UPDATE: This workshop has already been held. Workshop materials are provided as a reference to the draft assessment.
EPA is developing an updated IRIS assessment of hexavalent chromium. This assessment will evaluate the potential health effects of hexavalent chromium from oral and inhalation exposures. An important component of determining the cancer causing potential of ingested hexavalent chromium is understanding the rates at which this metal is effectively detoxified in the gastrointestinal tract. To address this, EPA convened a state of the science workshop where an expert panel discussed this issue. This workshop was open to the public, broadcast by webinar/teleconference, and took place over two non-consecutive days.
Background
Chromium exists in multiple oxidation states, but two forms are most important from a biological and health perspective – hexavalent chromium (also known as chromium 6) and trivalent chromium (also known as chromium 3). Hexavalent chromium can be converted, or “reduced,” to trivalent chromium but this process will not occur in the opposite direction in physiological systems (that is, trivalent chromium cannot “oxidize” to hexavalent chromium in the human body). Hexavalent chromium is a known human carcinogen when inhaled and has been shown to cause tumors in mice and rats when ingested in drinking water, but there is little evidence indicating that ingesting trivalent chromium, a dietary supplement, poses any toxic or carcinogenic risk to humans. This is because extracellular trivalent chromium (trivalent chromium that exists outside of the cell) is poorly absorbed, whereas extracellular hexavalent chromium is readily taken up by cells via nonspecific anionic transporters. Hexavalent chromium is toxic only after it is absorbed by the cells and then reduced (inside the cell) to trivalent chromium. Consequently, ingested hexavalent chromium that is reduced to trivalent chromium outside of the cells lining the gastrointestinal (GI) tract – before being absorbed by these cells – is effectively detoxified. Hexavalent chromium that is not reduced to trivalent chromium outside of the cells lining the GI tract is readily absorbed by these cells. Therefore, it is important to understand these two simultaneous and competing processes – absorption of hexavalent chromium by the cells and reduction of hexavalent chromium to trivalent chromium outside of the cell – since they are an important part of evaluating the cancer causing potential of ingested hexavalent chromium in humans.
To inform EPA’s ongoing IRIS assessment of hexavalent chromium, we invited experts representing scientific areas related to the reduction and absorption of ingested hexavalent chromium, including metals chemistry, toxicokinetics, and GI physiology and pathology to serve on a panel. The panelists prepared and presented discussion topics that will aim to highlight what is known and what remains unknown about the topic in relation to human cancer risk from ingested hexavalent chromium. This format encouraged scientific discussion about how current knowledge can be applied to the IRIS assessment of hexavalent chromium and how knowledge gaps might be filled to reduce uncertainty in the analysis.
The same panel convened for both workshop sessions and did not seek to reach a consensus on any discussion topic.
Workshop Details
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Date and Agenda
Date/Time:
The workshop was held on:
- Thursday, September 19th from 9:30am – 12:30pm (EDT)
- Wednesday, September 25th from 9:30 am – 12:30 pm (EDT)
Workshop Agenda
See: Workshop Agenda and Workshop Topics
- Day 1 (Thursday, September 19): Reduction, absorption, and transit of ingested hexavalent chromium in the human GI tract
The first workshop session focused on questions regarding the toxicokinetic properties of ingested hexavalent chromium that will inform estimates of the amount absorbed in unreduced form in different portions of the GI tract as a function of species and dose. - Day 2 (Wednesday, September 25): Factors affecting susceptible human populations and lifestages
The second workshop session focused on questions addressing what is currently known about how toxicokinetic processes may vary among human populations and/or lifestages and potentially impact susceptibility to hexavalent chromium-induced toxicity.
Workshop Panelists
- Co-Chair: Elaina M. Kenyon, Ph.D. - U.S. Environmental Protection Agency/National Health and Environmental Effects Research Laboratory
- Co-Chair: Gary Ginsberg, Ph.D. - Connecticut Department of Public Health
- Kim Barrett, Ph.D. - University of California, San Diego
- Max Costa, Ph.D. - New York University
- John Crison, Ph.D. - Bristol-Myers Squibb
- Silvio DeFlora, Ph.D. - University of Genoa
- Sean Hays, Ph.D. - Summit Toxicology
Learn more: Panelist Biosketches
Workshop Materials
- Chromium VI Workshop Presentations
- White paper on factors affecting the reduction and absorption of hexavalent chromium in the gastrointestinal (GI) tract
- Workshop Agenda (PDF)(2 pp, 415 K)
- Workshop Topics (PDF)(4 pp, 79 K)
- Panelist Biosketches (PDF)(3 pp, 132 K)
- Chromium VI Workshop Presentations (PDF)(66 pp, 5 MB)
- White paper on factors affecting the reduction and absorption of hexavalent chromium in the gastrointestinal (GI) tract (PDF)(9 pp, 233 K)