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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/75.1
                                              ORIGINAL : ENGLISH

                                                        
                                        
   DATA SHEETS ON PESTICIDES No. 1

   January 1975


   ENDRIN



         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.

                                          

                                      
                                       ENDRIN


    Part 1 - General information   

             CLASSIFICATION:

             Primary use: Insecticide

             Secondary uses: Acaricide, rodenticide

             Chemical group: Organochlorine compound

             Data sheet No. 1

             Date issued: January 1975


    1.1   COMMON NAME: endrin (ISO)

    1.1.1 Identity: 1,2,3,4,10,10-hexachloro-6,7-epoxy-1,4,4a,5,6,7,8,8a-
    octahydro-1,4-exo-exo-5, 8-dimethanonaphthalene.  In the convention of 
    the American Chemical Society the configuration is endo-endo. 

    Figure 1

    1.1.2 Synonyms: OMS 197              Local Synonyms

    1.2   SYNOPSIS: a highly toxic organochlorine pesticide which does not 
    accumulate in the tissues of man or animals, and which is not 
    persistent in the environment. 

        
    1.3   SELECTED PROPERTIES

    1.3.1 Physical characteristics: when pure, a white crystalline solid 
    m.p.> 200°C (with decomposition); the technical product is a light tan 
    powder, with a characteristic odour. 

    1.3.2 Solubility: water at 20°C, practically insoluble (<0.1 ppm), 
    alcohol, slightly soluble 74%); benzene and acetone, moderately soluble 
    (37 and 28%). 

    1.3.3 Stability: stable in alkali and acids, but rearranges to less 
    insecticidally active substances in the presence of strong acids, on 
    exposure to sunlight, or on heating above 200°C.  Compatible with most 
    biocides in present use. 

    1.3.4 Vapour pressure very low (2 x 10-7 mm Hg at 25°C).

            
    1.4 AGRICULTURE, HORTICULTURE AND FORESTRY

    1.4.1 Common formulations

    Emulsifiable concentrate 20%, wettable powder 25 to 50%, dusts and 
    granules 1 to 2%.  FAO specifications for technical endrin, 
    emulsifiable concentrates, dispersible powders and dusts have been 
    published.  A specification for granules is in course of preparation. 

    1.4.2 Pests mainly controlled

    Effective against a very wide range of insect species.  Main uses are 
    against cotton boll worms, corn borers, cut worms and leaf hoppers. 

    1.4.3 Use pattern

    Main use is to control pests of cotton; from one to ten applications in 
    a given crop season.  Also used for rice, small cereal grains, and 
    sugar cane.  Has limited use usually under local government authority 
    for control of mice in orchards and plantations. 

    1.4.4 Unintended effects

    Use, or possibly misapplication, in orchards and forest plantations to 
    control mice has resulted in casualties amongst farm and wild animals.  
    Contamination of water, e.g. in association with use on rice, has 
    resulted in kills of fish.  Not generally phytotoxic at insecticidal 
    concentrations. 


    1.5   PUBLIC HEALTH PROGRAMMES

          No recommended use. 


    1.6    HOUSEHOLD USE

          No recommended use (due to toxicity).

                                       ENDRIN

    Part 2 - Toxicology and risks      

             Common name:  endrin

             Data sheet No. 1

             Date issued:  January 1975

        
    2.1   TOXICOLOGY - MAMMALS

    2.1.1 Absorption route: absorbed by the intact skin as well as by 
    inhalation and from the gastrointestinal tract.

    2.1.2 Mode of action: central nervous system stimulant producing 
    convulsions.

    2.1.3 Excretion: rapidly metabolized and excreted in the faeces largely 
    as the 9-hydroxy derivative. 

    2.1.4 Toxicity, single dose

          Oral: LD50 rat (M) 18 mg/kg  
                         rat (F) 7.5 mg/kg         

          Dermal: LD50 rat (M) 18 mg/kg
                           rat (F) 15 mg/kg
           
          Dermal: LD50 rabbit 60-120 mg/kg

    2.1.5 Toxicity, repeated doses

    Oral: daily administration of 5 mg/kg for 50 days led to 3 deaths out 
    of 3 rats; there were no deaths when the dose was reduced to 2 mg/kg. 

    Inhalation: 2 out of 4 deaths when rabbits were exposed for 826 
    hours, 7 hours a day, 5 days a week to an atmospheric concentration of
    5.44 mg/m3 of endrin mist. 

