Page 451 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

418 SECTION | V Metals and Micronutrients

VetBooks.ir increased fecal excretion and kidney accumulation of cad- or oral administration of cadmium chloride. The nonlac-
tating ewes exhibited a low cadmium bioavailability
mium (Reddy et al., 1985), there were no adverse health
(0.12% 0.22%), a large steady-state volume of distribu-
effects noted in these cattle (Dorn et al., 1985). Similarly,
when corn silage or corn that was grown on sewage tion (23.8 6 5.4 L/kg), and a low blood clearance (0.20 6
sludge fertilized fields were fed to sheep or pigs, 0.03 L/kg/day) with a mean residence time of 113 6 28
respectively, significant increases in kidney cadmium days. The lactating ewes had a higher bioavailability
concentrations were measured, but no other adverse (0.33% 1.7%), and the mean residence time was close to
treatment-related effects were noted (Lisk et al., 1982; that of the nonlactating ewes, despite a greater blood
Telford et al., 1982). Although cadmium is of concern in clearance (0.46 6 0.013 L/kg/day), because the volume of
the environment, and cattle grazing on cadmium- distribution of cadmium in the body was larger. The cad-
contaminated pastures have increased tissue concentra- mium clearance in milk remained low in the lactating
tions of cadmium, two additional studies conclude that ewes (Houpert et al., 1997).
accumulation of cadmium in the liver and kidneys of In the body, cadmium is excreted very slowly, with
cattle may be a moderately effective screen for the entry daily losses of approximately 0.009% via the urine and
of cadmium into the human food chain, as long as liver 0.007% in the feces via the bile. Cadmium protein com-
and especially kidneys are not consumed (Sharma and plexes are excreted in the kidneys and then resorbed from
Street, 1980; Johnson et al., 1981). It has been reported the filtrate in the proximal tubules. This area of the renal
that regardless of the concentrations of cadmium fed to cortex accumulates cadmium, and is susceptible to damage
livestock, the amount in meat, milk, and eggs is always and necrosis. Depending on the species, the biological half-
lower than that in the diet that the animal was eating. life of cadmium can vary from months to years, which
Thus, foods derived from those products decrease human results in cadmium accumulating in animals as they age
exposure (Klasing, 2005). This is fortunate, as chronic (Klasing, 2005). For example, several studies have docu-
cadmium poisoning has been documented in humans. In mented age-related increases in cadmium in the kidneys of
these cases, it has been associated with osteoporosis, renal horses (Elinder et al., 1981a; Anke et al., 1989).
lesions, tissue mineral imbalances, and death. In addition, In mammals and birds, cadmium accumulates in the
the Department of Health and Human Services has deter- liver and kidneys at concentrations of 0.1 2.0 and
mined that cadmium and cadmium compounds may be 1 10 mg/kg wet weight, respectively. It has been discov-
reasonably anticipated to be carcinogens. ered that animals with long life spans, such as horses, can
accumulate large amounts of cadmium in their organs,
particularly in their kidneys. In samples of renal cortex
PHARMACOKINETICS/TOXICOKINETICS
from old horses, concentrations of up to 200 mg/kg have
In animals, cadmium exposure is primarily through oral been reported (Elinder, 1992).
ingestion. Compared to other divalent cations such as zinc
and iron, intestinal absorption of cadmium is relatively MECHANISM OF ACTION
low, ranging from approximately 1% 5% in most spe-
cies, with up to as much as 16% in cattle, dependent on Experimentally, acute exposure to high doses of inorganic
the dose (Klasing, 2005). Interestingly, cadmium bound cadmium leads to its accumulation in many organs, elicit-
to metallothionein in foods of animal origin is absorbed ing liver and, in some cases, testicular damage (Dixit et al.,
less efficiently than cadmium salts; therefore, it may be 1975; Habeebu et al., 1998; Klasing, 2005). Once inside
less available for uptake (Groten et al., 1990). After the cell, free cadmium binds to protein sulfhydryl groups,
absorption, cadmium is transported in the plasma bound disrupting the cellular redox cycle, depleting glutathione,
to albumin and, in lesser amounts, other serum proteins. It and eliciting intracellular oxidant damage. In addition, its
distributes throughout the body, with the highest concen- similarity to other divalent cations such as calcium inter-
trations in the liver and kidneys, which account for feres with their normal functioning (Klasing, 2005).
approximately one-half of the total cadmium in the body. Cadmium ions can displace zinc and other divalent metals
Muscle and bone do not accumulate high concentrations from their binding sites on metalloproteins. For example,
of cadmium. Blood cadmium concentrations are indica- in the testis, cadmium can interfere with zinc proteins,
tors of recent exposure, while urine cadmium is a better leading to widespread apoptosis and necrosis (Marettova
indicator of the body burden. Cadmium is not transported et al., 2015; Xu et al., 1999). In the liver, acute cadmium
well into milk or eggs, or across the placental barrier toxicity results in widespread hepatocyte apoptosis, fol-
(Klasing, 2005). In pregnant and lactating livestock, the lowed by varying degrees of necrosis, depending on the
toxicokinetics of cadmium have been compared. In dose (Habeebu et al., 1998). This is related, in part, to the
this study, the kinetics of cadmium were measured in lac- effects of resident liver macrophages (Kupffer cells) to
tating versus nonlactating ewes after a single intravenous potentiate and increase the initial liver damage caused by