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    IPCS INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY
    Health and Safety Guide No. 60

    ENDRIN
    HEALTH AND SAFETY GUIDE






    UNITED NATIONS ENVIRONMENT PROGRAMME

    INTERNATIONAL LABOUR ORGANISATION

    WORLD HEALTH ORGANIZATION




    WORLD HEALTH ORGANIZATION, GENEVA 1991

    This is a companion volume to Environmental Health Criteria 130:
    Endrin

    Published by the World Health Organization for the International
    Programme on Chemical Safety (a collaborative programme of the United
    Nations Environment Programme, the International Labour Organisation,
    and the World Health Organization)

    This report contains the collective views of an international group of
    experts and does not necessarily represent the decisions or the stated
    policy of the United Nations Environment Programme, the International
    Labour Organisation, or the World Health Organization


    WHO Library Cataloguing in Publication Data

    Endrin : health and safety guide.

    (Health and safety guide ; no. 60)

    1. Endrin - standards  I. Series

    ISBN 92 4 151060 9          (NLM Classification: WA 240)
    ISSN 0259-7268

    (c) World Health Organization 1991

    Publications of the World Health Organization enjoy copyright
    protection in accordance with the provisions of Protocol 2 of the
    Universal Copyright Convention.  For rights of reproduction or
    translation of WHO publications, in part or  in toto, application
    should be made to the Office of Publications, World Health
    Organization, Geneva, Switzerland.  The World Health Organization
    welcomes such applications.

    The designations employed and the presentation of the material in this
    publication do not imply the expression of any opinion whatsoever on
    the part of the Secretariat of the World Health Organization
    concerning the legal status of any country, territory, city or area or
    of its authorities, or concerning the delimitation of its frontiers or
    boundaries.

    The mention of specific companies or of certain manufacturers'
    products does not imply that they are endorsed or recommended by the
    World Health Organization in preference to others of a similar nature
    that are not mentioned.  Errors and omissions excepted, the names of
    proprietary products are distinguished by initial capital letters.

    CONTENTS

    INTRODUCTION

    1. PRODUCT IDENTITY AND USES
         1.1. Identity
         1.2. Physical and chemical properties
         1.3. Analytical methods
         1.4. Production and uses

    2. SUMMARY AND EVALUATION
         2.1. Exposure
         2.2. Uptake, metabolism, and excretion
         2.3. Effects on organisms in the environment
         2.4. Effects on experimental animals and in vitro test systems
         2.5. Effects on human beings

    3. CONCLUSIONS AND RECOMMENDATIONS
         3.1. Conclusions
         3.2. Recommendations

    4. HUMAN HEALTH HAZARDS, PREVENTION AND PROTECTION, EMERGENCY ACTION
         4.1. Main human health hazards, prevention and protection,
              first aid
              4.1.1. Symptoms of poisoning
              4.1.2. Medical treatment
              4.1.3. Health surveillance advice
         4.2. Safety in use
         4.3. Explosion and fire hazards
              4.3.1. Explosion hazard
              4.3.2. Fire hazard
         4.4. Storage
         4.5. Transport
         4.6. Spillage and disposal
              4.6.1. Spillage
              4.6.2. Disposal

    5. HAZARDS FOR THE ENVIRONMENT AND THEIR PREVENTION

    6. CURRENT REGULATIONS, GUIDELINES, AND STANDARDS
         6.1. Previous evaluations by international bodies
         6.2. Exposure limit values
         6.3. Specific restrictions
         6.4. Labelling, packaging, and transport
         6.5. Waste disposal
         6.6. Other measures

    BIBLIOGRAPHY

    ANNEX
    

    INTRODUCTION

    The Environmental Health Criteria (EHC) documents produced by the
    International Programme on Chemical Safety include an assessment of
    the effects on the environment and on human health of exposure to a
    chemical or combination of chemicals, or physical or biological
    agents.  They also provide guidelines for setting exposure limits.

    The purpose of a Health and Safety Guide is to facilitate the
    application of these guidelines in national chemical safety
    programmes. The first three sections of a Health and Safety Guide
    highlight the relevant technical information in the corresponding EHC. 
    Section 4 includes advice on preventive and protective measures and
    emergency action; health workers should be thoroughly  familiar with
    the medical information to ensure that they can act efficiently in an
    emergency.  Within the Guide is a Summary of Chemical Safety
    Information which should be readily available, and should be clearly
    explained, to all who could come into contact with the chemical.  The
    section on regulatory information has been extracted from the legal
    file of the International Register of Potentially Toxic Chemicals
    (IRPTC) and from other United Nations sources.

    The target readership includes occupational health services, those in
    ministries, governmental agencies, industry, and trade unions who are
    involved in the safe use of chemicals and the avoidance of
    environmental health hazards, and those wanting more information on
    this topic.  An attempt has been made to use only terms that will be
    familiar to the intended user.  However, sections 1 and 2 inevitably
    contain some technical terms.  A bibliography has been included for
    readers who require further background information.

    Revision of the information in this Guide will take place in due
    course, and the eventual aim is to use standardized terminology. 
    Comments on any difficulties encountered in using the Guide would be
    very helpful and should be addressed to:

    The Manager
    International Programme on Chemical Safety
    Division of Environmental Health
    World Health Organization
    1211 Geneva 27
    Switzerland

    THE INFORMATION IN THIS GUIDE SHOULD BE CONSIDERED AS A STARTING POINT
    TO A COMPREHENSIVE HEALTH AND SAFETY PROGRAMME

    1.  PRODUCT IDENTITY AND USES

    1.1  Identity

    Common name:                  endrin

    Molecular formula:            C12H8Cl6O

    Chemical structure:

    CHEMICAL STRUCTURE 1

    Synonyms:                     Endrex, Experimental Insecticide 269,
                                  Hexadrin, Nendrin, NCI-COO157, ENT 17251
                                  OMS 197, and Mendrin

    CAS chemical name:            (1a,2,2a,3,6,6a,7,7a)-3,4,5,6,9,9-
                                  hexachloro-1a,2,2a,3,6,6a,7,7a-
                                  octahydro-2,7:3,6-dimethanonaphth[2,3-b]
                                  oxirene (9CI-CAS).

