Pyrethroid-associated nephrotoxicity in channel catfish, Ictalurus punctatus, and blue catfish, I. furcatus, at a public aquarium.

Over the course of an approximately 11-month period, an outdoor, freshwater, mixed species, recirculating, display system at a public aquarium experienced intermittent mortalities of channel catfish (Ictalurus punctatus) and blue catfish (I. furcatus). Catfish acutely presented for abnormal buoyancy, coelomic distention, and protein-rich coelomic effusion. Gross lesions typically involved massive coelomic distension with protein-rich effusion, generalized edema, and gastric hemorrhage and edema. Microscopically, primary lesions included renal tubular necrosis, gastric edema with mucosal hemorrhages, and generalized edema. Aerobic culture and virus isolation could not recover a consistent infectious agent. Intracoelomic injection of coelomic effusion and aspirated retrobulbar fluid from a catfish into naïve zebrafish (bioassay) produced peracute mortality in 3 of 4 fish and nervous signs in the fourth compared with 2 saline-injected control zebrafish that had - no mortality or clinical signs. Kidney tissue and coelomic effusion were submitted for gas chromatography tandem mass spectrometry by multiple reaction monitoring against laboratory standards, which detected the presence of multiple pyrethroid toxins, including bioallethrin, bifenthrin, trans-permethrin, phenothrin, and deltamethrin. Detection of multiple pyrethroids presumably reflects multiple exposures with several products. As such, the contributions of each pyrethroid toward clinical presentation, lesion development, and disease pathogenesis cannot be determined, but they are suspected to have collectively resulted in disrupted osmoregulation and fluid overload due to renal injury. Pesticide-induced toxicoses involving aquarium fish are rarely reported with this being the first description of pyrethroid-induced lesions and mortality in public aquarium-held fish.

Mass spectrometric methods for evaluation of voriconazole avian pharmacokinetics and the inhibition of its cytochrome P450-induced metabolism.

Invasive fungal aspergillosis is a leading cause of morbidity and mortality in many species including avian species such as common ravens (Corvus corax). Methods were developed for mass spectral determination of voriconazole in raven plasma as a means of determining pharmacokinetics of this antifungal agent. Without further development, GC/MS/MS (gas chromatography-tandem quadrupole mass spectrometry) proved to be inferior to LC/MS/MS (liquid chromatography-tandem quadrupole mass spectrometry) for measurement of voriconazole levels in treated raven plasma owing to numerous heat-induced breakdown products despite protection of voriconazole functional groups with trimethylsilyl moieties. LC/MS/MS measurement revealed in multi-dosing experiments that the ravens were capable of rapid or ultrarapid metabolism of voriconazole. This accounted for the animals' inability to raise the drug into the therapeutic range regardless of dosing regimen unless cytochrome P450 (CYP) inhibitors were included. Strategic selection of CYP inhibitors showed that of four selected compounds including cimetidine, enrofloxacin and omeprazole, only ciprofloxacin (Cipro) was able to maintain voriconazole levels in the therapeutic range until the end of the dosing period. The optimal method of administration involved maintenance doses of voriconazole at 6 mg/kg and ciprofloxacin at 20 mg/kg. Higher doses of voriconazole such as 18 mg/kg were also tenable without apparent induction of toxicity. Although most species employ CYP2C19 to metabolize voriconazole, it was necessary to speculate that voriconazole might be subject to metabolism by CYP1A2 in the ravens to explain the utility of ciprofloxacin, a previously unknown enzymatic route. Finally, despite its widespread catalog of CYP inhibitions including CYP1A2 and CYP2C19, cimetidine may be inadequate at enhancing voriconazole levels owing to its known effects on raising gastric pH, a result that may limit voriconazole solubility.

Gas chromatography-tandem mass spectrometric analysis of metaldehyde and its metabolite acetaldehyde in initial assessment of hemodialysis abatement of toxicity in live animals.

