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NORA Manufacturing Sector Strategic Goals

9277148 - Development of New Research Initiatives in Occupational Health

Start Date: 10/1/1998
End Date: 9/30/2014

Principal Investigator (PI)
Name: Vincent Castranova
Phone: 304-285-6032
Organization: NIOSH
Sub-Unit: HELD
Funded By: NIOSH

Primary Goal Addressed

Secondary Goal Addressed


Attributed to Manufacturing


Project Description

Short Summary

The goal of this project is to provide a rapid and sound response to requests for scientific information concerning issues of occupational exposure and possible adverse health effects. This project will respond to requests from internal and external partners and provide data and advice on new and evolving issues in occupational Respiratory Disease of workers in construction, manufacturing, and nanotechnology. Such efforts will include fabrication of generation systems to produce aerosols of agents in question for animal exposures, development of technologies to identify and quantitate these agents, formulation and modification of methodologies to assay the biological effects of exposures, construction of dose and time-course relationships, and identification of etiological agents. Results will allow partners to apply this knowledge to resolve questions concerning relative toxicity and susceptibility and to develop prevention strategies for workplace hazards.


NIOSH is often requested by external partners to provide information and advice on new and evolving issues of occupational health. Such requests require the mobilization of expertise of a multidisciplinary nature to conduct the research and respond in a timely fashion.

The Health Effects Laboratory Division is a multidisciplinary research laboratory having instrumentation, and expertise to successfully address the above goals. The Pathology and Physiology Research Branch has expertise in in vitro and in vivo toxicology models, microscopy, pathology, molecular biology and analysis of reactive oxygen species (ROS), as well as expertise in generation and characterization of particles and fumes for exposure studies.

The goal of this project is to provide a rapid and sound response to requests for scientific information concerning issues of occupational exposure and adverse health effects. The specific aims of the project will vary depending on requests. They would all include: (1) literature surveys to determine the present state of knowledge and identify gaps in our understanding of the problem, (2) designing research studies to address critical knowledge gaps, (3) develop in vitro and in vivo assays which can be used to screen dusts, fumes or chemicals for potential toxicity, (4) elucidate possible etiologic agents in mixtures, (5) determine the time course and concentration-response relationship for biological reactions to exposure, (6) elucidate mechanisms in which an exposure agent induces its toxic response, and (7) develop biomarkers of exposure and/or response. Research to Practice (r2p) is an important component of this project.

The accomplishments include:

1. In response to a query from the National Cotton Council, have demonstrated that pulmonary response of guinea pigs to inhaled cotton dust varies linearly with the product of mass and exposure duration.

2. In collaboration with Mount Sinai Medical Center, have demonstrated that cocoa, rye, and tobacco dust extract endotoxin cause airway smooth muscle contraction in a dose-dependent manner.

3. Demonstrated that inhalation of cotton dust induces nitric oxide production from alveolar macrophages.

4. In collaboration with the DOD, have demonstrated that wood smoke particles generate radicals which can cause DNA damage.

5. In collaboration with the University of Rochester, have demonstrated that ultrafine particles contain radicals and that hydroxy radical production by ultrafine particles is augmented by metals.

6. In collaboration with DRDS, have demonstrated that the production of nylon flock generates respirable nylon fibers which are highly inflammatory to the lung.

7. In collaboration with DRDS, have demonstrated that artificial butter flavoring causes damage to the epithelial lining of airways.

8. In collaboration with Ewha Woman's Medical College, Korea, have investigated signaling pathways for silica-induced activation of inflammatory cytokine production.

9. In collaboration with the University of Pittsburgh and DART have evaluated the effects of fiber length on cytotoxicity to human alveolar macrophages.

10. In collaboration will the University of Pittsburgh have demonstrated that silica exposure induces the activation of arginase I.

These studies have resulted in numerous publications and presentations, which are highly cited by the scientific community and played a role in advancing occupational health science forward. In addition, data have been applied directly by customers to address their questions concerning occupational health issues as noted above. Results have also been used by HHE Teams to recommend prevention measures at problem worksites, e.g., nylon flocking and popcorn plants.

Specific surveillance information used was input from HHE activities in DRDS and the NIOSH Work-related Lung Disease Surveillance Report 2002.


The goal of this project is to provide a rapid and sound response to requests for scientific information concerning issues of occupational exposure and possible adverse health effects.

Outputs of this project will be data provided to customers, presentations at scientific meetings and publications in peer-reviewed journals.

Anticipated outcomes of this project are the use of results by the scientific community to advance progress and resolve knowledge gaps.

Results of this project can be used by NIOSH to support health hazard alerts, recommended exposure levels and prevention measures.

Results of this project support implementation of prevention strategies in affected worksites and communication of these strategies by industrial associations to members.

Achievement of project goals will be evaluated by determining the productivity of the project, i.e., data generated and published. Determination of impact of the data generated will be measured as scientific citations, usefulness to production of alerts and recommended exposure levels, and usefulness in the development of prevention strategies for worksites subject to HHE.

Mission Relevance

NIOSH is often requested by external partners to provide information and advice on new and evolving issues of occupational health. Such requests require the mobilization of effort to develop expertise in new areas and to conduct the necessary research to provide data to respond. Examples of such requests include: (1) request by DOD to collaborate on a study of the effects of diesel exhaust particulate on the ability of alveolar macrophages to fight pulmonary infections; (2) request by DOD to characterize reactive species generated on wood smoke particulate; (3) request by DRDS to characterize the biological effects of nylon fibers in support of an HHE; (4) request by the National Cotton Council to determine the effects of extended work shifts on the pulmonary reaction to cotton dusts; (5) request to support studies by Mount Sinai Medical Center on the ability of dusts from agricultural products to cause airway constriction; (6) request by DRDS to characterize the biological activity of popcorn flavoring; (7) request from DART to evaluate the toxicity of Expandosil particles (8) requests from EPA to serve on workgroups to develop testing strategies for man-made fibers and for nanoparticles; (9) request by DRDS to evaluate the pulmonary toxicity of fungal products; (10) request from the University of Rochester to provide data concerning the presence of radicals generated by ultrafine particles; (11) request from NASA to evaluate the pulmonary toxicity of lunar dust.

This project often relies on the surveillance activities of Health Hazard Evaluations (HHE) of worksites and the NIOSH Workrelated Lung Disease Surveillance Report to identify critical health problems This project evaluates information collected by HHE studies, identifies critical knowledge gaps, and devises laboratory experiments to resolve critical issues, such as etiologic agent, pulmonary response, time course and dose response. Results of this laboratory research are often directly applied by the HHE Team to implement prevention measures at the worksite.

Examples of such intervention include nylon flock and the popcorn butter flavoring issues.

This project will allow the Pathology and Physiology Research Branch to rapidly respond to both internal and external requests for information, to develop new initiatives, and to initiate new research partnerships with governmental agencies such as NTP, DOD, NASA, etc.

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