Comparative pathologic changes in broiler chicks on feed amended with Fusarium proliferatum culture material or purified fumonisin B1 and moniliformin.

Feed amended with autoclaved culture material (CM) of Fusarium proliferatum containing fumonisin B1 (FB1) (61-546 ppm), fumonisin B2 (FB2) (14-98 ppm) and moniliformin (66-367 ppm) was given to 228 male chicks in three separate feeding trials. In a fourth feeding trial, purified FB1 (125 and 274 ppm) and moniliformin (27 and 154 ppm) were given separately and in combination (137 and 77 ppm, respectively). Chicks that died during the trial periods, survivors and controls were subjected to postmortem examination. Specimens (liver, kidney, pancreas, lung, brain, intestine, testis, bursa of Fabricius, heart and skeletal muscle) were examined grossly and preserved for subsequent histopathologic and ultrastructural examination. Prominent gross lesions in affected birds fed diets amended with CM or purified FB1 and moniliformin included ascites, hydropericardium, hepatopathy, nephropathy, cardiomyopathy, pneumonitis, gizzard ulceration, and enlarged bursa of Fabricius filled with caseous material. The various concentrations of FB1 and moniliformin in the amended rations produced well-defined dose-response lesions in all groups in all four trials. Histopathologic changes included hemorrhage, leucocytic infiltration, fatty change or infiltration, individual cell necrosis and fibrosis in liver, kidneys, lungs, heart, intestines, gizzard, bursa of Fabricius and pancreas. Edema and hemorrhage were prominent in brains of treated birds. Ultrastructural changes included cytoplasmic and nuclear enlargement of cells in affected liver, lungs, kidneys, heart and pancreas. There were thickened membranes of the smooth endoplasmic reticulum, dilation of the rough endoplasmic reticulum with loss of ribosomes and vacuolated or deformed mitochondria.

Weakness, tremors, and depression associated with macadamia nuts in dogs.

The ASPCA National Animal Poison Center managed 29 cases of ingestion of commercially available macadamia nuts in dogs during a 5-y period. Clinical signs included, from most to least, weakness, depression, vomiting, ataxia, tremor, hyperthermia, abdominal pain, lameness, stiffness, recumbency, and pale mucous membranes. The onset of clinical signs was reported as < 12 h in 79% of the cases. The duration of clinical signs for the majority of cases was < 24 h. The amount of macadamia nuts ingested was estimated in 72% of the calls with a mean of 11.7 g/kg bw. In an attempt to reproduce the syndrome, 4 dogs were gavaged with 20 g macadamia nuts/kg bw in a water slurry. The experimentally dosed dogs developed weakness, manifested by the inability to rise 12 h after dosing, mild central nervous system depression, vomiting, and hyperthermia, with rectal temperatures up to 40.5 C. Mild elevations in serum triglycerides and serum alkaline phosphatase were detected. Lipase values peaked sharply at 24 h and returned to normal by 48 h after dosing. Other serum biochemical and electrolyte determinations were unremarkable. Serum lipoprotein electrophoresis determinations were unchanged from baseline. The mechanism of the syndrome is unknown. All field and experimental dogs recovered uneventfully within 1 to 2 d whether treated by a veterinarian or not.

Ibuprofen, aspirin and acetaminophen toxicosis and treatment in dogs and cats.

Toxicosis to 3 commonly available analgesics--ibuprofen, aspirin and acetaminophen--occurs in dogs and cats after acute ingestion or repetitive administration of therapeutic or excessive doses. Whereas in acute exposure, where the clinical course of an overdose to all 3 drugs is predictable in relation to the amount ingested, in chronic exposure to therapeutic doses of aspirin and ibuprofen, the development of gastric ulcers and analgesic nephropathy is unpredictable. Ibuprofen is not recommended for prolonged treatment in dogs and cats due to the likelihood of ulcer formation. Although gastric mucosal adaptation usually occurs with repeated therapeutic doses of aspirin, some individuals nevertheless develop gastric ulcers; simultaneous administration of the prostaglandin analogue misoprostol can reduce the risk. Following acute ingestion of aspirin or ibuprofen, treatment is essentially symptomatic and supportive following early decontamination procedures. Gastrointestinal protectants and i.v. fluids with sodium bicarbonate are generally recommended. Acetaminophen toxicosis is usually associated with single acute ingestion, and the primary target organs affected are the liver and the red blood cells in dogs and cats respectively. Because signs can progress rapidly with acute acetaminophen overdose, administration of N-acetylcysteine is always recommended, even when the history is unclear. This report summarizes the common clinical presentations of dogs and cats exposed to therapeutic or excessive doses of ibuprofen, aspirin or acetaminophen, and describes the treatment procedures advised by the ASPCA-National Animal Poison Control Center.

