Human Health Effects:
Human Toxicity Excerpts:
EGGS LAID BY LEGHORN CHICKENS DURING A FEEDING PERIOD OF BRODIFACOUM (0.005%) CONTAINED
NO TOXIC RESIDUES REPRESENTING A RISK TO CONSUMERS.
A 31 year old mentally disturbed woman ingested over a 2 day period approximately
thirty 50 gm packages of Talon (approximately 75 mg of brodifacoum). Two days later she
was brought to the hospital's psychiatric unit, without any physical signs or symptoms.
The routine laboratory tests showed a prothrombin time of 72 sec (control, 12 sec) and an
activated partial thromboplastin time greater than 100 sec (normal, 25-35 sec). ... Large
amounts of vitamin K1 and repeated infusion of fresh frozen plasma, the depression of the
prothrombin complex activity persisted for more than 45 days after ingestion.
A 17 year old boy who attempted suicide by ingesting approximately 7.5 mg (0.12 mg/kg)
brodifacoum. He was first seen for a gross hematuria, rapidly followed by epistaxis and
gum bleeding. The prothrombin time and the activated partial thromboplastin time were
considerably prolonged. The levels of plasma clotting factors II, VII, IX, and X were
decreased. Factor V was normal. Vitamin K1 and plasma therapy were instituted and had to
be continued for 55 days until the patient's coagulation remained normal and stable.
Acute clinical effects depend on the site of hemorrhage & include hemoptysis,
hematuria, gastrointestinal bleeding, abdominal or back pain (retroperitoneal hemorrhage),
hemarthrosis, epistaxis, cerebrovascular accidents, & multiple ecchymotic lesions.
/Anticoagulant rodenticides/
The usual mode of death is gastrointestinal hemorrhage. /Anticoagulant rodenticides/
A 36 mo old child had spontaneous hemorrhage from her nose, mouth and urinary tract and
a fall in hemoglobin of 20 gm/L (2 gm/dl). The prothrombin time and partial thromboplastin
time were markedly prolonged with a decrease in the vitamin K-dependent factors. The child
had ingested brodifacoum, a long acting rodenticide. Prolonged follow up and treatment
with vitamin K were necessary.
Medical Surveillance:
A complete history and physical examination: The purpose is to detect preexisting
conditions that might place the exposed employee at increased risk, and to establish a
baseline for future health monitoring. Persons with a history of blood disorders with
bleeding tendencies would be expected to be at increased risk from exposure. Examination
of the blood should be stressed. /Warfarin/
Emergency Medical Treatment:
Emergency Medical Treatment:
| EMT Copyright Disclaimer: |
| Portions of the POISINDEX(R) database are provided here for general
reference. THE COMPLETE POISINDEX(R) DATABASE, AVAILABLE FROM MICROMEDEX, SHOULD BE
CONSULTED FOR ASSISTANCE IN THE DIAGNOSIS OR TREATMENT OF SPECIFIC CASES. Copyright
1974-1998 Micromedex, Inc. Denver, Colorado. All Rights Reserved. Any duplication,
replication or redistribution of all or part of the POISINDEX(R) database is a violation
of Micromedex' copyrights and is strictly prohibited. The following Overview, *** ANTICOAGULANTS-LONG ACTING ***, is relevant for this HSDB record chemical. |
| Life Support: |
o This overview assumes that basic life support measures
have been instituted.
|
| Clinical Effects: |
SUMMARY OF EXPOSURE
0.2.1.1 ACUTE EXPOSURE
o In massive overdose, these agents have produced rapid
and persistent hypoprothrombinemia and associated
bleeding diathesis. Serious poisoning has been
reported in adults with deliberate usually chronic
surreptitious ingestion. Coagulopathy may persist for
6 weeks to many months.
o Children with ingestions of "mouth full" amounts have
occasionally developed mild signs of anticoagulation.
The minimum amount required to depress prothrombin
complex activity in rats was 0.1 mg/kg, equivalent to
1.5 mg in a child weighing 10 kg, or 30 g of 0.005%
bait.
o Cardiopulmonary injury and neurologic toxicity
developed with the indanediones in animals.
HEENT
0.2.4.1 ACUTE EXPOSURE
o Epistaxis and gingival bleeding may be noted.
CARDIOVASCULAR
0.2.5.1 ACUTE EXPOSURE
o Tachycardia and hypotension may develop in patients
with significant blood loss.
RESPIRATORY
0.2.6.1 ACUTE EXPOSURE
o Hemoptysis, hemothorax and diffuse alveolar hemorrhage
have been reported in patients with severe
coagulopathy.
NEUROLOGIC
0.2.7.1 ACUTE EXPOSURE
o Intracranial hemorrhage, headache, loss of
consciousness, seizures, and coma have been reported
after brodifacoum ingestion.
GASTROINTESTINAL
0.2.8.1 ACUTE EXPOSURE
o Spontaneous vomiting may occur after ingestion.
Gastrointestinal bleeding and retroperitoneal hematoma
may develop in patients with coagulopathy.
GENITOURINARY
0.2.10.1 ACUTE EXPOSURE
o Hematuria and excessive vaginal bleeding may develop in
patients with coagulopathy.
HEMATOLOGIC
0.2.13.1 ACUTE EXPOSURE
o Hemorrhage is the most common toxic sign and may be
manifested by epistaxis, gum bleeding, hemoptysis,
hematuria, GI bleeding, ecchymosis, bloody or melenotic
stools, bruising, abdominal and flank pain. Prolonged
prothrombin time may be evident within 24 hours and
maximal in 36 to 72 hours. In overdose PT prolongation
and clinical bleeding have persisted for 45 days to 8
months.
DERMATOLOGIC
0.2.14.1 ACUTE EXPOSURE
o Ecchymoses and hematomas are common in patients with
significant coagulopathy.
MUSCULOSKELETAL
0.2.15.1 ACUTE EXPOSURE
o Rhabdomyolysis is a rare effect.
|
| Laboratory: |
o Obtain an INR or PT 48 hours after exposure in
asymptomatic children with accidental ingestions.
o In adults with deliberate ingestions and children with
clinical evidence of bleeding, obtain and initial INR or
PT and PTT and repeat at 24 and 48 hours postingestion.
o If any significant prolongation or evidence of bleeding is
observed, repeat INR or PT every 6 to 12 hours.
o Factor assays (II, VII, IX, X) may be abnormal in patients
with a normal INR or PT and PTT and may provide earlier
evidence of significant ingestion.
o Follow serial hemoglobin and hematocrit in patients with
clinical evidence of bleeding or significant coagulopathy.
|
| Treatment Overview: |
ORAL EXPOSURE
o Emesis and gastric lavage are not generally recommended.
Gastric decontamination is unnecessary after accidental
"taste" ingestions in children. Lavage may increase
the risk of bleeding after deliberate ingestions in
adults.
o ACTIVATED CHARCOAL: Administer charcoal as slurry (240
mL water/30 g charcoal). Usual dose: 25 to 100 g in
adults/adolescents, 25 to 50 g in children (1 to 12
years), and 1 g/kg in infants less than 1 year old.
o VITAMIN K1 (PHYTONADIONE) - Is a specific antidote and
should be administered to any patient with a prolonged
PT or INR. Menadione (vitamin K3) should NOT be used.
