Molybdenum - Toxicology of Metals - page 718

5.4 Biological Half-Life
The excretion of molybdenum and its rapid clear-
ance from the liver, kidney, spleen, testis, and hard
tissues in animal studies show that the biological
half-life for the major part of the absorbed molyb-
denum must be in the order of hours and extending
to a maximum of approximately 1 day in laboratory
animals and cows (Bibr and Lener, 1973; Fairhall
et al ., 1945; Neilands et al ., 1948; Robinson et al ., 1964;
1968).
In healthy adults, the half-life is infl uenced by die-
tary intake and is much shorter when intake is high
than when it is low (Turnlund et al ., 1995a). Half-lives
of plasma clearance in humans were estimated to be
between 4 and 70 minutes for a fast component and
between 3 and 30 hours for a slow component (Werner
et al ., 2000). When a small dose was injected, 34% of
the dose was excreted in the urine within 1 day, and
60% was excreted when a large dose was injected.
Residence time in slow turnover tissues, based on
120-day studies, was estimated at between 56 and
267 days (Thompson and Turnlund, 1996; Thompson
et al ., 1996).
Studies in rats demonstrated that after a single sub-
cutaneous injection, the concentration of molybdenum
in blood decreases rapidly. After 24 hours, only approx-
imately l% of the maximum concentration remained.
During the next 10 days, concentrations in blood
diminished with a half-life of approximately 7 days
(Kselikova et al ., 1974). After application of doses up to
3

from 22-1400 g/day (Turnlund and Keyes, 2004).

Concentrations are usually <10 nmol/L (Versieck,
et al ., 1981). Blood concentrations rise after meals,
then return to basal levels (Cantone et al ., 1995).
Infused tracer doses disappear rapidly, with 2.5-5%
remaining after an hour (Cantone et al ., 1995, Rosoff
and Spencer, 1964).

µ

5.3 Excretion
Animal data indicate low retention and more or
less complete excretion of molybdenum, primarily
through urine, during the fi rst 2 weeks after single
exposures in guinea pigs, rats, goats, and swine
(Anke et al ., 1971; Bell et al ., 1964; Bibr and Lener, 1973;
Fairhall et al ., 1945; Kselikova et al ., 1974; Neilands
et al ., 1948). The main excretion route in cows was
reported to be through feces (Bell et al ., 1964). An
important excretion route related to the gastroin-
testinal excretion is the bile (Lener and Bibr, 1979).
Small amounts are excreted through milk and hair in
goats (e.g., approximately 2% and 0.2%, respectively)
(Anke et al ., 1971). A negligible amount of molybde-
num is excreted in the saliva (Lener, 1978).
The pattern and route of molybdenum excre-
tion in man is influenced by dietary intake. The
primary route of excretion is through the urine
(Rosoff and Spencer, 1964; Turnlund et al ., 1995a;
1995b). Excretion was studied by Rosoff and
Spencer (1964) after a single intravenous injec-
tion of radioactive molybdenum to terminally ill
patients. The cumulative 99 Mo excretion over 14
days was 24% in one subject and 29% in another,
whereas the corresponding fecal excretion was
6.8% and less than 1%, respectively. Controlled
human studies demonstrated that when intake
is very low, approximately 60% of the amount of
ingested molybdenum is excreted in the urine,
and approximately 40% is eliminated in the stools.
When intake is high, > 90% is excreted in the urine
and <10% in the stools (Turnlund et al ., 1995a,b).
The source of molybdenum in the stools is partly
unabsorbed dietary molybdenum and partly
endogenous molybdenum excreted into the gas-
trointestinal tract through the bile. The excretion
of urinary molybdenum in the United States aver-
aged 69

g/kg, the biological half-life was 47 hours. At doses
higher than 3

µ

g/kg, the biological half-life was 3 hours
for subcutaneous and 6 hours for intragastric applica-
tion (Bibr and Lener, 1973). After single subcutaneous
application of 0.02-1

µ

g Mo/kg to rats, the biological
half-life in the kidneys, liver, spleen, jejunoileum, and
skin varied between 2.5 and 4.7 days (Bibr and Lener,
1974).

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5.5 Molybdenum Defi ciency
Molybdenum is an essential element for animals
(Rajagopalan, 1988). It is a constituent of three mam-
malian enzymes, xanthine oxidase, aldehyde oxidase,
and sulfi te oxidase. These enzymes all contain the
molybdenum cofactor, a complex of molybdenum
and an organic component, molybdopterin (Higdon,
2003; Johnson, 1997; Turnlund, 2002). Sulfi te oxidase
oxidases sulfi te to sulfate, reducing molybdenum VI
to molybdenum IV, and is required for the metabolism
of the sulfur amino acids. Xanthine oxidase catalyzes
the breakdown of nucleotides to uric acid. Xanthine
oxidase and aldehyde oxidase catalyze a number

g/day (Paschal et al . 1998) and in Ger-
many ranged from 28-52

µ

µ g/day. German women

excreted 10 g molybdenum/day in milk on the

35th day of lactation (Anke, 2004).
Molybdenum excretion is infl uenced by copper
and sulfates, but the effect is not consistent and var-
ies among species studied (Mills and Davis, 1987). The
interaction is discussed in Section 7.3.

µ