Improving Methods for Identifying Noncancer Risks Application of Cell Kinetic Models for Methylmercury Risk Assessment

EPA Grant Number: R825358
Title: Improving Methods for Identifying Noncancer Risks Application of Cell Kinetic Models for Methylmercury Risk Assessment
Investigators: Faustman, Elaine , Leroux, Brian
Institution: University of Washington
EPA Project Officer: Klieforth, Barbara I
Project Period: October 1, 1996 through September 30, 1999
Project Amount: $390,827
RFA: Exploratory Research - Human Health (1996) RFA Text |  Recipients Lists
Research Category: Health Effects , Human Health , Health


The overall goal of this project is the improvement of procedures for estimating the risk of developmental toxicity in humans. The attainment of this goal requires the development of biologically based dose-response models for noncancer risks that can be used to estimate risks at low, environmentally relevant doses. This research project will focus on the further development of mathematical models to describe the dynamic and complex process of organogenesis, based on modeling of cell kinetics using branching processes and nonlinear mixed effects regression models. Biological experiments (in vivo and in vitro) are proposed for model developmental toxicants to provide detailed molecular and cellular information that will be incorporated into the models. Such information will include in vivo and in vitro data on timing, concentration, and rates of dynamic cell processes such as changes in cell cycle genes, in differentiation and migration as well as growth and replication rates. Initially, the developmental neurotoxicity of methyl mercury will be studied in detail during the early to mid organogenesis gestational period. This grant addresses four key EPA research needs in that it will: 1) improve our methods for quantifying noncancer risks by developing biologically based dose response models for developmental toxicity, 2) evaluate age-dependent responses to environmental contaminants, 3) improve our capabilities for animal to human extrapolation of health risks, and 4) evaluate factors contributing to inter- and intra-individual variability in factors that affect susceptibility.

Publications and Presentations:

Publications have been submitted on this project: View all 31 publications for this project

Journal Articles:

Journal Articles have been submitted on this project: View all 5 journal articles for this project

Supplemental Keywords:

non-cancer, development, modeling, risk assessment, rodent., RFA, Health, Scientific Discipline, Toxics, Water, National Recommended Water Quality, Environmental Chemistry, Health Risk Assessment, Risk Assessments, Susceptibility/Sensitive Population/Genetic Susceptibility, genetic susceptability, Mercury, interindividual variability, risk assessment, dose-response models, health risks, dose response, exposure, developmental toxicity, neurotoxicity, mercury cycling, human exposure, methylmercury, age dependent response, mixed effects regression model, age, cell kinetic models, heavy metals

Progress and Final Reports:

  • 1997
  • 1998
  • Final Report