    Former CAS chemical name:     1,2,3,4,10,10-hexachloro-6,7-epoxy-
                                  1,4,4a,6,7,8,8a-octahydro-1,4-endo,endo-
                                  5,8-dimethanonaphthalene)

    IUPAC chemical name:          (IR,4S,4aS,5S,6S,7R,8R,8aR)-
                                  1,2,3,4,10.10-h exachloro-
                                  1,4,4a,5,6,7,8,8a-octahydro-6,7-epoxy-
                                  1,4:5,8-dimethano-naphthalene

    CAS registry number:          72-20-8

    RTECS registry number:        IO1575000

     Technical product

    Trade name:                   Endrin

    Purity:                       Not less than 92%.  Impurities include
                                  dieldrin (0.42%), aldrin (0.03%),
                                  isodrin (0.73%), endrin half-cage ketone
                                  (1.57%), endrin aldehyde (0.05%), and
                                  heptachloro-norbornene (0.09%).

    1.2  Physical and Chemical Properties

    Endrin is a crystalline solid with a mild odour.  Technical endrin is
    stable when stored at ambient temperatures.  It is stable in
    formulations containing alkaline agents, emulsifiers, wetting agents,
    and solvents.  It decomposes with concentrated mineral acids, acid
    catalysts, acid oxidizing agents, and active metals.  When heated
    above 200C, endrin forms a less toxic and less insecticidally active
    compound, delta-ketoendrin.

    Some physical properties of endrin are given in Table 1.

    Table 1. Physical properties of endrin

                                                                         

    Melting point             226-230C (above 200C decomposition)
    Flash-point               None
    Explosion limits          Stable
    Vapour pressure           2.7 x 10-7mmHg at 25C 
                              (3.6 x 10-5Pa at 25C)
    Relative molecular mass   380.9
    Density                   1.64 g/ml at 20C
    Solubility in water       Practically insoluble
    Solubility in organic     Sparingly soluble in alcohols, petroleum
    solvents                  hydrocarbons, moderately soluble in
                              aliphatic hydrocarbons, and quite soluble
                              in solvents, such as acetone, benzene, 
                              carbon tetrachloride, and xylene
    Partition coefficient 
    log P octanol/water       5.34
                                                                         

    Conversion factors (20C):

    1 ppm = 16 mg/m3;
    1 mg/m3 = 0.063 ppm.

    1.3  Analytical Methods

    Analytical methods for the determination of endrin are mainly based on
    gas-liquid chromatography with electron-capture detection.

    1.4  Production and Uses

    Endrin has been manufactured since 1950, and was used throughout the
    world up to the early 1970s.  No actual production figures are
    available, but the use of endrin has declined since the early 1970s,
    because of severe restrictions on use, or banning, in several
    countries.

    It is a contact and stomach poison, used as a foliar insecticide,
    which acts against a wide range of pests, particularly Lepidoptera. 
    It can be used at 0.2-0.5 kg a.i./ha on cotton, maize, sugar cane,
    upland rice, and many other crops.

    Endrin formulations include emulsifiable concentrates (ECs) at
    190-200 g a.i./litre, wettable powders (WPs) at 500 g a.i./kg,
    granules at 10-50 g a.i./kg, field strength dusts (FSDs), and pastes.

    2.  SUMMARY AND EVALUATION

    2.1  Exposure

    Endrin is an organochlorine insecticide that has been used since the
    1950s to control a wide range of agricultural pests, mainly on cotton,
    but also on rice, sugar cane, maize, and other crops.  It is also used
    as a rodenticide and avicide.  Commercially, it is available in the
    form of a dust, granules, paste, and as an emulsifiable concentrate
    (EC).

    Endrin enters the air mainly through volatilization and aerial drift. 
    In general, volatilization takes place after application to soils and
    crops, and depends on many factors, such as the organic matter and
    moisture content of the soil, humidity, air flow, and the surface area
    of plants.

    The most important route of contamination of surface water is run-off
    from soil.

    Contamination from precipitation, in the form of snow or rain, is
    negligible.  Local contamination of the environment may occur from
    industrial effluents and careless application practices.

    The main source of endrin in the soil is its direct application to
    soil and crops.  In soil, endrin can be retained, transported, or
    degraded, depending on a number of factors.  The highest retention
    occurs in soils with a high organic matter content.  The persistence
    of endrin is highly dependent on local conditions.  Its half-life in
    soil can range up to 12 years.

    Volatilization and photodecomposition are primary factors in the
    disappearance of endrin from soil surfaces.  Under the influence of
    sunlight (UV radiation), the isomer delta-ketoendrin is formed.  In
    intense summer sunlight, about 50% of the endrin is isomerized to this
    ketoendrin in 7 days.  Microbial transformation (fungi and bacteria)
    takes place, especially under anaerobic conditions, yielding the same
    product.

    Aquatic invertebrates and fish take up endrin rapidly from water. 
    Bioconcentration factors ranging between 14 and 10 000 have been
    recorded after continuous exposure.  Exposed fish transferred to
    uncontaminated water lose endrin rapidly.  Soil invertebrates may also
    take up endrin readily.

    The occasional presence of low levels of endrin in air and in surface
    water or drinking-water (in agricultural areas) is of little
    significance from the point of view of public health.  The only
    exposure that may be of relevance is the dietary intake.  In general,
    the reported intake levels are far below the ADI of 0.0002 mg/kg body
    weight, established in 1970 (FAO/WHO, 1971).

    2.2  Uptake, Metabolism, and Excretion

    Unlike dieldrin, its stereoisomer endrin is rapidly metabolized by
    animals; accumulation in the fat of animals is very low compared with
    that of other compounds of similar chemical structure.  In rats, it is
    eliminated mainly in the faeces as endrin, anti-12-hydroxyendrin, and
    a hydroxylated endrin derivative; a third metabolite, 12-ketoendrin,
    accumulates in the tissues.

    Both uptake and excretion after oral administration are rapid in rats. 
    The biological half-life is 1-6 days, depending on the dose level.  A
    steady state, when the excreted amount equals the daily intake, is
    reached after 6 days.   Excretion of both endrin and its metabolites
    via the bile is much more rapid in male rats than in females,
    resulting in lower accumulation in adipose tissue in males.

    In rats, endrin and its metabolites are mainly eliminated via the
    faeces in the first 24 h (70-75%).  In rabbits, 50% of the metabolites
    are excreted in the urine, compared with only 2% in rats.  Only
    unchanged endrin is found in the faeces of rabbits.

