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NSG 4076 Discussion Aggregate Assessment

NSG 4076 Discussion Aggregate Assessment

NSG 4076 Discussion Aggregate Assessment

Discussion Question:

The community is the focus of care in community and public health nursing, hence the community is the client receiving care. The nurse’s job is to assess health concerns and establish a comprehensive plan of treatment to address them. Child care centers, towns, counties, elder centers, homeless shelters, ethnic groups, faith-based organizations, work sites, schools, and other populations are examples of aggregates or target populations in the community. Identify and identify a few targeted populations in your community that you are interested in, as well as the rationale for your choices.

 

Cumulative and aggregate exposure assessments are referred to as “combined exposure assessments” because cumulative assessments estimate exposure to multiple stressors by multiple routes. Aggregate assessments estimate exposures to a single stressor from multiple sources and by multiple routes.

Cumulative assessments more realistically depict real-world exposure, but also introduce a layer of complexity not found in traditional exposure assessments, which evaluate stressors individually.

Although exposure assessments conducted by EPA are usually focused on exposures to chemical, non-chemical stressors can be considered in a cumulative assessment – and can sometimes be very important. Biological threats (such as mold or other microorganisms), physical threats (e.g., noise, temperature), can cause direct effects on those exposed (such as hearing loss). They can modify the exposures or level of effects.

NSG 4076 Discussion Aggregate Assessment

NSG 4076 Discussion Aggregate Assessment

(U.S. EPA, 1992) Guidelines for Exposure Assessment

Whether a cumulative or aggregate approach (or some combination of the two) is used will vary according to the scope and objective of the assessment. The aggregate exposure assessment approach is commonly used when receptors can be exposed to a single contaminant in various ways.

For example, residues of the same pesticide could be found on multiple foods, in water, and/or in products used in and around the home. A receptor might have the opportunity to take up the contaminant via dermal contact, inhalation, ingestion, and other routes.

On the other hand, cumulative exposure assessments are conducted for contaminants that produce toxic responses by the same mode of action. For example, cumulative exposure could occur for a population in a specific location that is exposed to a variety of stressors

Cumulative exposure assessments can be conducted for chemical stressors and also for non-chemical stressors, including:

“current physical and mental health status and past exposure histories…and social factors such as community property values, sources of income, level of income, and standard of living” (U.S. EPA, 2003).

according to NSG 4076 Discussion Aggregate Assessment, examples of non-chemical stressors could include biological threats (e.g., mold or other microorganisms) and physical threats (e.g., noise, odor, and temperature). Non-chemical stressors might increase the vulnerability of a population to exposure or the effects of exposure to chemical stressors.

Cumulative exposures are of particular interest when conducting community-based assessments. Community-based assessment are intended to encompass exposure to both chemical and non-chemical stressors potentially affecting a community. A community can be defined as “a group of individuals in the same geographical area and/or with the same demographic attributes considered to be key factors in assessing human exposure” (Zartarian and Schultz, 2010).

EPA has developed a range of tools, guidelines, and other resources (including grant programs) intended for use by community groups or other organizations interested in evaluating cumulative exposure and risk for a community.

Cumulative, community-based assessments are a cornerstone of assessments of environmental justice issues because they can characterize exposures or risks that disproportionately and unfairly affect certain communities. (See EPA’s Environmental Justice website for more information.)

Listed below are characteristics typical of aggregate and cumulative assessments, but these are not necessarily components of all aggregate or cumulative assessments.

Aggregate Cumulative
Inputs
  • Single stressor (chemical only)
  • Individual action of stressor
  • Different modes of action
  • Summation of exposures across all pathways
  • Multiple stressors (chemicals and non-chemicals)
  • Consider interactions among stressors
  • Consider exposure to mixtures
  • Often similar mode of action
  • Additivity of exposure not assumed as a default approach
Aggregate exposure assessments often include a summation of all potential exposure pathways for a single stressor. This is a conservative, health-protective approach. It  assumes that a single receptor will be exposed to one stressor through all possible exposure pathways.

Cumulative exposures to multiple stressors, on the other hand, generally are not  unless they act via the same mode of action. Cumulative exposure assessments might also take into account .  It may also be necessary to determine how the various stressors interact to amplify or attenuate a response (i.e., , or additive).

Tools
  • Multipathway models
  • Models that consider a single chemical
  • Multimedia models
  • Models that consider exposure to mixtures
Both aggregate and cumulative assessments can use either a deterministic or a probabilistic approach.

