Page 652 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

Non-Anticoagulant Rodenticides Chapter | 47 617

VetBooks.ir of the kidney leads to renal failure and death.
Cholecalciferol and its metabolites exert their effects by
binding to vitamin D receptors in tissues. 1,25-
Dihydrocholecalciferol is the most metabolically active
form, with 500 times greater binding to the vitamin D
receptors than that of 25-hydroxycholecalciferol and 1000
times greater binding than that of cholecalciferol.

Toxicity
Cholecalciferol is of low toxicity to mammalian species,
as it is classified as a class III toxic chemical. The oral
LD 50 of cholecalciferol in rats is 43.6 mg/kg and 42.5 mg/
FIGURE 47.3 Structural formula of cholecalciferol.
kg in mice. The dermal LD 50 in rabbits is 2000 mg/kg.
Studies suggest that cholecalciferol is of low toxicity to
structural formula is shown in Fig. 47.3. Cholecalciferol
birds (oral LD 50 is .2000 mg/kg in mallard ducks and
has other names, and is marketed as a rodenticide under
dietary LC 50 is 4,000 ppm in mallard ducks and
the brand names Quintox, True Grit Rampage, and Ortho
2000 ppm in bobwhite quail).
Rat-B-Gone; it is also marketed as a feed additive under
Pets such as dogs are poisoned by ingesting rodenti-
thenameViactive.
cide bait, whereas farm animals are affected by overdose
of additive vitamin D 3 in the feed. Signs and symptoms
Background of poisoning are similar to those of hypercalcemia, such
as anorexia, fatigue, headache, itching, weakness, nausea,
Cholecalciferol is a rodenticide that is used in and around
vomiting, and diarrhea. In acute cases, cholecalciferol
buildings and inside transport vehicles. Vitamin D 3 ,as
causes severe polyneuropathy. Dogs poisoned with
such, does not have significant biological activity but, in
cholecalciferol-containing rodenticide bait usually show
two steps, is metabolized in the body to make an active
signs of depression, anorexia, vomiting, bloody diarrhea,
form. In the liver, cholecalciferol is hydroxylated to
cardiac irregularities, hypertension, seizures, and death. In
25-hydroxycholecalciferol (calcifedion) by the enzyme
dogs, signs of poisoning may occur with as little as a
25-hydroxylase. In the kidney, 25-hydroxycholecalciferol
2 mg/kg dose, and death may occur with a 10 mg/kg dose
serves as a substrate for 1-α-hydroxylase, forming
of cholecalciferol.
1,25-dihydroxycholecalciferol (calcitriol), which is the
biologically active form. Cholecalciferol is formulated in
the granular form (0.075% bait), and is very effective
Treatment
against Norway rats, roof rats, and house mice.
Decontamination, including induction of emesis, gastric
lavage, and administration of activated charcoal, is
Toxicokinetics beneficial. Administration of intravenous fluids helps
Very little information is available on the toxicokinetics reduce serum calcium levels by increasing urine produc-
of cholecalciferol. Cholecalciferol is transported in tion and calcium excretion. Biphosphonate pamidronate
blood bound to carrier proteins. The major carrier protein disodium is used to decrease serum calcium levels.
is a vitamin D-binding protein. The half-life of 25-hydro- Seizures can be controlled by diazepam or barbiturates.
xycholecalciferol is several weeks, whereas that of 1,25- Treatment needs to be continued for 2 or 3 weeks
dihydroxycholecalciferol is just a few hours. because the elimination half-life of cholecalciferol is
more than 2 weeks. Poisoned animals should receive
feed devoid of vitamin D 3 .
Mechanism of Action
Ingestion of cholecalciferol-containing bait is known to Conclusion
cause a marked increase in calcium level in blood and tis-
sues. Cholecalciferol not only increases the absorption of Cholecalciferol is a single- or multiple-dose rodenticide
calcium, but also mobilizes calcium and phosphorus from that has low toxicity to mammalian and avian species. It
bones to the circulation. High calcium causes heart pro- produces toxicity by marked increases in calcium and
blems and bleeding secondary to mineralization of the mineralization of tissues. Once animals develop severe
vessels, kidneys, stomach wall, and lungs. Mineralization signs, they usually die.