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

                                                      VBC/DS/85.62

                                                      ORIGINAL: ENGLISH






    DATA SHEETS ON PESTICIDES No. 62

    CHLOROPHACINONE






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

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

                                   CLASSIFICATION:

                                   Primary use: Rodenticide

                                   Secondary use:

                                   Chemical group: Indandione derivative

    1.  GENERAL INFORMATION

    1.1  COMMON NAME:

         Chlorophacinone (ISO, BSI and JMAF)

    1.1.1  Identity;

         IUPAC:  2-(2-(4-chlorophenyl)-2-phenylacetyl)indan-1, 3-dione

         CAS:    2-(2-(4-chlorophenyl)-phenylacetyl)-1H-indene-1,
                 3(2H)-dione

         CAS Reg. No.: 3691-35-8

         Molecular formula: C23H15ClO3

         Molecular weight: 374.8

         Structural formula:

    CHEMICAL STRUCTURE

    1.1.2  Synonyms:

         AFNORR; CaidR; chlorofacinon; chlorfacinon; chlorophacinone;
    DeltaR; DratR; LiphadioneR; LM 91R: MicrozulR; MuriolR;
    QuickR; RamucideR; RanacR; RatometR; RaviacR; RozolR;
    TopitoxR.

    1.2  SYNOPSIS:

         Chlorophacinone is a chlorinated, diphenyl indane derivative;
    an anti-coagulant and metabolic inhibitor which is highly toxic to

    rodents but of only slight toxicity to humans and other non-target
    organisms. It is compatible with a wide spectrum of bait carriers
    and has no repellent action.

    1.3  SELECTED PROPERTIES

    1.3.1  Physical characteristics

         Chlorophacinone is a white crystalline solid. It has a melting
    point of 140°C, it is non-corrosive.

    1.3.2  Solubility

         Chlorophacinone is sparingly soluble in water, but soluble in
    organic solvents.

    1.3.3  Stability

         Chlorophacinone is described as stable and resistant to
    weathering effects.

    1.3.4  Vapour pressure

         Negligible at 20°C.

    1.4  AGRICULTURE, HORTICULTURE AND FORESTRY

    1.4.1  Common formulations

         Chlorophacinone is available as a bait, 50-250 mg a.i./kg and
    in oil solution, 2.5 g a.i./L.

    1.4.2 Pests controlled

         Presently used against mice, moles, muskrats, rats, vampire
    bats, and voles - in controlled access areas and under field
    conditions.

    1.4.3  Use pattern

         Chlorophacinone is applied wherever the rodents have access to
    the bait. It may be replenished as it is consumed. A tracking powder
    is recommended in areas where rodents travel. It does not usually
    require more than one feeding for a kill. The oil solution may be
    used to impregnate or coat any desirable bait. Prevent food
    contamination.

    1.4.4  Unintended effects

         Chlorophacinone could be hazardous to other small mammals and
    birds if used indiscriminately. Persons with bleeding problems and
    children should not come in contact.

    1.5  PUBLIC HEALTH USE

         As in 1.4, for control of nuisance and disease vector rodent
    pests.

    1.6  HOUSEHOLD USE

         As in 1.4, for control of nuisance and disease vector rodent
    pests.

    2.  TOXICOLOGY AND RISKS

    2.1  TOXICOLOGY - MAMMALS

    2.1.1  Absorption route

         Chlorophacinone is primarily absorbed from the gastrointestinal
    tract; dermal absorption may also occur.

    2.1.2  Mode of action

         Chlorophacinone is an anticoagulant agent; it uncouples
    oxidative phosphorylation depressing hepatic synthesis of
    prothrombin and clotting factors VII, IX and X and, it causes direct
    damage to capillary permeability. The ultimate effect is widespread
    internal haemorrhage. In rodents, indandlones also cause neurologic
    and cardiopulmonary injuries which often lead to death before
    haemorrhage occurs.

    2.1.3  Excretion products

         No published information available.

    2.1.4  Toxicity, single dose

         A single dose of a 50 mg/kg bait kills  Rattus norvegicus from
    the fifth day.

