Foundations and Frameworks for 

Human Microbial Risk Assessment 

Submitted by: 

Rebecca T. Parkin, PhD, MPH 

Center for Risk Science and Public Health 

School of Public Health and Health Services 

The George Washington University Medical Center 

Washington, DC 

Submitted to: 

U.S. Environmental Protection Agency 

Washington, DC 

February 2008 
DISCLAIMER 

This report has been funded by the U.S. Environmental Protection Agency (EPA) under 

Contract EP07H000172 to The George Washington University Medical Center School of Public 

Health and Health Services. It does not necessarily reflect the views or policies of the EPA, and 

no official endorsement should be inferred. Mention of trade names or commercial products does 

not constitute endorsement or recommendation for use. 

ABSTRACT 

Risk assessment is one part of a comprehensive risk management process, known as risk 

analysis. The risk characterization step within microbial risk assessment (MRA) serves as the 

bridge between risk assessment and risk management. Although a variety of MRA approaches 

are in use, limited analyses of MRA frameworks or their underlying principles and concepts 

exist. Organizations’ desires to develop a unified MRA approach have been tempered by the 

realization that flexibility is essential for addressing various legislated mandates and regulations 

and for meeting diverse field application needs. This paper was developed to help EPA’s Risk 

Assessment Forum, Microbial Risk Assessment Working Group to obtain new knowledge and 

insights about the nature and characteristics of available MRA frameworks and applications. 

This report includes a review of recent MRA policies and guidelines and a comparative analysis 

of 13 MRAs conducted or sponsored by governments worldwide. Two forms of risk 

assessment—chemical risk assessment and ecological risk assessment—provide the foundations 

for MRA as it was practiced at the time of this review. The National Academy’s widely used 

four-step risk assessment paradigm is the prevailing context from which many modelers have 

approached microbial risk assessment. The most commonly cited underlying principles for 

MRA include: make public health protection the priority, base MRA on sound science, ensure 

transparency, use a structured and consistent approach, and allow for iterations. The dynamic 

aspects of pathogens, environmental processes, human populations, and the interrelationships of 

these entities are increasingly being noted as important MRA modeling issues. Four 

fundamental types of MRA frameworks were found: chemical risk assessment modified 

chemical risk assessment, problem definition followed by chemical risk assessment, and the 

International Life Sciences Institute (ILSI) framework. No agency has applied the ILSI 

framework in a complete MRA. Organizations use the chemical risk assessment paradigm for 

different purposes and work through the components in a variety of sequences and depths, 

tailoring the process to meet their needs. Few MRAs include problem formulation, but most 

i 
include a problem statement or definition. Some organizations have developed modules (selfcontained mathematical models) to represent parts of the source-to-health effects chain. Further, 

the report describes environmental media-specific issues and approaches. Recommendations are 

made for advancing MRA through systems methodologies and communication strategies. 

Preferred Citation: 

Parkin, RT. (2007). Foundations and frameworks for microbial risk assessments. Center for Risk Science and Public 

Health, School of Public Health and Health Services, The George Washington University Medical Center 

Washington, DC. Prepared for the U.S. Environmental Protection Agency National Center for Environmental 

Assessment. 

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CONTENTS 

LIST OF TABLES....................................................................................................... vi 

LIST OF ABBREVIATIONS AND ACRONYMS ................................................... vii 

PREFACE.................................................................................................................. viii 

AUTHORS, CONTRIBUTORS, AND REVIEWERS ............................................... ix 

EXECUTIVE SUMMARY ...........................................................................................x 

1. INTRODUCTION ...................................................................................................1 

1.1. BACKGROUND ............................................................................................1 

1.1.1. Historical Perspective .........................................................................1 

1.1.2. Origin of this Document .....................................................................3 

1.2. STATEMENT OF PURPOSE ........................................................................4 

2. FOUNDATIONS OF MICROBIAL RISK ASSESSMENT FRAMEWORKS.......5 

2.1. UNDERLYING FORMS OF RISK ASSESSMENT.....................................5 

2.1.1. Chemical Risk Assessment.................................................................5 

2.1.2. Ecological Risk Assessment ...............................................................7 

2.2. FORCES AFFECTING MICROBIAL RISK ASSESSMENT .......................8 

2.2.1. Regulatory Forces ...............................................................................9 

2.2.1.1. United States ..........................................................................9 

2.2.1.2. Canada..................................................................................11
 

2.2.1.3. United Kingdom...................................................................11
 

2.2.1.4. European Union ...................................................................12
 

2.2.1.5. United Nations .....................................................................12
 

2.2.2. Political and Programmatic Forces ...................................................13 

2.2.2.1. United States ........................................................................13 

2.2.2.2. Canada..................................................................................14 

2.2.2.3. Australia and New Zealand..................................................15 

2.2.2.4. France...................................................................................16 

2.2.2.5. The Netherlands...................................................................16 

2.2.2.6. Sweden.................................................................................16 

2.2.2.7. United Kingdom...................................................................16 

2.2.2.8. European Union ...................................................................17 

2.2.2.9. United Nations .....................................................................17 

2.2.3. Technical Forces ...............................................................................18 

2.2.3.1. United States ........................................................................18 

2.2.3.2. International .........................................................................19 

3. GUIDING PRINCIPLES AND CONCEPTS.........................................................20 

3.1. PRINCIPLES ................................................................................................20 

3.1.1. United States .....................................................................................24 

3.1.1.1. Interagency Risk Assessment Consortium...........................24 

3.1.1.2. Environmental Protection Agency.......................................25 

3.1.1.3. Food and Drug Administration ............................................25 

3.1.2. Canada...............................................................................................26 

3.1.3. Australia and New Zealand...............................................................26 

3.1.4. France................................................................................................27 

3.1.5. The Netherlands................................................................................27 

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3.1.6. Sweden..............................................................................................27 

3.1.7. United Kingdom................................................................................27 

3.1.8. European Union ................................................................................28 

3.1.9. United Nations ..................................................................................28 

3.1.9.1. Codex ...................................................................................28 

3.1.9.2. Joint FAO/WHO ..................................................................30 

3.1.9.3. World Health Organization..................................................32 

3.2. CONCEPTS ...................................................................................................33 

3.2.1. Pathogen Characteristics...................................................................34 

3.2.2. Environmental/Media Conditions.....................................................35 

3.2.3. Host Characteristics ..........................................................................36 

3.2.4. Exposure ...........................................................................................37 

3.2.5. Dose ..................................................................................................38 

3.2.6. Human Health Responses .................................................................38 

3.2.7. Modeling...........................................................................................39 

3.2.8 Sources of Data .................................................................................41 

4. MICROBIAL RISK ASSESSMENT FRAMEWORKS .......................................43 

4.1. UNITED STATES........................................................................................44 

4.1.1. Department of Agriculture................................................................44 

4.1.2. Food and Drug Administration .........................................................46 

4.1.2.1. Center for Food Safety and Applied Nutrition ....................46 

4.1.2.2. Center for Veterinary Medicine ...........................................49 

4.1.3. Environmental Protection Agency.....................................................49 

4.1.3.1. Office of Pesticide Programs ...............................................50 

4.1.3.2. Office of Water ....................................................................50 

4.1.3.3. National Center for Environmental Assessment..................53 

4.1.3.4. National Homeland Security Research Center ....................53 

4.1.4. Department of Defense ......................................................................55 

4.2. CANADA .....................................................................................................57 

4.2.1. Health Canada...................................................................................57 

4.2.2. Public Health Agency of Canada......................................................58 

4.3. AUSTRALIA AND NEW ZEALAND ........................................................58 

4.3.1. Australia............................................................................................58 

4.3.1.1. Drinking Water ....................................................................60 

4.3.1.2. Recycled Water....................................................................60 

4.3.2. New Zealand .....................................................................................60 

4.4. FRANCE.......................................................................................................61 

4.5. THE NETHERLANDS.................................................................................61 

4.6. SWEDEN......................................................................................................61 

4.7. UNITED KINGDOM ...................................................................................62 

4.8. EUROPEAN UNION ...................................................................................62 

4.8.1. European Commission on Food Safety.............................................63 

4.8.2. European Food Safety Authority ......................................................63 

4.9. UNITED NATIONS .....................................................................................65 

4.9.1. Joint FAO/WHO ...............................................................................65 

4.9.2. Codex Alimentarius Commission.....................................................67 

4.9.3. International Office of Epizootics.....................................................67 

4.9.4. World Health Organization...............................................................68 

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5. COMPARISON OF FRAMEWORKS...................................................................71 

5.1. OVERALL FRAMEWORK STRUCTURE.................................................72 

5.2. INDIVIDUAL FRAMEWORK COMPONENTS........................................79 

5.3. SIMILARITIES AMONG MICROBIAL RISK ASSESSMENTS..............83 

5.3.1. Scope and Framework.......................................................................83 

5.3.2. Components ......................................................................................84 

5.4. DIFFERENCES AMONG MICROBIAL RISK ASSESSMENTS..............87 

5.4.1. Scope and Framework.......................................................................87 

5.4.2. Components ......................................................................................88 

5.5. KEY ISSUES IN COMPARING MICROBIAL RISK ASSESSMENTS ...92 

6. ENVIRONMENTAL MEDIA AND MICROBIAL RISK ASSESSMENT..........95 

6.1. AIR................................................................................................................95 

6.2. DRINKING WATER....................................................................................95 

6.3. RECREATIONAL WATER.........................................................................99 

6.4. WASTEWATER.........................................................................................100 

6.5. FOOD..........................................................................................................100 

6.5.1. Fresh Foods.....................................................................................101 

6.5.2. Processed Foods..............................................................................101 

6.5.2.1. Raw Oysters.......................................................................104 

6.5.2.2. Shell Eggs and Egg Products .............................................105 

6.5.2.3. Whole Chickens.................................................................106 

6.5.2.4. Variety of Foods ................................................................108 

6.6. BIOSOLIDS................................................................................................109 

6.7. GENETICALLY MODIFIED ORGANISMS............................................110 

6.8. INTENTIONAL USES OF MICROBES ...................................................111 

6.8.1. Contamination.................................................................................111 

6.8.2. Clean-up..........................................................................................111 

6.9. KEY ISSUES RELATED TO ENVIRONMENTAL MEDIA...................111 

7. RECOMMENDATIONS......................................................................................113 

REFERENCES ..........................................................................................................115 

APPENDIX 1. PROCESSED FOOD MODULES....................................................125 

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LIST OF TABLES 

1. Comparison of microbial risk assessment principles...................................................23 

2. Key issues in modeling microbial pathogen risks........................................................41 

3. Categories of microbial risk assessment frameworks with MRA examples................43 

4. USDA salmonella MRA modules for shell eggs and egg products.............................45 

5. Microbial risk assessment framework structures compared with the basic 

 decision-making model................................................................................................74 

6. Type and level of component detail available for government-sponsored MRAs ......77 

7. Steps in the FDA and WHO frameworks ....................................................................84 

8. Summary of exposure pathway modules used in processed food MRAs..................103 

9. FDA and WHO raw oyster MRA modules and components.....................................105 

10. USDA Exposure assessment modules and components for shell eggs 

and egg products ........................................................................................................106 

LIST OF FIGURES 

1. Steps in the traditional risk assessment framework. ......................................................6 

2. Components of ecological risk assessment....................................................................8 

3. Components of a microbial risk assessment. ...............................................................51 

4. Australia’s risk management framework including risk assessment ...........................59 

5. WHO approach to the risk assessment of Salmonella enteriditis in eggs 

and broiler chickens .....................................................................................................70 

6. Source-to-response paradigm aligned with MRA steps based on the 

 NRC framework...........................................................................................................82 

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LIST OF ABBREVIATIONS AND ACRONYMS 

CDC U.S. Centers for Disease Control and Prevention 

CFSAN Center for Food Standards and Nutrition (U.S. FDA) 

Codex Codex Alimentarius Commission 

DALY disability adjusted life year 

ECFS European Commission on Food Safety 

EFSA European Food Safety Authority 

EPA U.S. Environmental Protection Agency 

EU European Union 

FAO Food and Agriculture Organization of the United Nations 

FDA U.S. Food and Drug Administration 

FSIS Food Safety and Inspection Service (USDA) 

HACCP hazard analysis and critical control point 

HSPD Homeland Security Presidential Directives 

ILSI International Life Sciences Institute 

IRAC Interagency Risk Assessment Consortium 

IRGC International Risk Governance Council 

JEMRA Joint FAO/WHO Expert Meetings on Microbial Risk Assessment 

LT2 Long Term 2 Enhanced Surface Water Treatment Rule 

MRA microbial risk assessment 

NCEA National Center for Environmental Assessment (U.S. EPA) 

NHMRC National Health and Medical Research Council (Australia) 

NRC National Research Council 

NRMMC Natural Resource Management Ministerial Council (Australia) 

NZFSA New Zealand Food Safety Authority 

U.S. Presidential/Congressional Commission 

SPS Agreement Agreement on the Application of Sanitary and Phytosanitary Measures 

UN United Nations 

USDA U.S. Department of Agriculture 

WHO World Health Organization 

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P/C 
PREFACE 

Although risk assessments have been conducted for decades, government-sponsored 

conduct of microbial risk assessments (MRA) is a relatively new endeavor. Expanded 

computing and software capabilities now permit dynamic modeling of complex systems, such as 

those involved with human health effects associated with environmental exposures to microbial 

pathogens; thereby stimulating new approaches and methods for modeling MRA components. 

