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NIOSH Program Portfolio

 

Manufacturing

NORA Manufacturing Sector Strategic Goals

927Z6RE - Bioavailability Estimates and Health Outcomes

Start Date: 10/1/2006
End Date: 9/30/2010

Principal Investigator (PI)
Name: Aleks Stefaniak
Phone: 304-285-6302
E-mail: boq9@cdc.gov
Organization: NIOSH
Sub-Unit: DRDS
Funded By: NIOSH

Primary Goal Addressed
5.0

Secondary Goal Addressed
None


Attributed to Manufacturing
100%

Project Description

Short Summary

The purpose of this project is to improve understanding of the relationship between beryllium particle properties and solubility in the context of exposure risk for sensitization and beryllium disease. This project will characterize the physical and chemical properties of particles that are or are not associated with increased risk of beryllium sensitization and disease and estimate beryllium solubility in artificial lung and skin sweat fluids and, for a subset of material, industrial lapping fluid. Upon completion, we will improve understanding and help to reduce the exposure risk of beryllium sensitization and disease among the one million ever beryllium exposed workers in the United States. Additionally, our exposure model is applicable to manufacturing industries with exposure limits that are not protective (e.g., cemented carbide production) or completely lacking (e.g., emerging nanotechnologies).



Description

The major objectives of this NORA program project are to address the following hypotheses regarding the role of bioavailable beryllium in development of beryllium sensitization and chronic beryllium disease:



1. The form and distribution of beryllium in aerosol particles differs among manufacturing processes.

2. Beryllium dissolution rate (from highest to lowest) is: hydroxide> metal> alloy ˜ oxide> silicates.

3. Beryllium dissolution rate differs between material associated with elevated risk of sensitization and disease versus materials not associated with risk.



To investigate these hypotheses, the following specific aims were set for this project:



1. Determine the physicochemical properties of aerosols collected from manufacturing processes that (based on epidemiology) confer or do not confer elevated risk of sensitization and disease.

2. Measure and compare the beryllium chemical dissolution rate constant of each aerosol material in vitro using a static dissolution technique with:

a. artificial biological fluids (extracellular lung fluid, cellular phagolysosomal fluid, skin sweat);

b. industrial lapping and cutting fluids that may contact skin.

3. Share unpublished and published data as it is generated with the other NORA Program projects to:

a. help understand the properties of particles that may contact the skin (Project 2, Project Officer Greg Day);

b. establish a science-based foundation for understanding the effectiveness of a comprehensive beryllium protection program (Project 3, Project Officer Christine Schuler);

c. plan toxicology studies to investigate beryllium exposure-response relationships (Project 4, Project Officer Ann Hubbs); and

d. contribute to ongoing longitudinal follow-up of worker cohorts to investigate historical risk factors for sensitization and beryllium disease.



Specific Aim #1 was completed in FY08. Efforts are underway towards specific aim #2 in FY08. Information was shared in the form of two journal publications with the other program projects.



Objectives

The long-term goal of this project is to support development of a categorical paradigm for risk for different beryllium exposure materials according to material bioavailability type. We hypothesize that a better understanding of the inter-relationships of production process influence on beryllium aerosol formation, physicochemical properties of exposure aerosols, beryllium bioavailability via dissolution (a process that is dependent upon particle physicochemical properties), and associated immune factors for sensitization and disease may help to improve the scientific basis for a beryllium exposure metric. To begin to address this working hypothesis, this project will investigate the following specific hypotheses:

1. The form and distribution of beryllium in aerosol particles differs among manufacturing processes.

2. Beryllium dissolution rate (from highest to lowest) is: hydroxide> metal> alloy ˜ oxide> silicates.

3. Beryllium dissolution rates differ between materials that (based on epidemiology) confer elevated risk of sensitization and disease versus materials that do not.

To investigate these four Project hypotheses, the following specific aims were set:

1. Determine the physicochemical properties of beryllium-containing aerosol materials that were collected from well-documented manufacturing processes that (based on epidemiology) confer or do not confer elevated risk of sensitization and chronic beryllium disease.

2. Compare the beryllium chemical dissolution rate constant of each aerosol material in vitro using a static dissolution technique with:

a. Artificial biological fluids that mimic conditions encountered in the lung (extracellular lung fluid, phagolysosomal fluid of lung cells) and on the skin (sweat, sebum);

b. Industrial lapping and cutting fluids that may contact skin.

3. Share unpublished and published data as it is generated with other Program projects to:

a. Help understand the properties of particles that may contact the skin;

b. Establish a science-based foundation for understanding the effectiveness of a comprehensive beryllium protection program;

c. Plan toxicology studies to investigate beryllium exposure-response relationships;

d. Contribute to ongoing longitudinal follow-up of worker cohorts to investigate historical risk factors for sensitization and beryllium disease.



Mission Relevance

Workers exposed to beryllium may become sensitized, meaning their immune system responds to beryllium. An unknown portion of beryllium-sensitized persons develop chronic beryllium disease, an incurable and potentially fatal lung disease. In the United States, over one million ever beryllium exposed workers are potentially at risk of developing disease in their lifetime. Total airborne beryllium mass concentration exposure data fail to predict beryllium-associated health risks, suggesting that particle properties that augment mass, i.e., physicochemical (size, chemical form, surface area) and bioavailability properties (dissolution rate and lifetime) may be important in exposure. The overall objective of the NORA Program "Beryllium and a novel control paradigm" is to prevent sensitization and disease among beryllium exposed workers. The goal of Program Project 1 (Bioavailability Estimates and Health Outcomes) is to support development of a categorical paradigm for risk for different beryllium exposure materials according to material bioavailability. This project directly supports:

• RDR cross-sector Intermediate Goal (09PPRDRIG2.4): prevent and reduce beryllium sensitization and chronic beryllium disease.

• Activity/Output Goal (09PPRDRAOG2.4.4): develop, refine and validate improved methods to assess exposure to beryllium; and determine whether complex exposure metrics taking estimated dissolved beryllium dose and dermal exposure into account are better predictors of adverse health effects than simple mass-based exposure metrics.



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