    Cumulation of compound: does not accumulate in mammalian tissues to 
    any significant extent; may be measured in blood and other tissues 
    during acute poisoning. 

    2.1.6 Dietary studies

    Short-term: significant increase in mortality when rats were fed 5 
    ppm (0.25 mg/kg/day) for 16 weeks but not when fed 1 ppm 
    (0.05 mg/kg/day). 

    Long-term: in a 2 year study there was increased liver to body-weight 
    ratios in males and increased kidney to body-weight ratios in females 
    fed 5 ppm (0.25 mg/kg/day); the no-effect level was 1 ppm (0.05 
    mg/kg/day). 

    2.1.7 Supplementary studies of toxicity

          Carcinogenicity

    Mouse: no increase in neoplasms from dietary levels up to 3 ppm 
    (0.15 mg/kg/day) of endrin (the highest level fed). 

    Rat: no increase in malignant tumours at dietary levels up to 12 ppm 
    (0.6 mg/kg/day) (the highest level fed). 

    Teratogenicity

    Rat: no terata reported to have been observed in a three-generation 
    reproduction study with dietary levels up to a maximum level of 2 ppm 
    (0.1 mg/kg/day). 

    2.1.8 Modifications of toxicity

    The acute toxicity of endrin was increased by a factor of 2.5 when rats 
    were fed a low protein diet. 

            
    2.2   TOXICOLOGY - MAN

    2.2.1 Absorption: see 2.1.1

    Ingestion has proved to be an important cause of poisoning with this 
    compound.

    2.2.2 Dangerous doses
        
    Single: it has been estimated that a single convulsion may result
    from ingestion of 0.2-0.25 mg/kg of endrin and repeated fits from 1 
    mg/kg. A level of about 150 ppm eaten in bread is reported to have 
    produced convulsions in man. 

          Repeated: no information.

    2.2.3 Observations of occupationally exposed workers

    Extensive observations of plant workers have been conducted. 
    Measureable levels of endrin in blood (0.05-0.1 µg/ml) were only found 
    in cases of intoxication and clinical recovery was complete within a 
    few hours. 

    2.2.4 Observations on exposure of the general population

    Not detected in the body fat of the general population in at least 
    three countries. 

    2.2.5 Observations of volunteers

          No information.

    2.2.6 Reported mishaps

    In two countries in Asia, four successive outbreaks of poisoning 
    occurred resulting in 874 people being hospitalized, of whom 26 died. 
    In two separate shipments when flour and endrin were transported 
    together, the flour became contaminated.  Bread made from the flour 
    contained 48-1500 ppm of endrin.  In a European country 59 cases of 
    poisoning with no deaths are believed to have been caused from eating 
    bread containing 150 ppm of endrin. 

    Spilled endrin had contaminated flour during shipment in a railway car.  
    In an African country three cases of poisoning with no deaths are 
    believed to have been caused from eating bread containing 126-172 ppm 
    of endrin.  The manner in which the contamination occurred is not known 
    - assumed to be during transport or storage. 

        
    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 
          precautions). 
     
    2.3.1 Fish
        
    Is very toxic to fish.  Has caused fish kills following use on rice. 

    2.3.2 Birds

    High toxicity.  Uses in orchards and similar sites have resulted in 
    bird kills.  The risks are from acute poisoning by ingestion of water 
    or seeds, not from long-term build-up of residues. 

    2.3.3 Other species

    Toxicity to bees is fairly high.  Described as moderately hazardous in 
    USDA classification.  Toxic to wildlife in general. 

                                       ENDRIN

    Part 3 - For regulatory authorities            

            Common name:  endrin

            Data sheet No. 1

            Date issued:  January 1975


    RECOMMENDATIONS ON REGULATION OF COMPOUND
        
    3.1   RECOMMENDED RESTRICTIONS ON AVAILABILITY

    (For definition of categories see introduction).  Liquid and solid 
    formulations above 10%:  category 2.  All other formulations:
    category 3. 


    3.2   TRANSPORTATION AND STORAGE

          All formulations

    UN classification 6.1. Should be transported or stored in clearly 
    labelled rigid and leakproof containers.  No food or drink should be 
    transported or stored in the same compartment.  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 used 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, TRAINING AND MEDICAL SUPERVISION OF WORKERS

          All formulations

    Pre-employment, and routine medical examination of workers desirable. 
    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 recognition of early symptoms of poisoning.  Use of flagmen not 
    recommended. Flagmen, if used, should wear overalls, a respirator, hat 
    and gloves, and be located well away from the dropping zone. 