         Oral LD50:

         Rat                  20.5 mg/kg bw; technical material

         Rabbit               50.0 mg/kg bw; technical material

         Dermal LD50:

         Rabbit              200.0 mg/kg bw; technical material

         A solution of 5 mg in 2 ml of liquid paraffin applied to 100
    cm2 of shaved skin on rabbits caused only a slight reduction of
    prothrombin rating.

    2.1.5  Toxicity, repeated doses

         No published information available.

         Cumulation of compound

         No published information available.

    2.1.6  Dietary studies

         No published information available.

    2.1.7  Supplementary studies of toxicity

         No published information available.

    2.1.8  Modification of toxicity

         No published information available.

    2.2  TOXICOLOGY - MAN

    2.2.1  Absorption

         Chlorophacinone is primarily absorbed from the gastrointestinal
    tract, it may also be absorbed through the intact skin and,
    inhalation of residual bait dust may also occur.

    2.2.2  Dangerous doses

         No published information available. It is assumed that, because
    of low bait concentrations and the delayed nature of the toxic
    effect, it would require the ingestion of over one kilogram of the
    bait to produce toxic effects. Persons with "bleeding problems"
    should avoid contact.

    2.2.3  Observations of occupationally exposed workers

         No published information available.

    2.2.4  Observations on exposure of the general population

         No published information available.

    2.2.5  Observations of volunteers

         Human volunteers tolerated a single dose of 20 mg a.i. without
    ill-effects.

    2.2.6  Reported mishaps

         No published information available. In reports of cases
    involving similar poisons the compounds were either taken
    deliberately, were absorbed chronically out of neglect of basic
    hygiene or were ingested when rodent baits were inadvertently used
    as food.

    2.3  TOXICITY TO NON-MAMMALIAN SPECIES

    2.3.1  Fish

         No published information available.

    2.3.2  Birds

         Chlorophacinone is of low toxicity to birds. Administration of
    15 daily doses of 2.25 mg to grey partridges produced no ill-
    effects.

         Oral LD50:

         Wild Birds          430 mg/kg bw; technical material

         Ducks               100 mg/kg bw; technical material

    3.  FOR REGULATORY AUTHORITIES - RECOMMENDATION ON REGULATION OF
        COMPOUND

    3.1  RECOMMENDED RESTRICTIONS ON AVAILABILITY

         (For definition of categories see introduction.) All
    formulations, categories 4 and 5.

    3.2  TRANSPORT AND STORAGE

         Formulations in category 4 - Should be transported in clearly
    labelled, rigid and leakproof containers out of reach of children,
    away from food and drink. Storage should be under lock and key and
    secure from access by children and other unauthorized persons.

         Formulations in category 5 - Should be transported and stored
    in clearly labelled, leakproof containers out of reach of children,
    away from food and drink.

    3.3  HANDLING

         Formulations in category 4 - Protective clothing should be
    used by all handling the compound. Adequate washing facilities
    should be available at all times during handling and they should be
    close to the site of handling. Eating, drinking and smoking should
    be prohibited during handling and before washing of hands and face
    after handling. Baits of chlorophacinone should be removed and the
    area thoroughly cleaned up after purpose has been fulfilled.

         Formulations in category 5 - No facilities other than those
    needed for the handling of any chemical are required. Baits of
    chlorophacinone should be removed and the area thoroughly cleaned up
    after purpose has been fulfilled.

    3.4  DISPOSAL AND/OR DECONTAMINATION OF CONTAINERS

         All formulations - Containers should not be decontaminated
    and should not be used for any other purpose. Containers should be
    burned or should be crushed and buried below topsoil. Care must be
    taken to avoid subsequent contamination of water sources.

    3.5  SELECTION, TRAINING AND MEDICAL SUPERVISION OF WORKERS

         Formulations in categories 4 and 5 - A pre-employment
    examination is essential to exclude from contact all persons with
    blood and vascular disorders predisposing them to haemorrhaging. A
    periodic medical examination should include tests of blood clotting
    time, prothrombin levels, capillary fragility and a record of
    evidence of blood in the excreta.

    3.6  ADDITIONAL REGULATIONS IF DISTRIBUTED BY AIRCRAFT

         NOT APPLICABLE

    3.7  LABELLING

         Formulations in category 5 - Minimum cautionary statement -
    "CAUTION". This formulation contains chlorophacinone, it may be
    poisonous if swallowed. Keep this material out of reach of children
    and well away from food, animal feed and food utensils. Avoid skin
    contact, wear impermeable gloves when handling and wash immediately
    after handling the compound. In case of contact, immediately remove
    contaminated clothing and wash the skin thoroughly with soap and
    water; for eyes, flush with water for 15 minutes.

