazards. The use of the related insecticide, acephate, may
give rise to methamidophos as a residue.
Degradation of methamidophos in soils and natural waters has been
found to be fairly rapid. The final degradation product is usually
phosphoric acid. The same has been observed when methamidophos is
applied to crops.
Occupational exposure to methamidophos, which may occur during
manufacturing, formulation, application, and storage, is mainly
through inhalation and dermal absorption. Higher occupational
exposures may occur in the case of accidents or as a result of
incorrect handling. With correct usage, there should not be any
exposure to hazardous amounts.
2.2 Kinetics and metabolism
Methamidophos, an anticholinesterase organophosphorus ester, is also a
metabolite of acephate. It is rapidly absorbed, distributed,
metabolized, and excreted in mammals. Excretion is mainly via the
urine in the form of acid metabolites and through expired air as
carbon dioxide.
On the basis of data on the solubility of methamidophos,
bioaccumulation would not be expected to occur. Biotransformation in
mammals results in the formation of metabolites that are
toxicologically insignificant.
2.3 Effects on experimental animals and in vitro test systems
Methamidophos is an acutely toxic pesticide with an acute oral LD50
of 15-30 mg/kg in the male rat, 30 mg/kg in the mouse, 30-50 mg/kg in
the guinea-pig, and 10-30 mg/kg in the rabbit. The acute dermal
LD50 in the male rat is 50-110 mg/kg. The inhalation LC50 in the
male rat is 525 mg/m3 for a 1-h exposure and 162 mg/m3 for a 4-h
exposure.
Animals poisoned with methamidophos show typical signs of
anticholinesterase poisoning. The signs appear rapidly (5-20 min) and
disappear in 4-6 days. The acute signs of poisoning can be relieved
with the aid of atropine and reactivators, such as 2-PAM.
Methamidophos exerts its primary effects on the red blood cell (and
presumably brain) cholinesterase in animal models. In humans, plasma
cholinesterase appears to be the more sensitive enzyme parameter.
Moderate erythema and oedema were observed in skin tests on the rabbit
ear. The chemical is also irritating to the eye.
In short- and long-term studies, no significant somatic effects were
noted. Cholinesterase depression was manifested in short-term
studies. In 90-day studies on dogs, cholinesterase depression was
observed at 5 mg/kg while a dietary level of 1.5 mg/kg (equivalent to
0.04 mg/kg body weight per day) did not cause any observable effects.
In a 2-year study on dogs, somatic effects were not noted at a level
of 0.75 mg/kg per day, but cholinesterase activity was not determined.
Depression of cholinesterase activity was observed in rat feeding
studies at dietary levels of 6 mg/kg or more, but a level of 2 mg/kg
did not induce any depression of cholinesterase activity. Maximum
tolerated doses in hens failed to cause delayed neuropathy.
In reproductive studies, several parameters were affected at
relatively low levels (the levels were, however, sufficient to cause
cholinesterase depression in the parents). No terata were induced in
the reproductive study or in special teratological studies on rabbits,
though the dose levels used in the latter studies were extremely low.
Methamidophos was found to be non-mutagenic in bacterial and in vivo
assays. There were no indications of oncogenicity in a mouse
oncogenicity study or in a long-term toxicity/oncogenicity study on
rats.
The following levels have been found not to cause any toxicological
effect (FAO/WHO, 1990):
Rat 2 mg/kg in the diet, equal to 0.1 mg/kg
body weight per day
Dog 2 mg/kg in the diet equal to 0.06 mg/kg
body weight per day)
Chicken 0.3 mg/kg body weight per day
Human 0.04 mg/kg body weight per day
2.4 Effects on humans
Several cases of methamidophos poisoning in humans have been reported.
In a controlled study in which a combined dose of methamidophos and
acephate was administered to groups of male and female volunteers,
cholinesterase depression was observed predominantly in those
receiving a higher methamidophos: acephate ratio (1:4 rather than
1:9). A higher total concentration (0.2 mg/kg), administered at the
lower ratio (1:9), did not result in any depression of enzyme
activity.
Excessive human exposure (among others, Senanayake & Johnson, 1982) to
methamidophos caused delayed polyneuropathy.
