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Fungi are a diverse group of organisms that possess multiple beneficial properties for human, animal, and ecological health, including the degradation of environmental pollutants, agricultural research, and medicinal and pharmaceutical therapies. Despite these vital applications, certain fungi are responsible for the death of many each year, with untold financial implications. Penitrems, aflatoxins, citrinin, ochratoxins, among others, are mycotoxins, or secondary metabolites produced by filamentous fungi that may cause a clinically significant toxic response (mycotoxicosis) when ingested by animals. These mycotoxins are naturally occurring contaminants and appear in widely consumed feedstuffs. Dogs are unusually susceptible to their hepatotoxic, nephrotoxic, immunosuppressive, and carcinogenic effects. Mycotoxins are rapidly absorbed in canines, and with high morbidity and mortality rates, treatment is mainly supportive, and euthanasia (or death) is often elected.

This paper comprehensively reviewed the current literature on mycotoxins, specifically tremorgenic mycotoxins, aflatoxins, and ochratoxins in companion animals, with a primary emphasis on canines. Electronic databases were reviewed for published articles between 1969 and the present, and 50 articles were identified for inclusion.

Our review suggests a widespread gap in information on the diagnosis and treatment of companion animal mycotoxicosises and the risk of chronic exposure to mycotoxin contamination of dog food is underexplored. And given that signs may masquerade as a variety of diseases, it is postulated that mycotoxicoses have a far greater prevalence than what has been consistently thought. There is a need to create standardized diagnostic means and reporting to eliminate inconsistencies in treatment strategies and improve patient survival outcomes.

Introduction

The safeguarding of pet foods from mycotoxin contamination is of interest to pet food manufacturers and pet owners because the health and well-being of pets have significant economic and emotional implications. Increased health and veterinary care costs, disposal of contaminated feed, pet food recalls, losses in both domestic and international trade of pet foods, and future investment in prevention and loss mitigation research all contribute to the growing concern about mycotoxicoses [1]. Many of the reported figures regarding fungal diseases are likely underrepresented because the symptoms of fungal diseases masquerade as other diseases and often go undiagnosed [2]–[5] and actual economic losses are difficult to assess in a uniform way [6]; importantly, the link of a pet’s illness to the food it ingests is not always clearly established or reported as mycotoxins can exhibit both acute and chronic manifestations, depending on the quantity and concentration of food consumed and exposure frequency and duration. In dogs, symptoms associated with mycotoxicosis are often attributed to the ingestion of moldy household food or commercially prepared foods containing ingredients such as corn, rice, and peanuts that have spoiled during some stage of harvesting, processing, or storage [2], [4], [7]–[17].

Mycotoxins, such as tremorgenic mycotoxins, aflatoxins, and ochratoxins, are produced primarily as secondary metabolites by Penicillium and Aspergillus spp. fungi, although Cloviceps and Neotyphrodium spp., among others, produce mycotoxins as well, under specific environmental circumstances (temperate and humid climates) that produce neurotoxic, hepatotoxic, nephrotoxic, immunosuppressive, and reproductive injury [2]–[4], [7]–[10], [12], [13], [15]–[22]. Carcinogenicity in companion animals is suspected but not supported in the literature reviewed [22], [23]; often, levels consumed are too high of a dose with too short of duration for neoplasia to occur [8], [10], [12], [20], [24]–[32]. That said, with such a high potential for lethality from as little as 0.2 mg/kg consumed in food, mycotoxin contamination in pet food poses a serious health threat to companion animals [4], [11], [21], [33], [34].

Background

Canine mycotoxicosis was reported in the literature in 1979 and first reported in the United States in 1952 when dogs fed toxic peanut meal died from hepatic failure. For the past fifty years, mycotoxins have continued to leave a devastating wake with recalls of contaminated pet food, with thousands of animals affected, died, or subsequently euthanized (Table I). In fact, the most recent pet food contamination occurred in 2021 when Sunshine Mills Inc. issued a voluntary recall of their dog food due to potentially elevated levels of aflatoxin. Before that, more than 70 dogs died, and more than 80 dogs were infirmed in December 2020, when Midwestern Pet Foods, Inc. voluntarily recalled several of its products due to elevated levels of aflatoxin linked to corn processed in an Oklahoma manufacturing plant [24].