Malignant hyperthermia-like reaction secondary to ingestion of hops in five dogs.

Five dogs, 4 of which were Greyhounds, suffered adverse effects secondary to the ingestion of spent hops. Mean time to onset of clinical signs was 3 hours, and clinical signs included marked hyperthermia, restlessness, panting, vomiting, signs of abdominal pain, and seizures. Four of the 5 dogs died despite aggressive therapeutic measures, and there was rapid onset of rigor mortis in 3. The overrepresentation of Greyhounds, coupled with the clinical signs, was suggestive of a malignant hyperthermia-like response to the ingestion of hops. It also is possible that hops contain an uncoupler of oxidative phosphorylation.

Can household pets be used as reliable monitors of lead exposure to humans?

We investigated the validity of dogs and cats as sentinels of environmental lead exposure to humans. This paper reports findings from a study conducted in Granite City, IL, during the summer of 1991. At this site, a former secondary lead smelter had been in activity for more than 80 years. The smelter was shut down in 1982. The surrounding area was found to be contaminated with lead, with soil lead concentrations above 5000 ppm in some places. The Illinois Department of Public Health conducted a survey in the community to determine the effects of lead on the local population. We sampled dogs and cats owned by these people. Our results suggest that living near a closed lead smelter, with heavy soil contamination, was not associated with high blood lead concentrations in pets, or their owners. There was a significant relationship between BLC (blood lead concentrations), in indoor pets and younger children, which was consistent with our hypothesis that pets could be used to monitor childhood lead exposure. We also found that, when there was one pet with a high BLC in a house, the likelihood of finding one person with a BLC above 10 micrograms/dl was significantly increased.

Treatment of acute isoniazid overdose in dogs.

The National Animal Poison Control Center received 28 calls of isoniazid (INH) exposures in dogs and cats between 1987 and 1993. The ingestion of a single 300 mg INH tablet was the most common complaint. Isoniazid has a low therapeutic margin and produces life threatening signs in dogs ingesting single 300 mg human tablets. The LD50 of INH in dogs is estimated at 50 mg/kg bw, which is probably similar to that for humans. However, rodents are among the species most resistant to INH and thus are not good animal models for toxic dose extrapolation. The more consistent clinical signs reported were recurrent clonic-tonic seizures followed by a stuporous state with poor response to stimulus. Ideal treatment combines vitamin B6 given as a single i.v. bolus at an equivalent dose to the amount of INH ingested and anticonvulsants such as 1 mg diazepam/kg bw. This combination acts synergistically to improve GABAergic transmission in the CNS and has proved effective in protecting animals from further convulsions and death, even after several seizure episodes, as often encountered in clinical situations.

Serohematologic alterations in broiler chicks on feed amended with Fusarium proliferatum culture material on fumonisin B1 and moniliformin.

Two hundred twenty-eight male broiler chicks (Columbia x New Hampshire) were given feed amended with autoclaved culture material of Fusarium proliferatum containing fumonisin B1 (FB1) at 61, 193, and 546 ppm, fumonisin B2 (FB2) at 14, 38, and 98 ppm, and moniliformin at 66, 193, and 367 ppm in 3 separate feeding trials (amounts of toxin in each trial, respectively). Birds were started on amended rations at days 1, 7, and 21 and continuing for 14 days. Of serum chemistry parameters, only glucose was significantly decreased. Significant increases were noted in serum cholesterol, sodium, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and gamma-glutamyl transferase. Of the hematologic parameters, significant decreases were noted in red blood cell counts, hemoglobin, packed cell volume, and white blood cell counts. Immunologic changes included impaired anti-Newcastle disease antibody hemagglutination inhibition titers associated with relative decreases in total serum globulins and increases in albumin/globulin ratios. The changes were noted in all treatment groups when compared to controls.