         If poisoning occurs, call a physician. Vitamin K is a specific
    antidote.

    3.8  RESIDUES IN FOOD

         Maximum residue levels have been recommended by the Joint
    FAO/WHO Meeting on Pesticide Residues.

    4.  PREVENTION OF POISONING IN MAN AND EMERGENCY AID

    4.1  PRECAUTIONS IN USE

    4.1.1  General

         Chlorophacinone is a rodenticide; an anticoagulant and a
    metabolic inhibitor. It depresses hepatic synthesis of factors
    essential to blood clotting and causes increased capillary
    permeability which ultimately lead to internal haemorrhage.
    Indandiones should be considered more toxic than warfarin though
    their health hazard to humans may be considerably diminished by
    their low concentration in most formulations and their delayed
    action. Chlorophacinone is primarily absorbed from the
    gastrointestinal tract; to a limited extent through intact skin;
    and, inhalation of bait dust may also occur.

    4.1.2  Manufacture and formulation - TLV

         No information. Closed systems and forced ventilation may be
    required to reduce, as much as possible, the exposure of workers to
    the chemical.

    4.1.3  Mixers and applicators

         When opening a container and when mixing, protective
    impermeable boots, clean overalls, impermeable gloves and a
    respirator should be worn. Mixing, if not mechanical, should always
    be carried out with a paddle of appropriate length. Avoid contact
    with mouth and eyes. Before eating, drinking or smoking, hands and
    other exposed skin should be thoroughly washed with alkaline soap.

    4.1.4  Other associated workers

         All persons exposed to the concentrate and associated with its
    formulation should observe the precautions described above in 4.1.3.

    4.1.5  Other populations likely to be affected

         With good agricultural practice, subject to 4.2 below, other
    populations are not likely to be exposed to hazardous amounts of the
    compound.

    4.2  ENTRY OF PERSONS INTO TREATED AREAS

         Chlorophacinone is relatively persistent, all exposed baits
    should be clearly marked and identified as a poison. Under these
    conditions, unprotected adult persons may enter the treated area
    immediately after application without being exposed to a health
    hazard.

    4.3  SAFE DISPOSAL OF CONTAINERS AND SPILLAGE

         Residues in containers should be emptied in a dilute form into
    a deep pit taking care to avoid contamination of ground waters.
    Decontamination of containers in order to use them for other
    purposes should not be permitted. Spillage should be removed as much
    as possible and as soon as possible into a deep dry pit and the
    residue washed away with large quantities of water. The residue and
    containers may also be burned in a well-ventilated location.

    4.4  EMERGENCY AID

    4.4.1  Early symptoms of poisoning

         The signs and symptoms of acute poisoning from a large dose are
    not likely to be immediately apparent. When the body's reserves of
    prothrombin have been diminished, after two or three days following
    a single large dose or after a few weeks of repeated ingestion of
    small doses, bleeding gums, pallor, swelling and tenderness of the
    joints, haematomata, blood in the urine and faeces, and abdominal
    pains may occur. Paralysis, haemorrhagic shock and death may follow
    in cases of severe poisoning. Cardiopulmonary and neurologic
    symptoms seen in rats have not been reported in human victims.

    4.4.2  Treatment before a person is seen by a physician

         Due to the delayed appearance of symptoms, it is unlikely that
    specific symptoms will be seen directly following exposure. If the
    compound has been swallowed, vomiting should be induced immediately
    if the person is conscious; call a physician immediately and
    transport the victim to hospital as soon as possible.

    5.  FOR MEDICAL AND LABORATORY PERSONNEL

    5.1  MEDICAL DIAGNOSIS AND TREATMENT IN CASES OF POISONING

    5.1.1.  General information

         Chlorophacinone is a rodenticide; an anticoagulant and a
    metabolic inhibitor; and, it may specifically inhibit Vitamin
    K1-epoxidase activity. It depresses hepatic synthesis of factors
    essential to normal blood clotting and causes increased fragility
    and permeability of capillaries leading to widespread internal
    haemorrhage. Chlorophacinone is absorbed primarily from the
    gastrointestinal tract and to a limited extent through the intact
    skin. It is highly toxic to rodents but it is considered to be
    slightly toxic to humans, in most formulations.

