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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/75.8 (Rev.1)
                                          ORIGINAL: ENGLISH


    DATA SHEETS ON PESTICIDES No. 8 Rev.1


    TEMEPHOS


    CLASSIFICATION:

    Primary use: Insecticide
    Secondary uses: None
    Chemical group: Organophosphorus compound
    Data sheet No. 8, Rev.1 (8/78)
    Date issued: March 1975



         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: Temephos.  This name is under consideration by ISO 
          but has not yet been adopted. 

    1.1.1 Identity: 0,0,0',0'-tetramethyl 0,0'-thiodi-p-
          phenylenephosphorothioate

    Figure 1

    1.1.2 Synonyms: OMS 786
                    "Abate"
                    difenphos (This was originally considered by ISO as a 
                    Common Name but was replaced by "temephos".)

          Local synonyms:

     
    1.2   SYNOPSIS - An organophosphorus insecticide of slight toxicity 
          which is used largely as a mosquito larvicide.  It is non-
          systemic and has some residual activity.  It is active upon 
          metabolism. 


    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 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. 


    R 983


    1.3   SELECTED PROPERTIES

    1.3.1 Physical characteristics - When pure a white crystalline solid,
          m.p. 30-30.5°C: the technical product is a brown viscous liquid. 

    1.3.2 Solubility - Practically insoluble in water at 20°C (less than 
          1 ppm).  Soluble in acetone, acetonitrile, ether and most 
          aromatic and chlorinated hydrocarbons. Insoluble in hexane. 

    1.3.3 Stability - Moderately stable to hydrolysis in contact with 
          aqueous alkali; no observed hydrolysis at pH 8 at room 
          temperature for several weeks or at pH 11 at 40°C for several 
          hours. 

    1.3.4 Vapour pressure - 7.17 x 10-8 mmHg at 25°C.

            
    1.4 AGRICULTURE, HORTICULTURE AND FORESTRY

    1.4.1 Common formulations - Wettable powder 50%; emulsifiable 
          concentrates 20%, 50%; granules 1%. 

    1.4.2 Susceptible pests - Main use is against mosquitos.  Also 
          effective against Lygus bugs, biting and chiromid midges, gnats, 
          cutworms, thrips, moth and sand-flies, blackflies and body lice. 

    1.4.3 Use pattern - Used as mosquito larvicide on ponds, marshes, 
          swamps and neighbouring ground at 0.1-0.5 kg/ha.  Also used for 
          mosquito control on premises.  Used experimentally on cotton, 
          alfalfa, citrus and other crops for control of cutworms, thrips 
          on citrus and Lygus bugs. Sometimes mixed with other insecticides 
          for broader spectrum control.  Used for mosquito control in 
          potable water. 

    1.4.4 Unintended effects - Young shrimp in treated tidal waters may be 
          injured.  Not phytotoxic and of low toxicity to most non-target 
          species. 

            
    1.5   PUBLIC HEALTH PROGRAMMES - Used at a level of 1 ppm in drinking-
          water to control Aedes aegypti larvae.  Also used to control the 
          larvae of black flies (Simulidae) vectors of onchocerciasis.  
          Used as a formulated powder for the control of body lice 
          (Pediculus humanus humanus). 

            
    1.6    HOUSEHOLD USE - Not used.
            

    2.    TOXICOLOGY AND RISKS

    2.1   TOXICOLOGY - MAMMALS

    2.1.1 Absorption route - Absorbed by all portals, but dermal absorption
          is of little significance because absorption by this route is 
          slow and the toxicity of the compound is inherently low. 

    2.1.2 Mode of action - Cholinesterase inhibition.

    2.1.3 Excretion products - Unchanged temephos constitutes the principal 
          compound excreted in the faeces along with smaller amounts of the 
          sulfoxide and phenolic hydrolysis products.  In the urine traces 
          of temephos are found, but the major urinary excretion products 
          are sulfate ester conjugates of phenolic hydrolysis products. 

    2.1.4 Toxicity, single dose

          Oral: LD50 rat (M): 8600 mg/kg
                LD50 rat (F):  1300 mg/kg

          Dermal: LD50 rat (M): > 4000 mg/kg 
                  LD50 rat (F): > 4000 mg/kg
                  LD50 rabbit: 1300-1400 mg/kg

          Mont susceptible species - Not known.  Reported to show marked 
          differences in different species. 

