PRINCIPLES OF TOXICOLOGY

492 EXAMPLE OF RISK ASSESSMENT APPLICATIONS
TABLE 19.8 Summary of Rodent Inhalation Studies of Antimony Trioxide
Species Exposure Animals with Lung Tumors Reference
Rat (female;
Fischer)
Rat (male and
female; Wistar)
Rat (male and
female; Fischer
344)
The Watt study is limited by the use of only one sex for carcinogenicity testing. In addition, the
precision of dose measurements in this study has been questioned, suggesting that antimony trioxide
exposures may have actually been higher than reported (Newton et al., 1994).
Groth et al. (1986) treated male and female Wistar rats with 0 or 45 mg/m 3 (time-weighted average)
antimony trioxide for 7 h/day, 5 days/week for 52 weeks followed by a 18–20 observation period before
terminal sacrifice (71–73 weeks after initiation of the study). Groth et al. (1986) also reported
significant fluctuations in the antimony exposure concentrations generated in the exposure chambers.
During the latter 6 months of exposure, air concentrations occasionally exceeded the calculated
time-weighted average concentration by 50–100 percent. Lung changes in treated rats included
interstitial fibrosis, alveolar-wall hypertrophy and hyperplasia, and cuboidal and columnar cell
metaplasia. These changes were more severe with increasing duration of exposure. The extent of
interstitial fibrosis continued to progress even after exposure ceased. Overall, 27% of treated females
(19/70) were observed with lung tumors. It is unusual that no tumors were observed in treated males.
Interpretation of the results of the Groth et al. study is limited by the use of only one very high dose
level, so no dose-response information can be derived from the study. Chronic tissue injury appears
likely as the mechanism for the eventual neoplasms, yet no insight can be gained from this study
regarding possible no-effect levels. Also, there is considerable uncertainty in the actual exposure levels
experienced by the test animals. Taken together, there are significant limitations in relying on this study
to extrapolate any potential human carcinogenic potential of antimony.
Newton et al. reported the effects of subchronic and chronic inhalation toxicity of antimony trioxide
in Fischer 344 rats. Male and female rats were exposed to air concentrations of 0, 0.06, 0.51 or 4.5
TABLE 19.9 Toxicity of Antimony Trioxide versus Carcinogenicity Potentials for Carbon Black and
Talcum Powder
Exposure
Test Material
Duration
(months)
Rate
(h/week)
Exposure
Period (h)
Concentration
(mg/m 3 Cumulative
Exposure
) [(mg/m 3 Tumor
) (h)]
Incidence
(percent)
Antimony trioxide a
12 35 1820 38 69,160 27
Carbon black 20 85 7395 6.0 44,370 25
24 80 8400 2.5 21,000 11
24 80 8400 6.5 54,600 67
Talc a
28 30 3660 6 21,960 0
28 30 3660 18 65,880 54
Source: Adapted from Hext (1994).
a Female rats only.
0, 1.6, 4.2 mg/m 3 6 h/day, 5
days/week for 13 months; 1
year postexposure observation
45 mg/m 3 7 h/day, 5 days/week
for 52 weeks; 20 weeks
postexposure observation
0, 0.06, 0.51, and 4.50 mg/m 3 6
h/day, 5 days/week for 52
weeks; 12-month
postexposure observation
0 mg/m 3 —0/13
1.6 mg/m 3 —1/17
4.2 mg/m 3 —14/18
Male rats—no lung tumors;
Female rats—19/70
Male rats—no lung tumors;
Female rats—no lung tumors
Watt (1983)
Groth et al. (1986)
Newton et al. (1994)