Chemistry Reference
In-Depth Information
Chromium trioxide (at a dose that produced mater-
nal toxicity) caused fetal death and increased the inci-
dence of cleft palate and skeletal anomalies in hamsters
on day 7, 8, or 9 of pregnancy; administration on day 10
or 11 had little effect (Gale, 1978; Gale and Bunch, 1979).
Different rates of malformations were also observed
in different strains of hamsters after chromium treat-
ment (Gale, 1982). Similar results of fetal lethality and
malformations in survivors were produced in mice
after intraperitoneal injection of approximately 20 mg
Cr(III)/kg (Matsumoto
et al
., 1976). However, no effects
were noted in pregnant mice receiving chromium (VI)
during organogenesis (Junaid
et al
., 1996b). Danielsson
and coworkers (1982) investigated the relative toxic
actions of chromium (III) and chromium (VI). Carti-
lage formation in differentiating chick fi broblast cul-
tures was sensitive to damage by chromium (VI) but
unaltered by chromium (III). These data suggest that
the developmental effects of chromium (VI), which are
greater than those of chromium (III), may result from
increased uptake and greater direct toxicity.
oral treatment is more likely to produce diminished
growth without increased frequency of malformations
(Ambrose
et al.,
1976). Available animal data suggest
that the developing fetus and neonates are sensitive
targets of nickel toxicity, although effects were often
reported at maternally toxic doses (Nieboer, 1988).
4.6 Arsenic
Human data about congenital malformations or
developmental effects potentially caused by arsenic
derive mainly from investigations of populations liv-
ing near smelting factories or arsenic-processing plants
(Nordstrom
et al
., 1978a,b; 1979a,b). In these studies,
however, the analyses gave limited consideration to
potential confounders (e.g., smoking), and there were
no data specifi cally relating the apparent effects to
arsenic exposure alone. After evaluating 13 studies
of human populations and 43 laboratory animal or
in
vitro
studies, DeSesso
et al
. (1998) concluded that nei-
ther the human nor the animal studies were of suffi -
cient robustness to be conclusive.
Structural malformations in experimental animals
were induced only when maternal arsenic blood
concentrations were very high and depended on the
route of administration under conditions not usual or
relevant for human exposure (Holson
et al
., 2000b).
The inhalation of high amounts of arsenic, as As
2
O
3
,
produced developmental effects in laboratory animals.
Exposures lower than 2.2 mg As/m
3
caused modest
decreases in fetal body weight, and those lower than
0.20 mg As/m
3
had no effects. However, it is unclear
whether these effects occur only at doses that cause
maternal toxicity (Nagymajtenyi
et al
., 1985).
In other experiments, no increases in fetal resorp-
tions, fetal mortality, or malformations, and no
decreases in fetal birth weight occurred when rats were
exposed to 0.2-7 mg As/m
3
(as As
2
O
3
) before mating
and during gestation. Around the 8 mg/m
3
exposure
level, toxicity was observed in the dams (Holson
et al
.,
1999).
4.5 Nickel
Nickel has not been shown to affect development in
humans, and available data are based on animal exper-
imental studies. In term infants, cord blood and mater-
nal concentrations of nickel are nearly equal. However,
detectable amounts of nickel have been identifi ed in
human fetal tissues and are somewhat higher than
concentrations in full-term infants (Casey and Robin-
son, 1978).
In experimental animals, nickel was localized within
embryos on day 8 of gestation after intramuscular or
intraperitoneal injections of nickel (Sunderman
et al
.,
1978) and in the visceral yolk sac, gastrointestinal tract,
and kidney of the fetus on day 16 in the mouse (Olsen
and Jonsen, 1979). Fetal tissue concentrations of nickel
are generally higher than maternal levels in late gesta-
tion (Jacobsen
et al
., 1978).
The embryotoxicity and teratogenic effects of nickel
have been reviewed by Sunderman
et al
. (1983). Malfor-
mations after the administration of soluble nickel salts
have been reported in hamsters (Ferm, 1972; Sunder-
man
et al
., 1980), mice (Lu
et al
., 1979; Storeng and Jon-
sen, 1981), and rats (Sunderman
et al
., 1979); anomalies
included ocular, skeletal, and neural defects and were
generally observed after single parenteral administra-
tion. Nickel carbonyl seems to be the most teratogenic
of the nickel salts even after exposure by inhalation
(Sunderman
et al
., 1979; 1980). Neither NiCl
2
nor Ni3S
2
produced malformations in rats when injected on
day 6 or 8 of gestation, although fetal weights were
reduced (Sunderman
et al.,
1978). Chronic and/or
4.7 Vanadium
Decreased fertility, embryolethality, fetotoxic-
ity, and teratogenicity have been demonstrated in
rats, mice, and hamsters after vanadium exposure,
but it is not certainly established whether vanadate
(V
+5
) and vanadyl (V
+4
) compounds are reproduc-
tive and developmental toxicants (Domingo, 1996).
The same author (Domingo, 2002) reported repro-
ductive, developmental, and behavioral toxicity, as
well as mitogenic activity affecting the distribution of
chromosomes during mitosis, inducing aneuploidy-
related endpoints.