Metaldehyde consumption by pets and other mammals constitute medical emergencies ideally requiring rapid poison removal. The purpose of this study was three-fold: 1) development of a sensitive method for metaldehyde quantitation in patient serum samples by gas chromatography combined with tandem quadrupole mass spectrometry (GC/MS/MS); 2) development of a sensitive method for quantitation of the volatile metaldehyde metabolite acetaldehyde by headspace analysis combined with GC/MS/MS; and 3) an initial assessment of the efficacy of combined dialysis and hemoperfusion treatments in diminishing toxin loads in canine victims of metaldehyde poisoning. Both mass spectrometric approaches relied on Multiple Reaction Monitoring (MRM) methodologies. Metaldehyde extracted via liquid-liquid partitioning from serum was detected with a limit of quantitation (LOQ) of 7.3 ± 1.4 ng/mL with linearity in the range 1-250 ng/mL with accuracy improved by inclusion of a deuterated metaldehyde internal standard. Acetaldehyde was determined to have an LOQ of 0.39 µg/mL with linearity in the range 1-1000 µg/mL. The developed methodologies were applied to canine samples taken over various time points during dialysis treatment. Two of three canine patients showed significant abatement of metaldehyde levels by over 50-fold from initial concentrations while a third was shown to be negative with no measureable metaldehyde. The toxic metabolite acetaldehyde was found in one of the metaldehyde-poisoned patients and the detected acetaldehyde was also reduced by roughly 200-fold during the course of treatment. The designed mass spectrometric techniques were thus successful in demonstrating the efficacy of the applied dialysis-hemoperfusion methods which may find wider applicability against other potentially lethal toxins in poisoned patients in future studies.

Pentafluorobenzylation and detection of sodium monofluoroacetate (compound 1080) in veterinary samples using gas chromatography/tandem quadrupole mass spectrometry with multiple reaction monitoring.

RATIONALE: The analytical detection of chemical residues from sodium monofluoroacetate (MFA) ingestion in targeted predatory wildlife and in pesticide misuse incidents perpetrated against nuisance companion animals remains a concern in veterinary forensic toxicology. There is a current need for chemically stable sample extracts with reliable and specific diagnostic methods for trace quantities in diverse diagnostic matrices. METHODS: Biphasic pentafluorobenzylation provided a simple combined extraction and derivatization procedure for removing MFA in a chemically stable form from a complex matrix such as stomach contents. Analysis of the derivatized extract using gas chromatography/tandem quadrupole mass spectrometry (GC/MS/MS) with multiple reaction monitoring (MRM) approaches specific to MFA provided greater specificity than simple scan or selected ion monitoring approaches. RESULTS: Collision-induced dissociation in GC/MS/MS showed that pentafluorobenzyl (PFB)-derivatized MFA (M+ m/z 258) generated m/z 258➔130, 149, 161, 177, 178, 180.1, and 181.1 transitions. Of these, the transition m/z 258➔181 provided a peak for quantitation, whereas m/z 258➔161 and 258➔178 provided specificity for qualifying MFA. Similarly, PFB-derivatized 2-chloropropionic acid (M+ m/z 288) was used as an internal standard, which generated m/z 288➔181 and 161. Of these, the transition m/z 288➔181 provided a peak for quantitation, whereas m/z 288➔161 and 181➔161 served to qualify the internal standard. CONCLUSIONS: The method was validated with a calculated limit of detection of 0.35 ppm and limit of quantitation of 1.09 ppm MFA. The method should have adequate sensitivity and reliability for veterinary toxicology labs analyzing specimens from animals poisoned by this predacide.

Phosphine detection in veterinary samples using headspace gas chromatography/tandem mass spectrometry with multiple reaction monitoring.

