Entry Pathways, Transport, and Trafficking

Cd enters the body mainly through the lungs and the gastrointestinal (GI) tract. The absorption of Cd from the lungs is much more effective than that from the gut. However, Cd absorption from the GI tract is the main route of Cd exposure in humans. 

After inhalation exposure, the absorption of Cd compotmds varies greatly depending on the physico-chemical properties of the Cd compounds involved, site of deposition in the lungs and particle size [22]. In the Itmgs, deposition, mucociliary clearance, and alveolar clearance determine the absorption of inhaled particles. Large particles, dusts ( 10 pm in diameter) tend to be deposited in the upper airways, while small particles, fumes, cigarette smoke (approximately 0.1 pm in diameter) penetrate into the alveoli, which are the major site of absorption. Between 50-100% of Cd in the alveoli are transferred to the blood. In the average 

In people with low body stores of Fe the absorption of Cd is higher than in subjects with normal Fe stores [44], which has been also observed in experimental animals [45]. Interestingly, dietary Cd absorption tends to be higher in females than in males [46] because of increased incidence of low Fe stores or overt Fe deficiency in women at fertile age [47,48]. Women with low body Fe stores, as refiected by low serum ferritin levels, have on average twice (about 10% but up to 20%) the normal rate of oral Cd absorption [49]. This may be explained by the close correlation between Cd absorption and the expression of DMTl, whose expression is induced by Fe deficiency and transports Fe and Cd into the mucosa cell equally well [34,50]. This situation is exacerbated during pregnancy when enterocytes have an increased DMT-1 density at the apical surface to optimize micronutrients absorption [46,48]. 

A dermal route of entry through contamination of the skin has been described in vitro but is extremely low [61]. Percutaneous absorption of Cd chloride from water and soil into and through human skin was performed using samples of cadaver skin and did not exceed 0.6%. This route of entry may therefore be of concern only in situations where concentrated solutions would be in contact with the skin for several hours or longer. 

The Cd concentration of the human placenta is usually about 5-20 pg/kg wet weight [62]. The placentas of women who smoke during pregnancy have higher Cd levels than those of non-smokers [63]. But placental transfer of Cd is limited. Cd concentration in newborn blood (umbilical cord) is on average 40-50% lower than in maternal blood [64]. Transplacental transport of Cd is minimized in the normal healthy placenta presumably by the binding of Cd to MT. Placental Cd accumulation in humans [65] and experimental animals [66] may be mediated by Cd transport via placental DMTl [67] and TRPV6 [68], which could indirectly affect the fetus. 

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