Chemistry Reference
In-Depth Information
and census data were used to identify groups with
potential metal exposure. In women belonging to the
union of metal workers, the rate of abortions was
slightly higher (7.82%, number of abortions;
n
= 195)
than the national average (7.34%;
n
= 24,107). The rate
of abortions for women belonging to union branches
with possible exposure to metals such as zinc, cobalt,
and arsenic was compared for pregnancies during
membership or for pregnancies before or after mem-
bership. The rate of abortions for conceptions during
membership was again slightly higher than for non-
membership periods.
In a community study in which the major site of
employment was a factory producing zinc and cobalt,
increased abortions were noted for economically active
women compared with all women in the community
and for wives of men employed at the metallurgy factory
compared with the wives of all industrial workers.
The number of pregnancies among the female workers
at the metallurgical factory was too low to be evalu-
ated. However, data gathered from census and hospi-
tal records showed that the rate of abortions among
welders (9.5%;
n
= 28) was higher than for all industrial
workers (8.2%;
n
= 2260) (Hemminki
et al.,
1983).
The effects of coexposure to metals on female repro-
ductive function was demonstrated in a study carried
out by Belles
et al
. (2002), focusing on the develop-
mental toxicity in mice of lead nitrate (25 mg/kg, sub-
cutaneously), methylmercury chloride (12.5 mg/kg,
orally), and sodium arsenite (6 mg/kg, subcutane-
ously). Metals were administered on gestation day 10
separately or in their binary and ternary combinations.
Maternal toxic effects were more remarkable in the
group concurrently exposed to Pb, Hg, and As than
in those given binary combinations of the elements
and in those given the metals separately. With regard
to developmental toxicity, the most relevant effects,
namely decreased fetal weight and cleft palate,
corresponded to the Hg-treated groups. These data
suggest that at the current doses, the interactive effects
of Pb and As on Hg-induced developmental toxicity
were not greater than additive. In contrast, exposure of
pregnant mice to Pb and As at doses that were practi-
cally nontoxic to dams, but administered concurrently
with organic Hg at a toxic dose, caused supraadditive
interactions in maternal toxicity.
lethality or other developmental effects. Although meth-
ylmercury is clearly teratogenic for humans, other met-
als such as nickel, arsenic, and lead have less severe
effects. Teratogenesis bioassays in rodents (hamsters,
mice, or rats) have yielded positive results for the com
pounds of many metals (Al, As, Bo, Cd, Co, Cr, Cu, Ga,
Hg, Li, Mn, Ni, Pb, Se, U, V, and Zn), producing fetal and
early postnatal deaths, as well as malformations such
as anencephaly, eye defects, cleft palate, and skeletal
anomalies (Sunderman, 1998). However, the relevance
of these fi ndings to human exposure is uncertain.
The effects produced by metals depend on the tim-
ing and duration of exposure, on their distribution and
accumulation in various organs such as the nervous
system, and on the ability to interfere with specifi c
developmental processes. Effects may be enhanced by
biochemical, physiological, and anatomical changes
occurring during development, which may result in a
modifi ed metabolism of the metal itself (Rice and Bar-
one, 2000). Interesting interactions between environ-
mental and congenital factors have been documented;
genetic polymorphisms can affect fetal susceptibility to
teratogens or maternal ability to detoxify and excrete
xenobiotics (Garcia, 2000).
Mechanisms of damage during development include
proliferation (cell division), cell death, cellular differen-
tiation, biosynthesis, cell-cell or tissue-tissue interac-
tions, and cellular movements. Damage may be related
to these kinds of epigenetic injury or to a direct genetic
action on developing tissues (Mottet and Perm, 1983).
The primary etiological factors and pathogenetic
mechanisms contributing to developmental effects
caused by metal exposures are only partly known. Neu-
rodevelopmental impairment may range from serious
mental retardation and other overt clinical syndromes
to subtle subclinical defi cits as sensory, motor, and cog-
nitive impairment that are diffi cult to identify. Subtle
effects, although less severe at an individual level, may
be important for public health policy. The damage may
not become apparent until after some latency period;
therefore, the critical periods of sensitivity and latent
effects may complicate the interpretation of many
experimental and epidemiological studies.
The symposium on Health Risks Associated with
Prenatal Metal Exposure held in 1995 was designed
to evaluate the health risks for mother and develop-
ing offspring associated with
in utero
exposure to met-
als commonly found in the workplace and/or ambient
environment. Epidemiological and toxicological evi-
dences of these effects were demonstrated, focusing on
the mechanisms associated with exposure to arsenic,
lead, and methylmercury (Zelikoff
et al
., 1995). Reviews
by Carpenter (2001) and Mendola
et al
. (2002) may pro-
vide further background information.
4 DEVELOPMENTAL EFFECTS
OF PRENATAL EXPOSURE
Exposure to metals during organogenesis may give
rise to fetal anomalies, and exposure during other
periods of development may result in embryo or fetal
