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    WORLD HEALTH ORGANIZATION             FOOD AND AGRICULTURE
                                          ORGANIZATION
    ORGANISATION MONDIALE DE LA SANTE     ORGANISATION POUR L'ALIMENTATION
                                          ET L'AGRICULTURE
                                                                          
                                           VBC/DS/75.7 (Rev.1)
                                           ORIGINAL: ENGLISH


    DATA SHEETS ON PESTICIDES  No.  7 Rev.1


    PARATHION-METHYL


    CLASSIFICATION:
    Primary use: Insecticide
    Secondary uses: Acaricide
    Chemical group: Organophosphorus compound
    Data sheet No. 7, Rev.1 (8/78)

         It must be noted that the issue of a Data Sheet for a
    particular pesticide does not imply endorsement of the pesticide by
    WHO or FAO for any particular use, or exclude its use for other
    purposes not stated. While the information provided is believed to
    be accurate according to data available at the time when the sheet
    was compiled, neither WHO nor FAO are responsible for any errors or
    omissions, or any consequences therefrom.

    The issue of this document does    Ce document ne constitue pas une
    not constitute formal              publication. Il ne doit faire
    publication. It should not be      l'objet d'aucun compte rendu ou
    reviewed, abstracted or quoted     résumé ni d'aucune citation sans
    without the agreement of the       l'autorisation de l'Organisation
    Food and Agriculture               des Nations Unies pour
    Organization of the United         l'Alimentation et l'Agriculture
    Nations or of the World Health     ou de l'Organisation Mondiale de
    Organization.                      la Santé.

    1.    GENERAL INFORMATION

    1.1   COMMON NAME: Parathion-methyl (ISO)

    1.1.1 Identity: O,O-dimethyl O-(4-nitrophenyl) phosphorothioate

    Figure 1

    1.1.2 Synonyms: OMS-213
                    methyl parathion - USA 
                    metaphos - USSR

          Local synonyms:


           
    1.2   SYNOPSIS: An organophosphorus pesticide of high mammalian 
          toxicity.  It may be absorbed through the skin, by inhalation and 
          via the gastro-intestinal tract.  It is active upon metabolism. 

          
    1.3   SELECTED PROPERTIES

    1.3.1 Physical characteristics - When pure a white crystalline solid;
          m.p. 35-36°C.  The technical material is a tan to brown liquid 
          with a pungent garlic-like odour;  m.p. about 29°C. 

    It must be noted that the issue of a Data Sheet for a particular 
    pesticide does not imply endorsement of the pesticide by WHO or FAO for 
    any particular use, or exclude its use for other purposes not stated. 
    While the information provided is believed to be accurate according to 
    data available at the time when the sheet was compiled, neither WHO nor 
    FAO are responsible for any errors or omissions, or any consequences 
    therefrom. 
                                          
                                          
    R 585

    The issue of this document does not constitute formal publication.   
    It should not be reviewed, abstracted or quoted without the   
    agreement of the Food and Agriculture Organization of the  
    United Nations or of the World Health Organization.          

    Ce document ne constitue pas une publication. Il ne doit faire l'objet
    d'aucun compte rendu ou résumé ni d'aucune citation sans l'autorisation
    de l'Organisation des Nations Unies pour l'Alimentation et l'Agriculture 
    ou de l'Organisation Mondiale de la Santé.                               


    1.3.2 Solubility - Water at 25°C very slightly soluble (50-60 mg/l), 
          soluble in most organic solvents, very slightly soluble in 
          petroleum and mineral oils. 

    1.3.3 Stability - Stable for several days in neutral aqueous
          suspensions, rapidly hydrolysed in alkaline media at a rate 4.3
          times greater than parathion.  Isomerizes readily to the OS-
          dimethyl isomer on heating.  Compatible with most other 
          pesticides. 