Relationship between soil lead, dust lead, and blood lead concentrations in pets and their owners: evaluation of soil lead threshold values.

This paper reports the results of a study conducted in Granite City, Illinois during the months of August through October 1991. The study involved a subpopulation of 77 households having 106 dogs and cats which was a corollary to a major study conducted in humans by the Illinois Department of Public Health to evaluate lead exposure. A secondary lead smelter had been in operation in this town for almost 80 years and was shut down in 1982. Important soil contamination with lead was reported and this paper presents data regarding levels of soil and dust lead and associated blood lead concentrations in animals and their owners in a total of 77 households. Overall, blood lead concentrations (BLC) were low (0-13 micrograms/dl in the animal owners; 0-28 micrograms/dl in pets). There was no significant relationship between soil or dust lead and BLC in humans; however, the relationship was significant in animals. Odds ratios were computed to determine whether 500 or 1000 ppm lead in environmental samples was associated with increased risk of having a high BLC. We could not find any increased risk in humans, while the risk did increase in animals. It is concluded that animals are more at risk than their owners of having a high BLC when exposed to the same contaminated environment and can be used to monitor the bioavailability of lead.

Toxicity of melaleuca oil and related essential oils applied topically on dogs and cats.

Cases of melaleuca oil toxicosis have been reported by veterinarians to the National Animal Poison Control Center when the oil was applied dermally to dogs and cats. In most cases, the oil was used to treat dermatologic conditions at inappropriate high doses. The typical signs observed were depression, weakness, incoordination and muscle tremors. The active ingredients of commercial melaleuca oil are predominantly cyclic terpenes. Treatment of clinical signs and supportive care has been sufficient to achieve recovery without sequelae within 2-3 d.

Low blood lead concentration associated with various biomarkers in household pets.

A former secondary lead smelter was in operation in Granite City, Ill, until the early 1980s. As a result, the surrounding area is heavily contaminated with lead. Soil concentrations as high as 5,000 ppm have been measured in prior studies. Because of growing concerns about health defects associated with low levels of lead exposure in human beings, a major study has been conducted on people living in the area. The study reported here was a corollary to the human exposure study. Lead concentration was determined in 84 dogs and 26 cats in the town and ranged between < 5 and 28 micrograms/dl. None of the dogs had clinical signs of lead poisoning. The CBC and serum biochemical values did not indicate many significant differences between dogs with a high (> or = 10 micrograms/dl) or low blood lead concentration (BLC). Hemoglobin concentrations were lower, and WBC counts were higher in dogs and cats with higher BLC, but they were still within reference ranges. Free erythrocyte protoporphyrin concentration was determined. Normal values appeared to be similar for dogs and cats. Only animals with BLC > or = 20 micrograms/dl were found to have somewhat increased concentration of free erythrocyte protoporphyrin. delta-Aminolevulinic acid dehydratase activity was measured and found to be negatively correlated with BLC. The relation was strong, even at low BLC (5 to 10 micrograms/dl) in both species. Age or sex difference was not observed. Therefore, biological changes associated with low BLC were limited to BLC in the 10- to 30-micrograms/dl range.

Lymphocyte cytotoxicity and erythrocytic abnormalities induced in broiler chicks by fumonisins B1 and B2 and moniliformin from Fusarium proliferatum.

