INTOX Home Page


    WORLD HEALTH ORGANIZATION             FOOD AND AGRICULTURE
                                          ORGANIZATION
    ORGANISATION MONDIALE DE LA SANTE     ORGANISATION POUR L'ALIMENTATION
                                          ET L'AGRICULTURE

                                          VBC/DS/79.38
                                          ORIGINAL:   ENGLISH


    LEPTOPHOS




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

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

    CLASSIFICATION:
    primary use: Insecticide
    Secondary use: Fungicide
    Chemical group: Organophosphorus compound
    Date issued: April 1979

    1.     GENERAL INFORMATION
    
    1.1    COMMON NAME: Leptophos (ISO)

    1.1.1  Identity: O-(4-bromo-2,5-dichlorophenyl) 0-methyl 
           phenylphosphonothioate 

           Structure

    1.1.2  Synonyms: 
           VCS 506
           Phosvel
           Abar
           
           Local synonyms:

    1.2    SYNOPSIS - An organophosphorus insecticide of high mammalian 
           toxicity which may produce a delayed neurotoxic effect.  It 
           should not be used if an alternative exists. 

    1.3    SELECTED PROPERTIES

    1.3.1  Physical characteristics - A white amorphous solid of melting 
           point 70.2-70.6°C (99.4% purity). 

    1.3.2  Solubility - Only very slightly soluble in water, 2.4 mg/i at 
           25°C.  Very soluble in benzene, 1.3 kg/l; cyclohexane 142 g/l; 
           acetone, 470 mg/l. 

    1.3.3  Stability - Very stable; it hydrolyses slowly under strongly 
           alkaline conditions and is stable under prolonged acid exposure 
           at normal temperatures.  Decomposition occurs above 350°C. 

    1.3.4  Vapour pressure - 1.5 x 10-5 mmHg at 25°C.

    1.4    AGRICULTURE, HORTICULTURE AND FORESTRY

    1.4.1  Common formulations - Emulsifiable concentrates 3 Ib a.i./US 
           gall (300 g/1).  Wettable powder 45%; dust 3%, granulets 5%. 

    1.4.2  Pests mainly controlled - Effective against lepidoptera 
           especially Prodenia litura, grasshoppers, bugs, fleas. 

    1.4.3  Use pattern - There is positive evidence of a temperature 
           coefficient against lepidoptera which may make it more useful in 
           warmer climates.  Moderately persistent.  Used as e.c. on cotton 
           at 1.5 lb a.i./acre (1.7 kg/ha).  Used as e.c. on vegetables and 
           fruit at 1.0 lb a.i./100 galls (1 g/1).  Use as granules on 
           maize at 1.5  kg a.i.,/hectare. 
    
    1.4.4  Unintended effects - Reported to have only minimal irritating 
           effect on eyes if handled with usual care. 

    1.5    PUBLIC HEALTH PROGRAMMES - Not recommended for any use in public 
           health programmes. 
    
    1.6    HOUSEHOLD USE: No household use.
    
    2.     TOXICOLOGY AND RISKS
    
    2.1    TOXICOLOGY - MAMMALS

    2.1.1  Absorption route - Leptophos may be absorbed through the intact 
           skin, by inhalation and from the gastrointestinal tract. 

    2.1.2  Mode of action - Inhibition of cholinesterase and "neurotoxic 
           esterase" after metabolic conversion to the oxygen analogue. 

    2.1.3  Excretion products - Most of an oral dose is eliminated within 
           24 hours.  By 96 hours 80-87% of C14 labelled leptophos is 
           accounted for in the urine and approximately 12% in the faeces.  
           Metabolites include the oxygen analogue, 0-methyl 
           phenylphosphonothioate and 1-bromo-2,5-dichlorophenol. 

    2.1.4  Toxicity, single dose
           Oral: LD50 rat (M): 53 mg/kg
                   rat (F): 43 mg/kg

           Dermal: LD50 rabbit > 800 mg/kg

    2.1.5  Toxicity, repeated doses
      
           Oral: Rats of both sexes were fed 1.0, 5.0, 10.0 mg/kg diet of 
           leptophos for 90 days.  All survived and there were no 
           alterations in body weights, plasma biochemistry or in brain, 
           plasma and erythrocyte cholinesterase.  Rats of both sexes were 
           fed 3.0, 10.0, 30.0 and 100 mg/kg diet for 10 days.  One rat 
           died at the 100 mg/kg level and there was marked inhibition of 
           brain and erythrocyte cholinesterase at 30 ppm in all but one 
           rat.  The rats surviving for 10 days at 100 mg/kg showed similar 
           cholinesterase inhibition. 

           Inhalation: The aerosol inhalation LC50 was found to be  
           2.7 g/m3 air based on a fourhour period of exposure for albino 
           rats.  Cholinesterase inhibition in blood was observed at 
           concentrations of 0.84 mg/litre of air.  Tremors, lacrimation, 
           salivation and blood stained ocular and nasal discharge were 
           observed. 

           Cumulation of compound:  Leptophos is not cumulative in body 
           tissues. 