    3.7   LABELLING

          Formulations

          All formulations

          Minimum cautionary statement


                                      "POISON"

                          (Skull and cross bones insignia)


          "Endrin is a highly toxic organochlorine compound which may be 
          very hazardous to man and animals if use is not strictly 
          controlled.  Contact with the skin, inhalation of dust or spray 
          or swallowing may cause convulsions and may be fatal.  Avoid skin 
          contact; wear protective gloves, clean protective clothing and a 
          respirator when handling this material.. Wash hands and exposed 
          skin 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 
          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, obtain medical attention."

    3.8   RESIDUES IN FOOD

    Apart from accidental gross contamination of foods, e.g. from 
    spillages, residues in foods have not resulted in major problems. 

    3.8.1 Maximum residue levels

    The Joint FAO/WHO meeting on Pesticide Residues (1972) has recommended 
    the following limits: 

          Cottonseed, cottonseed oil (crude)                     0.1 ppm

          Cottonseed oil (finished), maize (sweet), wheat,
           barley, sorghum, rice (brown or polished), apples     0.02 ppm

          Milk and milk products (fat basis)                     0.02 ppm

          Eggs (shell free)                                      0.2 ppm

          Fat of poultry                                         1.0 ppm

     
                                       ENDRIN

    Part 4 - Prevention of poisoning in man emergency aid

             Common name: endrin and
          
             Data sheet No. 1

             Date issued:  January 1975

        
    4.1   PRECAUTIONS IN USE

    4.1.1 General

    Endrin is a highly toxic organochlorine pesticide which penetrates the 
    intact skin and is also absorbed by inhalation as dusts and by the 
    gastrointestinal tract.  Formulations should be handled by trained 
    personnel wearing protective clothing. 

    4.1.2 Manufacture and formulation

          T.L.V.

    (A.C.G.I.H.) 0.1 mg/m3; (U.S.S.R.) - 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 dust mask should be worn.  Mixing, if 
    not mechanical, should always be carried out with a paddle of 
    appropriate length.  When spraying tall crops or during aerial applica-
    tion, a face mask 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, skin and eyes.  Particular 
    care is needed when equipment is being washed after use.  All 
    protective clothing should be washed immediately after use, including 
    the insides of gloves.  Splashes must be washed immediately from the 
    skin, hair and 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 endrin 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 endrin. 

        
    4.2   ENTRY OF PERSON 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

    Containers should be emptied in a diluted form into a deep pit taking 
    care to avoid contamination of ground waters.  Containers should be 
    destroyed (see 3.4). Decontamination of containers in order to use them 
    for other purposes should not be permitted.  Spillage should be washed 
    into a deep dry pit and the remainder washed away with large quantities 
    of water, taking care not to contaminate surface or ground waters. 


    4.4   EMERGENCY AID

    4.4.1 Early symptoms of poisoning

    Early symptoms of poisoning are headache, dizziness, nausea, vomiting, 
    weakness of the legs, loss of appetite and possibly insomnia and 
    temporary deafness.  Generalized convulsions may occur, and in some 
    cases are the first symptom. 

    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 water and soap, if available, and flush 
    the area with large quantities of water.  If swallowed, vomiting should 
    be induced, if the person is conscious. 


                                       ENDRIN

    Part 5 - For medical and laboratory personnel 

             Common name:  endrin

             Data sheet No. 1

             Date issued:  January 1975

        
    5.1   MEDICAL DIAGNOSIS AND TREATMENT OF CASES OF POISONING

    5.1.1 General information

    An organochlorine pesticide of high acute toxicity which may be 
    absorbed through the intact skin as well as by inhalation and via the 
    gastrointestinal tract.  Its mode of action is as a central nervous 
    system stimulant producing convulsions.  It is rapidly metabolized and 
    excreted in the faeces and does not persist in the tissues. 

    5.1.2 Symptoms and signs

    Mild symptoms of poisoning involve headache, dizziness, nausea, 
    vomiting, weakness of the legs, loss of appetite, and possibly insomnia 
    and temporary deafness.  More serious symptoms are convulsions of 
    several minutes duration followed by semi-consciousness for 15-30 
    minutes.  Terminal symptoms prior to death may be continuous 
    convulsions, causing anoxia and high fever. 