RATIONALE: Determination of phosphine exposure from zinc or aluminum phosphide fumigants continues to be a routine analytical requirement in veterinary forensic toxicology. There is a need for a more reliable and specific method than simple gas chromatography/mass spectrometry (GC/MS) analysis of sample solvent extracts, as GC/MS of extracts on capillary columns used for general screens involves significant interference from air peaks. METHODS: GC/MS/MS headspace analysis of acid-generated phosphine gas enabled study of the feasibility of devising multiple reaction monitoring (MRM) approaches to the determination of phosphine with greater specificity. RESULTS: Collision-induced dissociation in GC/MS/MS showed that phosphine generated m/z 34 → 31, 32 and 33 ion transitions by sequential proton release as well as minor transitions m/z 34 → 47, 34 → 63 and 63 → 31.5 by intermolecular collisions and double charging. Study of the formation of these product ions enabled development of MRM settings for a highly useful headspace method for phosphine detection. CONCLUSIONS: The method was validated over a working range of 5-100 ppm of phosphide generating phosphine gas which enabled retention of regular screen capillary columns without necessitating separation from air components. The method should have adequate sensitivity and reliability for veterinary toxicology laboratories confronting specimens from animals poisoned by crop fumigants.

Haloxyfop determination by gas chromatography/tandem mass spectrometry in eggs.

RATIONALE: Haloxyfop is a pre/post-emergence herbicide with known organ toxicities and teratogenic effects in mammals. The European Union Commission on Food Safety has an established maximum residue limit of 10 µg/kg in all agricultural products including eggs. A sensitive highly specific method would be of value in determination of haloxyfop residues in foodstuffs such as eggs. METHODS: The Michigan State University Veterinary Diagnostic Lab (MSU VDL) developed a method for the extraction of haloxyfop from eggs based on popular QuEChERS (quick, easy, cheap, effective, rugged, and safe) methodologies, essentially providing acetonitrile extracts following treatment with high ionic strength additives. Extracts derivatized with trimethylsilyl (TMS) groups were examined by gas chromatography/tandem mass spectrometry using developed multiple reaction monitoring (MRM) methodology. RESULTS: The MSU VDL received eggs from chickens exposed to 760 µg/kg haloxyfop in flaxseed. Haloxyfop-TMS m/z 374→73 MRM setting enabled quantitation across the 1-50 ppb range in comparison with an ibuprofen MRM transition as internal standard. CONCLUSIONS: The determined limit of quantitation was 2.5 ng/g, and the method successfully identified haloxyfop residues in five of six batches of the chicken eggs, with nonzero values ranging from 2.7 to 14.5 ng/g. These values were consistent with flaxseed incorporation into the diet at 4-7% and known excretion into eggs at 2-3% of daily haloxyfop exposure, and establish the utility of the method in identifying regulatory noncompliance and adulteration of food sources.

Liquid chromatography/tandem mass spectrometric analysis of penicillamine for its pharmacokinetic evaluation in dogs.

Copper storage disease occurs in multiple dog breeds and is one of the most common causes of chronic hepatitis in this species. The disease is caused by hereditary defects in copper metabolism in conjunction with high dietary copper levels. The progressive copper accumulation leads to hepatitis, cirrhosis, and eventually death if left untreated. Copper chelators are critical in modulating the effects of this disease. It is therefore of significant practicality to understand the pharmacokinetic (PK) parameters of chelating agents, particularly since they are oftentimes quite expensive. A liquid chromatography-tandem mass spectrometric (LC/MS/MS) method was developed to measure plasma levels of one of the most common chelators, d-penicillamine. The compound was discovered to exist in two forms, monomeric and dimeric, and various chemical derivatizations were tried to force the compound into one form or the other. Eventually, the simplest approach was individual determination of penicillamine and its dimer, with summation of the two quantities. This enabled determination of canine PK parameters for penicillamine based on comparison of oral and intravenous administration of the drug, including time to maximum drug level (Tmax), concentration at maximum (Cmax), clearance (Cls) and volume of distribution (Vdss). The drug was found to exist predominantly in the dimeric form in plasma, which is incapable of chelating copper owing to lack of free sulfhydryl groups and must therefore provide a storage form of the drug in equilibrium with its monomeric form in vivo. Mechanisms are discussed for the electrospray-induced fragmentation of penicillamine as well as of its dimer.

