Population exposure to multiple chemicals in air presents significant challenges for environmental public health. Air quality regulations distinguish criteria air pollutants (CAPs) (e.g., ozone, PM2.5) from hazardous air pollutants (HAPs)—187 chemicals which include carcinogens and others that are associated with respiratory, cardiovascular, neurological and numerous other non-cancer health effects. Evidence of the public’s cumulative exposure and the health effects of HAPs are quite limited. A multilevel model is used to assess differential exposure to HAP respiratory, neurological, and cancer hazards (2005) related to the Townsend Index of Socioeconomic Deprivation (TSI), after adjustment for regional population size and economic activity, and local population density. We found significant positive associations between tract TSI and respiratory and cancer HAP exposure hazards, and smaller effects for neurological HAPs. Tracts in the top quintile of TSI have between 38%–60% higher HAP exposure than the bottom quintile; increasing population size from the bottom quintile to the top quintile modifies HAP exposure hazard related to TSI, increasing cancer HAP exposure hazard by 6% to 20% and increasing respiratory HAP exposure hazard by 12% to 27%. This study demonstrates the value of social epidemiological methods for analyzing differential exposure and advancing cumulative risk assessment. Full article

Conventionally, in its decision-making, the U.S. EPA has evaluated the effects and risks associated with a single pollutant in a single exposure medium. In reality, people are exposed to mixtures of pollutants or to the same pollutant through a variety of media, including the air, water, and food. It is now more recognized than before that environmental exposure to pollutants occurs via multiple exposure routes and pathways, including inhalation, ingestion, and dermal absorption. Moreover, chemical, biologic, radiologic, physical, and psychologic stressors are all acknowledged as affecting human health. Although many EPA offices attempt to consider cumulative risk assessment and cumulative effects in various ways, there is no Agency-wide policy for considering these risks and the effects of exposure to these risks when making environmental decisions. This article examines how U.S. courts might assess EPA’s general authority and discretion to use cumulative risk assessment as the basis for developing data in support of environmental decision-making, and how courts might assess the validity of a cumulative risk assessment methodology itself. Full article

Cumulative risk assessment has been proposed as an approach to evaluate the health risks associated with simultaneous exposure to multiple chemical and non-chemical stressors. Physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) models can allow for the inclusion and evaluation of multiple stressors, including non-chemical stressors, but studies have not leveraged PBPK/PD models to jointly consider these disparate exposures in a cumulative risk context. In this study, we focused on exposures to organophosphate (OP) pesticides for children in urban low-income environments, where these children would be simultaneously exposed to other pesticides (including pyrethroids) and non-chemical stressors that may modify the effects of these exposures (including diet). We developed a methodological framework to evaluate chemical and non-chemical stressor impacts on OPs, utilizing an existing PBPK/PD model for chlorpyrifos. We evaluated population-specific stressors that would influence OP doses or acetylcholinesterase (AChE) inhibition, the relevant PD outcome. We incorporated the impact of simultaneous exposure to pyrethroids and dietary factors on OP dose through the compartments of metabolism and PD outcome within the PBPK model, and simulated combinations of stressors across multiple exposure ranges and potential body weights. Our analyses demonstrated that both chemical and non-chemical stressors can influence the health implications of OP exposures, with up to 5-fold variability in AChE inhibition across combinations of stressor values for a given OP dose. We demonstrate an approach for modeling OP risks in the presence of other population-specific environmental stressors, providing insight about co-exposures and variability factors that most impact OP health risks and contribute to children’s cumulative health risk from pesticides. More generally, this framework can be used to inform cumulative risk assessment for any compound impacted by chemical and non-chemical stressors through metabolism or PD outcomes. Full article

The purpose of this study is to apply the Human Security Index (HSI) as a tool to detect social and economic cumulative risk burden at a county-level in the state of Texas. The HSI is an index comprising a network of three sub-components or “fabrics”; the Economic, Environmental, and Social Fabrics. We hypothesized that the HSI will be a useful instrument for identifying and analyzing socioeconomic conditions that contribute to cumulative risk burden in vulnerable counties. We expected to identify statistical associations between cumulative risk burden and (a) ethnic concentration and (b) geographic proximity to the Texas-Mexico border. Findings from this study indicate that the Texas-Mexico border region did not have consistently higher total or individual fabric scores as would be suggested by the high disease burden and low income in this region. While the Economic, Environmental, Social Fabrics (including the Health subfabric) were highly associated with Hispanic ethnic concentration, the overall HSI and the Crime subfabric were not. In addition, the Education, Health and Crime subfabrics were associated with African American racial composition, while Environment, Economic and Social Fabrics were not. Application of the HSI to Texas counties provides a fuller and more nuanced understanding of socioeconomic and environmental conditions, and increases awareness of the role played by environmental, economic, and social factors in observed health disparities by race/ethnicity and geographic region. Full article