2.5 Effects on the environment
In mildly acidic or neutral aqueous solutions, methamidophos is stable
at temperatures up to 80 °C. Methamidophos is degraded in outdoor
natural water systems with half-lives of 15.9 days in water and 7.5
days in silt. Although methamidophos was leached from soils, it also
degraded rapidly in natural water systems.
It is degraded relatively rapidly in soils. Within 1 week, the
residue dropped to 10% of the level measured on the day of
application. Furthermore, there was no accumulation of the
insecticide, even after several applications.
Methamidophos is moderately toxic for fish as evidenced by 96-h
LC50s of 25 mg/litre for rainbow trout (Oncorhynchus mykiss), and
approximately 100 mg/litre for goldfish (Carassius auratus) and carp
(Cyprinus carpio). The LD50s for the mallard duck (Anas
platyrhynchos), Japanese quail (Coturnix coturnix Japonica), and
the hen (Gallus domesticus) are 29.5, 10, and 25 mg/kg,
respectively. This insecticide can also be harmful to bees.
3. CONCLUSIONS AND RECOMMENDATIONS
3.1 Conclusions
* Under proper conditions of use, exposure of the general
population to methamidophos is negligible.
* Methamidophos is highly toxic, but, using appropriate safety
precautions, exposure to methamidophos during manufacture,
formulation, application, and disposal should not pose an
unacceptable human health hazard.
* Methamidophos is rapidly degraded to non-toxic products in the
environment. However, care should be taken not to expose aquatic
invertebrates, bees, birds, fish, and wild mammals to this
insecticide.
3.2 Recommendations
* Safe re-entry periods under different conditions of use should
be determined.
* Effluent water from formulation plants should be treated.
* Methamidophos should be used only with proper precautions and
under proper supervision, in order to avoid overexposure.
4. HUMAN HEALTH HAZARDS, PREVENTION AND PROTECTION, EMERGENCY ACTION
4.1 Human health hazards, prevention and protection, first aid
The acute oral and dermal toxicities of methamidophos are high and it
can be hazardous for human beings if incorrectly handled. On
overexposure, typical signs and symptoms of organophosphorus poisoning
may occur rapidly. The human health hazards associated with certain
types of exposure to methamidophos, together with preventive and
protective measures and first aid, are listed in Table 2.
4.1.1 Advice to physicians
For a more complete treatise on the effects of organophosphorus
insecticides, especially their short- and long-term effects on the
nervous system, please refer to EHC 63: Organophosphorus insecticides
- a general introduction (WHO, 1986). The section on treatment from
the above monograph is reproduced as an Annex to this Guide.
4.1.1.1 Symptoms of poisoning
Signs and symptoms may include a feeling of exhaustion, headache,
blurred vision, weakness, and confusion. Vomiting, abdominal pain,
excessive sweating, and salivating may develop. The pupils are
constricted. Difficulty in breathing may be experienced, due to
congestion of the lungs and weakness of the respiratory muscles.
Arrhythmias and cardiac failure have been reported. On severe
poisoning, there will be muscle spasms, unconsciousness, and
convulsion. Breathing may stop, followed by death.
4.1.1.2 Medical treatment
If ingested and the formulation does not contain petroleum
distillates, induce vomiting, or preferably perform gastric lavage
using 5% sodium bicarbonate. In case of ingestion of liquid
formulations containing hydrocarbon solvents, vomiting involves a risk
of aspiration pneumonia. Instead, the stomach should be emptied, as
soon as possible, by careful gastric lavage (using a cuffed
endotracheal tube). If possible, identify the solvents present in the
formulation and observe the victim for additional toxic effects. As
early as possible, administer 2 mg of atropine sulfate iv and
1000-2000 mg pralidoxime chloride or 250 mg obidoxime chloride (adult
dose) iv to patients suffering from severe respiratory difficulties,
convulsions, and unconsciousness. Repeated doses of 2 mg of atropine
sulfate should be given, as required, based on the respiration, blood
pressure, pulse frequency, salivation, and convulsion conditions.