Lead Intoxication in Free-Ranging Bald Eagles ( Haliaeetus leucocephalus).

Lead toxicity due to ingestion of spent ammunition is an ongoing cause of mortality in bald eagles. While gross and histologic lesions of lead intoxication have been described in a few individuals of this species, the prevalence of lesions is underreported. A retrospective study of 93 bald eagles with severe lead intoxication was performed to describe the associated lesions and their prevalence and to compare the lesions with blood, liver, kidney, and/or bone lead concentrations. Gross lesions associated with lead toxicity were most frequent within the heart (51/93 birds) and consisted of multifocal myocardial pallor and rounding of the apex. Within the brain, gross lesions included petechiae or hemorrhagic necrosis (13/93 birds). Histologic lesions compatible with lead toxicity occurred within the heart (76/93 birds), brain (59/93 birds), and eyes (24/87 birds). Lead toxicity in bald eagles is characterized by fibrinoid necrosis of small- to medium-caliber arteries, most commonly affecting the heart, brain, and eyes. Gross and histologic lesions are consistent with ischemia caused by a primary vascular injury. A blood lead concentration of greater than 4 ppm and markedly elevated liver lead concentrations were associated with a greater likelihood of lesions in the heart. Severe lead intoxication is frequently associated with lesions that are histologically detectable in bald eagles. The presence of fibrinoid arterial necrosis and parenchymal degeneration, necrosis, and/or hemorrhage within the heart, brain, and/or eyes is suggestive of lead toxicity in bald eagles and warrants evaluation of liver or bone lead concentrations.

Short communication: Survey of hepatic copper concentrations in Midwest dairy cows.

Previous research from our laboratory and others indicates that liver copper concentrations in dairy cattle are commonly well above those recognized as adequate for the nutritional needs of the animal. It has also been speculated that hepatic copper concentrations have been increasing in recent years. Unlike other species, the threshold at which elevated liver copper concentrations becomes deleterious to hepatocytes is not known for cattle. Therefore, the objectives of this study were 3-fold: (1) to delineate differences in the range and mean dry matter hepatic copper concentration for dairy cattle in a retrospective analysis (January 1, 2007, to December 31, 2015), (2) to investigate hepatic copper concentrations in Midwest cull dairy cattle, and (3) to evaluate histologic changes in hepatocellular morphology in the context of copper concentration in cull cows. Furthermore, microscopic changes in hepatocellular morphology or architecture were examined and scored for evidence of inflammation, fibrosis, necrosis, and abundance of rhodanine-stained granules using hematoxylin and eosin and rhodanine staining. The retrospective analysis found copper concentrations within a range of 3 to 1,963 µg/g, with a mean of 473 µg/g. Hepatic copper concentrations in our retrospective study did not increase with time. In our abattoir analysis, copper concentrations ranged from 15 to 978 µg/g, with a mean of 390 µg/g. This study found that the range and mean hepatic copper concentrations were comparatively less in the current abattoir study than copper concentrations in our retrospective analysis. There was no evidence for hepatocellular changes associated with increased copper burdens in this study population.

Qualitative identification of imidacloprid in postmortem animal tissue by gas chromatography-tandem mass spectrometry.