Year Location Dogs affected Author Mycotoxin Feedstuff
1952 United States Unknown Seibold et al. [30] Aflatoxin Peanut meal
1966 Massachusetts, US 17 dogs, either euthanized or died Newberne et al. [16] Aflatoxin Experimental settings
1973 Indiana, US 23; 17 died Szczech et al. [4] Ochratoxin A Rice culture
1974 Indiana, US 3 died Szczech et al. [11] Ochratoxin A Experimental settings
1974 Alabama, US 7; 6 died Greene et al. [15] Aflatoxin Mixture of cornmeal, meat scraps, commercial diet
1975 Queensland, Australia 3 died Ketterer et al. [14] Aflatoxin Mixture of bread and commercial canned diet
1975 Western India Unknown Krishnamachari et al. [31] Aflatoxin Maize
1977 Indiana, US 35; 24 died Kitchen et al. [27], [33], [34] Ochratoxin A Experimental settings
1981 California, US 1 Richard JL, Arp LH [35] Penitrem Moldy walnuts
1986 Georgia, US 9 died Liggett et al. [36] Aflatoxin Cornmeal, soybean meal
1987 Germany 6 died Gareis et al. [32] Ochratoxin A Unknown
1988 Pretoria, Republic of South Africa 10 died Bastinello et al. [37] Aflatoxin Commerical diet
1990 Sao Paulo 2 died Hagiwara et al. [38] Aflatoxin Commerical diet
1991 Scotland 1 died Little et al. [39] Ochratoxin A Moldy food
1998 Texas, US 55 died Bingham et al. [5] Aflatoxin Commercialdiet
2002 Massachusetts, US 4 Boysen et al. [40] Penitrem Compost pile
2002 South Africa 2 Naude et al. [10] Penitrem Moldy rice
2002 Canada 1 Walter [18] Penitrem Restaurant garbage
2003 Iowa, US 1 Young et al. [3] Penitrem Moldy cream cheese
2003 Iowa, US 1 Young et al. [3] Penitrem Moldy mac and cheese
Dec. 2005–March 2006* United States 72 Dereszynski et al. [12] Aflatoxin Commerical diet
Dec. 2005–Feb. 2006 Israel 50 Bruchim et al. [17] Aflatoxin Commerical diet
2005* United States 9 died Newman et al. [41] Aflatoxin Commercial diet
2005* United States 23 died Zaki et al. [8] Aflatoxin Commerical diet
2005* Southeast United States >100 died Stenske et al. [13] Aflatoxin Commerical diet
2006 Korea 3 died Jeong et al. [20] Ochratoxin A Commerical diet
2010 Unknown 1 Eriksen et al. [19] Penitrem Moldy dog food
2010 Unknown 2 Eriksen et al. [19] Penitrem Rotten apples
2010 Unknown 1 Eriksen et al. [19] Penitrem Unknown
2010 Unknown 2 Eriksen et al. [19] Penitrem Unknown
2011 Southern Brazil 60 died Wouters et al. [23] Aflatoxin Commerical diet, corn meal, meat, left-over food
2011 South Africa >220 died Arnot et al. [28] Aflatoxin Pelleted dog food
Unknown Unknown 1 affected Referenced by Naude et al. [10] Penitrem Moldyhamburger bun
Table I. Summary Data of Published Mycotoxin Intoxication Cases in Canines from Various Sources throughout the Past Seventy-One Years

Despite the reported outbreaks, little has been published regarding any advancements in the therapeutic strategies or diagnostic techniques to improve the outcome of dogs affected. Furthermore, even though the toxicological effects of mycotoxins in mammalian species are known, little is described in the literature concerning canines. Therefore, this review comprehensively and systemically explored the current published literature on canine tremorgenic mycotoxins, aflatoxins, and ochratoxins with a focus on the clinical and clinicopathological findings, highlighting the knowledge gaps as applicable so as to provide a platform and a clear impetus for future research.

