Tellurium - Toxicology of Metals - page 802

hemolytic, anemia with signs of dose-related reduc-
tions in hemoglobin concentration and erythrocytes,
as well as hematuria (Sandrackaja et al ., 1962a,b).

increasing number of cytoplasmic lipid droplets in
myelinating Schwann cells. They are probably derived
from newly synthesized lipid rather than from the
early breakdown and internalization of myelin lipids.
The earliest observed biochemical abnormality in tel-
lurium neuropathy is an inhibition of the cholesterol
synthesis at the squalene epoxidase step, causing an
accumulation of squalene within the nerve (Goodrum
et al ., 1990). The metabolic changes observed in the
sciatic nerve, for example, probably initially involve
the inhibition of the conversion of squalene to 2,3-
epoxysqualene. This block in the cholesterol biosyn-
thesis pathway may, directly of indirectly, lead to the
inhibition of the synthesis of myelin components and
to the breakdown of myelin (Harry et al ., 1989; Morell
et al ., 1994).
Starting at postnatal day 21, weaned rats were fed a
diet containing 1.1% of elemental tellurium. After 7 days
of tellurium treatment and at several time points of
post-tellurium treatment, the animals were processed
for ultrastructural analysis, Schwann cell nuclei quan-
tifi cation, and teased fi ber preparations. Quantitative
determination of Schwann cell nuclei per transverse
section of sciatic nerve showed a dramatic increase of
Schwann cells 2 days after tellurium treatment com-
pared with control nerves. The number of Schwann cell
nuclei then decreased progressively during the long-
term period of recovery studied (330 days after tellu-
rium treatment). Dying cells exhibited morphological
features of apoptosis. Both healthy immature Schwann
cells and endoneurial macrophages were involved in
the phagocytosis of apoptotic Schwann cells. Also other
distinct biological mechanisms such as the persistence
of supernumerary Schwann cells in the endoneurium
and the shortening of internodal lengths are involved
in the regulation of Schwann cell numbers during the
remyelination stage (Berciano et al ., 1998).
Developing rats fed a diet containing 1.1% tellurium
get a primary demyelination of peripheral nerves,
which is followed by a period of rapid remyelination.
The demyelination that is caused by the limiting of the
supply of cholesterol leads to repression of the expres-
sion of mRNA for myelin-specifi c proteins. Tellurium
exposure was followed by an increase in total RNA
(largely rRNA) in sciatic nerve, which could not be
accounted for by cellular proliferation. The increased
concentrations of rRNA may be a reactive response
of Schwann cells to toxic insult and may relate to the
higher levels of protein synthesis required during
remyelination. On the other hand, steady-state levels
of mRNA, determined by Northern blot analysis, for
P0 and myelin basic protein were markedly decreased.
Message levels increased during the subsequent
period of remyelination and reached almost normal

7.2.1.4 Heart
Peking ducks fed tellurium tetrachloride in the diet
(50-1000 mg Te/kg, 2-4 weeks) developed myocardial
hemorrhage, hydropericardium, and cardiac muscle
necrosis (Carlton and Kelly, 1967). Similar changes,
including cardiac damage with hydropericardium and
myocardial hemorrhage, were observed in a study of
newly hatched ducklings fed a commercial diet with
500 mg of tellurium tetrachloride per kilogram of
feed for 2-4 weeks. A histopathological investigation
showed areas of acute hemorrhagic necrosis in the
ventricular myocardium, as well as signs of edema and
congestion (Van Vleet and Ferrans, 1982).

7.2.1.5 Nervous System
Rats fed 0.2 g/day of tellurium showed black brain
changes caused by dark tellurium particles that were
localized in lipofuscin granules in neuron cytoplasm
throughout the brain. The changes are probably due
to effects of tellurium on brain mitochondria (Duckett
and White, 1974).
Peroxidation-related effects on the brain have been
studied in 15 male Wistar rats fed drinking water con-
taining telluriumtetrachloride at a level of 100 mg/L.
Control rats were given tapwater. The rats were killed
in groups of fi ve 7, 21, and 35 days, respectively, after
the exposure. The succinic dehydrogenase activity
was above the control range after 21 days, whereas
the creatinine-kinase activity decreased or remained
stable. The brain glutathione content was above the
control range after 35 days (Valkonen and Savolainen,
1985).
Rats fed a diet containing 1.25% elemental tellurium
starting on postnatal day 20 developed garlic odor
within 48 hours and usually hind limb paresis within
72 hours. Treated rats showed progressive increases
in blood nerve barrier permeability 24-72 hours after
exposure. The blood-brain barrier, however, was not
affected. Other effects included increased numbers
of intracytoplasmic lipid droplets, intracytoplasmic
membrane delimited clear vacuoles, and cytoplas-
mic excrescences within myelinating Schwann cells
after 24 hours, axon demyelination after 48 hours, and
endoneurial edema after 72 hours. The synthesis of
cholesterol was sharply inhibited after 12 hours (Boul-
din et al ., 1989).
Weanling rats fed a diet containing elemental
tellurium may develop peripheral neuropathy char-
acterized by segmental demyelination and minimal
axonal degeneration. An early neuropathy sign is an