Oral therapy may be indicated in small ingestions or
mild coagulopathy. Administer 15 to 25 mg in adult and
5 to 10 mg in children. Daily maintenance doses of 100
to 125 mg/day may be required for 1.5 to 8 months in
severe cases.
1. IV injection is preferable in severe cases where rapid
correction is required. DOSE: ADULTS 10 mg IV
diluted in saline or glucose at a rate not exceeding
5% of the total dose/min. Subcutaneous injection may
be indicated in patients with less severe coagulopathy
where the risk of hematoma is low, DOSE: ADULT 5 to
10 mg. CHILD 1 to 5 mg.
o There is no specific therapeutic maneuver other than
restoration of PT and factor levels to normal if
toxicity occurs. Administer fresh frozen plasma and/or
factor concentrates in addition to packed red blood
cells and vitamin K in patients with active bleeding.
|
| Range of Toxicity: |
o Slightly prolonged PTs have been observed in children
ingesting mouthful amounts by history. 1 to 2 mg of
brodifacoum have produced clinical coagulopathy in adult
humans.
o BRODIFACOUM - In a retrospective review of 10,733 cases of
single acute unintentional brodifacoum ingestions in
children less than 7 years old, no deaths or major adverse
effects were reported.
|
Antidote and Emergency Treatment:
1. IF AMOUNTS OF BAIT INGESTED WERE ASSUREDLY NO MORE THAN A FEW MOUTHFULS OF COUMARIN-
OR INDANDIONE-TREATED BAIT, OR A FEW GRAINS OF BAIT TREATED WITH THE MORE TOXIC
BRODIFACOUM OR BROMADIOLONE COMPOUNDS, MEDICAL TREATMENT IS PROBABLY UNNECESSARY.
/RODENTICIDES (COUMARINS AND INDANDIONES)/
1A. IF THERE IS UNCERTAINTY ABOUT THE AMOUNT OF BAIT INGESTED OR THE GENERAL HEALTH OF
THE PATIENT, PHYTONADIONE (VITAMIN K1) GIVEN ORALLY PROTECTS AGAINST THE ANTICOAGULANT
EFFECT OF THESE RODENTICIDES WITH ESSENTIALLY NO RISK TO THE PATIENT. DOSAGE OF
PHYTONADIONE: ADULTS AND CHILDREN OVER 12 YEARS: 15-25 MG. CHILDREN UNDER 12 YEARS: 5-10
MG. ALTERNATIVELY, A COLLOIDAL SOLUTION OF PHYTONADIONE, AQUAMEPHYTON, MAY BE GIVEN
INTRAMUSCULARLY. FOR ADULTS AND CHILDREN OVER 12 YEARS, GIVE 5-10 MG; FOR CHILDREN UNDER
12 YEARS, GIVE 1-5 MG. CAUTION: PHYTONADIONE, SPECIFICALLY, IS REQUIRED. NEITHER VITAMIN
K3 (MENADIONE,HYKINONE) NOR VITAMIN K4 (MENADIOL) IS AN ANTIDOTE FOR THESE ANTICOAGULANTS.
/RODENTICIDES (COUMARINS AND INDANDIONES)/
1B. WHATEVER THE DOSAGE, INSURE THAT PATIENTS (ESPECIALLY CHILDREN) WILL BE CAREFULY
OBSERVED FOR 4-5 DAYS AFTER INGESTION. THE INDANDIONES AND THE MORE RECENTLY INTRODUCED
COUMARINS MAY HAVE OTHER TOXIC EFFECTS. /RODENTICIDES (COUMARINS AND INDANDIONES)/
2. IF LARGE AMOUNTS (1.0-1.5 MG/KG OF BODY WEIGHT) OF ANTICOAGULANT HAVE BEEN INGESTED
WITHIN SEVERAL HOURS PRIOR TO TREATMENT, EMPTY THE STOMACH BY GIVING SYRUP OF IPECAC,
FOLLOWED BY 1-2 GLASSES OF WATER. DOSAGES OF SYRUP OF IPECAC FOR ADULTS AND CHILDREN OVER
12 YEARS: 30 ML; DOSAGE FOR CHILDREN UNDER 12 YEARS: 15 ML. FOLLOWING EMESIS GIVE
ACTIVATED CHARCOAL AND SORBITOL. DOSAGE OF CHARCOAL AS AN AQUEOUS SLURRY: ADULTS AND
CHILDREN OVER 12 YEARS: 50-100 G IN 300-800 ML WATER. CHILDREN UNDER 12 YEARS: 15-30 G IN
100-300 ML WATER. DOSAGE OF SORBITOL (THE PREFERRED AGENT) ADDED TO CHARCOAL SLURRY:
ADULTS AND CHILDREN OVER 12 YEARS: 1.0-2.0 G/KG BODY WEIGH TO A MAXIMUM OF 150 G PER DOSE.
CHILDREN UNDER 12 YEARS: 1.0-1.5 G/KG BODY WEIGHT TO A MAXIMUM OF 50 G PER DOSE.
/RODENTICIDES (COUMARINS AND INDANDIONES)/
3. IF TREATMENT HAS BEEN DELAYED SEVERAL HOURS FOLLOWING INGESTION OMIT INDUCED EMESIS,
BUT GIVE ACTIVATED CHARCOAL AND SORBITOL ORALLY. /RODENTICIDES (COUMARINS AND
INDANDIONES)/
4. 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 SIGNIFICANTLY LENGTHENED, GIVE AQUAMEPHYTON,INTRAMUSCULARLY: DOSAGE
FOR ADULTS AND CHILDREN OVER 12 YEARS: 5-10 MG; DOSAGE FOR CHILDREN UNDER 12 YEARS: 1-5
MG. DECIDE DOSE WITHIN THESE RANGES 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.
/RODENTICIDES (COUMARINS AND INDANDIONES)/
5. IF VICTIM IS BLEEDING AS A RESULT OF ANTICOAGULANT POISONING ADMINISTER AQUAMEPHYTON
INTRAVENOUSLY: UP TO 10 MG IN ADULTS AND CHILDREN OVER 12 YEARS, AND UP TO 5 MG IN
CHILDREN UNDER 12 YEARS. INITIAL DOSAGE SHOULD BE DECIDED CHIEFLY ON THE BASIS OF THE
SEVERITY OF BLEEDING. REPEAT INTRAVENOUS AQUAMEPHYTON 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. /RODENTICIDE (COUMARIN AND INDANDIONES)/
5A. 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, BUT THE EFFECT MAY NOT ENDURE. THEREFORE, THE TRANSFUSIONS SHOULD BE GIVEN
ALONG WITH PHYTONADIONE THERAPY. /RODENTICIDE (COUMARINS AND INDANDIONES)/
5B. DETERMINE PROTHROMBIN TIMES AND HEMOGLOBIN CONCENTRATIONS EVERY 6-12 HOURS TO
ASSESS EFFECTIVENESS OF ANTIHEMORRHAGIC MEASURES. C. WHEN NORMAL BLOOD COAGULATION IS
RESTORED, IT MAY BE ADVISABLE TO DRAIN LARGE HEMATOMATA. D. FERROUS SULFATE MAY BE
APPROPRIATE IN THE RECUPERATIVE PERIOD TO REBUILD LOST ERYTHROCYTE MASS. /RODENTICIDES
(COUMARINS AND INDANDIONES)/
VETERINARY: Injured capillaries cannot be mended, but other measures may save the
animal. Restraint & handling should be minimized. A sedative or tranquilizer may be of
assistance in restraint, calming ... & reducing locomotion, thus decr tissue oxygen
demand. Oxygen may be given, but manual pumping of chest is not advisable. Dyspnea may be
relieved by thoracentesis. Clotting factors should be provided in form of blood
transfusion (20 ml/kg, 1/2 injected quickly). Warfarin should be antagonized with slow iv
injection of vitamin K1. Dogs & cats are given 5 mg/kg. This dose is repeated for 2
more days, using im route. Larger animals are given 0.5 to 1 mg/kg, & oral vitamin K1
should be admin daily for 4-6 days. The vitamin will not evoke a sudden dramatic cure; but
bleeding tendency will gradually abate as clotting factors begin to be synthesized ...
