Cholecalciferol (Vitamin D3) Toxicity in Animals

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CHOLECALCIFEROL (VITAMIN D3) TOXICITY IN ANIMALS
Chavhan S G3
, Brar R S1
, Banga H S1
and N D Singh2
1. Professor’s, Department of Veterinary Pathology, College of Veterinary Science, GADVASU, Ludhiana, Punjab-141004.
2. Assistant Professor, Dept. of Vety. Pathology, College of Veterinary Science, GADVASU, Ludhiana, Punjab-141004.
3. Corresponding Author: Dr. Sambhaji G. Chavhan, Assistant Professor, Department of Veterinary Pathology, Veterinary
College, KVAFSU, Bidar, Karnataka-585401.
Email: drsam24183@gmail.com, Website: www.vetclinpath.in
Vitamins are organic compounds needed in small amounts for the normal growth and
activity of the body. Most of the vitamins cannot be synthesized by the body but are naturally
found in foods obtained from the plants and animals. Vitamins are either water-soluble or fat-
soluble and water-soluble vitamins are excreted rapidly than fat soluble vitamins.
Vitamin D is not a single compound but different compounds are reported to have a
vitamin D activity (Smith, 1982). Among them vitamin D3 (cholecalciferol) and vitamin D2
(ergocalciferol) are important. Vitamin D3 was found to be approximately ten times more
toxic than vitamin D2 (Chen and Bosmann, 1964; Hunt et al., 1972). The vitamin D3 toxicity
reported to cause generalized calcification mainly of soft tissues (Long, 1984).
Nowadays use of vitamin D3 (cholecalciferol) in commercial pet, livestock and infant
feed supplements, multivitamin preparations and as a rodenticide increased risk of toxicity.
Various plant species reported to have a high concentration of vitamin D analogue have been
reported as a source of vitamin D3 toxicity in livestock. The most common source of vitamin
D3 toxicity in dogs and cats is accidental ingestion of rodenticide baits containing
cholecalciferol (Rumbeiha, 2006). So, in present article we summarized various aspects of
vitamin D3 toxicity in detail.
Sources of Toxicity:
 Vitamin D3 nowadays also used as rodenticide. The rodenticide preparations are available
in different formulations like granules, flakes, tablets, baits containing 0.075%
cholecalciferol. The most common source of vitamin D3 toxicity in dogs and cats is
accidental ingestion of rodenticide baits containing cholecalciferol (Rumbeiha, 2006).
 Vitamin D3 is widely used as feed supplement in commercial livestock, pet and infant
feeds. The presence of excessive amount of vitamin D3 in commercial feed supplements
reported causing toxicity especially in pets, swine and human infants (Stevenson et al.,
1976; Long, 1984; Morita et al., 1995; Roberson et al., 2000).

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 The plant species like golden oat grass (Trisetum flavescens), Cestrum diurnum and
Solanum nigricans are reported to have a high concentration of vitamin D3 analogue. The
grazing of livestock on pastures containing these plant species have been reported to
cause a disorder called enzootic calcinosis or Manchester wasting disease (Beasly, 1999).
 Accidental ingestion of human medications containing vitamin D analogues used for
treatment of number of diseases like hypophosphatemic disorders, hypoparathyroidism,
osteomalacia, osteoporosis and renal failure (Beasly, 1999).
Toxicity:
 Based upon clinical reports, toxicoses have occurred in dogs from the ingestion of
cholecalciferol at 0.5 - 3 mg/kg body weight. Administration of 10 - 20 mg/kg to dogs of
cholecalciferol-based rodenticide resulted in death in 4 dogs.
 Younger animals appear at higher risk to the development of toxicosis.
 Acute oral LD50 in dogs of technical material in oil has been reported to be 85 mg/kg.
This has lead to an underestimate of the actual hazard of the rodenticide products for this
species.
 Relay toxicosis: not reported in experimental studies.
 40 IU vitamin D = 1 mcg. Thus, 1 IU of vitamin D3 = 0.025 mcg of cholecalciferol.
Mechanism of Action:
 Physiologically vitamin D and its metabolites maintain normal calcium levels in blood by
increasing intestinal absorption of calcium, stimulating bone resorption and decreasing
renal excretion of calcium.
 In high doses, Vitamin D2 and D3 accelerate these mechanisms many a times leading to
marked hypercalcemia as result of which calcium salts are deposited in soft tissues such
as kidneys, blood vessels, heart and lungs. Thus, soft tissues tend to become calcified
while a bone tends to be rarified.
 The mineralization of vital organs viz. kidneys, heart and lungs cause structural damage
that leads to decreased functional capacity of these tissues and organs. The loss of
function contributes to the development of ongoing end stage clinical signs as well as
long term signs in animals that survive. The cause of death reported in vitamin D3 toxicity
includes cardiac and renal failure (Beasly, 1999; Morrow, 2001; Sandhu and Brar, 2009).

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Clinical Signs:
 Diarrhoea, subnormal body temperature and progressive wasting.
 Anorexia, dullness, rigidity of limbs and difficulty in movement.
 Affected animals cannot walk properly/ shows tumbling movements and even cannot
open mouth.
 Ruffled body coat, severe progressive emaciation, dehydration and weakness.
 Difficulty in respiration, exhibited snoring sound during respiration, shivering and
epistaxis.
 Before death, nervous signs like aimless running, rolling and epileptic seizures can be
seen (Chavhan et al., 2011).
Clinicopathological findings:
 Increased plasma levels of calcium (hypercalcemia), phosphorus and Blood Urea
Nitrogen (BUN). The gross postmortem findings include white chalky deposits of
calcium on epicardial surface of heart and serosal surface of intestine. The stomach and
intestines may reveal bloody ingesta in the lumen with marked hemorrhages on mucosa.
The pin point white chalky deposits of calcium can be observed on capsules of both
kidneys. Histopathologically, the mineralization of various visceral organs (viz. heart,
lungs, kidneys, aorta etc.) can be observed (Chavhan et al., 2011).
Diagnosis:
 History of ingestion of rodenticide or in case of grazing livestock, the pasture should be
checked for presence of calcinogenic plants.
 Clinical signs, elevated level of calcium, phosphorus and BUN.
 In dead animals, diagnosis can be done from gross postmortem and histopathological
findings (calcification/mineralization of various visceral organs).
Treatment:
 No specific antidote available for cholecalciferol toxicity. Treatment of Vitamin D3
toxicosis is aimed primarily at lowering the elevated serum calcium levels. The following
drugs can be used to lower the calcium level.
 Corticosteroids (cortisone and prednisone): Dogs & cats: 1-2 mg/kg, orally or
intramuscular, once daily.
 Salmon calcitonin: Dogs & cats: 4-6 IU/kg, 2-3 times daily.

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 Pamidronate: Dogs: 1.3-2 mg/kg, slow IV in 0.9% sodium chloride solution over a period
of 2-4 hours. It may be repeated at 96 hours.
 Fluid therapy along with diuretics (frusemide) helps to reduce hypercalcemia. Emesis or
gastric lavage, administration of activated charcoal and osmotic cathartic helps to remove
unabsorbed toxicant.
Prognosis: Prognosis of vitamin D based rodenticide toxicosis is guarded, if the clinical
signs are severe or advanced.
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