Effects of exposure to excessive quantities of lead on animals.

The present review updates and summarizes current information on the sources, solubility and toxicity of lead and its compounds, their absorption and concentration in blood, milk and various tissues and organs of the body and finally their excretion. Areas requiring further studies are also identified.

Effects of monensin on the bioavailability and elimination of selenium from blood in lambs.

A bioavailability study was conducted in lambs following intravenous and oral administration of sodium selenite (0.4 mg selenium/kg body weight) with and without concurrent oral monensin. Two- or three-compartment open models with first-order absorption after oral administration adequately described plasma selenium disposition irrespective of whether monensin was being administered. No significant differences were observed between groups of lambs receiving intravenous selenium with or without monensin with respect to distribution or elimination half-lives of selenium, areas under the concentration-time curve (AUC), volumes of distribution (Vd(ss)), or clearances (Cl). In lambs given selenium per os, no significant differences were observed with animals receiving monensin as well with respect to absorption and elimination half-lives, Vd(ss), or the time at which peak selenium concentrations occurred (tmax). However, peak selenium levels (Cmax) and AUC values were significantly higher in the group given monensin. The bioavailability of selenium with and without monensin was estimated to be 60% and 43%, respectively.

Effects of concurrent oral administration of monensin on the toxicity of increasing doses of selenium in lambs.

The effects of concurrent administration of monensin sodium on the toxicity of progressively increasing oral doses of selenium (0.2 to 2.4 mg per kg body weight), given as sodium selenite twice weekly, have been examined in growing lambs. To link the chemically determined selenium concentration in tissues with observable pathological changes, the histochemical method of Danscher, which visualizes selenium bonds within tissues, was utilized. Findings included damage to conduction and contractile myofibres in the heart, segmental sarcoplasmal necrosis with lysis and atrophic change in skeletal musculature and selective accumulation of Danscher reaction-product in damaged areas of the liver, kidney and secondary lymphoid tissue. Concurrent administration of monensin sodium at a constant safe dosage enhanced the toxicity of selenium as demonstrated by increased severity of the signs of intoxication, fatalities, tissue selenium concentrations and intensified gross, histopathological and histochemical changes.

Experimental acute selenium intoxication in lambs.

The toxic effects of 5 mg per kg body weight of selenium given as sodium selenite orally or parenterally to growing lambs were examined. There was considerable individual variation in both susceptibility to intoxication and the degree of pathological change displayed. The results affirm the previously reported deleterious effects on the cardiovascular, respiratory and urinary systems and highlight damage to secondary lymphoid tissue in various organs. The use of a histochemical method for detecting selenium bonds demonstrated correlation between the density of reaction-product and histopathological changes within tissues, and showed the distribution of selenium in other tissues in which the gross and histopathological findings were non-specific or minimal.

Detection of andromedotoxins for the diagnosis of Rhododendron poisoning in animals.

A method for the detection of andromedotoxin in plant material and relicta from cases of poisoning due to Rhododendron and other members of the Ericacea is described. This method, which overcomes the problems associated with basing the diagnosis on the clinical signs exhibited and untrained identification of plant materials, has been successfully applied to the investigation of a number of field outbreaks of Rhododendron poisoning in animals.

Biochemical and haematological effects of phenylbutazone in horses.

Five matched pairs of horses were used to investigate the effects of phenylbutazone on a range of physiological, biochemical and haematological variables. The drug was given by mouth daily for 15 consecutive days at the manufacturer's recommended dose rates to one group of horses (Group A); the second group (Group B) received equivalent doses of a placebo. For some of the measured parameters, significant changes were recorded in both groups, indicating background instability. Significant decreases in serum total protein, albumin, plasma pH, viscosity and magnesium, and an increase in albumin: globulin ratio occurred in Group A, but not in Group B. These changes were, therefore, attributed to phenylbutazone or its metabolites. Toxicologically, the change in pH is probably unimportant but the decrease in protein concentration may have resulted from a protein losing enteropathy and/or from decreased synthesis in the liver. In one animal which received phenylbutazone, clinical signs of toxicity (lethargy, inappetence, oedema) were observed and evidence of hepatotoxicity and haematological changes were also noted in this horse. It is concluded that recommended dose rates of phenylbutazone should never be exceeded and that the period for which the highest dose (4.4 mg/kg body weight twice daily for four days) is administered should be reduced. In clinical cases, where phenylbutazone toxicity is suspected, measurement of serum or plasma protein concentration might provide an indication of the need to reduce dose levels or stop therapy.

The vitamin D3 metabolite-type activity of Solanum malacoxylon.

1. Administration of an aqueous extract of the dried leaves of Solanum malacoxylon (DLSM) to rats causes a rapid hyperphosphataemia and a decrease in plasma alkaline phosphatase activity; the two effects are typical of 1,25(OH)2D3, the hormonally active metabolite of vitamin D3. 2. DLSM, like both vitamin D3 and parathyroid hormone, increases plasma calcium and citrate levels in rats. The effect of DLSM in influencing plasma citrate, and the role of this important metabolite in mineral metabolism is discussed. 3. A decrease of plasma magnesium levels occurs in rats following treatment with DLSM. This decrease, which is associated with a renal loss of this cation, is remarkably similar to that produced by hypervitaminosis D3. 4. Prolonged administration of DLSM to vitamin D deficient rats causes a polyuria, hypercalciuria, hyperphosphaturia, hypermagnesuria, an increase in urinary total hydroxyproline, an increase in plasma total hexosamines, and a corresponding decrease in the bone total hexosamines. These effects, some of which can also be produced by hyperparathyroidism, or following the administration of parathyroid extract (PTE), large doses of vitamin D3, or 1,25(OH)2D3, suggest that DLSM, like the latter compounds, is capable of causing bone mineral mobilization, and the dissolution of bone organic matrix.