Page 498 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

Molybdenum Chapter | 32 465

VetBooks.ir oxidase, glutaminase, cholinesterase, cytochrome oxidase dependent as acute poisoning. Oral lethal doses of Mo admin-
Subacute to chronic toxicity of Mo is just as species
(Venugopal and Luckey, 1978), ceruloplasmin, superox-
istered chronically to laboratory animals (rats, mice, guinea
ide dismutase, ascorbate oxidase, catechol activity, and
other copper dependent enzyme systems (Gould and pigs and rabbits) range from 60 to 333 mg Mo/kg body
Kendall, 2011). weight/day, while cattle are poisoned with as little as 3 mg
Mo/kg body weight/day (NRC, 2006). Literature reports of
toxic dietary Mo content range from 10 to 1200 ppm for rats,
TOXICITY
300 8000 ppm for poultry, 200 4000 ppm for rabbits,
Both acute and chronic toxicity of Mo varies greatly among 1000 8000 ppm for guinea pigs, 2.5 20 ppm for sheep, and
species. Ruminant animals are much more sensitive than 2 400 ppm for cattle (Pitt, 1976). Ruminants commonly suc-
monogastric animals, due to the rumen metabolism of sulfur cumb to molybdenosis when Mo intake is greater than
to sulfides and formation of thiomolybdates. The relative 20 ppm in the diet. However, due to the intrinsic nature of
tolerance to Mo has been ranked: horses. pigs . the molybdenum copper sulfur interactions, chronic Mo
rats . rabbits. guinea pigs . sheep . cattle (Venugopal poisoning in ruminants can be divided into three classes: die-
and Luckey, 1978), but more recent literature suggests tary Mo greater than 20 ppm, low Cu:Mo ratio (,2:1) and
horses may be more sensitive (Ladefoged and Sturup, high dietary sulfur with normal copper and Mo (Ward,
1995). In total, the toxicity of Mo needs to be evaluated 1978). The desired Cu:Mo ratio in ruminants is between 6:1
with consideration of dietary sulfur/sulfates and copper. and 10:1 (Thompson et al., 1991). Thus, Mo toxicosis can
This is with the knowledge that sulfates competitively occur at much low concentrations in association with copper
inhibit molybdate uptake from the intestinal tract, but deficient forages than those with diets adequate in copper.
metabolism in the rumen results in the formation of thiomo- Most clinical signs of chronic Mo poisoning are associ-
lybdates, which enhances the toxic effects on copper status. ated with induction of overt or functional copper defi-
Natural toxic effects of Mo are primarily via ingestion, ciency. Commonly, the first recognized clinical sign of
but toxicity has been demonstrated by both inhalation and chronic Mo poisoning is severe diarrhea (Dick, 1956;
Pitt, 1976; Pitt et al., 1980; Underwood, 1977; Ward,
injection in laboratory rodents. The intraperitoneal LD 50
of Mo in rats ranges from 22.8 to 99 mg/kg body weight 1978; Friberg and Lener, 1986; Mills and Davis, 1987;
(Venugopal and Luckey, 1978), with similar lethal doses Rajagopalan, 1988; Nielsen, 1996; Johnson, 1997;
in mice and guinea pigs. Chronic inflammatory lesions Coppock and Dziwenka, 2004; NRC, 2006). “Teart” is
and hyaline degeneration within the respiratory tree was used to refer to soil or plants that contain unusually high
3
induced by Mo trioxide exposure of 10 100 mg/m 6h amounts of Mo, thus the term teart scours is commonly
per day, 5 days a week (Chan et al., 1998). Increased inci- used to describe the diarrhea associated with excessive Mo
dence of respiratory adenomas was also seen in the rats intake. Although the exact mechanism is not well defined,
and mice. copper supplementation alleviates this clinical sign. Other
Concentrations of Mo required to produce acute poison- common clinical signs of chronic Mo poisoning include
ing orally differ significantly among species. For cats, rab- poor body weight gain, weight loss, anemia, poor immune
bits and guinea pigs, the oral LD 100 for Mo is 1310, 1020, function, decreased milk production, achromotrichia,
and 1200 mg/kg body weight, respectively, while the oral alopecia, limb deformities, bone fractures, periostosis,
LD 50 for rats is 125 370 mg/kg body weight (Venugopal lameness, poor reproductive performance, lack of libido,
and Luckey, 1978). Little acute toxicity data are available and ataxia. Abortions have been reported in horses.
for domestic animals, but cattle have been acutely poisoned Pathologic alterations of chronic Mo poisoning are not
with feed containing 7400 mg Mo/kg diet (group average specifically diagnostic. These lesions are secondary to
intake of 31 mg Mo/kg body weight/day) and Mo was induced copper deficiency and include emaciation, perios-
acutely lethal in sheep at 132 137 mg Mo/kg body tosis and epiphyseal plate growth abnormalities. Because
weight/day for 2 3days (Swan et al., 1998). of the nature of chronic Mo poisoning, primary copper
Clinical signs and pathologic lesions in acutely poi- deficiency must always be ruled out when these lesions
soned animals differ from those seen with more chronic are identified.
poisonings. Acutely poisoned cattle and sheep developed
feed withdrawal, lethargy, weakness, hind limb ataxia that TREATMENT
progressed to the front limbs and recumbency (Swan
et al., 1998). The cattle also had profuse salivation, ocular The two primary mechanisms for treating Mo toxicosis
discharge and mucoid feces. Hydropic hepatocellular involve removal from the source of high Mo and copper
degeneration/necrosis and hydropic degeneration/necrosis supplementation, but administration of sulfate to mono-
of the proximal and distal renal tubules was observed in gastrics will enhance elimination rates. Administration of
both cattle and sheep. sulfates to ruminants would not be recommended, as