Chemistry Reference
In-Depth Information
for the total 34-year period 1947-1980. Elevated stand-
ardized mortality ratios for malignant neoplasms have
been found in both battery and production workers, the
excess deaths being predominantly from gastrointesti-
nal tract cancer and lung cancer. In the battery work-
ers, there were 34 deaths from stomach cancer with
20.2 expected and 109 deaths from lung cancer with
87.8 expected, both standardized mortality ratios being
signifi cantly raised. A similar pattern was observed
in the lead production workers. In interpreting these
fi ndings, account should be taken of the complex eti-
ology of both lung and stomach cancer. The reference
population used was U.S. white men, and smoking his-
tories were not available. In the study, account could
not be taken of the marked temporal and spatial vari-
ation of stomach cancer and of its close relationship to
social class, and data were inadequate to seek a dose-
response relationship. However, the possibility cannot
be dismissed that heavy exposure to compounds of
lead, perhaps in association with other chemical agents,
has given rise to an excess of stomach and lung cancer;
further epidemiological studies are required.
as transcriptional regulators and reduce the binding
of these proteins to recognition elements in genomic
DNA. This suggests that lead may alter gene expres-
sion through an epigenetic mechanism (Silbergeld
et al.
, 2000). Again the reader is referred to the mecha-
nism chapter in this handbook as well as the chapter
on lead for further information.
1.6.3 Evaluation
An IARC Working Group (2004) reevaluated the
potential carcinogenic hazards to humans from expo-
sure to inorganic and organic lead. The widespread
occurrence of lead in the environment has been largely
the result of anthropogenic activity since prehistoric
times. Lead use has increased progressively with
industrialization and rose dramatically with the use of
lead auto batteries and leaded fuel. The predominant
use of lead is currently in batteries, construction mate-
rials, and lead-based chemicals. It is being progres-
sively phased out in pipes, paints, and gasoline. Recent
human exposure has arisen predominantly from the
widespread use of leaded gasoline and in areas near
lead mines and smelters with high environmental con-
centrations of lead. Occupationally, the highest poten-
tial exposure to lead includes mining, primary and
secondary smelting, production of lead acid batteries,
pigment production, construction, and demolition.
To evaluate the epidemiological evidence of possi-
ble carcinogenic hazards, the Working Group consid-
ered six occupational cohort studies of highly exposed
workers to be particularly informative, battery work-
ers in the United States and the United Kingdom, and
primary smelter workers in Italy, Sweden, and the
United States. In their evaluation, the IARC concluded
that inorganic lead compounds are probably carcino-
genic to humans (group 2A) and organic lead com-
pounds are not classifi able as to their carcinogenicity
to humans (group 3). The Working Group noted that
organic lead compounds are in part metabolized to
ionic lead. To the extent that ionic lead generated from
organic lead is present in the body, it will be expected
to exert the toxicity associated with inorganic lead.
The remaining metals considered in this section have
very little or no epidemiological evidence to incrimi-
nate them as carcinogens in human exposure situa-
tions. They have, however, been included here because
of limited data in animal experimental studies. A more
detailed review is given by Kazantzis (1981).
1.6.2 Animal Models and Short-Term Tests
Zollinger (1953) fi rst observed renal adenoma and
carcinoma in rats after the subcutaneous injection of
lead phosphate (Zollinger, 1953). This observation
has been confi rmed, and several investigations have
induced similar tumors after the administration in the
diet of lead subacetate in rats and mice and lead ace-
tate in rats (Boyland
et al.
, 1962; Van Esch and Kroes,
1969). Large doses of lead were used in these experi-
ments, which caused gross morphological damage to
the kidney, and which far exceeded doses tolerated
by humans. Although tumors at other sites, includ-
ing cerebral gliomas, have been reported, these have
not been confi rmed. Lead compounds have not given
rise to mutagenic effects in bacterial test systems, but
lead acetate has induced dose-related transformation
in hamster embryo cells (DiPaolo and Casto, 1979),
lead oxide enhanced transformation by simian virus
(Casto
et al.
, 1979), and lead chloride has been shown
to decrease the fi delity of DNA synthesis (Sirover
and Loeb, 1976b). Epidemiological and experimen-
tal work from recent studies confi rms that inorganic
lead compounds are associated with increased risks of
tumorigenesis (Silbergeld
et al.
, 2000). Several possible
mechanisms by which lead compounds cause tumors
have been shown that include direct DNA damage,
clastogenicity, or inhibition of DNA synthesis or repair,
and generation of reactive oxygen species that may
cause oxidative damage to DNA. In addition, lead can
also substitute for zinc in several proteins that function
1.7 Cobalt
Finely divided cobalt metal powder, cobalt oxide,
and cobalt sulfi de have given rise to injection-site
