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Brodifacoum (Talon, Havoc) - Chemical Profile 1/85

                                    brodifacoum
      CHEMICAL name:      2-[3-(4'-bromo[1-1'-biphenyl]-4-yl)-1,2,3,4-tetra-
                          hydro-1-napthalenyl]-4-hydroxy-2H-1-benzopyran-2-
                          one (56)
      TRADE name(S):      Klerat, Ratak Plus, Talon, Volid, Havoc (56)
      FORMULATION(S):     Ready-to-use grain-base bait in pellets, mini
                          pellets, and waterproof Weather-Blok bait
                          containing 0.005% brodifacoum (loose or
                          bait-packs).  Talon for professional operators;
                          Havoc for general usage (56).
      TYPE:               Rodenticide (anticoagulant)
      BASIC PRODUCER(S):  Syngenta
                          410 Swing Rd.
                          Greensboro, NC 27409
      STATUS:             General use
      PRINCIPAL USES:     A rodenticide of exceptional activity against a
      variety of pest rodents.  Currently registered in U.S. for control of
      Norway rats, roof rats, and house mice in public, industrial and
      commercial buildings, residential, as well as for urban outdoor use by
      professional pest control personnel and commercial rodent control in
      and around farm buildings (56).
                                    I.  EFFICACY
          Effective against rodents which are resistant to conventional
      anticoagulants.  Only a single feeding necessary for rodent death
      to occur (56).
           Its potency is such tht, unlike other anticoagulants, a rodent may
      absorb a lethal dose by taking a 50 mg/kg bait as part of its feed
      intake on only one occasion (62).
           It has an acute as well as chronic effect on rodents.  Slow acting
      with the rodents dying in 3-7 days (8c).
      BIOLOGICAL ACTIVITY:  Havoc is the most active anticoagulant on mice and
      rats.  Yet, research has shown Havoc to be less active on nontarget
      animals than some multiple feeding anticoagulants.  Listed below is a
      comparison of acute LD50 values for various anticoagulants on these
      rodents.
                              Acute Oral LD50 (mg/kg)
                                            Norway Rat         House Mouse
      Brodifacoum (Havoc)                     0.27                 0.40
      Warfarin                               58.0                347.0
      Diphacinone                             3.0                141.0
      Bromadiolone                            1.13                 1.75
      Havoc in the finished bait is effective in extremely small amounts on
      mice and rats.  However, there is sufficient specificity to create a
      margin of safety to nontarget species.  Listed below is a comparison of
      lethal doses for various finished baits indicating their toxicity to
      rodents as well as to nontarget species.
                        Amounts of Bait Necessary (in grams)
                                  To give an LD50
                                Mice 0.025 kg               Rats, 0.25 kg
                                 body weight                 body weight
      Havoc                     0.2 g (0.005%)              1.4 g (0.005%)
      Warfarin                 37.0 g (0.025%)             58.0 g (0.025%)
      Diphacinone              70.0 g (0.005%)             11.5 g (0.005%)
      Zinc Phosphide                                         .45 g (2.5%)
                        Amounts of Bait Necessary (in grams)
                                  To Give an LD50
                                Cats 2 kg                   Dogs 5 kg
                                 body wt                     body wt
      Havoc                    1000 g (0.005%)            355-1000 g (0.005%)
      Warfarin                 48-320 g (0.025%)          400-500 g (0.025%)
      Diphacinone              588 g (0.005%)             88 g (0.005%)
      Zinc Phosphide           1.6 g (2.5%)               4-8 g (2.5%)
      Laboratory Tests - Havoc bait at 0.005% (50 ppm) has been shown to be
      highly efficacious against commensal rodent species, as indicated in
      the table below.
                        Feeding Tests with 0.005% Havoc Bait
                             on Various Rodent Species
                                  Feeding       No. Days       %         No.
      Species     Distribution    Choice       of Feeding     Kill     Tested
      Rattus        Worldwide      None            1          100        25
      norvegicus                   Free            1           90        20
      (Norway Rat)                 Free            3           95       100
      Rattus        Johnston       None            1          100        12
      norvegicus    Cy., NC        Free            3          100        12
      (resistant)
      (Norway rat)
      Rattus        Worldwide      None            1           90        20
      rattus                       Free            2          100        20
      (Roof rat)                   Free            3          100        20
      Mus           Worldwide      None            1           95        20
      musculus
      (House mouse)
                     Efficacy of Havoc to Cross-Resistant Wild
                    Norway Rats (U.S. Data Jackson, Unpublished)
                                                    Treatment
        Test Criteria                Warfarin           Pival           Havoc
      Concentration (ppm)               50               50              50
      Mean Body Weight (g)             228               289             285
      Mean Dose Ingested (mg/kg)       25.6              25.9            16.4
      Mean Daily Consumption (g)       18.2              24.6            15.6
      Mortality                        0/7               0/7             7/7
      In similar testing with confirmed warfarin-resistant house mice Havoc
      killed 100% of the test population.  This demonstrates the
      effectiveness of Havoc against resistant house mice.
