Organophosphorus pesticides

   1.1 Substance
   1.2 Group
   1.3 Synonyms
   1.4 Identification numbers
      1.4.1 CAS number
      1.4.2 Other numbers
   1.5 Main brand names/main trade names
   1.6 Main manufacturers/main importers
   2.1 Main risks and target organs
   2.2 Summary of clinical effects
   2.3 Diagnosis
   2.4 First-aid measures and management principles
   3.1 Origin of substance
   3.2 Chemical structure
   3.3 Physical properties
      3.3.1 Colour
      3.3.2 State/Form
      3.3.3 Description
   3.4 Hazardous characteristics
   4.1 Uses
      4.1.1 Uses
      4.1.2 Description
   4.2 High risk circumstances of poisoning
   4.3 Occupationally exposed populations
   5.1 Oral
   5.2 Inhalation
   5.3 Dermal
   5.4 Eye
   5.5 Parenteral
   5.6 Others
   6.1 Absorption by route of exposure
   6.2 Distribution by route of exposure
   6.3 Biological half-life by route of exposure
   6.4 Metabolism
   6.5 Elimination and excretion
   7.1 Mode of action
   7.2 Toxicity
      7.2.1 Human data Adults Children
      7.2.2 Relevant animal data
      7.2.3 Relevant in vitro data
      7.2.4 Workplace standards
      7.2.5 Acceptable daily intake (ADI)
   7.3 Carcinogenicity
   7.4 Teratogenicity
   7.5 Mutagenicity
   7.6 Interactions
   9.1 Acute poisoning
      9.1.1 Ingestion
      9.1.2 Inhalation
      9.1.3 Skin exposure
      9.1.4 Eye contact
      9.1.5 Parenteral exposure
      9.1.6 Other
   9.2 Chronic poisoning
      9.2.1 Ingestion
      9.2.2 Inhalation
      9.2.3 Skin exposure
      9.2.4 Eye contact
      9.2.5 Parenteral exposure
      9.2.6 Other
   9.3 Course, prognosis, cause of death
   9.4 Systemic description of clinical effects
      9.4.1 Cardiovascular
      9.4.2 Respiratory
      9.4.3 Neurological Central nervous system Peripheral nervous system Autonomic nervous system Skeletal and smooth muscle
      9.4.4 Gastrointestinal
      9.4.5 Hepatic
      9.4.6 Urinary Renal Others
      9.4.7 Endocrine and reproductive systems
      9.4.8 Dermatological
      9.4.9 Eye, ears, nose, throat: local effects
      9.4.10 Haematological
      9.4.11 Immunological
      9.4.12 Metabolic Acid-base disturbances Fluid and electrolyte disturbances Others
      9.4.13 Allergic reactions
      9.4.14 Other clinical effects
      9.4.15 Special risks
   9.5 Others
   9.6 Summary
   10.1 General principles
   10.2 Life-supportive procedures and symptomatic/specific treatment
   10.3 Decontamination
   10.4 Enhanced Elimination
   10.5 Antidote treatment
      10.5.1 Adults
      10.5.2 Children
   10.6 Management discussion
   11.1 Case reports from the literature
   12.1 Specific preventive measures
   12.2 Other
    Organophosphorus Pesticides

    International Programme on Chemical Safety
    Poisons Information Monograph (Group Monograph) G001

    1.  NAME

        1.1  Substance

             Organophosphorus pesticides

        1.2  Group

             The group includes:

             Azinphos ethyl
             Azinphos methyl
             Bromophos ethyl
             Demephron -O and -S
             Demeton  -O and  -S



        1.3  Synonyms


        1.4  Identification numbers

             1.4.1  CAS number

             Acephate                30560-19-1

             1.4.2  Other numbers

             Azinphos methyl         86-50-0
             Bromophos               2104-96-3
             Bromophos ethyl         4824-78-6
             Chlorphoxim             14816-20-7
             Chlorpyrifos            2921-88-2
             Chlorpyrifos-methyl     5598-13-0
             Chlorthiophos           60238-56-4
             Coumaphos               56-72-4
             Crotoxyphos             7700-17-6
             Crufomate               299-86-5
             Cyanofenphos            13067-93-1
             Cyanophos               2636-26-2
             Demeton                 8065-48-3
             Demeton-O               298-03-3
             Demeton-S               126-75-0
             Demeton-S-methyl        919-86-8
             Demeton-S-methylsulphon 17040-19-6
             Diazinon                333-41-5
             Dichlofenthion          97-17-6
             Dichlorvos              62-73-7
             Dicrotophos             141-66-2
             Dimefox CAS             115-26-4
             Dimethoate              60-51-5
             Dioxabenzophos          3811-49-2
             Dioxathion              78-34-2
             Disulfoton              298-04-4
             Ditalmifos              5131-24-8
             Edifenphos              17109-49-8
             EPBP                    3792-59-4
             EPN                     2104-64-5

             ESP                     2674-91-1
             Ethion                  563-12-2
             Ethopropos              13194-48-4
             Etrimfos                38260-54-7
             Famphur                 52-85-7
             Fenamiphos              22224-92-6
             Fenchlorphos            299-84-3
             Fenitrothion            122-14-5
             Fensulfothion           115-90-2
             Fenthion                55-38-9
             Fonofos                 944-22-9
             Formothion              2540-82-1
             Heptenophos             23560-59-0
             Isothioate              36614-38-71
             Isoxathion              18854-01-8
             Jodfenphos              18181-70-9
             Leptophos               21609-90-5
             Malathion               121-75-5
             Mephosfolan             950-10-7
             Methamidophos           10265-92-6
             Methidathion            950-37-8
             Mevinphos               7786-34-7
             Monocrotophos           6923-22-4
             Naled                   300-76-5
             Omethoate               1113-02-6
             Oxydemeton-methyl       301-12-2
             Parathion               56-38-2
             Parathion-methyl        298-00-0
             Phenthoate              2597-03-7
             Phorate                 298-02-2
             Phosphamidon amide      16655-69-9
             Phospholan              947-02-4
             Phoxim                  14816-18-3
             Pirimiphos-ethyl        23505-41-1
             Profenofos              41198-08-7
             Propaphos               7292-16-21
             Prothiofos              34643-46-4
             Quinlphos               13593-03-8
             Schradan                152-16-9
             Sulfotep                3689-24-51
             Sulprofos               35400-43-2
             Temephos                3383-96-8
             TEPP                    107-49-3
             Terbufos                13071-79-9
             Tetrachlorvinphos       22248-79-9
             Thiometon               640-15-3
             Thionazin               297-97-2
             Triazophos              24017-47-8
             Trichlorfon             52-68-6
             Vamidothion             2275-23-2

                    The following UN transportation numbers have
                    been established for organophosphorus pesticides (UN,

                    2783             Organophosphorus pesticides,
                                     solid, toxic, NOS.

                    2784             Organophosphorus pesticides,
                                     liquid, toxic, flammable, NOS,
                                     freezing point < 61°C, closed cup.

                    3017             Organophosphorus pesticides,
                                     liquid, toxic, flammable, freezing
                                     point 23°C, closed cup.

                    3018             Organophosphorus pesticides,
                                     liquid, toxic, NOS.

        1.5  Main brand names/main trade names

             See individual organophosphorus pesticide

        1.6  Main manufacturers/main importers

             See individual organophosphorus pesticide

    2.  SUMMARY

        2.1  Main risks and target organs

             Organophosphorus pesticides can be absorbed by all
             routes, including inhalation, ingestion, and dermal
             absorption.  The toxicological effects of the 
             organophosphorus pesticides are almost entirely due to the
             inhibition of acetylcholinesterase in the nervous system,
             resulting in respiratory, myocardial and neuromuscular
             transmission impairment.  A few organophosphorus pesticides
             have produced the so-called "Intermediate Syndrome" and
             delayed neuropathy, the latter apparently unrelated to
             acetylcholinesterase inhibition.

             The main target organs are the nervous system, respiratory
             tract and cardiovascular system.

             Degradation products in the environment are not toxic to any
             significant extent.  Thermal decomposition products may be
             harmful by inhalation and skin contamination.  Toxicity may

             also be due to the effects of solvent vehicles or other
             components of formulated pesticides.

        2.2  Summary of clinical effects

             The signs and symptoms of acute organophosphate
             poisoning are an expression of the effects caused by excess
             acetylcholine (cholinergic syndrome); they may occur in
             various combinations and can be manifest at different
             Signs and symptoms can be divided into three groups:
             -  muscarinic effect
             -  nicotinic effect
             -  central nervous system effect.
             According to the degree of the severity of poisoning, the
             following signs and symptoms can occur:-
             *  Mild: anorexia, headache, dizziness, weakness, anxiety,
                substernal discomfort, fasciculations of the tongue and
                eyelids, miosis, and impairment of visual acuity.
             *  Moderate: nausea, salivation, bronchorrhoea, lacrimation,
                abdominal cramps, diarrhoea, vomiting, sweating,
                hypertension or hypotension, and muscular
             *  Severe: miosis or mydriasis, non-reactive pupils,
                dyspnoea, respiratory depression, pulmonary oedema,
                cyanosis, loss of  sphincter control, convulsions, coma,
                bradycardia or tachycardia, cardiac ischaemia, cardiac
                dysrhythmias, hypokalaemia, and hyperglycaemia.  Acute
                pancreatitis has also occurred.  Muscular paralysis may
                involve the respiratory muscles.
             Some organophosphorus pesticides have caused delayed
             peripheral neuropathy.
             Intermediate Syndrome: The "Intermediate Syndrome" has been
             described.  This occurs after initial improvement,
             approximately 1 to 8 days after poisoning.  Muscle weakness 
             leading to paralysis and sudden respiratory arrest

        2.3  Diagnosis

             In the absence of a reliable history, the diagnosis of
             organophosphorus pesticides poisoning may be initially
             clinical, as it is based on the clinical features given in
             section 2.2.  Foul smell (much like garlic) may be present in

             breath, faeces or vomit or in contaminated clothing, if
             sulphur-containing insecticides have been ingested.
             Favourable response to atropine is a more useful diagnostic
             aid than any cholinesterase assay since treatment must often
             be initiated before any laboratory results are available.
             Other relevant laboratory analysis:
             Complete blood cell count, serum electrolyte levels, arterial
             pH and blood gases, blood glucose, liver function tests,
             urine analysis. Investigations may also include ECG and chest
             Cholinesterase levels are helpful in diagnosing
             organophosphorus pesticide poisoning, but not in managing the
             illness.  The red cell (acetyl) cholinesterase level is a
             more accurate assessment of poisoning.  Blood should be drawn
             in a heparinised tube before treatment is begun.  In cases of
             unknown organophosphorus poisoning, the first aspirate or the
             formulation of the pesticide if available, may be used to
             identify the type of organophosphorus pesticide.