The identification of “environmental justice (EJ) communities” is an increasingly common element in environmental planning, policy, and regulation. As a result, the choice of methods to define and identify these communities is a critical and often contentious process. This contentiousness is, in turn, a factor of the lack of a commonly accepted method, the concern among many EJ advocates and some regulators that existing frameworks are inadequate, and ultimately, the significant consequences of such designations for both public policy and community residents. With the aim of assisting regulators and advocates to more strategically focus their efforts, the authors developed a Cumulative Environmental Vulnerability Assessment (CEVA). This CEVA is composed of a Cumulative Environmental Hazard Index and a Social Vulnerability Index, with a Health Index as a reference. Applying CEVA produces spatial analysis that identifies the places that are subject to both the highest concentrations of cumulative environmental hazards and the fewest social, economic and political resources to prevent, mitigate, or adapt to these conditions. We recommended that these areas receive special consideration in permitting, monitoring, and enforcement actions, as well as investments in public participation, capacity building, and community economic development. Full article

Susceptibility to chemical toxins has not been adequately addressed in risk assessment methodologies. As a result, environmental policies may fail to meet their fundamental goal of protecting the public from harm. This study examines how characterization of risk may change when susceptibility is explicitly considered in policy development; in particular we examine the process used by the U.S. Environmental Protection Agency (EPA) to set a National Ambient Air Quality Standard (NAAQS) for lead. To determine a NAAQS, EPA estimated air lead-related decreases in child neurocognitive function through a combination of multiple data elements including concentration-response (CR) functions. In this article, we present alternative scenarios for determining a lead NAAQS using CR functions developed in populations more susceptible to lead toxicity due to socioeconomic disadvantage. The use of CR functions developed in susceptible groups resulted in cognitive decrements greater than original EPA estimates. EPA’s analysis suggested that a standard level of 0.15 µg/m³ would fulfill decision criteria, but by incorporating susceptibility we found that options for the standard could reasonably be extended to lower levels. The use of data developed in susceptible populations would result in the selection of a more protective NAAQS under the same decision framework applied by EPA. Results are used to frame discussion regarding why cumulative risk assessment methodologies are needed to help inform policy development. Full article

The California Environmental Protection Agency (Cal/EPA) Environmental Justice Action Plan calls for guidelines for evaluating “cumulative impacts.” As a first step toward such guidelines, a screening methodology for assessing cumulative impacts in communities was developed. The method, presented here, is based on the working definition of cumulative impacts adopted by Cal/EPA [1]: “Cumulative impacts means exposures, public health or environmental effects from the combined emissions and discharges in a geographic area, including environmental pollution from all sources, whether single or multi-media, routinely, accidentally, or otherwise released. Impacts will take into account sensitive populations and socio-economic factors, where applicable and to the extent data are available.” The screening methodology is built on this definition as well as current scientific understanding of environmental pollution and its adverse impacts on health, including the influence of both intrinsic, biological factors and non-intrinsic socioeconomic factors in mediating the effects of pollutant exposures. It addresses disparities in the distribution of pollution and health outcomes. The methodology provides a science-based tool to screen places for relative cumulative impacts, incorporating both the pollution burden on a community- including exposures to pollutants, their public health and environmental effects- and community characteristics, specifically sensitivity and socioeconomic factors. The screening methodology provides relative rankings to distinguish more highly impacted communities from less impacted ones. It may also help identify which factors are the greatest contributors to a community’s cumulative impact. It is not designed to provide quantitative estimates of community-level health impacts. A pilot screening analysis is presented here to illustrate the application of this methodology. Once guidelines are adopted, the methodology can serve as a screening tool to help Cal/EPA programs prioritize their activities and target those communities with the greatest cumulative impacts. Full article

