Alternative Strategies for Quantification of Non-Cancer Health Risks, Utilizing Human Information on Interindividual VariabilityEPA Grant Number: R825360
Title: Alternative Strategies for Quantification of Non-Cancer Health Risks, Utilizing Human Information on Interindividual Variability
Investigators: Hattis, Dale
Current Investigators: Hattis, Dale , Goble, Robert
Institution: Clark University
EPA Project Officer: Klieforth, Barbara I
Project Period: November 18, 1996 through November 17, 1999 (Extended to December 1, 2000)
Project Amount: $331,537
RFA: Exploratory Research - Human Health (1996) RFA Text | Recipients Lists
Research Category: Health Effects , Human Health , Health
Description:This project will develop and illustrate a variety of methods for quantifying non-cancer health effects utilizing human data on the interindividual variability in susceptibility to toxicity and variability in functional reserve capacities for different physiological processes. The methods developed will be adapted for different combinations of: (1) quantal vs. continuous outcome parameters; (2) one-step (simple input-output) modeling vs. multistep modeling with intermediate biomarkers along the causal chain from exposure to end effect; and (3) deterministic vs stochastic models of the processes causing the ultimate harm. Specific case study examples may include:
- Quantal outcome, one-step modeling, deterministic process?Traditional log probit dose response analysis of the percentage of people showing hypersensitivity responses to dermally applied chromium(VI) solution is interpreted as a direct measure of the percentage of people who have thresholds below different doses.
- Quantal outcome, multi-step modeling, deterministic process?Overall interindividual variability in susceptibility is modeled as a combination of the variability of component processes?uptake, pharmacokinetic, pharmacodynamic.
- Continuous outcome, one-step modeling, deterministic process?Change in FEV1 from short term exposures to ozone; change in measures of kidney function from long term exposure/uptake/ urinary excretion of cadmium.
- Continuous outcome, multi-step modeling, deterministic process?Lead in house dust increases blood lead which in turn affects development of IQ in children or elevated blood pressure in adults.
- Quantal outcome, multi-step modeling, stochastic process?1) Changes in mortality as a function of cadmium-induced kidney damage; 2) Changes in male fertility as a function of toxicity-induced changes in sperm count and other sperm quality parameters; and 3) Changes in infant mortality as a function of toxicity-induced changes in birth weight.
- Quantal and Continuous outcomes, multi-step modeling, stochastic process?Number and severity of automobile injuries as a function of defined changes in hazard recognition and response times induced by alcohol and other neuroactive substances in experimental subjects.