CDC logoSafer Healthier People CDC HomeCDC SearchCDC Health Topics A-Z
NIOSH - National Institute for Occupational Safety and Health

Skip navigation links Search NIOSH  |  NIOSH Home  |  NIOSH Topics  |  Site Index  |  Databases and Information Resources  |  NIOSH Products  |  Contact Us

NIOSH Program Portfolio

 

Manufacturing

NORA Manufacturing Sector Strategic Goals

HELD007 - Early biomarkers for occupational silicosis

Start Date: 10/1/2010
End Date: 9/30/2014

Principal Investigator (PI)
Name: Pius Joseph
Phone: 304-285-6240
Organization: NIOSH
Sub-Unit: HELD
Funded By: NIOSH

Primary Goal Addressed
5.0

Secondary Goal Addressed
6.0


Attributed to Manufacturing
50%

Project Description

Short Summary

The purpose of the project is to develop a minimally invasive procedure that may be employed to monitor workers routinely for early detection of silicosis due to their occupational exposure to crystalline silica.

NIOSH has recommended the development of more definitive, non-invasive methods for earlier detection of silica-related pulmonary disease. Since blood is an easily available bio-fluid, the blood-based biomarkers for silicosis that may be identified based on the proposed studies may be employed for routine monitoring of workers for their occupational exposure to silica potentially resulting in illnesses and mortality. Being able to determine/predict the outcome of occupational exposure to silica at an early stage by employing minimally-invasive surrogate biomarkers present in blood may be helpful to develop appropriate intervention strategies to prevent/reduce the incidence of occupational silicosis and possibly other adverse pulmonary effects due to silica exposure. The findings of this project are, therefore, expected to contribute significantly to the strategic goals of NORA sectors (Construction and Manufacturing) and Cross-sectors (Cancer, Reproductive and Cardiovascular; Exposure Assessment) as described under the relevant sessions above.

The findings of the project will be presented in scientific meetings and published in peer-reviewed journals. A simple test to detect early silicosis using blood samples will be developed. These findings may be helpful for Physicians practicing occupational medicine as a sensitive approach to detect silicosis at an early stage potentially resulting in intervention of silicosis.



Description

Occupational exposure to respirable crystalline silica occurs in a variety of industries and occupations. NIOSH has estimated that approximately 2 million US workers are potentially exposed to respirable crystalline silica. In addition, an undetermined portion of 3.7 million US agricultural workers may be exposed to dust containing a significant percentage of respirable crystalline silica.

Workers in several US industries are occupationally exposed to crystalline silica at concentrations as much as 10-fold higher than the NIOSH recommended exposure level. Silicosis, an incurable but preventable disease, is the most common adverse health effect associated with exposure to crystalline silica. The currently available procedures to detect silicosis are either highly invasive in nature or not sensitive enough to detect silicosis at an early stage. NIOSH has recommended the development of more definitive, non-invasive methods for earlier detection of silica-related pulmonary diseases.

Recently, we have initiated studies to investigate whether the peripheral blood gene expression profile can be employed as minimally invasive and sensitive surrogate markers to detect target organ toxicity. Our studies have demonstrated that toxicity induced by several chemicals in rats may be detected and distinguished based on the peripheral blood gene expression profile.

We have also found that pulmonary toxicity induced by inhalation exposure of rats to respirable crystalline silica can be detected by their peripheral blood gene expression profile. The overarching goal of the current research proposal, a follow-up of our recent project, is to identify additional non-invasive markers for silica-induced pulmonary toxicity in rats, including silicosis, and to validate the findings of the animal studies using blood samples obtained from a population of workers who are occupationally exposed to respirable crystalline silica.

Since blood is an easily available bio-fluid, the blood-based biomarkers for silica toxicity that may be identified based on the proposed studies may be employed for routine monitoring of workers for their occupational exposure to silica potentially resulting in illnesses and mortality. Being able to determine/predict the outcome of occupational exposure to silica at an early stage by employing minimally invasive surrogate biomarkers present in blood may be helpful to develop appropriate intervention strategies to prevent/reduce the incidence of occupational silicosis and possibly other adverse pulmonary effects due to silica exposure.

The findings of this project are, therefore, expected to contribute significantly to the strategic goals of NORA sectors (Construction and Manufacturing) and Cross-sectors (Cancer, Reproductive and Cardiovascular; Exposure Assessment) as described under the mission relevance.

Studies will be conducted using experimental animals and human subjects to address the objectives of the research project. Rats will be exposed to respirable crystalline silica by intratracheal instillation to induce pulmonary toxicity including silicosis. Induction of pulmonary toxicity including silicosis in the rats will be determined based on biochemical and histological analysis of lungs.

Blood collected from the control and silica exposed rats will be profiled for the expression of mRNAs and microRNAs (miRNA).