Materials and Methods

Our search was conducted using a scoping style review of PubMed, Scopus, ISI Web of Science, and Google Scholar using search terms that included ‘mycotoxin’ and: ‘companion animal’, ‘tremorgenic’, ‘penitrem’, ‘aflatoxin’, ‘ochratoxin’, ‘dog’, ‘cat’, ‘food or feed’, and ‘contaminated’. The search provided over 70 articles, mostly (≈90%) dated after 2008. Abstract analysis narrowed the selection to well under 50 papers, according to their relevance and actuality as judged by the authors, an experienced veterinarian, environmental toxicologist, and an academic internal medicine clinician.

Pathogenesis of Mycotoxicoses in the Dog

Of the numerous fungal organisms that have mycotoxin-producing capabilities, isolates of the Penicillium, Aspergillus, and Fusarium genres are the most widespread, geographically diverse, and the deadliest to affect our companion animals [2]–[4], [7]–[10], [12], [15]–[22].

Both Penicillium and Aspergillus are ubiquitous in the soil and grow on food consumables such as corn, peanuts, rice, wheat, soybeans, oats, dried beans or fruit, coffee, and peppers, and they and their metabolites can also be found in meat, eggs, and dairy products such as milk and cheese. As such, the occurrence of mycotoxins in foods is not entirely avoidable; in fact, of the numerous studies examined, as high as 81% of pet food samples were contaminated with mycotoxins [21], though fortunately at concentrations lower than legally permitted. Both the Food and Drug Administration (FDA) and European Commission (EC) have established these amounts in foods and animal feeds of 20 ng/g specifically for aflatoxin, whereas only the EC has a guidance value of 25 ng/g OTA in cereals and cereal products used in feed. Neither the FDA nor EC have legal limits of penitrem in feed [36]. However, despite these regulations, most dogs affected have occurred due to moldy household food or poor-quality control measures in commercially prepared dry or solid-type pet food [2], [4], [8]–[11], [13], [14], [16], [17].

The pathogenesis by which these mycotoxins cause disease is not entirely understood, and various theories exist, though recent studies have improved upon previous knowledge gaps. Still, all exert harmful effects on vital cell processes, and mycotoxins of one fungal species often occur in conjunction with another to create synergistic and additive effects [3], [18], [27], [33]. These fungi produce a variety of secondary metabolites–bioactive or natural products not necessary for normal growth or development, and those with pathogenicity are the cause of mycotoxicoses in animals [25]. Production of these secondary metabolites is a consequence of environmental stimuli and depends on the parent fungus’ developmental stage (at the right time under the right circumstances). Hence, during the harvest, processing, or storage of feedstuffs, environments with higher moisture or humidity, warmer temperatures, or crops that have suffered insect or drought damage tend to have higher levels of mycotoxin production [2], [6], [8], [10], [12], [15], [17], [20].

Secondary metabolites produced by Penicillium and Aspergillus species include penitrem A–F (A and E are the most common), aflatoxin B1 (most hepatotoxic), B2, G1, G2, and ochratoxin A (most naturally occurring and most toxic [21]).

Neurotoxins produced from Penicillium spp. (P. Vindicatum, P. cyclopoium, P. crustosum (the most common), P. commune, P. roquefortine) and Aspergillus metabolites are thought to have dual roles affecting both inhibitory and excitatory neurotransmitters and synapses, causing an increase in the release of aspartate and glutamate and decreased release of GABA and glycine, which results in the loss of coordinated impulses affecting muscle action and brainstem reflexes. Additionally, they cause widespread destruction of Purkinje cells due to ischemic necrosis of the cerebellum, the portion of the brain responsible for coordinated motor control [3], [9], [10], [18].

