Health and Safety Guide No. 94






    This is a companion volume to Environmental Health Criteria 175:
    Anticoagulant Rodenticides

    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

    Health and safety guide for Bromadiolone

    (Health and safety guide ; no. 94)

    1.Rodenticides  2.Anticoagulants
    3.4-Hydroxycoumarins - toxicity  4.Environmental exposure  I.Series

    ISBN 92 4 151094 3          (NLM Classification: WA 240)
    ISSN 0259-7268

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         1.1. Identity
         1.2. Physical and chemical properties
         1.3. Analytical methods
         1.4. Production and uses

         2.1. Identity, physical and chemical properties, and analytical
         2.2. Sources of human and environmental exposure
         2.3. Environmental transport, distribution, and transformation
         2.4. Environmental levels and human exposure
         2.5. Kinetics and metabolism in laboratory animals and humans
         2.6. Effects on laboratory mammals and in vitro test systems
         2.7. Effects on humans
         2.8. Effects on other organisms in the laboratory and field
         2.9. Evaluation of human health risks and effects on the
               2.9.1. Evaluation of human health risks
               2.9.2. Evaluation of effects on the environment

         3.1. Conclusions
         3.2. Recommendations for the protection of human health and the

         4.1. Main human health hazards, prevention and protection,
               first aid
               4.1.1. Advice to physicians
               4.1.2. Health surveillance advice
         4.2. Explosion and fire hazards
         4.3. Storage
         4.4. Transport
         4.5. Spillage
         4.6. Disposal



         7.1. Previous evaluations by international bodies
         7.2. Exposure limit values
         7.3. Specific restrictions
         7.4. Labelling, packaging, and transport
         7.5. Waste disposal




    The Environmental Health Criteria (EHC) monographs 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 Director
    International Programme on Chemical Safety
    World Health Organization
    1211 Geneva 27



    1.1  Identity

    Common name:             bromadiolone

    Chemical formula:        C30H23BrO4

    Chemical structure:

                             CHEMICAL STRUCTURE

    Common synonyms:         broprodifacoum

    Trade names:             Apobas; Bromard; Bromatrol; Bromorat;
                             Contrac; Deadline; Hurex; Lanirat; Maki;
                             Morfaron; Musal; Ramortal; Ratimon; Rodine-c;
                             Slaymore; Super-caid; Toidon

    CAS chemical name:       3-[3[(4'-bromo-[1,1'-biphnyl]-4-yl)-3-
                             benzopyran-2 one (9CI)

                             3-[-[ p-( p-bromophenyl)-hydroxyphenethyl]-

    IUPAC chemical name:     3-[3-(4'-bromobiphenyl-4-yl)-3-hydroxy-1-

    CAS registry number:     28772-56-7

    RTECS registry number:   GN4934700

    1.2  Physical and Chemical Properties

    Bromadiolone is a white to off-white powder.  Its solubility in water
    is very low (less than 20 mg/litre at 20C). It is slightly soluble in
    ethanol and ethyl acetate, and soluble in dimethylformamide.  The
    flash-point temperature is 218C.

    Further physical and chemical properties of bromadiolone are given in
    the "Summary of Chemical Safety Information" (section 6).

    1.3  Analytical Methods

    The determination of bromadiolone is based on high-performance liquid
    chromatography with a detection limit of 0.01 mg/kg.

    1.4  Production and Uses

    The rodenticidal properties of bromadiolone were reported in 1976.  It
    is an anticoagulant that is effective against rats and mice, including
    those resistant to first generation anticoagulants.  It is used in the
    form of ready-to-use baits of low concentration containing 0.005%


    2.1  Identity, Physical and Chemical Properties, and Analytical

    Bromadiolone is a white to off-white powder.  It is stable at room
    temperature and has a melting point of 200-210C.  Its solubility in
    water is very low. It is slightly soluble in ethanol and ethyl
    acetate, and soluble in dimethylformamide.  The determination of
    bromadiolone is based on high-performance liquid chromatography.

    2.2  Sources of Human and Environmental Exposure

    Bromadiolone does not occur naturally.  It is used as a rodenticide in
    urban and farm rodent control and acts by disrupting the normal blood
    clotting mechanisms causing an increased tendency to bleed.