        2.4  First-aid measures and management principles

             It is important that the chemical be removed as quickly
             as possible, as well as atropine to be administered (see
             below).  Contaminated clothing and contact lenses should be
             removed as quickly as possible to prevent further absorption. 
             If skin contact occurs, the area should be washed carefully
             with soap and water.  Wash eyes for 15 to 20 minutes with
             running water.  First-aid personnel should wear rubber or
             plastic gloves to avoid contamination, which should be
             changed frequently.
             In massive overdoses, acute respiratory failure may occur. 
             It is important to keep the airway open and to prevent
             aspiration if nausea and vomiting occur. 
             Oxygen should be administered early if necessary.  The
             patient must be watched constantly and respiratory support
             should be instituted if necessary.  In the case of ingestion,
             gastric aspiration followed by lavage should be preferably
             performed within 1 hour of ingestion.
             Activated charcoal may be effective for organophosphorus
             The patient should be observed carefully during the early
             stages of treatment, because the principal concern is severe
             respiratory depression.  Certain drugs, such as
             phenothiazines, methylxanthines, central nervous system
             depressants, and parasympathomimetic agents are to be
             avoided.  Drugs metabolised by plasmacholinesterase are

             When muscarinic signs are present, organophosphate pesticide
             poisoning must be treated with atropine.  The oximes, such as
             pralidoxime or obidoxime may also be indicated.  Diazepam is
             used to treat seizures.
             Atropine: administered intravenously (IV) in doses of 1 to 2
             mg (0.05 mg/kg) every five to ten minutes until signs of
             atropinisation (dilated and fixed pupils, loss of salivation
             and bronchial hypersecretion) or complete reversal of
             symptoms occurs.  If IV therapy is not possible, atropine may
             be given intramuscularly (IM).  In severe cases, both
             tachycardia and mydriasis may be unreliable features, since
             they may result from nicotinic stimulation.  In very severe
             cases bolus injections of  > 10 mg may be necessary.  As
             such, adequate atropinisation should be assessed by dry mouth
             and the effect on bronchial hypersecretion; frequent
             auscultation is necessary.  Atropine must be continued to
             maintain atropinisation until the patient recovers.
             Pralidoxime: in doses of 30 mg/kg every four to six hours or,
             preferably, by slow intravenous (IV) infusion at a maximum
             rate of  8 to 10 mg/kg/h until full recovery occurs, or, 500
             mg/h continuously maintained until clinical improvement is
             Obidoxime: the adult dose is usually 3 mg/kg  given by slow
             IV; IM dosing is possible when the IV route is inaccessible.
             The maintenance dose is 0.4 mg/kg/h. 
             Diazepam: 5 to 10 mg (0.2 to 0.3 mg/kg) by slow intravenous
             (IV) over three minutes which may be repeated every 10 to 15
             min (maximum 30 mg) in order to control convulsions.
             Some organophosphorus pesticides may cause a delayed
             peripheral neuropathy. There is no specific therapy for this
             condition except for symptomatic measures; e.g.,


        3.1  Origin of substance

             Organophosphate pesticides are synthetic in origin and
             are normally esters, amides, or thiol derivatives of
             phosphoric, phosphonic, phosphorothioic, or phosphonothioic

        3.2  Chemical structure

             Figure 1.  General formula for organophosphorus

                       \  O  (or S)
                        \ "
                          P ---X

        3.3  Physical properties

             3.3.1  Colour

                    See individual organophosphorus pesticide

             3.3.2  State/Form

                    See individual organophosphorus pesticide

             3.3.3  Description

                    Over 100 organophosphorus compounds
                    representing a variety of chemical, physical, and
                    biological properties are presently in commercial
                    Most are only slightly soluble in water and have a
                    high oil-water partition coefficient and a low vapour
                    pressure. Most, with the exception of dichlorvos, are
                    of comparatively low volatility, and are all degraded
                    by hydrolysis, yielding water-soluble products. 
                    Parathion, for example, is freely soluble in alcohols,
                    esters, ethers, ketones, and aromatic hydrocarbons,
                    but is practically insoluble in water (20 ppm) or in
                    petroleum ether, kerosene, or spray oils (Gallo &
                    Lawryk, 1991).  Parathion is stable at a pH below

        3.4  Hazardous characteristics

             The majority of organophosphorus pesticides are liquid
             and have different vapour pressures at room temperature.  The
             compounds used for agricultural purposes are available mainly
             as emulsifiable concentrates or wettable powder formulations
             for reconstitution as liquid sprays, but also as granules for
             soil applications.  A limited number are also available as
             fogging formulations, smokes, impregnated resin strips for
             use indoors, and as animal or human pharmaceutical

             Dispersion of spray droplets by wind is possible, but in
             general, only small amounts are likely to be dispersed in
             this way.
             All organophosphorus pesticides are subject to degradation by
             hydrolysis, yielding water-soluble products that are believed
             to be non-toxic at all practical concentrations.  The toxic
             hazard is therefore essentially short-term in contrast to
             that of the persistent organochlorine pesticides, although
             the half-life at neutral pH may vary from a few hours for
             dichlorvos to several weeks for parathion.  At the pH of
             slightly acidic soils (pH 4 to 5), these half-lives will be
             extended many times.  However, constituents of soil and of
             river water may themselves catalyse degradation.
             Products of combustion:
             Powder, granular, and water-based products will not burn.
             Most liquid formulations will burn and are miscible with
             water. The products of combustion may be harmful by
             inhalation and dermal contamination.  Fire Service personnel
             should extinguish fires with alcohol-resistant foam, water
             spray, or dry powder.  Firefighters should wear full
             protective clothing including self-contained breathing
             Environmental risks:

             Three routes of entry into water sources are possible.  One
             is from industrial waste or effluent discharged directly into
             water. A second is by seepage from buried toxic wastes into
             water supplies.  Neither of these should be tolerated, since
             prior treatment of the waste with alkali (or acid in cases
             such as diazinon), followed by neutralisation, can destroy
             the toxic agents.  Thirdly, contamination of running water
             directly or from run-off during spraying operations can
             occur.  No studies on the degradation of organophosphorus
             pesticides in running water have been reported.  In static
             water, in a simulated aquatic environment, there is evidence
             that light, suspended particles, and bacteria contribute to
             degradation.  Thus, the degradation of fenitrothion in lake
             water under illumination occurred with a half-life of about 2
             days, compared with 50 days in the dark (Greenhalgh et al.,
             1980).  Furthermore, Drevenkar et al. (1976, as reported in
             Gallo & Lawryk, 1991) concluded that although temperature and
             pH were major factors controlling the rate of hydrolysis of
             dichlorvos in water, large differences in the half-life of
             this pesticide in different river waters must be attributed
             to microbiological factors.
             Degradation in the environment involves both hydrolysis and
             oxidation to mono- or di- substituted phosphoric or
             phosphonic acids or their thio analogues.  There is no

             evidence that these products are toxic to any
             significantextent (WHO, 1986).
             For guidance on safe disposal, see Section 12.2.

    4.  USES

        4.1  Uses

             4.1.1  Uses

                    Pesticide for use on invertebrate

             4.1.2  Description

                    Organophosphorus pesticides are used to control
                    insect vectors which are found in food and commercial
                    crops, and infestations in domestic and commercial
                    buildings, and in man or domestic animals.

                    Di-isopropanyl fluorophosphate (DFP) is used as an
                    ophthalmic cholinesterase inhibitor to treat

        4.2  High risk circumstances of poisoning

             Accidental poisoning of children can occur when
             pesticides are stored improperly in the home or garage.
             Occupational exposure among adult farm workers and secondary
             accidental exposure to their families can occur.
             Suicide attempts probably account for more severe and more
             frequent poisonings than accidental or occupational
             poisonings in some countries.
             Exposure of the general population through the consumption of
             foodstuffs treated incorrectly with pesticides or harvested
             prematurely before residues have declined to acceptable
             levels from contact with treated areas, or from domestic use
             has been reported.  Accidental poisonings can also occur
             through failure to observe the safe re-entry time after

        4.3  Occupationally exposed populations

             - Factory workers involved in synthesizing
             - Workers involved in formulating and dispensing
             - Agricultural spray workers.
             - Crop harvesters during disease vector control periods.

             - Public-health workers involved in vector control.
             - Health workers not following the correct procedures when
               handling poisoned patients, especially when ventilatory
               support is needed.


        5.1  Oral

             - Accidental ingestion, especially by children.
             - Ingesting food containing organophoshorus pesticide
               residues after incorrect treatment of foodstuffs or
               harvested prematurely before residues have declined to
               acceptable levels.
             - Oral ingestion may also occur through placing contaminated
               objects in the mouth during eating, drinking or smoking,
               or through violation of proper procedures, e.g., blowing
               out clogged spray nozzles by mouth.
             - Intentional ingestion is common in suicide attempts (see
               section 4.2).

        5.2  Inhalation

             The majority of organophosphorus pesticides are liquids
             that have different vapour pressures at room temperature
             (e.g., dichlorvos is much more volatile than parathion);
             thus, hazards due to inhalation of vapour vary from compound
             to compound.  Respiratory exposure is greater when dusts are
             applied than when dilute sprays are used.  However, aerosols
             of concentrated pesticide may be an even greater hazard

        5.3  Dermal

             Many accidental acute poisonings have occurred after
             spillage of a pesticide on skin and clothing.  The extent of
             uptake will depend on persistence time (related to
             volatility, clothing, coverage, and thoroughness of washing
             after exposure), and also on the presence of solvents and
             emulsifiers that may facilitate uptake.  Powder formulations
             also have a potential for skin absorption (Wolfe et

             Skin absorption is somewhat greater at high temperatures and
             may be much greater in the presence of dermatitis, thus,
             leading to serious poisoning after an exposure that would
             ordinarily cause no effects (Gallo & Lawryk, 1991).

        5.4  Eye

             Exposure to vapours, dusts, or aerosols can cause local
             effects on the smooth muscles of the eyes.  Systemic
             poisoning may follow.

        5.5  Parenteral

             Accidental or intentional (see section 11.2).

        5.6  Others

             No data available.