In dogs suffering from the deadly effects of Aspergillus spp. (A. Flavus, A. parasiticus), the liver is the organ most severely affected. Once ingested and absorbed, the secondary fungal metabolites are transported to the liver via the portal vein. They are ultimately transformed in the liver and activated into toxic forms, causing cellular damage through multiple means: a decrease in intracellular GSH, which results in secondary oxidative injury; irreversibly binding to cell enzymes, proteins, DNA, and possible mitochondrial DNA, causing impaired metabolism, gene transcription, protein synthesis, and cell energy production; depletion of hepatocyte glycogen stores. Aspergillus metabolites also have coumarin-like properties acting as anticoagulants, manifesting as petechiae and ecchymoses and widespread hemorrhage [2], [8], [12], [13], [15], [17], [25], [41].

Alternatively, OTA binds to proteins and accumulates in the kidneys, disrupting protein synthesis and causing damage to the proximal renal tubular epithelium, leading to interstitial fibrosis, which may be in part due to the transport of the toxin into the cell as part of the glomerular infiltrate as OTA and albumin can interact (although this theory is controversial as the amount of albumin in the glomerular filtrate of dogs is low) [26]. Moreover, OTA has been shown to alter cell adhesion and gap junction intercellular communications, inciting the programmed cell death pathway leading to apoptosis [7], [22]. OTA also binds to DNA and causes oxidative stress to the cell membrane, inducing tumor formation specifically in rodents and humans and is suspected to have similar effects in dogs [8], [11], [21], [27].

Clinical and Clinicopathological Findings and Lesions in the Dog

The mycotoxins studied have a high mortality and morbidity in dogs as the toxins are rapidly absorbed within 15 minutes to a few hours, leading to acute clinical signs and death within hours to days [9], [12], [40]. Even with treatment, the majority of dogs succumb or are euthanized. Doses as low as 60 ug/kg body weight have been reported to induce clinical signs in dogs [14] with lower doses inducing similar signs when fed over multiple days to weeks [21], [42]. Dogs, especially young ones, are generally more susceptible to mycotoxins [43], [44] often due to their indiscriminate eating habits, but it’s challenging for the clinician to attribute the observed effects to a certain toxin as fungal species can co-occur and can produce a variety of toxins [19]. LD50s for penitrem A, aflatoxin, and ochratoxin have been well established and are comparable throughout the published literature, yet the concentration of mycotoxins in feed consumed needed to induce clinical manifestations of the disease is sparsely reported and studied (Table II).

Toxin Penitrem A Aflatoxin B1 Ochratoxin A
LD50 (mg/kg body weight) >0.5 [10], [18] 0.5–1.5 [8], [13], [23], [26] 0.2 [4], [11], [21], [33], [34]
Concentration of myctoxin in feed needed to induce clinical manifestations of disease 31.3 mg/kg; 10 µg/kg–30 mg/kg vomitus [19] >60 µg/kg of toxin in feed or 0.05–0.3 mg toxin/kg pet food over 6–8 weeks [38], [45] 372.8 ppb in feed [35]
Table II. The Oral LD50 of Selected Mycotoxins in Dogs1 and the Concentration of Mycotoxins in Feed Related to Toxicity

Interestingly, dogs suffering from neurotoxicosis have a better prognosis than those affected by aflatoxin or ochratoxin [8], [9], [11], [13], [16], [17], [19], [21], [33], [34], [40], [41], [46]. Studies have demonstrated that clinical signs can resolve within a few days, even though there may be lasting signs years after the fact [9], [19], [22], [46]. If therapy continues, and the authors believe it should, a prolonged recovery does not mean a worse prognosis in these cases.