                      Efficacy of Havoc to Warfarin Resistant
                  Wild House Mice (U.S. Data Frantz, Unpublished)
                    Mean body weight              19.4 g
                    Mean ingested dose            12.9 mg/kg
                    Mortality                     10/10

      Rodenticides may be compared based on resistance factors.  These
      factors are a measure of a compound's potential activity against
      resistant rodents.  Below is a comparison of resistance factors for
      several anticoagulants.  The closer the number is to 1, the more
      potentially effective the compound is against resistant rodents.
                 Rattus Norvegicus (Norway rat) Resistance Factors
                 of Anticoagulants (from Hadler and Shadbolt, 1975)
                    Anticoagulant                 Resistance Factor
                    Brodifacoum                        1.3
                    Chlorophacinone                   90.9
                    Diphacinone                      227.3
                    Warfarin                         166.7
      FIELD RESISTANCE EFFICACY
           A field study was conducted at a site where a high level of
      resistance has been noted.  Tracking boards and consumption of bait
      were recorded prior to and after baiting with Havoc.  The site was a
      poultry farm with four buildings, each having a large population of
      Norway rats.  Havoc was very effective in controlling these rats with a
      documented high level of resistance to Warfarin.
                  Results From Site Having Confirmed Resistance to
                  Warfarin (from Apperson, Sanders and Kaukeinen)
                          Consumption                      % Inactive
                        (g/station day)                 Tracking Boards
      Building                         %                               %
         #        Pre      Post     Reduction     Pre      Post     Reduction
         1        10.2     1.3        87.5        0.7      86.3       99.2
         2        49.3     1.3        97.4        0.3      53.6       99.5
         3        15.1     0.8        94.9       11.8      77.0       84.7
         4        77.5     1.9        88.9        4.1      91.2       95.5
      PALATABILITY
           The grain-based formulations which are available surpass EPA
      acceptance requirements (33%) for conventional anticoagulants.
      Acceptance levels of over 60% have been documented for groups of wild
      Norway rats and house mice.
      SIX HOUR NO-CHOICE FEEDING
           In a laboratory experiment, 4 wild Norway rats were allowed to
      feed upon Havoc bait for 6 hours, in a no-choice situation.
      Twenty-three of the 24 rats died (96%) with an average day of death of
      just over 6 days.  In similar testing 2 groups of Norway rats were
      allowed to feed on Havoc bait for 24 hours.  All of the animals in both
      groups died with an average time of death near 6 days (20e).
                              II.  PHYSICAL PROPERTIES
      MOLECULAR FORMULA:   C31 H23 Br O3 (62)
      MOLECULAR WEIGHT:    523.4 (62)
      PHYSICAL STATE:      Off-white to fawn powder (62)
      MELTING POINT:       228-232 C (62)
      VAPOR PRESSURE:      <133 uPa at 25 C (62)
      SOLUBILITY:          <10 mg/l water at pH 7 at 20 C; it is a weak acid
                           which does not form water-soluble salts (62).
                          III.  HEALTH HAZARD INFORMATION
      OSHA STANDARD:  NA
      NIOSH RECOMMENDED LIMIT:  NA
      ACGIH RECOMMENDED LIMIT:  NA
      TOXICOLOGY
           A.  ACUTE TOXICITY
               DERMAL:  LD50 = 50 mg tech./kg, 200 mg a.i. (as dust)/kg for
                          6-hr. exposure (rat) (62).
                        LD50 = low dermal toxicity, practically nonirritating
                          to skin (rabbit, finished bait - 50 ppm brodifacoum)
                          (20 e).
               ORAL:  LD50 = 0.27 mg a.i./kg (male rat); 0.3 mg/kg (male
                        rabbit); 0.4 mg/kg (male mouse); 2.8 mg/kg (female
                        guinea pig); c. 25 mg/kg (cat); 0.25-1.0 mg/kg (dog);
                        4.5 mg/kg (chicken) (62).
                      LD50 = 5,600 mg/kg (rat, finished bait containing 50
                        ppm (0.005%) brodifacoum) (20e).