    6.  KINETICS

        6.1  Absorption by route of exposure

             Organophosphorus pesticides are absorbed by the skin as
             well as by the respiratory and gastrointestinal tracts.
             Oral exposure:
             When 32P-dimethoate was given orally to volunteers, it was
             absorbed and excreted rapidly: 76 to 100% of the
             radioactivity appeared in the urine in 24 hours (Edson et
             al., 1967).
             Inhalation exposure:
             Exposure by respiratory and dermal routes were compared in
             workers spraying parathion, who either breathed a pure air
             supply but did not wear protective clothing, or who wore
             total protective clothing but did not have any respiratory
             protection (Durham et al., 1972). Total urinary output of
             4-nitrophenyl as derived from the respiratory source,
             compared with that derived from the dermal source, was 1.2%
             in one test and 12% in another.
             Since the total exposures by the dermal and respiratory
             routes were in the proportion of 1000:1 and the efficiency of
             dermal absorption was 1 to 2%, it follows that the efficiency
             of dermal absorption by the respiratory route was more than
             20% and could well have been complete.
             Dermal exposure:
             Absorption by the skin tends to be slow, but because the
             pesticides are difficult to remove, dermal absorption is
             frequently prolonged.  Uptake of active ingredients through
             the skin from powdered and granulated formulations may be
             relatively inefficient; the presence of aqueous dispersing
             agents or organic solvents in a spray concentrate or
             formulation may greatly enhance uptake.  On the basis of
             radioautographic studies in man and animals, it appears that
             skin absorption of parathion is transepidermal (Fredriksson,
             1961).  The rate of dermal absorption of parathion in the
             rabbit is 0.059 mg/min/cm2) (Nabb et al., 1966).
             When 14C-malathion was applied to the ventral forearm of 12
             volunteers, radioactivity equivalent to a "corrected" average
             of 8.2% of the total dose was recovered from urine produced

             during the first 5 days (Feldmann & Maibach, 1970). This
             percentage is an essentially accurate indication of the
             absorption during the period because almost all (90.2%) of
             the radioactivity was recovered in the urine after IV
             injection of malathion.

        6.2  Distribution by route of exposure

             The intrinsically reactive chemical nature of
             organophosphorus pesticides means that any that enter the
             body are immediately liable to a number of biotransformations
             and reactions with tissue constituents, so that the tracing
             of radiolabelled material alone does not give any clue to the
             unchanged parent compound.  In view of the inherent
             instability of the organophosphorus pesticides, storage in
             human tissue is not expected to be prolonged.  Experimental
             animal studies indicate rapid excretion of these compounds.
             However, some organophosphorus pesticides are very lipophilic
             and may be taken into, and then released from, fat depots
             over a period of many days.
             The lipophilic diethyl phosphoryl pesticides:
             azinophos-ethyl, bromophos-ethyl, chlorpyrofos, coumaphos,
             diazinon, parathion, phosalone and sulfotep may remain in the
             body for many days or weeks in severe cases, and may promote
             a recurrence of clinical effects after an initial period of
             apparent recovery.  For example, a case of fenitrothion
             poisoning promptly treated by conventional therapy caused a
             recurrence of symptoms attributed to mobilisation of the
             organophosphate stored in adipose tissue. In contrast,
             dichlorvos (a dimethyl phosphate) and omethoate (a dimethyl
             phosphorothioate) are rapidly hydrolyzed by plasma and tissue
             esterases to inactive products and are unlikely to cause late
             clinical effects (Ecobichon et al., 1977; Minton & Murray,

        6.3  Biological half-life by route of exposure

             It is possible to determine the rate of disposal of
             metabolites and thereby to estimate an approximate half-life
             of the pesticide in the body.  The half-life of most
             organophosphorus pesticides and their inhibitory metabolites
             in vivo is comparatively short (WHO, 1986).  For example, the
             serum half-life of malathion was 2.89 hours in a 24-year-old
             white male who, in a suicide attempt, injected approximately
             3 mL of 50% malathion intravenously into his right forearm
             (Lyon et al., 1987).
             A few organophosphorus pesticides, however, are lipophilic
             and may remain in the body for many days or weeks (see
             section 6.2). For example, leptophos tends to persist in the
             fat of hens, and pharmacokinetic studies using radiolabelled

             leptophos showed an elimination half-life of 17 days
             (Abou-Donia & Graham, 1978).

        6.4  Metabolism

             Metabolism occurs principally by oxidation, and
             hydrolysis by esterases and by reaction with glutathione.
             Demethylation and glucuronidation may also occur.  Oxidation
             of organophosphorus pesticides may result in more or less
             toxic products.  In general, phosphorothioates are not
             directly toxic but require oxidative metabolism to the
             proximal toxin.  The glutathione transferase reactions
             produce products that are, in most cases, of low
             Hydrolytic and transferase reactions affect both the thioates
             and their oxons.  Numerous conjugation reactions follow the
             primary metabolic processes, and elimination of the
             phosphorus-containing residue may be via the urine or
             Parathion, for example, must be activated by an oxidative
             conversion via liver Cytochrome P450 microsomal enzymes to
             paraoxon, a potent cholinesterase inhibitor. Both compounds
             are rapidly hydrolyzed by plasma and tissue esterases, to
             diethylthiophosphoric acid, diethyl- phosphoric acid, and
             p-nitrophenol.  These products are excreted mostly in the
             urine and represent the majority of a dose of parathion
             (Baselt, 1982). Phosphorothioates containing a P = S bond
             need to be converted into the analogous oxone before they
             acquire substantial anticholinesterase activity.

        6.5  Elimination and excretion

             There is no evidence of prolonged storage of
             organophosphorus pesticides compounds in the body, but the
             process of elimination can be subdivided roughly according to
             the speed of the reactions involved.  Most organophosphorus
             pesticides are degraded quickly by the metabolic reactions
             described.  The elimination of the products, mostly in the
             urine with lesser amounts in the faeces and expired air, is
             not delayed, so that rates of excretion usually reach a peak
             within two days and decline quite rapidly (WHO, 1986).
             Experimental animal studies have shown that most of a
             radiolabelled dose of organophosphorus pesticides is rapidly
             excreted in expired air, urine, and faeces.  Thus, it was
             reported that from 67 to 100% of the administered
             radioactivity was recovered within 1 week in the combined
             urine and faeces of cows, rats and a goat that were given
             various doses of 32P-dichlorvos (Blair et al., 1975).


        7.1  Mode of action

             Organophosphorus pesticides exert their acute effects by
             inhibiting acetylcholinesterase in the nervous system with
             subsequent accumulation of toxic levels of acetylcholine.
             They may also inhibit butylcholinesterases as well as other
             esterases.  The function of butylcholinesterase is unknown,
             but its inhibition can provide an indication of exposure to
             an organophosphate.
             In many cases, the organophosphorylated enzyme is fairly
             stable, so that recovery from intoxication may be slow.
             Reactivation of inhibited enzyme may occur spontaneously, the
             rates of reactivation depending on the tissue as well as on
             the chemical group attached to the enzyme.
             Delayed neuropathy is initiated by an attack on a nervous
             tissue esterase distinct from acetylcholinesterase. The
             target has esterase activity and is called neuropathy target
             esterase (NTE) (formerly neurotoxic esterase). The disorder
             develops not because of loss of esterase activity, but
             because of a change brought about in the protein molecule
             that results from the process of ageing of inhibited NTE:
             catalytic activity of NTE appears in the nervous tissue, even
             during the period of development of neuropathy (WHO,

        7.2  Toxicity

             7.2.1  Human data


                             Most organophosphorus pesticides are
                             highly toxic. The level of toxicity
                             (described below) ranges from an estimated
                             human oral LD of < 5 mg/kg to 0.5 to 5
                             g/kg(Gosselin et al., 1984).
                             The estimated fatal dose of parathion for an
                             adult by ingestion or inhalation is 10 to 200
                             mg (Gosselin et al., 1984).
                             An oral dose of 7.2 mg parathion, when given
                             daily to volunteers for six weeks, reduced
                             cholinesterase activity to levels of 84% of
                             normal in erythrocytes and 63% in plasma; 28
                             days after the end of the experiment these
                             values were only partially restored to
                             re-experiment control values (Edson,

                             The estimated fatal dose of diazinon in
                             humans is 25 g by oral ingestion (Baselt,
                             Oral doses of diazinon given to volunteers
                             for 37 days at the rate of 0.02 mg/kg per day
                             reduced plasma cholinesterase levels to 86%
                             of pre-exposure levels: 0.05 mg/kg per day
                             for 28 days reduced the levels to 60 to
                             65%,but neither dosage affected the
                             erythrocyte cholinesterase levels (Baselt,
                             The mean fatal dose of malathion in humans is
                             estimated to be 60 g (Baselt, 1982).  The
                             mean lethal oral dose of malathion in an
                             untreated adult may be as low as 250 mg/kg
                             (Gosselin et al., 1984).


                             Children have died after ingesting
                             only 2 mg of parathion equal to a dose of
                             about 0.1 mg/kg.  Young animals are more
                             susceptible than adults of the same species,
                             and the same may be true of children
                             (Gosselin et al., 1984). A 34-month-old boy
                             survived a dose of about 190 mg/kg malathion,
                             and a boy only 40-days-old survived after a
                             dose of approximately 1750 mg (about 407
                             mg/kg) (Gallo & Lawryk, 1991).

             7.2.2  Relevant animal data

                    See Annex.
                    Animal studies have revealed slight microscopic
                    changes in the kidney; Renal toxicity has not been
                    shown to be a feature of acute organophosphorus
                    insecticide poisoning (Gallo & Lawryk, 1991).

             7.2.3  Relevant in vitro data

                    No general data available.

             7.2.4  Workplace standards

                    COMPOUND                   TLV           TLV (mg/m3)
                    Azinphos-methyl     -             0.2
                    Chlorpyrifos        -             0.2
                    Crufomate           -             5.0

                    Demeton             0.01          0.1
                    Diazinon            -             0.1
                    Dichlorvos          0.1           0.9
                    Dicrotophos         -             0.25
                    Disulfoton          -             0.1
                    Ethion              -             0.4
                    Fenamiphos          -             0.1
                    Fensulfothion       -             0.1
                    Fenthion            -             0.2
                    Fonophos            -             0.1
                    Malathion           -             10.0
                    Methylparathion     -             0.2
                    Mevinphos           0.01          0.092
                    Monocrotophos       -             0.25
                    Parathion           -             0.1
                    Phorate             -             0.05
                    Temaphos            -             10.0
                    TEPP                0.004         0.05
                    TLV = Threshold Limit expressed as the time-weighted
                    average concentration for a normal 8-hour workday and
                    a 40-hour workweek, to which nearly all workers may be
                    repeatedly exposed, day after day, without adverse
                    effect (Reference: ACGIH, 1991)

             7.2.5  Acceptable daily intake (ADI)

                    COMPOUND                     YEAR OF       ADI
                                          JMPR          (mg/kg
                                          MEETING       bodyweight)
                    Acephate              1990          0.03
                    Azinophos-ethyl       1973          No ADI
                    Azinophos-methyl      1991          0.005
                    Bromophos             1984          0-0.04
                    Bromophos-ethyl       1984          0-0.04
                    Carbophenothion       1983          0-0.0005
                    Chlorfenvinphos       1971          0-0.002
                    Chlorpyrifos          1983          0-0.01
                    Chlorpyrifos-methyl   1992          0.01
                    Chlorthion            1965          No ADI
                    Coumaphos             1990          No ADI
                    Crufomate             1972          0-0.1
                    Cyanofenphos          1983          ADI withdrawn
                    Demeton               1984          No ADI
                    Demeton-S-methyl      1989          0.0003
                    sulfoxide             1984          No ADI
                    Dialifos              1982          ADI withdrawn
                    Diazinon              1993          0.002
                    Dichlorvos            1993          0.004
                    Dimethoate            1987          0.01
                    Disulfoton            1991          0.0003

