Chemistry Reference
In-Depth Information
in the CNS and may also affect the immune system. The
latter type of effects are also known to be a result of
exposure to platinum, palladium, and beryllium, in the
latter case constituting the mechanism for development
of chronic beryllium disease, a form of pneumoconio-
sis (Chapters 11 and 21). Effects on the lungs in the
form of pneumoconiosis can also arise after exposure
to aluminum, antimony, barium, cobalt, iron, tin, and
tungsten or their compounds.
developmental effects are not well documented in human
exposures to other metals, but such effects have been
observed in animals after exposure to large doses of cad-
mium, indium, lithium, nickel, selenium, and tellurium
(Clarkson
et al.,
1985; Chapter 12). The diffi culties that
have occurred in the past when performing epidemiological
studies regarding these effects in humans are pointed out
in Chapter 12. Further studies with improved methods,
taking into consideration present knowledge about hu-
man reproductive endocrinology, developmental biology,
and metal toxicology, are urgently needed.
2.6 Metal Carcinogenesis and
Reproductive Toxicology
Recognition of the carcinogenicity of metals is of
ever-increasing public health importance. Conclusive
evidence based on epidemiological, experimental, and
mechanistic data has existed since the 1980s, with an in-
creasing number of metals evaluated by International
Agency for Research on Cancer (IARC). Chromium and
nickel were the fi rst metals classifi ed as carcinogens by
IARC. During the 1980s, animal studies with inorganic
arsenic confi rmed existing epidemiological evidence.
On the basis of the convincing evidence for carcino-
genicity of arsenic in humans and the fact that arsenic
is released from gallium arsenide
in vivo
in animals,
this compound has been classifi ed as a human carcino-
gen. For beryllium the situation is the reverse: results
of epidemiological studies have confi rmed earlier
experimental evidence. Cadmium can contribute to the
development of lung cancer and possibly to cancer of
the prostate. During the 1980s long-term studies on rats
inhaling cadmium chloride showed remarkable dose-
related incidence of lung cancer at low exposure levels.
Cadmium and its compounds have been classifi ed as
carcinogenic to humans by IARC. Lead and its inorgan-
ic compounds have recently been evaluated by IARC
and are classifi ed as probable human carcinogens based
on a combination of human and animal data. The expe-
rience with these metals emphasizes the importance
of carefully evaluating the consequences in humans of
exposures to metals proven to be carcinogenic in animals.
Cobalt compounds and antimony trioxide are examples
of a metal compounds considered to be possible hu-
man carcinogens mainly on the basis of animal data. A
few metal and metalloid derivatives have shown chro-
mosomal effects
in vitro
and
in vivo
, as well as point
mutations in, for example,
Salmonella
,
Escherichia coli
,
and
Drosophila
. However, for most of the carcinogenic
metals and their compounds, epigenetic mechanisms
are considered of importance in expressing their carci-
nogenicity. Carcinogenicity of metal compounds is fur-
ther discussed in Chapters 5, 10, and 14.
Prenatal effects are known to take place in poisoning
with lead, methyl mercury, and arsenic. Reproductive and
2.7 Toxicokinetics and Metabolism
Once reliable data on critical organs, critical con-
centrations, and critical effects have been established,
it may be possible to estimate the exposure required
to give rise to such concentrations, provided enough
information is available on the metabolism and kinet-
ics of the metal. A toxicokinetic model may then be set
up with data on the absorption, distribution, biotrans-
formation, and excretion of a given metal. In only a
few cases have adequate models been established, one
example being methyl mercury (Berglund
et al.
, 1971;
Chapter 23). Almost 100% of ingested methyl mercury
is taken up. The accumulation may be described by a
one-compartment model, indicating that the exchange
between the different organs is considerably faster
than the excretion of the metal. The biological half-time
is on average approximately 70 days. This means that
approximately 1% of the total body burden is excreted
daily, primarily through the bile.
The metabolism of cadmium is more complicated,
and an appropriate model is more diffi cult to establish.
Some facts are well recognized, however. The absorp-
tion of cadmium from food will average around 5%
in men and 10% in women, but under certain nutri-
tional conditions, such as a low intake of calcium or
iron, absorption levels as high as 20% may be reached
(Flanagan
et al.
, 1978; Chapters 3 and 23). Absorption
of cadmium after inhalation may vary between 10 and
50%, depending on particle size distribution. In long-
term, low-level exposures, several series of autopsy
data have shown that approximately one third of the
total body burden could be in the kidneys and about
one half in the kidneys and liver together. With higher
exposure, proportionally more cadmium would be
found in the liver. A physiologically based multicom-
partment model has been developed describing the be-
havior of cadmium. In long-term, low-level exposure,
the biological half-time is in the order of one to two
decades (Friberg
et al.
, 1985; Nordberg and Nordberg,
2002; Nordberg and Kjellstrom, 1979; WHO, 1992;
Chapters 3 and 23). The usefulness and validity of this