    When cows were administered 0.1 mg endrin/kg diet for 21 days, up to
    65% was excreted as metabolites in the urine, 20% was found in the
    faeces, partly as unchanged endrin, and 3% was excreted in the milk,
    also mainly as endrin.  Residue levels of 0.003-0.006 mg/litre in
    milk, 0.001-0.002 mg/ kg in meat, and 0.02-0.1 mg/kg in fat were
    found.

    Depending on dose levels, laying hens fed endrin showed residues of up
    to 0.1 mg/kg in meat and 1 mg/kg in fat; eggs (yolk) contained
    0.2-0.3 mg/kg and liver and kidneys each contained 0.2-0.5 mg/kg.  The
    residues found were mainly unchanged endrin, except in the liver and
    kidneys.  About 50% of the administered endrin was excreted in the
    faeces, mainly in the form of metabolites.

    It is clear that in the rat, rabbit, cow, hen, and man, the major
    biotransformation metabolites of endrin are anti-12-hydroxyendrin, and
    its sulfate and glucuronide conjugates.  Four other metabolites are
    present only in minor quantities.  In body tissues and milk, mainly
    unchanged endrin is found.

    After application of endrin to plants, unchanged endrin and
    transformation products including delta-ketoendrin and a very
    hydrophilic compound were identified.

    2.3  Effects on Organisms in the Environment

    The effects of endrin on soil bacteria and fungi are minimal.  Dose
    levels of between 10 and 1000 mg/kg soil did not have any effects on
    the decomposition of organic matter, denitrification, or the
    generation of methane.  Endrin is very toxic for fish, aquatic
    invertebrates, and phytoplankton; the 96-h LC50 values are mostly
    below 1.0 g/litre.  In a life-cycle test, a lowest-observed-effect
    level (LOEL) for the mysid shrimp  (Mysidopsis bahia) was established
    of 30 ng/litre.

    The reported acute toxicity tests on aquatic organisms have been
    conducted in aquaria without sediment.  The presence of sediment would
    be expected to attenuate the toxicity of endrin.  Heavily contaminated
    sediment had little effect on species living in open water, suggesting
    low bioavailability of sediment-bound endrin.  No tests have been
    conducted on sediment-living aquatic animals.

    The  LD50 values for terrestrial mammals and birds are of the order
    of 1.0-10.0 mg/kg body weight.  Endrin fed to Mallard ducks at doses
    of up to 3.0 mg/kg body weight, for 12 weeks, did not produce any
    effects on egg production, fertility, or hatchability.

    Resistance to endrin toxicity has been reported in several animal
    groups including: aquatic invertebrates, fish, and small mammals. 
    Exposure to several different organochlorine pesticides led to the
    selection of strains resistant to endrin.

    Fish-kills occurring in agricultural (run-off) and industrial
    (discharge) areas, and population decline in brown pelicans
    (Louisiana, USA) and sandwich terns (the Netherlands) have been
    attributed to a combination of endrin and other halogenated chemicals.

    2.4  Effects on Experimental Animals and In vitro Test Systems

    Endrin is a highly toxic pesticide.  The oral LD50 values for
    technical endrin in laboratory animals are in the range of 3-43 mg/kg
    body weight. Dermal LD50 values for the rat range from 5 to 20 mg/kg
    body weight.  No substantial differences were found in the acute oral
    and dermal toxicities of technical and formulated EC and wettable
    powder (WP) products.  Signs of intoxication are of a neurotoxic
    nature.

    Short-term oral toxicity studies were carried out on mice, rats,
    rabbits, dogs, and domestic animals.  In mice and rats, the maximum
    tolerated doses for 6 weeks were 5 and 15 mg/kg diet (equivalent to
    0.7 mg/kg body weight), respectivley.  Rats survived a 16-week
    exposure to a level of 1 mg/kg diet (equivalent to 0.05 mg/kg body
    weight).  Rabbits, administered repeated doses of 1 mg endrin/kg body
    weight, died.  In studies on dogs, a dietary level of 1mg/kg diet
    (approx. 0.025 mg/kg body weight), given over 2 years, did not induce
    any effects.

    At low doses, the neurologically based sign of intoxication is an
    inhibition of the GABA-ergic function.  As is the case with other
    chlorinated hydrocarbon insecticides, endrin also affects the liver. 
    Stimulation of enzyme systems involved in the metabolism of other
    chemicals was evident as shown by, for instance, a decreased
    hexobarbital sleeping time.

    Doses of 75-150 mg endrin/kg, applied dermally as the dry powder for
    2 h daily, caused convulsions and death in the rabbit, but did not
    result in skin irritation.  The production of systemic toxicity
    without irritation at the site of contact is noteworthy.

    Long-term toxicity/carcinogenicity studies were carried out on the
    mouse and rat.  No carcinogenic effects were found, but it should be
    mentioned that there were shortcomings in the studies, e.g., poor
    survival of the animals.  In a 2-year study on the rat, the
    no-observed-effect level was 1 mg/kg diet (ca 0.05 mg/kg body weight). 
    Tumour-promoting effects were not observed when endrin was tested in
    combination with subminimal quantities of animal carcinogens.  Endrin
    was not found to be genotoxic in several mutagenicity studies.  The
    WHO Task Group on Environmental Health Criteria for Endrin concluded
    that the data are insufficient to indicate that endrin is a
    carcinogenic hazard for human beings.

    Endrin was found not to be teratogenic in mice, rats, and hamsters,
    even at dose levels causing maternal or fetotoxicity.  NOELs of
    0.5 mg/kg body weight in mice and rats and 0.75 mg/kg body weight in
    hamsters were demonstrated.  Endrin, at a dose of 2 mg/kg diet (ca
    0.1 mg/kg body weight), did not induce reproductive effects over 3
    generations in the rat.

    A number of metabolites have acute toxicities that are similar to, or
    higher  than, that of endrin.  The transformation product
    delta-ketoendrin is less toxic.  12-Ketoendrin is considered to be the
    most toxic metabolite of endrin in mammals, with an oral LD50 in the
    rat of 0.8-1.1 mg/kg body weight.