Peripheral blood lymphocytes were isolated from broiler chicks that had ingested feed amended with autoclaved Fusarium proliferatum culture material containing fumonisin B1 (FB1), fumonisin B2 (FB2) and moniliformin. Lymphocyte viability was determined for birds that were placed on amended rations at day 1 or day 7 of age at three different levels of mycotoxins, ranging from 61-546 ppm FB1, 14-94 ppm FB2 and 66-367 ppm moniliformin. Reduction of the tetrazolium salt, MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide], to yield MTT formazan, based on mitochondrial metabolic activity, was used to assess cell viability. Lymphocyte cytotoxic effects were observed in all treatment groups on day 21; chicks that started on amended feed at day 1 of age were affected more than those that started at day 7. Abnormal erythrocytes resembling early stages of erythroblasts were observed in peripheral blood from test chicks. Abnormally shaped red cells (poikilocytes) having a spindle-shape with one or both ends pointed were present. Some red cells appeared to be undergoing mitosis. Both reduced lymphocyte viability and abnormal erythrogenesis occurred in chicks given feed amended with F. proliferatum culture material containing FB1, FB2 and moniliformin.

Mortality in broiler chicks on feed amended with Fusarium proliferatum culture material or with purified fumonisin B1 and moniliformin.

Two hundred twenty-eight male chicks (Columbia x New Hampshire) were given feed amended with autoclaved culture material (CM) of Fusarium proliferatum Containing fumonisin B1 (FB1), fumonisin B2 (FB2) and moniliformin in 3 separate feeding trials. Purified FB1 and moniliformin were given separately and in combination in a fourth feeding trial. Birds were given amended rations at day 1 (Trial 1 and 4), day 7 (Trial 2), and day 21 (Trial 3) and their respective ration was given for 28 days (Trial 1), 21 days (Trial 2), 7 days (Trial 3), and 14 days (Trial 4). FB1 concentrations were 546, 193, and 61 ppm; FB2 were 98, 38 and 14 ppm; and moniliformin were 367, 193, and 66 ppm in the first 3 feeding trial regimens. Chicks in Trial 4 were given dietary concentrations of purified FB1 at 274 and 125 ppm, and moniliformin at 154 and 27 ppm. FB1 and moniliformin, both alone and in combination, produced dose-responsive clinical signs, reduced weight gains and mortality in chicks. Age of birds given amended feeds had little difference in the clinical response; however, those given the rations from days 7 or 21 were slightly less susceptible than those given rations beginning at 1 day of age. Additive effects were noted when the toxins were given in combination. When toxins were given separately, adverse effects took longer to occur. A system to monitor pattern and rate of defecation (RD) was developed for assessing the chicks' approach to feed, water and heat source as illness progressed. Our results indicate that chicks fed corn heavily infected with F. proliferatum under field conditions could suffer acute death similar to that described for 'spiking mortality syndrome' during the first 3 weeks of age.

Embryopathic and embryocidal effects of purified fumonisin B1 or Fusarium proliferatum culture material extract on chicken embryos.

One hundred eight fertile eggs (Columbia x New Hampshire) were assigned to 10 groups of 10 eggs each (2 control groups had 14 eggs each). Five groups of eggs were inoculated on day 1 of incubation, while the other 5 groups were inoculated on day 10. The inoculum of the 4 treatment groups on both day 1 and 10 consisted of 1,10, or 100 microM purified fumonisin B1 (FB1) or a culture material extract (CME) of Fusarium proliferatum, having known amounts of FB1, FB2 and moniliformin (FB1 20 microM; FB2 4 microM and moniliformin 7 microM). Inoculum consisted of the respective toxin(s) dissolved in 100 microliters double distilled, autoclaved water (diluent). Control eggs were inoculated with diluent only. Mortality was both dose- and time-responsive in all treatments. Eggs inoculated on day 1 with 1 microM FB1 had 50% mortality; 10 microM FB1 had 70% mortality; 100 microM FB1 had 100% mortality; and CME had 100% mortality. Eggs inoculated on day 10 with 1,10 or 100 microM FB1 or CME had 30, 60, 90 and 80% mortality, respectively. Normal chicks were hatched from all control eggs. The median death times (MDT50) were inversely dose-responsive in all treatments, ranging from 3.0 to 7.4 days in embryos exposed on day 1 and from 3.2 to 9.0 days in those exposed on day 10. Early embryonic changes in exposed embryos included hydrocephalus, enlarged beaks and elongated necks. Pathologic changes were noted in liver, kidneys, heart, lungs, musculoskeletal system, intestines, testes and brain toxin-exposed embryos.