The Child-Specific Aggregate Cumulative Human Exposure and Dose (CACHED) framework integrates micro-level activity time series with mechanistic exposure equations, environmental concentration distributions, and physiologically-based pharmacokinetic components to estimate exposure for multiple routes and chemicals. CACHED was utilized to quantify cumulative and aggregate exposure and dose estimates for a population of young farmworker children and to evaluate the model for chlorpyrifos and diazinon. Micro-activities of farmworker children collected concurrently with residential measurements of pesticides were used in the CACHED framework to simulate 115,000 exposure scenarios and quantify cumulative and aggregate exposure and dose estimates. Modeled metabolite urine concentrations were not statistically different than concentrations measured in the urine of children, indicating that CACHED can provide realistic biomarker estimates. Analysis of the relative contribution of exposure route and pesticide indicates that in general, chlorpyrifos non-dietary ingestion exposure accounts for the largest dose, confirming the importance of the micro-activity approach. The risk metrics computed from the 115,000 simulations, indicate that greater than 95% of these scenarios might pose a risk to children’s health from aggregate chlorpyrifos exposure. The variability observed in the route and pesticide contributions to urine biomarker levels demonstrate the importance of accounting for aggregate and cumulative exposure in establishing pesticide residue tolerances in food. Full article

The maximum cumulative ratio (MCR) developed in previous work is a tool to evaluate the need to perform cumulative risk assessments. MCR is the ratio of the cumulative exposures to multiple chemicals to the maximum exposure from one of the chemicals when exposures are described using a common metric. This tool is used to evaluate mixtures of chemicals measured in samples of untreated ground water as source for drinking water systems in the United States. The mixtures of chemicals in this dataset differ from those examined in our previous work both in terms of the predicted toxicity and compounds measured. Despite these differences, MCR values in this study follow patterns similar to those seen earlier. MCR values for the mixtures have a mean (range) of 2.2 (1.03–5.4) that is much smaller than the mean (range) of 16 (5–34) in the mixtures in previous study. The MCR values of the mixtures decline as Hazard Index (HI) values increase. MCR values for mixtures with larger HI values are not affected by possible contributions from chemicals that may occur at levels below the detection limits. This work provides a second example of use of the MCR tool in the evaluation of mixtures that occur in the environment. Full article

We describe an approach to examine the association between exposure to chemical mixtures and a health outcome, using as our case study polychlorinated biphenyls (PCBs) and hypertension. The association between serum PCB and hypertension among participants in the 1999–2004 National Health and Nutrition Examination Survey was examined. First, unconditional multivariate logistic regression was used to estimate odds ratios and associated 95% confidence intervals. Next, correlation and multicollinearity among PCB congeners was evaluated, and clustering analyses performed to determine groups of related congeners. Finally, a weighted sum was constructed to represent the relative importance of each congener in relation to hypertension risk. PCB serum concentrations varied by demographic characteristics, and were on average higher among those with hypertension. Logistic regression results showed mixed findings by congener and class. Further analyses identified groupings of correlated PCBs. Using a weighted sum approach to equalize different ranges and potencies, PCBs 66, 101, 118, 128 and 187 were significantly associated with increased risk of hypertension. Epidemiologic data were used to demonstrate an approach to evaluating the association between a complex environmental exposure and health outcome. The complexity of analyzing a large number of related exposures, where each may have different potency and range, are addressed in the context of the association between hypertension risk and exposure to PCBs. Full article

In 2008, the statute authorizing the Minnesota Pollution Control Agency (MPCA) to issue air permits was amended to include a unique requirement to analyze and consider “cumulative levels and effects of past and current environmental pollution from all sources on the environment and residents of the geographic area within which the facility's emissions are likely to be deposited.” Data describing the Statute Area suggest it is challenged by environmental and socioeconomic concerns, i.e., concerns which are often described by the phrase ‘environmental equity’. With input from diverse stakeholders, the MPCA developed a methodology for implementing a cumulative levels and effects analysis when issuing air permits in the designated geographic area. A Process Document was created defining explicit steps a project proposer must complete in the analysis. An accompanying Reference Document compiles all available environmental health data relevant to the Statute Area that could be identified. The final cumulative levels and effects methodology is organized by health endpoint and identifies hazard, exposure and health indices that require further evaluation. The resulting assessment is summarized and presented to decision makers for consideration in the regulatory permitting process. We present a description of the methodology followed by a case study summary of the first air permit processed through the “cumulative levels and effects analysis”. Full article

Community-based cumulative risk assessment requires characterization of exposures to multiple chemical and non-chemical stressors, with consideration of how the non-chemical stressors may influence risks from chemical stressors. Residential radon provides an interesting case example, given its large attributable risk, effect modification due to smoking, and significant variability in radon concentrations and smoking patterns. In spite of this fact, no study to date has estimated geographic and sociodemographic patterns of both radon and smoking in a manner that would allow for inclusion of radon in community-based cumulative risk assessment. In this study, we apply multi-level regression models to explain variability in radon based on housing characteristics and geological variables, and construct a regression model predicting housing characteristics using U.S. Census data. Multi-level regression models of smoking based on predictors common to the housing model allow us to link the exposures. We estimate county-average lifetime lung cancer risks from radon ranging from 0.15 to 1.8 in 100, with high-risk clusters in areas and for subpopulations with high predicted radon and smoking rates. Our findings demonstrate the viability of screening-level assessment to characterize patterns of lung cancer risk from radon, with an approach that can be generalized to multiple chemical and non-chemical stressors. Full article