    2.5  Effects on Human Beings

    Several episodes of fatal and non-fatal accidental and suicidal
    poisoning have occurred.  Cases of acute non-fatal intoxication, due
    to accidental overexposure, have been observed in workers in an
    endrin-manufacturing plant.  The oral dose causing death was estimated
    to be approximately 10 mg/kg body weight.  The single oral dose
    causing convulsions was estimated to be 0.25-1.0 mg/kg body weight.

    The primary site of action of endrin is the central nervous system. 
    Exposure of humans to a toxic dose may lead to signs and symptoms of
    intoxication, such as excitability and convulsions, within a few
    hours, and death may occur within 2-12 h following exposure, if
    appropriate treatment is not administered immediately.  In cases of
    non-fatal poisoning, recovery is rapid and complete.

    Endrin does not accumulate in the human body to any significant
    extent.  Medical supervision of occupationally exposed workers
    (duration of exposure ranging from 4 to 27 years) showed that
    long-term adverse effects were not present (observation period for 232
    workers ranged from 4 to 29 years).  The only effect observed in the
    workers was indirect evidence of a reversible stimulation of drug
    metabolizing enzymes.

    Endrin was not detected in a large number of samples of adipose
    tissue, blood, and breast milk analysed in many countries.  The Task
    Group attributed this to the minor exposure of the general population
    to endrin and its rapid metabolism.

    Endrin could be detected in the blood (up to 450 g/litre) and tissues
    (adipose tissue, 89.5 mg/kg) in cases of fatal accidental poisonings. 
    No endrin was found in workers under normal circumstances.  The
    threshold level of endrin in the blood, below which no signs or
    symptoms of intoxication occur, has been estimated to be in the range
    of 50-100 g/litre.  The half-life of endrin in the blood may be of
    the order of 24 h.

    3.  CONCLUSIONS AND RECOMMENDATIONS

    3.1  Conclusions

    Endrin is an insecticide of high acute toxicity.  Overexposure through
    careless handling during manufacture or use, or from contaminated
    food, may cause severe poisoning.

    Exposure of the general population to endrin arises mainly through
    residues in food.  The reported intakes have generally been far below
    the Acceptable Daily Intake established by FAO/WHO.  Such exposure
    should not constitute a health hazard for the general population.

    When good work practices, hygiene measures, and safety precautions are
    enforced, endrin is unlikely to present a hazard for those
    occupationally exposed.

    It is clear that the high toxicity of endrin can cause acute
    environmental problems when there are uncontrolled discharges during
    its manufacture, formulation, or use.  Effects on wildlife from
    agricultural use are less clear, though fish and fish-eating birds are
    at risk from surface run-off.

    Declines in the populations of some bird species have been associated
    with high residues of various organochlorine pesticides in the tissues
    of adults and in the eggs.  While endrin has been found in some of
    these species, it is very difficult to separate the effects of the
    different organochlorines present.

    3.2  Recommendations

    Endrin should not be used, unless it is indispensable or less toxic
    alternatives are not available.

    For the health and welfare of workers and the general population, the
    handling and application of endrin should only be entrusted to
    competently supervised and well-trained operators, who will ensure
    adequate safety precautions and apply endrin according to good
    agricultural practice.

    The manufacture, formulation, agricultural use, and disposal of endrin
    should be carefully managed to minimize contamination of the
    environment, particularly surface waters.

    Periodic health evaluations should be carried out in those regularly
    exposed to endrin.

    Epidemiological studies of exposed populations of workers should be
    continued.

    In countries where endrin is still used, food should be monitored for
    endrin residues.

    If the use of endrin continues, more information is required on the
    presence, ultimate fate, and toxicity of 12-ketoendrin and
    delta-ketoendrin.

    4.  HUMAN HEALTH HAZARDS, PREVENTION AND PROTECTION, EMERGENCY ACTION

    4.1  Main Human Health Hazards, Prevention and Protection, First Aid

    Endrin is an organochlorine insecticide.  It is highly toxic (oral rat
    LD50 approximately 7 mg/kg) and can be hazardous for human beings,
    if incorrectly or carelessly handled.  It is therefore essential that
    the correct precautions should be observed during its handling and
    use.

    The human health hazards of endrin exposure, preventive and protective
    measures, and first aid are listed in Table 2.

    4.1.1  Symptoms of poisoning

    Endrin is readily absorbed and toxic by mouth, by skin contact, and by
    inhalation.  It acts as a stimulant of the central nervous system.  An
    oral dose of 0.25 mg/kg body weight has been reported to cause
    convulsions in human beings.

    Symptoms may appear between 20 min and 12 h following accidental
    ingestion or gross overexposure, and may include headache, dizziness,
    nausea, vomiting, weakness in the legs, and convulsions, sometimes
    leading to death.

    Organochlorine compounds can cause respiratory depression.  They may
    also sensitize the heart to endogenous catecholamines, leading to
    cardiac arrhythmias and, in severe exposure cases, to ventricular
    fibrillation and cardiac arrest.

    Respiratory depression may lead to metabolic acidosis, and, if
    necessary, blood gases should be checked.  The use of an ECG monitor
    is recommended if the symptoms are severe.

    4.1.2  Medical treatment

    Treatment of endrin poisoning requires immediate action; it is largely
    symptomatic and supportive and directed against convulsions and
    hypoxia.

    Endrin is quickly eliminated from the blood and can only be detected
    for 1 or 2 days following massive overexposures.  Signs and symptoms
    of poisoning occur only at concentrations in whole blood of more than
    50 g endrin/litre.