Menadione (vitamin K3) is not as effective as vitamin K1 ... Residual defects such as
lameness or CNS signs from localized hemorrhages may disappear with gradual resorption of
extravasated blood. Liver damage may be compensated by regeneration of hepatic cells.
/Warfarin/
... In a case of an intentional ingestion of brodifacoum, an analysis of the specific
coagulation factor derangements was carried out in an attempt to guide a future treatment
strategy for this type of toxicity. ... This analysis demonstrated a profound decr in
levels of factors II, VII, IX, X, lasting at least 43 days post ingestion. Treatment with
sc vitamin K1 in doses up to 100 mg/kg day was without complication and was effective in
reversing the coagulopathy produced by brodifacoum.
Vitamin C is no substitute for vitamin K but ascorbic acid may be a useful adjunct to K
therapy, as judged by animal studies. At least a dose of 100 mg of ascorbic acid several
times a day can do no harm. /Warfarin/
Animal Toxicity Studies:
Non-Human Toxicity Excerpts:
SINGLE ORAL DOSES OF 0.22-1.60 MG/KG BRODIFACOUM TO COMMON VOLES PRODUCED HEMORRHAGES
(LUNG, SUBMAXILLARY GLANDS, THYMUS) AND VARIOUS CYTOPLASMIC CHANGES IN THE PARENCHYMAL
ORGANS (LIVER, SUBMAXILLARY GLANDS, MYOCARDIUM).
0.005% BRODIFACOUM FED TO LEGHORN CHICKENS FOR 15 DAYS EITHER KILLED THEM OR PRODUCED
SERIOUS SYMPTOMS OF POISONING.
OWLS (BUBO VIRGINIANUS, AEGOLIUS ACADICUS, TYTO ALBA) DIED OF HEMORRHAGING AFTER
FEEDING ON RATS KILLED WITH BRODIFACOUM.
In a 42 day feeding study in rats a concentration of 0.1 ppm did not induce any adverse
effect. ... After being seen to ingest brodifacoum containing bait, a 17 kg cocker spaniel
developed depression and icterus accompanied by accelerated pulse and rapid and labored
respiration. Despite supportive therapy, the dog died the same day. The autopsy confirmed
the icter and showed approximately 1 liter of unclotted blood in the thoracic cavity and
100 ml in the pericardial sac. Numerous hemorrhagic areas were seen in the serous
membranes.
Six weeks after intravenous administration of a single 1 mg/kg dose of brodifacoum to
male New Zealand White rabbits, the prothrombin complex activity was still lower than 30%
of normal (in the early part of the study, subcutaneous injections of vitamin K were given
to prevent lethal hemorrhage). In the same study, it was shown that in the rabbit, the
maximal antagonism of vitamin K1 by warfarin was produced by a dose of 63 mg/kg, whereas a
similar result was obtained with only 1 mg/kg brodifacoum. ... In warfarin resistant and
warfarin sensitive rats, brodifacoum produced the same rate of degradation of prothrombin
complex activity as warfarin and significantly reduced the activity of clotting factors
II, VII, IX, and X without affecting factor V.
SHORT LAB FEEDING TESTS WERE CARRIED OUT WITH ANTICOAGULANTS ON A NUMBER OF EUROPEAN
RODENT SPECIES: CLETHRIONOMYS GLAREOLUS, MICROTUS AGRESTIS, M ARVALIS, APODEMUS
FLAVICOLLIS, A SYLVATICUS, MUS MUSCULUS, RATTUS RATTUS, AND R NORVEGICUS. ONLY 0.005%
BRODIFACOUM GAVE A COMPLETE MORTALITY IN MOST SPECIES AFTER 1 DAY'S FEEDING.
IN LAB TOXICITY TESTS USING INDIVIDUALLY-CAGED RICE FIELD RATS, COMPLETE MORTALITY
OCCURRED WHEN THE RATS WERE FED 0.002 & 0.005% BRODIFACOUM FOR 1 DAY.
BRODIFACOUM AT 0.005%, ALTHOUGH GIVING COMPLETE MORTALITY AFTER ONLY 8 DAYS' CONTINUOUS
FEEDING, WAS MORE TOXIC TO MERIONES SHAWI /SHAWS GERBIL/ THAN WARFARIN (0.025%),
COUMATETRALYL (0.0375%), DIFENACOUM (0.005%) AND
BROMADIOLONE (0.005%).
DOMESTICATED NEW ZEALAND WHITE RABBITS WERE FED BRODIFACOUM ON CARROT BAITS. IN THE
FIRST TRIAL, A DOSE OF APPROX 6 MG/KG CAUSED 100% MORTALITY & A DOSE OF APPROX 0.5
MG/KG GAVE 62% MORTALITY. TOXIN STRENGTH ON THE BAITS WAS 0.018% AND 0.002%, RESPECTIVELY.
IN THE SECOND TRIAL, CONSUMPTION OF APPROX 2.5 MG/KG GAVE 100% MORTALITY AND AT APPROX
1.25 MG/KG MORTALITY WAS 87%. THE TOXICANT CONCN USED WERE 0.01% AND 0.005%, RESPECTIVELY.
Repeated doses of these anticoagulant rodenticides interfere with production of
prothrombin in the liver and hence the clotting time of the blood is prolonged. The
capillaries are also damaged. The stresses of normal life are then sufficient to produce
fatal hemorrhage following very slight trauma to capillaries and small blood vessels.
Although single doses do not normally exert a lethal action, if very large they can cause
rapid vasodilatation and a consequent fall in blood pressure, and this vascular collapse
may prove fatal. /Warfarin and related anticoagulants/
The efficacy of three anticoagulant rodenticides was tested in a desert scrub grassland
in India. Brodifacoum, chlorophacinone, and coumatetralyl treated pearl millet grains were
placed for ten consecutive days in bait stations in 18 plots. Results indicated that
brodifacoum is significantly more effective than the other two anticoagulants.