    1.3.4 Vapour pressure (volatility): 0.14 mg/m3 at 20°C (cf. parathion 
          0.09 mg/m3).

            
    1.4 AGRICULTURE, HORTICULTURE AND FORESTRY

    1.4.1 Common formulations - Solutions up to 800 g/l dispersible 
          powders, usually 200-400 g/kg; emulsifiable concentrates 200-800 
          g/l; dusts 25 and 50 g/kg.  There are FAO specifications for the 
          technical material and for these formulations. 

    1.4.2 Susceptible pests - Broad-spectrum contact and stomach 
          insecticide with some fumigant action.  Effective against most 
          insects and phytophagous mites. 

    1.4.3 Use pattern - Pre-harvest treatment of a wide range of grain, 
          vegetable and fruit crops, and ornamentals.  Main use is on 
          cotton.  Application rates are in range 0.2-2 kg/hectare, or 250-
          750 mg a.i./kg.  The pre-harvest interval, depending on crop, is 
          usually 14-21 days, but twice as long in glasshouses.  Also used 
          as a mosquito larvicide on irrigated pastures. Not used on stored 
          food. 

    1.4.4 Unintended effects - Although generally non-phytotoxic, injury to 
          alfalfa under certain weather conditions and to some sorghum 
          hybrids, particularly lighter seeded varieties, has been 
          reported.  Toxic to wildlife but hazard reduced by brief 
          persistence. 

            
    1.5   PUBLIC HEALTH PROGRAMMES - Very limited use as a mosquito 
          larvicide. 

            
    1.6    HOUSEHOLD USE - Parathion-methyl is too toxic for-household use. 
            

    2.    TOXICOLOGY AND RISKS

    2.1   TOXICOLOGY - MAMMALS

    2.1.1 Absorption route - Absorbed by the skin as well as by inhalation 
          and from the gastrointestinal tract. 

    2.1.2 Mode of action - Cholinesterase inhibition after conversion to 
          the oxygen analogue paraoxon-methyl. 

    2.1.3 Excretion products - Parathion-methyl is biologically similar to 
          parathion and is metabolized to its oxygen analogue paraoxon-
          methyl. This is more quickly broken down than paraoxon and is 
          excreted as p-nitrophenol and methyl and dimethyl esters of 
          phosphoric and/or thiophosphoric acid. 

    2.1.4 Toxicity, single dose

          Oral: LD50 rat (M) 14 mg/kg
                LD50 rat (F) 24 mg/kg

          Dermal: LD50 rat (M) 67 mg/kg
                  LD50 rat (F) 67 mg/kg

          Most susceptible species: rat oral LD50 14-24 mg/kg.

    2.1.5 Toxicity, repeated doses:

          Oral: See dietary studies 
          Dermal: No information 
          Inhalation: No information
                                        
          Cumulation of compound: Parathion-methyl does not accumulate in 
          body tissue.  When 37-P labelled parathion-methyl was 
          administered orally to guinea-pigs, the phosphorus was found to 
          enter the organs almost immediately and the maximum tissue level 
          was attained in 1-2 h. 

          Cumulation of effect: Repeated exposure to sublethal amounts 
          may reduce cholinesterase activity to hazard levels. 

    2.1.6 Dietary studies

          Short-term: In dogs which were fed 5, 20 or 50 mg/kg diet 
          (0.25, 1.0, or 2.5 (mg/kg)/day) of parathion-methyl for 12 weeks,
          the no-effect level with respect to plasma cholinesterase was 5
          mg/kg (0.25 (mg/kg)/day) and possibly 20 mg/kg (1.0 mg/kg)/day).  
          Erythrocyte cholinesterase inhibition reached a maximum at 50 
          mg/kg at the end of the 12-week period but recovery was complete 
          4-8 weeks after withdrawal of the parathion-methyl. 

          Long-term: No information.

    2.1.7 Supplementary studies of toxicity

          Mutagenicity:

          Mouse: Seven-week dietary administration of 3 dosage levels to 
          male mice did not produce dominant lethal effects. 

