Health and Safety Guide No. 93






    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 Brodifacoum

    (Health and safety guide ; no. 93)

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

    ISBN 92 4 151093 5          (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 methods
         2.2. Sources of human and environmental exposure
         2.3. Environmental transport, distribution, and
         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. 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:             brodifacoum

    Chemical formula:        C31H23BrO3

    Chemical structure:

                             CHEMICAL STRUCTURE

    Common synonyms:         Super-warfarin, bromfenacoum, BFC, PP-581,
                             WBA 8119, ICI-581

    Trade names:             Finale, Folgorat, Havoc, Klerat, Matikus,
                             Mouser, Ratak +, Rodend, Talon, Volak, Volid

    CAS chemical name:       3-[3-(4'-bromo-[1,1'-biphenyl]-4-yl)-1,2,3,4-

    IUPAC chemical name:     3-[3-(4'-bromobiphenyl 4-yl)- 1,2,3,4-

    CAS registry number:     56073-10-0

    RTECS registry number:   GN4934750

    1.2   Physical and Chemical Properties

    Brodifacoum is an off-white powder, which is stable in the solid form. 
    Its solubility in water is very low (less than 10 mg/litre at 20C and
    pH 7); it is slightly soluble in benzene and soluble in acetone.

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

    1.3  Analytical Methods

    Analytical methods for the determination of brodifacoum include liquid
    chromatography with fluorescence detection and high-performance liquid
    chromatography, with detection limits of 0.001 mg/litre and
    0.002 mg/kg, respectively.

    1.4  Production and Uses

    The rodenticidal properties of brodifacoum were described in 1976.  It
    is an anticoagulant that is effective against rats and mice, including
    warfarin-resistant strains.  It is used in agriculture and urban
    rodent control as ready-to-use baits of low concentration (usually
    0.005% brodifacoum).


    2.1  Identity, Physical and Chemical Properties, and Analytical

    Brodifacoum is an off-white to fawn powder, which is stable at room
    temperature in the solid form and has a melting point of 228-232C. 
    Its solubility in water is very low; it is slightly soluble in benzene
    and chloroform and soluble in acetone.  Determination of brodifacoum
    is based on high-performance liquid chromatography.

    2.2  Sources of Human and Environmental Exposure

    Brodifacoum does not occur naturally.  It is used as a rodenticide
    against pest rodents and acts by preventing the production of
    essential blood-clotting factors.

    2.3  Environmental Transport, Distribution, and Transformation

    Brodifacoum does not enter the atmosphere, because of its low
    volatility.  It is practically insoluble in water.  Brodifacoum is
    strongly bound on soil particles and is not taken up by plants.  The
    rate of degradation is relatively slow and depends on soil type. 
    Residues in crops have never been detected in field studies.

    2.4  Environmental Levels and Human Exposure

    Brodifacoum is not intended for direct application to growing crops or
    for use as a food additive.

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

    Residues of brodifacoum were detected in dead barn owls in the United
    Kingdom at levels of 0.019-0.515 mg/kg.  Brodifacoum residues were
    also found in the liver, muscle, and fatty tissues of rabbits,
    intentionally poisoned during field trials with baits containing
    0.005% active ingredient, at concentrations of 4.4, 0.26, and
    0.86 mg/kg, respectively.

    2.5  Kinetics and Metabolism in Laboratory Animals and Humans

    Brodifacoum is absorbed through the gastrointestinal tract, skin, and
    respiratory system.  The major route of elimination in different
    species after oral administration is through the faeces.  The liver is
    the main organ of accumulation and storage.  Brodifacoum has mainly
    been found as an unchanged compound.  After a single oral dose to
    rats, liver concentrations remained high and relatively constant for
    96 h.  Elimination from the liver is slow and biphasic with an initial
    rapid phase lasting from 2 to 8 days after dosing and a slower
    terminal phase with an elimination half-life of 130 days.  In
    accidentally poisoned patients, the plasma half-life was found to be
    approximately 16-36 days.

    2.6  Effects on Laboratory Mammals and in vitro Test Systems

    Brodifacoum has a high acute oral toxicity (LD50 less than 1 mg/kg)
    for various species, including rodents and non-rodents.  The dermal
    and inhalation toxicities are also high.  Signs of poisoning are
    similar for all routes of administration and are those associated with
    an increased tendency to bleeding.

    Brodifacoum is a slight irritant for the skin and a mild eye irritant.

    In feeding studies on rats, the only effect was that associated with
    anticoagulant action.  No long-term studies have been reported. 
    Mutagenicity and teratogenicity studies did not show any mutagenic,
    embryotoxic, or teratogenic effects.

    2.7  Effects on Humans

    Symptoms of acute intoxication by brodifacoum vary from an increased
    tendency to bleed in less severe poisonings to massive haemorrhage in
    more severe cases.  The signs of poisoning develop with a delay of one
    to several days after ingestion.

