Development of Biomarkers for haloacetonitriles-induced cell injury in Peripheral Blood

EPA Grant Number: R825955
Title: Development of Biomarkers for haloacetonitriles-induced cell injury in Peripheral Blood
Investigators: Ahmed, Ahmed Elsayed
Institution: The University of Texas Medical Branch - Galveston
EPA Project Officer: Nolt-Helms, Cynthia
Project Period: October 1, 1997 through September 30, 2000 (Extended to November 10, 2002)
Project Amount: $485,147
RFA: Drinking Water (1997) RFA Text |  Recipients Lists
Research Category: Drinking Water , Water

Description:

Objectives/ Hypotheses:

Drinking waters are contaminated with a mixture of Halogenated hydrocarbons that are disinfection byproducts. Among those are a number of toxic and carcinogenic Halogenated acetonitriles that are known to stimulate a variety of acute and chronic adverse effects in man and in laboratory animals. The goal is to develop unique biomarkers, in a readily accessible compartment such 'as blood, for HAN exposure and HAN-induced cell injury. This injury may result from HAN-induced alkylative or oxidative damage to cellular macromolecules such as hemoglobin and DNA. We also plan to evaluate some of the responses to HAN in human peripheral blood cells in vitro and develop an animal model of dermal and inhalation exposure to HAN using female rats and mice.

Approach:

Methods will be developed for quantification of alkylative (cyanomethylated) and oxidative damage to cellular macromolecules ( hemoglobin and DNA) using a highly sensitive and specific techniques such as HPLC with electrochemical detection and Gas chromatography/Mass spectroscopic detection of alkylated molecules. These techniques will be applicable for assessing exposure to a wide variety of small environmental pollutants and will be a sensitive method for exposure assessment of in vivo alkylative and oxidative damage. Thus, we aim to address both methodology development for biomarkers of exposure and correlation of biomarkers in peripheral blood cells (erythrocytes and lymphocytes) with HAN-induced pathological signs.

Expected Results:

Expected Results will identify target tissues of toxicity, cellular injury and macromolecular damage, that will be used to identify and qunatitate biomarkers of the adverse effects of HAN. Data obtained will define how HAN reacts with peripheral blood cellular macromolecules. This will provide basis for the development of regulatory guidelines and policies governing the tolerance levels for chronic HAN exposure in man.

Publications and Presentations:

Publications have been submitted on this project: View all 23 publications for this project

Journal Articles:

Journal Articles have been submitted on this project: View all 7 journal articles for this project

Supplemental Keywords:

Drinking water disinfection, disinfection byproducts, haloacetonitriles, biomarkers of exposure, peripheral blood, DNA adducts, hemoglobin adducts, cyanomethyl guanine, cyanomethyl valine., RFA, Scientific Discipline, Water, Environmental Chemistry, Health Risk Assessment, Biochemistry, Drinking Water, dermal exposure, halogenated disinfection by-products, public water systems, biomarkers, haloacetonitriles, human health effects, exposure and effects, animal model, chemical byproducts, disinfection byproducts (DPBs), dose response, exposure, community water system, carcinogenicity, inhalation, toxicity, treatment, cell injury, halogenated hydrocarbons, drinking water contaminants, peripheral blood, DBP exposure

Progress and Final Reports:

  • 1998 Progress Report
  • 1999 Progress Report
  • 2000 Progress Report
  • 2001
  • 2002
  • Final Report