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November 2011


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NIEHS workshop tackles erionite-linked disease risk

By Eddy Ball
November 2011

NIEHS Senior Medical Advisor Aubrey Miller, M.D.

In an interview with Fairwarning(http://www.tucsonsentinel.com/nationworld/report/100711_erionite_cancer/officials-ponder-action-against-cancer-causing-erionite/) Exit NIEHS about the workshop's goals, Miller said, "At a minimum, we can begin to start to educate the public and policymakers." (Photo courtesy of Steve McCaw)

NIEHS/NTP Director Linda Birnbaum, Ph.D.

While Birnbaum enjoyed occasional comic relief, her message was serious and pointed. “Erionite is bad news,” Birnbaum told the attendees, “[and] there may be other deposits not yet known.” (Photo courtesy of Steve McCaw)

Matt Stout, Ph.D., Scott Masten, Ph.D. and Eugene Gibbs, Medicine Graduate Student

The NIEHS/NTP delegation included NTP toxicologists Matt Stout, Ph.D.(http://www.niehs.nih.gov/research/atniehs/labs/pob/staff/stout.cfm), left, and Scott Masten, Ph.D. Seated behind them, far right, is University of North Carolina at Chapel Hill translational medicine graduate student Eugene Gibbs(http://www.med.unc.edu/transmed/current-trainees-1/entered-in-2009/eugene-gibbs) Exit NIEHS. (Photo courtesy of Steve McCaw)

NIEHS clinical researcher and Acting Director of Clinical Research Fred Miller, M.D., Ph.D.

NIEHS clinical researcher and Acting Director of Clinical Research Fred Miller, M.D., Ph.D.(http://www.niehs.nih.gov/research/clinical/ea/index.cfm), called on his colleagues to explore the connection between erionite exposure and the more common immunological diseases. (Photo courtesy of Steve McCaw)

NIEHS Toxicology Liaison Chris Weis, Ph.D.

As one of the Institute's leading toxicologists, Weis played an important role at the workshop by moderating the session on exposure assessment. To a greater degree even than other exposures, it is far better to prevent erionite exposure than to try to treat resulting diseases. (Photo courtesy of Steve McCaw)

Pathologist Mary Ann Sens, M.D., Ph.D.

University of North Dakota pathologist Mary Ann Sens, M.D., Ph.D., reported on North Dakota's Autopsy and Tissue Program and Surveillance Efforts. (Photo courtesy of Steve McCaw)

Professor James Lockey, M.D., University of Cincinatti

University of Cincinnati professor James Lockey, M.D.(http://www.eh.uc.edu/dir_individual_details.asp?qcontactid=807) Exit NIEHS, argued that states need to identify where the erionite is and take measures to protect people without delay. “We have enough information now to take steps,” he said. (Photo courtesy of Steve McCaw)

Cmdr. Danielle DeVoney, Ph.D.

A participant of relatively few words during most of the workshop, Cmdr. Danielle DeVoney, Ph.D., used them well toward the end as she urged colleagues to include the entire family of fiber zeolites in their research and avoid building an asbestos-like box around erionite. DeVoney was part of the U.S. Environmental Protection Agency's team working on Libby amphibole asbestos. (Photo courtesy of Steve McCaw)

Erionite may not be a household word in most of the world yet, but a first-of-its-kind U.S. workshop specifically on this issue Oct. 12 at NIEHS should help raise its visibility among government and academic scientists.

Organized and chaired by NIEHS Senior Medical Advisor Aubrey Miller, M.D., with the help of his Bethesda-based colleague NIEHS Toxicology Liaison Chris Weis, Ph.D., the one-day interdisciplinary meeting gathered some 30 scientists to consider the state of the science related to erionite-induced disease and how best to advance research. Talks at the workshop ranged from the basic definition and speciation of the asbestos-like zeolite mineral, to promising strategies for prevention and treatment of the cancer that has been definitively linked to exposure in several Turkish villages, malignant mesothelioma (MM).