Further, new regulatory mandates and concerns about international trade have led to efforts 

worldwide for advancing MRA and harmonizing approaches. The Microbial Risk Assessment 

Working Group of EPA’s Risk Assessment Forum has undertaken activities for evaluating and 

advancing MRA principles, policies, approaches, practices and methods. 

This report was prepared under contract between EPA and The George Washington 

University (Contract #EP07H000172) to support the efforts of the Working Group by creating 

new knowledge about MRA foundations and frameworks used worldwide. Peer-reviewed 

literature, online government documents and MRAs, and materials presented at professional 

meetings served as crucial resources for the reviews and analyses presented in this report. The 

literature searches were completed in March 2007. Earlier drafts of this report were reviewed by 

EPA staff and external experts; the author gratefully acknowledges that the final report was 

improved by their insights and suggestions. 

viii 
 

AUTHOR, CONTRIBUTORS, AND REVIEWERS 

AUTHOR 

Rebecca T. Parkin 

Center for Risk Science and Public Health 

School of Public Health and Health Services 

The George Washington University Medical Center 

Washington, DC 

CONTRIBUTORS 

Contributors of expert guidance and/or original materials (including policy documents, 

completed microbial risk assessments, etc): 

Jamie Bartram 

Anna Lammerding 

Roland Lindqvist 

Martha Sinclair 

Brandolyn Thran 

REVIEWERS 

An earlier version of this document, completed in June 2006, was prepared under a 

subcontract between Eastern Research Group, Inc. (ERG) and The George Washington 

University Medical Center School of Public Health and Health Services under U.S. EPA 

Contract 68-C-02-060, Task Order 0112. Three experts (Dr. Chuck Haas, Dr. Chuck Gerba, and 

Dr. Greg Claycamp) reviewed this version in preparation for the author’s presentation of the 

initial findings at the 2006 Annual Meeting of the Society of Risk Analysis, Baltimore, MD. 

U. S. Environmental Protection Agency Reviewers: 

This document was reviewed by EPA Risk Assessment Forum staff and Interagency Microbial 

Risk Assessment Guidance Technical Panel members. 

ACKNOWLEDGMENT 

Finally, the author thanks Martha Embrey for her expert editing of the final report, and 

each of the following at The George Washington University Medical Center for their invaluable 

assistance: William Petersen, Amanda Raziano and Polly Thibodeau. 

ix 
 

EXECUTIVE SUMMARY 

In the past decade, concerns about microbial contaminants in food, water, human and 

animal waste, and sources of bioterrorism have grown, giving rise to several initiatives to 

advance microbial risk assessment (MRA), which is one tool for identifying and ultimately 

reducing these hazards. Simultaneously, concerns were growing about the safety of foods in 

international trade, the various methods for assessing foodborne hazards, and the need for more 

scientific rigor and transparency in decision-making. The anthrax attacks in the United States, 

the emergence of severe acute respiratory syndrome, and avian flu outbreaks have added further 

urgency to developing microbial risk assessment methodologies. The massive flooding of New 

Orleans after Hurricane Katrina in 2005 highlighted the need for crisis applications of MRA. 

Risk assessment is only one part of a comprehensive risk management process, known as 

risk analysis (EPA, 2005). The risk characterization step of MRA serves as the bridge between 

risk assessment and risk management activities (Nichols et al., 2005). Although various 

approaches are in use, limited analysis of MRA frameworks or their underlying principles and 

concepts exist. 

Statement of Purpose 

This paper was developed to help the U.S. Environmental Protection Agency’s (EPA) 

Risk Assessment Forum, Microbial Risk Assessment Working Group to obtain new knowledge 

and insights about the nature and characteristics of available MRA frameworks and applications. 

The purposes of this paper are to 

•	 Identify the underlying approaches, societal forces, principles and concepts that shape 

MRA frameworks 

•	 Describe existing MRA frameworks 

•	 Compare recently completed MRAs 

•	 Discuss issues that arise when microbial pathogen risks are assessed for different 

environmental media 

The scope of this paper includes recent MRA policies and MRAs that were either 

conducted or sponsored by governments worldwide. 

x 
Foundations of Microbial Risk Assessment Frameworks 

Two forms of risk assessment, chemical risk assessment and ecological risk assessment 

provided the foundations for MRA as it was practiced at the time of this review. The four-step 

model—involving hazard identification, dose-response, exposure assessment, and risk 

characterization—has been used extensively (NRC, 1983). As a result, the chemical risk 

assessment framework was the prevailing context that many modelers used when approaching 

microbial risk assessment. 

As the MRA field evolved, scientists recognized that terms were being used 

inconsistently to describe MRA concepts, and that frameworks and their underlying principles 

were diverging as well; a need for harmonizing terms and methods was apparent. The desire to 

develop a unified MRA approach has been tempered, however, by the realization that flexibility 

is essential for addressing legislated mandates and regulations. Forces affecting the development 

of microbial risk assessment frameworks include laws, regulations, guidelines, disease outbreaks, 

international conflicts over food safety requirements, scientific publications and debates, and the 

need for consistency and transparency. This paper reviews regulations, political and 

programmatic forces, as well as technical drivers found in international, European, North 

American, Australian, and New Zealand documents. 

Guiding Principles and Concepts 

Guidelines for MRA often include statements of principles and descriptions of conceptual 

issues to be considered when assessing the impacts of microbial pathogens. The majority of 

MRA guidelines and frameworks include fundamental principles and best practices for guiding 

the conduct of MRAs. Drawing from a wide range of documents, the most commonly found 

principles for MRA were 

•	 Make health protection the priority. 

•	 Conduct processes based on sound science, weighing the evidence. 

•	 Ensure transparency through mechanisms such as open processes and clear 

documentation. 

•	 Use and document structured, consistent processes. 

•	 Provide flexible guidelines, not rigid requirements. 

xi 
•	 Keep risk assessment and risk management functionally separate, while allowing for 

ongoing, transparent, and appropriate opportunities for information exchange. 

•	 Ensure clear, concrete, and specific questions early in the process. 

•	 Clarify assumptions and uncertainties. 

•	 Permit iterations of the process, allowing new information to be used and the assessment 

to be updated. 

• Provide outputs relevant and useful to decision-makers. 

One of the most important principles—transparency—typically refers to two issues: 1) 

documentation of methods, models, sources of data, assumptions and uncertainties, and 2) open 

decision-making processes. 

Some of the overarching concepts most often mentioned in MRA policy documents and 

peer-reviewed literature include 

•	 Consider the dynamic dimensions of the pathogen, environment, host, and human 

population. 

•	 Construct a conceptual model early in the process. 

•	 Model realistic conditions. 

•	 Use a comprehensive source-to-exposure pathway paradigm to organize information and 

construct a series of linked mathematical models. 

•	 Recognize the interrelated nature of steps in the paradigm, such as the sequence and 

timing of events. 

•	 Clearly define terms including “infection” and health outcomes. 

•	 Clearly define the outcome metrics (individual and/or population scale), and ensure that 

they link to the decision-makers’ needs. 

Two dominant types of MRA are risk-ranking exercises and product pathogen pathway 

analyses. Many issues in MRA differ importantly from chemical risk assessment, demanding 

different conceptual and practical modeling approaches (WHO, 2005; Schaub, 2004; 

FAO/WHO, 2003a; OECD/WHO, 2003; Eisenberg et al., 2002; Parkin, 2002; Medical Research 

Council Institute for Environment and Health, 2000; ILSI, 2000; Haas et al., 1999; ECFS, 1997). 

xii 
The unique characteristics of microorganisms and host populations and their dynamic aspects are 

be considered carefully when designing an MRA approach (Buchanan, 2003). 

Microbial Risk Assessment Frameworks 

Currently, four fundamental types of microbial risk assessment frameworks exist. One 

type uses the chemical risk assessment framework described in section 2.1.1. (NRC, 1983); 

another type uses a modified NRC framework, in which the two middle steps are sometimes 

reversed; a third framework builds on the NRC approach by adding a problem definition step 

(e.g., part of planning and scoping, or problem formulation) (U.S. EPA, 2005a, 2004b, 1989); 

and the final type of framework was developed by ILSI (2000). 

Although the NRC (1983) framework is the most commonly used framework, it is not 

used consistently; no agency has yet applied the ILSI model for a final risk assessment. Some 

agencies include MRA as part of a risk management paradigm, but very few have discussed risk 

communication as a consideration in MRA processes. 

Comparison of Frameworks 

To elucidate the similarities and differences between governments’ and agencies’ MRA 

approaches, this review includes the most recently completed and available MRA for each nation 

or agency, when there was more than one completed MRA per government, and evaluates the 

type of MRA framework used and the components included in the framework. MRAs were 

found for pathogens in air, drinking water, recreational water, foods (both fresh and processed), 

biosolids, modified organisms, and intentional uses of microbes. 

The analytic focus of this project centered on 12 recently published, governmentsponsored MRAs, and one series of EPA MRAs—for biopesticides, yielding 13 approaches. The 

MRAs compared for this project were 

•	 Cryptosporidium in drinking water (WHO, 2006a) 

•	 Cryptosporidium in drinking water in France (Pouillot et al., 2004) 

•	 Salmonella (non-typhoidal) in poultry (whole and pieces) in New Zealand (NZFSA, 

2004) 

•	 S. enteriditis in shell eggs and egg products in the United States (USDA, 2005b) 

•	 S. typhimurium in three sets of pig-meat products in the United Kingdom (Hill et al. 

2003) 

xiii 
 

 

•	 V. vulnificus in raw oysters (WHO, 2005) 

•	 V. parahaemolyticus in raw oysters in the United States (U.S. FDA, 2005) 

•	 Campylobacter in broiler meat in The Netherlands (Nauta et al., 2005) 

•	 L. monocytogenes in fish in Sweden (Lindqvist and Westöö, 2000) 

•	 Eight microbial pathogens in processed wild game in the United Kingdom (Coburn et 

al., 2005) 

•	 Ochratoxin A in foods (EFSA, 2006c) 

•	 The MRA portion of the economic analysis for the final Long Term 2 Enhanced 

Surface Water Rule (EPA, 2005b) 

An example of the U.S. biopesticides series is 

•	 Streptomyces lydicus WYEC 108 (U.S. EPA, 2004a) 

Microbial risk assessments involve many factors and complex relationships, including the 

dynamic aspects of pathogens and hosts and their environment. Tools such as risk assessment 

frameworks and modules help risk assessors organize the complex microbial risk conditions and 

model dynamic relationships. MRA frameworks provide a broad template to guide the 

organization of many factors into a series of technical steps and to identify data gaps and 

appropriate computational methods. 

The most basic decision-making model has been described by Drucker (2001) as 

including three phases: problem definition, analysis, and interpretation. Two of these three 

components are apparent in both the chemical and microbial risk assessment paradigms; the 

phase that clearly receives the least attention in MRA frameworks is problem definition. Most 

MRAs do not acknowledge problem formulation (or “problem definition”) as a step in the 

assessment process, but do have a section that states the purpose of the assessment and/or 

describes the problem. 

The MRAs in this paper handled scoping issues in different ways—in statements of 

purpose, risk profiles, or problem formulation steps. The 13 MRAs typically had a national 

scope, but few addressed place and time explicitly. The scope of most MRAs conducted to date 

has focused on specific places (e.g., Soller et al., 2003), foods (e.g., U.S. FDA, 2005), or 

pathogens in a limited number of foods (e.g., USDA, 2005b). Among the 13 MRAs, all but one 

xiv 
focused on a specific pathogen. Several MRAs investigated the impacts of a variety of 

environmental conditions (e.g., U.S. FDA, 2005) or a variety of foods (e.g., Coburn et al., 2005; 

USDA, 2005a). 

Most organizations that have published MRAs have used the traditional chemical risk 

assessment paradigm (NRC, 1983). For food-related MRAs, organizations tend to use a 

modification of this framework (e.g., U.S. FDA, 2003a; WHO, 2002). In a drinking water risk 

assessment, WHO (2006a) modified the traditional NRC steps in a unique manner: problem 

formulation was documented after hazard identification. The EPA National Homeland Security 

Research Center office has used the ILSI (2000) paradigm as the basis for its incident response 

assessments (Nichols et al., 2006). 