The data will be analyzed using appropriate statistical and computational programs to identify markers for silica-induced pulmonary toxicity. The mRNA and miRNA markers thus identified will be characterized for their specificity and sensitivity to detect silica-induced pulmonary toxicity. Experiments will also be conducted to determine whether the peripheral blood gene expression profile may be employed to predict susceptibility for silicosis in the rats. The findings of the rat experiments will be further validated using blood samples obtained from a population of workers consisting of miners. Dr. Mary Gulumian (National Institute for Occupational Health, Johannesburg, South Africa) is conducting a prospective study involving workers who are occupationally exposed to silica and has agreed to provide blood samples required for our study. Individuals with no known history of exposure to silica living in the same geographical area as those of the miners will be used as controls. Blood will be collected from the study participants after obtaining signed consent forms. The expression profile of the biomarkers for silicainduced pulmonary toxicity identified in the rat experiment will be used to evaluate the blood samples obtained from the study participants. In addition, a global gene expression profile in the blood samples obtained from the study participants will be determined to identify additional biomarkers, if any, for silica-induced pulmonary toxicity.

The main goals of the project and timeframe for their completion are:

1. To identify sensitive biomarkers (mRNA and miRNAs expression profile) in rat peripheral blood for early detection of silicosis (FY 11).
2. To characterize the rat blood-based silicosis biomarkers for their sensitivity and specificity to detect silicosis (FY12).
3. To identify mRNA and miRNA expression profiles in rat blood as predictive susceptibility markers to develop silicosis (FY13).
4. To validate the early biomarkers for silicosis identified in the rat blood using blood samples obtained from patients who have developed silicosis due to their occupational exposure to silica (FY14).



Mission Relevance

Occupational exposures to respirable crystalline silica occur in a variety of industries and occupations because of its extremely common natural occurrence and the wide range of materials and products that contain it. Virtually any process that involves movement of earth or disturbance of silica-containing products such as masonry and concrete may expose workers to silica.

NIOSH, based on the National Occupational Exposure Survey (NOES), estimates that at least 1.7 million US workers are potentially exposed to respirable crystalline silica. In addition, an undetermined portion of the 3.7 million U.S. agricultural workers may be exposed to dust containing a significant percentage of respirable crystalline silica. Workers in several US industries are occupationally exposed to crystalline silica at concentrations as much as 10-fold higher than the NIOSH Recommended Exposure Level (REL).

Occupational exposures to respirable crystalline silica are associated with the development of silicosis, lung cancer, pulmonary tuberculosis, airway diseases, autoimmune disorders, chronic renal disease and other adverse health effects. Silicosis, an incurable but preventable disease, is the most common adverse health effect associated with exposure to crystalline silica.

Recent epidemiologic studies demonstrate that workers have a significant risk of developing chronic silicosis when they are exposed to respirable crystalline silica over a working lifetime at the current Occupational Safety and Health Administration (OSHA) permissible exposure limit (PEL), the Mine Safety and Health Administration (MSHA) PEL, or the NIOSH REL.

The number of cases of silicosis and silica-related diseases in the United States today is unknown. However, approximately 200 deaths were reported to occur in the USA in 2005. Although the mortality associated with silicosis has declined over the past several decades, the number of deaths among persons aged 15 to 44 has not declined substantially. Prevention and elimination of silicosis and silica-related diseases in the United States are priorities of NIOSH. NIOSH has recommended the development of more definitive noninvasive methods for earlier detection of silicosis and silica-related pulmonary diseases. The current procedures to detect silicosis such as chest X-ray and pulmonary function test are not sensitive enough and, therefore, they can detect silicosis only when the pulmonary function is significantly compromised among the workers who are occupationally exposed to silica. Since silicosis is an incurable but preventable disease, early detection of the silicosis, before the appearance of clinical symptoms, is critical for its prevention.

A significant wealth of knowledge is available in the literature regarding the causes and incidence of silicosis among workers.
Research papers published by other investigators and NIOSH reports regarding silicosis were reviewed to determine the need for the current project as well as to design the studies to address the problem. In addition, discussion with other investigators involved in silicosis research was critical to understand the research problem as well as to design the project.

The main objective of the current research project is to identify specific and sensitive biomarkers in the blood that may be employed to monitor workers routinely for their potential to develop pulmonary toxicity including silicosis due to occupational exposure to respirable crystalline silica. During the course of the research project, experiments will be conducted by using relevant animal models for silicosis to identify molecular signatures (mRNA and microRNAs profiles) that may be used as sensitive biomarkers to detect silicosis at an early stage. The biomarkers thus identified will be further validated using blood samples obtained from workers who are occupationally exposed to crystalline silica. The population of silica exposed workers will consist of those who have developed silicosis and those without any detectable silicosis. Early detection of silicosis may be helpful to prevent/reduce illnesses and mortality due to occupational exposure to silica among workers; and this in turn, is expected to contribute to the mission of NIOSH.



Page last updated: June 3, 2011
Page last reviewed: May 23, 2011
Content Source: National Institute for Occupational Safety and Health (NIOSH) Office of the Director

 

NIOSH Program:

Manufacturing