Chemistry Reference
In-Depth Information
the range per dry weights was found to be as follows:
brain, 0.46-1.59
status in humans. In a study on rats, platelet GSH-px
was shown to respond quickly to decreased selenium
administration (Levander
et al
., 1983; Rayman, 2004). In
humans, studies of platelet GSH-Px responded within
weeks to selenium administration (Levander
et al
.,
1983; Thomson
et al
., 1985; Xia
et al
., 2005). Recently,
selenoprotein P was suggested as a better indicator
of selenium status, because this selenoprotein seems
to require a greater selenium intake to reach full
expression (Xia
et al
., 2005).
There are no specifi c biomarkers for excess selenium.
Garlic breath indicates high acute exposure; however,
other metals are also methylated, which may result in
garlic odor. Nonspecifi c clinical signs of chronic over-
exposure are those of selenosis described in Section
7.2.3.2 (i.e., nail and hair changes). Also clinical chemi-
cal signs are nonspecifi c such as signs of liver toxicity
(i.e., raised serum levels of liver aspartate aminotrans-
ferase [ASAT] and alanine aminotransferase [ALAT]
and increased prothrombin time).
µ
g/g; lung, 0.45-2.16
µ
g/g; liver, 0.58-
52
µ
g/g; kidney, 1.18 - 8.0
µ
g/g; muscle, 0.29-1.7
µ
g/g;
and bone, 0.48
µ
g/g.
6.2 Biomarkers of Exposure
The reference urinary level should not exceed
0.03
g/mL (Robberecht and Deelstra, 1984). It is
recommended that selenium in urine is measured in
24-hour samples or is related to the creatinine level.
Urinary levels in workers exposed to 0.2-0.4 mg Se/m
3
was usually <0.1 mg/L. At air concentrations as
high as 3.6 mg/m
3
times the urinary level averaged
0.25-0.45 mg/L. Garlic odor of the breath usually
accompanied these higher levels (Glover, 1967).
Toxic effects of selenium are refl ected by increased
blood, urine, and hair levels. In China, people con-
suming selenium-rich food and exhibiting signs of
selenosis had mean levels in blood, urine, and hair of
3.2
µ
g/g, respectively. The
corresponding values in people from a high selenium
area without selenosis were 0.44
µ
g/mL, 2.7
µ
g/mL, and 32.2
µ
µ
g/mL, 0.14
µ
g/mL,
7 EFFECTS AND DOSE-RESPONSE
RELATIONSHIPS
and 3.7
g/g in blood, urine, and hair, respectively. In
selenium-adequate areas, the levels were 0.095
µ
µ
g/mL,
0.026
g/g in blood, urine, and hair,
respectively (Yang
et al
., 1983).
Supplementation of the diet with yeast or wheat,
so that 200
µ
g/mL, and 0.36
µ
7.1 Acute Toxicity
7.1.1 Laboratory Animals
g Se/day was consumed, resulted in an
increased plasma level from 0.07-0.17
µ
Many selenium compounds are very toxic and kill
laboratory animals in single doses as small as 1.5-
6 mg/kg bw. Thus, selenite killed 75% of injected (intra-
peritoneally) rats within 2 days at doses of 3.25-3.5 mg
Se/kg; the corresponding lethal doses for selenate were
5.5-5.75 mg Se/kg, and for selenocysteine 4 mg Se/kg
(Wilber, 1980). However, some other compounds are
less toxic, such as selenium sulfi de, with an oral LD
50
in the rat of 138 mg/kg (Cummins and Kimura, 1971)
or dimethylselenide with an LD
50
(intraperitoneally)
in the rat of 1600 mg/kg (Wilber, 1980). Animals given
lethal doses acquire a garlic odor of the breath, show
signs of nervousness and fear, followed by somnolence.
Respiration becomes dyspneic and then opisthotonic;
tetanic spasms and ultimately clonic spasms develop
before the animal fi nally dies. The critical organ
under these conditions seems to be the CNS, whereas
morphological changes are dominated by liver fatty
degeneration or necrosis.
Acute poisoning after inhalational exposure to “sele-
nium dust” at a concentration of 30 mg/m
3
has also
been described (Hall
et al
., 1951). Ten percent of the
rats died; the major pathological change was intersti-
tial pneumonitis. At levels of 150-600 mg/m
3
, selenium
dioxide caused rapid death in all rats tested (Filatova,
1951). Selenium oxychloride is a strong vesicant, and
g/mL within
11 weeks (Levander
et al
., 1983). Supplementation
with selenate was less effi cient. On a low-selenium
diet (33
µ
µ
g/day), the level in breast milk was 5.8
µ
g/L.
At a higher dietary level (50
µ
g/day), the milk level
was 10.0
g/L (Kumpulainen
et al
., 1984). Many sup-
plementation studies have been carried out since then.
The highest levels are often achieved on supplementa-
tion with selenomethionine, a common form in plants
and which is nonspecifi cally incorporated into pro-
teins. The effi ciency of selenium compounds to raise
plasma selenium levels also depends on the selenium
status (Alexander and Meltzer, 1995; Johnsson
et al
.,
1997; Rayman, 2004) (see also Chapter 8 for blood lev-
els in humans).
In defi ciency, selenium in blood or plasma is
decreased.
µ
6.3 Biomarkers of Effect
Whereas selenium-dependent enzymes can be used
as biomarkers of selenium status at replete and low
levels, there does not seem to be any specifi c biomarker
of defi ciency in humans. Platelet GSH-px activity has
been suggested as a valuable indicator of the selenium