    Both intentional and unintentional poisoning incidents have been

    2.8  Effects on Other Organisms in the Laboratory and Field

    Brodifacoum was highly toxic for fish when tested as a technical

    Bird species varied in their susceptibility to brodifacoum, oral
    LD50s ranging from less than 1 mg/kg body weight to more than
    20 mg/kg body weight.

    The possible effects of brodifacoum on non-target organisms can be
    considered in two categories, i.e., primary (direct poisoning) and
    secondary (through consumption of poisoned rodents).

    Cases of abortion and haemorrhage in sheep and goats caused by the
    misuse of brodifacoum have been reported.

    Secondary poisoning through the consumption of rats and mice killed
    with brodifacoum may occur in dogs and cats in urban situations, but
    are 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

    Brodifacoum is widely used in urban rodent control and against rodent
    pests in agriculture. As it is used as low-concentration baits,
    increased levels in air are unlikely.  Being slightly soluble in
    water, its use cannot be a significant source of water contamination. 
    Brodifacoum is not intended for direct application to growing crops
    and no residues are expected in plant foodstuffs.  Occupational
    exposure may occur during manufacture, formulation, and bait
    application, but data indicating the levels of exposure are not

    Brodifacoum may be absorbed through the gastrointestinal tract, skin,
    and respiratory system.  The major route of elimination in different
    species, after oral administration, is through the faeces.  The urine
    is a very minor route of elimination.  The liver is the major organ
    for the accumulation and storage of brodifacoum, which has mainly been
    found as the unchanged parent compound.  Its elimination from the
    liver is slow.

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

    Both intentional and unintentional poisoning incidents have been

    Prothrombin time is a satisfactory guide to the severity of acute
    intoxication, and also for the effectiveness and duration of the

    Vitamin K1 is a specific antidote for both animals and humans (see
    section 4.1.1).

    2.9.2  Evaluation of effects on the environment

    Brodifacoum is applied to discrete sites in the form of
    low-concentration baits and  is stable under normal conditions.  The
    solubility of brodifacoum in water is low and, in bait formulation,
    its use is unlikely to be a source of water pollution.  As a technical
    material, it is highly toxic for fish.

    Brodifacoum appears to bind rapidly in the soil with very slow
    desorption and without leaching.

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

    Small pellets and whole grain baits are highly attractive to birds. 
    Wax-block formulations appear to decrease the attractiveness to the
    birds and this reduces the possibility of poisoning incidents.  Bird
    species vary in their susceptibility to brodifacoum.

    The main reason for the poisoning of domestic animals is direct
    consumption of brodifacoum baits.

    Brodifacoum shows a similar range of acute toxicity for non-target and
    target mammals.  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 animals must consume
    comparatively large amounts of bait with a concentration of 0.005%
    active ingredient.

    Some secondary toxicity laboratory studies on wildlife have shown that
    captive predators could be intoxicated by the no-choice feeding of
    brodifacoum-poisoned or dosed prey.  The significance of these results
    in terms of hazard under field conditions is difficult to assess,
    because the predators would not be expected to eat only poisoned
    animals.  However, predators may take poisoned, but not dead, small
    mammals 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 has been
    very widespread and constant use of the baits.


    3.1  Conclusions

    Exposure of the general population to brodifacoum 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 skin
    contact during manufacture and formulation.

    Brodifacoum is relatively persistent in the environment, but its
    specific use in the form of low-concentration bait formulations cannot
    be a significant source of air, water, soil or food contamination. 
    Direct and secondary poisoning of birds, domestic and farm animals,
    and wildlife has been observed.

    3.2  Recommendations for the Protection of Human Health and the

    Potentially exposed workers should receive appropriate biomonitoring
    and health evaluation.

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

    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, dermal, and inhalation toxicities of brodifacoum for mammals
    are extremely high (rat oral LD50 0.3 mg/kg; rat inhalation LC50
    0.005 mg/litre).  The ingestion of 1 mg of brodifacoum by an adult
    person was reported to produce bleeding that persisted for more than
    two months.  The average fatal dose for an adult man (60 kg) is
    estimated to be approximately 15 mg brodifacoum or 300 g of 0.005%

    The main features in less severe cases of brodifacoum poisoning 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 is seen in more severe cases.  The onset of the
    signs of poisoning may not be evident until a few days after

    Brodifacoum is a mild eye irritant and a slight skin irritant, but it
    is not a skin sensitizer.

    It is slowly metabolized by mammals and, following prolonged exposure,
    may accumulate in the liver reaching toxic levels.

    Full air-fed protection and an impervious suit, suitable for
    wash-down, are necessary when handling technical material or powder
    concentrates.  In operations involving liquid concentrates, it is
    necessary to wear PVC or nitrile-rubber gloves, armlets, and an apron,
    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 following ingestion has occurred recently (within a few
    hours), treatment involving gastric lavage and the administration of
    charcoal in repeated doses is recommended.