The clinical signs and laboratory changes of brodifacoum (BDF) intoxicated dogs and
their response to vitamin Kl treatment were examined. Brodifacoum ... was fed to four dogs
for 3 consecutive days producing a cumulative dose of 1.1 mg BDF/kg body weight. Monitored
laboratory parameters included: one stage prothrombin time (OSPT), activated partial
thromboplastin time (APTT), and activated coagulation time (ACT). ... Inappetence and
hemorrhagic tendencies were exhibited by day 5 postrodenticide exposure. One stage
prothrombin time, APTT and ACT were 25% greater than time zero values at 24, 24 and 72
hours postdosing, respectively. All laboratory parameters returned to normal within 48
hours of initiating vitamin Kl therapy (0.83 mg/kg orally TID for 5 days). Serum
brodifacoum concentrations were highest (1065-1215 ng/nL) during the 3 days after BDF
dosing and were detectable (3.0-7.5 ng/nL) until day 24 postexposure. A mean BDF
elimination half-life of 6 +/- 4 days was observed.
Six horses gavaged with a commercial brodifacoum at a dosage of 0.125 mg of BDF/kg of
body weight showed weight loss severe hypocoagulability and hemogram alterations. Four of
the horses became depressed and anorectic; one required vitamin K1 therapy. Increases in
clotting times were observed at 24 hr in the partial thromboplastin time (PTT) followed by
the thrombotest (TBT) and one stage prothrombin time (PT) at 48 hr. Elevated mean PTT, PT
and TBT were observed from days 4 to 8 (p< 0.051) with levels returning to pretreatment
levels by day 12. Maximum prolongation was a fourfold increase in PTT (day 4) a 2.5-fold
increase in TBT (day 6) and a twofold increase in PT (day 6). Thrombin clotting times
remained unchanged. In two horses prolongation in clotting time did not normalize until
day 23. The mean hematocrit (0.38 +/- 0.01 l/l) was decreased (p< 0.051 from day 8
(0.33 +/- 0.02 l/l) to day 14 (0.33 +/- 0.01 l/l). The hemoglobin concentration and
erythrocyte numbers were decreased (p< 0.051 from day 6 (20.1%, 17.6% respectively), to
day 14 (22%, 20% respectively). Platelet counts decreased on day 6 (17.2%) to nine
(14.6%). No other significant changes were observed in routine hematological and serum
biochemical parameters. ...
This study reports the comparative toxicities of three anticoagulants to Rattus rattus
rufescens in Pakistan. ... A nochoice, 4 day feeding test with small groups of rodents was
used. ... A value for the 4 day LC50 and LC95 can be statistically estimated from
mortality data using probit analysis. The 4-day approx lethal dose (ALD50 and ALD95) also
can be derived. Brodifacoum proved the most toxic followed by bromadiolone and
coumatetralyl giving 4 day LC50 s of 1.8, 2.1 and 19.6 ppm respectively and 4 day LC95's
of 8.4, 10.1 and 126.4 ppm respectively.
Non-Human Toxicity Values:
LD50 Rabbits oral 0.3 mg/kg
LD50 Mice oral 0.4 mg/kg
LD50 Guinea pigs oral 2.8 mg/kg
LD50 Cat oral about 25 mg/kg
LD50 Dog oral 0.25-1.0 mg/kg
LD50 Dog (under 2 yr old) oral 1.09 mg/kg
LD50 Dog (mixed ages) oral 3.56 mg/kg
Ecotoxicity Values:
LD50 HAMSTERS ORAL 0.33 MG/KG
LD50 VOLES ORAL 0.22 MG/KG
LD50 HARES ORAL 0.15 MG/KG
LD50 PHEASANTS ORAL 0.33 MG/KG
Metabolism/Pharmacokinetics:
Absorption, Distribution & Excretion:
Brodifacoum is absorbed through the gastrointestinal tract. When orally administered to
male Sprague-Dawley rats at doses ranging from 0.1 to 0.33 mg/kg , brodifacoum exhibited a
remarkably steep dose response curve; 0.1 mg/kg failed to show an effect on the plasma
prothrombin level within 24 hr, whereas 0.2 mg/kg reduced the prothrombin complex activity
to 7% of normal values and 0.33 mg/kg reduced it to 4% of normal. Concentrations in the
liver were rapidly established and remained relatively constant for at least 96 hr.
Six horses gavaged with a commercial brodifacoum at a dosage of 0.125 mg of BDF/kg of
body weight. ... Peak plasma concentrations of bromdifacoum occurred 2 to 3 hr after oral
amin; two horses had detectable levels of bromdifacoum at nine days. Pharmacokinetic
evaluation indicated that bromdifacoum has a half-life of 1.22 +/- 0.22 days, a body
clearance of 1073.1 +/- 53.21 ml/kg/day, a volume of distribution of 1853.7 +/- 26.41
ng/day/ml and closely approximates a one compartment model in the elimination phase.
Maximum plasma bromdifacoum concentrations and the highest area under the plasma drug
concentration time curve were found ln horses with the most severe clinical signs. ...
Biological Half-Life:
IN WARFARIN-SENSITIVE RATS DOSED ORALLY WITH 0.2 MG/KG BRODIFACOUM AND SACRIFICED AT
VARIOUS TIMES UP TO 120 HR AFTER DOSING, BRODIFACOUM DISAPPEARED SLOWLY FROM SERUM WITH A
HALF-LIFE OF 156 HR. DISAPPEARANCE FROM THE SMALL INTESTINE WAS RAPID, FOR 24 HR, BUT
INTESTINAL LEVELS BEGAN INCR FROM 24 TO 72 HR AFTER THE DOSE. CONCN IN LIVER WERE RAPIDLY
ESTABLISHED, AND EXCEEDED SERUM CONCN BY 20-FOLD. BRODIFACOUM LEVELS IN LIVER REMAINED
RELATIVELY CONSTANT FOR 96 HR.
... Brodifacoum ... was fed to four dogs for 3 consecutive days producing a cumulative
dose of 1.1 mg BDF/kg body weight. ... A mean BDF elimination half-life of 6 +/- 4 days
was observed.
Mechanism of Action:
BRODIFACOUM (1 MG/KG, SC) INHIBITED CLOTTING FACTOR FORMATION IN RABBITS. IT INCR THE
PLASMA RATIO OF (3)H-LABELED VITAMIN K1 EPOXIDE/VITAMIN K1. THE RATE OF DISAPPEARANCE OF
(3)H-VITAMIN K1 FROM PLASMA WAS NOT CHANGED. BRODIFACOUM ACTS BY INHIBITING VITAMIN K1
EPOXIDE REDUCTASE.
WARFARIN-SENSITIVE RATS WERE ADMIN DOSES OF BRODIFACOUM RANGING FROM 0.1 TO 0.33 MG/KG.
PHENOBARBITAL PRETREATMENT DECR THE ANTICOAGULANT EFFECT, WHEREAS SKF525A INCR IT,
SUGGESTING THAT A SUBSTANTIAL PORTION OF BRODIFACOUM-INDUCED HYPOPROTHROMBINEMIA IS
MEDIATED BY BRODIFACOUM ITSELF RATHER THAN BY METABOLITES.