During an avian mass mortality event investigation at the National Fish and Wildlife Forensic Laboratory in Ashland, OR, imidacloprid became an insecticide of concern. A qualitative analytical toxicology screen of seeds, plucks (tongue, esophagus, and trachea), and ventricular contents was requested. A method for the extraction and qualitative analysis of the insecticide in animal tissues was therefore developed. The procedure relies on a combined Food Emergency Response Network (FERN) and QuEChERS (Quick, Easy, Cheap, Effective, Rugged, and Safe) approach to sample extraction followed by qualitative analysis by gas chromatography-tandem mass spectrometry. Since imidacloprid is not amenable to the conditions of gas chromatography, a trimethylsilyl derivative was created and characterized. Proposed mechanisms for the creation of this derivative and its mass spectrum are described. The imidacloprid-trimethylsilyl (TMS) derivative was detected in all samples submitted.

A Cytochrome P450-Independent Mechanism of Acetaminophen-Induced Injury in Cultured Mouse Hepatocytes.

Mouse hepatic parenchymal cells (HPCs) have become the most frequently used in vitro model to study mechanisms of acetaminophen (APAP)-induced hepatotoxicity. It is universally accepted that APAP hepatocellular injury requires bioactivation by cytochromes P450 (P450s), but this remains unproven in primary mouse HPCs in vitro, especially over the wide range of concentrations that have been employed in published reports. The aim of this work was to test the hypothesis that APAP-induced hepatocellular death in vitro depends solely on P450s. We evaluated APAP cytotoxicity and APAP-protein adducts (a biomarker of metabolic bioactivation by P450) using primary mouse HPCs in the presence and absence of a broad-spectrum inhibitor of P450s, 1-aminobenzotriazole (1-ABT). 1-ABT abolished formation of APAP-protein adducts at all concentrations of APAP (0-14 mM), but eliminated cytotoxicity only at small concentrations (≦5 mM), indicating the presence of a P450-independent mechanism at larger APAP concentrations. P450-independent cell death was delayed in onset relative to toxicity observed at smaller concentrations. p-Aminophenol was detected in primary mouse HPCs exposed to large concentrations of APAP, and a deacetylase inhibitor [bis (4-nitrophenyl) phosphate (BNPP)] significantly reduced cytotoxicity. In conclusion, APAP hepatocellular injury in vitro occurs by at least two mechanisms, a P450-dependent mechanism that operates at concentrations of APAP ≦ 5 mM and a P450-independent mechanism that predominates at larger concentrations and is slower in onset. p-Aminophenol most likely contributes to the latter mechanism. These findings should be considered in interpreting results from APAP cytotoxicity studies in vitro and in selecting APAP concentrations for use in such studies.

Atypical bromethalin intoxication in a dog: pathologic features and identification of an isomeric breakdown product.

BACKGROUND: Definitive post mortem confirmation of intoxication by the neurotoxic rodenticide bromethalin can be challenging. Brain lesions are not specific and detection of bromethalin and its metabolites are unpredictable due to rapid photodegradation and inconsistent behavior in tissues. CASE PRESENTATION: A 2-year-old dog presented with rapid onset of severe muscle tremors and death within hours after a known ingestion of a reportedly low dosage of bromethalin and subsequent decontamination using activated charcoal. Marked meningeal hemorrhages and multifocal myelin sheath vacuolation were observed in the brain. A marked reactive astrocytosis and neuronal hypoxia/necrosis were identified using immunohistochemistry (IHC) for glial fibrillary acidic protein (GFAP) and for neuron specific protein (NeuN). Bromethalin exposure and tissue absorption was confirmed by identification of one of two isomeric 543.7 molecular weight (MW) breakdown products in the patient's adipose and kidney samples using gas chromatography (GC) combined with tandem quadrupole mass spectrometry (MS/MS). CONCLUSIONS: The severity of clinical signs and subsequent death of this dog was not expected with the low dosage of bromethalin reportedly ingested, and the use of activated charcoal possibly precipitated a hypernatremic status. Meningeal hemorrhages are atypical of bromethalin intoxication, and might have been caused by hyperthermia, secondary to tremors or hypernatremia. Identification of one of two isomeric breakdown products in the adipose tissue and kidney provides an additional molecule to the toxicologic testing regime for bromethalin intoxication.