           Cumulation of effect: Continued exposure to leptophos is likely 
           to have a cumulative effect on cholinesterase inhibition. 

    2.1.6  Dietary studies

           Short-term: Dogs of both sexes were fed leptophos at 3.0, 10.0 
           and 30.0 mg/kg diet for 90 days.  No biochemical abnormalities 
           were observed.  Body weight, food consumption, haematology and 
           urine analyses were normal.  At the completion of this study, 
           organ weights and gross and histopathologic examinations were 
           within normal limits . 

           Long-term: A two-year dietary feeding study in rats at 10, 20, 
           30 and 60 mg/kg diet revealed no significant abnormalities apart 
           from some inhibition of erythrocyte cholinesterase at 60 mg/kg 
           after 18 and 24 months exposure.  No significant effect on brain 
           cholinesterase was observed at any of the feeding levels. 

    2.1.7  Supplementary studies on toxicity

           Carcinogenicity: During the two-year feeding study described 
           above (2.1.6) a tumour incidence was assessed at the conclusion 
           of the investigation.  The incidence of tumours in the treated 
           and control animals was comparable and considered normal. 

           Teratogenicity: Rabbits dosed with leptophos at 1.0 and 3.0 
           mg/kg from days 6-18 of gestation revealed no increase in 
           resorptions, foetal mortality or abnormal offspring.  Body 
           weights of foetuses from both test groups compared well with the 
           untreated contro group. 

           Mutagenicity: A dominant lethal mutagenic study designed to 
           evaluate the potential effects of leptophos upon male germinal 
           cells in mice was conducted.  Both orai and intraperitoneal 
           dosage were employed and by both routes, doses of 15 and 30 
           mg/kg were used.  None of the animals showed any impairment in 
           mating ability. 

           Delayed neurotoxicity: Delayed ataxia and paralysis in hens has 
           been reported with this compound after single oral doses of 400 
           and 500 mg/kg.  The oxon metabolite of leptophos is an extremely 
           active inhibitor of the "neurotoxic esterase" in vitro, normally 
           a clear warning of potential hazard. 

           Local irritative effect: Transient conjunctival irritation has 
           been observed in rabbits after instillation of 100 mg of 
           leptophos.  The reaction was most marked at 24 hours and had 
           disappeared 72 hours after exposure. 

    2.1.8  Modifcation of toxicity - No information available.
    
    2.2    TOXICOLOGY - MAN

    2.2.1  Absorption - Leptophos may be absorbed through the intact skin, 
           by inhalation and frothe gastrointestinal tract. 

    2.2.2  Dangerous doses

           Single: Not known.

           Repeated: Not known.

    2.2.3  Observations on occupationally exposed workers - No information 
           available. 

    2.2.4  Observations on exposure of the general population - No 
           information available. 
    
    2.2.5  Observations of volunteers - No information available.

    2.2.6  Reported mishaps - 1200 water buffalo were suspected of being 
           poisoned with leptophos. Some fatalities were recorded and there 
           were reports of persistent paralysis in some of the survivors. 

    2.3    TOXICITY TO NON-MAMMALIAN SPECIES

    2.3.1  Fish - Harmful - rainbow trout: as toxic as DDT
                            goldfish:  much more toxic than DDT
    
    2.3.2  Birds - Subacutely toxic to quail.  Neurotoxic to hens at high 
           dosage. 

    2.3.3  Other species - No harmful effects reported following widespread 
           foliar and soil treatments at 1-2 kg/ha on arable and 
           horticultural crops in several countries.  Regarded however as 
           potential toxicant to wild life if used contrary to labels. 

    3.     FOR REGULATORY AUTHORITIES - RECOMENDATIONS ON REGULATION OF 
           COMPOUND
         
    3.1    RECOMMENDED RESTRICTIONS ON AVAILABILITY

           (for definition of categories, see Introduction to Data Sheets)
    
           All formulations Category 1: This compound has an adjusted 
           classification in the WHO Recommended Classification of 
           Pesticides by Hazard due to its potential to cause delayed 
           neurotoxicity. 

           Granular formulations only below 2%, category 5.

    3.2    TRANSPORTATION AND STORAGE

           All formulations - Should be transported in clearly labelled 
           rigid and leakproof containers and in a separate compartment not 
           containing any food or 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 CONTAINER

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

    3.5    SELECTION, TRAINING AND MEDICAL SUPERVISION OF WORKERS

           All formulations - Prc-employment medical examination of workers 
           necessary.  Workers suffering from active haptic, renal or 
           neurological disease should be excluded from contact.  Pre-
           employment and periodic cholinesterase test for workers 
           desirable.  Special account should be taken of the workers' 
           ability to comprehend and follow instructions. 

    3.6    ADDITIONAL REGULATIONS RECOMMENDED IF DISTRIBUTED BY AIRCRAFT

           All formulations - Should not be applied from the air.

    3.7    LABELLING

           All formulations "POISON" (skull and crossbones insignia).

