Selenium - Toxicology of Metals - page 774

of GSHpx1 mRNA. Of further interest is that SeCys
tRNA exists in two isoforms, with or without a methyl
group that may regulate the mammalian SeCys inser-
tion machinery (Hatfi eld and Gladyshev, 2002). In
addition to the Se status, GSHpx4 is also regulated by
several other factors (Sneddon et al ., 2003).
Recent data indicate that GSH selenopersulfi de
(GSSeH) is further metabolized to selenosugars in the
liver (Kobayashi et al ., 2002).

trimethylselenoium ion were recovered in rat urine
after selenite administration in drinking water. In
young rats, the trimethylselenoium ion concentration
increased with dose, but not in adult rats (Suzuki et al .,
2005). Unmetabolized selenite has also been recovered
in urine (Francesconi and Pannier, 2004).
The fate of selenate at a dose of 0.3 mg Se kg −1 body
weight administered intravenously to rats was studied.
The results suggest that in contrast to selenite, which is
taken up by and reduced in RBCs, and then transferred
to the liver, approximately 20% of the selenate admin-
istered to rats was excreted into the urine without any
change in its chemical form, and the major portion of
selenate was taken up by the liver, reduced, and then
used for the synthesis of selenoproteins or excreted into
the urine after being methylated (Shiobara et al ., 1999).
Forty pregnant long-tailed macaques were treated
daily for 30 days with 0, 25, 150, or 300

5.3.4 Excretion

Under most conditions, urine is the major excretory
pathway, but the fraction excreted depends on the nutri-
tional status of the animal and the amount administered.
However, fecal excretion may dominate in cases of defi -
ciency states and with tracer doses (Burk et al ., 1972).
With an adequate supplementation of the diet (1.0 mg/
kg.), 67% of a tracer dose of selenite was excreted in the
urine, whereas in a state of defi ciency only 6% of the
same dose was excreted (Burk et al ., 1972). It has been
reported by several authors that trimethylselenonium is
the dominating urinary metabolite at high doses, par-
ticularly in experimental animal studies (1.5 mg/kg),
but the true nature of this high dose metabolite has been
questioned (Francesconi and Pannier, 2004).
At high or toxic dose levels, excretion through
expired air becomes important and even predomi-
nant. In one study on rats, it was shown that only
0.2% was exhaled when selenite was given as a small
dose (0.005 mg/kg bw), whereas as much as 50-60%
was exhaled at lethal doses (McConnell and Roth,
1966). The only metabolite identifi ed in the breath
is dimethylselenide. Results available on selenite
biotransformation and excretion are thus compatible
with the idea that biotransformation to methylated
selenides mainly serves to facilitate excretion of high
or potentially toxic amounts of ingested selenium.
Other selenium compounds that have been stud-
ied seem to have excretion patterns similar to those of
selenite. Available data also suggest that man excretes
selenium compounds in a way similar to that shown
for rats (Bopp et al ., 1982).
In a recent critical review, selenium metabolites
found in urine have been listed (Francesconi and
Pannier, 2004). It was mentioned that previously held
views that methylselenol and trimethylselenoium ions
are major human urinary metabolites seems unjusti-
fi ed. Instead, a selenosuger (methyl 2-acetamido-2-
deoxy-1-seleno-

g selenium as
L-selenomethionine/kg body weight. Hair selenium
was the most sensitive indicator of L-selenomethionine
dose, but urinary excretion, plasma, erythrocyte, and
fecal selenium also responded. Erythrocyte and plasma
glutathione peroxidase specifi c activities increased 154
and 69% over controls, respectively. Toxicity was asso-
ciated with erythrocyte selenium >2.3

µ

µ g/mL, plasma

selenium >2.8 µ g/mL, and hair selenium >27 µ g/g

(Hawkes et al ., 1992).

5.3.5 Biological Half-Time

Several studies indicate at least biphasic elimina-
tion of whole-body selenium in rats (Ewan et al ., 1967)
and dogs (Weissman et al ., 1983). The amount excreted
during this initial phase has been shown to be dose
dependent in rats (Burk et al ., 1972). A second phase,
which does not seem to be infl uenced by selenium
dose, has a half-time of approximately 30-70 days in
most species (Weissman et al ., 1983).
In studies on humans, three phases of elimination
can usually be identifi ed after selenite administration.
The half-time of the fi rst phase is approximately 1 day,
the second 8-20 days, and the third 65-116 days (Bopp
et al ., 1982). In some studies (cf. Griffi ths et al ., 1976),
the half-time of the terminal phase for selenium elimi-
nation was longer when selenomethionine was used
instead of selenite. This fi nding is in agreement with
results discussed in Section 5.3.2.

6 BIOLOGICAL MONITORING

-D-galactopyranoside) has been found
to be a major metabolite in rat and human urine, and
low and moderate doses of selenium are excreted in
this way (Kobayashi et al ., 2002). However, in a re-
cent study, both the selenosuger metabolite and the

β

6.1 Levels in Tissues and Biological Fluids
Levels in organs have been compiled from differ-
ent publications (Thomassen and Aaseth, 1986), and