                    Edifenphos            1981          0-0.003
                    Ethion                1990          0.002
                    Ethoprophos           1987          0.0003
                    Etrimfos              1986          0.003
                    Fenamiphos            1987          0.0005
                    Fenclorphos           1983          0-0.01
                    Fenitrothion          1988          0-0.005
                    Fensulfothion         1982          0-0.0003
                    Fenthion              1983          0-0.001
                    Formothion            1978          0-0.02
                    Isophenphos           1986          0.001
                    Leptophos             1978          ADI withdrawn
                    Malathion             1984          0-0.02
                    Mecarbam              1986          0.002
                    Methacrifos           1990          0.006
                    Methamidophos         1990          0.004
                    Methidathion          1992          0.001
                    Mevinphos             1972          0-0.0015
                    Monocrotophos         1993          0-0.0006
                    Omethoate             1985          0-0.0003
                    Oxydemeton-methyl     1989          Evaluated under
                                                        methyl related
                    Parathion             1984          0-0.005
                    Parathion-methyl      1984          0-0.02
                    Phenthoate            1984          0-0.003
                    Phorate               1985          0-0.0002
                    Phosalone             1993          0.001
                    Phosmet               1979          0-0.02
                    Phosphamidon          1986          0-0.0005
                    Phoxim                1984          0-0.001
                    Pirimiphos-methyl     1992          0.03
                    Thiometon             1979          0-0.003
                    Triazophos            1993          0.001
                    Trichlorfon           1978          0-0.01
                    Trichloronat          1971          No ADI
                    Vamidothion           1988          0.008
                    ADI = Acceptable Daily Intake
                    JMPR = Joint Meeting on Pesticides Residues
                    (reference: IPCS, 1996)
                   Re-entry Level           Pesticide
                   24 hours                 Any pesticide with registered
                                            agricultural uses when used on
                                            crops requiring workers to
                                            perform labour-intensive
                                            activities, unless the

                                            pesticide has been granted an
                   48 hours                 azinphos-methyl
                                            methyl parathion
                   7 days                   ethyl parathion
                   (Reference: Ellenhorn et al., 1997)

        7.3  Carcinogenicity

             Many organophosphorus pesticides have not shown
             carcinogenic potential in animal experiments, but some
             chemicals (e.g. dichlorvos, tetrachlorvinphos) do induce
             tumours in rats and mice.  For other chemicals (e.g.
             malathion), interpretation of the findings has not found
             general agreement (IARC, 1983; Huff et al., 1985; IPCS,

        7.4  Teratogenicity

             Teratogenic effects have been reported for trichlorofon
             in pigs, but few teratogenic effects have been reported for
             other compounds (WHO, 1986).  Detailed data on the effects of
             organophosphate occupational exposure on pregnant women and
             their foetuses are not available, although such information
             would be valuable.
             In humans only a few cases of acute organophosphorus
             insecticide poisoning during pregnancy have been described. A
             24-year-old woman in her third month of pregnancy injected
             herself malathion in a suicide attempt.  A therapeutic
             abortion was performed 2 months later.  Continuation of the
             pregnancy was considered to be dangerous, although the
             condition of the foetus was not described (Gadoth & Fisher,
             Two patients in their second and third trimesters of
             pregnancy ingested organophosphorus pesticides in suicide
             attempts (Karalliedde et al., 1988).  On management of the
             acute cholinergic and the intermediate phases of poisoning,

             recovery was complete and the pregnancies continued to term
             Weis et al. (1983) also reported a 21-year-old patient, who
             was about 34 to 35 weeks pregnant, who was admitted to
             hospital showing signs of severe organophosphorus pesticide
             poisoning.However, caesarean section was performed 11 hours
             after admission to allow an optimal atropine dosage for the
             mother. Acetylcholinesterase levels were less than 2% of
             normal in the infant and atropine infusion was given for
             eight days.
             Both mother and child made uneventful recoveries and were
             discharged 30 days post-admission (Weis et al., 1983).

        7.5  Mutagenicity

             Many organophosphorus pesticides have been tested for
             their mutagenic potential. No generalisations can be made
             since some compounds exhibit mutagenic activity, whereas
             other compounds do not.

        7.6  Interactions

             Because different classes of enzymes may be inhibited,
             the effects of organophosphorus pesticide poisoning may be
             complex and potentially at least could involve interactions
             with drugs as well as with other pesticides or chemicals.
             Potentiation may also involve solvents or other components of
             formulated pesticides (Gallo & Lawryk, 1991).  Certain drugs
             such a phenothiazines, antihistamines, CNS depressants,
             barbiturates, xanthines (theophylline), aminoglycosides and
             parasympathomimetic agents are to be avoided because of
             increased toxicity.



        9.1  Acute poisoning

             9.1.1  Ingestion

                    The clinical picture of organophosphorus
                    pesticide poisoning results from accumulation of
                    acetylcholine at nerve endings. Signs and symptoms can
                    be divided into three groups: muscarinic,
                    nicotinic,and central nervous system (CNS) effects
                    (see table 9.1.1).  Some of these effects may be more
                    prominent than others or may occur first.
                    Table 9.1.1  Clinical Effects of Organophosphorus
                    Pesticide Poisoning

                    MUSCARINIC EFFECTS
                    - increased bronchial secretion, excessive sweating,
                      salivation, and lachrymation
                    - pinpoint pupils, bronchoconstriction, abdominal
                      cramps (vomiting and diarrhoea)
                    - bradycardia
                    NICOTINIC EFFECTS
                    - fasciculation of muscles. In more severe cases,
                      paralysis of diaphragm and respiratory muscles
                    - tachycardia and elevation of blood pressure
                    - headache, dizziness, restlessness, and anxiety
                    - mental confusion, convulsions and coma
                    - depression of the respiratory centre and vasomotor
                    (Reference: WHO, 1986)
                    Systemic effects are, in general, similar,
                    irrespective of the route of absorption, but the
                    sequence and times may differ. Respiratory and ocular
                    symptoms are expected to appear first after exposure
                    to airborne organophosphates. Gastrointestinal
                    symptoms and localised sweating are likely to appear
                    after oral and dermal exposure, respectively.
                    Following ingestion, the onset of symptoms is usually
                    rapid, within a few minutes to 1 or 3 hours. Clinical
                    effects vary according to the amount ingested (see
                    table 9.1.1). All of the symptoms and signs may occur
                    in various combinations and can be manifest at
                    different times, ranging from a few minutes to many
                    hours, depending on the chemical, dose, and route of
                    exposure.  Mild poisoning may include muscarinic and
                    nicotinic signs and symptoms only.  Severe cases
                    always show CNS involvement; the clinical picture is
                    dominated by respiratory failure, sometimes leading to
                    pulmonary oedema, due to the combination of the
                    effects of all three groups.

             9.1.2  Inhalation

                    Respiratory and ocular symptoms are expected to
                    appear first after exposure to airborne
                    organophosphorus pesticides.

                    Effects on the respiratory tract include
                    bronchoconstriction, and increased activity of the
                    secretory glands and pulmonary oedema.

             9.1.3  Skin exposure

                    Localised sweating and fasciculation at the
                    site of contact, with systemic effects occurring
                    following absorption.  Secondary exposure of children
                    through contact with their parents' contaminated
                    clothing can also occur.

             9.1.4  Eye contact

                    Early miosis and blurred vision may be followed
                    by cholinergic effects if the substance is appreciably
                    A 12-month-old boy who had received one drop of 0.1%
                    Di-isopropyl fluorophosphate (DFP) in each eye daily
                    for two months experienced two brief apnoeic spells.
                    Examination revealed miotic, unreactive pupils,
                    rhinorrhoea, and slight cholinesterase inhibition
                    (Verhulst & Crotty, 1965, as reported in Gallo &
                    Lawryk, 1991).
                    Miosis, caused by direct contact of the eye with
                    organophosphorus pesticides, may be incorrectly
                    interpreted as a sign of systemic poisoning.

             9.1.5  Parenteral exposure

                    Intradermal injection of paraoxon or surface
                    application of maloxon or dichlorvos to human skin
                    produced a long-lasting, local sweating response in a
                    few minutes (McLaughlin & Sonneschein, 1960).
                    Intramuscular administration of DFP to people with
                    schizophrenia, manic-depressive psychosis, and to
                    normal controls at a rate of 2 mg/man per day (about
                    0.028 mg/kg per day) for seven days caused anorexia,
                    vomiting, and diarrhoea, somewhat more severe in
                    normal than in psychotic people (Rowntree et al.,

             9.1.6  Other

                    No data available.

        9.2  Chronic poisoning

             9.2.1  Ingestion

                    No data available.

             9.2.2  Inhalation

                    No data available.

             9.2.3  Skin exposure

                    No data available.

             9.2.4  Eye contact

                    No data available.

             9.2.5  Parenteral exposure

                    No data available.

             9.2.6  Other

                    True chronic poisoning following exposure to
                    organophosphorus pesticides does not occur.
                    Organophosphorus pesticides in common use are rapidly
                    biotransformed and excreted, and sub-acute or chronic
                    poisoning by virtue of accumulation of the compounds
                    in the body does not occur. However, acute
                    intoxications or chronic exposure maylead to
                    long-term, or delayed, adverse effects.  Several of
                    the organophosphorus pesticides produce slowly
                    reversible inhibition of cholinesterase, and
                    accumulation of this effect can occur.  Thus an
                    individual may experience progressive ChE inhibition
                    but remain asymptomatice.  Signs and symptoms of
                    poisoning that resemble those produced by a single
                    high dose will occur when the accumulated inhibition
                    of cholinesterase produced by smaller, repeated doses
                    reaches a critical level.  Cessation of exposure
                    normally results in complete recovery (Ecobichon,
                    The cholinesterase-inhibition from organophosphorus
                    pesticides sometimes persists for 2 to 6 weeks. Thus,
                    an exposure that would not produce symptoms in a
                    person not previously exposed might produce severe
                    symptoms in a person previously exposed to smaller
                    amounts.  Leptophos (Phosvel), Trichlorphon
                    (Dipterex), and Dichlorvos (Divipan) are reported to
                    cause peripheral nerve damage with persistent muscular
                    weakness (Dreisbach & Robertson, 1987) (see also

        9.3  Course, prognosis, cause of death

             The first four to six hours are the most critical in
             acute poisoning.  If there is improvement in symptoms after

             initial treatment then the patient is very likely to survive
             if adequate treatment is continued. Delayed toxicity
             represents an onset of effects on the central and peripheral
             nervous systems appearing days to weeks after exposure.  This
             may occur independently of the effects observed in acute
             poisoning due to cholinesterase inhibition.  Death in cases
             of heavy exposure is usually related to respiratory collapse,
             reflecting depression of the respiratory centre, weakness of
             the muscles of respiration, bronchoconstriction and excessive
             pulmonary secretions.  Death may also result from cardiac
             arrest, due to cardiac dysrhythmias and various degrees of

        9.4  Systemic description of clinical effects

             9.4.1  Cardiovascular

                    Cardiac dysrhythmias, various degrees of heart
                    block, and cardiac arrest may occur. Cardiac rhythm
                    disturbances have occurred with a frequency of less
                    than 5%. These are of many types, such as ventricular
                    rhythm disturbances, alterations of ST segments, T
                    waves, prolongation of the QT interval, complete heart
                    block, and asystole. Tachycardia and ST-wave
                    abnormalities may also be induced by hypoxia (Gallo &
                    Lawryk, 1991). Patients may have elevated blood
                    pressure and tachycardia (nicotinic effects), rather
                    than bradycardia or hypotension (muscarinic effects),
                    depending on the balance between muscarinic and
                    nicotinic receptors (Ellenhorn et al., 1997).