A comparison of the traditional risk assessment steps yielded the following observations: 

among the MRAs reviewed, the hazard identification step showed the least variation in content; 

all MRAs described host characteristics and disease outcomes and modeled the dose-response 

pathogen-host relationship in the hazard characterization (or dose-response) step; in 10 of the 

MRAs, the exposure assessment step was the most extensively documented. Risk assessors used 

this step to effectively identify and model the complexity of the pathogen pathway and routes of 

exposure and to describe their modeling approaches and outputs. Although levels of detail differ, 

all agencies used the risk characterization step to present, describe, and interpret their modeling 

results. Most MRAs also evaluated and described the sources of uncertainty and variability that 

affected the final MRA estimate. 

While the frameworks used in the 13 MRAs were quite similar (some form of problem 

description precede the four traditional risk assessment steps), they differed in the 

implementation and depth of the framework components. The ability to conduct an effective 

MRA may be constrained by several factors, including the lack of skilled personnel to fully 

implement the analytic steps. Important gaps in knowledge about disease processes and 

microbial pathogen lifecycles require assumptions and uncertainty analysis (Parkin, 2002). An 

incomplete understanding of source-pathway-receptor elements and linkages also limits the 

conduct of MRAs (Godfrey and Smith, 2005). 

A recent and key contribution to MRA is the development of a modular approach, 

particularly to exposure assessments’ pathway analyses. Currently, the extent of missing or 

insufficient data is much greater in most MRAs than in chemical risk assessments, resulting in a 

greater degree of uncertainty. Additionally, the extent to which MRA components vary is largely 

xv 
unknown; the value of conducting sensitivity and probabilistic analyses to reveal the impacts of 

variations in MRA components cannot be overestimated. 

Environmental Media and Microbial Risk Assessment 

Issues related to pathogens in specific environmental media have been identified in 

various MRAs. Media-specific factors and characteristics are important to pathogen survival, 

persistence, growth, and die-off. The significance of having a comprehensive organizational 

structure and components to characterize the pathogen’s progress from source to host is key. 

Each environmental medium or matrix entails different challenges and opportunities for 

pathogens. It is easy for assessors to miss important factors in such complex conditions without 

the benefit of a conceptual model and systematic framework to guide the consideration of the 

many factors and their inter-relationships. These pathways are complex, requiring detailed 

compilation of concepts and data to adequately inform and conduct MRAs. Furthermore, 

translation of the factors and relationships into tractable formulas requires technical skill and 

attention to detail. 

Developing broad, flexible categories of MRA elements is an important goal in module 

development. It is recommended that modules not be rigid lists of steps or elements to consider 

in every MRA, but could be groupings of characteristics to be considered in specific risk 

assessments, thereby serving as guides for risk assessors to assure that complete and effective 

MRAs are implemented. Modules produce more transparent organization and greater description 

of the many factors that contribute to pathogen-related health risks. Modules can be constructed 

to assure that they align with functional components of the pathogen’s pathway and facilitate the 

design and conduct of mathematical models. 

Recommendations 

Although similarities exist among many microbial risk assessment frameworks, the 

differences may result in important variations in MRA results. Beginning with effective planning 

and scoping, problem formulation, definitions, and a sound conceptual model are essential to 

conducting a meaningful and relevant risk assessment. Getting the questions right early in the 

process through dialogue with risk managers is a crucial step. Developing a sound and 

comprehensive conceptual model may require several iterations, but identifying the fundamental 

components of the model should be done early, so the model will focus on risk managers’ needs. 

xvi 
Furthermore, agencies responsible for specific types of MRAs (e.g., food, water) may be 

able to identify modules that they will commonly need for the MRAs within their authorities. A 

large number of the elements required for each module could be listed and organized in advance, 

and the elements could be further refined when specific applications are defined. 

With comprehensive paradigms to help risk assessors identify and consider the many 

potential factors involved in pathogen-related illness, MRAs will become increasingly 

informative and contribute to more effective public health interventions. 

xvii 
 

 

 

 

1. INTRODUCTION1 

1.1. BACKGROUND 

The public health significance of microbial pathogen-related disease is widely known and 

confirmed by public health data. The U.S. Centers for Disease Control and Prevention (CDC) 

has estimated that annually in the United States, there are 76 million foodborne illnesses, 

325,000 hospitalizations and 5,000 deaths (Mead et al., 1999). The World Health Organization 

(WHO) has estimated that, worldwide, contaminated drinking water causes 1.8 million deaths 

and disables tens of millions more people each year (WHO, 2004a). The United Nations has 

identified water as a basic human right and has asserted that providing safe water is a clear 

responsibility of governments. However, nearly a billion people worldwide remain without 

ready access to safe water (Davison et al., 2005). In the past decade, concerns about microbial 

contaminants in food and water from human and animal waste and from sources of bioterrorism 

have grown, giving rise to several initiatives to advance microbial risk assessment (MRA), which 

is one tool for identifying and ultimately reducing these hazards. 

1.1.1. Historical Perspective 

People have been concerned about reducing disease risks since prehistoric times; the 

earliest known rational framework2 for addressing these risks was used in ancient Greece 

(Rosen, 1993). Although scientists recognized microorganisms as disease agents in the midnineteenth century, many of the remedial actions taken to control these agents during the 

subsequent Sanitary Reform Movement were motivated more by beliefs than by scientific 

knowledge (Webster, 1993; Rosen, 1993; Walker, 1968). In the twentieth century, the United 

States developed federal laws and government agencies to address contaminants in food and 

water. First, the U.S. Food and Drug Administration (FDA) was established in 1906 and 

mandated by the Federal Food, Drug, and Cosmetics Act of 1938 (U.S. FDA, 1938) to 

implement the first health-based standard of protection. As a result of this and other legislation, 

essential concepts and methods evolved for quantifying and controlling contaminant-related 

health risks in food, water, and other media (Hutt, 1997). 

1

Dr. Parkin is a Professor of Environmental and Occupational Health in the School of Public Health and 

Health Services of The George Washington University Medical Center in Washington, DC. Portions of this report 

have been drawn from Parkin R. “Microbial Risk Assessment” in Robson MG, Toscano WA (eds.) 2007. Risk 

assessment for environmental health. Washington, DC: Jossey-Bass. 2

Framework is defined as “an integrated, holistic and structured approach ... by which we can investigate 

risk issues and the governance processes and structures pertaining to them” (IRGC, 2005). 

1
 
Second, the U.S. Public Health Service and later the U.S. Environmental Protection 

Agency (EPA) developed drinking water standards, in part, to control microbial pathogen 

hazards. From the 1970s, EPA and the CDC used increasingly systematic and quantitative ways 

for addressing human health hazards. Methods were improved to detect and classify pathogens, 

identify sources of pathogens, and conduct public health surveillance. Methods developed by 

EPA for estimating environmentally related human health risks required new data, such as the 

population’s consumption rates of various foods and water. In response, FDA collected 

consumption data and defined protocols for assessing health effects (Hutt, 1997; Rhomberg, 

1995). 

As EPA, FDA, and other agencies became more involved in risk assessment, the needs 

emerged for estimating risks at unmeasurable exposure levels, organizing diverging risk 

assessment concepts and approaches, and establishing determinations of safety before products 

were allowed onto the market. The National Research Council (NRC) addressed these needs by 

publishing a risk assessment paradigm that remains in wide use today (NRC, 1983). However, 

the framework was designed for addressing chemical carcinogens, which were the foodborne and 

environmental health risks of concern at that time. 

An early MRA approach was proposed in the 1970s (Mossel and Drion, 1979), and Haas 

(1983) proposed methods for dose-response relationships. Others explored dose-response 

relationships to address pathogens in drinking water (Regli et al., 1991; Rose et al., 1991), and 

EPA used these studies as the basis to choose an acceptable level for the risk of infection (1 

case/10,000 people/year) (Regli et al., 1991). However, little advancement of MRA occurred 

until the 1990s. 

In 1992, the United Kingdom Health and Safety Executive organized a conference that in 

part considered human health risks associated with food- and water-borne pathogens, and 

genetically modified organisms. In 1993, not only did the U.S. National Advisory Committee on 

Microbial Criteria for Food establish a working group to study microbial risk assessment, but 

also the International Life Sciences Institute of Europe convened a workshop to identify the 

scientific bases for MRA (ACDP, 1996). 

The importance of advancing microbial risk assessment became even more apparent 

following the 1993 cryptosporidiosis outbreak in Milwaukee, which was linked to the city’s 

drinking water supply. Researchers have estimated that thousands of people were hospitalized 

and over 100 died (Griffin et al. 1998; Kramer et al., 1996; MacKenzie et al., 1994). This 

outbreak motivated legislators to take action for public health protection. With the passage of 

2
 
the 1996 Amendments to the Safe Drinking Water Act and the Food Quality Protection Act, 

EPA’s and FDA’s attention to microbial risk assessment became even more critical (U.S. FDA, 

1996; U.S. 104th Congress, 1996). 

Simultaneously, concerns were growing about the safety of foods in international trade, 

the various methods for assessing foodborne hazards, and the need for more scientific rigor, and 

transparency in decision-making. The Codex Alimentarius Commission (Codex) developed 

guidelines for practicing risk assessment for food products, and in 1993, adopted the Hazard 

Assessment-Critical Control Point (HACCP) system to protect the global food supply (WHO, 

2006b). 

The 2001 anthrax attacks in the United States, the emergence of severe acute respiratory 

syndrome, and avian flu outbreaks have added further urgency to developing microbial risk 

assessment methodologies. The massive flooding of New Orleans after Hurricane Katrina in 

2005 highlighted the need for crisis applications of MRA. Clearly, there are ever-increasing 

reasons to advance microbial risk assessment frameworks that can also be used to rapidly assess, 

characterize, and address pathogen hazards in a tiered approach, and to communicate the hazards 

effectively to decision-makers and the public. 

1.1.2. Origin of the Document 

Risk assessment is only one part of a comprehensive risk management process (Jardine et 

al., 2003), known as risk analysis (U.S. EPA, 2005a). The risk characterization step of MRA 

serves as the bridge between risk assessment and risk management activities. The risk 

management context is very important in shaping the scope and focus of the MRA, while the 

results of the assessment are crucial for sound decision-making about actions to reduce human 

health risks effectively. 

Through its recent deliberations, the Interagency Risk Assessment Consortium has 

identified the need to harmonize and advance MRA methodologies (IRAC-MRAF, 2002). 

Although various approaches are in use, limited analyses of MRA frameworks or their 

underlying principles and concepts exist. The desire to develop a unified MRA approach has 

been tempered, however, by the realization that flexibility is essential for addressing legislated 

mandates and regulations that apply to a variety of both environmental media and microbial 

pathogens. 

This paper was developed to assist EPA’s Risk Assessment Forum—Microbial Risk 

Assessment Working Group in obtaining new knowledge and insights about the nature and 

3
 
 

characteristics of available MRA frameworks and applications. The structure of this document 

was prepared in consultation with the professional staff of EPA’s Office of Water. 

1.2. STATEMENT OF PURPOSE 

The goal of risk assessment is to estimate the probability of possible consequences due to 

exposure to specific risk agents. However, risk issues are fraught with complexity, uncertainty, 

and ambiguity. Many organizations have developed comprehensive, consistent, and yet flexible 

frameworks for systematically applying analytical methods and generating risk estimates (IRGC, 

2005). 

Asano and colleagues (2007) have described microbial risk assessment as “The process 

that is used to evaluate the likelihood of adverse human health effects that can occur following 

exposure to pathogenic microorganisms or to a medium in which pathogens occur. ...the MRA 

process includes evaluation and consideration of quantitative information; however, qualitative 

information is also employed as appropriate....” 

The purposes of this paper are to 

•	 Identify the underlying approaches, societal forces, principles and concepts that shape 

MRA frameworks 

•	 Describe existing MRA framework 

•	 Compare recently completed MRAs 

•	 Discuss issues that arise when microbial pathogen risks are assessed for different 

environmental media 

The scope of this paper includes recent MRA policies and MRAs that were either conducted or 

sponsored by governments. The most recently completed MRA available for a government 

agency was selected for this study. Online tools (Google Scholar, Scopus, etc.), traditional 

literature search methods (interlibrary loans) and personal communications with professional risk 

assessors were used to search for policies and completed MRAs. The United Nations (FAO and 

WHO), the European Union, and several nations were found to have policies describing 

approaches for assessing and managing microbial pathogen risks. MRAs were found for several 

nations in Europe and North America, New Zealand, the European Union and the United 

Nations. A total of 13 MRAs are presented and compared in this review. 