Higher-tier or more refined exposure assessments for combined exposures are more common for aggregate exposure scenarios than for cumulative scenarios. This is due to the complexities of determining exposure that encompasses information about multiple stressors and multiple pathways.

Aggregate and cumulative exposure assessments can include both deterministic and probabilistic components. See the Deterministic and Probabilistic Module in this tool set for more information and resources. Screening-level assessments for combined exposures are typically more resource-intensive and complex, than screening-level assessments for single stressors.

Aggregate exposure can be assessed using tools available for exposure to agricultural and residential pesticides (e.g., CALENDEX, CARES, LifeLine), or exposure to chemicals in the environment (e.g., SHEDS, TRIM).

Cumulative exposures can be assessed using similar tools (e.g., APEX, CALENDEX). Fewer tools are available for non-chemical stressors, although some guidelines and resources have been developed by EPA and other groups.

Results
  • Effect of single stressor
  • Useful to inform cumulative assessments
  • Generally quantitative
  • Combined effects of stressors
  • Greater ability to assess population vulnerability
  • Quantitative and/or qualitative
according to NSG 4076 Discussion Aggregate Assessment, an aggregate approach produces a summation of all potential exposure pathways for a single chemical stressor. This approach does not consider stressors beyond the single chemical of interest.

For example, this is commonly used in the regulation of pesticides. EPA conducts risk assessments for active ingredients in pesticides by evaluating all of the potential pathways of exposure for pesticide residues to determine the potential risk from aggregate exposure.

NSG 4076 Discussion Aggregate Assessment states that, Cumulative assessments address the overall impact on human health of multiple stressors (chemical and non-chemical) that often act by the same mechanism of toxicity. The presence of multiple stressors, however, does not necessarily mean that all of the stressors will cause or contribute to an adverse effect.

according to NSG 4076 Discussion Aggregate Assessment, cumulative exposure assessment is not always the simple sum of multiple, aggregate exposure assessments. Incorporating the effects of exposure to non-chemical stressors often results in a qualitative description of exposure or risk because numeric values for these factors are often not available.

Identification and characterization of in terms of /sensitivity in populations is limited when using aggregate approaches. However, it may be possible with cumulative approaches, provided a relationship exists between these factors and changes in risk U.S. EPA, 2003). Research to improve the ability of cumulative exposure assessments to identify areas of high exposure and high vulnerability is underway.


Guidance Tools

The following resources provide information for conducting aggregate and cumulative exposure assessments.

