Biomarker Application and Risk Assessment of Cr(VI)EPA Grant Number: R830682
Title: Biomarker Application and Risk Assessment of Cr(VI)
Investigators: Qu, Qingshan , An, Feiyun , Cohen, Beverly S. , Costa, Max , Shore, Roy E.
Institution: New York University
Current Institution: New York University , Central South University School of Public Health - China
EPA Project Officer: Fields, Nigel
Project Period: September 1, 2002 through August 31, 2005
Project Amount: $898,601
RFA: Issues in Human Health Risk Assessment (2001) RFA Text | Recipients Lists
Research Category: Health Effects , Human Health Risk Assessment , Health
There has been an increasing public concern regarding the potential toxic and carcinogenic effects of exposure to Cr(VI) at low levels, since Cr(VI) is one of the major contaminants found in most of the superfund sites. However, the risk assessment of Cr(VI) associated toxicity and neoplasm had been mainly conducted through either high- to low-concentration or animal-to-human extrapolation. The validity of this extrapolation is uncertain. The primary objective of this study is first to validate a number of biomarkers in humans with broad range of Cr(VI) exposure and then to apply those validated markers in human populations exposed to Cr(VI) at low levels for making direct and reliable health risk assessment of Cr(VI).
The biomarkers to be validated include Cr levels in erythrocytes, lymphocytes, and plasma, as well as DNA-protein crosslinks. The study will be conducted in Chinese occupational populations to: (1) determine if these candidate markers can at least reliably detect differences between unexposed subjects and exposed workers at levels encountered in the industrial settings; (2) examine the reproducibility of these biomarkers and to assess their inter- and intra-individual variabilities; (3) estimate the effective half-lives of the exposure markers and evaluate whether they relate to the most current exposure or to integrated exposures over a period of time; (4) determine whether these markers can be reliably used to differentiate between unexposed subjects and exposed subjects at low ambient levels and characterize their exposure-response relationships; (5) investigate the specificity of these biomarkers and identify possible effects of general confounding factors, such as smoking, diet, age, gender and other metal exposures, on the levels of these markers; and (6) evaluate how individual capacity of plasma reduction interacts with Cr(VI) exposure in determining the levels of biomarkers and specifically examine the potential effect of plasma levels of vitamin C and its redox status on Cr(VI) exposure-biomarker response relationship. Finally, the characterized exposure-biomarker response model will be used for direct risk assessment of Cr(VI).
Successful completion of the proposed study will generate a valid data set for the responses of biomarkers to Cr(VI) exposure at low levels. The direct application of these human exposure-response data at low levels will reduce the assumptions and uncertainties that arise from extrapolations from animal to human or from high to low concentrations, thereby making health risk assessments more reliable, meaningful, and cost effective. The study will contribute to an improved understanding of the importance of an integrated approach to exposure assessment and provide useful inputs to health risk analysis.