4
 
 

 

2. FOUNDATIONS OF MICROBIAL RISK ASSESSMENT FRAMEWORKS 

Decision support tools or frameworks are used to rank issues, prioritize needs, and 

allocate resources. All of these functions can be met using stepwise risk assessment approaches, 

but all rely on the availability of sufficient knowledge, data, methods, and analytic tools. The 

thoroughness of a risk assessment relies on its objectives and the data available. However, the 

very broad and generic steps for conducting risk assessment—problem definition, data collection 

and analysis, and interpretation—depend on neither specific purposes nor data. 

Governmental agencies in North America, Europe, and other areas have published 

microbial risk assessment frameworks; other organizations have applied approaches for 

pathogen-specific MRAs without publishing explicit frameworks. 

The purpose of this section is to identify the societal forces that have contributed to the 

development of MRA frameworks and describe the two fundamental frameworks that have been 

the primary, essential inputs to existing MRA approaches and applications. 

2.1. UNDERLYING FORMS OF RISK ASSESSMENT 

Two forms of risk assessment—the chemical risk assessment paradigm and ecological 

risk assessment—provide the foundations for MRA as it was practiced at the time of this review. 

2.1.1. Chemical Risk Assessment 

Chemicals in foods were first addressed in a public policy framework in the mid-1800s, 

when they were viewed as adulterants. In the early twentieth century, chemicals were considered 

food safety and poisoning issues; these chemicals were later regulated as if a “safe threshold” 

existed, below which people could be exposed to chemicals without harm (Hutt, 1997; NRC, 

1983). As animal testing produced more data, the underlying assumptions used to estimate 

chemical risks came under question and led to intense debates. One result of these tensions was 

the publication of the National Research Council’s (NRC) “Red Book” (NRC, 1983). This 

document codified the approach to assess chemical risks and described the state of knowledge 

and underlying assumptions for the method. 

The four-step model—involving hazard identification, dose-response, exposure 

assessment, and risk characterization3—was used extensively in the following decades (see 

3

 The following definitions have been derived from the materials presented in U.S. EPA, 2005a: 

•	 Hazard identification is used to determine whether a microbial pathogen can cause adverse health 

effects in humans and what those effects might be. 

5
 
 

 

Figure 1). As a result, the chemical risk assessment framework was the prevailing context from 

which many modelers approached microbial risk assessment. 

Hazard 

Identification 

Dose 

Response 

Assessment 

Exposure 

Assessment 

Risk
 

Characterization 

Figure 1. Steps in the traditional risk assessment framework. 

Source: Adapted from NRC, 1983 

In the early 1990s, several risk assessors applied the chemical risk assessment paradigm 

to microbial pathogen issues. However, each set of investigators identified problems with using 

this framework (Haas et al., 1993; Sobsey et al., 1993; Regli et al., 1991; Rose et al., 1991), and 

other researchers have identified additional issues since then (e.g., Eisenberg et al., 2006; 

Eisenberg et al., 2002). As Eisenberg et al. (2006) pointed out, MRA is fundamentally different 

from chemical risk assessment; most importantly, infectious disease processes (including 

infectivity and incubation periods, etc.) and immunity are key issues not considered in chemical 

risk assessment. Further, chemical risk assessment relies on static modeling techniques, which 

cannot represent dynamic processes such as disease transmission, and on the assumption that 

each exposure is an independent event. Infection is a function of dose and, rather than mortality, 

may be the health outcome of concern. In MRA, the population is separated into the immune and 

•	 Dose-response is the quantitative relationship between an exposure and the extent of disease produced. 

Dose-relationship is often one component of hazard characterization. 

•	 Exposure assessment is the step used to identify the pathways by which pathogens may reach 

individuals, estimate the extent of pathogen exposure among humans, and estimate the likely number 

of persons exposed. 

•	 Hazard characterization is a description of the potential adverse health effects attributable to a specific 

pathogen, the mechanisms by which it exerts its effects, and the associated dose, route, duration, and 

timing of exposure. 

•	 Risk characterization is the integration of information about the hazard, exposure, and dose-response, 

and the estimation of the likelihood of adverse health effects among exposed individuals. Descriptions 

of the modeling assumptions, uncertainties and variability, along with possible risk management 

options are also included in this step. 

6 
susceptible subpopulations to effectively estimate risk. When secondary transmission is 

involved, dynamic modeling and population scale measures of risk are crucial (Eisenberg et al., 

2006). 

Some of the problems that researchers have identified as not being addressed by the “Red 

Book” paradigm for microorganisms include 

•	 Microorganisms can grow, evolve into different life stages, and die off. 

•	 Virulence varies during a pathogen’s life cycle and between different pathogen 

strains. 

•	 Pathogens behave differently under different temperature and time conditions (e.g., in 

food processing and preparation), as well as in different media and matrices (e.g., 

water vs. food, and different types of foods and soils). 

•	 Microbial pathogens are not evenly distributed in the environment, and may be found 

in clumps, which present very uneven probabilities of exposure. 

•	 Secondary or person-to-person transmission occurs in many infectious disease 

processes, while chemical exposure assessment occurs in the individual. 

•	 Attack rates and infection rates differ and asymptomatic carriers exist. 

•	 Multiple, independent exposures occur as part of the infectious disease process. 

Although the microbial risk assessment steps are often the same as for chemical risk 

assessments, the emphasis, elements, and conduct are different in various stages of MRAs due to 

the dynamic natures of the agent and population (ECFS, 1997). In particular, changes in the 

population’s immunity and susceptibility status are not considered in the traditional risk 

assessment paradigm or in chemical risk assessments themselves. 

2.1.2. Ecological Risk Assessment 

During the 1980s and early 1990s, ecological risk assessment evolved at EPA (U.S. EPA, 

1992). Although ecologic modelers were informed by the chemical risk assessment approach, 

they recognized that as a paradigm, it did not entirely fit their needs. Ecological risk assessment 

demands a comprehensive, systems-oriented context, which requires modelers with different 

backgrounds and training. As a result, a lack of a clearly defined problem statement makes 

ecological risk assessments difficult and inefficient. Because the Red Book did not include a 

7
 
 

problem formulation4 step, ecological risk assessors created one and explained how to 

implement it (U.S. EPA, 1992). 

The three primary steps in ecological risk assessment frameworks used in North America 

are problem formulation, analysis, and risk characterization (U.S. EPA, 1998; Environment 

Canada, 1996). The middle step involves characterizations of exposures and effects (see Figure 

2). Ecological risk assessors’ work contributed valuable insights for advancing microbial risk 

assessment concepts and methods, such as interactions between agents (which may include 

microbial pathogens) and hosts that are living entities with several life stages. 

Problem 

Formulation 

Analysis 

Characterization 

of Exposure 

Characterization of 

Ecological Effects 

Risk 

Characterization 

Figure 2. Components of ecological risk assessment. 

Source: Adapted from Jardine et al., 2003 

2.2. FORCES AFFECTING MICROBIAL RISK ASSESSMENT 

Forces that have affected the development of microbial risk assessment frameworks 

include laws, regulations, guidelines, disease outbreaks, international conflicts over food safety 

requirements, scientific publications and debates, and the need for consistency and transparency. 

Underlying all of these drivers, however, was a growing awareness that natural and manmade 

microbial pathogens are potentially very harmful to humans and the environment and thus 

merited more rigorous risk assessment and management strategies. As the MRA field evolved, 

4

 Problem formulation was first used in EPA’s ecological risk assessment framework (U.S. EPA, 1992). 

This refers to the initial systematic planning step in which the purpose of the assessment is stated, goals and 

objectives are defined, the endpoints and conceptual model for the assessment are described, major factors and data 

needs are recognized, and the contexts for the assessment are presented (U.S. EPA, 2005a; EPA, 2004b). 

8
 
scientists recognized that terms were being used inconsistently to describe MRA concepts, and 

that frameworks and their underlying principles were diverging as well; a need for harmonizing 

terms and methods became apparent. Furthermore, the public and officials were increasingly 

expressing concerns, seeking more scientifically sound processes to control microbial risks, and 

looking for assurances that limited resources were being used to address the risks effectively. 

2.2.1. Regulatory Forces 

2.2.1.1. United States 

Laws and regulations, an Executive Order, and Agency Directives have influenced the 

development of MRA policies and approaches in the United States. The agencies primarily 

affected have been EPA, FDA, and the U.S. Department of Agriculture (USDA). A summary of 

these agency-related regulatory forces follows. 

2.2.1.1.1. Environmental Protection Agency. The 1996 Amendments to the Safe Drinking 

Water Act required EPA to list unregulated microbial pathogens known or expected to occur in 

public water systems and that may require regulation; the Contaminant Candidate List including 

microbial pathogens was issued in 1998 and updated in 2005. To obtain evidence about pathogen 

occurrence, the Information Collection Rule was promulgated in 1996; it required water utilities 

serving over 10,000 people to test source and finished water monthly. Further, the Long Term 2 

Enhanced Surface Water Treatment Rule (LT2) required health-based approaches for 

establishing new rules to reduce microbial pathogen hazards associated with drinking water (U.S. 

EPA, 2005b). The intent of the LT2 rule was to supplement microbial pathogen treatment 

requirements where greater public health protection is necessary; the primary pathogen concern 

was cryptosporidium. The rule also considered the tradeoffs of controlling both pathogen and 

disinfection byproduct risks. Concerns about the potential hazards associated with microbial 

products of biotechnology were raised in the 1980s, causing EPA to evaluate its existing 

regulations and determine that the agency had the power to regulate such hazards. Since 1986, 

EPA has been reviewing notices on new microorganisms under section 5 of the Toxic Substances 

Control Act. To implement notification procedures specific for microorganisms, EPA 

promulgated an additional rule in 1997 (U.S. EPA, 1997). 

EPA promulgated the Part 503 Rule in 1993 to set standards for the use and disposal of 

biosolids, but—unlike for chemical pollutants—pathogen limits were not based on risk 

9
 
assessment but on performance, technological or other bases (Eisenberg et al., 2006). More 

recently, in response to Homeland Security Presidential Directives HSPD-7, 9, and 10 (Nichols 

et al., 2006), EPA has begun to conduct MRAs related to bioagents that may be used 

intentionally to harm populations. The Presidential Directives required EPA to 

•	 Be the sector-specific lead agency for critical water infrastructure safety and security 

(HSPD-7) 

•	 Create a fully coordinated surveillance and monitoring program for early detection of 

bioagents (HSPD-9) 

•	 Develop a nationwide laboratory network to support routine monitoring and response 

requirements (HSPD-9) 

•	 Serve as the nation’s lead agency in decontamination efforts (HSPD-10) 

2.2.1.1.2. Food and Drug Administration. The FDA derives its food safety authorities from the 

Federal Food, Drug, and Cosmetics Act of 1938 (FDCA), which defined the conditions for 

“adulterated” food. The agency is responsible for regulating the safety of all foods, substances 

intentionally added to food and used in food processing, and manmade and natural food 

contaminants. The scope of these authorities covers all activities between production and retail 

sale. Additional authorities were directed to FDA through the Food Additives Amendment of 

1958. FDA carries out its food safety authorities through the Center for Food Safety and 

Applied Nutrition (CFSAN), which establishes policies and standards, manages the premarket 

approval program, and sets priorities for the field inspection and compliance force. These legal 

foundations are not explicitly stated in FDA’s MRAs, but clearly give the agency authority to 

conduct MRAs for protecting the public from foodborne pathogens. The provisions of the Food 

Quality Protection Act of 1996 call for evaluations of the safety of potential contaminants in the 

food supply, particularly in reference to susceptible subpopulations such as infants and children. 

The review of toxicological data for assessing biopesticide safety in preparation for registration 

and use complies with the requirements of the Act. (e.g., U.S. EPA, 2004a). 

2.2.1.1.3. U.S. Department of Agriculture. The USDA has statutory authority over meat, 

poultry, and processed egg products. This agency’s authority derives from several acts: the 

Federal Meat Inspection Act, the Poultry Products Inspection Act, and the Egg Products 

10
 
 

 

Inspection Act. Like the Food, Drugs, and Cosmetics Act, all of these acts define conditions for 

“adulterated.” The USDA food safety program is primarily carried out by the Food Safety and 

Inspection Service (FSIS), which has rulemaking authority and establishes standards. In 1996, 

FSIS required all meat and poultry processing plants to adopt the hazard analysis and critical 

control point (HACCP) system. Like FDA, USDA does not explicitly state its legal authorities 

for conducting its MRAs. The Food Safety Commission was established in the USDA through 

enactment of the Farm Security and Rural Investment Act of 2002. This law mandated 

improvements to the food safety system, building on a National Academy of Sciences report that 

criticized the inefficiencies of the U.S. food safety system (IOM/NRC, 1998). These 

recommendations added incentives for the USDA to advance its MRA methodologies as a tool 

for improving the safety of food processes. 

