Cobalt - Toxicology of Metals - page 512

7.5.1 Animal Data 20 years since fi rst exposure, a signifi cant excess of

mortality by lung cancer was found (7 cases observed
vs 2.5 expected; SMR 2.78 95% CI, 1.11-5.72).
Several reports addressing cancer risks among work-
ers in hard metal production facilities in France pro-
vide evidence of an increased lung cancer risk related
with exposure to hard metal dust. The risk seems to
be highest among those exposed to unsintered rather
than sintered hard metal dust. There is evidence for
an increasing lung cancer risk with increasing dura-
tion of exposure in analyses that took into account
potential confounding by smoking and other occu-
pational carcinogens. A mortality study (Lasfargues
et al ., 1994) in workers from the hard metal industry
in France showed an increased mortality by lung can-
cer (SMR 2.13, 95% CI, 1.02-3.93, 10 cases observed)
that was related to the intensity of exposure (SMR 5.03
in the highest exposure group, 95% CI, 1.85-10.95, 6
cases observed). The excess of lung cancers could not
be explained by a confounding effect of smoking. This
study has been extended to a cohort of 7459 workers
from all hard metal plants in France. The mortality by
lung cancer in this cohort was signifi cantly increased
(SMR 1.30, 95% CI, 1.00-1.66, 63 cases observed), and a
relationship with the intensity and duration of simul-
taneous exposure to cobalt metal and tungsten carbide
particles was found (Moulin et al., 1998). An additional
study conducted in one plant already included in the
multicentric cohort demonstrated that the risk was
the highest among workers exposed in hard metal pro-
duction before sintering and increased with duration
of exposure, exposure scores, and estimated cumu-
lative dose (Wild et al., 2000). On the basis of these
data, IARC concluded that “there is limited evidence in
humans for the carcinogenicity of cobalt metal with
tungsten carbide” (IARC 2003).
A mortality study was conducted among Danish
women exposed to poorly soluble cobalt-aluminate
spinel in a porcelain factory (Tüchsen et al ., 1996). The
airborne cobalt levels in this plant were high (often
>1000

In experimental animals, early studies performed
with cobalt oxides found local tumors at injection sites
and lung tumors after intratracheal instillation. No
increased incidence of tumors was recorded by Wehner
et al . (1977) when hamsters were exposed by inhalation
to cobalt oxide at a concentration of 10 mg/m 3 7 hours/
day for 5 days a week in a lifelong experiment. Early
studies conducted with cobalt metal alone or alloyed
with chromium and molybdenum (Vitallium) did not
provide evidence of carcinogenicity except local site
tumors induced after injection. Other soluble cobalt
compounds (chloride, naphtenate) also produced local
tumors at injection sites. In a 2-year inhalation study,
cobalt sulfate heptahydrate (0.3, 1.0, or 3 mg/m 3 )
has been shown to induce lung tumors in two spe-
cies (B6C3F1 mice and F344 rats) and adrenal tumors
in female rats (Bucher et al., 1999). The incidence of
alveolar and bronchiolar neoplasms was signifi cantly
increased in rats exposed to 1.0 and 3 mg/m 3 and mice
exposed to 3 mg/m 3 . Cobalt sulfate has been recom-
mended to be listed as “reasonably anticipated by the
National toxicology Program to be a human carcino-
gen on the basis of suffi cient evidence in animals,” is
classifi ed as a category 2 carcinogen (labeled R49; “can
cause cancer by inhalation”) by the European Union,
and IARC has concluded that there was suffi cient evi-
dence in experimental animals for the carcinogenicity
of cobalt sulfate (IARC, 2003). Inhalation studies with
cobalt metal or hard metal particles are not available.

7.5.2 Human Data

Occupational cohorts have been followed up for
cancer mortality in cobalt production plants, in the
hard metal industry, and in a porcelain factory.
The follow-up of a cohort of workers employed
in an electrochemical plant producing cobalt and
sodium, and previously studied from 1950 to 1980 by
Mur et al . (1987), was extended for 7 additional years
(Moulin et al ., 1993) and did not confi rm the hypothesis
of a relationship between lung cancer and cobalt expo-
sure (SMR 0.85 [95% CI, 0.18-2.50, 3 cases observed]).
IARC concluded that there was “ inadequate evidence in
humans for the carcinogenicity of cobalt metal without
tungsten carbide” (IARC 2003).
Hogstedt and Alexandersson (1990) examined ret-
rospectively a cohort of more than 3000 workers from
one of three plants in Sweden. There were 292 deaths
among persons younger than 80 years of age during
the study period (SMR 0.96; 95% CI, 0.85-1.08) and 17
cases of lung cancer versus 12.7 expected (SMR 1.34;
95% CI, 0.77-2.13). Among those workers with more
than 10 years employment and deceased more than

g/m 3 ). The exposed group had a nonstatisti-
cally signifi cant elevated relative risk ratio of 1.2 for
lung cancer (95% CI, 0.4-3.8, 8 cases observed) com-
pared with controls, but no relation with duration or
intensity of exposure could be found. The infl uence of
smoking could not be taken into account in this study.
Among the eight cases of lung cancer identifi ed in
the exposed cohort, three had been exposed to cobalt
spinel for less than 3 months only. Overall, this study
does not provide solid evidence of an increased risk of
lung cancer associated with exposure to cobalt spinel.
No study examining the cancer mortality or incidence
in populations exposed to other cobalt compounds (sol-
uble salts, oxides) could be located.

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