The effects of natural exposure to high levels of zinc and cadmium in the immature pony as a function of age.

To study the effects of environmental exposure to zinc and cadmium in immature foals, five pregnant ponies were raised within 2.9 km of the New Jersey Zinc Smelter in Palmerton, Pennsylvania. The mares and their foals were kept outdoors on timothy hay and orchard grass. The foals were examined daily for signs of illness and blood samples were taken monthly for estimation of serum zinc, copper, and ceruloplasmin levels. The foals were sacrificed at 2.5, 4.5, 8.5, 13.5, and 18.5 months of age. Necropsy revealed generalized osteochondrosis in joints of the limbs and cervical vertebrae, lymphoid hyperplasia, and eosinophilia. Two of the foals had developed mild lameness. The concentrations of zinc, cadmium, copper, lead, magnesium, and calcium were determined in liver, kidney cortex, and pancreas. The concentration of cadmium and zinc were the only elements that were greatly elevated in all three tissues as compared to control animals. The concentration of cadmium was directly correlated with age in the three tissues (e.g., 23.9 to 212.7 micrograms/g wet wt in kidney cortex), whereas zinc was significantly increased (range 132 to 954 micrograms/g wet wt in liver) but there was no correlation with age. It was concluded that the development of osteochondrosis is associated with increased exposure to zinc and possibly cadmium. The classical signs of cadmium toxicosis, such as renal damage and osteomalacia, were not observed.

Pharmacokinetic disposition of theophylline in horses after intravenous administration.

The pharmacokinetics of theophylline were determined in 6 healthy horses after a single IV administration of 12 mg of aminophylline/kg of body weight (equivalent to 9.44 mg of theophylline/kg). Serum theophylline was measured after the IV dose at 0.25, 0.5, 1, 2, 4, 6, 8, 12, and 15 hours. Serum concentration plotted against time on semilogarithmic coordinates, indicated that theophylline in 5 horses was best described by a 2-compartment open model and in 1 horse by a 1-compartment open model. The following mean pharmacokinetic values were determined; elimination half-life = 11.9 hours, distribution half-life = 0.495 hours, apparent specific volume of distribution = 0.885 +/- 0.075 L/kg, apparent specific volume of central compartment = 0.080 L/kg, and clearance = 51.7 +/- 11.2 ml/kg/hr. Three horses with reversible chronic obstructive pulmonary disease were serially given 1, 3, 6, 9, 12, and 15 mg of aminophylline/kg in single IV doses (equivalent to 0.8, 2.4, 4.7, 7.1, 9.44, and 11.8 mg of theophylline/kg, respectively). The horses were exposed to a dusty barn until they developed clinical signs of respiratory distress and were then given the aminophylline. Effects of increasing doses on different days were correlated with clinical signs, blood pH, and blood gases. The 3 horses had a decrease in the severity of clinical signs after the 9, 12, or 15 mg doses of aminophylline/kg. The horses at 0.5 hour after dosing had a significant decrease in PaCO2 (43.6 +/- 5.5 to 39.4 +/- 6.7 mm of Hg, P less than 0.001) and a significant increase in blood pH (7.38 +/- 0.017 to 7.41 +/- 0.023, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacokinetics of phenytoin (diphenylhydantoin) in horses.

The pharmacokinetics of the anti-convulsant phenytoin were investigated in clinically healthy horses after oral (p.o.) and intravenous (i.v.) administration. A single dose of phenytoin (8.8 mg/kg body weight) was given i.v. as a bolus to nine horses and one horse received 13.2 mg/kg. A two-compartment open model was used to describe the disposition of phenytoin. Four of the horses that received an i.v. dose (three at 8.8 mg/kg and one at 13.2 mg/kg) were then given the same dose 3 days later by the oral route. Phenytoin achieved a peak concentration in serum within 1-4 h after p.o. administration and was poorly absorbed with a bioavailability of 34.5 +/- 8.6%. Oral dosage regimens were calculated on the basis of a dosing interval of 8 h to provide average serum steady-state concentrations of 5 and 10 micrograms/ml for phenytoin.

Effect of hunters' switch from lead to steel shot on potential for oral lead poisoning in ducks.