    2.3  Environmental Transport, Distribution, and Transformation

    Bromadiolone is unlikely to enter the atmosphere, because of its low
    volatility.  It is practically insoluble in water.  Bromadiolone is
    readily adsorbed on soils rich in clay and organic compounds, with no
    leaching.  Degradation in soil is significant with half-lives ranging
    from 1.8 to 7.4 days.

    2.4  Environmental Levels and Human Exposure

    Bromadiolone is not intended for direct application to growing crops
    and never for use as a food additive.

    No information is available on concentrations in air, water, and soil.

    2.5  Kinetics and Metabolism in Laboratory Animals and Humans

    Bromadiolone is absorbed through the gastrointestinal tract, skin, and
    respiratory system.  The major route of elimination in different
    species after oral administration is via the faeces.  The liver is the
    main organ of accumulation and storage.  Bromadiolone has been found
    in the liver as the unchanged parent compound.  Elimination from the
    liver is biphasic with an initial rapid phase of 2-8 days and a slower
    phase with a half-life of 170 days.  No data are available on the
    kinetics and metabolism of bromadiolone in humans.

    2.6  Effects on Laboratory Mammals and in vitro Test Systems

    Bromadiolone has a high, acute oral toxicity (LD50 of 1-3 mg/kg) for
    various species including rodents and non-rodents.  The dermal
    toxicity is also high (LD50 of 9.4 mg/kg in rabbits).  Signs of
    poisoning are those associated with an increased tendency to bleed.

    Bromadiolone is non-irritant to the skin. It is a slight irritant for
    the eye.

    In feeding studies on rats, the only effect found has been that
    associated with anticoagulant action.  In a 12-week feeding study on
    rats, the maximum tolerated dose was 10 g/kg body weight per day.

    Mutagenicity and teratogenicity studies have not shown any mutagenic,
    embryotoxic, or teratogenic effects.

    2.7  Effects on Humans

    Symptoms of acute intoxication by bromadiolone include an increased
    tendency to bleed in less severe cases of poisoning, and massive
    haemorrhaging in more severe cases.  The signs of poisoning develop
    with a delay of one to several days after ingestion.

    Incidents of poisoning have been reported.

    2.8  Effects on Other Organisms in the Laboratory and Field

    Bromadiolone has shown toxicity for aquatic organisms.  The LC50
    (96-h) for various fish species ranged from 1.4 to more than
    3 mg/litre.

    Bird species appear to be less susceptible to bromadiolone than
    mammals with a reported acute, oral LD50 of at 138 mg/kg.

    Secondary poisoning through the consumption of rats and mice killed
    with bromadiolone may occur in dogs and cats in urban situations, but
    more likely in farm situations.

    2.9  Evaluation of Human Health Risks and Effects on the Environment

    2.9.1  Evaluation of human health risks

    As bromadiolone is mainly used in urban rodent control in the form of
    low-concentration baits, increased levels in air are unlikely. 
    Furthermore, as it is only slightly soluble in water, its use cannot
    be a significant source of water contamination.  Bromadiolone is not
    intended for direct application to growing crops and no residues in
    plant food-stuffs are expected.  Occupational exposure may occur
    during manufacture, formulation, and bait application, but data
    concerning the levels of exposure are not available.  Bromadiolone may
    be absorbed through the gastrointestinal tract and also through the
    skin.  The major route of elimination is via the faeces.  The liver is
    the major organ for the accumulation of bromadiolone, which has mainly
    been found as the unchanged parent compound.  Elimination from the
    liver is slow.

    As a technical material, bromadiolone is extremely toxic for many
    mammalian species.  Signs of poisoning in all species, including
    humans, are associated with an increased tendency to bleed.

    Incidents of poisoning  have been reported.

    The level of prothrombin time is a satisfactory guide to the severity
    of acute intoxication, and also the effectiveness and duration of the

    The specific antidote is vitamin K1 in both animals and man (see
    section 4.1.1).

    2.9.2  Evaluation of effects on the environment

    Bromadiolone is applied to discrete sites in the form of
    low-concentration baits and is stable under normal conditions. 
    Bromadiolone is poorly soluble in water and, in a bait formulation, it
    is is unlikely to be a source of water pollution.  As a technical
    material, it is toxic for aquatic organisms.

