Titanium - Toxicology of Metals - page 843

Hygienists (ACGIH, 2005) suggested a threshold limit
value/time-weighted average (TLV-TWA) for TiO 2
(CAS 13463-67-7) of 10 mg/m 3 .

because of overload (Bermudez et al ., 2002; 2004). It is
suggested that small amounts of titanium dioxide can
enter the general circulation from the lungs (Lee et al .,
1985). The absorption and transference of titanium
to the liver and spleen in rats exposed to 10 mg/m 3
titanium tetrachloride aerosol for 6 hours per day,
5 days per week, for 2 years, have been reported (Lee
et al ., 1986).

5 METABOLISM

An important property of titanium is that, on expo-
sure to air or various liquids, it rapidly develops a
layer of oxide, which reduces its reactivity (Olmedo
et al ., 2003).

5.2 Distribution
Several transport mechanisms have been described
for titanium, including systemic dissemination by the
vascular system in solution or as particles (Edel et al .,
1985; Meachin and Williams, 1973; Merritt and Brown,
1995) and lymphatic dissemination as free particles or
as phagocytosed particles within macrophages (Bianco
et al ., 1996).
Titanium concentrations of 2-9 mg/kg wet weight
were found in the parenchymatous organs—such as
the heart, lungs, spleen, liver, and kidneys—of mice
that had been given titanium oxalate in their drinking
water at a level of 5 mg/L throughout their lifetime.
The concentrations were similar to those observed in
wild mice, but were fi ve times higher than the concen-
trations found in untreated animals (Schroeder et al .,
1964). Six hours after titanium dioxide was adminis-
tered to rats through intravenous injection at 250 mg/kg
body weight, the highest concentration appeared in
the liver; after 24 hours, the highest concentration was
detected in the celiac lymph nodes, which fi lter the
lymph from the liver (Huggins and Froehlich, 1966).
In the general population, titanium has been
detected in various parenchymatous organs, with the
highest concentrations consistently being found in the
lungs (Hamilton et al ., 1972/1973), probably as a result
of inhalation of titanium-containing dust particles.
Teraoka (1980) reported even higher concentrations in
the hilar lymph nodes than in the lungs. In coal min-
ers, lung concentrations have been reported to be sev-
eral times than those found in the general population
(Crable et al ., 1967; 1968). Titanium was demonstrated
in the lymphatic systems of three workers engaged in the
processing of titanium dioxide pigments (Elo et al ., 1972).

5.1 Absorption
A number of studies have indicated that titanium
is absorbed mainly through ingestion, but different
conclusions have been drawn as to the extent. One
study undertaken by Schroeder et al . (1964) found
that titanium levels in the organs of mice given potas-
sium titanium oxalate at a concentration of 5 mg/L in
their drinking water during their entire life span were
fi ve times higher than those observed in control ani-
mals. Translocation of TiO 2 (rutile) particles to intes-
tinal tract-associated tissues and other organs was
observed in rats administered 12.5 mg/kg/day TiO 2
by gavage for 10 days (Jani et al ., 1994). In another
study that used mice, a very low degree of absorp-
tion from the gastrointestinal tract was observed: the
whole-body count of experimental animals given 44 Ti
intragastrically did not exceed the background level
after 24 hours (Thomas and Archuleta, 1980). Blood
titanium levels were found to increase after oral
administration of TiO 2 (anatase) to human volunteers
(Böckmann et al ., 2000).
Many data indicate that titanium is absorbed poorly
from the gastrointestinal tract in human beings. It is
likely that transferrin may act as a specifi c carrier of
titanium ions and may play a central role during the
transporting and biodistribution of soluble titanium
species throughout the organism (Ishiwata et al ., 1991).
Titanium concentrations found generally in urine
(approximately 10 g/L) suggest an absorption of <5%,

assuming a daily intake of at least 300

µ

g. Although
this estimate agrees with that reported by Schroeder
et al . (1963), it may be erroneous because other possible
routes of excretion, especially intestinal, were not been
taken into consideration.
The deposition of titanium dioxide dust in the
lungs of rats is similar to that observed for other par-
ticles (Ferin et al ., 1983). Titanium dioxide is found
in the lymphocytes and regional nodes in the lungs,
indicating that a slow rate of removal occurs by this
process. Clearance is also signifi cantly decreased, or
even ceases, at high exposure over a period of time

µ

5.3 Biological Half-Time
At present, there is still an insuffi cient amount of
data for estimating the biological half-time of titanium
in humans or animals. The ICRP calculated a half-life
of 320 days (ICRP, 1959). Although a half-life in mice
was reported to be 640 days, the authors speculated
that in man the half-life might be even longer (Thomas
and Archuleta, 1980).