In 1997 and 1998, President Clinton announced the interagency Food Safety Initiative, 

proposed additional resources be dedicated to international food safety issues, and established 

the President’s Council on Food Safety (Executive Order 13100, 1998). Federal agencies 

subsequently increased their attention to microbial risk assessment, and produced new MRA 

approaches (e.g., USDA, 2005b; U.S. FDA/CFSAN, 2005; ILSI, 2000). 

2.2.1.2. Canada 

The Federal-Provincial Subcommittee on Drinking Water (of the Federal-ProvincialTerritorial Committee on Environmental and Occupational Health) developed Canada’s 

Guidelines for Canadian Drinking Water Quality. These guidelines rely on the concepts that 

science-based assessments and flexible approaches are necessary to accommodate diverse needs 

across the nation (Health Canada, 2000; 1999a). No MRA completed and published by a 

government agency was found at the time of this project. 

2.2.1.3. United Kingdom 

The Food Standards Act of 1999 authorized the Food Standards Agency (Medical 

Research Council Institute for Environment and Health, 2000). The Agency focused its attention 

on developing methodologies for addressing microbial hazards. 

11
 
 

 

 

2.2.1.4. European Union 

The European Union (EU) has several legal bases relevant to microbial risk assessments. 

These regulations apply to the conduct of MRAs and serve as the basis for the EU’s guidance for 

the risk assessment of genetically modified organisms (EFSA, 2005). 

•	 The General Food Law (Regulation [EC] 178/2002) defines “risk assessment” and the 

general principles of food safety. It also describes the principles of food law and 

procedures for food safety, as well as the responsibilities of the European Food Safety 

Authority (EFSA). This regulation defines risk analysis, risk assessment (as the four 

traditional steps), risk management and risk communication (EFSA, 2006b). 

•	 The regulation on genetically modified food and feed (EC Regulation 1829/2003) 

requires marketing decision-making to be based on scientific risk assessment 

conducted by the EFSA. 

•	 European regulations for wild game meat (EC Regulation 853/2004) have motivated 

nations to characterize the risks in wild processed game to ensure the products can 

enter international trade routes (e.g., Hill et al., 2003). 

•	 European Commission Regulation No. 466/2001 set maximum levels for certain 

contaminants in foods, which was amended by Regulation 123/2005. These were the 

regulations that mandated the Ochratoxin A in food toxicological review and opinion, 

issued in 2006 (EFSA, 2006c). 

2.2.1.5. United Nations 

Several key United Nations declarations have focused more attention on microbial 

hazards and resulted in the development of MRA principles and frameworks. Among these, 

several stand out in importance: 

•	 The 1992 World Declaration and Plan of Action for Nutrition, adopted by the 

International Conference on Nutrition, explicitly stated that the protection of food is 

an essential responsibility of governments. In response, the Food and Agriculture 

Organization of the United Nations (FAO) and WHO were requested to involve all 

member countries in Codex activities, including MRA consultations (FAO/WHO, 

1995). 

•	 In 1995, the Uruguay Round of Trade Agreements’ General Agreement on Tariffs 

and Trades and the subsequent Agreement on the Application of Sanitary and 

Phytosanitary Measures (or the SPS Agreement)5

 affirmed that no member should be 

5

 This Agreement can be found at http://www.wto.org/English/tratop_e/sps_e/spsagr.htm. Last accessed on 

March 4, 2006. 

12
 
 

 

 

 

prevented from adopting or enforcing measures needed to protect health (WTO, 

1995). The SPS Agreement specifically cited Codex’s standards, guidelines, and 

recommendations as reflections of international consensus about protecting human 

health from foodborne hazards. This international trade agreement required World 

Trade Organization members to conduct risk assessments for setting limits on health 

risks in foods. The SPS Agreement also served as the foundation for the Joint 

FAO/WHO Expert Consultation on Application of Risk Analysis to Food Standards 

Issues (WTO, 1995). 

•	 The 1995 Agreement on Technical Barriers to Trade prompted more attention to 

addressing international food trade concerns, including microbial risks (FAO/WHO, 

2002a; 1995). FAO and WHO conducted a series of expert consultations that have 

resulted in several reports to guide risk assessments of foodborne pathogens.6 

Building on these bases, Codex prepared principles and guidelines for MRA (Codex, 

1999). 

•	 The 2000 United Nations (UN) World Health Assembly food safety resolution called 

on members to recognize food safety as an essential public health function and 

develop systems to reduce the burden of foodborne disease. It also directed members 

to support its MRA advisory body (the Joint FAO/WHO Expert Meetings on 

Microbial Risk Assessment, or JEMRA), which conducts MRAs and provides expert 

advice to members. 

2.2.2. Political and Programmatic Forces 

2.2.2.1. United States 

A number of policies and activities promulgated by U.S. agencies and other influential 

organizations affected the direction and development of risk assessment: 

•	 A pivotal report of EPA’s Science Advisory Board described efforts to rank order 

environmental hazards, and recommended funding levels in alignment with real, not 

perceived, risks for reducing risks more effectively (U.S. EPA, 1990). While this 

report did not have major effects on EPA’s budget, it did stimulate extensive debate, 

which noted that microbial pathogens were largely ignored but significant hazards. 

•	 Public concerns about the scientific integrity of risk assessments led Administrator 

Browner to issue a policy for risk characterization in March 1995. In her statement, 

she reaffirmed the principles and guidance issued by EPA in 1992, and asserted that 

risk assessments across the Agency must be transparent, clear, reasonable, and 

consistent agency-wide (See Appendix A in U.S. EPA, 2000a). 

6

 These documents can be found at http://www.who.int/foodsafety/micro/en. Last accessed on March 4, 

2006. 

13
 
 

•	 Foodborne hazards have been addressed through the HACCP approach, which was 

developed through an intensive public-private sector process. 

•	 In 1997 the interagency National Food Safety Initiative focused on reducing 

foodborne pathogen-related illness rates by improving farm-to-fork MRA methods, 

including dose-response modeling. The group recommended the use of risk 

assessment as one means for addressing food safety issues. The political and financial 

support that resulted from the Initiative’s report helped improve microbial risk 

assessment and research capabilities (Dennis et al., 2001–2002). 

•	 A 1998 Institute of Medicine/National Research Council report recommended basing 

food safety system reforms on sound science and risk assessment, and noted that risk 

assessment is an essential component in setting priorities and allocating resources 

effectively (Taylor et al., 2003; IOM/NRC, 1998). 

•	 In response to three Homeland Security Presidential Directives (HSPD-7, 9, and 10), 

EPA established a comprehensive National Homeland Security Research Center. One 

of the Center’s initiatives is the development of a microbial risk assessment 

framework. A preliminary approach for incident response to bioagents has been based 

on existing methodologies and is organized into three tiers: Site/Incident Assessment, 

Exposure and Hazard Assessments, and Risk Characterization (Nichols et al., 2006). 

Throughout this period, agencies such as the EPA, FDA, and USDA were gaining 

experience with the concepts, models, and conduct of MRA. The agencies produced several 

interagency MRAs, which built capacity for conducting assessments across agency boundaries. 

Workshops were held to discuss key concepts, evaluate the work completed, and review lessons 

that should be shared and used to identify potential improvements. 

2.2.2.2. Canada 

Canada has also had a number of agencies and organizations whose activities and policies 

have had an impact on microbial risk assessment: 

•	 Lammerding (2006) of the Public Health Agency of Canada has described risk 

assessment as “a structured, systematic approach to integrate and evaluate 

information....” and has presented the Codex (1999) four-compartment approach as 

appropriate for MRA. 

•	 In 1999, Health Canada examined the presence and hazards associated with 

Escherichia coli O157:H7 in raw ground beef. Because Canada’s food, drug, and 

meat inspection laws did not cover this microorganism, the agency developed 

guidelines for reducing E. coli O157:H7 in raw ground beef (Health Canada, 1999b). 

14
 
 

 

•	 The Animal Plant and Food Risk Analysis Network within the Canadian Food 

Inspection Agency is responsible for animal and plant health risk assessments.7 

•	 The 2000–2002 water-related disease outbreaks that occurred in Walkerton and the 

Battlefords resulted in governmental inquiries into the causes for these tragic 

episodes. These major governmental responses led to several reports, some of which 

recommended the proactive use of microbial risk assessment strategies (Krewski et 

al., 2004). 

•	 Since 2002, Canada’s federal departments, funding agencies, and industry 

associations have been participating in the Canadian Research Coalition for Safe 

Food and Water to identify and fund research priorities for public health protection. 

The first two years resulted in seven interdisciplinary teams focused on gathering 

environmental and health data to improve outbreak surveillance and risk assessment 

and management approaches (CIHR, 2006). 

2.2.2.3. Australia and New Zealand 

The microbial risk assessment activities in these two countries have been mainly focused 

on drinking water. The bases for the Australian Drinking Water Guidelines (NHRMC-NRMMC, 

2004) and the National Guidelines for Recycled Water (NRMMC, 2006) are: HACCP principles 

(Codex, 1997), the Australian/New Zealand Standard on Risk Management (AS/NZS, 1999), and 

WHO policies (WHO, 2004b; 2001). The 1996 Australian drinking water guidelines were based 

on state-of-the-art WHO guidance, but officials realized that conducting a comprehensive review 

of the guidelines in the future would be too time-consuming and costly. As a result, the National 

Health and Medical Research Council (NHMRC) and the Natural Resource Management 

Ministerial Council decided to revise the guidelines on a “rolling” basis (NHMRC-NRMMC, 

2004). A major change between the 1996 and 2004 versions of the drinking water guidelines is 

the inclusion of a risk management framework; the 2004 version of the drinking water guidelines 

also draws on AS/NZS 4360 (1999). 

The need for the recycled water guidelines grew out of the recognition that efforts to 

reduce risks would require assessment of risks, determinations of acceptable or tolerable risk and 

also health-based targets (NRMMC, 2006). The recycled water guidelines rely on Australia’s 

drinking water guidelines (NHRMC-NRMMC, 2004). 

7

 Building on the Animal Plant and Food Risk Analysis Network’s methods to address plant and animal 

health and food safety risks, Ontario’s Ministry of Agriculture, Food, and Rural Affairs developed a risk 

management framework in which risk assessment—involving hazard identification, risk characterization, and 

biological recommendations—provides the scientific basis for decision-making (Jardine et al., 2003). 

15
 
2.2.2.4. France 

MRA has been conducted in response to government officials’ requests for analyses and 

recommendations for supporting decision-making processes. For example, French authorities 

have asked the French food safety agency (Agence Francaise de Sécurité Sanitaire des Aliments) 

to make risk management recommendations that incorporate social and institutional views of 

acceptable risk. The bases for such recommendations have been quantitative risk assessments 

(Pouillot et al. 2004). 

2.2.2.5. The Netherlands 

MRAs have been conducted to aid decision-making for public health protection 

improvements. Assessments have included systematic examinations of the health impacts of 

various sources and routes of exposure and various interventions. The results have assisted 

decision-makers in determining the most effective and feasible risk management options (Nauta 

et al., 2005). 

2.2.2.6. Sweden 

In the 1990s, a listeriosis outbreak was associated with widely consumed processed foods 

(Ericsson et al., 1997). Furthermore, Loncarevic et al. (1996) suggested that salmon and rainbow 

trout were causes of listeriosis. These results raised public concerns about the safety of 

traditional foods. 

The scientific findings and public concerns led the National Food Administration to 

characterize related public health risks and identify ways for reducing them. (Lindqvist and 

Westöö, 2000). 

2.2.2.7. United Kingdom 

Several initiatives in the United Kingdom (UK) have addressed MRA-related issues, and 

several risk assessment policies are relevant to microbial pathogen risks. 

•	 In the late 1990s, the UK relied on HACCP to address foodborne pathogen risks, but 

officials recognized that this method might be insufficient for meeting international 

food trade needs. To advance beyond HACCP, the Ministry of Agriculture, Fisheries 

and Food funded a collaboration of academic centers (FORA or Food Risk 

Assessment) to improve risk assessment methods (Medical Research Council Institute 

for Environment and Health, 2000). The UK developed and published principles for 

16
 
 

 

transparent, consistent risk assessment to ensure the safety of food commodities 

(Minister of Agriculture, Fisheries and Food [UK], 1998). 

•	 The UK Strategy Unit (2002) includes risk assessment in its risk management 

paradigm. 

•	 One goal of the Food Standards Agency is to reduce the baseline number of 

foodborne disease cases by 20% in five years (FSA, 2003 cited in Hill et al. 2003). 