Mallards and black ducks (n = 409) killed by hunters during the 1980 and 1981 hunting seasons in Pennsylvania (Susquehanna River and Crawford County) were examined to evaluate the effectiveness of regulations that converted the studied areas from lead to steel shotgun pellets in 1977-1978. Gizzards were examined for ingested lead and steel shot, and liver specimens were analyzed for lead. Since there is no evidence to suggest that ducks preferentially ingest steel or lead shot, it was concluded that ducks with steel shot would have contained lead shot. Therefore, we concluded that the conversion to steel shotgun pellets accounted for the decreased prevalence of ingested lead shot from 11.2% to 5.6%. Toxic concentrations of lead (greater than or equal to 6 ppm, wet weight) in the liver were found in 6 of 23 ducks that contained lead shot, whereas only 2 of 386 ducks without lead pellets had toxic concentrations. It was concluded that the conversion to steel shotgun pellets in the studied areas probably has decreased the exposure of ducks to lead shot, thereby decreasing the potential for lead poisoning.

Environmental zinc and cadmium pollution associated with generalized osteochondrosis, osteoporosis, and nephrocalcinosis in horses.

Several suspect causes of chronic zinc/cadmium toxicosis in horses near a zinc smelter were investigated following observations of lameness, swollen joints, and unthriftiness, particularly in foals. Two foals born and raised near the smelter were lame and had joint swellings that were attributable to severe generalized osteochondrosis. Zinc and cadmium concentrations were markedly increased in the pancreas, liver, and kidney. The serum of 1 foal, zinc and potassium concentrations were high, whereas calcium and magnesium concentrations were low. Marked nephrocalcinosis and osteoporosis were observed in this foal. Nephrocalcinosis also was observed in his dam, who died of a punctured lung following rib fractures, though there was no history of trauma. The joint cartilage lesions were similar to those induced experimentally in animals fed high-zinc diets and may have been the result of zin-induced abnormality of copper metabolism. The osteoporosis and nephrocalcinosis were consistent with chronic cadmium toxicosis.

The value of zinc protoporphyrin in equine lead poisoning: a case report.

A diagnosis of lead poisoning in a foal was established based on clinical signs and the presence of an elevation in the concentration of blood lead (40 microgram/dl). Additionally, ZPP was determined in whole blood and found to be significantly elevated compared to 10 normal horses not exposed to lead (634 vs 73 microgram/dl). An elevation in ZPP in man has been found to be a sensitive biochemical indicator of lead toxicity even before overt clinical signs are present. This report suggests that ZPP may be a useful screening test for evaluating biological toxicity due to lead in horses and possibly other species.

Lead poisoning in dogs at the University of Pennsylvania Veterinary Hospital.

Twenty-seven dogs with lead poisoning were admitted to the University of Pennsylvania Veterinary Hospital from July, 1963, to April, 1975. The major source of the lead was paint. A common history was ingestion of plaster or paint scrapings during room renovation. Most of the dogs were less than 1 year old and had clinical signs referable to the gastrointestinal or the nervous system, or both. The gastrointestinal signs, in order of frequency, were vomiting, anorexia, tender abdomen, diarrhea, and constipation. The neurologic signs, in order of frequency, were hysteria, convulsions, ataxia, blindness, and mydriasis. The finding of many nucleated erythrocytes without severe anemia was nearly pathognomonic for lead poisoning. Of 14 affected dogs subjected to abdominal radiography, 9 had evidence of ingested radiopaque material. A mean blood lead concentration of 18.8 mug/100 ml, with a range of 0 to 50 mug/100 ml, was found for 26 dogs that were hospitalized for problems unrelated to lead poisoning. Of the 27 dogs with lead poisoning, 22 had their blood analyzed for lead. This group had blood lead values ranging from 40 to 530 mug/100 ml. Seven of the affected dogs were monitored throughout their period of treatment with calcium ethylenediaminetetraacetate. The concentration of lead in the blood decreased quickly after the initiation of treatment but leveled off after 2 or 3 days. The initial rapid phase probably corresponded to the removal of weakly bound or extracellular lead, whereas the slow phase probably corresponded to strongly bound or intracellular lead.