Diazepam should be given in all but the mildest cases in doses of
10 mg, sc or iv, which may be repeated as required. For children, the
doses are 0.04-0.08 mg of atropine/kg body weight, 250 mg of
pralidoxime chloride per child or 4-8 mg of obidoxime chloride per kg
body weight.
Artificial respiration should be applied if required.
Morphine, barbiturates, phenothiazine derivatives, tranquillizers,
and all kinds of central stimulants are contraindicated in the
absence of artificial respiration.
The diagnosis of intoxication should be confirmed, as soon as
possible, by determination of the cholinesterase activity in venous
blood.
In all cases of clinical poisoning with methamidophos and other
organophosphorus insecticides, it is essential to maintain general
surveillance and cholinesterase and cardiac monitoring for at least 14
days, and longer if necessary, and to adopt general supportive and
specific therapy in accordance with the findings.
As stated earlier, more information on the treatment of
organophosphorus insecticide poisoning can be obtained from EHC No.
63: Organophosphorus insecticides - a general introduction (WHO,
1986) and also the Annex to this Guide.
4.1.2 Health surveillance advice
In human beings exposed to methamidophos, the cholinesterase activity
of the blood should be monitored regularly. Measurement of whole
blood acetylcholineaterase (AChE) is the most widely adopted method.
Because physiological variations of blood cholinesterase (ChE) levels
occur in a healthy person and among populations, it is preferable to
compare the results with pre-exposure ChE levels.
Table 2. Human health hazards, prevention and protection, first aid
HAZARDS/SYMPTOMS PREVENTION AND PROTECTION FIRST AID
GENERAL: Readily absorbed via skin,
ingestion, and inhalation; may cause
organophosphate poisoning: weakness,
headache, vomiting, excessive sweating
and salivation, pinpoint pupils; in
severe cases: convulsions,
unconsciousness, and death due to
respiratory paralysis
SKIN: Irritation; redness; extensive Wear PVC or neoprene gloves and Remove and wash contaminated
contamination may cause poisoning apron; rubber boots clothing; wash contaminated skin
with water and soap; obtain medical
attention immediately
EYES: Irritation; redness Wear safety goggles or face shield Flush eyes with clean water for at
least 15 min; if irritation persists,
obtain medical attention immediately
INHALATION: Overexposure may Avoid breathing the vapour; use In case of signs and symptoms, remove
cause poisoning proper (exhaust) ventilation or a from contaminated area and obtain
respirator or mask approved for toxic medical attention immediately
dust and organic vapours
INGESTION: An unlikely occupational Wash hands before eating, drinking, -
hazard using the toilet, and after work
Accidental or intentional ingestion - Obtain medical attention immediately;
may rapidly lead to severe poisoning induce vomiting, if subject is consciousa;
if breathing has stopped, apply
artificial respiration
HAZARDS/SYMPTOMS PREVENTION AND PROTECTION FIRST AID
REPEATED EXPOSURE THROUGH As above As above
INHALATION OR INGESTION, OR
THROUGH SKIN: may gradually lead
to signs and symptoms of inhibition of
cholinesterase activity
a Caution: If methamidophos is dissolved in solvents, e.g., petroleum solvents,
vomiting may cause pulmonary aspiration.
Depressions of AChE or ChE levels of 20-25% are considered diagnostic
of exposure, but not necessarily indicative of hazard. Depressions of
30-50% or more are considered indicators for removal of an exposed
individual from further contact with pesticides, until levels return
to normal. Work procedures and hygiene should also be checked.
4.2 Explosion and fire hazards
Liquid formulations may be flammable. With sufficient burning or
external heat, methamidophos will decompose, emitting toxic fumes.
Fire-fighters must wear protective clothing and a self-contained
breathing apparatus. Extinguish fires with alcohol-resistant foam or
powder. Confine the use of water spray to the cooling of unaffected
stock, thus avoiding polluted run-off from the site.
4.3 Storage
Technical methamidophos and its formulations should be stored in the
original labelled containers in locked, well ventilated storage areas,
preferably dedicated to insecticides. Do not expose to direct
sunlight. Keep products out of reach of children and unauthorized
personnel. Do not store near animal feed or foodstuffs.
