Cadmium, Environmental Exposure, and Health Outcomes

Soisungwan Satarug; Scott H. Garrett; Mary Ann Sens; Donald A. Sens

Disclosures

Environ Health Perspect. 2010;118(2):182-90. 

In This Article

Cadmium Body Burden

Sex and Tissue Differential Cadmium Accumulation

Tissue collected from postmortem examinations has been used to define cadmium accumulation levels in tissues and organs of human subjects (Table 6). In an analysis of 61 environmentally exposed subjects between 2 and 89 years of age (mean 38.5 years), Satarug et al. (2002) revealed that renal cadmium accumulation was greater in younger age groups with little increase, or even a reduction, in the older age groups. Some investigators have suggested that younger individuals have high rates of renal cadmium accumulation because of a very high rate of dietary cadmium absorption (Horiguchi et al. 2004; Kikuchi et al. 2003). Conversely, a lack of renal cadmium accumulation in older individuals may be caused by a fall in dietary absorption rate plus a reduction in tubular reabsorptive capacity, which is associated with the aging of the kidney. A few studies have examined sex differences and cadmium accumulation. For example, Satarug et al. (2002) showed that Australian women had twice the level of cadmium in their livers than did their male counterparts; they also noted a trend for higher cadmium content in the kidneys of the female subjects. Uetani et al. (2006) documented differences in cadmium accumulation in a range of tissues and organs between 72 men and women who lived in areas with no apparent cadmium pollution. In addition, several studies on human eyes have shown that the retinal pigment epithelium and choroids contained more cadmium than did the retina (Erie et al. 2005; Wills et al. 2008). These studies also found that women, men and women of older age, and smokers of both sexes had elevated levels of cadmium accumulation in eye tissues. Additional studies have demonstrated sex differences in ocular metal content in nondiseased eyes and those afflicted with AMD (Wills et al. 2008, 2009).

Intestinal Absorption of Metals, Body Burden Variability, and Metal Transporters

Highly efficient absorption, transport, and cellular uptake mechanisms have evolved in living organisms to ensure an optimal supply of essential metals. Such mechanisms are crucial for metals, because they cannot be synthesized or destroyed by the cells and must be mined from the external environment (Clemens 2006). As predicted from the U-shaped doseresponse curve characteristics of essential metals, mechanisms designed to prevent deficiency or overdose toxicity have likely evolved for maintenance of homeostasis (Slikker et al. 2004). Cadmium has no known physiologic function, and no mechanism would have been expected to be evolved for its selective transport and homeostasis. In all likelihood, cadmium is acquired by transport mechanisms developed for essential metals. From physical and chemical properties, those metals are most likely to be zinc (Zn2+), iron (Fe2+), manganese (Mn2+), and calcium (Ca2+). In the literature, a considerable range defines the possible intestinal absorption rate for cadmium. For instance, it was estimated to be between 3 and 7% in humans and between 0.3 and 3.5% in rats. These values were used to assign an average 5% absorption rate in deriving a safe exposure level for cadmium (IPCS 1992; WHO 1989). However, higher cadmium absorption rates (2040%) were shown in balanced studies (Horiguchi et al. 2004; Kikuchi et al. 2003). These studies also observed enhanced rates among young subjects and considered the possible biliary excretion and reuptake via enterohepatic circulation. Many investigators have shown the influence of body iron stores on absorption rate and body burden of cadmium. Satarug et al. (2004) found a 3- to 4-fold increase in cadmium body burden among Thai women who had low iron stores when compared with those of the same age and of normal iron stores. Kippler et al. (2007) found increased cadmium burden among Bangladeshi women associated with low iron stores only among those with adequate zinc status. An inverse correlation between serum iron and blood cadmium was observed among Canadian subjects: men had higher serum iron, blood lead, and serum selenium values than did women, and women had higher serum copper and blood manganese than did men (Clark et al. 2007; Copes et al. 2008). The higher blood manganese in women might be expected because low iron stores have been associated with enhanced manganese absorption (Finley 1999; Kippler et al. 2009). Some studies have shown no influence on body iron stores, but these were conducted in chronic high-exposure situations where metal transporters would likely be saturated with metal. Current data thus suggest metal transporters could be one of the determinants of cadmium body burden—a factor that may explain the variability in blood cadmium levels observed by Björkman et al. (2000) in a cohort of 61 monozygotic and 103 dizygotic twin pairs.

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