•	 MRA has been conducted to aid the Food Standard Agency’s Zoonoses Action Plan 

in improving the abattoir surveillance program. The results were used to help 

develop targeted interventions on high-risk farms; thereby reducing the risks of 

human infection (Coburn et al., 2005). 

2.2.2.8. European Union 

In 1997, the Scientific Committee on Food of the European Commission adopted 

principles for microbial risk assessments. The committee produced a report, available on the 

European Union’s website.8

 In addition, EFSA’s guidance for genetically modified 

microorganisms and their derived products for use as food or feed describes numerous policy 

documents that serve as the foundation for the guidance (see p. 59 of EFSA, 2006d). 

2.2.2.9. United Nations 

The United Nations (UN) has numerous policies and activities that are relevant to MRA. 

•	 As early as 1991, the Joint FAO/WHO Conference on Food Standards, Chemicals in 

Foods, and Food Trade recognized the need for greater consistency and transparency 

in Codex’s risk analyses (FAO/WHO, 1995). 

•	 From 1995, joint FAO/WHO expert groups and consultations have been held to 

discuss MRA issues and to develop principles and guidelines for MRAs. 

•	 In 1996, the Codex Committee of Food Hygiene recommended that efforts be 

undertaken to advance and harmonize microbial risk management strategies. 

•	 The Joint FAO/WHO international risk assessment advisory body was convened in 

1997. Within two years, Codex declared microbial pathogen risks urgent issues and 

adopted guidelines for MRA conduct (Codex, 1999). 

•	 WHO prepared a draft international MRA strategy and mechanism (FAO/WHO, 

1999). 

8 Http://www.europa.eu.int/comm/food/fs/sc/oldcomm7/out07_en.htm. Accessed on March 4, 2006. 

17
 
•	 The Codex Committee of Food Hygiene prioritized 21 pathogen-commodity 

combinations as public health concerns, and recommended that FAO and WHO 

evaluate these jointly through expert consultations (WHO, 1999). The agencies 

established the Joint FAO/WHO Expert Meetings on Microbial Risk Assessment to 

design and conduct MRAs. 

•	 WHO’s initiative to address Vibrio spp. risks related to seafood led to the conduct of 

MRAs by WHO (2005) and FDA/CFSAN (2005). 

•	 WHO’s Guidelines for Drinking Water Quality served as the basis for the agency’s 

recent MRA of cryptosporidium in drinking water supplies (WHO, 2006a). 

2.2.3. Technical Forces 

Trends among scientific and technical experts also supported the development of MRA 

frameworks, methods, and tools. Although microbial risks were recognized as important, the 

typical risk management strategy focused on control of indicator organisms rather than 

assessments of risks. 

2.2.3.1. United States 

In the early 1990s, several research teams applied the chemical risk assessment paradigm 

to microbial pathogen issues, but found the NRC paradigm problematic and limiting in cases 

where agent or pathogen dynamics needed to be incorporated in the assessment. Modifying a 

framework proposed by EPA staff, Sobsey et al. (1993) proposed a framework specifically for 

MRA. 

The EPA Office of Water and ILSI convened a workshop of experts to develop a 

framework for all microbial pathogens in all media (ILSI, 1996). This conceptual framework 

was developed to organize information for quantitative microbial risk assessment of all forms of 

microbial pathogens in all types of aqueous media. Two case studies were commissioned to 

study the value and flexibility of this framework that resulted in a revised model expected to be 

applicable to a wider range of exposure routes (ILSI, 2000; Soller et al., 1999; Teunis and 

Havelaar, 1999). This ILSI initiative stimulated other researchers to examine key issues related 

to MRA, such as social risk factors and susceptible subpopulations (Balbus and Parkin, 2000; 

ILSI, 2000). 

18
 
2.2.3.2. International 

In 2000, the International Workshop on Promotion of Technical Harmonisation on RiskBased Decision Making was held in Europe to develop generic standards for risk-based decisionmaking (Jardine et al., 2003). One outcome of this workshop was a list of five decision steps: 

identification/characterization, analysis, assessment, management, and decision-making. The 

workshop report also noted that risk decisions are highly context-dependent and require early 

involvement of stakeholders. Because of these realities, a suggested—not prescriptive—risk 

assessment framework was recommended. While technical steps were laid out generically and 

methods and approaches suggested, the exact steps were not detailed. 

19
 
3. GUIDING PRINCIPLES AND CONCEPTS 

Guidelines for MRA often include statements of principles and descriptions of conceptual 

issues that are considered when assessing the impacts of microbial pathogens. Many peerreviewed articles and governmental policy documents are available to guide both risk assessors 

and risk managers for developing MRA processes and procedures both for general purposes as 

well as specific applications to real-world concerns. 

The purposes of this section are to define “principles” and “concepts,” present ones that 

have been linked to MRA, and point out ones emphasized by specific governmental entities. 

3.1. PRINCIPLES 

In a comprehensive review of risk management frameworks, Jardine et al. (2003) defined 

“principles” as “a standard, ideal, rule, or code of conduct”; they also noted that agencies use the 

term “principles” differently. Their definition was used in this project for identifying and 

organizing the standards and rules for MRA found in peer-reviewed literature and governmental 

documents. 

The majority of MRA guidelines and frameworks include fundamental principles and 

best practices for guiding the conduct of MRAs (Table 1). The overarching goal of MRA is to 

identify pathogen scenarios and options for reducing hazards; thereby assisting decision-makers 

by meeting their informational needs. MRA can be considered as both process and product. It 

provides a structure for compiling and evaluating scientific information and produces a statement 

about the probability and extent of harm to exposed populations. 

Drawing from a wide range of documents, the most commonly found principles for MRA 

were 

•	 Make health protection the priority. 

•	 Conduct processes based on sound science, weighing the evidence. 

•	 Ensure transparency, through mechanisms such as open processes and clear 

documentation. 

•	 Use and document structured, consistent processes. 

•	 Provide flexible guidelines, not rigid requirements. 

•	 Keep risk assessment and risk management functionally separate, while allowing for 

ongoing, transparent and appropriate opportunities for exchanges of information. 

20
 
•	 Ensure clear, concrete and specific questions early in the process. 

•	 Clarify assumptions and uncertainties. 

•	 Permit iterations of the process, allowing new information to be used and the 

assessment to be updated. 

•	 Provide outputs relevant and useful to decision-makers. 

One of the most important principles—transparency—typically refers to two issues: 1) 

documentation of methods, models, sources of data, assumptions and uncertainties, and 2) open 

decision-making processes including forums with stakeholder participation, selection of peer 

reviewers, and means to review and update MRAs when new data and/or conditions may affect 

related goals or outcomes. Transparency is improved when MRA modeling results are evaluated 

and clearly presented with information about the impacts of assumptions and sources of 

uncertainty. 

One of the less frequently found principles was that the precautionary principle can guide public 

health protection strategies. Other less commonly noted principles were that MRAs could 

•	 Begin with a clearly defined statement of purpose 

•	 Rely on a simple conceptual model sufficient to meet decision-makers’ needs 

•	 Ensure efficiency, effectiveness, equity, fairness, and accountability 

•	 Not allow available data to dictate the model 

•	 Base models on physiopathology and the natural course of disease 

•	 Use a strategic focus and sustainable approach 

•	 Simulate realistic scenarios 

•	 Use clear methods 

•	 Consider all available scientific evidence 

•	 Use reasonable and consistent assumptions 

•	 Be based on defined principles and procedural steps 

•	 Be evaluated 

In microbiology, there is no “zero-risk” option, which refers to the common assumption 

that only one microorganism can initiate disease. As a result, risk managers tend to take a 

21
 
conservative public health approach and identify interventions that will provide the level of 

safety expected by society. Because pathogens are pervasive in the environment, and it is 

impossible to remove them entirely, the HACCP approach, for example, has typically been 

adopted as a viable method to minimize risk to populations (WHO, 2006b). 

The following sections discuss how various government agencies approach MRA and 

present the principles that agencies emphasize. 

22
 
Table 1. Comparison of microbial risk assessment principles 

Principles 

Year Source Health 

Protection Priority 

Sound Science/ Weight of Evidence 

Transparency Structured, 

Documented and Consistent 

Flexible Separate 

Risk Assessment and Risk Management 

Problem Formulation 

AssumptionsUncertaintieStated 

1983 NRC X 

1993 Sobsey X 

1995 WHO X 1996 ACDP X X 

1997 ECFS X X X X X 

1997 FAO/ 

WHO 

X X X X X X 

1997 P/C X X 1998 EPA – X 

Ecology 

1998 UK X X X 

2000 FAO/WHO X X X X X 

2000 Health X X X 

Canada 

2000 ILSI X X X X X 

2000 WHO X X X X X X 

2001 FDA X X 

2002 FAO/ 

WHO 

X 

X X X 

2000 EC X X X X 

2003 FAO/ 

WHO 

X 

X X 

2003 EPA – 

Yoe 

X X X X 

2003 OECD/WHO X 

2004 Canada X 

2004 NHMRCNRMMC X X X X X 

2005 IRGC X X X 

2006 NHMRC X X X X X 

2006 FAO/ 

WHO 

X 

X X 

23
 
3.1.1. United States 

3.1.1.1. Interagency Risk Assessment Consortium 

To help the Interagency Risk Assessment Consortium (IRAC) develop risk assessment 

guidelines suitable for pathogen risks in water and food, the EPA Office of Water and FDA’s 

CFSAN supported a grant to evaluate USDA, FDA, ILSI, and Codex MRA frameworks and 

interview experienced microbial risk assessors (Yoe, 2003; IRAC-MRAF, 2002). The important 

principles that were common among these sources were 

•	 Frameworks be generic but flexible for implementing a variety of pathogen-hostenvironment scenarios. 

•	 Frameworks should be clear and sufficiently descriptive to facilitate implementation. 

•	 The conceptual model be developed early. 

•	 Assumptions be tracked throughout the MRA. 

•	 Documentation be developed during the MRA to ensure appropriate recall of the 

assumptions and work conducted. 

Based on the interviews, final recommendations to improve MRAs (Yoe, 2003) included 

•	 Adding a formal problem formulation step to the MRA process 

•	 Clarifying the scope of the assessment 

•	 Assuring early development of a conceptual model 

•	 Avoiding constraint of initial risk assessment questions, due to limited data 

availability 

•	 Developing an explicit list of questions iteratively to guide the MRA 

•	 Designing realistic time lines and resources to support the work 

•	 Defining roles and responsibilities 

•	 Tracking and documenting assumptions throughout the conduct of the MRA 

24
 
 

 

• Assuring unbiased and thorough review processes 

• Emphasizing stakeholder involvement 

• Stating how researchers can develop needed data and knowledge 

The risk assessors interviewed also recommended that the conceptual model be 

developed early, the assumptions be tracked throughout the MRA, and documentation be 

developed during the MRA to ensure appropriate recall of the assumptions and work conducted. 

The results of this initiative indicated the importance of ensuring flexibility in a generic 

framework, allowing for elements to be used as appropriate for the risk issue and its contexts 

(Yoe, 2003). 

3.1.1.2. Environmental Protection Agency 

This agency has published many guidance documents to clarify the process and principles 

to be used in its risk assessments.9 Its risk characterization guidelines (U.S. EPA, 1995) describe 

the importance of 

• Transparency of the policies and process 

• Clarity of the methods and assumptions used 

• Reasonableness of the assumptions 

• Consistency of the methods and assumptions among risk assessments 

These four characteristics were established by agency policy in 1995 (U.S. EPA, 2000a). 

3.1.1.3. Food and Drug Administration 

CFSAN has published guiding principles for risk assessment (U.S. FDA, 2002) that 

highlight the value of 

• Iteration of risk assessments, with more quantification as data allow 

9

 See EPA’s Risk Assessment Forum website at http://cfpub.epa.gov/ncea/raf/rafguid.cfm Last accessed on 

February 15, 2007. 

25
 
•	 Open exchange of information and ideas among risk assessors and decision-makers 

•	 Focusing risk assessments on meeting decision-makers’ needs 

•	 Simplicity of the model, using approaches sufficient to meet decision-makers’ needs 

•	 Transparency of the modeling and decision-making processes 

•	 Use of high-quality data, assured through data audits and verifications 

•	 Credibility through the validation of models, analysis of uncertainty, and peer review 

of risk assessments 

To improve the management of MRA processes, realistic time frames and resources, and 

opportunities for staff to build MRA capabilities have been recommended (U.S. FDA/CFSAN, 

2002). 