4.4 Transport
Comply with any local regulations regarding the movement of hazardous
goods. Do not transport with animal feed or foodstuffs. Food and
animal feed should not be transported in vehicles that have been used
for the transport of pesticides. Before dispatch, make sure that
containers are in good condition and that the labels are undamaged.
4.5 Spillage and disposal
4.5.1 Spillage
Avoid skin contamination and inhalation of vapour. Cover contaminated
areas and absorb spilled liquid with a 1:3 mixture of sodium carbonate
crystals and damp sawdust, lime, sand, or earth. Sweep up and place
in an impervious container. Ensure that the container is tightly
closed and labelled before transfer to a safe place for disposal.
Spills and powders should be cleaned up using a dustless method (e.g.,
by a vacuum cleaner suitable for use with toxic dusts).
Alternatively, mix with damp saw-dust and place in a separate
container for subsequent disposal. Dry brushing should not be carried
out, as this creates dust clouds.
Prevent liquid from spreading and contaminating other cargo,
vegetation, or waterways by using a barrier of the most suitable and
readily available material, e.g., earth or sand.
Empty any of the product remaining in the damaged/leaking container
into a clean empty container, which should then be tightly closed and
suitably labelled. Decontaminate emptied leaking containers with a
10% sodium carbonate (washing soda) solution, added at a rate of at
least 1 litre/20-litre drum. Swirl round to rinse walls, empty, and
add rinsings to sawdust. Do not re-use containers for any other
purpose. Puncture and crush the container to prevent reuse.
4.5.2 Disposal
Large amounts should be incinerated at high temperature in a unit with
effluent gas scrubbing. When no incinerator is available, bury in an
approved dump, or in an area where there is no risk of contamination
of surface or groundwater. Before burying, liberally mix with sodium
carbonate (washing soda) crystals, to help neutralize the product, and
with soil rich in organic matter. Comply with any local legislation.
5. HAZARDS FOR THE ENVIRONMENT AND THEIR PREVENTION
As it is readily degraded, methamidophos is non-persistent in the
environment. Under normal conditions of usage, it will not
accumulate. However, it is toxic for aquatic invertebrates, birds,
bees, fish, and wild mammals.
Avoid contamination of the soil, water, and atmosphere by proper
methods of use, storage, transport, handling, and waste disposal. In
case of spillage, use the methods advised in section 4.5.1.
6. CURRENT REGULATIONS, GUIDELINES, AND STANDARDS
The information given in this section has been extracted from the
International Register of Potentially Toxic Chemicals (IRPTC) legal
file and other United Nations sources. A full reference to the
original national document from which the information was extracted
can be obtained from IRPTC.
The reader should be aware that regulatory decisions about chemicals
taken in a certain country can only be fully understood in the
framework of the legislation of that country. Furthermore, the
regulations and guidelines of all countries are subject to change and
should always be verified with the appropriate regulatory authorities
before application.
6.1 Previous evaluations by international bodies
Methamidophos was evaluated by the Joint FAO/WHO Meeting on Pesticide
Residues (JMPR) in 1976, 1982, 1985, and 1990. An acceptable daily
intake (ADI) for man of 0-0.004 mg/kg body weight was estimated in
1990.
In the WHO recommended classification of pesticides by hazard and
guidelines to classification, 1992-93 (WHO 1992), technical
methamidophos is classified as highly hazardous (Class 1b), when
handled in accordance with instructions.
The FAO/WHO Codex Alimentarius Commission (FAO/WHO, 1986, 1989, 1990)
recommended Maximum Residue Limits (MRLs) in several food
commodities, ranging from 0.01 to 5 mg/kg as follows:
Commodity MRL (mg/kg)
Carcass meat and fat of cattle,
goats and sheep, milk, tree tomato 0.01a
Soya bean (dry), sugar beet 0.05
Rapeseed 0.1
Brussels sprouts, cucumber, lettuce
(head), sugar beet (leaves or tops) 1
Alfalfa forage (green) 2
Hops (dry) 5
a Approximate limit of determination.