    If endrin is swallowed, the stomach should be emptied as soon as
    possible, by careful gastric lavage (with a cuffed endotracheal tube
    already in place), avoiding aspiration into the lungs.  In a rural
    situation, where this is not feasible, vomiting should be induced
    immediately, if the victim is conscious.  This should be followed by
    intragastric administration of 50 g of activated charcoal and 30 g


        TABLE 2. HUMAN HEALTH HAZARDS, PREVENTIVE AND PROTECTIVE MEASURES, AND FIRST AID

                                                                                                                                         

    HAZARDS/SYMPTOMS                        PREVENTION AND PROTECTION                    FIRST AID
                                                                                                                                         

    SKIN: may cause poisoning in            Avoid contact with skin;                     After contact with skin, wash immediately
    contact with skin                       wear suitable, impervious, protective        with plenty of water and soap; remove 
                                            clothing and gloves                          all contaminated clothing immediately
                                                                                         and launder separately

    EYES: may cause irritation to           Avoid contact with eyes; wear                In case of contact with eyes, rinse 
    eyes                                    eye protection                               immediately with plenty of water and seek
                                                                                         medical advice

    INHALATION: dusts and mist may          Do not breathe dusts or spray;
    cause poisoning by inhalation           wear appropriate dust mask or
                                            respirator

    INGESTION: unlikely occupational        Do not eat, drink, or smoke during
    hazard                                  work; wash hands before eating, 
                                            drinking, or smoking
    Accidental or intentional ingestion                                                  If swallowed, seek medical advice immediately
    may cause poisoning                                                                  and show container or label; keep at rest and
                                                                                         ensure a clear airway; if gastric lavage is
                                                                                         not possible in a rural situation, induce
                                                                                         vomiting (only if victim is conscious)
                                                                                                                                         
    

    magnesium or sodium sulfate in a 30% aqueous solution.  Oily
    purgatives are contraindicated.  No fats, oils, or milk should be
    given.

    If convulsions occur, anticonvulsants should be given immediately,
    e.g., 10 mg of diazepam, slowly, intravenously (children 1-5 mg),
    repeated as necessary; or thiopental sodium or hexobarbital sodium
    slowly, intravenously, in a dose of 10 mg/kg, with a maximum total
    dose of up to 750 mg for an adult, or 5 ml of paraldehyde by
    intramuscular injection.  These short-acting anticonvulsants should
    always be followed by phenobarbital given orally at 3 mg/kg (up to
    200 mg for an adult), or phenobarbital sodium given intramuscularly at
    3 mg/kg (also up to 200 mg for an adult).

    Morphine and its derivatives, adrenaline and noradrenaline, should
    never be given.

    An unobstructed airway must be maintained.  Respiratory inadequacy,
    which may be accentuated by barbiturate anticonvulsants, should be
    corrected, and oxygen and/or artificial ventilation may be needed.

    Some guidelines on the management of major status epilepticus are
    provided in Annex 1.

    4.1.3  Health surveillance advice

    A complete medical history and physical examination of regularly
    exposed workers should be made at least annually, and a pre-employment
    examination is recommended.  Special attention should be paid to liver
    function and signs and symptoms of stimulation of the central nervous
    system (see 4.1.1).

    4.2  Safety in Use

    Handling liquid formulations:      Wear protective neoprene or PVC
                                       gloves, cotton overalls, rubber
                                       apron and boots, and face shield.

    Handling powder formulations:      Avoid raising a dust cloud.  Wear
                                       protective gloves, cotton overalls,
                                       rubber boots, and an appropriate
                                       dust-mask or respirator.  Follow
                                       the advice relating to personal
                                       hygiene.

     Application in the field

    Aerial application:                Ensure that flag-men (markers) do
                                       not stand in the spray-path of the
                                       aircraft; do not spray over
                                       residences occupied by human beings
                                       or over surface waters, and avoid
                                       spraying over ditches, canals,
                                       rivers, streams, ponds, or lakes.

    Ground spraying:                   Wear suitable protective clothing
                                       (i.e., cap or hat, cotton overalls
                                       or long-sleeved cotton shirt and
                                       long trousers, boots or shoes);
                                       when spraying tall crops or when
                                       there is a risk of accidental
                                       contamination by the spray, an
                                       impermeable hood and jacket should
                                       be worn; always avoid exposure to
                                       the spray mist; do not spray into
                                       the wind.

    After application:                 Take off heavily splashed or
                                       contaminated clothing; wash hands
                                       and exposed skin before eating,
                                       drinking, or smoking; wash
                                       overalls, boots, hat, and other
                                       protective clothing thoroughly,
                                       especially the inside of gloves;
                                       keep application equipment in good
                                       condition, and free from leaks and
                                       external contamination; keep
                                       contents tightly closed in original
                                       labelled container, when not fully
                                       used; do not re-use empty
                                       containers for any other purpose;
                                       keep containers in a safe place
                                       away from food, children, and
                                       animals; empty containers must be
                                       washed out and disposed of, as
                                       advised in section 4.6.2.

    4.3  Explosion and Fire Hazards

    4.3.1  Explosion hazard

    The explosion hazard depends on the solvent used in the formulation
    and on the characteristics of the dust.

    4.3.2  Fire hazard

    Liquid formulations containing organic solvents may be flammable. 
    Extinguish fires with alcohol-resistant foam, carbon dioxide, or
    powder.  With sufficient burning or external heat, endrin will
    decompose, emitting toxic fumes.  Fire-fighters should be equipped
    with self-contained breathing apparatus, eye protection, and full
    protective clothing.

    The use of water spray should be confined to the cooling of unaffected
    containers, thus avoiding the accumulation of polluted run-off from
    the site.

    4.4  Storage

    Products should be stored in locked buildings, preferably buildings
    dedicated to insecticides, and in compliance with label
    recommendations.  They should be segregated from incompatible
    chemicals.

    Keep the products out of reach of children and unauthorized personnel. 
    Do not store near foodstuffs or animal feed.

    4.5  Transport

    Comply with any national or local requirements regarding movement of
    hazardous goods or wastes.  Do not transport in the same compartment
    as foodstuffs or animal feed.  Before dispatch, check that containers
    are sound and labels undamaged.

    4.6  Spillage and Disposal

    4.6.1  Spillage

    Before dealing with any spillage, precautions should be taken as
    required, and appropriate personal protection should be used (section
    4.2).  Empty any product remaining in damaged/leaking containers into
    a clean empty drum, which should then be tightly closed and suitably
    labelled.

    Prevent liquid from spreading or contaminating other cargo and
    vegetation, and avoid pollution of surface waters and ground water by
    using the most suitable available material, e.g., earth or sand.

    After emptying, leaking containers should be rinsed with at least
    1 litre of water per 20-litre drum.  Swirl around to rinse the walls
    of the container, empty, and add the rinsings to the sawdust or earth. 
    Puncture or crush the container to prevent re-use.

    As soon as possible after the spillage, and before re-use, cover all
    contaminated areas with damp sawdust, sand, or earth.  Sweep up and
    place in a closeable container for later transfer to a safe place for
    disposal.

