Chromium - Toxicology of Metals - page 493

information on the “frequency” of lung cancer in his
study, but assuming that six lung cancer deaths in 1947
were “average” incidence for the cohort, the absolute
risk might have been approximately 1.500 × 10 −5 /
year, which is equivalent to the highest absolute risk
reported recently.

compounds in cell cultures and in vivo and found that
chromate was able to induce chromosomal damage
in cell culture and in vivo in bone marrow after drink-
ing water exposure (Ginter, et al ., 1989; Sen and Costa
1986; Sen et al ., 1987). Vitamin C was found to inhibit
the ability of chromate compounds to induce micronu-
clei in bone marrow of guinea pigs given chromate by
ingestion (Ginter et al ., 1989). Chromate mutagenesis in
tissue culture may have been diffi cult to study because
of the absence of ascorbic acid in cells grown in cul-
ture. This vitamin is the major reducer of hexavalent
Cr in vivo, and because it is not added to tissue culture
media, the only source of it comes from the fetal bovine
serum that is added to cultured media. Thus, the lev-
els of this vitamin are low, and, in general, chromate
compounds are not potent mutagens in tissue culture,
although they induce chromosomal damage and form
DNA adducts. A recent study has suggested that the
actual Cr adducts on DNA may not be very mutagenic,
because they bind to the phosphate backbone of DNA
and do not distort the DNA helix very much (Blank-
ert, 2003). This fi nding may explain the discrepancy
between the DNA damage observed by chromate com-
pounds and their low mutagenicity (Aiyar, 1991; Cupo,
1985a,b; Tsapakos, 1981).
Chromate compounds have been found to induce
DNA damage in vivo in experimental animals and in
lymphocytes of chromate-exposed workers (Cheng et
al ., 2000; Costa et al ., 1993; Taioli, 1994; Toniolo, 1993).
Thus, chromate exposure by inhalation is able to induce
DNA damage in blood cells or in other organs that may
be distant from the exposure site (Cheng, 2000).

7.3.3 Interaction with Other Carcinogenic Factors

7.3.3.1 Animals
Nettesheim et al . (1971) induced 13 lung adenomas
in 136 virus-infected mice exposed to 13 mg calcium
chromate/m 3 5 hours a day, 5 days a week for a life-
time. In rodents, Balansky et al . (2000) failed to reveal
any additive interaction between cigarette smoking
and Cr(VI) in inducing clastogenic damage.

7.3.3.2 Humans
In the fi rst article by Bidstrup (1955), there was
some suggestion on possible potentiating interaction
between inhalation exposure to Cr(VI) and smoking
in inducing lung cancer. However, no subsequent epi-
demiological study has confi rmed such an interaction
between the two exposure factors. It is still possible that
interaction may take place between the two factors, but
few epidemiological studies among Cr(VI)-exposed
workers have reported smoking habits in suffi cient
details to permit studying such a possible interaction.
In the study by Tsuneta (1982), 25 lung cancer cases
were reported. Smoking was confi rmed among 20
case subjects, and four were reported to be nonsmok-
ers. Moulin et al . (2000) studied lung cancer in workers
manufacturing stainless steel and metallic alloys but
did not unravel confounding of tobacco smoking when
adjusting for that exposure factor. Antilla et al . (1989)
found that average lung tissue levels of Cr in smokers
was 6.4

7.3.5 Teratogenic Effects

By use of a whole-body radioautographic method,
Diab and Södermark (1972) demonstrated Cr in the
skin and the vertebral bone of the fetuses 1 hour after
intravenous administration of isotonic 51 CrCl 3 to preg-
nant mice. The later in the pregnancy the dose was
administered, the more Cr could be demonstrated in
the fetuses. Visek et al . (1953) detected only minute
amounts of Cr in the fetuses of rats after intravenous
administration of both the Cr(VI) and the Cr(III) form.
Many details on the mechanisms of Cr transport
through the placental membranes are still unknown.
It has, however, been demonstrated that intravenous
administration of 8 mg CrO 3 /kg to pregnant golden
hamsters induced cleft plates in a great number of the
fetuses (Gale and Buch, 1979). Gilani and Marano (1979)
injected CrO 3 in saline into embryonating chicken eggs
at a dose ranging from 0.002-0.05 mg per egg. They
demonstrated a high incidence of malformations,
such as reduced body weight, microphthalmia, short
and twisted limbs, ectopic heart, and everted viscera.

g/g in nonsmoking referents,
which is likely to result from Cr in tobacco smoke.
Many workers exposed to Cr(VI) have undoubt-
edly also been exposed to asbestos fi bers. However,
no author has reported specifi cally on the possible
interaction between exposure to Cr(VI) and asbestos.
Numerous Cr electroplaters have also carried out Ni
electroplating, having been exposed to both Cr(VI) and
Ni compounds. Also in SS welding, the welders are
exposed to both Cr and Ni compounds. However, no
author has attempted to differentiate between the two
carcinogenic factors to scrutinize possible interaction
between the two.

µ g/g versus 2.2 µ

7.3.4 Mutagenic and Genotoxic Effects

Chromium compounds are mutagenic in bacte-
rial and mammalian systems (IARC, 1990). Early
studies examined the clastogenic effects of chromium