Agency for Toxic Substances and Disease Registry
Case Studies in Environmental Medicine (CSEM) 

Chromium Toxicity
Biological Fate

Biological Fate

The entry routes of chromium into the human body are inhalation, ingestion, and dermal absorption. Occupational exposure generally occurs through inhalation and dermal contact, whereas the general population is exposed most often by ingestion through chromium content in soil, food, and water.

• Cr (VI) is better absorbed from the lungs, gut, and skin than is Cr (III).

Rates of chromium uptake from the gastrointestinal tract are relatively low and depend on a number of factors, including valence state (with Cr [VI] more readily absorbed than Cr [III]), the chemical form (with organic chromium more readily absorbed than inorganic chromium), the water solubility of the compound, and gastrointestinal transit time. In humans and animals, less than 1% of inorganic Cr (III) and about 10% of inorganic Cr (VI) are absorbed from the gut; the latter amount is slightly higher in a fasting state.

• After absorption, Cr (VI) is reduced to Cr (III).

The percentage of chromium absorption from the lungs cannot be estimated. Within the bronchial tree, epithelium lining fluids directly reduce Cr (VI) to Cr (III). Data from a few animal experiments indicate that with equal solubility, Cr (VI) compounds are absorbed more readily than Cr (III) compounds, probably because Cr (VI) readily penetrates cell membranes. Data from volunteers and indirect evidence from occupational studies indicate that absorption of certain Cr (VI) compounds can occur through intact skin.

• The difference in bioavailability and bioactivity between Cr (III) and Cr (VI) might account for the differences in toxicity.

After entering the body from an exogenous source, Cr (III) does not readily cross cell membranes, but binds directly to transferrin, an iron-transporting protein in the plasma. In contrast, Cr (VI) is rapidly taken up by erythrocytes after absorption and reduced to Cr (III) inside the cell. Regardless of the source, Cr (III) is widely distributed in the body and accounts for most of the chromium in plasma or tissues. The greatest uptake of Cr (III) as a protein complex is via bone marrow, lungs, lymph nodes, spleen, kidney, and liver. Autopsies reveal that chromium levels in the lungs are consistently higher than levels in other organs.

• Only Cr (III) is excreted, primarily in the urine.

Excretion of chromium occurs primarily via urine, with no major retention in organs. In humans, the kidney excretes about 60% of an absorbed Cr (VI) dose in the form of Cr (III) within 8 hours of ingestion. Approximately 10% of an absorbed dose is eliminated by biliary excretion, with smaller amounts excreted in hair, nails, milk, and sweat. Clearance from plasma is generally rapid (within hours), whereas elimination from tissues is slower (with a half-life of several days). Doses of Cr (VI) administered to volunteers were more rapidly eliminated than doses of Cr (III).

Challenge

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