    4.6.2  Disposal

    Any surplus product, contaminated absorbents, and containers should be
    disposed of in an appropriate way.  Waste material should be burned in
    a proper incinerator designed for organochlorine waste disposal, with
    effluent gas scrubbing.  If this is not possible, bury in an approved
    dump or landfill, where there is no risk of contamination of surface
    or ground water.  Comply with any local requirements regarding the
    disposal of toxic wastes.  Puncture and/or crush all containers to
    prevent re-use.

    5.  HAZARDS FOR THE ENVIRONMENT AND THEIR PREVENTION

    Endrin is highly toxic for all animal species, especially fish and
    other aquatic organisms.  It is readily bioaccumulated in fish, but
    disappears rapidly when exposure is discontinued.  It does not persist
    for long periods in the water, but may persist in sediments.

    Discharges from the manufacture, formulation, or use of endrin, and
    any spillage or unused product, must be prevented from polluting the
    environment and spreading to vegetation or waterways, and must be
    treated and disposed of properly (section 4.6.2).

    6.  CURRENT REGULATIONS, GUIDELINES, AND STANDARDS

    The information given in this section has been extracted from the
    International Register of Potentially Toxic Chemicals (IRPTC) legal
    file and other United Nations sources.  Its intention is to give the
    reader a representative, but not an exhaustive, overview of current
    regulations, guidelines, and standards.

    The reader should be aware that regulatory decisions about chemicals,
    taken in a certain country, can only be fully understood in the
    framework of the legislation of that country.  Furthermore, the
    regulations and guidelines of all countries are subject to change and
    should always be verified with the appropriate regulatory authorities
    before application.

    6.1  Previous Evaluations by International Bodies

    The International Agency for Research on Cancer (IARC) reviewed endrin
    in 1974 and 1987 and concluded that there was inadequate evidence for
    the carcinogenicity of endrin in experimental animals and data in
    humans were inadequate.  Endrin was classified in Group 3: not
    classifiable as to carcinogenicity to humans.

    WHO classifies technical endrin as highly hazardous in normal use
    (WHO, 1990). A data sheet on endrin was issued in 1978 (WHO/FAO,
    1978).

    Endrin was evaluated by the Joint FAO/WHO Meeting on Pesticide
    Residues (JMPR) in 1963, 1965, and 1970.  In 1970, the JMPR
    established an Acceptable Daily Intake (ADI) for man of 0-0.0002 mg/kg
    body weight.

    The maximum residue limits (MRL) established for endrin by the Joint
    FAO/WHO Codex Alimentarious Commission 1986 are shown in Table 3.

    6.2  Exposure Limit Values

    Some exposure limit values are shown in the table on pages 28 and 29.

    Table 3. Maximum residue limits for endrin

                                                                         

    Commodity                             MRLa
                                    in mg/kg product
                                                                         

    Apples                                0.02b
    Barley                                0.02b
    Cottonseed                            0.1
    Cottonseed oil (crude)                0.1
    Cottonseed oil (edible)               0.02b
    Eggs                                  0.2
                                 (on a shell-free basis)
    Meat                                  0.1c
                                 (in the carcass fat)
    Milk                                  0.0008c
    Poultry                               1
                                 (in the carcass fat)
    Rice, husked or polished              0.02bb
    Sorghum                               0.02b
    Sweet corn                            0.02b
    Wheat                                 0.02b
                                                                         

    a Definition of residue: Sum of endrin and delta-ketoendrin.
    b Level at, or about, the limit of determination.
    c ERL:extraneous residue limit.

    6.3  Specific Restrictions

    The use of endrin is prohibited (with minor exceptions) in several
    countries, including, Australia, the countries of the European
    Community, Hungary, India, Japan, and Sweden.  In the USSR, endrin is
    prohibited for use in agriculture.

    In some other countries, endrin is registered only for certain uses,
    e.g., in Argentina, Brazil, and the USA.

    6.4  Labelling, Packaging, and Transport

    The United Nations Committee of Experts on the Transport of Dangerous
    Goods classifies endrin in:

    Hazard Class 6.1:             poisonous substance;

    Packing Group I:              substances and preparations presenting a
                                  very severe risk of poisoning, when the
                                  content of the active ingredient is
                                  60-100%;

    Packing Group II:             substances and preparations presenting a
                                  serious risk of poisoning, when the
                                  content of active ingredient is 6-60%;

    Packing Group III:            substance presenting a relatively low
                                  risk of poisoning in transport, when the
                                  content of active ingredient is 1-6%
                                  (solid) or 0.5-6% (liquid).

    As endrin may be carried in solution in flammable solvents, a
    "Flammable liquid" subsidiary risk label (red) is also required when
    the flash point of the solution is below or equal to 61C (closed
    cup); the flammable risk takes precedence when the flash-point is
    below or equal to 23C (closed cup); the solution is then classified
    in Class 3, with a Class 6.1 subsidiary risk.

    For the purposes of international transport, the types of labelling
    shown below (page 30) are required by:

    *    the United Nations Committee of Experts on the Transport of
         Dangerous Goods;

    *    the International Maritime Dangerous Goods (IMDG) Code;

    *    the ICAO Technical Instructions for the Safe Transport of
         Dangerous Goods by Air;

    *    the European Agreement concerning the International Carriage of
         Dangerous Goods by Road (ADR);

    *    the Regulations concerning the International Carriage of
         Dangerous Goods by Rail (RID).


        TABLE 4. EXPOSURE LIMIT VALUES

                                                                                                                                         

    Medium      Specification       Country/            Exposure limit description                   Value                Effective
                                    organization                                                                          date
                                                                                                                                         

    AIR         Workplace           Germany,            Maximum worksite concentration (MAK)                              1985
                                    Federal             - time weighted average (TWA)                0.1 mg/m3a
                                    Republic of         - short term exposure limit (STEL)           1.0 mg/m3
                                                          (30 min; 1  /shift)

                                    United Kingdom      Recommended limit (RECL)                                          1985
                                                        - time-weighted average (TWA)                0.1 mg/m3a
                                                        - short term exposure level (STEL)           0.3 mg/m3
                                                          (10-min TWA)

                                    USA - OSHA          Permissible Exposure Limit (PEL)                                  1989
                                                        - time-weighted average (TWA)                0.1 mg/m3a

    FOOD        Intake from         FAO/WHO             Acceptable daily intake (ADI)                0-0.0002 mg/kg       1970
                                                                                                     body weight 

                Residue             FAO/WHO             Maximum residue limit                        0.0008-1mg/kg        1986
                                                        (for specified products)

    WATER       Ambient             Mexico              Maximum permissible concentration
                                                        (for drinking-water purification)            0.001 mg/litre       1973
                                                        (coastal)                                    0.0002 mg/litre      1973
                                                        (estuarine)                                  0.002 mg/litre       1973

                                    USA                 Maximum permissible concentration                                 1981
                                                        (bottled water for human consumption)        0.0002 mg/litre

                                                                                                                                         

    a Skin absorption.
        FIGURE 1

    Note:     The text on the label is optional, and is not required by
              RID/ADR. The class number at the bottom of the main hazard
              is not required by RID/ADR, but is not optional for the
              other modes.