Dogs suffering from penitrem intoxication are likely to demonstrate clinical signs associated with neurologic diseases such as seizures, intention muscle tremors (often worsened with loud noises and handling of the patient), ataxia, fasciculations, vocalization, hyperextension of the limbs, opisthotonos, paddling, recumbency, nystagmus, mydriasis, hypersalivation, tachycardia, vomiting and diarrhea, blepharospasm, hyperthermia (with temperatures often greater than 106 F), hyperemic mucous membranes, and aspiration pneumonia [3], [9], [18], [19], [40]. Moreover, dogs evaluated have varied liver, kidney, and muscle enzymes, as noted in Table III, with only a few studies referencing true kidney damage, but overall, clinical pathologic data are not overtly diagnostic. Sodium, total bilirubin, total protein concentrations were not significantly affected.

Laboratory test Penitrem A [9], [19], [40] Aflatoxin B1 [2], [12], [13], [15]–[17], [41] Ochratoxin A [34]
CBC Increased HCT Lack of stress leukogram Decreased platelets
Chemistry Increased liver values: ALT, ALKP, AST, GGT Increased liver values: ALT, ALKP, AST, TBILI Increased PT/PTT Increased renal values: BUN, CREA, PHOS
Increased bile acids Decreased liver proteins: ALB, Ca, CHOL Normal to slight increase in liver values: AST, ALT
Increased CPK Coagulopthay evidenced by: increased PT/PTT; decreased fibrinogen, FVII:C
Urinalysis Dilute USG Orange colored urine Evidence of renal damage: Proteinuria, Glucosuria, Ketonuria, Granular casts, Renal epithelial cells
Table III. Relevant Clinical Pathologic Summary Data from Various Sources of Three Mycotoxins1

Dogs with aflatoxin B1 (AFB1) intoxication have signs mainly associated with the level of aflatoxin in the diet and the amount of feed consumed, which manifests as either acute, subchronic, or chronic liver failure: jaundice, anorexia, lethargy, vomiting +/– blood, peripheral edema, and abdominal effusion, widespread petechiae and ecchymoses and bleeding from orifices, diarrhea that progresses to hematochezia or melena, polyuria and polydipsia, dehydration, and terminal encephalopathy (depression, stupor, coma, seizures, vocalization). Moreover, AFB1 has been shown to cause abortion, placental hemorrhages, and fetal maceration [2], [4], [12], [13], [15]–[17], [23], [28], [36]. Additionally, clinical findings observed related to blood chemistry and coagulation tests are noted in Table III; changes specifically mentioned in the literature are increases in alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, prothrombin and partial thromboplastin time and decreases in protein C, antithrombin and fibrinogen. Decreases in total protein and albumin are noted in acute poisonings.

Microscopic findings are consistent with hepatocyte lipid vacuolation, hepatocellular cholestasis, and biliary hyperplasia. Ultrasonographic results are consistent with a hyperechoic liver and hypoechoic liver nodules, irregular hepatic surface, thick gallbladder wall, increased mesenteric lymph nodes, anechoic abdominal effusion, and gastric atony [2], [13]–[17], [23], [26], [28], [37], [41].

In contrast, dogs suffering from OTA often have normal livers, but abnormal kidneys as evidenced by congestion, atrophied cortices, and yellowish lesions, including increased blood urea nitrogen and creatinine consistently increased above the reference range of normal dogs, low urine specific gravity, renal proteinuria, and urine:protein creatinine ratio greater than 0.5, and concentrations of serum electrolytes consistently decreased below those of normal dogs on blood work [34], as listed again in Table III. Clinical signs associated with renal failure experienced by dogs include weight loss, retching and vomiting, dehydration, bloody diarrhea, fevers often >104 F, anorexia, polyuria and polydipsia, tenesmus, prostration, enlarged lymph nodes, tonsilitis, and conjunctivitis manifested by mucopurulent bilateral ocular discharge, and death. Such intoxicated dogs are often dead or euthanized within two weeks, similar to that seen in dogs suffering from aflatoxicoses [4], [8], [20], [21], [23], [33], [34], [41]. Meucci et al. [21] showed that even though OTA concentrations in feed are lower than values legalized by the EC, dogs with chronic kidney disease (CKD) have higher levels of serum OTA, thereby highlighting the association between chronic low level dosage of toxin ingestion and the development of CKD.