These compounds depress the hepatic synthesis of vitamin K1-dependent clotting factors
(II, VII, IX, X) by inhibiting the vitamin K1 2,3-reductase enzyme in the vitamin
K1-epoxide cycle. /Anticoagulant rodenticides/
THE EFFECTS OF COUMARINS & INDANDIONES ON PROTHROMBIN SYNTHESIS & CONVERSION OF
VITAMIN K1 2,3-EPOXIDE TO VITAMIN K1 WERE MEASURED. RESULTS PROVIDED EVIDENCE FOR THE
PROPOSED MECHANISM OF ACTION BY PREVENTING REGENERATION OF VITAMIN K1 FROM ITS METABOLITE.
/COUMARINS AND INDANDIONES/
... DERIVATIVES OF COUMARIN ... BLOCK HEPATIC SYNTHESIS OF PROTHROMBIN AT THE EXPENSE
OF VITAMIN K. SOME ... ALSO INTERFERE WITH SYNTHESIS OF PROCONVERTIN AND OF FACTORS IX AND
X WITHOUT CHANGING PROACCELERIN. /COUMARIN DERIVATIVES/
Interactions:
The relationship between pharmacological response and disposition of a dose of vitamin
K1 (10 mg/kg iv) in normal rabbits and in rabbits treated with the coumarin anticoagulant
brodifacoum has been studied. After iv admin of vitamin K1, plasma concentrations of the
vitamin declined in a tri-exponential fashion. There were no differences between the two
groups over the first 24 hr of the experiment. However between 24 hr and the end of the
study plasma concentrations of vitamin K1 ln the presence of brodifacoum were
significantly below those of vehicle treated rabbits. ... Three hours after admin of
vitamin K1 the concentratlons of the vitamin in whole liver were 46.6 +/- 4.3 ug/g in the
presence of brodifacoum, and 32.8 +/- 6.4 ug/g in the absence of brodifacoum; and were
significantly greater than normal (1127.7 +/- 44.3 ng/g). Likewise microsomal
concentrations of vitamin K1 (4.00 +/- 2.38 ug/mg protein and 2.65 +/- 1.01 ug/ng protein
in the presence and absence of brodifacoum, respectively) were significantly ... greater
than normal (16.0 +/- 3.5 ng/mg) protein).
Pharmacology:
Interactions:
The relationship between pharmacological response and disposition of a dose of vitamin
K1 (10 mg/kg iv) in normal rabbits and in rabbits treated with the coumarin anticoagulant
brodifacoum has been studied. After iv admin of vitamin K1, plasma concentrations of the
vitamin declined in a tri-exponential fashion. There were no differences between the two
groups over the first 24 hr of the experiment. However between 24 hr and the end of the
study plasma concentrations of vitamin K1 ln the presence of brodifacoum were
significantly below those of vehicle treated rabbits. ... Three hours after admin of
vitamin K1 the concentratlons of the vitamin in whole liver were 46.6 +/- 4.3 ug/g in the
presence of brodifacoum, and 32.8 +/- 6.4 ug/g in the absence of brodifacoum; and were
significantly greater than normal (1127.7 +/- 44.3 ng/g). Likewise microsomal
concentrations of vitamin K1 (4.00 +/- 2.38 ug/mg protein and 2.65 +/- 1.01 ug/ng protein
in the presence and absence of brodifacoum, respectively) were significantly ... greater
than normal (16.0 +/- 3.5 ng/mg) protein).
Environmental Fate & Exposure:
Environmental Standards & Regulations:
FIFRA Requirements:
As the federal pesticide law FIFRA directs, EPA is conducting a comprehensive review of
older pesticides to consider their health and environmental effects and make decisions
about their future use. Under this pesticide reregistration program, EPA examines health
and safety data for pesticide active ingredients initially registered before November 1,
1984, and determines whether they are eligible for reregistration. In addition, all
pesticides must meet the new safety standard of the Food Quality Protection Act of 1996.
Pesticides for which EPA had not issued Registration Standards prior to the effective date
of FIFRA, as amended in 1988, were divided into three lists based upon their potential for
human exposure and other factors, with List B containing pesticides of greater concern and
List D pesticides of less concern. Brodifacoum is found on List B. Case No: 2755;
Pesticide type: Insecticide, Rodenticide; Case Status: RED Approved 09/97; OPP has made a
decision that some/all uses of the pesticide are eligible for reregistration, as reflected
in a Reregistration Eligibility Decision (RED) document.; Active ingredient (AI):
3-(3-(4'Bromo-(1,1'-biphenyl)-4-yl)-1,2,3-tetrahydro -1-napthalenyl) -4-hydroxycoumarin;
Data Call-in (DCI) Date(s): 06/07/91; AI Status: OPP has completed a Reregistration
Eligibility Decision (RED) document for the case/AI.
Chemical/Physical Properties:
Molecular Formula:
C31-H23-BR-O3
Molecular Weight:
523.44
Color/Form:
OFF-WHITE TO FAWN POWDER
Odor:
Odorless
Melting Point:
228-230 DEG C
Solubilities:
INSOL IN WATER; SLIGHTLY SOL IN ALC, BENZENE; SOL IN ACETONE, CHLOROFORM
MODERATELY SOL IN ETHYL ACETATE
INSOL IN PETROLEUM ETHER
Solubility in water <10 mg/l at 20 degC, pH 7.
Acetone 6-20 g/l; chloroform 3 g/l.
Vapor Pressure:
less than 1.33x10-7 kPa (1x10-6 mm Hg) at 25 deg C.
Other Chemical/Physical Properties:
FORMS AMINE SALTS OF LIMITED SOLUBILITY IN WATER
...weak acid which does not readily form water-soluble salts
No loss in 30 days in direct sunlight
Chemical Safety & Handling:
DOT Emergency Guidelines:
Health: Toxic; may be fatal if inhaled, ingested or absorbed through skin. Inhalation
or contact with some of these materials will irritate or burn skin and eyes. Fire will
produce irritating, corrosive and/or toxic gases. Vapors may cause dizziness or
suffocation. Runoff from fire control or dilution water may cause pollution. /Coumarin
derivative pesticide, liquid, flammable, poisonous; Coumarin derivative pesticide, liquid,
flammable, toxic; Coumarin derivative pesticide, liquid, poisonous flammable; Coumarin
derivative pesticide, liquid, toxic, flammable/
Fire or explosion: Highly flammable: Will be easily ignited by heat, sparks or flames.
Vapors may form explosive mixtures with air. Vapors may travel to source of ignition and
flash back. Most vapors are heavier than air. They will spread along ground and collect in
low or confined areas (sewers, basements, tanks). Vapor explosion and poison hazard
indoors, outdoors or in sewers. Some may polymerize (P) explosively when heated or
involved in a fire. Runoff to sewer may create fire or explosion hazard. Containers may
explode when heated. Many liquids are lighter than water. /Coumarin derivative pesticide,
liquid, flammable, poisonous; Coumarin derivative pesticide, liquid, flammable, toxic;
Coumarin derivative pesticide, liquid, poisonous flammable; Coumarin derivative pesticide,
liquid, toxic, flammable/
Public safety: Call Emergency Response Telephone Number on Shipping Paper first. If
Shipping Paper not available or no answer, refer to appropriate telephone number listed on
the inside back cover. Isolate spill or leak area immediately for at least 100 to 200
meters (330 to 660 feet) in all directions. Keep unauthorized personnel away. Stay upwind.
