MOLYBDENUM TOXICITY
MOLYBDENUM TOXICITY (MOLYBDENOSIS)
Molybdenum is an essential trace element, a component of
several enzymes. Excessive dietary intake of molybdenum induces a secondary hypocuprosis.
The syndrome, predominately reported in ruminants. Cattle and sheep are
~10-fold more susceptible than other species. Acute toxicity associated with
massive doses is rarely encountered.
Ingestion of hay contaminated by Mo
from industrial sources (iron foundaries, steel works). Industrial
contamination associated with mining or metal production or areas using
molybdenum-contaminated fertilizers result in enhanced uptake of molybdenum by
plants used as a feed source. Deficiency of copper in soils and in vegetation
increases the toxicity of Mo which can then prove toxic at levels which are
normally considered to be safe.
Toxicodynamics
The interactions associated with copper, molybdenum, and
sulfate metabolism related to the utilization, bioavailability, and kinetics of
copper are among the most biologically significant interrelationships in
veterinary medicine. In ruminants, various molybdates react with sulfides to
produce thiomolybdate compounds, which react with copper to form an insoluble
complex that is poorly absorbed. The reduced copper absorption impairs copper
utilization and the synthesis of a variety of copper-dependent proteins. The
reduced bioavailability of copper ultimately induces secondary copper
deficiency. Excessive molybdenum intake also enhances the excretion of copper.
Based on this observation, the administration of tetrathiomolybdates may be a
useful treatment for chronic copper poisoning. The limited bacterial formation
of thiomolybdates in monogastric animals is primarily responsible for the tolerance
to molybdenum encountered in these species. Excessive molybdenum exposure may
also impair a variety of enzymes
involved in collagen and elastin maintenance and stability, which has been
associated with cardiovascular disorders. Molybdenum exposure may reduce phospholipid synthesis in nervous
tissue, resulting in demyelination and neurologic disorders clinically.
The susceptibility to molybdenum toxicity in ruminants
depends on a number of factors, including
1) dietary copper
content - susceptibility increases as the copper content decreases;
2) dietary sulfate
content - susceptibility increases with high sulfate levels by impairing copper
utilization, whereas low sulfate content enhances susceptibility by reducing
molybdenum excretion;
3) the chemical form of
molybdenum - water-soluble forms found in fresh feed are more toxic;
4) sulfur-containing
amino acids may alter copper utilization or molybdenum excretion;
5) animal species - cattle
are more susceptible;
6) age - young animals
are more susceptible, and excretion of molybdenum into milk may produce
toxicoses in nursing calves;
7) season of year -
molybdenum concentrations in plants increase in the fall;
8) plant species - legumes
bioaccumulate more molybdenum; and
9) breed differences - seen
in sheep and goats.
The manifestations of molybdenum
toxicity are related primarily to impaired copper metabolism and utilization,
resulting in secondary copper deficiency. Typically, the syndrome is a herd
problem, with morbidity as high as 80%.
Gastrointestinal
Watery, foetid diarrhoea refractory to all treatment (severe,
persistent diarrhea with the presence of green, liquid feces containing gas
bubbles, often referred to as peat or
teart scours).
Skeletal
Molybdenum competes with phosphorus utilization,
resulting in reduced mineralization of bone.
Deformation of the long bones of the body (exostoses).
Limping (due to skeletal pain).
Presence or absence of osteophytes.
Spontaneous fractures of the long bones.
Joint pain characterized by lameness, and osteoporosis
often manifested by bone fractures.
In sheep, particularly in lambs <30 days old, the
animals exhibit stiffness of the back and legs and have difficulty rising. The
syndrome in sheep is known as enzootic
ataxia, or sway back.
Abnormal development of connective tissue and growth
plates are apparent in affected animals.
Cutaneous
Fragile hair, easily pulled out.
Disturbance of hair pigmentation (yellow discolouration
in white-coated species). Depigmentation,
resulting in fading achromotrichia of the hair coat is evident in black animals
associated with impaired tyrosinase activity and reduced melanin synthesis.