Due to the vast number of possible combinations of chemicals to which individuals are exposed and the resource-intensive nature of cumulative risk assessments, there is a need to determine when cumulative assessments are most required. This paper proposes the use of the maximum cumulative ratio (MCR) as a tool for this evaluation. MCR is the ratio of the cumulative toxicity received by an individual from exposure to multiple chemical stressors to the largest toxicity from a single chemical stressor. The MCR is a quantitative measure of the difference in an individual’s toxicity estimated using a chemical-by-chemical approach and using an additive model of toxicity. As such, it provides a conservative estimate of the degree to which individuals’ toxicities could be underestimated by not performing a cumulative risk assessment. In an example application, MCR is shown to be applicable to the evaluation of cumulative exposures involving up to 81 compounds and to provide key insights into the cumulative effects posed by exposures to multiple chemicals. In this example, MCR values suggest that individuals exposed to combinations of chemicals with the largest Hazard Indices were dominated by the contributions of one or two compounds. Full article

Systematic evaluation of cumulative health risks from the combined effects of multiple environmental stressors is becoming a vital component of risk-based decisions aimed at protecting human populations and communities. This article briefly examines the historical development of cumulative risk assessment as an analytical tool, and discusses current approaches for evaluating cumulative health effects from exposure to both chemical mixtures and combinations of chemical and nonchemical stressors. A comparison of stressor-based and effects-based assessment methods is presented, and the potential value of focusing on viable risk management options to limit the scope of cumulative evaluations is discussed. The ultimate goal of cumulative risk assessment is to provide answers to decision-relevant questions based on organized scientific analysis; even if the answers, at least for the time being, are inexact and uncertain. Full article

Regulatory agencies are under increased pressure to consider broader public health concerns that extend to multiple pollutant exposures, multiple exposure pathways, and vulnerable populations. Specifically, cumulative risk assessment initiatives have stressed the importance of considering both chemical and non-chemical stressors, such as socioeconomic status (SES) and related psychosocial stress, in evaluating health risks. The integration of non-chemical stressors into a cumulative risk assessment framework has been largely driven by evidence of health disparities across different segments of society that may also bear a disproportionate risk from chemical exposures. This review will discuss current efforts to advance the field of cumulative risk assessment, highlighting some of the major challenges, discussed within the construct of the traditional risk assessment paradigm. Additionally, we present a summary of studies of potential interactions between social stressors and air pollutants on health as an example of current research that supports the incorporation of non-chemical stressors into risk assessment. The results from these studies, while suggestive of possible interactions, are mixed and hindered by inconsistent application of social stress indicators. Overall, while there have been significant advances, further developments across all of the risk assessment stages (i.e., hazard identification, exposure assessment, dose-response, and risk characterization) are necessary to provide a scientific basis for regulatory actions and effective community interventions, particularly when considering non-chemical stressors. A better understanding of the biological underpinnings of social stress on disease and implications for chemical-based dose-response relationships is needed. Furthermore, when considering non-chemical stressors, an appropriate metric, or series of metrics, for risk characterization is also needed. Cumulative risk assessment research will benefit from coordination of information from several different scientific disciplines, including, for example, toxicology, epidemiology, nutrition, neurotoxicology, and the social sciences. Full article

Simultaneous or sequential exposure to multiple chemicals may cause interactions in the pharmacokinetics (PK) and/or pharmacodynamics (PD) of the individual chemicals. Such interactions can cause modification of the internal or target dose/response of one chemical in the mixture by other chemical(s), resulting in a change in the toxicity from that predicted from the summation of the effects of the single chemicals using dose additivity. In such cases, conducting quantitative cumulative risk assessment for chemicals present as a mixture is difficult. The uncertainties that arise from PK interactions can be addressed by developing physiologically based pharmacokinetic (PBPK) models to describe the disposition of chemical mixtures. Further, PK models can be developed to describe mechanisms of action and tissue responses. In this article, PBPK/PD modeling efforts conducted to investigate chemical interactions at the PK and PD levels are reviewed to demonstrate the use of this predictive modeling framework in assessing health risks associated with exposures to complex chemical mixtures. Full article