Molybdenum Poisoning: Introduction - The Merck Veterinary Manual

Molybdenum Poisoning: Introduction

Molybdenum is an essential micronutrient that forms molybdenoenzymes, which are necessary for the health of all animals. In ruminants, the dietary intake of excessive molybdenum causes, in part, a secondary hypocuprosis. Toxicosis due to massive doses of molybdenum is rare. Domestic ruminants are much more susceptible to molybdenum toxicity than nonruminants. The resistance of other species is at least 10 times that of cattle and sheep.

Etiology:

The metabolism of copper, molybdenum, and inorganic sulfate is a complex and incompletely understood interrelationship. It appears that the ruminal interaction of molybdates and sulfides gives rise to thiomolybdates (mono-, di-, tri-, and tetrathiomolybdates). Copper reacts with thiomolybdates (primarily tri-and tetrathiomolybdates) in the rumen to form an insoluble complex that is poorly absorbed. On this basis, tetrathiomolybdate is used in treating and preventing copper toxicity ( Copper Poisoning: Introduction) in sheep. Some thiomolybdates are absorbed and decrease blood copper availability and also appear to directly inhibit copper-dependent enzymes. Therefore, the susceptibility of ruminants to molybdenum toxicity depends on a number of factors: 1) copper content of the diet and intake of the animal—tolerance to molybdenum toxicity decreases as the content and intake of copper decrease; 2) the inorganic sulfate content of the diet—high dietary sulfate with low copper exacerbates the condition, while low dietary sulfate causes high blood molybdenum levels due to decreased excretion; 3) chemical form of the molybdenum—water-soluble molybdenum in growing herbage is most toxic, while curing decreases toxicity; 4) presence of certain sulfur-containing amino acids; 5) species of animal—cattle are less tolerant than sheep; 6) age—young animals are more susceptible; 7) season of year—plants concentrate molybdenum beginning in spring (maximum level reached in fall); and 8) botanic composition of the pasture—legumes take up more of the element than other plant species.

Molybdenum toxicity associated with copper deficiency has been seen in areas with peat or muck soils, where plants grow in alkaline sloughs (eg, western USA), as a result of industrial contamination (mining and metal alloy production), where excess molybdenum-containing fertilizer has been applied, and where applications of lime appeared to increase plant molybdenum uptake.

In the diet of cattle, copper:molybdenum ratios of 6:1 are considered ideal; 2:1-3:1, borderline; and <2:1, toxic. Dietary molybdenum of >10 ppm can cause toxicity regardless of copper intake; as little as 1 ppm may be hazardous if copper content is <5 ppm (dry-weight basis). Mixing errors may occur; concentrations above 1,000 mg/kg (as sodium molybdate) cause growth retardation while concentrations of 2,000-4,000 mg/kg cause death within 40 days.

Clinical Findings and Diagnosis:

Most of the clinical signs attributed to molybdenum toxicity arise from impaired copper metabolism and are the same as those produced by simple copper deficiency. Molybdenum toxicity in cattle is characterized by persistent, severe scouring with passage of liquid feces full of gas bubbles ( peat scours or teart). Depigmentation, resulting in fading of the hair coat, is most noticeable in black animals and especially around the eyes, which gives a spectacled appearance. Other signs include unthriftiness, anemia, emaciation, joint pain (lameness), osteoporosis, and decreased fertility. Effects on reproduction, particularly in heifers, include delayed puberty, decreased weight at puberty, and reduced conception rates. It appears that fertility is uniquely vulnerable to the effects of molybdenum or thiomolybdates and alone responds indirectly to copper acting as an antidote. Some studies have suggested that relatively low levels of molybdenum may exert these direct effects on certain metabolic processes, particularly reproduction, independent of alterations in copper metabolism. Sheep, and young animals in particular, show stiffness of the back and legs with a reluctance to rise (called enzootic ataxia in Australia). Joint and skeletal lesions appear to be due to defects in development of connective tissue and growth plates. Clinical signs appear within 1-2 wk of grazing affected pasture.

In molybdenum toxicity, low copper levels in blood and tissue and the occurrence of clinical signs of copper deficiency in cattle are poorly correlated. A provisional diagnosis can be made if the diarrhea stops within a few days of oral dosing with copper sulfate; the diagnosis is further supported if other causes of diarrhea and unthriftiness (including GI parasites) are ruled out. Diagnosis is confirmed by demonstrating abnormal concentrations of molybdenum and copper in blood or liver and by a high dietary intake of molybdenum relative to copper.

The disease may be confused with many other enteritides and is commonly mistaken for internal parasitism, especially in young cattle. In pastured animals, it is not uncommon for the diseases to occur simultaneously.

Effects in cattle and sheep poisoned with massive concentrations of molybdenum are unlike the chronic induced copper deficiency described above. Cattle lose appetite within 3 days and deaths begin to occur within 1 wk and continue for months after exposure ends. Animals appear lethargic, display hind limb ataxia that progresses to involve the front limbs, salivate profusely, and produce scant, mucoid feces. The molybdenum is toxic to hepatocytes and renal tubular epithelial cells, producing periacinar to massive hepatic necrosis and nephrosis.

Prevention and Treatment:

Signs of severe acute toxicosis are reversed by providing copper sulfate in the diet. In areas where the molybdenum content of the forage is <5 ppm, the use of 1% copper sulfate (CuSO₄•5H₂O) in salt has provided satisfactory control of molybdenosis. With higher levels of molybdenum, 2% copper sulfate has been successful; up to 5% has been used in a few regions where the molybdenum levels are very high. In areas where, for various reasons, cattle do not consume mineral supplements, the required copper may be supplied as a drench given weekly, as parenterally administered repository copper preparations, or as a top-dressing to the pasture. Copper glycinate injectable has been used successfully as an adjunct to therapy.