3.1.2. Canada 

Canada’s fundamental principles for risk management (Health Canada, 2000) include 

•	 Improving health through a “precautionary” approach 

•	 Involving stakeholders in a process tailored to fit the issue in its real-world context 

•	 Communicating effectively 

•	 Using a broad perspective, as well as integrated and collaborative approaches 

•	 Using sound scientific advice 

•	 Making the risk assessment and decision-making processes transparent 

3.1.3. Australia and New Zealand 

Important principles cited in MRA policy documents for these two nations include 

•	 The goal of MRA is to protect public health. 

•	 MRA can identify significant issues and hazards. 

26
 
•	 MRA requires a structured, systematic and transparent process. 

•	 The breadth and depth of the MRA approach should align with the complexity of the 

problem and the potential risk level. 

•	 MRA outcomes should be evaluated. 

•	 Uncertainties need to be addressed in MRA. 

•	 Risk management decisions should be based on health-related values derived from 

MRA. 

•	 MRA targets should be verified using monitoring and field audits. 

•	 MRA should involve stakeholders and other agencies in the process. 

•	 Risk communication strategies should involve approaches suitable for the public and 

agency employees. 

•	 Public trust and confidence must be maintained. 

3.1.4. France 

The French Food Safety Agency relies on the risk assessment principles put forth by the 

FAO/WHO (FAO/WHO, 2002a cited in Pouillot et al., 2004). 

3.1.5. The Netherlands 

MRAs in The Netherlands focus on representing reality as comprehensively as possible. 

They construct a series of mathematical models aligned in a “farm-to-fork” chain. This is the 

approach that was used by Nauta et al. (2005). 

3.1.6. Sweden 

The Swedish food safety agency’s MRA principles include: transparency, 

clearly stated assumptions, and evaluation of uncertainty and variability. Sweden has promoted 

the use of Monte Carlo methods for effective evaluation of MRA (Lindqvist and Westöö, 2000). 

3.1.7. United Kingdom 

Principles that guide MRAs in the UK are based on the 1999 guidelines of Codex 

Alimentarius Commission (see section 3.1.9.1 below and Hill et al., 2003). Additionally, the UK 

emphasizes: 

27
 
 

 

 

• Examination of the impacts of parameters on possible control strategies 

• Iterative processes 

• Identification of data limitations 

• The use of HACCP principles 

Furthermore, the UK’s Advisory Committee on Dangerous Pathogens articulated the 

importance of ensuring that MRAs are conducted consistently and explicitly, based on science, 

and open for public and expert scrutiny (ACDP, 1996). 

3.1.8. European Union 

The Scientific Steering Committee has issued a number of reports to harmonize risk 

assessment practices, articulating many of the same concepts found in the United States and 

other nations. Efforts to advance exposure assessment have led to a modular process risk model, 

which represents six components in the farm-to-fork pathway: growth, inactivation, portioning, 

mixing, removal, and cross contamination. A model is developed for each of these modules,10 

based on available scientific data. The assumptions, uncertainties, and limitations are noted when 

the outputs of the exposure assessment are presented to decision-makers. This report also notes 

the importance of risk assessors effectively communicating their data needs and assessment 

products to risk managers and other scientists. Recommendations for ensuring effective 

communications are included in the report (EC, 2000). 

3.1.9. United Nations 

3.1.9.1. Codex 

This organization’s seminal statement of principles for microbial risk management was 

published in 1999, along with guidelines for conducting MRAs (Codex, 1999). The principles 

emphasize the importance of 

10 The term “module” is used in this report to refer to self-contained units that perform a specific task or 

function within an overall problem system. Modular approaches to microbial risk assessment have been developing 

through initiatives of the FAO/WHO committees and food-related agencies of The Netherlands and United States. 

28
 
•	 Sound science 

•	 Functional separation of risk management and risk assessment 

•	 Use of the traditional four-compartment model (e.g., NRC, 1983) 

•	 Clarification of the MRA’s purpose and constraints 

•	 Transparency of the process 

•	 Description of uncertainties 

•	 Use of good quality data 

•	 Consideration of the dynamics of microbial life cycles 

•	 Reiteration and evaluation of the results, as needed to keep the information current 

Codex expanded these principles a few years later (FAO/WHO, 2002b), adding and 

emphasizing the following concepts. 

•	 Priority of human health protection 

•	 Clear risk manager-stakeholder communication 

•	 Documented processes 

•	 Clear MRA objectives defined in advance 

•	 Role of uncertainty in informed decision-making 

•	 Need for precautionary approaches 

•	 Use of a comprehensive, structured process; e.g., involving the whole food chain 

(from production to consumption) and identification of available risk management 

options 

•	 Necessity of feasible and effective risk controls 

Codex also defined ten principles to facilitate the conduct of MRAs (Codex 2003). These 

include 

29
 
 

 

•	 Clarifying the scope and purpose of the MRA 

•	 Selecting experts in a transparent process 

•	 Conducting MRAs in accordance with defined principles and steps 

•	 Using all available scientific data 

•	 Examining all risk-related components from production to consumption 

•	 Declaring constraints 

•	 Stating assumptions 

•	 Describing uncertainties 

•	 Using realistic exposure scenarios 

•	 Presenting the final results in usable forms 

3.1.9.2. Joint FAO/WHO 

The Joint FAO/WHO Expert Meetings on Microbial Risk Assessment (JEMRA) provide 

technical support to Codex for its deliberations, conduct risk assessments, and provide 

information and advice to Codex and its member countries (FAO/WHO, 2003a). By 2000, 

JEMRA had produced several reports that documented the principles for MRAs and how MRAs 

should be conducted.11 

A joint consultation in 2002 revealed important lessons for further development of MRA 

principles and guidelines (FAO/WHO, 2002a). As in other workshops, the participants noted the 

importance of transparency, credibility, and the use of good quality data and peer reviews.12 

Participants in this consultation noted the need for 

•	 Risk managers and assessors to communicate throughout the MRA process to ensure 

that the purpose and scope are clear 

•	 Sufficient resources to start and complete the assessment 

11 See WHO’s website at http://www.who.int/foodsafety/publications/en
 

12 See Table 1. 

30
 
•	 Continuing coordination of contributors 

•	 Useful products 

Annex III of the consultation report defines the purpose of an MRA as “the objective 

interpretation of relevant scientific knowledge to help the risk manager make an informed 

decision” and describes how to develop an MRA’s scope and conduct the MRA process 

(FAO/WHO, 2002a). The report also points out that existing MRA modules (e.g., for the 

production-consumption chain of events examined in exposure assessment) could be shared 

among risk assessors, thereby reducing time and effort in subsequent MRAs. 

In 2003, FAO and WHO articulated the following principles specifically for MRA 

(FAO/WHO, 2002b; 2003a): 

•	 MRA should provide risk managers with a “best estimate” of the risk and doseresponse relationship, as free from bias as possible. 

•	 Uncertainty and variability should be tracked throughout the model and included in 

the final estimate. 

•	 Independence and separation of hazard characterization and risk management are 

essential. 

•	 Interaction between risk assessors and managers is necessary to ensure that the final 

product is useful, understandable, and relevant to policy-makers. 

•	 Transparency requires full documentation of the process, including sources of data, 

an evaluation of the quality of the data, and any assumptions made to implement the 

MRA. 

•	 When selecting mathematical models, issues to consider include the goodness-of-fit, 

conservativeness, mechanistic relevance, and flexibility of the model. They noted that 

modelers should be wary of becoming too attached to any particular model; modelers 

can achieve objectivity by thoroughly checking the fit of the model to the data. 

These agencies also state that the MRA process will vary due to the nature of the 

pathogen being analyzed and the interdependence of steps and the sequence and timing of events 

in the process being modeled. Furthermore, modelers carefully define “infection” and the 

spectrum of adverse outcomes linked to exposure to the pathogen. These definitions ought to be 

31
 
based on a thorough understanding of the physiopathology of the disease and the “natural 

history” of the disease (FAO/WHO, 2003a). 

An additional principle of “substantial equivalence” was stated in a joint FAO/WHO 

expert consultation on the safety assessment of foods derived from genetically modified animals 

(FAO/WHO, 2003b); for example, traditional food products should serve as the baseline for 

judging safety of newly derived foods. 

3.1.9.3. World Health Organization 

In 2002 WHO issued a set of draft principles and guidelines to conduct any type of 

microbial risk management process, including risk assessment (FAO/WHO, 2002b). These 

principles were 

•	 Protection of human health should be the primary consideration in risk management 

decisions. 

•	 Risk management should include clear, interactive communication between 

stakeholders during various aspects of the process, as appropriate. 

•	 Processes and decisions should be transparent and fully documented. 

•	 The establishment of risk assessment policy is a responsibility of the risk managers. 

The objective of risk assessment should be clearly defined before the risk assessment 

begins. 

•	 The scientific integrity of the risk assessment process should maintain the functional 

separation of risk management and risk assessment, while ensuring transparent and 

appropriate interaction between them. 

•	 Risk managers should take into account the uncertainty of the risk estimate when 

making risk management decisions. 

•	 In the case where scientific knowledge of the risk is insufficient, it may be 

appropriate for risk managers to apply a precautionary approach, through interim 

measures. 

•	 To arrive at a decision, risk management should follow a structured process and must 

include identification of available risk management options and their likely impact on 

mitigating risk to human health. 

•	 Risk management decisions should take into account the whole food chain from 

primary production to consumption including imported foods, and should be 

32
 
implemented in the context of appropriate food safety infrastructures (e.g., regulatory 

enforcement, food product tracing systems). 

•	 Risk managers should ensure that any control measures that are to be implemented 

should be feasible, effective, and proportionate to the risks identified. 

•	 Risk management decisions should always be open to review when new information 

becomes available that substantively alters the conclusions of the risk assessment or 

its associated degree of uncertainty or as new risk management options become 

available. 

•	 The effectiveness of risk management measures should be assessed periodically with 

regard to the risk management goals, and the measures should be revised as 

appropriate. 

•	 Risk management goals should be periodically assessed in order to encourage 

continuous improvements relating to public health risk. 

3.2. Concepts 

The term “concept” usually refers to general ideas or understandings that are derived 

from and informative for addressing specific instances or occurrences. This report adopts the 

term “concepts” to compile the key issues noted by assessors and managers of microbial 

pathogen risks. Some of the overarching concepts most often mentioned in MRA policy 

documents and peer-reviewed literature include 

•	 Consider the dynamic dimensions of the pathogen, environment, host, and human 

population. 

•	 Construct a conceptual model early in the process. 

•	 Model realistic conditions. 

•	 Use a comprehensive source-to-exposure pathway paradigm to organize information 

and construct a series of linked mathematical models. 

•	 Recognize the interrelated nature of steps in the paradigm, such as the sequence and 

timing of events. 

•	 Clearly define terms including “infection” and health outcomes. 

•	 Clearly define the outcome metrics (individual and/or population scale), and ensure 

that they link to the decision-makers’ needs. 

33
 
Two dominant types of MRA are risk-ranking exercises and product pathogen pathway 

analyses. Risk ranking has been used to prioritize multiple risks and determine resource 

allocations (U.S. FDA/CFSAN, 2002). Pathway analyses assess the entire pathogen transmission 

process from environmental source to human exposure. This organizational tool helps risk 

assessors and modelers identify the many elements to consider for the model, recognize the types 

and sources of data needed for modeling and the relative importance of elements to consider 

when constructing the mathematical models. For instance, the comprehensive framework used 

in FDA’s risk assessment of raw oysters (2005) demonstrates that a rich mix of data sources can 

be combined to implement an effective MRA. Pathway modeling results are used to estimate the 

risk of adverse outcomes within a population. MRAs of pathogens in recreational water (Soller et 

al., 2003), biosolids (Eisenberg et al., 2004), and processed foods (USDA, 2005b) have included 

more comprehensive pathway modeling than is typically seen in chemical risk assessments. 

Many issues in MRA differ importantly from chemical risk assessment, demanding 

different conceptual and practical modeling approaches (WHO, 2005; Schaub, 2004; 

FAO/WHO, 2003a; OECD/WHO, 2003; Eisenberg et al., 2002; Parkin, 2002; Medical Research 

Council Institute for Environment and Health, 2000; ILSI, 2000; Haas et al., 1999; ECFS, 1997). 

The unique characteristics of microorganisms and host populations and their dynamic aspects 

ought to be considered carefully when designing an MRA approach (Buchanan, 2003). Specific 

concepts that should be addressed in MRAs are highlighted in the following sections; these are 

listed according to their likely placement in a source-to-response model. 

3.2.1. Pathogen Characteristics 

In the absence of seasonality or other data, modelers assume that microbes are spread 

evenly in the environment, although heterogeneous distribution is likely. Similarly, there are 

limited data to indicate the number of organisms necessary to cause adverse health effects. Due 

to variations in strain, life stage, and survivability, not all individual pathogens in the 

environment are capable of inducing illness; however, for modeling purposes they are all 

assumed to be viable and pathogenic. Following is a summary of pathogen characteristics that 

may contribute to the MRA modeling process: 

•	 Microorganisms can self-replicate. Even if one cell is not sufficient in and of itself to 

induce pathogenicity in humans, one microorganism may have the capacity to grow 

within the body and develop a colony that is sufficient to induce a pathogenic process 

(Haas et al., 1999). 