Tool
Type
Tools Description
Agency for Toxic Substances and Disease Registry (ATSDR). (2004). Framework for Assessing Health Impacts of Multiple Chemicals and Other Stressors This manual provides guidance on assessing exposure to chemical mixtures at hazardous waste sites and in determining how that exposure might impact public health due to additivity and/or interactions of a combination of chemicals.
enHealth. (2012). Environmental Health Risk Assessment: Guidelines for Assessing Human Health Risks from Environmental Hazards   Exit This guidance document provides information on basic concepts in environmental health risk assessment, including problem formulation, tiered approaches to exposure assessment. Specific guidance is provided for several topics related to exposure assessment including: assessing exposure from multiple routes and sources of exposure, probabilistic exposure modelling, and biomonitoring.
enHealth. (2002). Guidelines for Assessing Human Health Risks from Environmental Hazards   Exit This Australian guidance document provides a methodology and checklist designed for environmental health risk assessment of chemical health hazards with the goal of streamlining environmental health risks assessments to increase precision and timeliness of reports and increase transparency of the decision-making process. Although the methodology was designed for chemical health hazards, it can be applied to a broad range of environmental health risk assessments including physical, microbiological, and mixtures of environmental health hazards.
Interagency Microbiological Risk Assessment Guideline Workgroup. (2012). Microbial Risk Assessment (MRA) Guideline: Pathogenic Microorganisms with Focus on Food and Water This document developed jointly by U.S. EPA and USDA Food Safety and Inspection Service provides a framework for conducting risk assessments of pathogens in food and water. The document provides a flexible set of approaches, methods, and tools for use in microbial risk assessment.
Meek, ME; Boobis, AR; Crofton, KM; Heinemeyer, G; van Raaij , M; Vickers, C. (2011). WHO/IPCS Assessment of Combined Exposures to Multiple Chemicals   Exit This resource describes the WHO/IPCS prioritization framework resulting from a workshop on aggregate and cumulative risk assessment. The framework uses a hierarchy to organize approaches according to refinement, taking into account both exposure and hazard. Predictive and probabilistic techniques, uncertainty, and real world applications are discussed in this document.
National Environmental Justice Advisory Council (NEJAC). (2004). Ensuring Risk Reduction in Communities with Multiple Stressors: Environmental Justice and Cumulative Risks/Impacts This document provides NEJAC’s recommendations on short-term and long-term actions EPA should take to implement the concepts contained in its Framework for Cumulative Risk Assessment to ensure environmental justice for all communities and tribes.
National Research Council (NRC). (2008). Phthalates and Cumulative Risk Assessment: The Tasks Ahead   Exit This book provides guidance for assessing the risk of phthalates, chemicals found in many consumer products that have been shown to affect the development of the male reproductive system of laboratory animals. The book suggests an approach for cumulative risk assessment that can serve as a model for evaluating the health risks of other types of chemicals.
U.S. EPA. Assessing Pesticide Cumulative Risk This resource provides information related to EPA’s framework for conducting cumulative risk assessment of pesticides, specifically 5 groups of pesticides—grouped according to common mechanisms of toxicity: organophosphates, n-methyl carbamates, triazines, chloroacetanilides, and pyrethrins/pyrethroids. The website includes links to other resources, including guidance documents and exposure assessment models.
U.S. EPA. (2004). Chapter 14 – Overview and Getting Started: Planning and Scoping the Multipathway Risk Assessment. In Air Toxics Risk Assessment (ATRA) Reference Library Volume 1: Technical Resource Manual Chapter 14 provides an overview of multipathway exposure assessment, a discussion of planning and scoping, and tiered multipathway risk assessments. It is included in Part III of Volume I – Human Health Risk Assessment: Multipathway.
U.S. EPA. (2004). Chapter 15 – Problem Formulation: Multipathway Risk Assessment. In Air Toxics Risk Assessment (ATRA) Reference Library Volume 1: Technical Resource Manual Chapter 15 discusses the development of the multipathway conceptual model and includes sections on identifying exposure pathways, exposed populations, and endpoints and metrics. It is included in Part III of Volume I – Human Health Risk Assessment: Multipathway.
U.S. EPA. (2003). Chapter 2 – The Planning, Scoping, and Problem Formulation Phase. In Framework for Cumulative Risk Assessment Chapter 2 of this report discusses problem formulation in cumulative risk assessments. Sections on planning and scoping, developing the conceptual model, constructing an analysis plan, and lessons learned related to planning and scoping are included.
U.S. EPA. (2004). Community Air Screening How-To Manual, A Step-by-Step Guide to Using Risk-Based Screening to Identify Priorities for Improving Outdoor Air Quality This document presents a step-by-step guide for communities to conducting a cumulative risk assessment focused on emissions of pollutants to air as part of EPA’s Community Action for a Renewed Environment (CARE) program.
