Validation of Diesel Exhaust BiomarkersEPA Grant Number: R832097
Title: Validation of Diesel Exhaust Biomarkers
Investigators: Zhang, Junfeng , Fiedler, Nancy , Kipen, Howard , Laumbach, Robert , Lioy, Paul J. , Ohman-Strickland, Pamela , Zhang, Lin
Current Investigators: Zhang, Junfeng , Fiedler, Nancy , Kipen, Howard , Laumbach, Robert , Lioy, Paul J. , Ohman-Strickland, Pamela , Stern, Alan , Zhang, Lin
Institution: University of Medicine and Dentistry of New Jersey , New Jersey Department of Environmental Protection
Current Institution: Environmental and Occupational Health Sciences Institute , New Jersey Department of Environmental Protection , University of Medicine and Dentistry of New Jersey
EPA Project Officer: Hahn, Intaek
Project Period: May 1, 2005 through April 30, 2008
Project Amount: $572,497
RFA: Application of Biomarkers to Environmental Health and Risk Assessment (2004) RFA Text | Recipients Lists
Research Category: Health Effects , Health
Health risk associated with diesel exhaust (DE) has been a concern of EPA and other agencies for over 30 years, but is still poorly characterized, partly due to the lack of DE-specific markers or biomarkers of exposure. This study will explore the development and validation of more specific biomarkers of DE exposure, namely nitro-PAHS.
Urinary 1-hydroxypyrene, a major metabolite of pyrene, has been used as a DE biomarker in occupational settings, but pyrene has numerous environmental sources. Nitro-PAHs are emitted specifically by diesel engines and their urinary metabolites, amino-PAHs, have been measured in DE exposed workers in a recent occupational study. Based on these data and our preliminary study of 7 subjects exposed to diesel-powered city bus exhaust, we propose to piggy-back the proposed study onto a current DE health effects study to (i) validate novel biomarkers of DE exposure to effectively quantify environmentally relevant exposures, and (ii) explore the effects of a range of demographic and health variables on urinary biomarker levels.
We will test the following hypotheses in 50 healthy and nonsmoking men and women during two (previously approved and funded) one-hr controlled exposure sessions, to DE at 300 �g/m3 PM10 and to clean air: (a) Exposure to DE at environmentally relevant levels leads to increases in urinary levels of amino-PAHs. (b) Increases in urinary levels of amino-PAHs, in response to DE exposure, are more consistent across individuals than increases in urinary levels of 1-hydroxypyrene. The target amino-PAHs are 1-aminopyrene, 1-aminonaphthalene, 2- aminonaphthalene and 3-aminobenzanthrone.
Specifically, we will: (1) optimize an amino-PAH analysis method to increase the sensitivities and recoveries and reduce the cost of sample analysis; (2) determine how long after DE exposure urinary amino-PAH concentrations reach maximum levels; (3) quantify inhalation exposure to the parent nitro-PAHs of each of the target biomarkers during the entire time window of urinary monitoring and minimize potential interferences from exposures that may occur before and after the controlled exposure session; (4) estimate the fraction of inhaled nitro-PAHs converted into amino-PAH metabolites and excreted in the urine; and (5) assess inter-individual biomarker variability, with respect to gender, age, BMI, chemical intolerance, and a suite of the health endpoints measured in the existing health study.
We expect the validated biomarkers to have a large potential for use in DE health risk assessment because the sensitivity and specificity of these biomarkers are adequate to identify not only individuals who are occupationally exposed but also those who are exposed to elevated environmental levels of DE. Moreover, measurement of these novel biomarkers requires only noninvasive human urine collection and commonly available HPLC-fluorescence instrumentation. The cost-effective integration with the current health study will enable exploratory analyses of biomarkers in relation to health endpoints. This is an important step towards understanding the biological mechanisms underlying the exposure-dose-effect continuum for nitro-PAHs resulting from DE exposure.