Bromethalin
Bromethalin was developed and released in 1985 to combat
a world-wide problem of rodent resistance to warfarin-like
anticoagulant rodenticides.Bromethalin is not an anticoagulant
but is a highly potent rodenticide that provides a lethal
dose to rodents in a single feeding. Death occurs within 24
to 36 hours after ingestion. It is a pale, odorless, crystalline
solid compound in the diphenylamine family. Its mechanism
of action is to uncouple oxidativephosphorylation in the mitochondria
of the central nervous system. This leads to a decreased production
of ATP. Low levels of ATP inhibit the activity of the Na/K
ATPase and lead to a subsequent buildup of cerebral spinal
fluid and vacuolization of myelin. The increased CSF results
in high intracranial pressure, causing damage to nerve axons,
inhibiting neural transmission and leading to paralysis, convulsions
and death.
The LDso of pure bromethalin for dogs is 4.7 ing/kg body
weight and 1.8 mg/kg for cats. Minimum lethal doses of bait
are 25 g/kg in the dog and 4.5 g/kg in the cat. A typical
package contains 21 grams of 0.01% bromethalin. Thus, a five
kg dog would have to consume five to six packages to reach
toxic levels and a five kg cat would have to consume one to
two packages to reach toxic levels. Signs of a sub-lethal
dose include hind limb ataxia, depression, extensor rigidity,
opisthotonus, lateral recumbency and vomiting. High doses
may bring about severe muscle fasiculations, hind limb hyper-reflexia,
seizures, hyperthennia, depression and death.
There are no antemortem tests available, although through
clinical signs, a history of exposure, irregular electroencephalographic
measurements and cerebral edema (fundic exam) may lead to
an antemortem diagnosis. There is no specific antidote for
bromethalin poisoning. Therefore, prevention of absorption
is of the utmost importance. Treatment is most successful
in dogs and cats when emesis is induced and activated charcoal
with a saline cathartic are given immediately after ingestion.
Treatments with osmotic diuretics and steroids have been utilized
but are not as successful as removal of the toxin from the
gastrointestinal tract.
The gross lesions seen on post-mortem examination are limited
to those caused by cerebral edema which include narrowing
of suici and flattening of gyri. Mild pulmonary congestion
may be seen in some cases. The predominant histological
change is seen in the brain. There is diffuse spongiform degeneration
of the white matter and vacuolization of myelin such as occurs
in the optic nerve. There can be microgliosis of the cerebellum
and cerebrum.
Bromethalin or its metabolitedesmethy-bromethalin can be
detected in liver, fat, kidney, and brain. Samples should
be submitted frozen and kept in the dark (wrap in aluminum
foil). Bromethalintoxicosis must be considered as a potential
differential diagnosis for neurologic Syndromes and may resemble
toxicity from lead, strychnine and organophosphate compounds.
Bromethalintoxicosis must also be differentiated from syndromes
producing seizures, such as epilepsy and paralytic syndromes,
such as trauma, larval migration and neoplasia.
- by Paul Klausen, Class of 1997
- edited by Stephen Hooser, DVM, PhD
References:
Dorman,DC,
Simon,J,Harlin,KA, Buck, WB.Diagnosis of BromethalinToxicosis
in the Dog. Journal of Veterinary Diagnostic Investigation.
1990, 2: 123-128.
Dorman,DC,
Parker,AJ, Buck, WB.BromethalinToxicosis in the Dog.Journal
of the AmericanAnimalHospital
Association. 1990, 26:589-598.
Dorman, DC.
Anticoagulant,Cholecalciferol, and Bromethalin based rodenticides.Veterinary
Clinics of North America, Small Animal
Practice. 1990,20: 339-352.
Dreikom,B.,O'Dorherty, GO. The Discovery and Development
of Bromethalin, an Acute Rodenticide with a Unique Mode of
Action. American Chemical Society. 1984, 45-63.
Jackson, WB. BROMETHALIN-A PROMISING NEW RODENTICIDE.Proceedings
Tenth Vertebrate Pest Conference.
R.E.MarshUniversity
of CaliforniaDavis.
1982,10-14
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