6.2 Exposure limit values
Pre-harvest intervals (the time between the last application of
methamidophos and the harvest of the treated plants) have been set in
many countries. These intervals vary from 3 to 90 days (most of them
14-21 days), depending on the crop, harvesting technique, and the
country, and should be verified with the competent national authority.
The FAO/WHO Maximum Residue Limits (MRLs) for methamidophos are shown
in section 6.1.
The MRL in fruits and vegetables in Finland is 0.2 mg/kg.
6.3 Specific restrictions
Methamidophos is approved as a pesticide in many countries. Specific
uses, limitations, and precautions are listed in national regulatory
documents. In the USA, methamidophos is classified for restricted
use, and its preparations may only be handled by certified operators.
In Germany, it may not be handled by adolescents and pregnant and
nursing women.
6.4 Labelling, packaging, and transport
The United Nations Committee of Experts on the Transportation of
Dangerous Goods classifies methamidophos in:
- Hazard Class 6.1: poisonous substance;
- Packing Group 2: substances and preparations presenting a
serious risk of poisoning, for formulations
containing 15-100% active material;
- Packing Group 3: harmful substances and preparations
presenting a relatively low risk of
poisoning, for solid formulations containing
3-15% active material and liquid formulations
containing 1.5-15% active material.
The label should be as follows:
In the International Maritime Dangerous Goods (IMDG) Code,
methamidophos is classified as a marine pollutant. It should bear the
following mark on the label:
For flammable formulations, the following subsidiary label is required
when the flash point of the solution is below, or equal to, 61 °C
(closed cup):
There is no WHO specification for methamidophos, as the material is
not used in public health. However, proposals for FAO specifications
for methamidophos are under preparation. These include the following:
All packages should bear, durably and legibly marked on the container,
the following:
- manufacturer's name;
- technical methamidophos to specification;
- batch or reference number, and date of test;
- net weight of contents;
- date of manufacture.
and, in the case of the formulated products:
- manufacturer's name;
- methamidophos to specification;
- methamidophos ... g/kg;
- batch or reference number, and date of test;
- net weight of contents;
- instructions for dilution;
- date of formulation.
and the following minimum cautionary notice:
Methamidophos is an organophosphorus compound that inhibits
cholinesterase. It is poisonous if swallowed or inhaled. It
may be absorbed through the skin. Avoid skin contact: wear
protective gloves, clean protective clothing, and a respirator
when handling the material. Wash thoroughly with soap and water
after using.
Keep the material out of the reach of children and well away
from foodstuffs and animal feed and their containers.
If poisoning occurs, call a physician. Atropine and pralidoxime
are specific antidotes, and artificial respiration may be
needed.
The methamidophos content should be declared (minimum 73% for the
technical products) and should not differ from the declared percentage
by more than 2% for the technical product and 5-10% for its
formulations.
Containers should be suitable, clean, dry, and as specified in the
order, and should not adversely affect, or be affected by, the
product, but should adequately protect it from external conditions.
Containers should comply with pertinent national and international
transport and safety regulations.
Specifications for storage stability are given.
The European Community Legislation requires labelling as dangerous
substance using the symbol:
The label must read:
Very toxic by inhalation, in contact with skin and if swallowed;
keep locked up; keep away from food, drink and animal feeding
stuffs; after contact with skin, wash immediately with plenty of
- - - - (to be specified by the manufacturer); in case of
accident or if you feel unwell, seek medical advice (show the
label where possible).
The European Economic Community legislation on the labelling of
pesticide preparations classifies pesticide preparations that contain
methamidophos in Class 1A as toxic at concentrations >1% and as
harmful at >0.05-1%. Member States should ensure that pesticides
cannot be placed on the market unless their packaging, fastenings, and
labels comply with the requirements laid down.
6.5 Waste disposal
In the USA, any non-domestic waste containing methamidophos is
considered a hazardous waste and should be notified. Permits are
required for its handling, transport, treatment, storage, or disposal.
Waste incinerators must achieve 99.99% destruction and removal of this
substance.
BIBLIOGRAPHY
CEC (1987) Legislation on dangerous substances - Classification and
labelling in the European Communities. Vol. 1 & 2. Commission of the
European Communities, London, Graham & Trotman, Ltd.