             9.4.2  Respiratory

                    Exposure to organophosphorus pesticides by all
                    routes can exert effects on the smooth muscles of the
                    respiratory tract resulting in
                    bronchoconstriction, increased activity of the
                    secretory glands and pulmonary oedema.  The immediate
                    cause of death in organophosphate poisonings is
                    asphyxia.  Contributing factors are the muscarinic
                    actions of bronchoconstriction and increased bronchial
                    secretions, nicotinic action leading to paralysis of
                    the respiratory muscles and depression of the
                    respiratory centre.

             9.4.3  Neurological

            Central nervous system

                             Depression of the respiratory centre
                             can occur.  Accumulation of acetylcholine in
                             the CNS is believed to be responsible for the
                             tension, anxiety, restlessness, insomnia,

                             headache, emotional instability and neurosis,
                             excessive dreaming and nightmares, apathy,
                             and confusion that have been described after
                             organophosphorus pesticide poisoning. 
                             Slurred speech, tremor, generalised weakness,
                             ataxia, convulsions, and coma are the other
                             CNS effects (Echobichon, 1996).
                             Changes have been associated with a
                             demonstrable depression of plasma or red cell
                             cholinesterases, and are manifest as
                             alterations in psychomotor performance,
                             memory, speech and mood, with features of
                             depression, anxiety, and irritability. Acute
                             confusional psychosis of short duration has
                             occurred following prolonged spraying of
                             diazinon by a farm worker (Minton & Murray,
                             Additional neurological investigations may be
                             helpful in elucidating cerebral disturbances:
                             electroencephalographic changes have occurred
                             in organophosphate poisoning and have been
                             considered to represent a specific effect on
                             the mid-brain (Metcalf & Holmes, 1969);
                             computerized cerebral tomography may be of
                             use in the diagnosis and follow-up by
                             cholinesterase inhibitors as generalised
                             cerebral atrophy has been demonstrated (Pach
                             et al., 1987).

            Peripheral nervous system

                             A few organophosphorus pesticides
                             (e.g. mipafox, leptophos, merphos,
                             trichlorphon, chlorpyrifos have produced
                             delayed and persistent neuropathy, apparently
                             unrelated to anticholinesterase action (Hayes
                             & Law, 1991).  In man, the delay may be up to
                             4 weeks after the first exposure.  The first
                             symptoms are often sensory, with tingling and
                             burning sensation in the limb extremities,
                             followed by weakness in the lower limbs and
                             ataxia.  This progresses to a paralysis
                             which, in severe cases, affects the upper
                             limbs also.  Children are less severely
                             affected than adults.  Recovery is slow and
                             seldom complete in adults. With the passage
                             of time the clinical picture changes from a
                             flaccid to a spastic type of paralysis (WHO,
                             1986).  This neuropathy, in the absence of a
                             history of acute poisoning, may need to be
                             distinguished from other neuropathies such as

                             that in the Guillan-Barré syndrome and
                             sub-acute combined degeneration (see also
                             section 11.1, merphos case history).
                             Electromyographic studies may be used to
                             confirm distal neuropathies and have helped
                             with the understanding of the functional
                             basis of this clinical

            Autonomic nervous system

                             Both muscarinic and nicotiniceffects
                             may occur, depending on the severity of
                             poisoning (see table 9.1.1).

            Skeletal and smooth muscle

                             Muscle fasciculations occur and may
                             be followed by profound weakness and
                             eventually flaccid paralysis. The cholinergic
                             nerve endings on smooth muscle and glands are
                             less susceptible than those on skeletal
                             muscle to blocking by an excess of
                             acetylcholine. Therefore, in poisoning,
                             bronchospasm, cramping of the intestinal
                             muscles, and excessive secretions often
                             persist after weakness of the voluntary
                             muscles have become severe.  Contraction of
                             the smooth muscle of the bladder and tenesmus
                             may also occur (Gallo & Lawryk, 1991).
                             Rhabdomyolysis is a well-known complication
                             of severe poisonings and appears to be also
                             relatively frequent in severe
                             organophosphorus pesticide intoxications. In
                             the acute phase this may cause acute renal
                             failure and in later stages paresis if not
                             treated correctly.

             9.4.4  Gastrointestinal

                    Gastrointestinal manifestations are usually the
                    first to appear after ingestion and some of them maybe
                    due to local anti cholinesterase action in the
                    gastrointestinal tract.  These symptoms include
                    increased gastrointestinal tone and peristalsis.
                    Nausea, vomiting, abdominal cramps, diarrhoea,
                    tenesmus, and involuntary defecation may

             9.4.5  Hepatic

                    In poisonings by parathion and by a wide range
                    of unrelated compounds, serum creatinine, creatinine
                    phosphokinase, and serum alanine aminotransferase are
                    frequently elevated. The fact that lactate
                    dehydrogenase (LDH) and serum aspartate
                    aminotransferase do not undergo a parallel change, and
                    that creatinine occurs almost exclusively in the
                    muscles, suggest that the striated muscles undergo
                    hypoxic damage during poisoning and exclude
                    substantial liver involvement.  However, temporary
                    liver damage (increased urinary urobilinogen, or
                    delayed excretion of bromosulphothalein) may occur
                    (Gallo & Lawryk, 1991).

             9.4.6  Urinary


                             Acute renal insufficiency has been
                             described in one patients exposed to
                             malathion spray (Reynolds, 1996.).
                             Rhabdomyolysis is a well-known complication
                             of severe poisonings and appears to be also
                             relatively frequent in severe
                             organophosphorus pesticide intoxication,
                             including diazinon.  In the acute phase
                             thismay cause acute renal failure and in
                             later stages paresis if not treated correctly
                             (Abend et al., 1994).


                             Symptoms may include strangury and
                             also frequent and involuntary urination due
                             to contraction of the smooth muscle of the

             9.4.7  Endocrine and reproductive systems

                    Animal studies have shown that radioactive
                    parathion passes the placental barrier (Villeneuve et
                    al., 1972).  In animal feeding studies, low dietary
                    levels of parathion did not affect reproduction;
                    however, at higher dietary levels approaching those
                    dangerous to adults, litters are produced but the
                    young may die (Gallo & Lawryk, 1991).  The greater
                    susceptibility of weanlings is thought to be due to
                    their poorly developed microsomal enzymes and also to

                    a great inherent susceptiblity of the young brain
                    (Benke & Murphy, 1975).
                    Transient hyperglycaemia and glycosuria are often
                    found in severe organophosphorus insecticide poisoning
                    (Namba et al., 1971).
                    Pancreatitis after ingestion of organophosphorus
                    pesticides may be painless and terminate fatally,
                    although all children in one study had a complete
                    recovery (Ellenhorn et al., 1997).

             9.4.8  Dermatological

                    Local effects of dermal exposure include
                    localised sweating and contact dermaitis. It may be
                    associated with fasciculations at the site of contact
                    (Reichert et al., 1978). (see also Section 9.4.13
                    Allergic reactions).

             9.4.9  Eye, ears, nose, throat: local effects

                    Exposure to organophosphorus pesticides can
                    have local effects on the smooth muscles of the eyes
                    causing early miosis and blurred vision due to spasm
                    of accommodation, and also conjunctivitis and
                    keratitis.  The secretory glands of the respiratory
                    tract, as well as the smooth muscles of the eyes may
                    be affected by minimal inhalational exposure to the
                    organophosphates leading to watery nasal discharge and
                    hyperemia. Acute rhinitis and pharyngitis can also
                    occur (Ecobichon, 1996).

             9.4.10 Haematological

                    Blood coagulation abnormalities have been
                    described in patients poisoned with parathion (von
                    Kaulla & Holmes, 1961) including both hypo- or
                    hyper- coagulability, with prolonged or shortened
                    prothrombin times respectively. However, because of
                    the low incidence of these findings (< 1.2%), it is
                    unlikely that these changes are of clinical

             9.4.11 Immunological

                    Some deficiency in immune responses has been
                    reported in animals dosed with quantities of
                    organophosphorus pesticides that depressed
                    acetylcholinesterase levels, but not at doses that did
                    not affect acetylcholinesterase (WHO, 1986).

             9.4.12 Metabolic

           Acid-base disturbances

                             Metabolic disturbances may occur in
                             more severe cases. Metabolic acidosis may
                             occur in severe organophosphorus

           Fluid and electrolyte disturbances

                             Electrolyte and fluid imbalance may
                             occur following vomiting and diarrhoea
                             associated with organophosphorus pesticide
                             poisoning. Hypokalaemia is common in
                             organophosphorus poisoning.


                             No data available.

             9.4.13 Allergic reactions

                    Allergic contact sensitivity has been reported
                    with malathion exposure (Milby & Epstein, 1964). Other
                    sporadic cases of contact dermatitis with various
                    organophosphates have also been described; however,
                    these appear to reflect individual sensitivities and
                    are not representative of the usual clinical picture
                    of organophosphorus pesticide exposure (Gallo &
                    Lawryk, 1991).

             9.4.14 Other clinical effects

                    No data available.

             9.4.15 Special risks

                    Animal studies have shown that
                    organophosphorus pesticides can cross the placental
                    barrier, thus posing potential risk to the foetus;
                    weanlings may also be at risk due to their poorly
                    developed microsomal enzyme systems (Gallo &
                    One frequently unrecognised mechanism for the fall in
                    plasma cholinesterase activity is pregnancy.  Studies
                    in healthy women demonstrated that cholinesterase
                    levels fall in the first trimester of pregnancy (range
                    17 to 46%), but they return to normal levels by the
                    third trimester.  No mechanism has been given for this
                    phenomenon; however, this fact should be considered
                    when there is an unexplained cholinesterase drop
                    (Howard et al., 1978).

