Page 452 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

Cadmium Chapter | 24 419

VetBooks.ir cadmium alone. This has been demonstrated in several sys- median cadmium concentration was low, at or below
0.6 ppm in the kidneys of cattle, swine, and dogs, the
tems in which inhibition of Kupffer cells significantly
median concentration in the kidneys was four times
decreases liver damage caused by a toxic dose of cadmium
(Sauer et al., 1997a,b). greater in horses (Penumarthy et al., 1980). One study has
Cadmium readily binds to, and induces, the production indicated that horses may be more at risk for cadmium
of metallothionein, a cysteine-rich, metal-binding protein. toxicity than other species. In this Swedish study, the cad-
Binding to metallothionein does not have a major effect mium concentrations in the kidney cortices of 69 other-
on the uptake of cadmium, but is, in part, responsible for wise normal horses were measured and correlated to any
retention of cadmium within cells and its long half-life histological lesions that were noted. In that study, renal
(greater than 10 years in humans). Metallothionein does cadmium concentrations ranged from 11 to 186 μg Cd/g
this by decreasing cadmium elimination, especially in wet weight, with an average of 60 μg Cd/g. This study
bile. Within hepatocytes, metallothionein binds to cad- found a correlation between increased chronic interstitial
mium, decreasing its hepatotoxicity. Experimentally, rats nephritis and increasing cadmium concentrations in the
that have greater induction of metallothionein in the liver renal cortex. There was no obvious relationship between
are somewhat protected from cadmium hepatotoxicity the age and the frequency of renal lesions (Elinder et al.,
(Kuester et al., 2002). However, in the kidneys the cad- 1981a). These same authors also found that cadmium con-
mium metallothionein complex is nephrotoxic, and has centrations in the kidney cortices were approximately 15
been theorized that it may play a role in chronic poisoning times greater than those in the liver of the same animals
in humans (Klaassen and Liu, 1997). (Elinder et al., 1981b). Age-dependent increases in kidney
metallothionein and cadmium have also been reported in
horses (Elinder et al., 1981a; Jeffrey et al., 1989; Plumlee
TOXICITY
et al., 1996). However, these later studies and others
Increased exposure to cadmium in combination with zinc, (Holterman et al., 1984) have not reported renal lesions
lead, and/or other metals continues to occur in the vicinity similar to those reported by Elinder et al. (1981a). One
of nonferrous metal smelters and processing facilities. diagnostic investigation has reported lameness and swol-
These exposures have resulted in toxicoses, although it len joints (i.e., lesions of osteochondrosis) in addition to
can be difficult to separate the effects of cadmium from osteoporosis and nephrocalcinosis in horses near a zinc
those of lead, zinc, and other metals. In one such case in smelter in Pennsylvania. In the horses examined, kidney
the Netherlands, kidney cadmium concentrations were zinc and cadmium concentrations were elevated. It this
found to be twice those of cattle in control areas. case, it was postulated that the osteoporosis that was
However, although hemoglobin, blood iron concentra- observed in one foal and the nephrocalcinosis seen in the
tions, and iron-binding capacity were lower in the foal and its dam were related to the elevated renal cad-
cadmium-exposed cattle compared to controls, no adverse mium (Gunson et al., 1982). When ponies were raised
clinical effects were observed (Wentink et al., 1992). In near a similar zinc smelter for periods of time up to 18.5
an additional study in the Netherlands, bulls fed diets con- months, there were significant elevations in tissue zinc
taining increased concentrations of cadmium, lead, mer- and cadmium concentrations. Increases in tissue cadmium
cury, and arsenic had increased concentrations of concentrations were correlated with increasing age,
cadmium in the kidney and liver, but did not exhibit his- although increases in tissue zinc concentrations were not.
tological lesions related to the intake of heavy metals Generalized osteochondrosis was present in joints of the
(Vreman et al., 1988). However, more recently, deaths in limbs and cervical vertebrae, as well as lymphoid hyper-
horses exposed to cadmium, lead, and zinc from a nonfer- plasia. From this study, it was concluded that the develop-
rous metal processing plant in Eastern Europe were attrib- ment of osteochondrosis was associated with increased
uted to ingestion of these metals in their feed. Analysis of exposure to zinc and, possibly, cadmium. However, other
tissues from a number of these horses revealed extremely lesions of cadmium toxicosis, such as renal damage or
high concentrations of cadmium (40 100 times normal) osteomalacia, were not present (Kowalczyk et al., 1986).
and three to six times the normal concentrations of lead In wildlife, white-tailed deer (Odocoileus virginianius)
(Bianu and Nica, 2004). Toxicoses have also been harvested within 20 km of zinc smelters in Pennsylvania
reported in sheep and horses in the vicinity of nonferrous had very high kidney concentrations of cadmium and
metal smelters in China. Analysis of the tissues from zinc. These deer were also reported to have had joint
these animals revealed lead and cadmium concentrations lesions similar to zinc-poisoned horses from the same
significantly higher than those of controls (Liu, 2003). area (Sileo and Beyer, 1985).
A survey of cadmium concentrations in tissues from In humans, occupational exposure to cadmium has
healthy swine, cattle, dogs, and horses in the Midwestern been associated with renal dysfunction and osteomalacia
United States was conducted in the mid-1970s. While the with osteoporosis. One of the earliest effects of chronic