Chemistry Reference
In-Depth Information
fi brosarcoma after subcutaneous injection and to
rhabdomyosarcoma after intramuscular injection in
rats (Gilman, 1966). They were able to produce such
neoplasms with fi ne particles from surgical prosthe-
ses made from a cobalt-chromium alloy. Cobalt chlo-
ride has been shown to decrease the fi delity of DNA
synthesis
in vitro
(Sirover and Loeb, 1976a), to induce
morphological transformation, and to enhance viral
transformation of hamster embryo cells (Casto
et al.
,
1979; DiPaolo and Casto, 1979).
There have been few reports of cancer in cobalt
workers despite past occupational heavy exposure.
In certain nickel extraction plants in the U.S.S.R., an
increased mortality from lung cancer was found in
the cobalt-recovery shops and in the nickel-processing
departments (Saknyn and Shabynina, 1973). However,
exposure to arsenic-containing dust was heavy, and
these workers may also have been exposed to nickel.
There are no convincing reports of cancer having arisen
in relation to surgical prostheses with cobalt-containing
alloys, despite raised blood and urinary cobalt levels.
IARC (1991) considered that cobalt and cobalt com-
pounds are possibly carcinogenic to humans (group
2B) (IARC 1991). Again the reader is referred to the
mechanism chapter in this handbook and the chapter
on cobalt for further information.
transformations in hamster embryo cells and only
enhanced viral transformations in very high concen-
trations (Casto
et al.
, 1979). Iron did not decrease the
fi delity of DNA synthesis in the cell-free system of
Sirover and Loeb (1976) (DiPaolo and Casto, 1979).
There has been speculation on the role of iron oxide
as a possible carcinogen common to hematite, asbestos,
nickel, and chrome workers, but there is little evidence
to support such a hypothesis. Boyd
et al.
(1970) observed
a signifi cantly increased mortality rate from lung can-
cer in hematite miners in Cumberland, England, but
this excess risk could also be attributed to ionizing
radiation from radon and radon daughters present in
the atmosphere of the mine (Boyd
et al.
, 1970). Excess
lung cancer mortality has also been observed in iron-
ore miners from a number of other countries. Raised
levels of ionizing radiation were found in the iron ore
mines of Kiruna, Sweden, but measurements have not
been made in all mines where a lung cancer hazard
has been shown to exist. An increased mortality risk
from lung cancer in iron and steel foundry workers
has been attributed to exposure to polycyclic hydro-
carbons. Exposure to high levels of iron oxide in the
production of sulfuric acid from iron pyrites showed
no excess mortality from cancer at any site (Axelson
and Sjoberg, 1979).
On the basis of the experimental animal studies and
on what they termed suggestible evidence in man,
the IARC (1976) classifi ed iron-dextran as “probably
carcinogenic for humans.” In regard to occupational
exposure, the IARC concluded on the basis of epide-
miological evidence that underground hematite min-
ing does increase the risk of lung cancer in man, but
that the evidence is inadequate to classify hematite
as the carcinogen. A number of confounding factors
have to be taken into account before the role of iron
in human carcinogenesis can be adequately assessed.
Again the reader is referred to the mechanism chapter
in this handbook.
1.8 Iron
Iron-dextran and certain other polysaccharide iron
complexes have induced local sarcomas in mice, rats,
rabbits, and hamsters after subcutaneous or intra-
muscular injection in large doses with evidence of a
dose-response relationship (Haddow and Horning,
1960; Richmond, 1959; Roe and Carter, 1967). The
signifi cance of these observations arises in relation
to iron therapy. Although many of these compounds
have been administered parenterally in the treatment
of anemia over the past 30 years or so, sarcoma at the
injection site has been rarely reported. In a survey of all
72 soft tissue sarcomas found over a 2-year period in a
defi ned area, no history of past parenteral iron therapy
could be obtained (McIllmurray and Langman, 1978).
The repeated intratracheal installation, in hamsters,
of ferric oxide suspended in normal saline did not give
rise to lung tumors (Saffi otti
et al.
, 1968). However,
given together with benzo(a)pyrene or with systemi-
cally administered diethylnitrosamine, an increased
yield of lung tumors was obtained. Ferric oxide was
thought to be a carcinogenic cofactor, possibly acting
by retarding clearance of an inhaled carcinogen or
by inducing cytopathological changes that make the
cells of the respiratory tract more susceptible to car-
cinogens. Iron oxide did not produce morphological
1.9 Manganese
In a single experiment, rats were given intramus-
cularly pure manganese powder, manganese dioxide,
or manganous acetylacetonate suspended in triocta-
noin in multiple treatments. Although no difference in
tumor incidence between treated and control animals
was found with manganese powder and manganese
dioxide, a signifi cant number of fi brosarcomas devel-
oped at the injection site in the rats given manganous
acetylacetonate, with a mean latent interval of 17
months (Furst, 1978). Enhanced viral transformation
of hamster embryo cells was obtained with manganese
chloride (Casto
et al.
, 1979), and this compound also