U.S. EPA. (2007). Concepts, Methods, and Data Sources for Cumulative Health Risk Assessment of Multiple Chemicals, Exposures and Effects: A Resource Document This resource provides concepts, methods, and data sources for conducting cumulative risk assessments for populations exposed to multiple chemicals, considering multiple exposure routes and multiple health endpoints. This document also address complications associated with evaluating multiple chemicals, such as toxicological interactions and environmental transformations of the chemical components.
U.S. EPA. (2003). Framework for Cumulative Risk Assessment The Framework for Cumulative Risk Assessment outlines the basic steps for conducting a cumulative risk assessment. Guidance is provided on general concepts of cumulative risk. The framework is not intended to serve as a step-by-step guide, but rather a resource for cumulative risk assessment and a building block toward the development of future guidance.
U.S. EPA. (2001). General Principles for Performing Aggregate Exposure and Risk Assessments for Pesticides This resource provides information on data inputs for aggregate exposure assessments, framework for expanded aggregate exposure, and questions to consider when conducting aggregate assessments.
U.S. EPA. (2002). Guidance on Cumulative Risk Assessment of Pesticide Chemicals That Have a Common Mechanism of Toxicity This guidance document provides information on evaluating and estimating potential human risks associated with multichemical and multipathway exposures to pesticides that act by a common mechanism of toxicity.
U.S. EPA. (1997). Guidance on Cumulative Risk Assessment, Part 1: Planning and Scoping This document precedes EPA’s Framework for Cumulative Risk Assessment and provides information on the planning and scoping stage of cumulative risk assessments. This resource also documents EPA’s movement beyond traditional single-stressor, single-pathway assessments.
U.S. EPA. (1992). Guidelines for Exposure Assessment The Guidelines for Exposure Assessment is the “go to” resource for planning and conducting human exposure assessments. Guidance is also provided on general concepts of exposure, including definitions, uncertainty, suggestions for presenting results, and tools used for conducing exposure assessments. Information relevant to wildlife exposure to chemicals and human exposure to biological, radiological, and noise agents is also discussed in this resource.
U.S. EPA. (1986). Guidelines for the Health Risk Assessment of Chemical Mixtures The 1986 guidelines describe procedures on evaluating and estimating potential human risks associated with exposures to chemical mixtures consisting of two or more chemicals.
U.S. EPA. (1997). Guiding Principles for Monte Carlo Analysis Guiding Principles for Monte Carlo Analysis provides a minimum set of principles to ensure good scientific practices when developing a probabilistic assessment with a focus on Monte Carlo analysis. This resource also includes guidance for assessors on selecting input data and distributions for probabilistic assessments.
U.S. EPA. Revised Organophosphate Cumulative Risk Assessment (OPCRA) EPA conducted a cumulative exposure assessment for organophosphate pesticides revising the preliminary cumulative risk assessment conducted in 2001. The preliminary assessment was designed to test and improve method for conducting cumulative risk assessments in the future. The revised assessment evaluated more than 1,000 organophosphate pesticides in food, water, and other potential residential exposures.
U.S. EPA. (1989). Risk Assessment Guidance for Superfund (RAGS): Volume I: Human Health Evaluation Manual (Part A) The Risk Assessment Guidance for Superfund (RAGS): Volume I: Human Health Evaluation Manual (Part A) provides guidance for evaluating human health effects as part of a baseline risk assessment. This guidance document includes 10 chapters and two appendices describing topics including: planning, data collection and evaluation, exposure and toxicity assessment, and risk characterization.
U.S. EPA. (2000). Supplementary Guidance for Conducting Health Risk Assessment of Chemical Mixtures This supplemental guidance document details principles and procedures mentioned but not thoroughly explained in 1986 Guidelines for the Health Risk Assessment of Chemical Mixtures.
World Health Organization (WHO)/International Programme on Chemical Safety (IPCS). (2009). Assessment of Combined Exposures to Multiple Chemicals: Report of a WHO/IPCS International Workshop   Exit This document reports on a workshop on aggregate/cumulative risk assessment conducted to help develop a framework for the assessment of combined risk from exposure to multiple chemicals. The goal of the workshop was to describe the state of the art in this area of risk assessment and identify next steps.
World Health Organization (WHO)/International Programme on Chemical Safety (IPCS). (2009). Draft WHO/IPCS Framework for Risk Assessment of Combined Exposures to Multiple Chemicals   Exit This website contains a description of the draft WHO/IPCS Framework for Risk Assessment of Combined Exposures to Multiple Chemicals, which is a document that describes a framework for the assessment of combined risk from exposure to multiple chemicals. The frameworks for exposure and hazard assessments are presented as tiers—from simple (Tier 0) to more refined (Tier 3). This document is supplemented by two case studies that apply the frameworks—one case study on polybrominated diphenyl ethers (PBDEs) and the other on carbamates.