FAO (1985a) Guidelines for the packaging and storage of pesticides.
Rome, Food and Agriculture Organization of the United Nations.
FAO (1985b) Guidelines for the disposal of waste pesticides and
pesticide containers on the farm. Rome, Food and Agriculture
Organization of the United Nations.
FAO (1985c) Guidelines on good labelling practice for pesticides.
Rome, Food and Agriculture Organization of the United Nations.
FAO (1986) International code of conduct on the distribution and use
of pesticides. Rome, Food and Agriculture Organization of the United
Nations.
FAO/WHO (1964-present) Evaluations of pesticide residues in food.
Rome, Food and Agriculture Organization of the United Nations.
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ANNEX
TREATMENT OF ORGANOPHOSPHATE INSECTICIDE POISONING IN MAN1
All cases of organophosphorus poisoning should be dealt with as an
emergency and the patient sent to hospital as quickly as possible.
Although symptoms may develop rapidly, delay in onset or a steady
increase in severity may be seen up to 48 h after ingestion of some
formulated organophosphorus insecticides.
Extensive descriptions of treatment of poisoning by organophosphorus
insecticides are given in several major references (Kagan, 1977;
Taylor, 1980; UK DHSS, 1983; Plestina, 1984) and will also be included
in the IPCS Health and Safety Guides to be prepared for selected
organophosphorus insecticides.
The treatment is based on:
(a) minimizing the absorption;
(b) general supportive treatment; and
(c) specific pharmacological treatment.
A.1 Minimizing the absorption
When dermal exposure occurs, decontamination procedures include
removal of contaminated clothes and washing of the skin with alkaline
soap or with a sodium bicarbonate solution. Particular care should be
taken in cleaning the skin area where venepuncture is performed.
Blood might be contaminated with direct-acting organophosphorus esters
and, therefore, inaccurate measures of ChE inhibition might result.
Extensive eye irrigation with water or saline should also be
performed. In the case of ingestion, vomiting might be induced, if
the patient is conscious, by the administration of ipecacuanha syrup
(10-30 ml) followed by 200 ml water.
This treatment is, however, contraindicated in the case of pesticides
dissolved in hydrocarbon solvents. Gastric lavage (with addition of
bicarbonate solution or activated charcoal) can also be performed,
particularly in unconscious patients, taking care to prevent
aspiration of fluids into the lungs (i.e., only after a tracheal tube
has been put into place).
1 From EHC 63: Organophosphorus insecticides - a general introduction.
Geneva, World Heralth Organization, 1986.
The volume of fluid introduced into the stomach should be recorded and
samples of gastric lavage frozen and stored for subsequent chemical
analysis. If the formulation of the pesticide involved is available,
it should also be stored for further analysis (i.e., detection of
toxicologically relevant impurities). A purgative can be administered
to remove the ingested compound.
A.2 General supportive treatment
Artificial respiration (via a tracheal tube) should be started at the
first sign of respiratory failure and maintained for as long as
necessary.
Cautious administration of fluids is advised, as well as general
supportive and symptomatic pharmacological treatment and absolute
rest.
A.3 Specific pharmacological treatment
A.3.1 Atropine
Atropine should be given, beginning with 2 mg iv and given at
15-30-min intervals. The dose and the frequency of atropine treatment
varies from case to case, but should maintain the patient fully
atropinized (dilated pupils, dry mouth, skin flushing, etc.).
Continuous infusion of atropine may be necessary in extreme cases and
total daily doses up to several hundred mg may be necessary during the
first few days of treatment.
A.3.2 Oxime reactivators
Cholinesterase reactivators (e.g., pralidoxime, obidoxime)
specifically restore AChE activity inhibited by organophosphates.
This is not the case with enzymes inhibited by carbamates. The
treatment should begin as soon as possible, because oximes are not
effective on "aged" phosphorylated ChEs. However, if absorption,
distribution, and metabolism are thought to be delayed for any
reasons, oximes can be administered for several days after
intoxication. Effective treatment with oximes reduces the required
dose of atropine. Pralidoxime is the most widely available oxime. A
dose of 1 g pralidoxime can be given either im or iv and repeated
2-3 times per day or, in extreme cases, more often. If possible,
blood samples should be taken for AChE determinations before and
during treatment. Skin should be carefully cleansed before sampling.