    5.1.3 Laboratory

    Blood levels of endrin associated with poisoning are 0.05-0.1 µg/ml. 
    The electroencephalogram may show bilateral synchronous spikes, spike 
    and wave complexes and slow theta waves.  It returns to normal 
    gradually and usually has become normal three months after the incident 
    of poisoning. 

    5.1.4 Treatment

    If the pesticide has been ingested, gastric lavage should be performed 
    with 2-4 litres of tap water followed by saline purgatives (30 g sodium 
    sulfate in 250 ml of water).  Barbiturates (preferably phenobarbitone 
    or pentobarbitone) or diazepam should be given I.M. or I.V. in 
    sufficient dosage to control restlessness or convulsions. Mechanical 
    respiratory assistance with oxygen may be required.  In addition, 
    calcium gluconate, 10% in 10 ml, may be injected four hourly. 
    Contraindications are oily purgatives, epinephrine and other adrenergic 
    drugs and central stimulants of all types. 

    5.1.5 Prognosis

    If the convulsions are survived the chances of complete recovery are 
    good.  However, in very severe cases there is a possibility of 
    permanent brain damage secondary to continued hypoxia if the 
    convulsions are not promptly controlled. 

    5.1.6 References of previously reported cases

    The following references give methods of treatment and diagnosis used 
    in cases of poisoning: 
            
    1.    Davies, G. M. L Lewis, I. (1956) Brit. med. J., 2, 393-398.

    2.    Weeks, D. E. (1967) Bull. Wld Hlth Org., 37, 499-512.
     

    5.2   SURVEILLANCE METHODS

    There are no readily available techniques to determine the degree of 
    absorption prior to the appearance of symptoms.  Endrin can only be 
    detected in the blood in situations of acute gross overexposure.  The 
    threshold level below which no signs-or symptoms of intoxication occur 
    appears to be in the range of 0.05-0.1 µg/ml of endrin in the blood 
    (limit of detection). 


        
    5.3   LABORATORY METHODS

    5.3.1 Detection and analysis

    Endrin residues in foodstuffs can be determined by the multi-residue 
    methods of the AOAC (United States Food and Drug Administration, 
    Pesticides Analytical Manual, 1971) and of de Faubert Maunder et 
    al. (1964), Wood (1969) and Abbott et al. (1969).  All these are gas 
    chromatographic methods, but involve various clean-up procedures.  
    Identity can be confirmed by derivative formation. Several references 
    to gas chromatographic methods for determination of organochlorine
    pesticides-in blood are cited by Jager (1970), in particular the method
    described by Richardson et al. (1967) for the determination of 
    dieldrin.  For the examination of grossly contaminated materials or of 
    samples of formulated products, an infrared spectro-scopic method can 
    be used (AOAC method, see CIPAC Handbook, Vol. 1, pp. 378-390). 

    5.3.2 Other tests in cases of poisoning
         
     Electroencephalographic changes after endrin poisoning are described 
    in Hoogendam, I., Versteeg, J. P. J. & de Vlieger, M. (1962), Arch. 
    environm. Hlth., 4, 86-94


                                     REFERENCES

    Abbott, D. C., Holmes, D. C. & Tatton, J. O'G. (1969) Pesticide 
          residues in the total diet in England and Wales, 1966-1967.  II. 
          Organochlorine pesticide residues in the total diet, J. Sci. Food 
          Agric., 20, 245 

    Faubert Maunder, M. J. de et al. (1964) Clean-up of animal fats and 
          dairy products for the analysis of chlorinated pesticide 
          residues, Analyst., 89, 168 

    Jager, K. W. (1970) Aldrin, dieldrin, endrin and telodrin, Elsevier,
          Amsterdam, p. 34

    Richardson, A. et al. (1967) Determination of dieldrin (HEOD) in blood, 
          Arch. environm. Hlth, 14, 703

    United States Food and Drug Administration (1971) Pesticide Analytical
          Manual, Vol. I, Sections 211, 212

    Wood, N. F. (1969) Extraction and clean-up of organochlorine pesticide 
          residues by column chromatography, Analyst, 94, 399 
See Also:
        Endrin (EHC 130, 1992)
        Endrin (IARC Summary & Evaluation, Volume 5, 1974)