    Endrin has been identified as a severe marine pollutant in the
    International Maritime Dangerous Goods (IMDG) Code, therefore a
    "Marine pollutant" mark is required for the transport by sea of all
    concentrations greater than or equal to 1%.

    FIGURE 2

    The FAO specifications for plant protection products containing endrin
    specify the composition and purity of the technical product and its
    formulations.  They also advise on methods for checking this.  The
    endrin content should be stated and may not differ by more than 4%
    from this for the technical product (and up to 10% for some
    formulations).  Technical endrin should contain a minimum of 92%w/w
    active material.

    The European Economic Community legislation on the labelling of
    pesticide preparations classified endrin in Class I/a for the purpose
    of determining the label for preparations containing endrin and other
    active ingredients.

    The European Economic Community legislation requires labelling as a
    dangerous substance using the symbol:

    FIGURE 3

    The label must read:

          Very toxic by inhalation, in contact with skin and if swallowed;
          keep locked up; keep away from food, drink and animal feeding
          stuffs; after contact with skin, wash immediately with plenty of
          water; in case of accident or if you feel unwell, seek medical
          advice (show the label where possible).

    6.5  Waste Disposal

    In the USA, any non-domestic waste containing endrin and its
    metabolites must be treated as a hazardous waste.  Specific
    instructions are given for notification and incineration.
    Owners/operators of vessels or onshore or offshore facilities must
    notify the US Government (National Response Center) of any release of
    endrin in or on navigable waters, adjoining shorelines, in the
    contiguous zone or beyond the contiguous zone or to any other
    environmental media (air, land, or ground water) in an amount equal
    to, or greater than, one pound (0.454 kg).

    An owner or operator of a hazardous waste incinerator must achieve
    99.99% destruction and removal efficiency for this substance.

    6.6  Other Measures

     Aquatic environment

    The European Economic Community legislation has established limit
    values for the discharge of, and quality objectives for, aldrin,
    dieldrin, endrin, and isodrin in the aquatic environment.

    The limit values for emission standards are:

    (a) Plants producing aldrin and/or dieldrin and/or endrin, including
    formulation of these substances on the same site, must:

    *    on a monthly average value, not exceed 3 g in effluent per tonne
         of production capacity (g/tonne) or a concentration in effluent
         of 2 g/litre of water discharged (to be complied with as from
         1 January 1989).

    *    on a daily average value, not exceed 15 g in effluent per tonne
         of production capacity (g/tonne) or a concentration in effluent
         of 10 g/litre of water discharged (to be complied with as from
         1 January 1989).

    (b) For inland surface waters, estuary waters, internal coastal waters
    other than estuary waters, territorial waters, for the compounds
    aldrin, dieldrin, endrin, and isodrin together:

    *    30 ng/litre (to be complied with as from 1 January 1989); and
         10 ng/litre for aldrin, 10 ng/litre for dieldrin, 5 ng/litre for
         endrin, and 5 ng/litre for isodrin (to be complied with as from
         1 January 1994).

    BIBLIOGRAPHY

    FAO (1985a)  Guidelines for the packaging and storage of pesticides.
    Rome, Food and Agriculture Organization of the United Nations.

    FAO (1985b)  Guidelines for the disposal of waste pesticides and
     pesticide containers on the farm. Rome, Food and Agriculture
    Organization of the United Nations.

    FAO (1985c)  Guidelines on good labelling practice. Rome, Food and
    Agriculture Organization of the United Nations.

    FAO (1986)  International code of conduct on the distribution and use
     of pesticides. Rome, Food and Agriculture Organization of the United
    Nations.

    FAO/WHO (1986)  Guide to Codex recommendations concerning pesticide
     residues. Part 8.  Recommendations for methods of analysis of
     pesticide residues., 3rd ed. Rome, Codex Committee on Pesticide
    Residues.

    FAO/WHO (1986)  Codex maximum limits for pesticide residues. CAC/Vol.
    XIII. 2nd ed., Rome, Codex Alimentarius Commission, Food and
    Agriculture Organization of the United Nations.

    FAO/WHO (1964-present)  Evaluation of some pesticide residues in food.
    Rome, Food and Agriculture Organization of the United Nations.

    GIFAP (1982)  Guidelines for the safe handling of pesticides during
     their formulation, packing, storage and transport. Brussels,
    Groupement International des Associations Nationales des Fabricants de
    Produits Agrochimiques.

    GIFAP (1983)  Guidelines for the safe and effective use of pesticides.
    Brussels, Groupement International des Associations Nationales des
    Fabricants de Produits Agrochimiques.

    GIFAP (1984)  Guidelines for emergency measures in cases of pesticide
     poisoning. Brussels, Groupement International des Associations
    Nationales des Fabricants de Produits Agrochimiques.

    GIFAP (1987)  Guidelines for the safe transport of pesticides.
    Brussels, Groupement International des Associations Nationales des
    Fabricants de Produits Agrochimiques.

    IARC (1972-present)  IARC monographs on the evaluation of carcinogenic
     risk of chemicals to man. Lyon, International Agency for Research on
    Cancer.

    IRPTC (1986)  IRPTC legal file 1986. Geneva, International Register
    of Potentially Toxic Chemicals, United Nations Environment Programme.

    IRPTC (1985)  IRPTC file on treatment and disposal methods for waste
     chemicals. Geneva, International Register of Potentially Toxic
    Chemicals, United Nations Environment Programme.

    PLESTINA, R. (1984)  Prevention, diagnosis, and treatment of
     insecticide poisoning. Geneva, World Health Organization
    (unpublished WHO document VBC/84.889).

