Cholecalciferol (Vitamin D₃)

Sources

Rodenticides containing cholecalciferol are used overseas. In NZ cholecalciferol is available for possum control. It is also highly toxic to cats and dogs.

Toxicity

Toxicity has been reported in levels as low as 3mg/kg while serious toxicity is likely above 10mg/kg. Cats are more sensitive to cholecalciferol than dogs and young animals are the most sensitive.

Pathogenesis

After ingestion, vitamin D₃ is absorbed completely and rapidly from the jejunum. It appears first in the lymph before the blood. The highest concentrations of vitamin D₃ are found in plasma, liver, kidneys and adipose tissue. Calcifediol is a storage form of the vitamin. Vitamin D₃ crosses the placenta and will cause supravalvular aortic stenosis in rabbits born to does treated with vitamin D₃. It is metabolised by the liver and kidney and excreted mainly in the faeces. A small amount is excreted in the urine (about 2%).

Metabolism of Vitamin D₃ or cholecalciferol

Vitamin D₃ or cholecalciferol is a positive regulator responsible for calcium homeostasis in the body. Excessive amounts of vitamin D₃ cause hypercalcaemia which leads to a number of body changes. These include:

• Increased absorption of calcium and phosphorus from the intestinal tract.
• Mobilisation of calcium from bone.
• Decreased renal excretion.
• Bradycardia with conduction dysfunction, the QT interval is shortened and the PR interval is prolonged when blood calcium is greater than 3.49 mmol/L or 14mg/dL depending on the value used by the diagnostic laboratory.
• Calcium deposits appear throughout the body tissues in the heart, blood vessels, kidneys and lungs.
• Vasoconstriction occurs with increased vascular resistance and increased output of renin leading to:
  • Severe renal ischemia and tubular necrosis, a decrease in ADH levels, polyuria or oliguria.
  • Electrolyte disturbances (Na⁺ and K⁺ loss).
  • Finally renal failure and heart failure. The renal calcium deposits appear particularly in the loop of Henle and the collecting ducts.

Clinical Signs

The main signs of cholecalciferol toxicity often develop within 12 - 36 hours after the consumption of a toxic dose and include:

• Hypercalcaemia and hyperphosphataemia appear at 12 - 24 hours.
• Lethargy, weakness, anorexia, vomiting and constipation.
• Severe gastrointestinal signs such as haematemesis and bloody faeces.
• Dehydration.
• Polyuria or oliguria and polydipsia.
• Cardiac abnormalities ECG shows the PR interval lengthened and the QT interval shortened.
• Hypertension.
• Neurological signs include: twitching, seizures, depression and stupor.

Laboratory Diagnosis

The following tests are of value to confirm a diagnosis of vitamin D₃ toxicity.

• A serum calcium level higher than 4.99 mmol/L is characteristic and highly suggestive of vitamin D₃ toxicosis.
• An elevated serum phosphorus level may precede the hypercalcaemia by as much as 12 hours and could serve as an early nonspecific indicator.
• Urine specific gravity is 1.002 - 1.006.
• Increased BUN and creatinine levels occur as the toxicosis develops.
• Excessive active 1,25 dihydroxyvitamin D metabolites are present in renal tissue, but the analysis is difficult and few laboratories would perform it.

Post Mortem

Gross lesions include petechial haemorrhages in tissues, pale streaks in kidney tissue and raised plaques in the intima of large blood vessels.

Microscopic lesions may include mineralisation of the kidney tubules, coronary arteries, gastric mucosa, parietal pleura, pulmonary bronchioles, pancreas and urinary bladder. The renal tubules may be necrotic or degenerative.

Treatment

Detoxification therapy is essential when the exposure is recent (3 - 4 hours). The first treatment with activated charcoal should include or be followed by a laxative.

Activated charcoal is essential and should be repeated for several days due to the enterohepatic circulation of cholecalciferol and its metabolites. Treat the hypercalcaemia with fluid therapy of normal saline and frusemide for diuresis.

• Saline diuresis promotes calcium excretion.
• Frusemide for diuresis (5 mg/kg IV initially then 3 mg/kg q8h)
• Corticosteroid administration of prednisone (2mg/kg q8-12h) inhibits the release of osteoclastactivating factors, reduces intestinal calcium absorption and promotes hypercalciuria.
• Pamidronate has been shown to be effective in lowering calcium levels. The dose is 1.3 - 2.0 mg/kg in saline given over two hours intravenously. Saline fluids are continued until calcium levels return to normal. Continue to monitor calcium levels daily for 4 days. If calcium levels become elevated a second treatment of pamidronate may be required. Alternatively, Salmon calcitonin (4 - 6 IU/kg subcutaneously q3h increase to 10 - 20 IU/kg if the animal does not respond) may be administered to reduce excessive serum calcium levels. The treatment is not as effective as pamidronate and reactions to calcitonin may occur. It is not recommended to use both drugs concurrently.
• Avoid sunlight.

Prognosis

The prognosis is generally guarded to poor depending on the severity and responsiveness of the hypercalcaemia.

References

Carothers, M and Chew, D.J. (1991). Management of Cholecalciferol Rodenticide Toxicity. The Compendium, Small Animal. 13 (7): 1058 1062.

Eason, C. Meikle, L. Henderson, R (1996). Testing cats for secondary poisoning by cholecalciferol. Vetscript lX No.3 26.

Lofti, El Bahri (1990). Poisoning in Dogs by Vitamin D₃ Containing Rodenticides. The Compendium, Small Animal. 12 (10): 1414 1417.

Rumbeiha WK, Fitzgerald SD, Kruger JM, Braselton WE, Nachreiner R, Kaneene JB and Frese KK.( 2000) Use of pamidronate disodium to reduce cholecalciferol induced toxicoses in dogs. AmJ Vet Res. 61(1).

top