          Rat: In a three-generation reproduction study there was reduced 
          reproductive performance at a dietary level of 30 mg/kg (1-5 
          (mg/kg)/day) but there was no such effect at 10 mg/kg (0.5 
          (mg/kg)/day).  There is no information on cholinesterase activity 
          levels in this study. 

          Teratogenicity:

          Mouse: Teratogenic effects were observed in the offspring of 
          mice injected once on day 10 of gestation with 60 mg/kg of 
          parathion-methyl.  Retardation of ossification of the caudal
          vertebrae, increased incidence of cervical rib and cleft palate
          were observed.  A similar effect was not seen in rats injected
          with 15 mg/kg on day 12 of gestation. 

    2.1.8 Modifications of toxicity: No information.


            
    2.2   TOXICOLOGY - MAN

    2.2.1 Absorption - See 2.1.1

    2.2.2 Dangerous doses

          Single: The dangerous dose is not known; based upon animal 
          studies and the relatively good occupational safety record it is 
          assumed to be higher than for parathion, since parathion-methyl 
          is more rapidly hydrolysed. 

          Repeated: See "Observations on volunteers".

    2.2.3 Observations on occupationally exposed workers - See 2.2.6 
          "Reported mishaps". 

    2.2.4 Observations on exposure of the general population - Based upon 
          information on the dietary intake of all organophosphorus 
          pesticides in one country it can be assumed that the general 
          public will not be exposed to hazardous amounts of parathion-
          methyl. 
                
    2.2.5 Observations on volunteers - No reduction in plasma or 
          erythrocyte cholinesterase activity and no side effects were 
          observed in human subjects given a maximum of 4.0 mg/day for 43 
          days.  In subjects given a maximum of 6.5 mg/day for 35 days, 
          followed by 7.0 mg/day for 24 days, the maximum in plasma 
          cholinesterase activity was approximately 15% reduction.  When 
          doses of 7, 7.5, 8 and 9 mg/day of parathion-methyl were given 
          for 30 days the plasma and erythrocyte cholinesterase activities 
          were within 20'/ of the control values. 

    2.2.6 Reported mishaps - Unlike its ethyl analogue parathion, 
          parathion-methyl has not been associated with a large number of 
          cases of intoxication and death.  All confirmed cases of human 
          poisoning have had substantial exposure.  Most of the reported
          fatal cases appear to be suicide. 

            
    2.3   TOXICOLOGY, OTHER SPECIES

          The entries in these sections are intended to draw attention to
          special risks and to give warnings of any needs for special
          protection.

    2.3.1 Fish: Toxic to fish (LC50 for bluegills and rainbow trout in 
          range 5-10 mg/l). 

    2.3.2 Birds: Toxic to birds.

    2.3.3 Other species - Toxic to bees.


            
     3.    FOR REGULATORY AUTHORITIES

    3.1   RECOMMENDED RESTRICTIONS ON AVAILABILITY

          All formulations in category 3 (for definition of categories
          see introduction) 


    3.2   TRANSPORTATION AND STORAGE

          All formulations

          United Nations Classification 6.1 No. 1893 - Should be 
          transported or stored in clearly labelled rigid and leakproof 
          containers, and away from containers of food and drink. Storage 
          should be under lock and key and secure from access by 
          unauthorized persons and children. 

            
    3.3   HANDLING

          All formulations - Full protective clothing (see Part 4) should 
          be provided for all handling of the compound.  Adequate washing 
          facilities should be available at all times during handling and 
          should be close to the site of handling.  Eating, drinking and 
          smoking should be prohibited during handling and before washing 
          after handling. 

            
    3.4   DISPOSAL AND/OR DECONTAMINATION OF CONTAINERS

          All formulations - Container must either be burned or crushed 
          and buried below topsoil.  Care must be taken to avoid subsequent 
          contamination of water sources.  Decontamination of containers in 
          order to use them for other purposes should not be permitted. 

