Hexavalent Chrome: Threshold Concept for Carcinogenicity
摘要
Certain hexavalent chromium (Cr~(6+)) compounds when administered via inhalation at high doses have the potential to induce lung tumors in humans and experimental animals. Trivalent chromium (Cr~(3+)) is an essential human and animal nutrient at levels of 50 to 200 μg/day. Recent data have shown that the human body is able to reduce Cr~(6+) to Cr~(3+). This reduction occurs in bodily fluids such as gastric juice, epithelial lining fluid of.the respiratory tract, blood, and other fluids. Secondary reduction occurs at the cellular level by the cytosol, mitochondria, and microsomes. Thus, at low levels of exposure hexavalent chromium ions are reduced befor the 6+ ions can interact with DNA unless the dose is sufficient to overwhelm the body's reduction capacity. This paper summarizes the available data concerning the reducing ability of the body and formulates the steps in the mechanism of cancer induction. These steps include: (1) only certain Cr~(6+) compounds have the capacity to interact with cellular components; (2) Cr~(6+) is reduced by body fluids and excess Cr~(6+) enters the cell (Cr~(3+) is poorly absorbed across membranes); (3) cellular organelles and the cytoplasm reduce Cr~(6+) to Cr~(3+); (4) excess Cr~(6+) can enter the nucleus; (5) Cr~(6+) reduction through 5+ and 4+ to 3+ has a potential to interact with the DNA molecule; and (6) if unrepaired, this DNA damage can lead to cancer induction. On the basis of current evidence Cr~(6+) has a threshold for carcinogenic potential in humans that is greater than the current TLV. 1990 Academic Press. Inc.