        9.5  Others

             Intermediate Syndrome
             This occurs occasionally in patients who have not needed
             ventilation as well as patients who have been disconnected
             from a ventilator early because their condition has appeared
             to improve after a period of therapy and artificial
             respiration.  It is expressed as a sudden loss of respiratory
             ability associated with profound weakness of certain
             respiratory and neck muscles. The syndrome was originally
             seen following the ingestion of highly lipophilic
             organophosphorus pesticide-compounds, such as fenthion, but
             it is not confined to a few distinct compounds (De Bleecker
             et al., 1993). If not immediately fatal, the condition
             usually regresses within a few days of re-intubation
             (Senanayake and Karalliedde, 1987; 1992). The effect may be
             an outcome of prolonged nicotinic cholinergic stimulation
             causing functional paralysis of neuromuscular transmission
             (Besser et al, 1989) followed by local necrotic damage at the
             motor endplate (Dettbarn, 1984) and skeletal muscle (Bright
             et al, 1991; Karalliedde & Henry, 1993).

        9.6  Summary


        10.1 General principles

             Treatment of organophosphorus pesticide poisoning
             should begin with decontamination and resuscitation if
             needed.  Decontamination is vital in reducing the dose of the
             pesticide absorbed, but care must be taken not to contaminate
             others, such as medical and paramedical workers.  In the case
             of ingestion, lavage can be performed, and activated charcoal
             administered.  The patient should be observed carefully
             during the early stages of treatment because respiratory
             arrest may occur.
             Phenothiazines, parasympathomimetics and antihistamines are
             contraindicated since they have anticholinesterase activity
             and may potentiate organophosphorus pesticide toxicity. 
             Without possibility for artificial ventilation, central
             nervous system depressants (e.g., opiates) should be avoided
             since they may increase the likelihood of respiratory arrest
             (Ellenhorn et al., 1997).
             Solvent vehicles and other components of the formulated
             organophosphorus pesticide may complicate the clinical
             picture and should be taken into consideration.

        10.2 Life-supportive procedures and symptomatic/specific

             Supportive measures should be directed towards the
             cardiorespiratory system with particular emphasis on
             maintenance of ventilation, cardiac rhythm and blood
             pressure; the removal by suction of respiratory and oral
             secretions which may cause respiratory distress; and the
             oxygenation of the patient. Respiratory arrest may be a
             feature of organophosphate poisoning (Minton & Murray, 1988). 
             When assisted ventilation is required and a neuro-muscular
             blocker is needed, the ganglion blocker, suxamethonium, is to
             be avoided because undue sensitivity to this agent may lead
             to prolonged respiratory paralysis (Seldon & Curry, 1987). 
             Suxamethonium is normally metabolised rapidly by
             pseudocholinesterase (Gilman et al., 1985); hence, an
             alternative neuromuscular blocking agent should be used (e.g.
             pancuronium bromide).
             Organophophorus pesticide poisoning can be treated with
             atropine and oximes (see section 10.6).
             Severely poisoned patients disconnected from the ventilator
             when the general condition improves, must be carefully
             watched for rapid deterioration and development of the
             Intermediate Syndrome (see section 9.5) during the following
             few days in the Intensive Care Unit.
             Seizures should be treated with diazepam as follows:
             Adults:     5 to 10 mg intravenously (IV) slowly over three
             minutes which may be repeated every 10 to 15 minutes (maximum
             30 mg).
             Children:   0.2 to 0.3 mg/kg intravenously (IV) slowly over
             three minutes (maximum 5 mg in children between one month and
             five years old; maximum 10 mg in children five years old and
             Some organophosphorus pesticides may cause a delayed
             peripheral neuropathy. There is  no specific therapy for this
             condition except for symptomatic measures; e.g.,

        10.3 Decontamination

             Ingested organophosphates should be removed by early
             gastric aspiration and then lavage, with protection of the
             airway because they are mostly dissolved in aromatic
             hydrocarbons; this may be the best remedy in unconscious
             patients.  Gastric lavage is most effective within 30 minutes
             of ingestion (but might be still effective up to 4 hours post
             ingestion) as organophosphates are rapidly absorbed from the
             gastrointestinal tract.  Do not induce vomiting.  In the

             case of ingestion, gastric aspiration followed by lavage
             should be performed, preferably within 1 hour.-
             Administration of oral activated charcoal, in conventional
             doses, may also be considered for reducing further absorption
             of some organophosphorus pesticides (Haddad & Winchester,
             1983; WHO, 1986).  If poisoning has occurred by inhalation,
             the patient should be removed from the source of exposure and
             given oxygen; the rescuer should first take adequate
             Dermal exposure may be managed by removing and discarding
             contaminated clothing (particularly leather which absorbs
             pesticides) into sealed bags and repeated vigorous washing of
             exposed skin with soap and plenty of warm water.  Delayed
             inadequate washing with ordinary soap and water removed only
             50 to 70% of the radiolabelled parathion (Fredrikkson, 1961). 
             Special attention should be given to washing in skin creases,
             around the ears, and the external auditory canals, around the
             umbilicus and genitalia and under the nails (AAP, 1983).
             Ocular contamination should be managed by continuous
             irrigation of the affected eye with clean water for 15 to 20
             minutes.  Contact lenses should be removed and irrigated with
             soap and water.

        10.4 Enhanced Elimination

             Elimination techniques have not been effective in the
             treatment of organophosphorus pesticide poisoning.

        10.5 Antidote treatment

             10.5.1 Adults

                    Depending on the severity, organophosphorus
                    pesticide poisoning can be treated with:
                    (a) atropine, which is the antidote of choice and is
                    useful in reversing the muscarinic features;
                    (b) oximes, which reactivate cholinesterases inhibited
                    by organophosphorus pesticides.
                    Atropine acts as a physiological antidote by
                    competitively blocking the action of acetylcholine at
                    muscarinic receptors, and will reverse the excessive
                    parasympathetic stimulation which results from
                    acetylcholinesterase inhibition.  A trial dose of
                    atropine should be instituted on clinical grounds when
                    one suspects organophosphate insecticide poisoning. 
                    The fact that large doses of atropine can be given

                    without observable adverse effects is diagnostic of
                    organophosphorus pesticide poisoning.
                    Oxime reactivators (e.g., pralidoxime, obidoxime)
                    specifically restore cholinesterase activity.  The
                    treatment should be administered within 24 to 48 hours
                    of poisoning since it is ineffective as an antidote
                    once "ageing" of phosphorylated cholinesterase
                    enzymes, with irreversible loss of function, has
                    occurred.  The timing of administration, however, is
                    controversial (see section 10.7).
                    If absorption, distribution, and metabolism are
                    thought to be delayed for any reasons, oximes can be
                    administered for several days after poisoning. 
                    Effective treatment with oximes reduced the required
                    dose of atropine.
                    An initial trial dose of atropine, 1 to 2 mg (0.05
                    mg/kg) intravenously (IV), should be given, and then
                    repeated every five to ten minutes if there is no
                    observable adverse effect.  Atropine may then be
                    repeated or increased in increments at 15 to 30 minute
                    intervals until the patient demonstrates signs of
                    atropinisation.  Atropine in doses of 0.5 mg/kg per
                    hour may be necessary in extreme cases, sometimes by
                    continuous infusion; total daily doses up to several
                    hundred milligrams may be necessary during the first
                    few days of treatment.
                    The dose and the frequency of atropine varies with
                    each patient, but the patient should remain fully
                    atropinised (signs include dilated pupils, dry mouth,
                    skin flushing).  Repeated evaluations of the quantity
                    of the secretions through regular auscultation of the
                    lungs is the only adequate measure of atropinization
                    in the severely poisoned patient.
                    Precautions: cyanotic patients should be oxygenated
                    and, if necessary, intubated at the same time that
                    atropine is administered to avoid ventricular
                    tachyarrhythmias. Patients should be weaned slowly
                    from atropine, particularly if they have had atropine
                    for several days.
                    Adverse effects: possible hypersensitivity to
                    cholinergic stimulation (tremors, rigidity) after
                    prolonged atropine therapy.
                    Pralidoxime chloride, methylsuphate or mesylate should
                    be administered in a dose of 500 mg/h, continuously

                    maintained until clinical improvement is obtained, or
                    30 mg/kg body weight bolus intravenously (IV) over 4
                    to 6 hours or 8 to 10 mg/kg/h intravenously (IV) until
                    full recovery occurs (Ellenhorn et al., 1997).
                    Precautions and contraindications: the iodide salt of
                    pralidoxime should no longer be used because of the
                    risk of cardiac arrest.  Pralidoxime iodide also
                    causes iodism.
                    Obidoxime: the adult dose is usually 250 mg given by
                    slow intravenous(IV)injection followed by continuous
                    infusion of 750 mg/24h (0.4mg/kg/h) to reach plasma
                    concentrations of 10-20 Fmol/l. intramuscular (IM)
                    dosing is possible when the IV route is inaccessible.
                    Concerning the dosage of oxime, it is essential to
                    adjust the appropriate plasma concentration, i.e. for
                    pralidoxime 20 to 40 mg/L and for obidoxime about 4
                    mg/L.  This concentration is usually attained by a
                    daily dose of 10 to 15 g P2S or PAMCl and 0.75 to 1.0g
                    obidoxime, respectively, either given divided in 4 to
                    6 single bolus doses or, preferably, by continuous
                    intravenous infusion, following the first loading dose
                    (2 g pralidoxime and 0.25g obidoxime, respectively).
                    It is essential for the oxime treatment to be
                    continued until full clinical recovery (usually 2 to 4
                    days).  There are no published data concerning the
                    duration and safety of uses.  The administering
                    physician is advised to monitor closely the liver
                    function, with a view to better understanding possible
                    hepatoxicity, particularly with obidoxime.

             10.5.2 Children

                    For diagnosis, use an intravenous (IV) dose of 0.015
                    mg/kg and watch for signs of atropinisation (dilated
                    pupils, dry or red skin, confusion, tachycardia,
                    fever, ileus) (Ellenhorn et al., 1997). 
                    For a therapeutic intravenous (IV) dose in symptomatic
                    patients, use 0.015 to 0.05 mg/kg every 15 minutes as
                    needed (Ellenhorn et al., 1997).
                    The dose of Obidoxime is 3 to 6 mg/kg slowly
                    administered intravenously (IV) over at least 5

                    Pralidoxime chloride, methylsuphate or mesylate should
                    be administered in a dose of 25 mg/kg IV for 15 to 30
                    minutes, folowed by a continuous infusion of 10 to 20
                    mg/kg/h. The therapy can continue for 18 hours or
                    longer, depending on the clinical status (Ellenhorn et
                    al., 1997).

