Integrating Environmental Justice into Public Health: Approaches for Understanding Cumulative Impacts

Communities located near multiple sources of pollution, including current and former industrial sites, major roadways, and agricultural operations, are often predominantly low-income, with a large percentage of minorities and non-English speakers. These communities face additional challenges that can affect the health of their residents, including limited access to health care, a shortage of grocery stores, poor housing quality, and a lack of parks and open spaces. Research is now showing that environmental exposures can interact with social stressors, thereby worsening health outcomes. Age, nutrition, genetic characteristics, and preexisting health conditions also increase the risk of adverse health effects from exposure to pollutants. There are existing approaches for characterizing cumulative impacts, which vary in their analytical method and level of community engagement. Biomonitoring, health risk assessment, ecological risk assessment, health impact assessment, burden of disease, and cumulative impacts mapping have all been used to evaluate aspects of this issue. Although such approaches have merit, they each also have significant constraints. New developments in exposure monitoring, mapping, toxicology, and genomics, especially when informed by community participation, have the potential to advance the science on cumulative impacts and to improve prioritization, resource allocation, and risk reduction

Addressing human variability in next-generation human health risk assessments of environmental chemicals

International audienceCharacterizing variability in the extent and nature of responses to environmental exposures is a critical aspect of human health risk assessment. 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. 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. 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. Despite these inherent challenges, opportunities exist to incorporate evidence from emerging data streams for addressing interindividual variability in a range of decision-making contexts

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

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

Assessing health risks from multiple environmental stressors: Moving from G×E to I×E.

Research on disease causation often attempts to isolate the effects of individual factors, including individual genes or environmental factors. This reductionist approach has generated many discoveries, but misses important interactive and cumulative effects that may help explain the broad range of variability in disease occurrence observed across studies and individuals. A disease rarely results from a single factor, and instead results from a broader combination of factors, characterized here as intrinsic (I) and extrinsic (E) factors. Intrinsic vulnerability or resilience emanates from a variety of both fixed and shifting biological factors including genetic traits, while extrinsic factors comprise all biologically-relevant external stressors encountered across the lifespan. The I×E concept incorporates the multi-factorial and dynamic nature of health and disease and provides a unified, conceptual basis for integrating results from multiple areas of research, including genomics, G×E, developmental origins of health and disease, and the exposome. We describe the utility of the I×E concept to better understand and characterize the cumulative impact of multiple extrinsic and intrinsic factors on individual and population health. New research methods increasingly facilitate the measurement of multifactorial and interactive effects in epidemiological and toxicological studies. Tiered or indicator-based approaches can guide the selection of potentially relevant I and E factors for study and quantification, and exposomics methods may eventually produce results that can be used to generate a response function over the life course. Quantitative data on I×E interactive effects should generate a better understanding of the variability in human response to environmental factors. The proposed I×E concept highlights the role for broader study design in order to identify extrinsic and intrinsic factors amenable to interventions at the individual and population levels in order to enhance resilience, reduce vulnerability and improve health

State-of-the-Science Workshop Report: Issues and Approaches in Low-Dose–Response Extrapolation for Environmental Health Risk Assessment

Low-dose extrapolation model selection for evaluating the health effects of environmental pollutants is a key component of the risk assessment process. At a workshop held in Baltimore, Maryland, on 23–24 April 2007, sponsored by U.S. Environmental Protection Agency and Johns Hopkins Risk Sciences and Public Policy Institute, a multidisciplinary group of experts reviewed the state of the science regarding low-dose extrapolation modeling and its application in environmental health risk assessments. Participants identified discussion topics based on a literature review, which included examples for which human responses to ambient exposures have been extensively characterized for cancer and/or noncancer outcomes. Topics included the need for formalized approaches and criteria to assess the evidence for mode of action (MOA), the use of human versus animal data, the use of MOA information in biologically based models, and the implications of interindividual variability, background disease processes, and background exposures in threshold versus nonthreshold model choice. Participants recommended approaches that differ from current practice for extrapolating high-dose animal data to low-dose human exposures, including categorical approaches for integrating information on MOA, statistical approaches such as model averaging, and inference-based models that explicitly consider uncertainty and interindividual variability

Meeting Report: Moving Upstream—Evaluating Adverse Upstream End Points for Improved Risk Assessment and Decision-Making

Background Assessing adverse effects from environmental chemical exposure is integral to public health policies. Toxicology assays identifying early biological changes from chemical exposure are increasing our ability to evaluate links between early biological disturbances and subsequent overt downstream effects. A workshop was held to consider how the resulting data inform consideration of an “adverse effect” in the context of hazard identification and risk assessment. Objectives Our objective here is to review what is known about the relationships between chemical exposure, early biological effects (upstream events), and later overt effects (downstream events) through three case studies (thyroid hormone disruption, antiandrogen effects, immune system disruption) and to consider how to evaluate hazard and risk when early biological effect data are available. Discussion Each case study presents data on the toxicity pathways linking early biological perturbations with downstream overt effects. Case studies also emphasize several factors that can influence risk of overt disease as a result from early biological perturbations, including background chemical exposures, underlying individual biological processes, and disease susceptibility. Certain effects resulting from exposure during periods of sensitivity may be irreversible. A chemical can act through multiple modes of action, resulting in similar or different overt effects. Conclusions For certain classes of early perturbations, sufficient information on the disease process is known, so hazard and quantitative risk assessment can proceed using information on upstream biological perturbations. Upstream data will support improved approaches for considering developmental stage, background exposures, disease status, and other factors important to assessing hazard and risk for the whole population

EXponene

1986 (Prop 65) as "known to the state to cause reproductive toxicity. " I have been asked by Syngenta, based upon my knowledge about the potential reproductive and developmental toxicology of atrazine and my experience at US EPA, to review and comment on the evidence presented in the Notice of Intent to List. This letter expresses my opposition to the proposed listing of atrazine based on the lack of sufficient data to support the stated reproductive effects. The pertinent regulation requires that the determination of sufficiency take into account: "the adequacy of the experimental design and other parameters such as, but not limited to, route of administration, frequency and duration of exposure, numbers of test animals, choice ofspecies, choice of dosage levels, and consideration of maternal toxicity, indicating that an association between adverse reproductive effects in humans and the toxic agent in question is biologically plausible." OEHHA did not fully take into account these factors and the current state of knowledge regarding atrazine. In particular, when the reproductive effects reported in rats are considered in light of the mechanism of action (MOA) for atrazine and pharmacokinetics from the studies that compare gavage and dietary exposure to atrazine, it is clear that theMarch 21, 2014 Page 2 reproductive effects seen in rodents are not relevant to humans. These factors are described in greater detail below, and demonstrate that the potential for reproductive toxicity from atrazine exposure in humans lacks biological plausibility