    SAX, N.I. (1984)  Dangerous properties of industrial materials. New
    York, Van Nostrand Reinhold Company, Inc.

    UNEP/IEO (1990)  Storage of hazardous materials: a technical guide for
     safe warehousing of hazardous materials. United Nations Environment
    Programme, Industry and Environment Office, Paris, 80 pp..

    UNITED NATIONS (1984)   Consolidated list of products whose
     consumption and/or sale have been banned, withdrawn, severely
     restricted or not approved by governments, 1st ed. revised, United
    Nations, New York.

    UNITED NATIONS (1986)  Recommendations on the transport of dangerous
     goods. 6th ed. New York, United Nations.

    US NIOSH/OSHA (1981)  Occupational health guidelines for chemical
     hazards. 3 vol., Washington, DC, US Department of Health and Human
    Services, US Department of Labor (Publication No. DHHS (NIOSH)
    01-123).

    WHO (1990)  The WHO recommended classification of pesticides by hazard
     and guidelines to classification 1990-1991. Geneva, World Health
    Organization (unpublished document WHO/PCS/90.1).

    WHO (in preparation)  Environmental Health Criteria 130: Endrin.
    Geneva, World Health Organization.

    WHO/FAO (1978)  Data sheets on pesticides: Endrin. Geneva, World
    Health Organization (unpublished document).

    WORTHING, C.R. & WALKER, S.B. (1987)  The pesticide manual. 8th ed.,
    Lavenham, Lavenham Press Limited, British Crop Protection Council.

    ANNEX.  MANAGEMENT OF MAJOR STATUS EPILEPTICUS IN ADULTSa

    (A)  Initial management

    1.  Assess the patient, verify the diagnosis, remove false teeth and
    place in the lateral semi-prone position, establish an airway. 

    2.  Diazepam, iv (see Note 1), (10 mg in 2 ml), 0.15-0.25 mg/kg,
    usually 10 mg (2 ml) bolus followed immediately by a further 10 mg
    (2 ml) over 1-2 minutes.  This may be repeated according to response.

    3.  Take blood for determination of anticonvulsant drug levels, blood
    alcohol level, and blood sugar (5 ml of blood in a sugar tube), also
    blood for determination of calcium (5 ml in a plain tube), and a drop
    of blood to determine blood glucose.

    4.  If this shows a low blood glucose level: administer glucose 50%,
    iv, 25ml, preferably by catheter, and not into a small distal vein.

    If alcohol is likely to be a factor: administer thiamine, iv, 100 mg.

    5.  Phenytoin, iv, 250 mg in 5 ml, 10-15 mg/kg, no faster than 50 mg
    (1 ml) per minute, by infusion pump or slow iv injection (see Note 2).

    (B)  If fits continue, transfer to an intensive care unit, and consult
    an anaesthetist

    6.  Chlormethiazole, iv (8 mg/ml). A loading dose of up to 800 mg
    (100 ml) over 10 minutes (10 ml/min);  maintain  with  0.5-1 ml/min
    (4-8 mg).

    7.  Thiopental, iv, 5 mg/kg loading dose, then 1-3 mg/kg per hour, to
    a maximum blood thiopental level of 100 mg/litre.

    8.  If this fails - consult a neurologist.


              

    a Adapted from a guideline prepared by Guy's Hospital, London.

    NOTES

    1.  Diazepam: A bolus injection of 10 mg may cause respiratory
    depression and hypotension, which may be pronounced if there is
    concurrent use of other CNS depressant drugs, especially
    phenobarbital.

    Diazepam must not be given:

    *    intramuscularly;

    *    added to an intravenous infusion;

    *    with phenobarbital unless artificial ventilation is available.

    Rectal diazepam (using a rectal administration set), 5 or 10 mg in
    2.5 ml, may be used for the immediate treatment of epilepsy instead of
    intravenous diazepam.

    2.  Phenytoin must not be given:

    *    intramuscularly;

    *    by central line;

    *    into a dextrose infusion;

    *    with any other drug.

    Intravenous phenytoin should be monitored with continous ECG
    recording.  If this is not available, it may be safer to use a diluted
    solution of 250 mg (5 ml) in 250 ml of normal saline, no faster than
    50 mg/min.  The diluted solution should be used immediately, provided
    there is no evidence of precipitation (this use of phenytoin is not
    licensed).

    OPTIONS

    The following drugs may also be used:

    1.  Paraldehyde: 2 x 5 ml by separate, deep, intramuscular injection,
    or 10ml diluted into 100 ml of normal saline given intravenously over
    10-15 minutes.

    Note: paraldehyde should only be used with glass syringes.

    2.  Phenobarbital (200 mg/ml). Should not be given intravenously,
    except where artificial ventilation is available, and not at all if
    the patient normally takes phenobarbital.  The maximum rate of
    infusion is 100 mg/min, to a maximum dose of 15 mg/kg.

    3.  Lignocaine, iv, 100 mg, by slow intravenous injection, followed by
    50-100 mg of lignocaine in 250 ml of 5% dextrose at 1-2 mg/min.

    Note: It is essential that this treatment is given with ECG
    monitoring.

    4.  Diazepam, iv (10 mg in 2 ml), 40 mg in 500 ml of 5% dextrose, at a
    maximum infusion rate of 100 mg/h.

    5.  Sodium valproate, iv (400 mg in 4 ml), 400-800 mg, iv, over
    3-5 minutes (up to 10 mg/kg), followed by intravenous infusion, to a
    maximum of 2.5 g/day (unlicensed).

    Paediatric Doses

    For children, dosing should be adapted as follows:

         Diazepam            0.2-0.3 mg/kg intravenous.

         Phenytoin           10-20 mg/kg intravenous.

         Chlormethiazole     5-10 mg/kg per hour, which is equivalent to
                             0.6-1.25 ml/kg per hour.

    


    See Also:
       Toxicological Abbreviations
       Endrin (EHC 130, 1992)
       Endrin (ICSC)
       Endrin (FAO Meeting Report PL/1965/10/1)
       Endrin (AGP:1970/M/12/1)
       Endrin (WHO Pesticide Residues Series 4)
       Endrin (WHO Pesticide Residues Series 5)
       Endrin (IARC Summary & Evaluation, Volume 5, 1974)