Sources

Aflatoxins (the most prevalent of which is aflatoxin B₁) are specific chemical compounds produced by some toxicogenic strains of the Aspergillus group (e.g., A. flavus, A. parasiticus, and A. nomius) of fungi. These fungi grow when the moisture content of the substrate is 25% to 35% and air temperatures are 24° C to 35° C.¹ Aflatoxin contamination can be additive in foods, beginning in the preharvest crop and accumulating further during harvest, drying, storage, and processing.² Dogs have been poisoned by eating moldy food items (e.g., bread)^3,4 or contaminated grains (e.g., corn) used in the production of food.^5,6

Toxic dose

Dogs have been poisoned through the ingestion of dog food containing 100 to 300 ppb of aflatoxin⁵ or moldy bread that was reported to contain 6.7 or 15 ppm of aflatoxin.^3,4 As observed in other species, young males and pregnant females may be more susceptible to the effects of aflatoxin.

Experimentally, cats (oral median lethal dose [LD₅₀] = 0.55 mg/kg) are reported to be about as sensitive as dogs (oral LD₅₀ = 0.80 mg/kg) to purified aflatoxin.⁷ However, there have been no reported clinical cases of aflatoxicosis in cats.

Toxicokinetics

Following ingestion, aflatoxins are absorbed from the intestine and are largely taken up by the liver. Metabolic activation of aflatoxin to its 8,9-epoxide by a cytochrome P450 is necessary for toxicity.⁸ This activation occurs in hepatocytes, proximal renal tubular epithelial cells, and, to a lesser extent, in other cells throughout the body. The highly reactive 8,9-epoxide then binds to and damages macromolecules (including DNA and proteins) throughout the cell. Detoxification in the liver occurs largely through binding to glutathione and some biliary excretion.⁹

Mechanism of toxicity

Following cytochrome P450 activation of aflatoxin to its reactive epoxide, binding to various intracellular macromolecules (e.g., DNA, RNA, and proteins) is thought to be responsible for injury to and necrosis of hepatocytes and other metabolically active cells. This damage can ultimately lead to biliary hyperplasia, hepatic fibrosis, and decreased liver function.⁷

Clinical signs

Dogs are very sensitive to the hepatotoxic effects of aflatoxin, and the clinical signs primarily reflect varying degrees of liver damage. In most reported cases, relatively short exposures of 1 to several days are thought to be involved, as opposed to the chronic exposures of weeks to months often seen in livestock and avian species. Acute poisoning with large dietary concentrations of aflatoxin results in weakness, depression, severe gastrointestinal disturbances (e.g., vomiting and diarrhea), bleeding (sometimes with hemorrhage into the lumen of the intestine and elsewhere throughout the body), and icterus. Death can occur suddenly or within several days following the onset of clinical signs. Chronic exposure to lower levels of aflatoxin can result in anorexia, depression, vomiting, diarrhea, bleeding disorders (e.g., melena, epistaxis, and hemarthrosis), and icterus.^1,4,6

Minimum database

A minimum database should include a complete blood count, serum chemistry panel, urinalysis, and ammonia and bile acid levels. The most commonly reported alterations are increases in the serum activity of hepatic enzymes (e.g., alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase). Hypoalbuminemia, hyperbilirubinemia, hyperbilirubinuria, and elevations in serum or plasma ammonia concentrations can also occur. In severely affected dogs, prolongation of bleeding times, thrombocytopenia, elevation in bile acids, and anemia may be observed.

Confirmatory tests

The most common confirmatory test is analysis of the suspected contaminated food items for aflatoxins.¹⁰ Histological examination of a liver biopsy sample can be useful to assist in ruling out other causes of hepatic disease. If the amount of ingested aflatoxin was recent and very large, liver analysis may be of value. Analysis of fresh liver (50 g) for aflatoxin residue (by thin-layer chromatography [TLC] or high-performance liquid chromatography) is offered by some diagnostic laboratories.

Treatment

Treatment aims include prevention of further absorption by identification and removal of the contaminated feed and supportive care (e.g., maintenance of adequate caloric intake with a high-quality protein diet and intravenous fluids supplemented with dextrose and vitamins K and B₁₂).