Methods

  • Tools for Conducting Aggregate and Cumulative Assessments

Thoughtful planning, scoping, and problem formulation is important. It can help to determine the stressor(s) of interest, the potential effects of the stressor(s), and possible interactions between stressors.

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Topics that might require consideration when conducting a combined exposure assessments include the following.

  • Combined Effects of Multiple Stressors – Potential synergistic and antagonistic interactions related to exposure to multiple stressors can increase or decrease the expected effects of the stressors.
  • Time – Exposure during susceptible lifestages might lead to increased effects; these are often described as “critical windows of exposure.” In addition, the sequence of exposure should be considered especially for stressors known to have synergistic or antagonistic effects.
  • Background Sources of Exposure – When examining combined exposures, background sources are typically considered to be important sources of exposure.
  • Assessing Exposure to Mixtures – Mixtures can be assessed as whole mixtures or as multi-component mixtures, but for either approach, describing the assumptions made (e.g., additive effects, toxicologic similarity) and the potential uncertainty in tNSG 4076 Discussion Aggregate Assessment states that the assessment is critical.
  • Assessing Effect of Exposure to Non-Chemical Stressors – Non-chemical stressors include biological, radiological, and other physical stressors as well as socioeconomic stressors and lifestyle conditions. Combining the effects of exposure to chemical and non-chemical stressors is an area of continued research. For example, epigenetic studies examine how chemical and non-chemical stressors lead to changes in gene expression.
  • Quantification of Risks – Combining exposure and effects of chemical and non-chemical stressors with numeric exposure or risk estimates is difficult and sometimes qualitative descriptions (e.g., high, medium, low, weight of evidence descriptors) are necessary to summarize the expected exposure or risk.

Organizations in the United States and in other countries have begun to develop frameworks and guidance for combined exposure and risk assessments.  However, but this branch of exposure assessment science is continuing to develop as more combined exposure assessments are conducted and more of the complexities resolved.


Tools for Conducting Aggregate and Cumulative Assessments

The following resources provide information for conducting aggregate and cumulative exposure assessments.

Tool
Type
Tools Description
ILSI Research Foundation. Cumulative and Aggregate Risk Evaluation System (CARES)   Exit According to this website, “CARES® (Cumulative and Aggregate Risk Evaluation System) was originally developed in 2001 as a population, calendar-based, probabilistic model for estimating aggregate and cumulative exposure and risk across multiple routes: food, water, and residential for pesticides. The model is undergoing significant upgrades to meet current and future needs . . .”
Novigen Sciences, Inc. Dietary Exposure Evaluation Model – Food Commodity Intake Database (DEEM-FCID)/Calendex Model DEEM-FCID/Calendex integrates different pathways (e.g., dietary [food and water] and residential) and routes of exposure (oral, dermal, inhalation) using a calendar-based probabilistic approach. One of the important factors of this approach is that it provides estimates of risk that reflect aggregate and cumulative exposure to discrete individuals, with exposure pathways and routes appropriately linked for the scenarios being assessed. according to NSG 4076 Discussion Aggregate Assessment, DEEM-FCID/Calendex also allows one to estimate exposure before and after the use of a chemical, as well as during degradation periods. Calendar-based assessments maintain the integrity of the individual by capturing the location of the exposed individual, the time of year in which he or she was exposed, and the patterns of exposure. Calendex also allows for a variety of time-breakout options for the analysis of exposure.
The Lifeline Group. LifeLine™ User Manual v1.0 (Archived) LifeLine™ software for modeling aggregate and cumulative exposure to pesticides was designed to characterize population-based risks from pesticide residues in food and tap water as well as in the home following residential uses.
U.S. EPA. Analysis and Products from NHEXAS; National Human Exposure Assessment Survey This website provides links to NHEXAS work products.
U.S. EPA. Community-Focused Exposure and Risk Screening Tool (C-FERST) EPA developed C-FERST as a “one-stop-shop community mapping and assessment tool” that assessors can use when conducting multimedia community assessments. The tool is a web-based geographic information system (GIS) and information resource to be used to characterize cumulative risk from chemical and non-chemical stressors and identify communities affected by these stressors. C-FERST was developed to help assess disproportionate impacts in communities and serve as a tool in environmental justice efforts.
U.S. EPA. Stochastic Human Exposure and Dose Simulation (SHEDS) The Stochastic Human Exposure and Dose Simulation (SHEDS) is a model that can be used to simulate chemical exposures for a population over time. This model estimates exposure for a variety of multimedia and multipathway environmental chemicals and has been modified for use in specific exposure scenarios (e.g., SHEDS-Wood and SHEDS-Pesticides). Other SHEDS modules have been developed to address toxic chemicals in the air (SHEDS-ATOX) and to predict exposures to particulate matter (SHEDS-PM). SHEDS-Multimedia includes the SHEDS-Residential and SHEDS-Dietary modules.
U.S. EPA. (1987). Total Exposure Assessment Methodology (TEAM) Study EPA designed this study to develop methods to measure individual total exposure (through air, food, and water) to toxic and carcinogenic chemicals, including VOCs, pesticides, and carbon monoxide. Breath, personal air, outdoor air, and water samples were collected for 30 VOCs.