    Bromadiolone is readily adsorbed on soil, rich in clay and organic
    compounds, with no leaching;  degradation in soil is significant.

    Non-target organisms are potentially at risk from direct consumption
    of baits (primary hazard) and through eating poisoned rodents
    (secondary hazard).

    Whole-grain baits are highly attractive to birds.  Bird species appear
    to be less susceptible to bromadiolone than rodents.

    The primary hazard is usually expressed by the amount of finished bait
    that must be consumed to approach the lethal dose.  To reach the toxic
    or lethal dose, the non-target species must consume comparatively
    large amounts of bait with a concentration of 0.005% active

    Some secondary toxicity laboratory studies on wildlife have shown that
    captive predators could be intoxicated by no-choice feeding of
    bromadiolone-poisoned or dosed prey.  The significance of these
    results in terms of hazards under field conditions is difficult to
    assess, because the predators would not be expected to eat only
    poisoned animals.  However,  predators may take poisoned small mammals
    that are still alive, preferentially.  In areas close to baiting,
    poisoned rodents may represent a high proportion of the diet for
    individual birds.  However, only few individuals will be affected,
    unless there is very widespread and constant use of the baits.

    Therefore, some kills of owls can be expected, but there will be no
    severe population effects.  This ties in with small numbers of
    poisoned owls observed in the field.


    3.1  Conclusions

    Exposure of the general population to bromadiolone through air,
    drinking-water, or food is unlikely and does not constitute a
    significant health hazard.  Poisoning incidents may occur in cases of
    massive intentional, or unintentional, ingestion, or prolonged
    exposure during manufacture and formulation.

    Bromadiolone is relatively persistent in the environment, but its
    specific use as low-concentration bait formulations cannot be a
    significant source of air, water, soil, and food contamination. 
    Direct and secondary poisoning of birds, domestic and farm animals,
    and wildlife may occur.

    3.2  Recommendations for the Protection of Human Health and the

    Potentially exposed workers should receive appropriate biomonitoring
    and health evaluation.

    To prevent primary poisoning, baits should be placed where they cannot
    be readily available to non-target species, e.g., in bait stations.

    Killed rodents should be burned or buried to prevent secondary
    poisoning in predators.


    4.1  Human Health Hazards, Prevention and Protection, First Aid

    The oral toxicity of bromadiolone for mammals is extremely high (rat
    oral LD50, 1.12 mg/kg; rabbit oral LD50, 1 mg/kg).  The dermal
    toxicity is also very high (rabbit LD50 9.4 mg/kg).  No definite
    toxic dose has been established for humans, because of the limited
    clinical reports available.

    The main features of bromadiolone poisoning in less severe cases are
    excessive bruising, nose and gum bleeding, and blood in the urine and
    faeces. Bleeding from several organs within the body leading to shock
    and possibly death occurs in more severe cases.  The onset of the
    signs of poisoning may not be evident until one to several days after

    Bromadiolone is non-irritant to the skin, but is slightly irritant to
    the eye.

    Bromadiolone is slowly metabolized by mammals and may accumulate in
    the liver reaching toxic levels with repeated exposure.

    Handling of technical material or powder concentrates will require the
    use of full air-fed protection and an impervious suit, suitable for
    wash-down.  In operations with liquid concentrates, PVC or
    nitrile-rubber gloves, armlets, and an apron should be worn together
    with a face shield and rubber boots.

    All persons who are bleeding must obtain medical attention.

    4.1.1  Advice to physicians

    If poisoning has occurred recently (within a few hours), gastric
    lavage and the administration of charcoal in repeated doses is

    A venous blood sample should be taken to measure the haemoglobin
    level, prothrombin time, blood grouping, and cross-matching.

    If a patient is bleeding severely, 25 mg of vitamin K1
    (phytomenadione) should be given by slow intravenous injection.  The
    patient should be transfused with whole blood or plasma.  Fresh,
    frozen plasma may be given.  Prothrombin time should be checked at 3-h
    intervals and injections of vitamin K1 repeated, if no improvement
    occurs.  Administration of factor concentrate may be considered to
    avoid volume overload.