            
    3.5   SELECTION AND TRAINING AND MEDICAL SUPERVISION OF WORKERS

          All formulations - Pre-employment medical examination of workers 
          necessary.  Workers suffering from active hepatic or renal 
          disease should be excluded from contact.  Pre-employment and 
          periodic cholinesterase test for workers desirable.  A periodic 
          urinary p-nitrophenol test may be used as an alternative.  
          Special account should be taken of the workers' mental ability to 
          comprehend and follow instructions. Training of workers in 
          techniques to avoid contact essential. 


                
    3.6   ADDITIONAL REGULATIONS RECOMMENDED IF DISTRIBUTED BY AIRCRAFT

          All formulations - Pilots and loaders should have special 
          training in application methods and early symptoms of poisoning, 
          and must wear a suitable respirator.  Use of flagmen not 
          recommended.  Flagmen, if used, should wear protective clothing 
          and be located well away from the dropping zone. 

       
    3.7   LABELLING

          Minimum cautionary statement - All formulations.

                                      "POISON"

                          (skull-and-cross-bones insignia)

          "Parathion-methyl is an organophosphorus compound which inhibits 
          cholinesterase. it is a very toxic substance.  Contact with the 
          skin, inhalation of dust or spray, or swallowing may be fatal. 
          Wear protective gloves, clean protective clothing, and a 
          respirator of the organic-vapour type when handling this 
          material.  Bathe immediately after work. 

          "Ensure that containers are stored under lock and key.  Empty 
          containers must be disposed of in such a way as to prevent all 
          possibility of accidental contact with them.  Keep the material 
          out of reach of children and well away from foodstuffs, animal 
          feed and their containers. 

          "In case of contact, immediately remove contaminated clothing and 
          wash the skin thoroughly with soap and water; for eyes, flush 
          with water for 15 minutes. 

          "If poisoning occurs, call a physician.  Atropine and pralidoxime 
          are specific antidotes and repeated doses may be necessary. 
          Artificial respiration may be needed." 

              
    3.8   RESIDUES IN FOOD

    3.8.1 Maximum residue levels - The Joint FAO/WHO Meeting on Pesticide 
          Residues has recommended maximum residue levels.

            
    4.    PREVENTION OF POISONING IN MAN AND EMERGENCY AID

    4.1.  PRECAUTIONS IN USE

    4.1.1 General - Parathion-methyl is a highly toxic organophosphorus 
          pesticide.  it penetrates the intact skin and is also absorbed by 
          inhalation and via the gastro-intestinal tract.  Most 
          formulations should be handled by trained personnel wearing 
          protective clothing. 

    4.1.2 Manufacture and formulation

          T.L.V. - 0.2 mg/m3.  Levels o f 0.1 mg/m3 have been established
          in Hungary and Romania.  Closed systems and forced ventilation 
          may be required to reduce as much as possible the exposure of 
          workers to the chemical.  Formulation should not be attempted 
          without advice from the manufacturer. 

    4.1.3 Mixers and applicators - When opening the container and when 
          mixing, protective impermeable boots, clean overalls, gloves and 
          respirator should be worn.  Beware of possible positive pressure 
          build up, especially with liquid formulations in metal containers 
          with inverted pour spouts. Mixing, if not mechanical, should 
          always be carried out with a paddle of appropriate length.  When 
          spraying tall crops or during aerial application, a respirator 
          should be worn as well as an impermeable hood, clothing, boots 
          and gloves.  The applicator should avoid working in spray mist 
          and avoid contact with the mouth.  Particular care is needed when 
          equipment is being washed after use.  All protective clothing 
          should be washed immediately after use, including the inside of 
          the gloves.  Splashes must be washed immediately from the skin or 
          eyes with large quantities of water.  Before eating, drinking or 
          smoking, hands and other exposed skin should be washed. 