               INHALATION:  No toxicological response evoked in tests (rat,
                            finished bait - 50 ppm brodifacoum) (20e).
           B.  SUBACUTE AND CHRONIC TOXICITY:
           In 42-day feeding trials rats receiving 0.1 mg/kg diet suffered no
      ill-effect (62).
                         IV.  ENVIRONMENTAL CONSIDERATIONS
         Acute oral LD50 = 2.0 mg/kg for mallard duck (62).
         LC50 (96 hr) is:  for bluegill 0.165 mg/l; for rainbow trout 0.051
         mg/l (62).
         Effective at such low rates that the risk of secondary poisoning to
      other animals is minimal.  Relatively non-toxic to bird species (8c).
         This product can be toxic to wildlife and can pose a secondary
      hazard to birds of prey and mammals.  Extensive research with predatory
      animals, such as barn owls, has shown that such predators are not
      normally at risk when Havoc is used according to label directions
      (Kaukeinen 1982) (20e).
                       V.  EMERGENCY AND FIRST AID PROCEDURES
           The chemical information provided below has been condensed from
      original source documents, primarily from "Recognition and Management
      of Pesticide Poisonings", 3rd ed. by Donald P.  Morgan, which have been
      footnoted.  This information has been provided in this form for your
      convenience and general guidance only.  In specific cases, further
      consultation and reference may be required and is recommended.  This
      information is not intended as a substitute for a more exhaustive
      review of the literature nor for the judgement of a physician or other
      trained professional.
           If poisoning is suspected, do not wait for symptoms to develop.
      Contact a physician, the nearest hospital, or the nearest Poison
      Control Center.
      FREQUENT SYMPTOMS AND SIGNS OF POISONING:
           Coumarins, indandiones, and other anticoagulants:  In most cases
      of ingestion of anticoagulants, victims have remained asymptomatic, due
      to the small dosage taken.  Even in cases involving ingestion of
      substantial amounts of anticoagulant compound (more often medication
      than rodenticide), hypoprothrombinemia has occurred without symptoms of
      poisoning.  Hemorrhage appears only when extraordinary amounts have
      been absorbed.  In reported cases, the anticoagulants were either taken
      deliberately, were absorbed over long periods out of neglect of
      elementary hygienic standards, or were ingested by starving indigents
      who used quantities of rodent bait as food.
           Victims of large doses exhibit HEMATURIA, NOSEBLEED, HEMATOMATA,
      BLEEDING GUMS, and MELENA, ABDOMINAL PAIN and BACK PAIN probably
      reflect hemorrhage in the abdominal and retroperitoneal tissues.
      WEAKNESS occurs as a result of ANEMIA.  RENAL COLIC often complicates
      severe hematuria.  Nasal and gastrointestinal hemorrhages have
      occasionally caused death from exsanguination (25).
      NOTES TO PHYSICIAN:
           Coumarins, indandiones, and other anticoagulants
      1.   If only a few grains of anticoagulant bait have been ingested by
           an adult or child having no antecedent liver or blood clotting
           disease, treatment is probably unnecessary.
           A.  If there is uncertainty about the amount of bait ingested or
               the general health of the patient, PHYTONADIONE (vitamin K1,
               Mephyton) given orally protects against the anticoagulant
               effect of these rodenticides.  For adults, give 15-25 mg; for
               children under 12, give 5-10 mg.  Alternatively, a colloidal
               solution of phytonadione, Aquamephyton, may be given
               intramuscularly.  For adults, give 5-10 mg; for children under
               12, give 1-5 mg.
               CAUTION:   PHYTONADIONE, specifically, is required.  Neither
                          vitamin K3 (menadione, Hykinone) nor vitamin K4
                          (menadiol) is an antidote for these anticoagulants.
           B.  Whatever the dosage, insure that patients (especially
               children) will be CAREFULLY OBSERVED for 4-5 days after
               ingestion.  The indandiones and the more recently introduced
               anticoagulants have toxic effects apart from anticoagulation
               that are not yet well defined.
      2.   If LARGE AMOUNTS of anticoagulant were ingested in the preceding
           2-3 hours, INDUCE VOMITING with SYRUP OF IPECAC, followed by 1-2
           glasses of water.  For adults, give 30 ml; for children under 12,
           15 ml.  Following emesis, give 30-50 gm ACTIVATED CHARCOAL in 4-6
           ounces of water to limit absorption of anticoagulant remaining in
           the gut.
      3.   If anticoagulant has been ingested any time in the preceding 15
           days, determination of PROTHROMBIN TIME provides a basis for
           judging the severity of poisoning.