    5.1.2  Symptoms and signs

         The victims of small ingested doses and even those of
    substantial, hypoprothrombinemia inducing doses are usually
    asymptomatic,. The onset of clinical signs of poisoning may be
    delayed several days after exposure to a single large dose or after
    a few weeks of repeated ingestion of small doses. The signs of
    poisoning are epistascis and bleeding gums; pallor and sometimes
    petechial rash; massive ecchymoses and/or haematomata (especially of
    the articulating joints); blood in urine and faeces; occasionally
    paralysis due to cerebral haemorrhage; and, haemorrhagic shock and
    death. Cardiopulmonary and neurologic signs and symptoms, common in
    rat poisonings, have not been reported in human cases.

    5.1.3  Laboratory

         The principle diagnostic test in a demonstration of markedly
    reduced prothrombin activity in blood plasma, as measured by the
    method of Quick or one of its modifications. The test should be
    repeated at least twice daily until a normal prothrombin time is
    established. Also, the blood clotting time and the bleeding time
    should be obtained. Blood is often demonstrable in the excreta.
    Secondary anaemia (hypochromic and microcytic) may be marked.

    5.1.4  Treatment

         If small amounts of the compound have been ingested by either
    an adult or a child and the victim is asymptomatic, treatment is
    probably unnecessary. If there is uncertainty about the dose or the
    general health of the victim, Vitamin K1 may be given orally as a
    prophylactic treatment. Observe the patient for 4-5 days.

         If the dose is known to be large or the victim is showing signs
    of poisoning, induce vomiting with Syrup of Ipecac or perform a
    gastric lavage within 2-3 hours of ingestion. Follow with activated

    charcoal treatment to limit absorption of any toxicant remaining in
    the gastrointestinal tract. Vitamin K1 is a specific antidote, 5-
    10 mg by subcutaneous or intramuscular injection may be repeated if
    necessary. Only if the victim is bleeding severely or otherwise in
    serious distress should the drug be given intravenously at a rate no
    more than 1 mg/min. On subsequent days Vitamin K1 treatment may be
    continued, if necessary. The usual precautions in Vitamin K1
    therapy should be followed. Small transfusions of fresh whole blood
    may be necessary or an immediate and temporary source of prothrombin
    and erythrocytes. Vitamin C may be a useful adjunct to Vitamin K1
    therapy, at 100 mg several times a day as necessary. Neither
    Vitamins K3 nor K4 are effective antidotes in cases of
    Indandione poisoning.

         Following the establishment of control of haemorrhage and the
    repair of the coagulation defect, iron replacement therapy should be
    initiated to correct the secondary anaemia. In severe incidences it
    may also be necessary to aspirate the haematomas after normal blood
    clotting has been restored.

    5.1.5  Prognosis

         If the acute toxic effect is survived, the chances of complete
    recovery are very good provided that subdural haemorrhages or
    vascular lesions in other tissues do not: produce secondary effects.

    5.1.6  References of previously reported cases

         No information available.

    5.2  SURVEILLANCE TESTS

         Blood clotting time and bleeding time could be monitored in
    chronically exposed individuals. Also, vigilance for blood in the
    excreta and peripheral signs of capillary fragility is appropriate.
    The blood levels of active Vitamin K1 relative to Vitamin
    K1-expoxide or the level of Vitamin K1 epoxidase would also
    prove useful to assess overexposure or the progress of therapy.

    5.3  LABORATORY METHODS

    5.3.1  Detection and assay of compound

         Bullard, R. W. et al. (1975) J. Agric. Food Chem., 23(1), 72.
    Davis, R. S. (1977), Bull. OEPP, 7(2), 477. Grant, R. G. & Pike,
    R. K. (1979), J. Assoc. Off. Anal. Chem, 62(5), 1001. Kawano, Y. &
    Chang, W. (1980), J. Assoc. Off. Anal. Chem, 63(5), 996. Reynolds,
    R. (1980), Proc. Annu. Meet. Am. Assoc. Vet. Lab.; 23, 187. Vigh,
    G. et al. (1981), J. Chromatogr., 214(3), 335.