Keep out of low areas. Ventilate closed spaces before entering. /Coumarin derivative
pesticide, liquid, flammable, poisonous; Coumarin derivative pesticide, liquid, flammable,
toxic; Coumarin derivative pesticide, liquid, poisonous flammable; Coumarin derivative
pesticide, liquid, toxic, flammable/
Protective clothing: Wear positive pressure self-contained breathing apparatus (SCBA).
Wear chemical protective clothing which is specifically recommended by the manufacturer.
It may provide little or no thermal protection. Structural firefighters' protective
clothing is recommended for fire situations only; it is not effective in spill situations.
/Coumarin derivative pesticide, liquid, flammable, poisonous; Coumarin derivative
pesticide, liquid, flammable, toxic; Coumarin derivative pesticide, liquid, poisonous
flammable; Coumarin derivative pesticide, liquid, toxic, flammable/
Evacuation: Spill: See the Table of Initial Isolation and Protective Action Distances
for highlighted substances. For non-highlighted substances, increase, in the downwind
direction, as necessary, the isolation distance shown under "Public safety".
Fire: If tank, rail car or tank truck is involved in a fire, isolate for 800 meters (1/2
mile) in all directions; also, consider initial evacuation for 800 meters (1/2 mile) in
all directions. /Coumarin derivative pesticide, liquid, flammable, poisonous; Coumarin
derivative pesticide, liquid, flammable, toxic; Coumarin derivative pesticide, liquid,
poisonous flammable; Coumarin derivative pesticide, liquid, toxic, flammable/
Fire: CAUTION: All these products have a very low flash point. Use of water spray when
fighting fire may be inefficient. Small fires: Dry chemical, CO2, water spray or
alcohol-resistant foam. Large fires: Water spray, fog or alcohol-resistant foam. Move
containers from fire area if you can do it without risk. Dike fire control water for later
disposal; do not scatter the material. Do not use straight streams. Fire involving tanks
or car/trailer loads: Fight fire from maximum distance or use unmanned hose holders or
monitor nozzles. Cool containers with flooding quantities of water until well after fire
is out. Withdraw immediately in case of rising sound from venting safety devices or
discoloration of tank. ALWAYS stay away from the ends of tanks. For massive fire use
unmanned hose holders or monitor nozzles; if this is impossible, withdraw from area and
let fire burn. /Coumarin derivative pesticide, liquid, flammable, poisonous; Coumarin
derivative pesticide, liquid, flammable, toxic; Coumarin derivative pesticide, liquid,
poisonous flammable; Coumarin derivative pesticide, liquid, toxic, flammable/
Spill or leak: Fully encapsulating, vapor protective clothing should be worn for spills
and leaks with no fire. ELIMINATE all ignition sources (no smoking, flares, sparks or
flames in immediate area). All equipment used when handling the product must be grounded.
Do not touch or walk through spilled material. Stop leak if you can do it without risk.
Prevent entry into waterways, sewers, basements or confined areas. A vapor suppressing
foam may be used to reduce vapors. Small spills: Absorb with earth, sand or other
non-combustible material and transfer to containers for later disposal. Use clean
non-sparking tools to collect absorbed material. Large spills: Dike far ahead of liquid
spill for later disposal. Water spray may reduce vapor; but may not prevent ignition in
closed spaces. /Coumarin derivative pesticide, liquid, flammable, poisonous; Coumarin
derivative pesticide, liquid, flammable, toxic; Coumarin derivative pesticide, liquid,
poisonous flammable; Coumarin derivative pesticide, liquid, toxic, flammable/
First aid: Move victim to fresh air. Call emergency medical care. Apply artificial
respiration if victim is not breathing. Do not use mouth-to-mouth method if victim
ingested or inhaled the substance; induce artificial respiration with the aid of a pocket
mask equipped with a one-way valve or other proper respiratory medical device. Administer
oxygen if breathing is difficult. Remove and isolate contaminated clothing and shoes. In
case of contact with substance, immediately flush skin or eyes with running water for at
least 20 minutes. Wash skin with soap and water. Keep victim warm and quiet. Effects of
exposure (inhalation, ingestion or skin contact) to substance may be delayed. Ensure that
medical personnel are aware of the material(s) involved, and take precautions to protect
themselves. /Coumarin derivative pesticide, liquid, flammable, poisonous; Coumarin
derivative pesticide, liquid, flammable, toxic; Coumarin derivative pesticide, liquid,
poisonous flammable; Coumarin derivative pesticide, liquid, toxic, flammable/
Health: Highly toxic, may be fatal if inhaled, swallowed or absorbed through skin.
Avoid any skin contact. Effects of contact or inhalation may be delayed. Fire may produce
irritating, corrosive and/or toxic gases. Runoff from fire control or dilution water may
be corrosive and/or toxic and cause pollution. /Coumarin derivative pesticide, liquid,
poisonous; Coumarin derivative pesticide, liquid, toxic; Coumarin derivative pesticide,
solid, poisonous; Coumarin derivative pesticide, solid, toxic/
Fire or explosion: Non-combustible, substance itself does not burn but may decompose
upon heating to produce corrosive and/or toxic fumes. Containers may explode when heated.
Runoff may pollute waterways. /Coumarin derivative pesticide, liquid, poisonous; Coumarin
derivative pesticide, liquid, toxic; Coumarin derivative pesticide, solid, poisonous;
Coumarin derivative pesticide, solid, toxic/
Public safety: CALL Emergency Response Telephone Number on Shipping Paper. If Shipping
Paper not available or no answer, refer to appropriate telephone number listed on the
inside back cover. Isolate spill or leak area immediately for at least 25 to 50 meters (80
to 160 feet) in all directions. Keep unauthorized personnel away. Stay upwind. Keep out of
low areas. /Coumarin derivative pesticide, liquid, poisonous; Coumarin derivative
pesticide, liquid, toxic; Coumarin derivative pesticide, solid, poisonous; Coumarin
derivative pesticide, solid, toxic/
Protective clothing: Wear positive pressure self-contained breathing apparatus (SCBA).
Wear chemical protective clothing which is specifically recommended by the manufacturer.
Structural firefighters' protective clothing is recommended for fire situations ONLY; it
is not effective in spill situations. /Coumarin derivative pesticide, liquid, poisonous;
Coumarin derivative pesticide, liquid, toxic; Coumarin derivative pesticide, solid,
poisonous; Coumarin derivative pesticide, solid, toxic/
Evacuation: Spill: See the Table of Initial Isolation and Protective Action Distances
for highlighted substances. For non-highlighted substances, increase, in the downwind
direction, as necessary, the isolation distance shown under "PUBLIC SAFETY".
