home edit2 whole TSD November 2002 PDF format - OEHHA

In conclusion, given the low level of arsenic exposure and the evidence indicating a deficit of smokers in
this cohort, DHS staff decided that the apparent association between cadmium exposure and lung
cancer were not likely to be explained by confounding from smoking and/or arsenic exposure.
To summarize the DHS staff's findings with regard to the study by Thun et al. (1985) - the SMR of 2.3
in those with more than 2 years of cadmium exposure and the dose-response relationship are unlikely to
be explained by chance, by bias, or by confounding from smoking and/or arsenic exposure. The staff of
DHS concluded that the excess of lung cancer deaths in the study by Thun et al. (1985) is best
explained by exposure to high levels of cadmium. The DHS staff further concluded that this study
constitutes strong evidence of human carcinogenicity.
Animal Studies
Cadmium has been the subject of numerous studies in experimental animals to determine its carcinogenic
potential. These studies have been extensively reviewed elsewhere (IARC 1973, 1976; EPA 1981,
1985); only the inhalation and intratracheal administration studies will be discussed here.
Sanders and Mahaffey (1984) examined the carcinogenic potential of cadmium oxide in male rats by
intratracheal instillation. The rats were treated one, two or three times with 25 µg of cadmium oxide.
The first administration was given at 70 days of age and then at 100 and 130 days of age depending on
the total dose to be given (25, 50, or 75 µg). The animals were then followed for their lifetime. No
differences were found in survival times or organ weights between treated and control groups. Using
life-table and contingency table statistical analyses a significant increase in benign mammary
fibroadenomas was observed in the high dose group. Additionally, there was a significant increase in the
number of rats in the high dose group that had three or more tumor types.
Hadley et al. (1979) exposed a group of 61 male Wistar strain rats one time to an airborne cadmium
oxide aerosol concentration of 60 mg/m 3 for 30 minutes. The mass median diameter of the particles
was 1.4 µm with a geometric standard deviation of 1.9 µm. Seventeen animals were used as controls.
Twenty-seven exposed animals died within three days from acute pulmonary edema. The remaining
animals were then observed for one year. No morphological changes were noted in the lungs of
exposed animals, although one animal did have a well-differentiated pulmonary adenocarcinoma. The
authors observed that this tumor's relatively short latency period and the low spontaneous incidence
(0.1%) of such tumors suggested that it resulted from cadmium exposure.
Both the Sander and Mahaffey (1984) study and the Hadley et al.(1979) study were not adequate to
assess carcinogenic potency, since the animals were only exposed for short periods and, in the Hadley
et al. (1979) study, were not followed for sufficient time. Without continuous exposure, effects in the
lungs may not occur or the study may not be sensitive enough to detect adverse effects.
In the only long-term inhalation study available to the cadmium TAC document, Takenaka et al. (1983)
exposed rats to several concentration of a cadmium chloride aerosol. Groups of 40 male Wistar rats
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