Antimony - Toxicology of Metals - page 354

female rats, but not male rats, developed lung neo-
plasms. The authors attributed this difference to a
lower immunological responsiveness in female rats
(Groth et al ., 1995). A subchronic and chronic inhala-
tion study of Sb 2 O 3 in rats did not lead to increased
frequencies of neoplasms (Newton et al ., 1994). Watt
(1983) found that female rats exposed to antimony
trioxide at concentrations of 1.6 and 4.2 mg Sb/m 3 for
6 hours per day, 5 days per week for 1 year followed
by a 15-month observation period, showed a high
frequency of lung neoplasias (see also Section 7.1.1).
The lung neoplasias were either scirrhous carcinomas,
squamous cell carcinomas, or bronchioalveolar ade-
nomas. There was evidence of local invasion, but no
metastasis was observed.
Human carcinogenicity of antimony is diffi cult to
evaluate because of the frequent coexposure to arsenic
(De Boeck et al ., 2003). In a study of U.S. antimony
workers, excess mortality from cancers of the liver,
biliary tract, and gallbladder was found in a cohort
of antimony smelter workers (Schnorr et al ., 1995).
The American Conference of Governmental Indus-
trial Hygienists (ACGIH, 1983) refers to unpublished
data on mortality among workers in a large antimony
smelter in the U.K. In the 1960s, exposure to antimony,
mainly in the form of antimony trioxide, ranged from
0.5-40 mg/m 3 . Apart from antimony, the workers were
also exposed to zirconium. The data cited are diffi cult
to interpret, but there seems to be an increased pro-
portional mortality from lung cancer among the most
heavily exposed men. On the basis of these data, the
ACGIH (1983) concluded that antimony oxide should
be regarded as a suspected carcinogen.
Overall, the International Agency for Research on
Cancer (IARC) fi nds the available data on the carcino-
genicity of antimony to be inconclusive. IARC classi-
fi es antimony trioxide as possibly carcinogenic to humans
(Group 2B) and antimony trisulfi de as not classifi able as
to its carcinogenicity to humans (Group 3) (IARC, 1989).
Antimony compounds display genotoxic activ-
ity in vivo and in vitro . They behave clastogenically
(Gurnani et al ., 1992a; 1992b; 1993) but are not directly
mutagenic (Kuroda et al ., 1991). Genotoxicity is
valence-dependent. The trivalent species (Sb 2 O 3 and
SbCl 3 ) were genotoxic in the sister chromatid exchange
test with V79 cells, whereas the pentavalent species
(Sb 2 O 5 and SbCl 5 ) were not (Kuroda et al ., 1991). Gebel
et al . (1997) used the sister chromatid test to assess the
genotoxicity of extracts of soil containing high con-
centrations of antimony and arsenic, both in the pen-
tavalent state. They found low genotoxicity, as well as
partial antagonism. Andrewes et al . (2004) tested fi ve
antimony compounds for genotoxicity. Stibine and
trimethylstibine were genotoxic when tested using a

pBR 322 plasmid DNA-nicking assay, whereas potas-
sium antimony tartrate, potassium hexahydroxyanti-
monate, and trimethyl antimony dichloride were not.
There is a scarcity of data on the mechanism of action.
A biomonitoring study of 23 textile workers exposed
to Sb 2 O 3 assessed genotoxicity using the sister chro-
matid assay and cytokinesis-block micronucleus
(MN) tests and the enzyme (Fpg)-modifi ed comet
assay. Results support the theory that genotoxicity is
due to oxidative DNA damage (Cavallo et al ., 2002;
USEPA, 2004).

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