Fire: If tank, rail car or tank truck is involved in a fire, ISOLATE for 800 meters (1/2
mile) in all directions; also, consider initial evacuation for 800 meters (1/2 mile) in
all directions. /Coumarin derivative pesticide, liquid, poisonous; Coumarin derivative
pesticide, liquid, toxic; Coumarin derivative pesticide, solid, poisonous; Coumarin
derivative pesticide, solid, toxic/
Fire: Small fires: Dry chemical, CO2 or water spray. Large fires: Water spray, fog or
regular foam. Move containers from fire area if you can do it without risk. Dike fire
control water for later disposal; do not scatter the material. Do not use straight
streams. Fire involving tanks or car/trailer loads: Fight fire from maximum distance or
use unmanned hose holders or monitor nozzles. Do not get water inside containers. Cool
containers with flooding quantities of water until well after fire is out. Withdraw
immediately in case of rising sound from venting safety devices or discoloration of tank.
ALWAYS stay away from the ends of tanks. For massive fire, use unmanned hose holders or
monitor nozzles; if this is impossible withdraw from area and let fire burn. /Coumarin
derivative pesticide, liquid, poisonous; Coumarin derivative pesticide, liquid, toxic;
Coumarin derivative pesticide, solid, poisonous; Coumarin derivative pesticide, solid,
toxic/
Spill or leak: Do not touch damaged containers or spilled material unless wearing
appropriate protective clothing. Stop leak if you can do it without risk. Prevent entry
into waterways, sewers, basements or confined areas. Cover with plastic sheet to prevent
spreading. Absorb or cover with dry earth, sand or other non-combustible material and
transfer to containers. DO NOT GET WATER INSIDE CONTAINERS. /Coumarin derivative
pesticide, liquid, poisonous; Coumarin derivative pesticide, liquid, toxic; Coumarin
derivative pesticide, solid, poisonous; Coumarin derivative pesticide, solid, toxic/
First aid: Move victim to fresh air. Call emergency medical care. Apply artificial
respiration if victim is not breathing. Do not use mouth-to-mouth method if victim
ingested or inhaled the substance; induce artificial respiration with the aid of a pocket
mask equipped with a one-way valve or other proper respiratory medical device. Administer
oxygen if breathing is difficult. Remove and isolate contaminated clothing and shoes. In
case of contact with substance, immediately flush skin or eyes with running water for at
least 20 minutes. For minor skin contact, avoid spreading material on unaffected skin.
Keep victim warm and quiet. Effects of exposure (inhalation, ingestion or skin contact) to
substance may be delayed. Ensure that medical personnel are aware of the material(s)
involved, and take precautions to protect themselves. /Coumarin derivative pesticide,
liquid, poisonous; Coumarin derivative pesticide, liquid, toxic; Coumarin derivative
pesticide, solid, poisonous; Coumarin derivative pesticide, solid, toxic/
Protective Equipment & Clothing:
Adequate protective clothing should be worn at all times. In the lab this will consist
of a lab coat, rubber or polyethylene gloves & a /NIOSH approved respirator/ or
respirator of a type applicable to the specific chemical being handled. /Rodenticides/
Preventive Measures:
CARE SHOULD BE TAKEN ... NOT TO CONTAMINATE FOODSTUFFS ... NOT TO LEAVE MATERIAL WITHIN
REACH OF CHILDREN; TO USE PREPARED BAITS RATHER THAN SCATTER POISON; TO COLLECT &
DESTROY DEAD RODENTS; TO BURY BAITS & POWDER WHEN OPERATION IS COMPLETED. /COUMARIN
DERIVATIVES/
Whereever possible, toxic chemicals, concentrates & bait preparations should be
handled in a fume cupboard. When bait mixing has been done in the field, operators should
take care to remain sheltered from the wind. /Rodenticides/
Scrupulous personal hygiene must be adhered to when dealing with poisons. All cuts
& abrasions on the hands & forearms must be covered with waterproof adhesive
dressings before any operations are started. When the work is finished or when a break is
taken in the middle /of the day/, protective clothing should be removed & hands washed
thoroughly with soap & hot water. Contaminated protective clothing must not be taken
into "clean" areas. /Rodenticides/
Smoking, eating & drinking must be strictly prohibited in all rooms in which
poisons are present. /Rodenticides/
In event of accidental poisoning in humans, it is important that proper medical help is
enlisted at once. ... Local hospitals should be notified of the potential dangers that
exist in places where rodenticides are present & be given precise details of the
specific poisons that are used, with revelant information about antidotes, symptoms, etc.
/Rodenticides/
Normal first-aid facilities should be available ... & as many staff as possible
should have proper first-aid training. /Rodenticides/
Stability/Shelf Life:
STABLE AS A SOLID UNDER NORMAL STORAGE CONDITIONS
Shipment Methods and Regulations:
No person may /transport,/ offer or accept a hazardous material for transportation in
commerce unless that person is registered in conformance ... and the hazardous material is
properly classed, described, packaged, marked, labeled, and in condition for shipment as
required or authorized by ... /the hazardous materials regulations (49 CFR 171-177)./
The International Air Transport Association (IATA) Dangerous Goods Regulations are
published by the IATA Dangerous Goods Board pursuant to IATA Resolutions 618 and 619 and
constitute a manual of industry carrier regulations to be followed by all IATA Member
airlines when transporting hazardous materials.
The International Maritime Dangerous Goods Code lays down basic principles for
transporting hazardous chemicals. Detailed recommendations for individual substances and a
number of recommendations for good practice are included in the classes dealing with such
substances. A general index of technical names has also been compiled. This index should
always be consulted when attempting to locate the appropriate procedures to be used when
shipping any substance or article.
Storage Conditions:
KEEP CONTAINER CLOSED TO MAINTAIN FRESHNESS OF BAIT.
Occupational Exposure Standards:
Manufacturing/Use Information:
Major Uses:
Rodenticide
Indirect anticoagulant active against rats and mice including strains resistant to
other anticoagulants and against rodent species, such as hamsters, that are difficult to
control with other anticoagulants.
Manufacturers:
Zeneca Professional Products, 1800 Concord Pike, Wilmington, DE 19897, (800)759-4500
HACCO, Inc., P.O. Box 7190, Randolph, WI (608)221-6200
Methods of Manufacturing:
PRODUCED BY CONDENSING 4-HYDROXYCOUMARIN WITH
3-(4'-BROMOBIPHENYL-4-YL)-1,2,3,4-TETRAHYDRO-1-NAPHTHOL...
General Manufacturing Information:
CURRENTLY REGISTERED IN USA 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.
AFTER TREATMENT, REMOVE AND BURY UNEATEN BAIT AND RODENT BODIES.
PLANTED SEEDS, ESP MAIZE AND SUGAR BEET, WERE PROTECTED AGAINST RODENT DAMAGE BY
DRESSING THEM WITH BRODIFACOUM PRIOR TO /PLANTING/.
BRODIFACOUM IS AN INDIRECT ANTICOAGULANT ACTIVE AGAINST RATS AND MICE INCL STRAINS
RESISTANT TO OTHER ANTICOAGULANTS, AND AGAINST RODENT SPECIES, SUCH AS HAMSTERS, THAT ARE
DIFFICULT TO CONTROL WITH OTHER ANTICOAGULANTS. ITS POTENCY IS SUCH THAT, UNLIKE OTHER
ANTICOAGULANTS, A RODENT MAY ABSORB A LETHAL DOSE BY TAKING ONLY A 50 MG/KG BAIT AS PART
OF ITS FOOD INTAKE ON ONLY ONE OCCASION. THIS MAKES BRODIFACOUM PARTICULARLY PROMISING FOR
NON-COMMENSAL RODENT CONTROL.