Macroscopic and Microscopic Lesions

Of the case studies evaluated, dogs diagnosed with neurotoxicoses that were necropsied with histopathology were noted to have hemorrhages in the cerebellum, liver (hepatic centrilobular changes with hepatocyte degeneration and necrosis), lung, stomach, small intestines, and tubulonecrosis of the kidneys [18].

Dogs diagnosed with AFB1 and necropsied developed widespread hemorrhage of subcutaneous tissues, intestinal hemorrhage, and ulceration, severe edema of the gallbladder wall, hydroperitoneum, hydrothorax, pulmonary congestion, pulmonary edema, lymph node edema, anasarca, glomerulopathy, kidney nephrosis, atrophy of the lymph nodes and bone marrow hypoplasia. Moreover, the liver was enlarged and had a friable yellow appearance, and icterus was noted in the mucous membranes and sclera [2], [13]–[17], [23], [28], [37], [41].

Similarly, dogs with OTA had acute vacuolar changes with tubular necrosis to the kidneys, edematous, hyperemic, and necrotic lymphoid tissue, most commonly affecting the thymus and tonsils along with necrotic Peyer’s patches and cytoplasmic vacuolation and disarray, on necropsy and histopathology [11], [20], [27], [33].

Diagnostic Considerations for Canine Mycotoxicoses

Of the literature reviewed, diagnostic strategies involved a minimum database consisting of baseline bloodwork, urinalysis, coagulation profile, and cytologic, histopathologic, and radiographic findings, where applicable. Remarkably, in the literature, there is a lack of data and guidance on comprehensive testing and recommendations for mycotoxin screening in the veterinary hospital.

Since patients may present with an unknown exposure or duration, mycotoxicoses in canines are most often diagnoses of exclusion, and other diagnostic differentials should be considered; validated diagnosis is found only post-mortem, and rarely that, or by analysis of suspected contaminated feed (ideally, 1 kg dry food or four cans [13], either frozen or at room temperature in sealed containers) or vomitus via the use of specialized equipment like gas chromatography, mass spectrometry, thin layer or high-performance chromatography, or liquid chromatography-tandem mass spectrometry [3], [9], [10], [13], [19], [21]–[25], [29], [40], [41], [47].

Organ and tissue samples can also be analyzed with these methods but are limited in the scope of veterinary practice as very few diagnostic laboratories test for tissue mycotoxins, and they are usually limited to aflatoxin B1. Because of the demanding requirements for organ analysis and the need for mycotoxin metabolite standards, tissue analysis and urine analysis are usually a research discussion. As a result, the ability to diagnose mycotoxins as the causative factor in the hospital within a timely period, coupled with the fast rate of absorption and onset of clinical signs, critically delays appropriate and aggressive management. Therefore, many diagnoses are made on the basis of clinical signs and history provided, more so in cases of suspected poisoning or multi-pet affected households. And, as mentioned previously, since certain fungal species can occur simultaneously and each species can produce a variety of toxins, it is challenging to ascribe the observed effect to a certain level of a specific toxin.

Real-time pet food recall announcements to the public or participation in social media live updates by pet food companies can lead to prompt discontinuation and screening of a potentially contaminated diet, along with suggestive diagnosis of pets presenting with characteristic clinical signs, but with any animal suspected of feed related mycotoxicoses, the food should be immediately discontinued and diet changed.