    In less severe cases of poisoning, vitamin K1 may be given in lower
    doses together with fresh, frozen plasma for rapid restoration of
    blood clotting factors.  Prothrombin time should be checked after
    8-10 h and vitamin K1 administration repeated, if necessary.

    Once the prothrombin time has stabilized, treatment with oral vitamin
    K1 (10 mg) should be continued four times daily.  Oral treatment may
    be sufficient in minor cases.

    The patient should be kept in hospital until the prothrombin time has
    remained normal for three days.

    The patient should be discharged from hospital with the following
    treatment:  oral vitamin K1 (10 mg) twice daily for up to 60 days
    with close monitoring of the prothrombin time.  It may be possible to
    reduce the length of treatment.

    4.1.2  Health surveillance advice

    Workers handling concentrates must undergo periodic determination of
    the potential disturbances of the clotting mechanisms, using the most
    appropriate method, i.e., by measuring circulating descarboxy-
    prothrombin, prothrombin concentration, or prothrombin time.

    4.2 Explosion and Fire Hazards

    High temperature decomposition or burning in air will lead to the
    formation of toxic gases, which may include carbon monoxide and traces
    of bromine and hydrogen bromide, as well as fumes of unchanged
    rodenticide;  breathing apparatus must be worn in fire fighting.

    Heating of containers will cause a pressure rise, with the risk of
    bursting and subsequent ignition.  Fire-exposed containers should be
    kept cool by spraying with water.

    Extinguishers recommended for small fires are carbon dioxide or dry
    powder;  foam or water fog are recommended for larger fires.  A water
    jet should not be used.

    Run-off water from the fire should be prevented from entering
    surface-water drains or water sources.

    4.3  Storage

    Technical material and formulations should be stored in sealed
    containers in locked, well-ventilated, dry areas, away from frost,
    direct sunlight, and sources of heat and ignition.  Keep products out
    of reach of children and unauthorized personnel.  Do not store near
    food or animal feed.

    4.4  Transport

    Comply with local regulations regarding the movement of hazardous
    goods.  Before despatch, ensure that the containers are sound and that
    labels are securely fixed and undamaged.

    4.5  Spillage

    During decontamination, the operator must wear protective clothing,
    PVC gloves, a face shield, and rubber boots.

    Dry spillages should be collected at once, by suction, and disposed of
    as toxic waste according to local legislation.

    Liquid spillages should be adsorbed onto vermiculite or other inert
    adsorbent and treated similarly.

    Contaminated areas should be washed down with cold water containing
    surfactant; the washings must be prevented from entering surface-water

    4.6  Disposal

    Disposal should be carried out according to national regulations.


    Bromadiolone is stable but rapidly binds on the soil with very slow
    desorption and without leaching.  Bromadiolone is slightly soluble in
    water and, in the form of bait-formulations, it is unlikely to be a
    source of water contamination.

    Do not place baits where domestic or farm animals and birds can reach
    them.  Burn or bury any uneaten bait.  Do not dump it in water.  Look
    for dead rats and mice and burn or bury them.


     This summary should be easily available to all health workers
     concerned with, and users of, bromadiolone. It should be displayed at,
     or near, entrances to areas where there is potential exposure to
     bromadiolone, and on processing equipment and containers.  The summary
     should be translated into the appropriate language(s).  All persons
     potentially exposed to the chemical should also have the instructions
     in the summary clearly explained.

     Space is available for insertion of the National Occupational Exposure
     Limit, the address and telephone number of the National Poison Control
     Centre, and local trade names.


    Chemical formula: C30H23BrO4
    CAS chemical name:3-[3-(4'-bromo-[1,1'-biphenyl]-4-yl)-3-hydroxy-1-phenylpropyl]-4-hydroxy-2H-1-benzopyran-2 one (9CI)
    IUPAC chemical name: 3-[3-(4'-bromobiphenyl-4-yl)-3-hydroxy-1-phenylpropyl]-4-hydroxycoumarin
    CAS registry number: 28772-56-7
    RTECS number: GN4934700