        10.6 Management discussion

             Main alternatives or controversies

             The usefulness of gastric lavage after four hours of
             ingestion and the effectiveness of activated charcoal for gut
             decontamination remain to be demonstrated conclusively.  The
             use of emetics may be dangerous due to possible aspiration of 
             the solvent.  Whole bowel irrigation has not been
             demonstrated to be of value and may not be practicable for
             severely poisoned patients in coma or on a ventilator.
             Haemoperfusion is not considered to be generally effective in
             the management of organophosphorus poisonings.
             Atropine is the therapeutic agent of choice for controlling
             the muscarinic features of organophosphorus pesticide
             poisoning and should be carefully dosed, according to
             bronchial and other hypersecretions as well as heart rate to
             maintain mild atropinisation  Although there are no
             controlled clinical trials, oxime therapy is considered
             beneficial, in combination with atropine and other supportive
             treatment.  Oximes are ineffective if the OP-AchE complex is
             aged.  Therefore, in poisoning with OP where ageing occurs
             relatively rapidly, e.g. dimethyl compounds (halftime of
             ageing 3-4 h) oxime treatment has to be started not later
             then 12 hours after exposure to be effective.  High
             persisting concentrations of the poison in the body prevent
             net reactivation by reinhibition of the reactivated enzyme.
             Nonetheless in the poisoning with OP with slow ageing
             potential as diethyl OP (halftime of ageing about 30 h) rapid
             initiation of oxime therapy and continous infusion is
             indicated even at persisting poison in the body and initially
             lacking reactivation. After the concentration of the poison
             decreases in these cases, net reactivation can be expected
             even 1 week after poisoning.
             Differences between countries
             While health care in developing countries may be accessible
             to organophosphorus pesticide poisoned patients, intensive
             care medical treatment facilities may not be.  In these
             latter circumstances, especially where the exposure is not
             massive, antidotal therapy is particularly useful, in
             addition to decontamination and supportive care and

             appropriate management of organophosphorus pesticide-induced
             convulsions, e.g. with benzodiazepines.
             Identification of research needs
             There appears to be a relationship between enzyme
             reactivation and the disappearance of the muscarinic and
             nicotinic features, i.e. improvement in the clinical
             condition of the patient, provided that there are no
             complications.  A reliable, simple and cheap method should be
             established for measuring AChE activity in red blood cells. 
             Such a method, using non sophisticated equipment would be
             useful for all countries.

             Although clinical observations indicate a possible value of
             bicarbonate in organophosphorus pesticide poisoning
             treatment, this needs further investigation both in animal
             experiments and clinical studies. 
             Further research is required concerning the therapeutic and
             adverse effects of the oximes in organophosphorus pesticide
             There is a clear need for systematic collection of harmonised
             data on organophosphorus pesticide poisoning cases, including
             long-term follow-up, with a view to comparing cases,
             situations and treatment regimens, and also to pool data on
             exposure to a particular substance.  There is also a need for
             a universally agreed severity grading system for reporting
             cases.  It would also be useful to consider developing
             criteria for predicting outcome which takes into
             consideration the organophosphorus pesticide, the dose, and
             clinical features, with a view to identifying the optimum
             treatment procedure for a particular case.  This work is
             being undertaken by the IPCS and its partners in developing a
             severity grading, and case data  harmonisation and collection
             system, which should be further promoted.
             Further research is needed to better understand the
             Intermediate Syndrome, as well as the longer-term
             neurological and other sequelae, and to relate these to the
             biochemical and physiological evolution of organophosphorus
             pesticide poisoning.
             It is recommended that the health sector in each country make
             appropriate plans for undertaking studies in follow-up of
             major incidents involving exposure by organophosphorus
             pesticides to population groups. International guidelines
             for data collection should be developed in order to promote
             comparability of data.


        11.1 Case reports from the literature

             Worrell (1975) as reported in Gallo & Lawryk (1991)
             successfully treated a 2-year-old boy who weighed 13.6 kg,
             poisoned by diazinon, with a total of 707.2 mg
             atropineadministered over a period of 19 days.  The boy
             received 32.5 mg during the first 12 hours; the largest
             single dose was 15 mg.
             Adults, animals, oral ingestion
             Flour contaminated with carbophenthion was used to make
             tortillas which were subsequently eaten by seven members of a
             family. Four to six hours after ingestion symptoms appeared,
             ranging from nausea and vomiting in one patient who did not
             need to be admitted, to 4 patients who became comatose and
             were hospitalised; one severely poisoned patient remained
             critically ill for 4 days, even though he received 66 mg
             atropine and 8 g pralidoxime before he regained
             consciousness; all patients fully recovered within 6 days.
             The family pets fed leftover tortillas fared worse; eight
             chickens, one dog and one cat died (Older & Hatcher,
             Adult dermal exposure
             A 19-year old man accidentally splashed about 570 mL liquid
             emulsion concentrate of monocrotophos on to his bare chest
             and arms during a transfer operation.  He tried to
             decontaminate himself by washing the exposed area, but he did
             not remove any clothing.  Twenty-eight hours after exposure,
             he had muscle weakness and blurred vision, followed by chest
             pains and "blackouts".  He was hospitalised 38 hours
             postexposure;  on admission he was vomiting, pale,
             perspiring, confused, and miotic. Treatment with atropine and
             pralidoxime led to a marked recovery within 48 hours and he
             was essentially symptom-free on the third day. However, as a
             precaution, pralidoxime was continued through day 8.  He was
             discharged on day 10 but continued to have headaches and some
             numbness of the head and arms. Red cell cholinesterase
             activity took 8 weeks to return to the normal range (Simson
             et al., 1969).  This case demonstrates the need for thorough
             decontamination (the report gives no indication of later
             attempts to decontaminate either pre- or post- admission).
             The long delay between exposure and the onset of serious
             symptoms may be been due to factors such as slow dermal
             absorption and poor decontamination.
             Adult, dermal exposure
             A similar exposure involved a 28-year-old man accidentally
             exposed to a 72% formulation of liquid merphos.  Not only did
             he fail to adequately decontaminate himself, but he had

             further exposures over the next 2 days.  Four days
             postexposure he noted weakness in his upper limbs which
             gradually progressed to paralysis of the limbs, and 2 days
             later he presented to hospital.  He did not have the
             classical signs of anticholinergic poisoning.  Substantial
             doses of atropine and pralidoxime chloride were given, but
             there was no improvement on side effects.  Although vital
             capacity, arterial blood gases, plasma cholinesterase level,
             and other measured laboratory findings were normal, he was
             totally unable to move his extremities but retained cutaneous
             sensation.  Electromyography showed decreased voltage of   
             muscle action, potentials, delayed conduction capacity in
             motor nerve fibres, increased insertional activity, and
             denervation potentials.  He received supportive care and
             intense physiotherapy.  Six weeks postexposure, he was
             discharged but had residual weakness and required a walking
             aid; 14 weeks after discharge he had recovered completely
             (Fisher, 1977).  This case is typical of delayed neuropathy
             following exposure to some organophosphates including merphos
             (see section  It has been claimed that EMG studies
             give sensitive indications of exposure to organophosphorus
             pesticides, even in situations where blood cholinesterase
             activity has returned to normal levels; however, there is
             still considerable doubt about the validity of some published
             studies (WHO, 1986).
             Adult, oral ingestion
             A 26-year-old farmer was found 2 hours after swallowing
             methidathion. Seven hours post-ingestion, gastric lavage was
             performed and he was treated with substantial doses of
             atropine and obidoxime over several days.  Artificial
             respiration was required until day 15. Deep coma was a
             feature of the early illness, as well as high fever, and
             jaundice (no cause assigned) which occurred from days 4 to 8. 
             Obidoxime treatment was stopped after day 3 "due to its known
             hepatotoxicity" but reinstituted on days 7 to 8, during which
             time serum bilirubin increased.  Follow-up examinations
             several months after discharge revealed no delayed neuropathy
             or other abnormality (Teitelman et al., 1975). It is
             interesting to note that De Kort et al. (1988) have reported
             that after prolonged use of obidoxime, transaminase values
             may increase. This is apparently reversible, and whether it
             indicates actual liver damage is uncertain.  Thus, the
             prolonged use of high-dose obidoxime in organophosphorus
             insecticide treatment should be accompanied by regular
             monitoring of liver function.
             Adult, parenteral exposure
             A 24-year old white male injected approximately 3 mL of 50%
             malathion (1.8 g) intravenously into his right forearm
             approximately 1 hour prior to seeking medical attention.  He
             had pinpoint pupils and muscular fasciculations and was given
             atropine 5 mg.  He was admitted to hospital 2 hour

             postexposure and complained of headache, nausea, and
             increased urination.  No respiratory difficulty was observed.
             There were bowel sounds and he was having hallucinations and
             delusions.  During the course of his 2-day stay, pralidoxime
             1 g and atropine 7 mg, were administered.  He was transferred
             to a psychiatric hospital (Lyon et al., 1987).


        12.1 Specific preventive measures

             It is essential that persons intending to use
             organophosphorus pesticides are provided with adequate health
             precautions and other safety instructions prior to usage. 
             This information should be provided by the manufacturer in
             the form of either an information leaflet or a label attached
             to the pesticide container.
             Protective clothing is important.  Organophosphorus
             pesticides can be dermally absorbed, resulting in poisoning.
             The risk is greatest in hot weather when the user is
             sweating.  Protective measures may include a long-sleeved
             shirt, long trousers or overalls, and a hat of some sort. The
             more toxic organophosphorus pesticides will require gloves,
             waterproof outerwear (preferably made of heavy PVC), and
             rubber boots.  The label should list these details.
             Clothing worn during spraying should be washed daily after
             use. Contaminated clothing should be washed separately from
             the general wash to avoid cross-contamination.  When working
             with liquid concentrates, there is often a danger that they
             will splash the eyes.  This not only can damage the eyes, but
             also can allow a significant amount of the chemical to be
             absorbed into the bloodstream.  Simple goggles or a face
             shield will protect against this danger.  Eye protection is
             most important if contact lenses are worn, because the
             chemical may seep in behind the lenses.  The lenses must be
             removed before the eyes are washed, and in the time it takes
             to remove them, serious damage can occur.  With some
             pesticides, a respirator may be required.  The label will
             specify when this is necessary.  The correct canister or
             cartridge must be used.
             Greater precautions are necessary when mixing the
             concentrated material than when spraying.  Measurements
             should be accurate and spillages should be cleaned up
             promptly.  Mix the chemicals carefully, using a stick or
             paddle.  Ensure that there is minimal skin exposure by
             wearing gloves. If any concentrate is spilled on the skin,
             wash it off as soon as possible.