    2.1.5 Toxicity, repeated doses

          Oral: Rats, rabbits and guinea-pigs were found to tolerate daily 
          oral administration of 10 mg/kg of temephos without observable 
          clinical effect.  White rats were fed temephos at doses of 0, 1, 
          10, 100 mg/kg/day for 44 days.  Cholinesterase values remained 
          normal for the rats receiving 1 mg/kg/day throughout the 
          experiment.  The rats receiving 10 mg/kg/day showed 31% 
          inhibition of erythrocyte cholinesterase after 14 days and 47% 
          inhibition after 44 days.  The animals never showed symptoms of
          organic phosphorous poisoning.  The rats given 100 mg/kg/day 
          developed typical symptoms of organic phosphorus poisoning after 
          three doses when their erythrocyte cholinesterase was inhibited 
          by 64%.  Gradual recovery from symptoms occurred while dosing 
          progressed, even though the erythrocyte cholinesterase continued 
          to fall to 87% inhibition after 11 days of dosing.  Some of the 
          rats were allowed to recover for 32 days without receiving 
          temephos and erythrocyte cholinesterase returned to a level of 
          27% inhibition at the end of this period. 

          Rabbits were administered temephos at doses of 0.1, 1, and 10 
          mg/kg/day, for 35 days.  No significant inhibition of 
          cholinesterase occurred in the groups receiving 0.1 or 1 
          mg/kg/day throughout the experiment.  After seven days of dosage, 
          the rabbits on 10 mg/kg/day had developed 26% inhibition of 
          erythrocyte cholinesterase, and inhibition of erythrocyte 
          increased to 47% at the end of 35 days of dosage.  None of the 
          animals developed symptoms of organic phosphorus poisoning. 

          Male guinea-pigs given a daily dose of 100 mg/kg temephos for 
          five days showed no signs of organic phosphorus poisoning. 

          Inhalation:  No information.

          Dermal: Groups of 10 male and 10 female young albino rats
          received dosages of 12 mg/kg/day or 60 mg/kg/day of temephos, 
          applied as an aqueous emulsion, five days per week for three 
          weeks.  One half of the animals within each group had the skin 
          abraded at the site of the application. 

          There were no deaths during the test period and the overall 
          behaviour and appearance of all animals was good.  No gross 
          lesions or tissue changes were referable to the treatments.  In 
          male rats receiving 60 mg/temephos/kg on intact skin, mean food 
          intake was less than that of their controls.  Intact and abraded 
          skin males receiving 60 mg/temephos/kg had lower mean weight gain 
          than their control. 

          Five-day repeated applications to intact rabbit skin show that 
          0.4 ml (178 mg a.i.)/kg/day for five consecutive days, did not 
          cause death. Diarrhoea occurred in 7/10 treated animals but not 
          in the controls. Cholinesterase activity was reduced in treated 
          animals. 

          Cumulation of compound: No information.  Can be expected to be 
          stored to some extent in body tissues as indicated by the 
          excretion of metabolites in the urine. 
                                                                
          Cumulation of effect: In spite of its low toxicity continued 
          ingestion of temephos can be expected to reduce cholinesterase 
          activity to hazardous levels. 

    2.1.6 Dietary studies

          Short-term: In a 90-day feeding study with rats, 350 ppm (17.5
          mg/kg/day) in the diet was without observable clinical effect and 
          6 ppm (0.3 mg/kg/day) did not affect cholinesterase activity.  
          Dogs fed a diet containing 500 ppm (25 mg/kg/day) of temephos 
          showed signs of cholinesterase inhibition while 18 ppm (0.9 
          mg/kg/day) did not affect the appearance of the dogs or inhibit 
          cholinesterase activity. Dogs fed 3 to 4 mg/kg/day over a 129-day 
          test period tolerated the treatment. 

          Long-term: Study in progress.

    2.1.7 Supplementary studies of toxicity

          Reproduction: When rats were fed large enough doses to inhibit
          cholinesterase and cause some symptoms of toxicity (500 ppm in 
          the diet - 25 mg/kg/day) they still reproduced normally.  Their 
          young were viable and there was no increase in congenital 
          defects.  Reproduction studies with rats receiving 125 ppm of 
          temephos in their diet (10 mg/kg/day) through three generations 
          did not produce lesions in the parents or lesions or anomalies in 
          the offspring which could be attributed to the compound. 

    2.1.8 Modifications of toxicity: There is neither significant 
          antagonism nor potentiation of acute toxicity between temephos 
          and 23 other cholinesterase inhibiting pesticides when they were 
          administered in equitoxic proportions. 

            
    2.2   TOXICOLOGY - MAN

    2.2.1 Dangerous doses

          Single: Not known.

          Repeated: Not known - >> 256 mg/man/day for five days.

    2.2.2 Observations of occupationally exposed workers - No information: 
          no ill effects have been observed in spraymen. 

    2.2.3 Observations on exposure of the general population - No clinical 
          symptoms attributable to temephos were observed among members of 
          a village in which water storage containers were treated monthly 
          with 1% temephos granules over a 19-month period. (Monthly 
          treatment in this fashion should maintain a level of 0.5 ppm 
          temephos in the water.) 