Therapeutic Strategies

Treatment primarily consists of supportive care for all dogs suffering from mycotoxicosis, as there is no antidote. If a mycotoxin is suspected or known, first and foremost, the feed should be immediately discontinued. Decontamination either with an emetic agent (apomorphine is the emetic of choice) and gastric lavage followed by activated charcoal, or a single cathartic agent should be administered. However, as the toxins are rapidly absorbed, the ability to remove toxic substances from the patient is limited. At this point, the therapy paradigm shifts toward supportive care and symptomatic resolution efforts. Not surprisingly, there is no specific treatment reported for dogs suffering from OTA toxicosis. Even though studies have advocated for treatment for acute kidney failure, dogs generally succumb to the disease or are euthanized [4], [8], [11], [20], [21], [23], [33], [34], [41]. Dogs suffering from neurotoxicants are given anticonvulsants and sedatives (phenobarbital, diazepam, methocarbamol, propofol, and gas inhalant); antiemetics such as metoclopramide, dolasetron, ondansetron, to decrease the risk of secondary aspiration pneumonia; intravenous fluid therapy; thermoregulatory therapies such as fans, cool water baths, or combination of the two. IV lipid emulsion therapy has even been purported in the case of penitrem intoxication as penitrem is lipid soluble [3], [9], [10], [18], [19], [40].

Dogs suffering from liver failure attributed to AFB1 or similar metabolites are often provided with intravenous fluid support along with blood products such as fresh frozen plasma not only to correct the dehydration associated with fluid loss and to correct acid-base and electrolyte disturbances but also to treat and inhibit the anticoagulative effects of the toxin. Non-specific liver protectants such as SAMe and milk thistle derivatives (Silymarin) enhance GSH production by increasing GST activity, reducing the bioactivation of certain toxins and acting as free radical scavengers and antioxidants [48]. N-acetylcysteine has equivalent properties and provides the essential amino acid L-cysteine for the synthesis of GSH. L-carnitine helps decrease oxidative damage, and Vitamin K1 activates and provides certain coagulation factors. Antiemetics (as mentioned previously) and antibiotics such as metronidazole and neomycin or lactulose are given to combat the effects of hepatic encephalopathy and decrease the risk of bacteremia and sepsis due to a compromised gastrointestinal barrier [13].

Conclusions and Recommendations

In summary, the safety of pet food is of special concern as the health and well-being of pets pose significant financial and emotional interest to pet food manufacturers and consumers. Mycotoxin contamination in pet food is a known source of pet food-related toxicoses and is challenging for veterinary practitioners to treat as therapeutic options are limited to supportive care and ameliorating clinical signs. Yet, despite best efforts, dogs suffering from aflatoxicosis and ochratoxicosis either died or are humanely euthanized. Without timely and intensive medical attention, dogs afflicted with tremorgenic mycotoxins often suffered the same fate. Moreover, the true incidence of mycotoxin disease remains elusive, and many deaths go undiagnosed as many outbreaks and pet food recalls remain unpublished, which may involve the death of untold numbers of animals. Of what is published, aflatoxicosis in dogs is the most widely documented and reported, followed by canine tremorgenic mycotoxins, and only a few case studies of OTA have been published.

Canine mycotoxins, such as penitrem A, aflatoxin, and OTA, remain a challenge for veterinarians as diagnosis is usually made presumptively based on the history the dog owner provides and food analysis, if possible. More of a research discussion and of little utility in the hospital, tissue samples, along with postmortem histopathology, when permitted, can confirm diagnosis. To the authors’ knowledge, there is no acute bedside test that can aid with a quick diagnosis and that provides prognostic information for the veterinarian. Although systems are in place to detect the presence of contamination, they are not full-proof, and preventing intoxication remains an opportunity. Moreover, whereas there is a low incidence of toxic levels of mycotoxin concentrations in pet foods, there yet remain untold risks for chronic low-level exposure and further long-term studies are warranted.

Although knowledge about mycotoxins has improved throughout the years, it is still limited. The studies reviewed in this paper reframe the problem as serious in terms of morbidity and mortality, not fully understood, and may well be chronically under- or mis-diagnosed. The authors acknowledge that understanding the unique metabolism of each respective mycotoxin in the canine, specifically OTA, combined mycotoxin exposure, chronic low-level exposure risks, and carcinogenicity, is a future topic not explored in the current paper. Despite these drawbacks, the usual call for more research could not be more salient: improved prognosis for animals suffering from any mycotoxicosis lies with more studies addressing alternative and novel diagnostic and treatment options in conjunction with long-term survival studies.

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