Results of the assays should influence the decision whether to
continue oxime therapy after the first 2 days.
There are indications that oxime therapy may possibly have beneficial
effects on CNS-derived symptoms.
A.3.3 Diazepam
Diazepam should be included in the therapy of all but the mildest
cases. Besides relieving anxiety, it appears to counteract some
aspects of CNS-derived symptoms that are not affected by atropine.
Doses of 10 mg sc or iv are appropriate and may be repeated as
required (Vale & Scott, 1974). Other centrally acting drugs and drugs
that may depress respiration are not recommended in the absence of
artificial respiration procedures.
A.3.4 Notes on the recommended treatment
A.3.4.1 Effects of atropine and oxime
The combined effect far exceeds the benefit of either drug singly.
A.3.4.2 Response to atropine
The response of the eye pupil may be unreliable in cases of
organophosphorus poisoning. A flushed skin and drying of secretions
are the best guide to the effectiveness of atropinization. Although
repeated dosing may well be necessary, excessive doses at any one time
may cause toxic side-effects. Pulse-rate should not exceed 120/min.
A.3.4.3 Persistence of treatment
Some organophosphorus pesticides are very lipophilic and may be taken
into, and then released from, fat depots over a period of many days.
It is therefore quite incorrect to abandon oxime treatment after
1-2 days on the supposition that all inhibited enzyme will be aged.
Ecobichon et al. (1977) noted prompt improvement in both condition and
blood-ChEs in response to pralidoxime given on the 11th-15th days
after major symptoms of poisoning appeared due to extended exposure to
fenitrothion (a dimethyl phosphate with a short half-life for aging of
inhibited AChE).
A.3.4.4 Dosage of atropine and oxime
The recommended doses above pertain to exposures, usually for an
occupational setting, but, in the case of very severe exposure or
massive ingestion (accidental or deliberate), the therapeutic doses
may be extended considerably. Warriner et al. (1977) reported the
case of a patient who drank a large quantity of dicrotophos, in error,
while drunk. Therapeutic dosages were progressively increased up to
6 mg atropine iv every 15 min together with continuous iv infusion of
pralidoxime chloride at 0.5 g/h for 72 h, from days 3 to 6 after
intoxication. After considerable improvement, the patient relapsed
and further aggressive therapy was given at a declining rate from days
10 to 16 (atropine) and to day 23 (oxime), respectively. In total,
92 g of pralidoxime chloride and 3912 mg of atropine were given and
the patient was discharged on the thirty-third day with no apparent
sequelae.
References to Annex
ECOBICHON, D.J., OZERE, R.L., REID, E., & CROCKER, J.F.S (1977) Acute
fenitrothion poisoning. Can. Med. Assoc. J., 116: 377-379.
KAGAN, JU.S. (1977) [Toxicology of organophosphorus pesticides.,
Moscow, Meditsina, pp. 111-121, 219-233, 260-269 (in Russian).
PLESTINA, R. (1984) Prevention, diagnosis, and treatment of
insecticide poisoning. Geneva, World Health Organization
(Unpublished document VBC/84.889).
TAYLOR, P. (1980) Anticholinesterase agents. In: Goodman, L.S. &
Gilman, A., ed. The pharmacological basis of therapeutics. 6th ed.,
New York, Macmillan Publishing Company, pp. 100-119.
UK DHSS (1983) Pesticide poisoning: notes for the guidance of
medical practitioners. London, United Kingdom Department of Health
and Social Security, pp. 41-47.
VALE, J.A. & SCOTT, G.W. (1974) Organophosphorus poisoning. Guy's
Hosp. Rep., 123: 13-25.
WARRINER, R.A., III, NIES, A.S., & HAYES, W.J., Jr (1977) Severe
organophosphate poisoning complicated by alcohol and terpentine
ingestion. Arch. environ. Health, 32: 203-205.