Emerging Technologies

Quick Finder

The Issue | Science Objectives | Research Highlights | Impact and Outcome

The Issue

A major problem facing risk assessors is an incomplete understanding of the modes or mechanisms by which environmental agents produce their toxicity. Mode of action information may be used in the risk assessment process to reduce default assumptions, such as extrapolation from laboratory animal data to humans. It also may provide the basis for assessing cumulative risk based on mode of action as required by the Food Quality Protection Act of 1996. The application of emerging molecular methods to better understand mode of action has been facilitated by the development of micro-array approaches to measure changes occurring at the genetic level. These new methods potentially can measure simultaneous changes in thousands of genes, which could accelerate EPA's ability to identify toxic effects, as well as the cellular and biochemical pathways that underlie those effects.

Science Objective

The objectives of this research effort are to identify and develop molecular methods that can be used in other research to identify and characterize modes of action in the risk assessment context.

Research Goals:

Identify key toxicity pathways that underlie cancer and noncancer outcomes for high-priority environmental pollutants
Identify biomarkers that could be used to identify susceptible subpopulations
Identify key biological events that could be used to evaluate cumulative risk of chemicals with a similar mode of action.
Identify key differences or similarities in response that could improve extrapolation from laboratory animals to humans, in vitro to in vivo, and high to low dose in risk assessment
Identify possible genetic differences as the basis for intrahuman variability (i.e., differential responsiveness of some groups in human populations)
Develop "omic" methods that could be used to develop approaches to screen and test chemicals based on mode of action information. "Omics" refers to three scientific disciplines: genomics or the study of genes and their function; proteomics which is defined as the study of the full set of proteins encoded by a genome' and metabonics which is defined as the study of the total metabolite pool

Research Highlights

Identification of plasma proteins and mRNA populations in blood cells as biomarkers of effects in humans exposed to air pollutants.
Assessment of oxidative stress as an underlying mechanism by which many pollutants cause adverse effects.
Development of a respiratory cell culture model that is predictive of animal responses to inhaled pollutants.
Identification of genetic polymorphisms that can predict susceptibility of healthy humans to air pollutants.

Impact and Outcomes

Human Health Research Contributions: