shown that particle size is a major determinant of toxicity, whereas the chemical form of cadmium is relatively unimportant (Hirano et al. 1989a,b; Rusch et al. 1986). Similarly, oral-exposure studies of inorganic cadmium compounds have shown that absorption of the divalent ion (Cd2+) results from ingestion of all soluble salts and that uptake rates of free cadmium ions and those complexed with proteins are similar.
Except at very high exposures, absorbed cadmium is bound almost totally to the protein metallothionein. The cadmium-metallothionein complex is readily filtered by the glomerulus and is largely reabsorbed in the proximal tubules of the kidney (Foulkes 1978).
The toxic effects of cadmium in humans and animals are similar. The major toxic effects are acute and chronic inflammation of the respiratory tract, renal tubular effects, and lung cancer.
In general, respiratory effects occur after cadmium exposures that are usually seen only in occupational settings, and environmental exposures to cadmium are unlikely to result in acute or chronic respiratory disease. Whereas animal studies have shown that inhaled cadmium can cause lung cancer in rats (Takenaka et al. 1983; Oldiges et al. 1989), human data are less convincing. Thun et al. (1985) reported an exposure-response relationship between cumulative cadmium exposure and lung cancer. On the basis of those findings, EPA has classified cadmium as a group B1 (Probable) human carcinogen by inhalation; a unit risk4 of 1.8 × 10-3 per µg/m3 was calculated (EPA 1992b).
Human and animal data on the neurotoxicity of cadmium are sparse, but there is evidence that neurobehavioral changes appear in adults and children after exposures smaller than those causing renal effects (Marlowe et al. 1985; Struempler et al. 1985; Hart et al. 1989). Animal studies have found behavioral and structural nervous system changes after relatively small oral or parenteral cadmium exposures.
Other toxic effects include cardiovascular effects, hematologic changes, and gastrointestinal changes. These occur after very high exposures after which respiratory and renal changes are also prominent.
ATSDR has estimated inhalation cadmium exposures that pose minimal risk to humans (minimal-risk levels, MRLs) (1997a). An MRL is defined as an estimate of the greatest daily human exposure to a substance that is likely to be without an appreciable risk of noncancer adverse effects over a specified duration of exposure. On the basis of a no-observed-adverse-effects level (NOAEL) of 0.7 µg/m3 in a study of workers that reported a prevalence of proteinuria of 9% after a 30-year exposure at 23 µg/m3 (Jarup et al. 1988), ATSDR (1997a)
In its Integrated Risk Information System (IRIS), EPA defines inhalation “unit risk” as the upper- bound excess lifetime cancer risk estimated to result from continuous exposure to an agent at a concentration of 1 µg/m 3 in air.