    2.2.4 Observations of volunteers - Human subjects tolerated levels of 
          256 mg/man/day for five days or 64 mg/man/day for 28 days without 
          developing clinical symptoms attributable to temephos.  No 
          inhibition of plasma or erythrocyte cholinesterase was found. 

    2.2.5 Reported mishaps - No information.  Poisoning in humans by 
          temephos has not been reported. 

            
    2.3   TOXICITY TO NON-MAMMALIAN 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 - Generally low toxicity to fish but some species are 
          susceptible: the LC50 (24 hours' exposure) for rainbow trout is 
          8 ppm.  Possibility of injury to young shrimps when used in tidal 
          waters. 

    2.3.2 Birds - Toxicity to birds varies both between and within species.  
          Pheasants, pigeons and sparrows are among the more susceptible 
          species.  Not likely to be hazardous under normal conditions of 
          use. 
                
    2.3.3 Other species - Low toxicity to bees.

            
     3.    FOR REGULATORY AUTHORITIES - RECOMMENDATIONS ON REGULATION OF 
          COMPOUND

    3.1   RECOMMENDED RESTRICTIONS ON AVAILABILITY

          (for definition of categories see introduction)

          All formulations Category 5

            
    3.2   TRANSPORTATION AND STORAGE

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


            
    3.3   HANDLING

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

            
    3.4   DISPOSAL AND/OR DECONTAMINATION OF CONTAINERS

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

            
    3.5   SELECTION, TRAINING AND MEDICAL SUPERVISION OF WORKERS

          All formulations - Pre-employment medical examination and
          periodic cholinesterase test for workers desirable.  Workers 
          suffering from active hepatic or renal disease should be excluded 
          from contact.  Warning of workers to avoid contact essential. 

            
    3.6   ADDITIONAL REGULATIONS RECOMMENDED IF DISTRIBUTED BY AIRCRAFT - 
          No special regulations recommended. 

            
    3.7   LABELLING

          All formulations - Minimum cautionary statement: Temephos is an 
          organophosphorus compound which inhibits cholinesterase.  It is 
          of low toxicity but may be poisonous if swallowed.  Keep the 
          material out of reach of children and well away from foodstuffs, 
          animal feed and their containers.  If poisoning occurs call a 
          physician.  Atrophine and pralidoxime are specific antidotes and 
          artificial respiration may be needed. 

            
    3.8   RESIDUES IN FOOD - Maximum residue levels have not yet been 
          recommended by the Joint FAO/WHO meeting on Pesticide Residues. 

            
    4.    PREVENTION OF POISONING IN MAN AND EMERGENCY AID

    4.1   PRECAUTIONS IN USE

    4.1.1 General - Temephos is an organophosphorus insecticide of low 
          toxicity.  It can be absorbed by mouth, by inhalation of the dust 
          and to some extent through the intact skin, although the dermal 
          route is of little significance because absorption by it is slow 
          and the toxicity of the compound is inherently low.  In liquid 
          formulations the vehicle (solvent) may be more toxic than the 
          insecticide. 
                
    4.1.2 Manufacture and formulation

          T.L.V.: 15 mg/m3 (ACGIH); USSR.  Although volatility is low, 
          vapour and dust should be controlled.  Protective equipment for
          skin and respiratory protection may be desirable. 

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

          Splashes should be washed immediately from the skin or eyes with 
          large quantities of water.  Before eating, drinking or smoking, 
          hands and other exposed skin should be washed. 

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

    4.1.5 Other populations likely to be affected - Populations using 
          drinking-water containing up to 0.5 ppm of temephos to control 
          mosquito larvae will not be exposed to hazardous amounts of 
          temephos. 

            
    4.2   ENTRY OF PERSON INTO TREATED AREAS - Persons may enter treated 
          areas immediately after spraying without being exposed to 
          hazardous amounts of temephos. 

            
    4.3   DECONTAMINATION OF SPILLAGE AND CONTAINERS - Residues in 
          containers should be emptied in a diluted form into a deep pit 
          taking care to avoid ground waters.  The empty container may be 
          decontaminated by rinsing two or three times with water and 
          scrubbing the sides.  An additional rinse should be carried out 
          with 5% sodium hydroxide solution which should remain in the 
          container overnight.  Impermeable gauntlets should be worn during 
          this work and a soakage pit should be provided for the rinsings.  
          Decontaminated containers should not be used for food and drink.  
          Spillage of temephos and its formulations should be removed by 
          washing with 5% sodium hydroxide solution and then rinsing with 
          large quantities of water. 


            
    4.4   EMERGENCY AID

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

    4.4.2 Treatment before person is seen by a physician, if these symptoms
          appear following exposure - If swallowed, vomiting should be 
          induced if the person is conscious.  In the event of a collapse, 
          artificial respiration should be given. 