    A venous blood sample should be taken for measurement of the
    haemoglobin level, prothrombin time, blood grouping, and

    If a patient is bleeding severely, give 25 mg of vitamin K1
    (phytomenadione) by slow intravenous injection.  Transfuse patient
    with whole blood or plasma.  Fresh, frozen plasma may be given.  Check
    prothrombin time at 3-h intervals and repeat injections of vitamin
    K1 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 and also fresh, frozen plasma to rapidly restore the blood
    clotting factors.  Check prothrombin time after 8-10 h and repeat
    vitamin K1 administration, if necessary.

    Once the prothrombin time has stabilized, continue treatment with oral
    vitamin K1, giving 10 mg four times daily.

    Oral treatment may be sufficient in mild cases.

    Keep the patient in hospital until the prothrombin time has remained
    normal for three days.

    Discharge the patient from hospital with the following treatment:
    vitamin K1, 10 mg to be taken orally, 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 have periodic determination of the
    potential disturbances of the clotting mechanisms by the most
    appropriate method, such as, circulating descarboxyprothrombin,
    prothrombin concentration, or prothrombin time.

    4.2  Explosion and Fire Hazards

    Brodifacoum is a combustible solid.  Most industrial operations
    involve the solution concentrates with flash point of solvents higher
    than 90C.

    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.

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

    Carbon dioxide or dry powders are recommended for extinguishing small
    fires, and foam or water fog 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 brodifacoum 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 and animal feed.

    4.4  Transport

    Comply with any 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, 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.

    Brodifacoum is stable, but is rapidly bound to the soil, with very
    slow desorption and without leaching.  It is only 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.


    Brodifacoum is stable, but is rapidly bound to the soil, with very
    slow desorption and without leaching. It is only slightly soluble in
    water and, in the form of bit 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 bury them.


     This summary should be easily available to all health workers
     concerned with, and users of, brodifacoum. It should be displayed at,
     or near, entrances to areas where there is potential exposure to
     brodifacoum, 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:   C31H23BrO3
    CAS chemical name: 3-[3-(4'-bromo-[1,1'-biphenyl]-4-yl)-1,2,3,4-tetrahydro-1-naphthalenyl]-4-hydroxy-2H-1-benzopyran-2-one
    IUPAC chemical name: 3-[3-(4'-bromobiphenyl 4-yl)-1,2,3,4-tetrahydro-1-naphtyl]-4-hydroxycoumarin
    CAS registry number: 56073-10-0
    RTECS number: GN4934750

    PHYSICAL PROPERTIES                                                    OTHER CHARACTERISTICS

    Physical state                         powder                          Brodifacoum is an anticoagulant rodenticide; it is formulated as
    Colour                                 off-white                       low-concentration baits (usually 0.005% active ingredient)
    Relative molecular mass                523.4
    Melting point (C)                     228-232
    Vapour pressure (25C)                 less than 0.13 mPa
    Solubility in water                    less than 0.01 g/litre
    at 20C, pH 7
    in acetone                             6-20 g/litre
    in benzene                             <0.6 mg/litre
    in chloroform                          3 g/litre


    HAZARDS/SYMPTOMS                           PREVENTION AND PROTECTION                 FIRST AID

    GENERAL: Readily absorbed                  Avoid exposure                            Obtain medical attention; antidote - vitamin K1
    following ingestion, inhalation or
    through the skin; if absorbed, may
    cause increased bleeding tendency
    to massive haemorrhage

    SKIN: Slight irritant; significant         Wear gloves when handling                 Wash with soap and water; seek medical
    skin absorption occurs with liquid         concentrate                               advice
    concentrates; the baits are not

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

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

    INGESTION:  Nausea/vomiting                Wash hands before eating, drinking,       Rinse out the mouth with water; transfer
    acute anticoagulant poisoning in           or smoking                                to hospital immediately
    several hours or days may occur


    SPILLAGE                                   STORAGE                                   FIRE/EXPLOSION

    Wear protective clothing during            Store in sealed containers in a dry,      Combustible solid;  burning in air will lead
    decontamination; dry spillage -            ventilated, and locked storeroom,         to the formation of toxic gases; for small fires
    collect by suction and dispose of as       away from children, unauthorized          use carbon dioxide, halons, or dry powder;
    toxic waste; liquid spillage - absorb      persons, domestic animals, food, and      for larger fires, use foam or water fog;
    onto vermiculite or other inert            animal feed                               keep 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

    Technical brodifacoum has been classified by WHO in Class Ia -
    Extremely Hazardous, based on acute oral LD50 of 0.3 mg/kg for rats.

    A  Poisons Information Monograph for brodifacoum has been issued by

    7.2  Exposure Limit Values

    No information is available.

    7.3  Specific Restrictions

    Brodifacoum has been officially 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 Community legislation requires labelling of technical
    brodifacoum as very toxic with a hazard symbol T+ and the following

    FIGURE 1

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

    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 (1992) Poisons information monograph - brodifacoum, IPCS/
    INTOX/Project, Geneva, World Health Organization (unpublished document

    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, World Health
    Organization (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 edition,
    Surrey, United Kingdom,  British Crop Protection Council.

    See Also:
       Toxicological Abbreviations
       Brodifacoum (PIM 077)