Addressing Human Variability in Next-Generation Human Health Risk Assessments of Environmental Chemicals

Lauren Zeise,¹ Frederic Y. Bois,² Weihsueh A. Chiu,³ Dale Hattis,⁴ Ivan Rusyn,⁵ and Kathryn Z. Guyton³

¹Office of Environmental Health Hazard Assessment, California Environmental Protection Agency, Oakland, California, USA; ²Institut National de l’Environnement Industriel et des Risques (INERIS), Verneuil en Halatte, France; ³National Center for Environmental Assessment, U.S. Environmental Protection Agency, Washington, DC, USA; ⁴George Perkins Marsh Institute, Clark University, Worcester, Massachusetts, USA; ⁵Department of Environmental Sciences and Engineering, University of North Carolina–Chapel Hill, Chapel Hill, North Carolina, USA


Abstract

Background: Characterizing variability in the extent and nature of responses to environmental exposures is a critical aspect of human health risk assessment.


Objective: Our goal was to explore how next-generation human health risk assessments may better characterize variability in the context of the conceptual framework for the source-to-outcome continuum.


Methods: This review was informed by a National Research Council workshop titled “Biological Factors that Underlie Individual Susceptibility to Environmental Stressors and Their Implications for Decision-Making.” We considered current experimental and in silico approaches, and emerging data streams (such as genetically defined human cells lines, genetically diverse rodent models, human omic profiling, and genome-wide association studies) that are providing new types of information and models relevant for assessing interindividual variability for application to human health risk assessments of environmental chemicals.


Discussion: One challenge for characterizing variability is the wide range of sources of inherent biological variability (e.g., genetic and epigenetic variants) among individuals. A second challenge is that each particular pair of health outcomes and chemical exposures involves combinations of these sources, which may be further compounded by extrinsic factors (e.g., diet, psychosocial stressors, other exogenous chemical exposures). A third challenge is that different decision contexts present distinct needs regarding the identification—and extent of characterization—of interindividual variability in the human population.


Conclusions: Despite these inherent challenges, opportunities exist to incorporate evidence from emerging data streams for addressing interindividual variability in a range of decision-making contexts.


Key words: environmental agents, genetics, human health risk assessment, modeling, omics technologies, susceptible populations, variability. 


Environ Health Perspect 121:23–31 (2013). http://dx.doi.org/10.1289/ehp.1205687 [Online 19 October 2012]


Address correspondence to L. Zeise, California Environmental Protection Agency, 1515 Clay St., 16th Floor, Oakland, CA 94612 USA. Telephone: (510) 622-3195. Fax: (510) 622-3211. E-mail: Lauren.Zeise@oehha.ca.gov


This review was informed by the discussions and presentations at a National Research Council (NRC) workshop titled “Biological Factors that Underlie Individual Susceptibility to Environmental Stressors and Their Implications for Decision-Making” held in April 2012 in Washington, DC.


We thank the staff, particularly K. Sawyer and M. Shelton-Davenport, and members of the NRC’s Committee on Emerging Science for Environmental Health Decisions. We also thank I. Cote for her thoughtful comments.


The views in this article are those of the authors, and do not necessarily reflect the views or policies of the U.S. Environmental Protection Agency or the California Office of Environmental Health Hazard Assessment.


The authors declare they have no actual or potential competing financial interests.


Received 28 June 2012; Accepted 19 October 2012; Online 19 October 2012.