Fatal diphenhydramine poisoning in a dog.

We report a fatal diphenhydramine poisoning of a 10-year-old, male poodle-cross dog with pre-existing conditions and suspected co-ingestion of ethanol. This case illustrates that diphenhydramine overdose can be fatal in certain circumstances and that analytical toxicology may play an important role in animal death investigations.

Empoisonnement mortel à la diphenhydramine chez un chien. Nous signalons un empoisonnement mortel à la diphenhydramine chez un caniche croisé mâle âgé de 10 ans ayant des conditions préexistantes et une co-ingestion soupçonnée d'éthanol. Ce cas illustre qu'une surdose de diphenhydramine peut être mortelle dans certaines circonstances et qu'une toxicologie analytique peut jouer un rôle important dans les enquêtes sur la mort d'animaux.(Traduit par Isabelle Vallières).

Lisdexamfetamine dimesylate (Vyvanse) toxicosis in a dog.

OBJECTIVE: To describe the presentation, management, and postmortem examination findings in a dog with confirmed lisdexamfetamine dimesylate (LDX) toxicosis. CASE SUMMARY: A 3-year-old female neutered mixed breed dog initially presented with neurological signs suspected to be secondary to LDX toxicosis. The dog was treated as typical for amphetamine toxicoses but developed severe respiratory and cardiovascular signs throughout their hospitalization. The progression of the cardiopulmonary signs led to cardiopulmonary arrest, for which CPR was unsuccessful. Postmortem examination exhibited severe hemorrhage throughout multiple organ systems. Toxicology testing confirmed the presence of unaltered LDX and its metabolite, amphetamine. NEW OR UNIQUE INFORMATION PROVIDED: This is the first case report documenting a severe progression of clinical signs and postmortem examination findings in a case of confirmed LDX toxicosis in a dog. Although the patient did not survive treatment, postmortem examination and microscopic evaluation of tissues allowed visualization of the extent of systemic pathophysiology. With prompt treatment, the prognosis of amphetamine toxicosis in dogs is generally considered good; however, this case report demonstrates a severe case in which even prompt and appropriate treatment did not prevent mortality. This suggests a need to establish negative prognostic indicators for which to monitor in cases of amphetamine toxicosis. Finally, this report is also unique in the fact that the LDX toxicosis was confirmed using a toxicological analysis technique not previously described clinically in dogs.

Rhinoceros horn mineral and metal concentrations vary by sample location, depth, and color.

Poaching is again driving rhinos to the brink of extinction due to the demand for rhino horn products consumed for cultural, medicinal, and social purposes. Paradoxically, the same horn for which rhinos are killed may contain valuable clues about the species' health. Analyses of horn composition could reveal such useful bioindicators while elucidating what people actually ingest when they consume horn derivatives. Our goals were to quantify minerals (including metals) in rhino horn and investigate sampling factors potentially impacting results. Horns (n = 22) obtained during necropsies of white (n = 3) and black (n = 13) zoo rhinos were sampled in several locations yielding 182 specimens for analysis. Initial data exposed environmental (soil) contamination in the horn's exterior layer, but also confirmed that deep (≥ 1 cm), contaminant-free samples contained measurable concentrations of numerous minerals (n = 18). Of the factors examined in deep samples, color-associated mineral differences were the most profound with dark samples higher in zinc, copper, lead, and barium (p < 0.05). Our data demonstrate that rhino horns contain both essential and potentially toxic minerals that could be relevant to rhino health status, but low concentrations make their human health benefits or risks unlikely following consumption.

Dried blood spot analysis for elements of nutritional concern as demonstrated in studies of Galápagos land iguanas (Conolophus species).