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Erionite deposits have been found in at least twelve Western states in the U.S., Miller said, raising concerns about a repeat of what happened in the Turkish cancer villages and Libby, Mont. A recent study co-authored by Miller examined the use of erionite in gravel applied to roads and parking lots in North Dakota, which could pose a potential threat that won't materialize for 20 to 50 years. According to the paper's introduction, animal tests suggest that erionite is many times more toxic than asbestos and may be the most toxic naturally occurring fibrous mineral known.

Starting with the basics

Although erionite has been listed as a known carcinogen in the NTP Report on Carcinogens since 1994, NIEHS/NTP Director Linda Birnbaum, Ph.D., explained in her welcome to attendees, “There are no regulations on erionite.”

As she compared the erionite workshop to one held in 2009 on asbestos, Birnbaum cautioned attendees to look beyond what they already know about asbestos to see erionite and other fibrous minerals in a new light. She pointed to the need for answering dose-response questions, development of early biomarkers, discovery of genetic susceptibility markers, and information about possible effects distant from the lung, such as autoimmune response and gastrointestinal disorders.

Weighing what we know and don't know

Scientists and officials from NIEHS, regulatory agencies, and several universities attended the workshop.

Attendees heard talks ranging from an introduction to zeolite mineralogy and morphology by U.S. Geological Survey geologist Greg Meeker and University of Iowa geological engineer Umran Dogan, Ph.D.(http://www.engineering.uiowa.edu/news/newsDetail.php?newsID=162) Exit NIEHS, to promising research from University of Hawaii Cancer Center (UHCC) pathologist Haining Yang, Ph.D.(http://www.crch.org/profiles/profileyang.htm) Exit NIEHS, that has identified a protein, high-mobility group box 1 (HMGB1), that may prove to be a biomarker and therapeutic target in early stages of development of MM and work by New York University cardiothoracic surgeon Harvey Pass, M.D., who discussed his research to develop a panel of markers for MM.

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Yet another promising report by UHCC Director Michele Carbone, M.D., Ph.D.(http://www.crch.org/profiles/profilecarbone.htm) Exit NIEHS, described his team's discovery of a biomarker for genetic susceptibility, germline BAP1 mutations. The team's findings may help answer the question of why everyone exposed to erionite will not develop MM.

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Looking ahead

When he opened the workshop Miller talked about two major objectives - getting participants on the same page in respect to the science about erionite, and trying to identify some steps to move the needed research and public health discussions forward among the participating scientists and their organizations. While the objectives were somewhat lofty for a first meeting, by the end of the meeting this diverse group of scientists had worked through a large amount of information and were making some shorter-term recommendations for next steps to be taken.

For example, there was general agreement with respect to the need to update old maps regarding the locations of erionite deposits in the US, as well as to further evaluate known locations. Also, researchers identified the need for standardized mineral identification, sampling, and analysis strategies that can be used across sites to better understand mineral compositional variability and associated exposures.

The issue of mixtures came up several times, and Birnbaum suggested opening a dialogue with the nanomaterials research community to see if findings about engineered particles shed any light about natural ones. She also said that indoor exposures need further study. Lastly, there was broad support for raising public awareness about the potential hazards associated with erionite exposure. “At a minimum, just having this meeting has elicited a public health response,” Miller concluded.

Citations:

Carbone M, Baris YI, Bertino P, Brass B, Comertpay S, Dogan AU, Gaudino G, Jube S, Kanodia S, Partridge CR, Pass HI, Rivera ZS, Steele I, Tuncer M, Way S, Yang H, Miller A.(http://www.ncbi.nlm.nih.gov/pubmed/21788493) Exit NIEHS 2011. Erionite exposure in North Dakota and Turkish villages with mesothelioma. Proc Natl Acad Sci U S A 108(33):13618-13623.

Testa JR, Cheung M, Pei J, Below JE, Tan Y, Sementino E, Cox NJ, Dogan AU, Pass HI, Trusa S, Hesdorffer M, Nasu M, Powers A, Rivera Z, Comertpay S, Tanji M, Gaudino G, Yang H, Carbone M.(http://www.ncbi.nlm.nih.gov/pubmed/21874000) Exit NIEHS 2011. Germline BAP1 mutations predispose to malignant mesothelioma. Nat Genet 43(10):1022-1025.



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