           A.  If the prothrombin time is lengthened, give Aquamephyton,
               intramuscularly:  adult dose, 5-10 mg; child's dose:  1-5 mg.
               Decide dose according to the degree of prothrombin time
               lengthening and, in children, the age and weight of the child.
           B.  Repeat prothrombin time in 24 hours.  If it has not decreased
               from the original value, repeat Aquamephyton dosage.
      4.   If victim shows SYMPTOMS or SIGNS of ANTICOAGULANT POISONING
           (bleeding) in addition to hypoprothrombinemia, administer
           Aquamephyton intramuscularly, up to 25 mg in the adult, and up to
           0.6 mg/kg in children under 12 years.  Phytonadione administration
           may be repeated in 24 hours if bleeding continues.
           A.  In cases of SEVERE BLEEDING, it may be necessary to give
               Aquamephyton intravenously.  This is especially true if the
               bleeding tendency is so severe that intramuscular injection is
               likely to cause hematoma formation.  Dosage is up to 25 mg in
               the adult, up to 0.6 mg/kg in children under 12 years.  Repeat
               this dose in 24 hours if bleeding continues.  Inject at rates
               not exceeding 5% of the total dose per minute.  INTRAVENOUS
               INFUSION of the Aquamephyton DILUTED IN SALINE OR GLUCOSE
               SOLUTION is recommended.  Bleeding is usually controlled in
               3-6 hours.
               CAUTION:   Adverse reactions, some fatal, have occurred from
                          INTRAVENOUS phytonadione injections, even when
                          recommended dosage limits and injection rates were
                          observed.  For this reason, the INTRAVENOUS route
                          should be used ONLY IN cases of SEVERE POISONING.
                          Flushing, dizziness, hypotension, dyspnea, and
                          cyanosis have characterized adverse reactions.
           B.  Antidotal therapy IN cases of SEVERE BLEEDING should be
               supplemented with TRANSFUSIONS of FRESH BLOOD or FRESH FROZEN
               PLASMA.  Use of fresh blood or plasma represents the most
               rapidly effective method of stopping hemorrhage due to these
               anticoagulants.
           C.  Determine PROTHROMBIN TIMES (and hemoglobin concentrations, if
               appropriate) every 6-12 hours to assess effectiveness of
               antihemorrhagic measures.
           D.  When normal blood coagulation is restored, it may be advisable
               to drain large hematomata.
           E.  Ferrous sulfate therapy may be appropriate in the recuperative
               period to rebuild lost erythrocyte mass (25).
                        VI.  FIRE AND EXPLOSION INFORMATION
           To be developed.
                                VII.  COMPATIBILITY
           To be developed.
                             VIII.  PROTECTIVE MEASURES
      STORAGE AND HANDLING:  Keep away from children, domestic animals and
      wildlife.  Wash hands after handling bait.  Avoid all contact by
      mouth.  Do not allow to contaminate food, feed or water supplies.
      After treatment, remove and bury uneaten bait and rodent bodies.  Keep
      container closed to maintain freshness of bait.  Do not reuse empty
      container (56).
           Finished bait is stable 2 years at ambient temperatures in sealed
      packages (20e).
                        IX.  PROCEDURES FOR SPILLS AND LEAKS
                      IN CASE OF EMERGENCY, CALL, DAY OR NIGHT
                                   (800) 424-9300
                       PESTICIDE TEAM SAFETY NETWORK/CHEMTREC
                               X.  LITERATURE CITED
       8c. Thomson, W.T.  1980.  Agricultural chemicals - book III:
               fumigants, growth regulators, repellents, and rodenticides.
               1981 revised ed.  Thomson Publications, Fresno, CA.  182 pp.
      20e. ICI Americas, Inc., Agricultural Chemicals Division.  1983.
               Technical information:  Havoc rodenticide.  Wilmington,
               DE.
      25.  Morgan, D.P.  1982.  Recognition and management of pesticide
               poisonings, 3rd ed.  U.S. Environmental Protection Agency,

               Washington, DC.  120 pp.
      56.  Farm Chemicals Handbook, 70th ed.  1984.  R. T. Meister, G. L.
               Berg, C. Sine, S. Meister, and J. Poplyk, eds.  Meister
               Publishing Co., Willoughby, OH.
      62.  The Pesticide Manual:  A World Compendium, 7th ed.  1983.  C.R.
               Worthing, ed.  The British Crop Protection Council, Croydon,
               England.  695 pp.
      1/18/85