Biliary excretion and enterohepatic cycling of zearalenone in immature pigs.

The disposition of the estrogenic mycotoxin, zearalenone (ZEN) in female, 10- to 14-week-old Yorkshire pigs was investigated. Pigs were administered [3H]ZEN intravenously (IV; n = 4; 5 mg/kg; 15 microCi/kg), orally (n = 4; 10 mg/kg; 30 microCi/kg), or intravenously with bile removal (IVB; n = 2; 5 mg/kg; 15 microCi/kg). Plasma, urine, feces, and bile (IVB pigs only) were serially collected and analyzed for radioactivity. Metabolite profiles were determined in plasma and bile by HPLC. The biological half-life of total plasma radioactivity in IV and orally dosed pigs (86.6 hr) was much larger than that of IVB animals (3.34 hr). Metabolite profiles of plasma concentration vs time demonstrated secondary peaks in concentration during the terminal elimination phase in IV and orally dosed pigs. In IVB pigs these peaks were absent, relative metabolite profiles were altered, and ZEN and metabolites were no longer detectable after 16 hr post-dosing. Biliary recovery of radioactivity, principally as glucuronide conjugates, was extensive (45.61 +/- 4.7%) in IVB pigs and significantly greater (p < 0.05) than that of fecal recovery of radioactivity in IV (6.56 +/- 0.78) or orally dosed (21.74 +/- 1.56%) pigs. Intraduodenal administration of bile containing [3H]ZEN and metabolites resulted in recovery of 64.56 +/- 4.89% of the dose in bile, 20.78 +/- 3.94% in urine, and the presence of glucuronide conjugates of ZEN and alpha-zearalenol (ZEL) in portal and jugular plasma. Differences in metabolite profiles between administered bile and sampled plasma suggest that the intestinal mucosa was active in reducing ZEN to ZEL and conjugating these metabolites with glucuronic acid. These studies provide evidence for extensive biliary secretion and enterohepatic cycling of ZEN and metabolites in pigs.

Neuropathologic findings of bromethalin toxicosis in the cat.

Ten random source male domestic shorthair cats, 2 to 6 years old and 3.0-4.4 kg body weight, were each given a single oral dose (1.5 mg/kg) of bromethalin (cat Nos. 1-5) or bait vehicle carrier (cat Nos. 6-10). Bromethalin-dosed cats developed a toxic syndrome characterized by ataxia, focal motor seizures, vocalization, decerebrate posture, decreased conscious proprioception, recumbency, depression, and semicoma. Bromethalin-dosed cats were euthanatized if seizure activity or hindlimb paralysis developed. Survival times were 48 hours (cat No. 1), 89 hours (cat No. 2), 90 hours (cat No. 3), and 97 hours (cat No. 4). Control cats (cat Nos. 6-10) and one bromethalin-dosed cat (cat No. 5) were euthanatized on day 20 after dosing. Spongy change (edema--characterized by the formation of vacuoles in extracellular spaces and myelin lamellae), hypertrophied fibrous astrocytes, and hypertrophied oligodendrocytes were observed in the white matter of the cerebrum, cerebellum, brain stem, spinal cord, and optic nerve of all bromethalin-dosed cats. Spongy change occasionally extended into contiguous cerebellar Purkinje cell layer and cerebral cortical gray matter. The severity of lesions varied among cats but was most pronounced in cat No. 5 (480 hours after dosing). A leukocytic inflammatory response, gitter cell (macrophage) response, or axonal degeneration was not observed in the vacuolated areas. Ultrastructural findings included separation of myelin lamellae at the interperiod lines with the formation of intramyelinic vacuoles (intramyelinic edema), rupture and coalescence of intramyelinic vacuoles into larger extracellular spaces (spongy change), and pronounced cytosolic edema of astrocytes and oligodendroglial cells.

Case reports of lead poisoning in dogs from the National Animal Poison Control Center and the Centre National D'Informations Toxicologiques, Veterinaires: anecdotes or reality?