MR HADLER, RS SHADBOLT, GERMAN PATENT 2,424,806 CORRESPONDING TO US PATENT 3,957,824
(1975, 1976 TO WARD, BLENKINSOP & CO); SHADBOLT RS ET AL; J CHEM SOC PERKIN TRANS I:
1190 (1976).
Formulations/Preparations:
Matikus bait (30 mg/kg); Bait (20 or 50 MG ai/kg); 'TALON', Bait (50 mg/kg).
Ready-to-use grain-base bait in pellets, mini pellets, and wax blocks...Bait containing
0.005% Brodifacoum (loose or bait-packs).
Laboratory Methods:
Analytic Laboratory Methods:
A METHOD FOR THE ROUTINE MONITORING OF BRODIFACOUM IN WHEAT-BASED BAITS COMPRISES
EXTRACTION WITH METHANOL, FOLLOWED BY REVERSED-PHASE HIGH-PERFORMANCE LIQUID
CHROMATOGRAPHY. RECOVERY OF BRODIFACOUM WAS 98.8% AFTER 8-HR EXTRACTION FROM BAITS
CONTAINING 5-70 PPM BRODIFACOUM.
ANALYSIS: MACRO: BY REVERSED-PHASE LIQUID CHROMATOGRAPHY. ... A PORTION IS INJECTED
INTO A LIQ CHROMATOGRAPH FITTED WITH A PARTISIL-5 0DS COLUMN AND UV DETECTOR.
AN IMPROVEMENT OF THE HIGH-PERFORMANCE LIQ CHROMATOGRAPHY METHOD OF AJ KIEBOOM & CG
RAMMELL (1981) FOR DETERMINING BRODIFACOUM IN ANIMAL TISSUES PERMITTED A MEAN RECOVERY OF
88% EVEN FROM MUSCLE AND FATTY TISSUE. THE DETECTION LIMIT WAS 0.1 NG/40 MUL INJECTION.
NORMAL PHASE SILICA GEL THIN LAYER CHROMATOGRAPHY WAS USED TO IDENTIFY BRODIFACOUM IN
DIAGNOSTIC TOXICOLOGY.
Residues of warfarin, coumatetralyl, difenacoum,
brodifacoum, bromadiolone, diphacinone, and chlorophacinone in animal tissues were
extracted with CHCl3-MeCO. Extracts were cleaned-up by an integrated gel permeation and
adsorption chromatography procedure which divided the rodenticides into 2 groups. Residues
were then determined and confirmed using normal-phase, ion-pair and weak ion-exchange HPLC
techniques. Ion-pair gradient separation resolved all 7 rodenticides in a single
chromatographic analysis. UV detection methods were employed for all 7 rodenticides. Use
of a diode array detection system permitted additional confirmation of residues down to
0.1 mg/kg by matching UV spectra and derivations of spectra. Sensitive fluorescence
detection was possible for the coumarin-based rodenticides, but not for diphacinone and
chlorophacinone. Post-column pH-switching fluorescence detection methods were superior to
other methods of fluorescence detection of coumarin-based rodenticides. Recoveries from
spiked liver tissue were around 90% at levels from 0.05 to 1 mg/kg. Detection limits of
around 0.002 mg/kg for most rodenticides and of 0.01 mg/kg for warfarin could be achieved
with animal tissue extracts.
Method 983.11. Brodifacoum (Technical) and Pesticide Formulations. Liquid
Chromatographic Method.
Special References:
Synonyms and Identifiers:
Related HSDB Records:
1786 [WARFARIN] (Analog)
Synonyms:
2H-1-BENZOPYRAN-2-ONE,
3-(3-(4'-BROMO(1,1'-BIPHENYL)-4-YL)-1,2,3,4-TETRAHYDRO-1-NAPHTHALENYL)-4- HYDROXY-
**PEER REVIEWED**
BROMFENACOUM
**PEER REVIEWED**
3-[3-(4'-BROMO[1,1'-BIPHENYL]4-YL)-1,2,3,4-TETRAHYDRO-1-NAPHTHALENYL]-4-
HYDROXY-2H-1-BENZOPYRAN-2-ONE
**PEER REVIEWED**
PP-581
**PEER REVIEWED**
RATAK+
**PEER REVIEWED**
TALON
**PEER REVIEWED**
WBA 8119
**PEER REVIEWED**
Formulations/Preparations:
Matikus bait (30 mg/kg); Bait (20 or 50 MG ai/kg); 'TALON', Bait (50 mg/kg).
Ready-to-use grain-base bait in pellets, mini pellets, and wax blocks...Bait containing
0.005% Brodifacoum (loose or bait-packs).
Shipping Name/ Number DOT/UN/NA/IMO:
UN 3024; Coumarin derivative pesticides, liquid, flammable, toxic, NOS, flashpoint less
than 23 deg C
UN 3025; Coumarin derivative pesticides, liquid, toxic, flammable, NOS, flashpoint 23
deg C or more
UN 3026; Coumarin derivative pesticides, liquid, toxic, NOS
UN 3027; Coumarin derivative pesticides, solid, toxic, NOS
IMO 3.0; Coumarin derivative pesticides, liquid, flammable, toxic, NOS, flashpoint less
than 23 deg C
IMO 6.1; Coumarin derivative pesticides, liquid, toxic, NOS; coumarin derivative
pesticides, liquid, toxic, flammable, NOS, flashpoint 23 deg C or more; coumarin
derivative pesticides, solid, toxic, NOS
RTECS Number:
NIOSH/GN4934700
Administrative Information:
Hazardous Substances Databank Number: 3916
Last Revision Date: 20010516
Last Review Date: Reviewed by SRP 11/1/1994
Update History:
Complete Update on 05/16/2001, 1 field added/edited/deleted.
Complete Update on 03/09/2000, 1 field added/edited/deleted.
Complete Update on 02/08/2000, 1 field added/edited/deleted.
Complete Update on 02/02/2000, 1 field added/edited/deleted.
Complete Update on 09/21/1999, 1 field added/edited/deleted.
Complete Update on 08/27/1999, 1 field added/edited/deleted.
Complete Update on 06/02/1998, 1 field added/edited/deleted.
Complete Update on 03/08/1998, 1 field added/edited/deleted.
Complete Update on 10/31/1997, 1 field added/edited/deleted.
Complete Update on 04/23/1997, 2 fields added/edited/deleted.
Complete Update on 01/28/1997, 1 field added/edited/deleted.
Complete Update on 10/18/1996, 1 field added/edited/deleted.
Complete Update on 05/13/1996, 1 field added/edited/deleted.
Complete Update on 03/12/1996
Complete Update on 01/27/1996, 1 field added/edited/deleted.
Complete Update on 06/07/1995, 34 fields added/edited/deleted.
Field Update on 12/28/1994, 1 field added/edited/deleted.
Complete Update on 03/25/1994, 1 field added/edited/deleted.
Field update on 12/31/1992, 1 field added/edited/deleted.
Field update on 03/06/1990, 1 field added/edited/deleted.
Complete Update on 10/03/1986
Record Length: 78983
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