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workers, building, architect

NORA Manufacturing Sector Strategic Goals

92700A0 - Biomarker Development for Field Studies

Start Date: 10/1/2004
End Date: 9/30/2009

Principal Investigator (PI)
Name: Clayton B'hymer
Phone: 513-533-8148
Organization: NIOSH
Sub-Unit: DART
Funded By: Environmental Protection Agency

Primary Goal Addressed

Secondary Goal Addressed


Attributed to Manufacturing


Project Description

Short Summary

Biomarker Development for Field Studies is an ongoing methods development project for the Molecular and Genetic Monitoring Team designed to provide the biomonitoring analyses required for field investigations of occupational exposures. Biomarker methods will be developed and applied for occupational toxicants to assess exposure and susceptibility and will target the Manufacturing, and Healthcare and Social Assistance Sectors. In FY09, efforts will continue to the study biomarkers of susceptibility, as they related to metabolism and DNA repair pathways, with respect to acrylamide and include further proteomic study. These biomarkers methods will improve the assessment of internal dose and early biological effect in field studies of occupational exposures. Some other smaller projects will be involved and collaborative work with the EPA.


The purpose of this Molecular and Genetics Monitoring Team "umbrella" project is to identify and develop biomarkers of exposure, biomarkers of susceptibility and biomarkers of effect for occupational toxicants which is an integral part of the biomonitoring program at NIOSH. This project will provide guidance for branch collaborative studies involving biomarker research that are not large enough in scope to be stand alone. Biomarkers have an important application for human field studies. Workers can be better protected by the knowledge gained from more accurate determinations of exposure from the use of the appropriate biomarkers. This project addresses the need to relate exposure and susceptibility markers to markers of early effects and to determine which markers must be characterized to best reflect exposure or early indicators of disease.

All proteomic investigations will employ a Surface Enhanced Laser Desorption/Ionization (SELDI) protein chip system. Urine samples from acrylamide exposed workers and spiked urine samples were analyzed previously and the raw data will be processed in FY09. Additional sample are expected to be collected in the field in 2008 and will have to be analyzed. Analytical methods used to support the healthcare worker project are finished and data analysis and publication preparation is planned. Research also will focus upon the development and identification of susceptibility biomarkers; research to be conducted in FY09 includes further characterization of genetic polymorphisms in genes in DNA damage repair pathways and in genes important in metabolism from acrylamide. This is a genetic method development project, and in FY09 methods will be developed to remove inhibitors that interfere with genotyping from DNA isolated from urine. After these techniques are developed, preparation of DNA from urine can be initiated in order to identify polymorphisms in metabolism that alter the relationship between exposure and internal exposure in manicurists. Results will provide data necessary to determine if biomarkers of susceptibility reflecting metabolism of occupational toxicants must be characterized in similar field studies whenever biomarkers of internal exposure are to be used. In addition, partnering with the U.S. Environmental Protection Agency (EPA) on the development and possible validation of analytical methods for the detection of chemical warfare degradation products utilizing high-performance liquid chromatography – mass spectrometry (HPLC-MS) and HPLC-MS/MS is included within this project. Chemical warfare agents generally are not persistent and usually degrade quickly to less toxic degradation products. Work with wipe testing methods devised by Dr. Jack Pretty would be included after chromatographic analysis procedures are established.


• Applications of biomarker methods for occupational toxicants to assess exposure with internal or external partners will be tracked and reported.

• Track output of data to partners.

• Conduct internet searches such as use of the ISI Web of Science to determine citation counts for any of the publications listed.

• Track invited presentations as an indicator of successful marketing of this research.

• Contact with partners and stakeholders to determine if information or data used to make changes to work environment.

Mission Relevance

All forms of biomarkers are routinely incorporated into the design of both epidemiological and health outcome studies so that exposure and effects of exposure can be more accurately characterized. Biomarker studies are needed that relate internal dose with external exposure and relate exposure to disease so that the associated health risk can be fully understood. Biomarker data can be used to document the existence of an exposure problem, a health effect related to exposure, or to indicate the adequacy of control technologies and intervention strategies. Biomarkers studied and developed during this project will have application for exposure assessment studies (both planned as well as requests from partners for assistance), and for evaluating intervention effectiveness. For FY09, activities will complete data analysis for healthcare worker study and proteomic method development of biomarkers in collaboration of the acrylamide worker project as well as characterization of polymorphisms in DNA repair pathways in samples collected from ongoing field studies of acrylamide workers. It has been estimated that occupational exposures could be attributed to as many as 40,000 new cases of cancer a year within the United States. Specifically for acrylamide, an NOES survey has indicated that as many as 10,000 workers are exposed to acrylamide in the United States. This project addresses goals in both the Healthcare and Social Assistance (09PPHSASG2) and Manufacturing (09PPMNFSG6) Sectors, specifically to the Activity/Output Goal 2a.1.2 (09PPHSAAOG2a1.2): Evaluate exposures to carcinogens and teratogens in the HSA Sector. This project also aligns to the Cancer, Reproductive and Cardiovascular Diseases Cross Sector Activity/Output Goal 1.1.3. (09PPCRCAOG1.1.3); Develop and evaluate biomonitoring methods for the determination of carcinogen exposures and health effects in workers and Activity/Output Goal 1.1.6. (09PPCRCAOG1.1.6); Assess how cancer risk is influenced by the interaction of human genetic variation with modifiable risk factors and the Exposure Assessment Cross Sector Intermediate Goal 2.4 (09PPEXAIG2.4): Develop biomonitoring methods including biomarkers that are useful for mixed exposures.

Activity/Output 2.4.1 (09PPEXAAOG2.4.1): Development of new biomonitoring methods; Activity/Output 2.4.2 (09PPEXAAOG2.4.2): Laboratory and field validation of biomonitoring methods to document and characterize their performance characteristics, including specificity, sensitivity, accuracy, and other performance measures; Activity/Output 2.4.3 (09PPEXAAOG2.4.3): Application of these methods to evaluate occupational exposure.