This paper presents case reports of lead toxicoses from 2 major animal poison control centers in Europe and North America, gathered from 1985 through 1989. All results examined here involved cases assessed as "toxicosis" or "suspected toxicosis" by the National Animal Poison Control Center (NAPCC) or the Centre National d'Informations Toxicologiques Veterinaries (CNITV). 537 cases were reported to the NAPCC, most of them concerning dogs (59%). In France, most of the 362 cases involved cattle (57.2%). There was an increased number of cases reported during late summer and early fall, and a decreased number of cases in November and December, in both centers. Dogs intoxicated were predominantly young animals (60% were less than 2 years old). No sex difference was noted. Pure bred dogs appeared more often involved than mixed-breed ones, but the breed distribution closely resembles dog breed distribution in the US. The source of lead was usually unknown and, when information was available, paint seemed to be the most common cause of poisoning. Clinical signs reported to the animal poison control centers involved the CNS and GI tract. Results from the French and the American database showed similar trends. They are compared to data from veterinary clinics and veterinary colleges in the US and Australia. In each case, data are very similar to what was reported to the CNITV and the NAPCC. It is concluded that animal poison control centers databases can provide a useful tool for better knowledge of animal poisoning. They can also help identify unexpected toxicologic problems related to drug administration or pesticide use.

Effects of an extract of Gingko biloba on bromethalin-induced cerebral lipid peroxidation and edema in rats.

The effects of administration of a commercially available extract of Gingko biloba (EGB) on bromethalin-induced brain lipid peroxidation and cerebral edema in adult male Sprague-Dawley rats was determined. Gingko biloba extract was given (100 mg/kg) by gavage immediately after bromethalin (1.0 mg/kg) administration. Rats were euthanatized at 24 hours after dosing. Brain lipid peroxidation was determined by measurement of brain malonaldehyde-thiobarbituric acid chromophore (MDA-TBA) concentration, brain sodium concentration, and brain water content. Treatment of bromethalin-dosed rats (10/group) with EGB was associated with a statistically significant (P less than 0.05) decrease in clinical sign severity, compared with bromethalin-dosed saline solution-treated rats. All rats given bromethalin and saline solution developed clinical signs of toxicosis including CNS depression, hind limb weakness, ataxia, paralysis, and coma. Some rats given bromethalin and EGB developed clinical signs, however, none developed hind limb paralysis. The brain MDA-TBA concentration (2.4 +/- 0.5 delta MDA-TBA concentration/mg of protein), percentage of water in brain tissue (80.3 +/- 0.30%), and brain sodium concentration (6.68 +/- 0.21 mg/g of dry weight) were significantly increased in rats given bromethalin and saline solution, compared with control rats given saline solution (1.0 +/- 0.1 delta MDA-TBA concentration/mg of protein; 78.1 +/- 0.33% water in brain tissue; 4.83 +/- 0.30 mg of brain Na+/g of dry weight) and rats given bromethalin and EGB (1.6 +/- 0.2 delta MDA-TBA concentration/mg of protein; 79.3 +/- 0.31% water in brain tissue; 5.37 +/- 0.34 mg of brain Na+/g of dry weight).(ABSTRACT TRUNCATED AT 250 WORDS)

Regional brain blood flow in swine following T-2 toxin administration.

Three groups of swine (6/group) were used to assess alterations in regional brain blood flow induced by T-2 toxin. One group served as vehicle (70% ethanol) control, and groups were dosed intravascularly with T-2 toxin at 0.6 or 2.4 mg/kg body weight. Cerebral, cerebellar, and brain stem blood flows were evaluated at 0 h (predosing) and at 90-min intervals for 6 h postdosing. Fifteen-micron diameter radionuclide labeled microspheres were used to determine blood flow. Hemodynamic variables were determined at the same time points. The infusion of T-2 toxin resulted in dose-dependent reductions in both cardiac index and mean arterial pressure, accompanied by significant increases in heart rate. In animals given the lower dose of T-2 toxin, significant reductions in blood flow were evident in the cerebrums and cerebellum but not in the brain stem. Reductions in blood flow to all regions of the brain were evident in those animals given 2.4 mg T-2 toxin/kg. Brain blood flow was less severely compromised than was cardiac output, suggesting intact local autoregulation.