BACKGROUND: Dried blood spot (DBS) technology is valuable in providing simple means of storing blood samples from wildlife with small blood volumes. Methods designed for heavy metal analysis on DBS become more useful if extended to elements of nutritional significance. PURPOSE: (1) Development of procedures for measuring Mn, Fe, Co, Cu, Zn, Se and Mo in DBS; (2) use the designed methods in health assessments of Galápagos land iguanas (Conolophus species). PROCEDURES: Elements were measured by inductively coupled plasma/mass spectrometry (ICP-MS) following acid digestion of whole blood or DBS from the same animal for direct comparison. Study animals comprised free-ranging iguanas from separate islands in the Galápagos archipelago. MAIN FINDINGS: DBS spikes (Mn, Fe, Co, Cu, Zn, Se and Mo) demonstrated accuracy to ∼100 ppb; reporting limits were set there except for Fe and Zn which were set at 1000 ppb. Plasma samples - generally preferable for nutritional element diagnostics - were submitted from Galápagos land iguanas along with DBS as part of a large-scale health assessment. In plasma versus DBS concentration comparisons, Fe, Cu, Se and Mn correlated well with R^2 values of 0.799, 0.818, 0.896 and 0.899, respectively, and slopes ranging 0.88 - 1.3. Co and Zn showed greater scatter. Mo had insufficient points above its reporting limit and offered advantages for toxicity assessments. Bland-Altman diagrams showed flat scatter between 2x standard deviation boundaries with no undue trends except for Mn which had few points above its reporting limit. Bias, defined as the average difference [DBS - plasma] divided by the average value, was relatively low throughout, with values of - 19.3 % (Fe), - 48.7 % (Co), - 19.6 % (Cu), - 6.9 % (Zn), - 21.4 % (Se) and + 40.7 % (Mn). Normal distribution assessment of iguana Cu, Zn, Se and Fe plasma values showed unanticipated divergences between two species. CONCLUSIONS: The DBS approach for nutritional element analysis offers a suitable methodology for determining crucial elements Mn, Fe, Co, Cu, Zn, Se, and Mo in veterinary samples. Analyses of samples from Conolophus species revealed interesting divergences particularly for Cu, Zn, Se and Fe, elements generally associated with defense against oxidative stress.

Sulfaquinoxaline Toxicosis in a Juvenile Broiler Breeder Flock.

A flock of 50,000 28-day-old broiler breeder chickens experienced an elevated mortality event. Chickens from that flock, five pullets and six cockerels, were submitted for diagnostic investigation. Necropsy revealed bacterial septicemia with fibrinous polyserositis in the majority of the birds while two cockerels had coccidial typhlitis. Because sulfadimethoxine was not available at the time, sulfaquinoxaline (SQ) was prescribed at label dosage with water treatment for 2 days, followed by 3 days of no medication, followed by 2 days of medication. The mortality rose dramatically 9 days after the last treatment. Lesions at that time consisted of skin discoloration, subcutaneous petechiation, and enlarged pale kidneys. Mortality remained elevated for 14 days. Analysis of blood, kidney, and liver revealed elevated levels of SQ. Recalculation of dosage, water consumption, amount of drug administered, remaining drug stock, and concentration of supplied SQ were analyzed and determined to be as predicted.

Reporte de caso- Toxicosis por sulfaquinoxalina en una parvada de reproductores de pesados jóvenes. Una parvada de 50,000 pollos de engorde de 28 días de edad experimentó un evento de mortalidad elevada. Pollos de esa parvada, cinco pollitas y seis gallitos, se enviaron para una investigación de diagnóstico. La necropsia reveló septicemia bacteriana con poliserositis fibrinosa en la mayoría de las aves, mientras que dos gallos tenían tiflitis coccidial. Debido a que la sulfadimetoxina no estaba disponible en ese momento, se prescribió sulfaquinoxalina (SQ) de acuerdo a la dosis de la etiqueta con tratamiento en el agua durante dos días, seguidos por tres días sin medicación, y por último, seguidos por dos días de medicación. La mortalidad aumentó dramáticamente nueve días después del último tratamiento. Las lesiones en ese momento consistían en decoloración de la piel, petequias subcutáneas y riñones agrandados y pálidos. La mortalidad se mantuvo elevada durante 14 días. El análisis de sangre, riñón e hígado reveló niveles elevados de sulfaquinoxalina. Se analizó el recálculo de la dosis, el consumo de agua, la cantidad de fármaco administrado, el stock de fármaco restante y la concentración de sulfaquinoxalina suministrada y se determinó que eran los previstos.