             The hazards of spraying increase dramatically on windy days
             because there is an increased risk of inhaling spray drift or
             contaminating the skin.  Also, the risk of drift on to other
             properties or crops is increased.
             Always wash hands before eating, drinking or smoking.  After
             spraying, shower and change clothing.
             By preference, all chemicals should be stored in a locked
             shed, out of the reach of children and animals.  Chemicals
             should also be kept away from work areas and separate from
             other stored materials such as animal foods.  Always leave
             chemicals in their original containers.  If they must be
             transferred to another container, ensure that it is one not
             normally used for food or drink.  This secondary container
             should be labelled properly and be of a variety that is not
             likely to leak.
             Following spillage, empty any of the product remaining in
             damaged/leaking container(s) into a clean empty container(s),
             which should then be tightly closed and suitably labelled. 
             If it is a liquid product, prevent it from spreading or
             contaminating other products, vegetation, or waterways by
             building a barrier of the most suitable available material,
             e.g., earth or sand.  Sweep up the spillage with sawdust,
             sand, or earth (moisten the powders), and place it in a
             suitable container for disposal.  Decontamination and
             clean-up procedures utilise the instability of
             organophosphorus pesticide products with alkali. The
             following procedure has been developed for decontaminating
             spills of organophosphorus pesticides (Shell, 1982):
             Apply a 10% sodium carbonate (washing soda solution) to the
             contaminated area, brush well in, and leave for at least 8
             Absorb into sawdust, sand, or earth and then rinse.
             Contaminated sawdust, sand, earth, and containers should be
             burnt in a proper incinerator.  When no incinerator is
             available, bury in an approved dump or in an area where there
             is no risk of contamination of surface water.  Before
             burying, mix liberally in sodium carbonate (washing soda)
             crystals to hydrolyse the product.
             It is essential that any personnel involved in these
             procedures be adequately protected before beginning clean-up
             Empty containers must be disposed of carefully, so as to
             ensure that rivers, streams, and other water sources are not
             polluted, and that people or animals are not exposed to

             residues of concentrate.  Crushing or burning, followed by
             burial, is generally the best method.
             Workers involved in harvesting crops must adhere carefully to
             re-entry standards which have been set in order to prevent
             the asymptomatic depression of cholinesterase and the
             possibility of the development of an insidious, but low-level
             chronic intoxication syndrome.
             For workers who are exposed on a regular basis to
             organophosphorus pesticides, it is advisable for them to have
             a pre-employment examination to determine their baseline
             cholinesterase levels.  These tests should be undertaken on a
             regular basis to determine whether exposure is occurring with
             sub-clinical findings.  When the red blood cell or plasma
             cholinesterase falls below 25% of baseline levels, workers
             should be taken off the job and should not return to work
             until their cholinesterase levels return to normal.

        12.2 Other

             No data available.


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        poisoning.  JAMA, 238: 1950-1951.
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        paraoxon.  Arch Environ Health, 3: 67-70.
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        Authors:    Dr W.A. Temple
                    National Toxicology Group
                    Otago University
                    Medical School
                    P.O.Box 913
                    New Zealand
                    Dr N.A. Smith
                    Pharmacy School
                    Otago University
                    P.O.Box 913
                    New Zealand
                    Tel: 64-3-4797244
                    Fax: 64-3-4770509
                    e-mail: wtemple@gandalf.otago.ac.nz

             Date:  19 July 1989
             Reviewer:       London Poisons Unit
                             New Cross Hospital
                             Avonley Road
                             London SE14 5ER
                             United Kingdom
                    Tel: 44-71-9555095
                    Fax: 44-71-6392101
                    Date: 1989
                    Peer Review: Hamilton, Canada, 1989
                    Post JMPR, Working Group on Review PIMs on Pesticides,
                    Geneva, Switzerland, 26 September 1991
                    Update:  Geneva, July 1994
                             Brazil, September 1994
                             Geneva, August 1996, AHP van Heijst
                             Cardiff, September 1996
                             Brazil, September 1997
                             Brazil, October 1999 (INTOX 11: Drs Dr L.
                             Szinicz, L. Karalliedde, Y. Ostapenko, Dr W.
                             Jonitz, M. Balali-Mood, A. Wong, J. Socrates

                    Editor:  Dr M.Ruse, March 1998
        Organophosphorus Pesticides: Relevant Animal Data (LD50 for the
        rat mg/kg bodyweight)
                         "Extremely Hazardous"

                                   ORAL                   DERMAL
                          SOLIDS (S) LIQUIDS (L)    SOLIDS (S) LIQUIDS (L)
                          5 mg/kg 20 mg/kg          10 mg/kg 40 mg/kg
    Chlorvinohos          (L) 10 mg/kg
    Chlormephos           (L) 7 mg/kg
    Chlorthiophos         (L) 9.1 mg/kg
    Coumaphos             (L) 7.1 mg/kg
    Demephron -O and -S   (L) 15 mg/kg
    Demeton -O and -S     (L) 2.5 mg/kg
    EPN                   (S) 14 mg/kg
    Ethopropos                                      (L) 26 mg/kg
    Fenamiphos            (L) 15 mg/kg
    Fensulfothion         (L) 3.5 mg/kg
    Fonofos               (L) c  8 mg/kg
    Leptophos             (S) 50 mg/kg
    Mephosfolan           (L) 9 mg/kg
    Mevinphos                                       (L) 4 mg/kg
    Parathion             (L) 13 mg/kg
    Parathion-methyl      (L) 14 mg/kg
    Phorate               (L) 2 mg/kg
    Phospholan            (L) 9 mg/kg
    Phosphamidon          (L) 7 mg/kg
    Prothoate             (L)  8 mg/kg
    Schradan              (L) 9 mg/kg
    Sulfotep              (L) 5 mg/kg
    TEPP                  (L) 1.1 mg/kg
    Terbufos              (L)  c  2 mg/kg
    Thionazin             (L) 11 mg/kg
        Organophosphorus Pesticides: Relevant Animal Data (LD50 for the
        rat mg/kg bodyweight)

                           "Highly Hazardous"
                             SOLIDS  (S)       LIQUIDS  (L)
                             5 - 50 mg/kg      20 - 200 mg/kg
    Azinphos ethyl           (S)12 mg/kg
    Azinphos methyl          (S)16 mg/kg
    Bromophos ethyl                            (L)71 mg/kg
    Cadusofos                                  (L)37 mg/kg
    Carbophenythion                            (L)32 mg/kg
    Crotoxyphos                                (L)74 mg/kg
    Demeton-S-methyl                           (L)40 mg/kg
    Demeton-S-methylsulphon  (S) 37 mg/kg
    Dichlorvos                                 (L)56 mg/kg
    Dicrotophos                                (L)22 mg/kg
    Dioxathion                                 (L)23 mg/kg
    Edifenphos                                 (L)150 mg/kg
    ESP                                        (L)105 mg/kg
    Famphur                  (S)48 mg/kg
    Fosmethilan              (S)49 mg/kg
    Heptenophos                                (L)96 mg/kg
    Isazofos                                   (L)60 mg/kg
    Isofenphos                                 (OIL) 28 mg/kg
    Isothioate                                 (L) 150 mg/kg
    Isoxathion                                 (L)112 mg/kg
    Methamidophos                              (L)50 mg/kg
    Oxydemeton-methyl                          (L)103 mg/kg
    Pirimiphos-ethyl                           (L) 140 mg/kg
    Propaphos                                  (L) 70 mg/kg
    Propetamphos                               (L) 106 mg/kg
    Thiometon                                  (OIL) 120 mg/kg
    Triazophos                                 (L) 82 mg/kg
    Vamidothion                                (L) 103 mg/kg
             Organophosphorus Pesticides: Relevant Animal Data
             (LD50 for the rat mg/kg bodyweight)
                         "Moderately Hazardous"
                      SOLIDS (S)               LIQUIDS  (L)
                      50 - 500 mg/kg           200 - 2000 mg/kg
    Chlorpyrifos      (S) 135 mg/kg
    Cyanofenphos      (S) 89 mg/kg
    Cyanophos                                  (L) 610 mg/kg
    Dialifos          (S) 145 mg/kg

    Diazinon                                   (L) 300 mg/kg
    Dichlofenthion                             (L) 270 mg/kg
    Dimethoate        (S) c  150 mg/kg
    Dioxabenzophos    (S) 125 mg/kg
    EPBP                                       (OIL) 275 mg/kg
    Ethion                                     (L) 208 mg/kg
    Etrimfos                                   (L) 1,800 mg/kg
    Fenchlorphos                               (L) 1,740 mg/kg
    Fenitrothion                               (L) 503 mg/kg
    Fenthion                                   (L) 586 mg/kg
    Formothion                                 (L) 365 mg/kg
    Methacrifos                                (L) 678 mg/kg
    Naled                                      (L) 430 mg/kg
    Phenthoate                                 (L) c  400 mg/kg
    Phosalone                                  (L) 120 mg/kg
    Phosmet           (S) 230 mg/kg
    Phoxim                                     (L) 1,975 mg/kg
    Profenofos                                 (L) 358 mg/kg
    Prothiofos                                 (L) 925 mg/kg
    Pyraclofos                                 (L) 237 mg/kg
    Quinlphos         (S) 62 mg/kg
    Sulprofos                                  (OIL) 130 mg/kg
    Organophosphorus Pesticides: Relevant Animal Data 
     (LD50 for the rat mg/kg bodyweight)

                            "Slightly Hazardous"
                      SOLIDS  (S)             LIQUIDS  (L)
                      More than 500 mg/kg     More than 2000 mg/kg
    Acephate          (S) 945 mg/kg
    Azamethiphos      (S) 1,010 mg/kg
    Bromophos         (S) c  1,600 mg/kg
    Crufomate         (S) 770 mg/kg
    Malathion                                 (L) c 2,100 mg/kg
    Menazon           (S) 1,950 mg/kg
    Pirimiphos-methyl                         (L) 2,018 mg/kg
    Pyridaphenthion   (S) 769 mg/kg
    Trichlorfon       (S) 560 mg/kg
        Organophosphorus Pesticides: Relevant Animal Data 
        (LD50 for the rat mg/kg bodyweight)

                      "Unlikely to Present an Acute Hazard"
                          SOLIDS (S)               LIQUIDS (L)
    Chlorphoxim           (S) + 2,500 mg/kg
    Chlorpyrifos-methyl                            (L) + 3,000 mg/kg
    Ditalmifos            (S) 5,660 mg/kg
    Jodfenphos            (S) 2,100 mg/kg
    Temephos                                       (L) 8,600 mg/kg
    Tetrachlorvinphos     (S) 4,000 mg/kg
             Organophophorus insecticides: a general introduction 
             (EHC 63, 1986)

    See Also:
       Toxicological Abbreviations