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

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.

Impact of Nonalcoholic Fatty Liver Disease on Toxicokinetics of Tetrachloroethylene in Mice

“…Interindividual variability is a major challenge for the assessment of human health burden associated with exposure to environmental contaminants (Zeise et al, 2013). Variability in toxicokinetics and ensuing metabolic activation of the parent chemical to relatively more toxic metabolites is often the underlying cause of the variability in adverse health responses (Bois et al, 2010).…”

Cumulative Environmental Impacts: Science and Policy to Protect Communities

“…For instance, environmental exposures and social vulnerability can increase rates of health conditions, thereby heightening biological susceptibility to additional environmental exposures (40,76). One example is the association between poor housing quality and exposure to indoor antigens from cockroaches or mold, thereby increasing the risk of respiratory symptoms and in turn increasing host vulnerability to outdoor air pollutants such as ozone.…”

Uncertainties of testing methods: What do we (want to) know about carcinogenicity?

“…A relevant case study example of the literature screening and integration of epidemiological and toxicological information for cancer outcomes of concern for three pesticides was recently conducted by the WHO FAO Joint Meeting on Pesticide Residues 5 . Also, literature on human variability may be critical for conclusions (Zeise et al, 2013;WHO, 2014;. In any case, the correlation between results from new approaches and reference data will be influenced by two aspects, i.e., the reliability (i.e., variability and uncertainty) of the new approach and of the reference data, and the correlation of mean values from the new approach and the reference data.…”