           Minimum cautionary statement - Leptophos is an organophosphorus 
           compound which inhibits cholinesterase, an may cause delayed 
           disorders of the nervous system.  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 kept under 
           lock and key.  Keep the material out of the reach of children 
           and well away from foodstuffs, animal feed and their containers.  
           If splashed, irmnediately remove contaminated clothing and wash 
           the skin thoroughly with soap and water.  For splashes in eyes, 
           flush with water for 15 minutes. 

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

    3.8    RESIDUES IN FOOD: Maximum residue limits have been recommended 
           by the Joint FAO/WHO Meeting on Pesticide Residues.  These are 
           subject to review by the Joint Meeting which is held annually. 

    4.     PREVENTION OF POISONING IN MAN AND EMERGENCY AID

    4.1    PRECAUTIONS IN USE

    4.1.1  General - Leptophos is an organophosphorus pesticide of high 
           toxicity.  It penetrates The intact skin and is also absorbed by 
           inhalation and from the gastrointestinal tract.  All 
           formulations should be handled by trained personnel wearing 
           protective clothing. 

    4.1.2  Manufacture and formulation

           T.L.V.: No information available.

    4.1.3  Mixers and applicators - When opening the container and when 
           mixing, protective impermeable boots, clean overalls, gloves and 
           respirator should be worn.  Mixing, if not mechanical, should 
           always be carried out with a paddle of appropriate length.  When 
           spraying tall crops 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 insides 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 - Persons exposed to leptophos 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 leptophos. 

    4.2    ENTRY OF PERSONS INTO TREATED AREAS - Unprotected persons should 
           be kept out of treated areas for at least one day. 

    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 leptophos 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 - 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 leptophos. 
    
    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 can be absorbed through the intact skin as 
           well as by inhalation and from the gastrointestinal tract.  It 
           is partially converted in vivo to the oxon analogue which is an 
           active inhibitor of acetylcholinesterase.  Continued exposure to 
           low amounts may inhibit blood cholinesterase to dangerous 
           levels.  By a different mechanism (inhibition of "neurotoxic 
           esterase"), dying-back process may be initiated in which the 
           long axons are particularly affected (delayed neurotoxic 
           effect). 

    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 may include 
           convulsions, coma, loss of reflexes, and loss of sphincter 
           control.  In survivors, delayed neurotoxicity may become 
           manifest by persistent ataxia and paralysis of the limbs. 

    5.1.3  Laboratory - The most important laboratory findings is reduction 
           in blood cholinesterase activity. 

    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.  if skin contact has 
           occurred the skin should be washed with soap and water.  If the 
           compound has entered the eyes, they should be washed with a 
           large quantity of isotonic saline or water.  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 

           should be given as needed.  Persons with severe intoxication, 
           with respiratory dif f iculties, convulsions and unconsciousness 
           should immediately be given atropine and a reactivator.  In such 
           severe cases 4-6 mg of atropine sulfate at 5-10 minute 
           intervals.  The patient's condition, including respiration, 
           blood pressure, and pulse rate, should be carefully observed as 
           a guide to further administration of atropine.  If the patient 
           is cyanotic, atropine and artificial respiration or oxygen as 
           required may be administered simultaneously.  If necessary, 
           intubation should be performed.  Diazepam may be given to 
           control fits.  Contraindicated are morphine, barbiturates, other 
           tranquillizers and central stimulants of all kinds. 

    5.1.5  Prognosis - There is no specific treatment for delayed 
           neurotoxic effects.  In people surviving the acute toxic effect 
           the chances of complete recovery are not certain as it is 
           possible that persistent ataxia and paralysis of limbs may be a 
           sequel of poisoning. 

    5.1.6  Reference of previously reported case - No cases of poisoning in 
           man have so far reported. 

    5.2    SURVEILLANCE TESTS

           Test                   Normal level*    Action level*     
           
           Plasma cholinesterase       100%             50%              
             
           Erythrocyte cholin-
           esterase                    100%             70%
            
           Symptomatic level
                  
                variable

               usually 40%

           Urinary levels of ether extractable organic phosphorus may also 
           be used to determine the degree of exposure. 

    5.3    LABORATORY METHODS -  References are given only.

    5.3.1  Detection and assay of compound - It is unlikely that unchanged 
           leptophos will be detectable in human tissue after exposure as 
           it will be fairly rapidly broken down to a number of 
           metabolites. 

           Product analysis is by infra-red absorption at 9.62 microns.  
           Residues are determined by electron capture G.L.C. Particulars 
           of the methods can be obtained from the Velsicol Chemical 
           Corporation, Chicago, or from Bowman, M. C. & Beroza, M. (1969) 
           J. Agr. Food Chem., 17, 1054. 

    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 and Ellman, G. L. et al. (1961)   
           Biochem. Pharmacol., 7, 88. 

           Levels of phosphate esters in urine may also be determined in 
           order to give an indication of the extent of exposure. See 
           methods given in 5.3.1 above. 


          * Expressed as percentage of pre-exposure activity.
           


                                    = = =       


See Also:
        Leptophos (PIM 304)