Common Toxicosis.

Veterinarians are often called upon to diagnose health-related issues on the farm that may be related to trace mineral deficiencies or toxicities. Trace mineral feeding rates are often not available due to the proprietary nature of the trace mineral premixes provided by nutritional consultants. The veterinarian needs to be aware of the common clinical signs of trace mineral deficiencies and toxicities, interactions between trace minerals that may result in deficiencies, clinical samples that are necessary for the proper diagnosis, and the recommended normal ranges of each trace mineral depending on the age of the animal.

Single oral or intravenous administration of voriconazole achieved recommended therapeutic minimum inhibitory concentrations against Aspergillus in the common raven (Corvus corax).

OBJECTIVE: To determine the pharmacokinetics of voriconazole after single IV or orally administered boluses in common ravens (Corvus corax). ANIMALS: 8 healthy common ravens. PROCEDURES: Voriconazole (5 mg/mL, 10 mg/kg IV) was administered to 8 birds, and then plasma voriconazole concentrations were measured at various time points by high-pressure liquid chromatography with mass spectrometry. Starting 6 months later in a randomized 3-treatment 3-period regimen, birds received a single oral dose of voriconazole suspension (10 mg/mL; 6, 12, and 24 mg/kg PO). The study period was May 2015 to March 2016. RESULTS: Voriconazole (10 mg/kg IV) achieved an initial plasma concentration of 6.31 µg/mL when measured over 21 hours. After oral administration of voriconazole at 6, 12, and 24 mg/kg, the relative bioavailability was 67.5%, 209%, and 183%, respectively. For the 6-mg/kg dose, the maximum plasma concentration was reached at 30 minutes after administration and remained in the therapeutic range of 0.5 to 1 µg/mL for approximately 15 hours. The 12- and 24-mg/kg doses resulted in concentrations in a potentially toxic range. CLINICAL RELEVANCE: Voriconazole was well tolerated. All 4 doses resulted in plasma concentrations of voriconazole > 0.5 µg/mL, which is the minimum inhibitory concentration recommended for pathogenic species of Aspergillus fungi known to affect birds. A single dose of voriconazole administered as 10 mg/kg IV or 6 mg/kg PO resulted in recommended target plasma concentrations. Administration of voriconazole 6 mg/kg PO 2 to 3 times daily may be adequate for treatment without exceeding the toxic range.

Heroin Fatality in a Feline: A Case Report with Postmortem Liver Concentrations.

A case of feline intoxication and fatality with the illicit drug heroin is described. A 5-year-old castrated male domestic shorthair cat was recently diagnosed with an active pneumonitis and left at home for a couple of days under the care of another resident. Upon return, the owner found his cat dead with strong suspicion of foul play. The cat was necropsied by a local veterinary clinic to retrieve the liver for diagnostic toxicology. The postmortem liver sample screened positive for 6-acetylmorphine and 6-acetylcodeine by gas chromatography mass spectrometry. Deconvolution techniques were applied to chromatograms, which revealed the additional presence of morphine and mirtazapine. Subsequent quantitation of mirtazapine, heroin, morphine, 6-acetylmorphine and 6-acetylcodeine was performed by gas chromatography--tandem quadrupole mass spectrometry. Although companion animal fatalities arising from toxicities are a likely consequence of drug abuse in a home, this is the first reported case of a malicious feline fatality resulting from heroin with quantitation of heroin metabolites.