            
    5.    FOR MEDICAL AND LABORATORY PERSONNEL

    5.1   MEDICAL DIAGNOSIS AND TREATMENT OF CASES OF POISONING

    5.1.1 General information - An organophosphorus insecticide of low 
          toxicity which can be absorbed by the mouth and by inhalation.  
          Absorption may occur slowly through the dermal route but this 
          route is of little significance since the toxicity of the 
          compound is inherently low.  It is a weak inhibitor of acetyl 
          cholinesterase.  It is metabolized and excreted in the urine and 
          faeces.  Poisoning in man has not been reported.  In liquid 
          formulations the vehicle may be more toxic than the insecticide. 
                                                                  
    5.1.2 Symptoms and signs - Based upon studies and upon symptoms of 
          poisoning from other organophosphorus pesticides, initial 
          symptoms of poisoning may include excessive sweating, headache, 
          weakness, giddiness, nausea, vomiting, stomach pains, blurred 
          vision, slurred speech and muscle twitching.  In the event of 
          ingestion of an excessive dose more advanced symptoms of 
          poisoning may be convulsions, coma, loss of reflexes and loss of 
          sphincter control. 

    5.1.3 Laboratory - The most important finding is reduction in activity
          of blood cholinesterases.  Urinary levels of ether-extractable 
          organic phosphorus have been used as a measure of exposure. 

    5.1.4 Treatment - If pesticide has been ingested, unless the patient is 
          vomiting, rapid gastric lavage should be performed using 5% 
          sodium bicarbonate, if available.  In spite of the low dermal 
          toxicity after skin contact, it is advisable to wash the skin 
          with soap and water.  If the compound has entered the eyes, they 
          should be washed with isotonic saline.  Persons without signs of 
          respiratory inefficiency but with manifest peripheral symptoms 
          should be treated with 2-4 mg of atropine sulfate and 1000-2000 
          mg of pralidoxime chloride or 250 mg of toxogonin (adult dose) by 
          slow intravenous injection.  More atropine may be given as 
          needed.  Persons with severe intoxication with respiratory 
          difficulties, convulsions and unconsciousness should immediately 
          be given atropine and a reactivator.  In such severe cases 4-6 mg 
          of atropine sulfate should be given initially followed by 
          repeated doses of 2 mg at 5-10 minute intervals.  The patient's 
          condition including respiration, blood pressure, pulse frequency, 
          salivation and convulsions should be carefully observed as a 
          guide to further administration of atropine.  If the patient is 
          cyanotic, artificial respiration should be given first, then 
          atropine sulfate. 

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

    5.1.6 References of previously reported cases - None.

        
    5.2   SURVEILLANCE TESTS
      

    Test                     Normal     Action     Symptomatic
                               level     level       level

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

        
          Urinary levels of ether-extractable organic phosphorus have also 
          been used to determine degrees of exposure. 


    ----------
        * Percentage of pre-exposure activity by any test.


        
    5.3   LABORATORY METHODS

          References are given only,

    5.3.1 Detection and assay of compound - To determine levels of temephos 
          in potable water, see Dale & Miles (1969).  A flame photometric 
          gas-chromatographic method for determining temephos in mosquito 
          larvae and suspensions is also reported (Bowman et ai., 1968). 

    5.3.2 Other tests in cases of poisoning

          Levels of cholinesterase in blood provide the most useful 
          diagnosis of poisoning.  See: Michel, N. 0. (1949) J. Lab. Clin. 
          Med., 34, 1564-1568; Ellman, G. L., Courtney, K. D., Andreas,
          V. jr & Featherstone, R. M. (1961) Biochem. Pharmacol., 7, 
          88-95 

          Urinary levels of ether-extractable organic phosphorus (Mattson & 
          Sledak, 1960) or dimethyl phosphate and phosphorothionate (Shafik 
          & Enos, 1969) can also be used to determine exposure. 


                                     REFERENCES

    Bowman, N. C., Ford, H. R., Lofgren, C. S. & Weidhaas, D. E. (1968)
          Residues of Abate: Analysis in Mosquito Larvae and Larvicide 
          Suspensions by Flame Photometric Gas Chromatography, J. Econ. 
          Entomol., 61, 1586 

    Dale, W. E. & Miles, J. W. (1969) Gas Chromatographic Determination of
          Abate using Flame Photometric and Electron-Capture Detectors, J.
          Agric. Fd Chem., 17, 60 

    Mattson, A. M. & Sledak, V. A. (1960) Ether-extractable urinary 
          phosphates in man and rats derived from malathion and similar 
          compounds, J. Agric. Fd Chem., 8, 107 

    Shafik, M. T. & Enos, H. F. (1969) Determination of Metabolic and
          Hydrolytic Products of Organophosphorus Pesticide Chemicals in 
          Human Blood and Urine, J. Agric. Fd Chem., 17, 118 



    See Also:
       Toxicological Abbreviations
       Temephos (ICSC)