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

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

            
    4.2   ENTRY OF PERSON INTO TREATED AREAS - Unprotected persons should 
          be kept out of treated areas for several days. Periods of 6-21 
          days, according to crops, have been recommended. 

    4.3   SAFE DISPOSAL Of CONTAINERS AND SPILLAGE - Residues in containers 
          should be emptied in a diluted form into a deep pit taking care 
          to avoid contamination of ground waters. Decontamination of 
          containers in order to use them for other purposes should not be 
          permitted.  Spillage of parathion-methyl and its formulations 
          should be removed by washing with 5% sodium hydroxide solution 
          and then rinsing with large quantities of water. 


            
    4.4   EMERGENCY AID
            
    4.4.1 Early symptoms of poisoning - Early symptoms of poisoning may 
          include excessive sweating, headache, weakness, giddiness, 
          nausea, vomiting, stomach pains, blurred vision, slurred speech, 
          and muscle twitching.  Later there may be convulsions, coma, loss
          of reflexes and loss of sphincter control. 


    4.4.2 Treatment before person is seen by a physician, if these symptoms 
          appear following exposure - The person should stop work 
          immediately, remove contaminated clothing and wash the affected 
          skin with soap and water, if available, and flush the area with 
          large quantities of water.  If swallowed, vomiting should be 
          induced if the person is conscious.  In the event of collapse, 
          artificial respiration should be given, bearing in mind that if
          mouth-to-mouth resuscitation is used vomit may contain toxic 
          amounts of parathion-methyl. 

            
    5.    FOR MEDICAL AND LABORATORY PERSONNEL

    5.1   MEDICAL DIAGNOSIS AND TREATMENT IN CASES OF POISONING

    5.1.1 General information - An organophosphorus pesticide of high acute 
          toxicity which is easily absorbed through the intact skin as well 
          as by inhalation and via the gastrointestinal tract.  It is 
          converted in vivo to the oxygen analogue paraoxon-methyl which 
          then inhibits acetyl cholinesterase. Continued exposure to low 
          amounts may reduce blood cholinesterase to dangerous levels. 

    5.1.2 Symptoms and signs - Initial symptoms of poisoning may include 
          excessive sweating, headache, weakness, giddiness, nausea, 
          vomiting, stomach pains, blurred vision, slurred speech and 
          muscle twitching.  More advanced symptoms of poisoning may be 
          convulsions, coma, loss of reflexes and loss of sphincter 
          control. 
                
    5.1.3 Laboratory - The most important laboratory finding is reduction 
          in activity of blood cholinesterases.  Other findings are raised 
          urinary levels of p-nitrophenol. 

    5.1.4 Treatment - if the pesticide has been ingested, unless the 
          patient is vomiting, rapid gastric lavage should be performed 
          using 5% sodium bicarbonate, if available.  For skin contact, the 
          skin should be washed with soap.and water.  If the compound has 
          entered the eyes, they should be washed with isotonic saline. 

          Persons without signs of respiratory inefficiency but with 
          manifest peripheral symptoms should be treated with 2-4 mg of 
          atropine sulfate and additionally with 1000-2000 mg of 
          pralidoxime chloride or 250 mg of toxogonin (adult dose) by slow 
          intravenous injection.  More atropine may be given as needed.  
          Persons with severe intoxication with respiratory difficulties, 
          convulsions and unconsciousness should immediately be given 
          atropine and a reactivator.  In such severe cases 4-8 mg of 
          atropine sulfate should be given initially followed by repeated 
          doses of 2 mg at 5-10 minute intervals.  The patient's condition 
          including respiration, blood pressure, pulse frequency, 
          salivation and convulsions should be carefully observed as a 
          guide to further administration of atropine.  If the patient is 
          cyanotic, artificial respiration should be given at the same time 
          as atropine. 

          The airways should be kept free and artificial respiration should 
          be applied, if required, preferably by mechanical means. If 
          necessary, intubation should be performed. 

