Agency for Toxic Substances and Disease Registry 
Case Studies in Environmental Medicine (CSEM) 
Chromium Toxicity
What Is the Biologic Fate of Chromium in the Body?

Learning Objectives

Upon completion of this section, you will be able to

• explain the metabolic difference between Cr(III) and Cr(VI).

Introduction

In vivo reduction of Cr(VI) to Cr(III) has been widely studied. Ingested Cr(VI) is efficiently reduced to the Cr(III) by the gastric juices [De Flora, Badolati et al. 1987]. Cr(VI) can also be reduced to the Cr(III) in the epithelial lining fluid of the lungs by ascorbate and glutathione (Petrilli, Rossi et al. 1986; Suzuki and Fukuda 1990).

Absorption

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.

Once absorbed into the bloodstream, Cr(VI) is rapidly taken up by erythrocytes after absorption and reduced to Cr(III) inside the red blood cells. In contrast, Cr(III) does not readily cross red blood cell membranes, but binds directly to transferrin, an iron-transporting protein in the plasma (EPA 1998; ATSDR 2000; Dayan and Paine 2001].

Reduction of Cr(VI) in the red blood cells occurs by the action of glutathione. Since the red blood cell membrane is permeable to Cr(VI) but not Cr(III), the Cr(III) formed by reduction of Cr(VI) is essentially trapped within the red blood cell. Eventually the diffusion of Cr(VI), the reduction to Cr(III), and complexing to nucleic acids and proteins within the cell will cause the concentration equilibrium to change [ATSDR 2000].

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 [ATSDR 2000].

Metabolic Pathways

The first defense against Cr(VI) after oral exposure is the reduction of Cr(VI) to Cr(III) in the gastric environment where gastric fluid [De Flora, Badolati et al. 1987] and ascorbate [Samitz 1970] play important roles [ATSDR 2000].

Excretion of absorbed chromium occurs primarily via urine. 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 [Kiilunen, Kivisto et al. 1983; ATSDR 2000].

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) [ATSDR 2000].

Key Points

• Cr(VI) is better absorbed from the lungs, gut, and skin than is Cr(III).
• After absorption, Cr(VI) is reduced to Cr(III).
• The difference in bioavailability and bioactivity between Cr(III) and Cr(VI) might account for the differences in toxicity. Cr(III) is an essential dietary nutrient whereas Cr(VI) poses a significant risk of lung cancer.
• Cr(III) is excreted, primarily in the urine.

Progress Check

To review relevant content, see Absorption and Metabolic Pathways in this section.