Input Data

Data availability ranges from relatively abundant for many chemical stressors to somewhat sparse for many biological and radiological stressors. Almost no information is available for the many other types of stressors (U.S. EPA, 2003).

In many cases, data may need to be collected specifically to support a combined risk assessment. For example, data used for a cumulative assessment should ideally “conserve the covariance and dependency structures associated with the [stressors] of concern” [ILSI (1999) as cited in EPA (2003)]. Moreover, because the exposure and dose-response analyses cannot easily be separated in a combined assessment, extremely detailed exposure estimates are only useful when the dose-response data are equally detailed.

Descriptions of the input data for aggregate and cumulative assessments can be found in multiple Tool Sets on the home page. In fact, the Indirect Estimation (Scenario Evaluation) module of the Approaches Tool Set includes the following categories for input data:

  • Sources and Releases
  • Fate and Transport
  • Concentrations
  • Characterizing Populations
  • Exposure Factors

Tools related to input data for fate and transport, concentrations, and exposure factors are also described in the Media and Routes Tool Sets.

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Quantitative input data to characterize the effects of non-chemical stressors are often lacking, but recent journal articles and symposia have proposed strategies for incorporating these effects. Refer to:

  • Lewis, AS; Sax, SN; Wason, SC; Campleman, SL. (2011). Non-chemical stressors and cumulative risk assessment: An overview of current initiatives and potential air pollutant interactions. International Journal of Environmental Research and Public Health 8:2020-2073.
  • Rider, CV; Dourson, ML; Hertzberg, RC; Mumtaz, MM; Price, PS; Simmons, JE. (2012). Incorporating nonchemical stressors into cumulative risk assessments. Toxicol Sci.: 127(1):10-7.

Applications

A number of example assessments are available that demonstrate the application of a combined exposure approach.

Programs Using a Combined Approach to Estimate Exposure and Risk

according to NSG 4076 Discussion Aggregate Assessment, cumulative assessments of pesticides and residual risks of air toxics by EPA are examples of a how a combined approach has been used. These example illustrate how these approaches can be used to better understand the complicated relationships that exist when analyzing multiple chemicals, routes of exposure, and pathways.

  • Pyrethroids and Pyrethrins
    EPA’s Office of Pesticide Programs conducted a cumulative exposure assessment for the pyrethroid pesticides. Pyrethroids are a family of chemicals with similar neurotoxic modes of action. EPA considered acute and chronic exposure to residues of pyrethroids in food, water, and other potential residential exposures; oral, dermal, and inhalation exposures were considered.
  • Revised Organophosphate Cumulative Risk Assessment (OPCRA)
    EPA conducted a cumulative exposure assessment for organophosphate pesticides. The preliminary assessment was designed to test and improve method for conducting cumulative risk assessments in the future. The revised assessment evaluated more than 1,000 organophosphate pesticides in food, water, and other potential residential exposures.
  • OAQPS National Air Toxics Assessments (NATA)
    EPA’s National-Scale Air Toxics Assessment (NATA) is a screening tool to prioritize pollutants, emission sources, and locations of interest for further study. NATA estimates exposures at census blocks and then estimates risk at the population level, and the number of people estimated to be above certain cancer risk levels. Since 1996, four NATA assessments have been completed to characterize the chronic cancer risk estimates and noncancer hazards from inhaling air toxics

References

  • Lewis, AS; Sax, SN; Wason, SC; Campleman, SL. (2011). Non-Chemical Stressors and Cumulative Risk Assessment: An Overview of Current Initiatives and Potential Air Pollutant Interactions  [Review]EXIT . Int J Environ Res Public Health 8: 2020-2073.
  • Rider, CV; Dourson, ML; Hertzberg, RC; Mumtaz, MM; Price, PS; Simmons, JE. (2012). Incorporating Nonchemical Stressors Into Cumulative Risk AssessmentsEXIT . Toxicol Sci 127: 10-17.
  • U.S. EPA. (1992). Guidelines for Exposure Assessment. (EPA/600/Z-92/001). Washington, DC.
  • U.S. EPA. (2003). Framework for Cumulative Risk Assessment. (EPA/630/P-02/001F). Washington, DC.
  • Zartarian, VG; Schultz, BD. (2010). The EPA’s Human Exposure Research Program for Assessing Cumulative Risk in CommunitiesEXIT . J Expo Sci Environ Epidemiol 20: 351-358
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