Page 655 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

620 SECTION | VIII Rodenticides

VetBooks.ir of ATP levels by inhibiting energy production in most 30 min and 4 h after exposure. The common symptoms
are vomiting, involuntary hyperextension of the limbs,
cells of the body, leading to a slow and painful death as
convulsions and, finally, cardiac and respiratory failure.
the body “suffocates from within.” Compound 1080
causes damage to tissue of high energy needs, such as Dogs usually show CNS signs such as convulsions and
brain, heart, lungs, and fetus. Accumulated levels of cit- uncontrollable running, whereas sheep and cattle show
rate cause chelation of divalent metal ions, especially predominantly cardiac signs. Dogs appear to be highly
21
Ca . Depletion of these ions in the CNS may be respon- sensitive to fluoroacetate, and mass poisonings of dogs
sible for seizures in certain species (Hornfeldt and eating contaminated poultry have been documented
Larson, 1990). (Egyed, 1979).
Fluoroacetate/fluorocitrate also affects activities of The main target organs affected are the central ner-
other enzymes, including mitochondrial citrate carriers, vous, cardiovascular, and respiratory systems. This causes
pyruvate dehydrogenase kinase (Taylor et al., 1977), metabolic derangement that includes alteration in trans-
succinate dehydrogenase (Mehlman, 1967), glutamine aminase, calcium, and glucose levels apart from acidosis
synthetase, phosphofructokinase (Godoy and del Carmen and renal failure. Clinical effects are associated with neu-
Villarruel, 1974), and ATP-citrate lyase (Rokita and rological and cardiac systems. CNS effects include tremu-
Walsh, 1983). lousness, hallucinations, convulsions, and respiratory
depression. Cardiac effects include arrhythmias, ventricu-
lar fibrillation, and cardiac arrest. If the patient survives
Toxicity
the first 24 h after ingestion of sodium fluoroacetate,
Severity of signs is dose-related, and the oral route is the recovery is favorable. Acute exposure often results in
most important in cases of compound 1080 poisoning. complete recovery or death. Of course, in some cases,
Most species are sensitive to fluoroacetate (1080); how- exposure results in cardiac damage.
ever, rodents and dogs are the most sensitive species. The The fluorocitric acid is, itself, highly toxic, and
oral LD 50 of 1080 is 0.1 0.22 mg/kg in rats, 0.1 mg/kg in therefore, sodium fluoroacetate can cause secondary
mice, 0.34 mg/kg in rabbits, and 0.3 mg/kg in guinea poisoning—i.e., poisoning in an organism that has con-
pigs. The oral LD 50 s of this compound in the house sumed a part of an organism already poisoned.
sparrow, red-winged blackbird, starling, and golden eagle The development of tolerance to increasing doses of
are 3.0, 4.22, 2.37, and 1.25 5 mg/kg, respectively. fluoroacetate has been reported in rats and mice, whereby
Measured LD 50 of this rodenticide in mammalian wildlife a doseof0.5 mg/kgprotectsratsagainst adoseof 5 mg/kg
is 0.22 0.44 mg/kg in mule deer, 1.41 mg/kg in male fer- for a period of 48 h (Chenoweth, 1949). The mechanism of
rets, and 0.5 1.0 mg/kg in bears. fluoroacetate resistance in certain species is not well-
In general, fluoroacetate is very toxic to mammalian, understood, but the rate of defluorination does not appear
bird, and wildlife species, whereas it is of low toxicity to to play a significant role (Mead et al., 1985).
fish. Toxicity of 1080 is different according to route of Studies suggest that sodium fluoroacetate has no carci-
exposure (i.e., ingestion or inhalation), and symptoms nogenic, mutagenic, or teratogenic potential.
vary widely among species. Species have been catego-
rized into four groups according to symptomatology:
Diagnosis
1. Rabbit, goat, horse, sheep, and spider monkey: CNS
Diagnosis is based on evidence of exposure, clinical
effects are not observed, and death is due to cardiac
signs, necropsy findings, and chemical confirmation.
effects with ventricular fibrillation.
Samples for chemical confirmation should include sus-
2. Cat, pig, rhesus monkey, and human: Heart and CNS
pected bait, vomitus, stomach content, liver, and kidney.
are affected, and death usually results from respiratory
Testing for compound 1080 should be performed on the
failure during convulsions, but is occasionally due to
vomited stomach content. In the case of ruminants, rumen
ventricular fibrillation.
content needs to be analyzed for fluoroacetate. Significant
3. Dog and guinea pig: Epileptiform convulsions pre-
elevation of citric acid levels in blood and kidney is a reli-
dominate, with death being due to cessation of respira-
able biochemical marker of fluoroacetate or fluorocitrate
tory activity following running movements such as
poisoning (Bosakowski and Levin, 1986). Hyperglycemia,
those of strychnine poisoning.
hypocalcemia, and hypokalemia are characteristic labora-
4. Rat and hamster: Respiratory depression and delayed
tory findings. Other metabolic/biochemical changes include
bradycardia are the main features.
metabolic acidosis resulting from a buildup of citric acid,
In general, 1080 produces convulsions, involuntary lactic acid, and ammonium in blood and organs. Metabolic
urination, vomiting, and ventricular fibrillation. The acidosis is also associated with elevated serum creatinine
onset of symptoms of poisoning is usually between and transaminase levels.