General
Anaemia (microcytic hypochromic anemia).
Pica, unthriftiness, loss of weight, cachexia.
Death occurs within a few days to several weeks.
Reproductive
In heifers, fertility is reduced. Delayed puberty, poor
conception rates, decreased weight at puberty, and decreased milk production
are common. Reduced libido has been reported in bulls.
Manifestations appear within 1–2 wk if molybdenum levels
are excessive.
Occasionally, acute toxicity may be
encountered in cattle or sheep. Anorexia and lethargy may be evident within 3
days. Deaths begin within 1 wk and may continue for many months. Neonates
frequently exhibit hindlimb ataxia that often progresses to the forelimbs.
Salivation and scant mucoid feces are common.
Emaciation (reduced body fat), cachexia, osteoporosis,
deformation of the long bones, greenstick fractures, haemorrhages and breakdown
of the periosteum, hypochromic anaemia, loss of hair pigmentation. At necropsy,
hemosiderosis, periacinar to severe hepatic necrosis, and nephrosis are
evident. In affected sheep, neuronal degeneration, demyelination, and lysis of
white matter are seen in nervous tissue.
Distinguishing between primary copper
deficiency and secondary copper deficiency related to excessive molybdenum
exposure is important. Often with molybdenum toxicity, there is a poor
correlation between tissue concentrations of copper and clinical disease.
Clinical improvement after copper sulfate administration provides valuable
support for the diagnosis. Analysis of the ration for copper and molybdenum
concentrations is recommended. In cattle rations, a copper:molybdenum ratio of
6:1 is optimal. If the ratio is less than 2:1, molybdenum toxicity will occur.
Ratios exceeding 15:1 may cause chronic copper poisoning. Absolute molybdenum
concentrations in the diet >10 mg/kg will cause poisoning independent of
copper consumption. Massive molybdenum exposure in the ration >2,000 mg/kg
will result in death. Analysis of the liver and plasma for molybdenum provides
useful insight to confirm the diagnosis, but the concentrations must be
interpreted in association with the comparable tissue concentrations of copper.
In cattle, liver concentrations >2 ppm (wet weight) and plasma
concentrations >0.1 ppm are consistent with a diagnosis of molybdenum
poisoning in the presence of a low copper status.
Other disease syndromes characterized by emaciation or
unthriftiness (parasite infections, selenosis, fluorosis, ergotism), diarrhea
(metal poisonings, GI infections), and lameness or bone abnormalities
(fluorosis, selenosis, ergotism, lead poisoning) may resemble molybdenum
poisoning and should be investigated as possible etiologies.
If the source of molybdenum can be
removed, excess molybdenum is rapidly eliminated and food products are safe for
consumption within a relatively short time.
If the dietary exposure cannot be reduced, elimination of
molybdenum in the milk may produce toxicosis in nursing calves. Dietary
supplementation with copper sulfate will reduce the bioavailability of
molybdenum in the GI tract, ultimately reducing absorption and enhancing
excretion.
In feed containing molybdenum at >5 mg/kg,
supplementation with 1% copper sulfate in salt will control development of the
syndrome.
In recovered mining areas, the supplementation may need
to be increased to as much as 5% copper sulfate in the salt.
When the consumption of mineral supplements is
impractical, the treatment may be administered as a weekly drench. Injectable
products such as copper glycinate or copper edetate (Cu-EDTA) may be given at a
dose of 120 mg/cow.
Oral copper sulphate (solution), 1g/50kg body weight.
Copper sulphate, 1-5%, in mineral salt licks.
I.M. copper glycinate, 60 mg for calves, 120 mg for adult
cattle, repeated every 6 months.
Most treatment options are associated with the biological
interactions associated with copper, molybdenum, and sulfate. Under
circumstances in which dietary exposure is difficult to eliminate, simple
treatment with copper products may be futile.
Laboratory investigations
Liver, blood;
Sample of contaminated feed.
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