Chemistry Reference
In-Depth Information
was observed in rats after the administration of man-
made titanium phosphate fi bers having lengths of 10-
20
abnormality. A study of 136 workers exposed to ilmen-
ite and rutile in Sri Lanka did not fi nd any signifi cant
difference in the incidence of radiological lesions of
the chest compared with that of the general popula-
tion (Uragoda and Pinto, 1972). A study of 207 workers
engaged in the production of titanium dioxide from
ilmenite, with an exposure time of 20 years for 90% of
the workers, suggested that 47% of the subjects had
the obstruction discovered by spirometry, which the
authors suggested may have been caused by irritant
effects associated with the sulfate process; no fi brotic
effects attributable to the titanium dioxide exposure
were noted, however (Daum
et al
., 1977). Chen and
Fayerweather (1988) studied the rate of mortality
among 1576 male employees who had been exposed
to TiO
2
for more than 1 year in two TiO
2
-producing
plants in the United States. The mortality of the mem-
bers of the group was monitored from 1935 to 1983.
No excess mortality from nonmalignant respiratory
disease was observed. Members of part of the group,
336 workers, were examined with X-rays; no cases of
fi brosis were detected. A European multicenter epide-
miological study monitored workers employed in 11
plants producing TiO
2
in six European countries. The
mortality over a 30-year period from nonmalignant
respirator disease was less than expected (Bofetta,
2004). A similar multicenter study in the United States
monitored 4241 workers exposed in TiO
2
-manufac-
turing plants. A mortality follow-up study, covering
40 years, did not reveal any adverse effects related to
TiO
2
exposure (Fryzek
et al
., 2003).
Acute (short-term) exposure of humans to tita-
nium tetrachloride may result in marked congestion
of mucous membranes of the pharynx, vocal cords,
and trachea and stenosis (constriction) of the larynx,
trachea, and upper bronchi. Workers producing tita-
nium tetrachloride have developed hyperemia and
thinning of the mucosa of the respiratory tract, as well
as bronchitis, possibly because of the production of
hydrochloric acid on the rapid hydrolysis of titanium
tetrachloride by water (EPA, 1985). Chronic inhalation
exposure may produce upper respiratory tract irrita-
tion, chronic bronchitis, coughing, bronchoconstric-
tion, wheezing, chemical pneumonitis, and pulmonary
edema in humans. Pleural diseases of workers involved
in titanium metal production have been linked with
their chronic (long-term) occupational exposure to tita-
nium tetrachloride. This fi nding suggests that chronic
exposure to titanium tetrachloride may result in restric-
tive pulmonary changes (ATSDR, 1997).
m (Gross
et al
., 1977).
Administration of a total dose of 75 mg of barium
titanate, given in three weekly doses as a 5% suspen-
sion, through intratracheal instillation, did not pro-
duce any fi brotic changes in guinea pigs for up to 12
months (Pratt
et al
., 1953). Inhaling titanium hydride
for 16 months, however, produced weak fi brogenic
effects (Skurko and Brahnova, 1973).
µ
m and diameters of 0.2-0.3
µ
7.1.1.2 Other Sites and Implants
Studies on rats given single intraperitoneal injec-
tions of 25 mg of titanium dioxide (Sethi
et al
., 1973)
or an intravenous injection of 250 mg/kg body weight
(Huggins and Froehlich, 1966) indicated that the com-
pound is biologically inert.
Most of the medical reports regarding titanium in the
early 1980s focused on whether titanium alloys were
suitable implantation materials (e.g., Brunette
et al
.,
1983; Kallus and Hensten-Pettersen, 1983; Kasemo,
1983; Schroeder
et al
., 1981). The general inertness of
titanium has been demonstrated convincingly in sev-
eral studies. The lack of irritation, the good degree of
wound healing, and the encapsulation of the metal by
fi brous tissues after the implantation of titanium metal
in dogs all suggest that soft tissue has a high tolerance
for titanium metal (Shpak and Margolin, 1971).
7.1.2 Humans
7.1.2.1 Lungs
Elo
et al
. (1972) studied lung specimens from three
factory workers exposed for 9 years to the processing
of titanium dioxide pigments; they found deposits in
the pulmonary interstitium with cell destruction and
slight fi brosis. Clearance of titanium dioxide through
the lymphatic system was demonstrated by the obser-
vation of particles in the lymph nodes. A subsequent
report (Maatta and Arstila, 1975) revealed the presence
of aluminum and silica in the macrophages, in addition
to titanium particles. It was suggested that the simul-
taneous exposure to silica compounds was responsible
for the fi brotic changes, rather than the exposure to
titanium dioxide. Clinical and epidemiological stud-
ies have generally confi rmed the experimentally dem-
onstrated lack of fi brogenicity of titanium dioxide.
Through an autopsy study, extensive titanium dioxide
deposits were discovered in two heavily exposed work-
ers, but fi brosis was not detected (Ophus
et al
., 1979).
There are several epidemiological studies describ-
ing the effects of titanium dioxide. Studies on men
exposed to titanium dioxide for prolonged periods
did not reveal any signs of clinical or radiological
7.1.2.2 Other Sites and Implants
Titanium is used widely as an implant material in
orthopedics, oral surgery, and neurosurgery, because