    PHYSICAL PROPERTIES                                                       OTHER CHARACTERISTICS

    Physical state                                 powder                     Bromadiolone is an anticoagulant rodenticide; it is
    Colour                                         off-white                  formulated as low-concentration baits (usually 0.005%
    Relative molecular mass                        527.4                      active ingredient)
    Melting point (C)                             200-210
    Vapour pressure (20C)                         2  10-6 Pa
    Solubility in water at 20C                    19 mg/litre
    Solubility in
    dimethylformamide                              730 g/litre
    ethanol                                        8.2 g/litre
    ethyl acetate                                  25 g/litre


    HAZARDS/SYMPTOMS                           PREVENTION AND PROTECTION                 FIRST AID

    GENERAL: Readily absorbed following        Avoid exposure                            Obtain medical attention; antidote - vitamin K1
    ingestion or inhalation, or through
    the skin; if absorbed, effects
    may range from an increased tendency
    to bleed to massive haemorrhaging

    SKIN: Non-irritant; skin absorption        Wear gloves when handling concentrate     Wash with soap and water; seek medical
    may occur from liquid concentrate          attention

    EYES: Slight irritant                      Use face shield when handling             Flush eyes with water for at least 15 min

    INHALATION: Significant vapour             Avoid inhaling concentrate aerosols or    Obtain medical attention, if necessary
    exposure unlikely                          bait dust

    INGESTION: An unlikely                     Wash hands before eating, drinking,       Transfer to hospital immediately; rinse out
    occupational hazard                        or smoking                                the mouth with water

    Accidental or intentional ingestion        Keep out of reach of children, under
    may lead to poisoning in several           lock and key
    hours or days


    SPILLAGE                                   STORAGE                                   FIRE/EXPLOSION

    Wear protective clothing during            Store in sealed containers in a dry,      Combustible solid;burning in air will lead to
    decontamination; dry spillage -            ventilated, and locked storeroom, away    the formation of toxic gases; for small fires,
    collect and dispose of as toxic            from children, unauthorized persons,      use carbon dioxide, halons, or dry powder;
    waste; liquid spillage - absorb            and domestic animals, food, and animal    for larger fires, use foam or water fog; keep
    on vermiculite or other inert              feed                                      containers cool by spraying with water
    absorbent and treat similarly;
    do not contaminate surface-water

    WASTE DISPOSAL                             NATIONAL INFORMATION

    Proper incineration is the method
    of choice

    7.1  Previous Evaluations by International Bodies

    Bromadiolone (technical) has been classified by WHO in Class Ia -
    Extremely Hazardous, based on the acute oral LD50 of 1.12 mg/kg for

    7.2  Exposure Limit Values

    No information is available.

    7.3  Specific Restrictions

    Bromadiolone has been approved for use as a rodenticide in many
    countries.  In some countries, specific uses are defined, as well as
    limitations and precautions.

    7.4  Labelling, Packaging, and Transport

    The European Economic Community legislation requires labelling of
    technical brodifacoum as very toxic with a hazard symbol T+ and the
    following pictogram:

    FIGURE 1

    The United Nations in its Recommendations on the Transport of
    Dangerous Goods classified bromadiolone in Category 6.1 as a poisonous
    substance (No. 3027).

    R26/27/28   Very toxic by inhalation, contact with the skin and by

    R48         Risks of serious effects to health in case of prolonged

    7.5  Waste Disposal

    No specific information is available.


    Hayes WJ Jr & Laws ER Jr (1991) Handbook of pesticide toxicology,
    Vol. 3, New York, Academic Press.

    IPCS (1995) Environmental Health Criteria 175: Anticoagulant
    rodenticides, Geneva, World Health Organization.

    WHO (1994) The WHO recommended classification of pesticides by hazard
    and guidelines to classification 1994-1995, Geneva (unpublished
    document WHO/PCS/94.2).

    Widdershoven J, van Munster P, De Abreu R, Bosman H, van Lith Th, van
    der Putten-van Meyel M, Motohara K, & Matsuda I (1987) Four methods
    compared for measuring des-carboxy-prothrombin (PIVKA-II),  Clin Chem
    33(11): 2074-2078.

    Worthing CR & Hance RJ, ed. (1991) The pesticide manual, 9th ed.,
    Farnham, United Kingdom, The British Crop Protection Council.

    See Also:
       Toxicological Abbreviations