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

    5.1.5 Prognosis - If the acute toxic effect is survived and adequate 
          artificial respiration has been given, if needed, the chances of 
          complete recovery are good.  However, in very severe cases, 
          particularly if artificial respiration has been inadequate, 
          prolonged hypoxia may give rise to permanent brain damage. 

    5.1.6 References of previously reported cases - Case histories and 
          general methods for treatment are given in: Hayes, W. J., jr 
          (1963) Clinical Handbook on Economic Poisons, United States 
          Public Health Service,No. 476, revised.  See also "Safe use of 
          pesticides in public health" (1967) Wld Hlth Org. techn. Rep. 
          Ser., No. 356, pp. 58-59. 


    5.2   SURVEILLANCE TESTS
        
    Test                     Normal     Action    Symptomatic
                               level     level      level

    Plasma cholinesterase       100%          50%       variable
        
    Erythrocyte cholinesterase  100%          70%       usually < 40%  

            
    5.3   LABORATORY METHODS

          References are given only.

    5.3.1 Detection and assay of compound - It is unlikely that unchanged 
          parathion-methyl will be detectable in human tissue unless there 
          has been gross exposure.  Determination of the activities of 
          blood cholinesterases and p-nitrophenol in the urine (see 5.3.2 
          below) should be used in cases of suspected poisoning.  For 
          parathion-methyl in foodstuffs, determination can be made by 
          using the colorimetric method of Averell & Norris (1948).  
          Specific detection of parathion-methyl is possible by paper and 
          thin-layer chromatography, see: Abbott et al. (1965) and Getz 
          (1965).  There are also a number of gas-liquid chromatographic 
          methods, see: Nelson (1966), Egan et al. (1964) and Guiffrida et 
          al. (1966).  A multi-detection method is also reported by Bowman 
          & Beroza (1968). 
                
    5.3.2 Other tests in cases of poisoning

          Levels of cholinesterase in the blood, particularly plasma, 
          provide the most useful diagnosis of poisoning, see: Michel, N. 
          0. (1949) J. Lab. Clin. Med., 34, 1564; Ellman, G. L.,
          Courtney, K. D., Andres, V., jr & Featherstone, R. M. (1961)
          Biochem. Pharmacol., 7, 88. 

          Urinary levels of p-nitrophenol are also an index of poisoning: 
          p-nitrophenol may be determined colorimetrically (Elliott et al., 
          1960) or by gas chromatography (Crammer, 1970). 

          Levels of phosphate esters in urine may also be determined in 
          order to give an indication of the extent of exposure by the 
          method of Shafik & Enos (1969) as modified by Shafik et al. 
          (1970). 


                                     REFERENCES

    Abbot, D. C., Crosby, N. T. & Thomson, J. (1965) Proc. Soc. Anal.
          Chem. Conf., p. 121

    Averell, P. R. & Norris, M. V. (1948) Anal. Chem., 20, 753

    Bowman, M. C. & Beroza, M. (1968) (1948) Anal. Chem., 20, 753

    Cranmer, M. (1970) Bull. Environm. Contamin. Toxicol., 5, 329

    Egan, H., Hammon, E. W. & Thomson, J. (1964) Analyst., 89, 175

    Elliott, J. W., Walker, K. D., Penick, A. E. & Durham, W. F. (1960) J.
          Agr.  Fd. Chem., 8, Ill 

    Getz, M. E. (1963) Res. Rev., 2, 9

    Guiffrida, L., Ives, N. F. & Bostwick, D. C. (1966) J. Assoc. Offic.
          Anal.  Chem., 49, 8 

    Shafik, M. T. & Enos, H. F. (1969) J. Agr. Fd. Chem., 17, 1186

    Shafik, M. T., Bradway, D., Biros, F. J. & Enos, H. F. (1970) J. Agr.
          Fd.  Chem., 18, 1174 
See Also:
        Methyl parathion (EHC 145, 1992)
        Methyl parathion (ICSC)
        Parathion methyl (PIM 666)