34
 
•	 Strains vary in virulence. For example, the variations in infectivity of strains of 

Cryptosporidium parvum have been identified based on human challenge trials 

(Chappell et al., 1999), but the significance of these variations at the human 

population scale has not yet been determined. Such variations may affect doseresponse relationships (Coleman et al., 2004). 

•	 Pathogens may evolve in terms of their virulence and other key characteristics, (e.g., 

as they pass through various infected individuals and other hosts). Some pathogens 

may lose their virulence as they pass from the initial human (animal) host to a second 

and/or third host, accounting in part for the decline in disease outbreaks. 

•	 Microorganisms can grow as conditions change during the movement of food from 

the farm to the table. The pH, water content, temperature, and salinity of food 

matrixes are known to be important, influential characteristics of foods that affect 

pathogen dynamics (e.g., USDA, 2005a). 

•	 Characteristics of the microorganism, such as viability and resistance, may also affect 

the dynamics of disease outbreaks. For example, the chemical and/or thermal 

processes used in food processing and/or water treatment systems reduce the viability 

and survival of many microorganisms before foods, food products, and drinking 

water reach consumers. Furthermore, if microorganisms are not viable and infective 

when susceptible hosts come in contact with them, they will not cause infection in 

those hosts. 

•	 Pathogens vary in detectability, and sampling recovery rates. Sampling collection and 

laboratory detection procedures may not preserve 100% of the actual concentration 

levels of the pathogen in environmental media (air, water, foods, etc.). The degree of 

loss between the environment and the laboratory detection level varies, and ought to 

be considered in MRA modeling whenever possible. 

3.2.2. Environmental/Media Conditions 

When developing the pathway component of conceptual models, assessors thoroughly 

consider the ways in which a pathogen moves from its source(s) to humans. Pathogens are found 

in air, drinking water, recreational water, wastewater, biosolids/manure, soil, fresh and processed 

foods, products such as industrial and pesticidal formulations, etc. In each of these media, 

pathogens encounter environments that are more or less favorable to their growth, transport, 

survivability, viability, and pathogenicity. Mechanisms of release from sources, intermediate 

hosts or reservoirs, life stages and forms, and the impacts of human interventions (such as 

chlorination and filtration of drinking water supplies) should be considered. Environmental 

conditions frequently change the number, concentration, and form of pathogens in human 

exposures. For example, 

35
 
 

 

•	 Pathogens are not usually suspended evenly in water or other media. Food and soilrelated matrices tend to have more specific, localized boundaries (e.g., egg shells, 

packaged, food products, biosolids) and binding properties that permit focused 

microbial growth and more readily identifiable contamination than do media without 

such binding properties or specific boundaries (e.g., ambient air, flowing bodies of 

water). 

•	 Environmental conditions may permit long-term survival of the microorganism. 

Because of specific life cycle and other characteristics, some pathogens (such as 

anthrax) can infect humans decades after the pathogens have appeared in the ambient 

environment. 

•	 Other species may serve as intermediate hosts providing additional pathways for the 

microorganism to spread. For some pathogens, animal and insect vectors may be 

important steps in the disease transmission process (Haas et al., 1999), which may 

need to be considered in MRA models. 

•	 Intervention strategies such as chlorination and irradiation may affect the viability of 

the pathogen. Worldwide chlorination has been successfully used to inactivate 

microbial pathogens in drinking water (Embrey et al., 2002). 

3.2.3. Host Characteristics 

For MRAs, characteristics of hosts need to be considered on individual and population scales. 

Age, gender, prior disease and exposure, and medication status, immune status, socioeconomic 

status, and other factors may all be needed to implement MRAs. Although many of these 

variables can be considered in a conceptual model, they usually cannot be modeled 

mathematically due to the lack of appropriate data; however, some MRAs (e.g., U.S. EPA, 

2005b; Makri et al., 2004) have been able to account for at least several of these aspects of 

human response. Information on specific host characteristics to consider in microbial risk 

assessment include the following. 

•	 Susceptibility to infection and disease depends not just on individuals’ health status, 

but also their pre-existing immunity and pathogen exposures.13 Individual 

susceptibility depends on many factors, some that are host-specific and some that are 

not. Determinants of susceptibility include age, pre-existing chronic disease, and 

simultaneous pathogen exposures (Haas et al., 1999). 

13 Population variations in genetic makeup and immune-susceptible proportions are important. For 

example, strains of Campylobacter jejuni and related population immunity and illness rates vary around the world 

(Parkin and Hawkshead, 2003). 

36
 
•	 Human populations are not homogeneous in their genetic makeup or immune and 

asymptomatic carrier status. The proportion of immune and susceptible individuals in 

a population varies; for example, strains of Campylobacter jejuni and related 

population immunity and illness rates vary in different parts of the world (Parkin and 

Hawkshead, 2003). 

•	 Subpopulations which may be of concern include the young, the elderly (especially 

those with underlying diseases), the malnourished, and persons with HIV/AIDS or 

other immunocompromised conditions, lupus, cystic fibrosis, and transplant and 

chemotherapy patients (Rose, 1997). 

•	 A pathogen’s persistence in an individual and the individual’s shedding of the 

pathogen leads to continued risk of secondary and tertiary spread. The longer a 

pathogen is viable and shed in infective form by hosts, the longer that the 

microorganism has the capacity to initiate pathogenic processes in additional hosts. 

•	 Population characteristics, such as immunity and social behavior, are potentially 

important. Social factors that may affect immunity include access to health care; for 

example, the lack of access increases the probability of chronic disease conditions 

being under-treated, thereby reducing the individual’s capacity to mount an effective 

immunological defense (Balbus and Parkin, 2000). 

•	 Intervention strategies such as vaccination and pasteurization may affect the disease 

process on individual and population scales. Public health interventions have 

historically contributed to declines in the occurrence of infectious disease, and may 

serve as the bases for developing risk management options for selected pathogens 

with effective interventions (e.g., HACCP controls for foodborne pathogens such as 

salmonella). 

3.2.4. Exposure 

The number and/or concentration of pathogens per unit volume are needed for exposure 

assessment. Estimating the number of pathogens that may come into contact with humans are 

very challenging and require considerable modeling skill. 

Depending on the medium in which the pathogen is found, rates of inhalation, ingestion, 

and/or dermal contact may be needed for risk calculations. Although detailed consumption data 

sometimes exist, the data often do not describe foods or consumption patterns in sufficient detail, 

include information on sensitive subpopulations, or provide sufficient details about food 

processes. As a result, risk assessors have had to rely on aggregated, insufficiently detailed, or 

inaccurately targeted data (Barraj and Petersen, 2004). Most modelers use a point estimate or 

population average (e.g., two liters of water/person/day) (U.S. EPA, 2000b). 

Other exposure factors to consider include 

37
 
•	 Single exposures are sufficient to present risk. To implement a conservative public 

health approach in MRAs, modelers often assume that only one, single, exposure to a 

microorganism is sufficient to induce a pathogenic process in human hosts (Haas et 

al., 1999). Although this concept may conflict with evidence for some pathogens 

(e.g., where family members are the predominant hosts or secondary hosts in an 

outbreak), the single-exposure assumption aligns with the no-threshold, doseresponse approach typically used in MRAs. 

•	 Each exposure is an independent, non-cumulative event. For the purposes of MRA 

modeling, current statistical methods require that each exposure be treated as an 

independent event (Haas et al., 1999). Although each exposure may not be 

independent in an outbreak (e.g., where family members are exposed to the same case 

over days or weeks), current statistical methods cannot account for the 

interdependence of related exposures. 

•	 Exposure to pathogens may lead to immunity. Humans can develop immunity to 

many pathogens from one or more exposures, but the determining factors of 

immunity are unclear. Dynamic disease models either include the known proportion 

of the population that is immune, based on clinical and/or field evidence, or assume 

that a proportion of the host population can become immune to a pathogen (ideally 

based on evidence for a similar pathogen) (e.g., Eisenberg et al., 1996). 

3.2.5. Dose 

Estimating whether a microbial pathogen can overcome physiological barriers and reach 

the target tissue is not always easy. MRA typically deals with a single cell or unit of infection. 

In many cases, modelers have assumed a non-threshold approach⎯that one pathogen reaching 

the target tissue is sufficient to initiate the disease process (Haas et al., 1999). 

Researchers have used many data sets to develop dose-response curves for a variety of 

microorganisms. These efforts have produced about ten different mathematical forms to consider 

for MRAs (Haas et al., 1999). For many microbial pathogens, two-parameter models, such as 

the commonly used beta-Poisson model, have been found to perform at least as well and 

sometimes better than more complex models (Moon et al., 2004). 

3.2.6. Human Health Responses 

Additional issues in MRA modeling arise from the need to recognize that a pathogen may 

be capable of inducing a range of human health responses both in individuals (e.g., 

asymptomatic infection, acute illness, sequelae, death) and populations (e.g., incident case rates, 

hospitalization rates, mortality rates). On the population scale, the rate of disease spread varies 

depending on numerous factors, such as 

38
 
•	 The proximity of infected and susceptible populations 

•	 The viability and concentration of the pathogen in the material excreted by one host 

and transmitted to another (secondary spread) 

•	 The virulence of the strain 

On the individual scale, there may be a wide range of clinical outcomes linked to a 

specific pathogen (Asano et al., 2007), and the range of severity of outcomes linked to a specific 

pathogen can be considerable (Haas et al., 1999). For example, in individuals, C. jejuni is known 

to cause Guillain-Barré Syndrome in a small portion of the population, along with more 

common, acute episodes of diarrhea (WHO, 2002b). Some Guillain-Barré cases resolve in three 

weeks with no paralysis, while others result in long-term, significant paralysis (WHO, 2002b). 

Data on pathogen and disease dynamics and the impacts on susceptible subpopulations can be 

effectively modeled for some pathogens (Eisenberg et al., 2004). Furthermore, social and 

economic impacts secondary to health impacts can be modeled as proxies when direct health data 

are not available. For example, data on the use of over-the-counter medications, visits to hospital 

emergency departments, and days of lost work or school time may be used to estimate the 

impacts on human health. 

3.2.7 Modeling 

Converting a conceptual model or pathway model into a series of mathematical models 

requires attention to technical and data quality concerns. Following is a summary of modeling 

issues to consider in microbial risk assessment: 

•	 It is recommended that mathematical models be flexible and represent the level of 

conservatism set by risk managers, and effectively model parameter relationships as 

judged by goodness-of-fit evaluations. 

•	 Static models for MRA have been in use for several decades (Haas, 1983), but are not 

the most useful for all pathogens (Asano et al., 2007). 

•	 Where infectivity or pathogen life cycle dynamics are important determinants of 

disease in human populations, infectious disease models may be more appropriate 

(e.g., Eisenberg et al., 1996). However, such dynamic models usually require more 

39
 
extensive data, and potentially more computing power, which limits their feasibility 

(Asano et al., 2007). 

•	 Dynamic aspects of agent and host populations—including population changes in 

susceptibility and behaviors—can be considered. Both microbial pathogens and 

human hosts are living entities that change in many ways during their life cycles. The 

changes that occur in each may affect the probability of human disease in both direct 

and indirect ways (Haas et al., 1999). 

•	 Modeling processes may be highly complex, and may be incomplete or infeasible due 

to the lack of data. Conceptual models covering pathogen sources to human illness 

usually involve many steps (e.g., U.S. FDA/CFSAN and USDA/FSIS and CDC, 

2003). The availability of data to characterize all of the components and processes in 

such a model is quite variable, which leads to cumulative, extensive uncertainties in 

the final results. 

•	 Few MRA models have been validated because of the lack of data to test models for 

different locales and/or conditions. 

•	 Data gaps limit the precision of MRAs. Uncertainty in modeling is often related to the 

lack of relevant empirical data to quantify the concentration of pathogens in the 

environment and in exposures; to accurately determine the shape of the dose-response 

relationship curve; and to measure the magnitude of epidemic (as distinct from 

endemic) adverse health effects (Haas, 2002; Haas et al., 1999). 

•	 The impacts of uncertainty and variability need to be assessed on MRA results and 

communicated to risk managers. 

A summary of key issues in modeling microbial pathogen risks are shown in Table 2. 

40
 
 

Table 2. Key Issues in Modeling Microbial Pathogen Risks 

Microbial Pathogen • Taxonomy 

• Strain 

• Ecology 

• Survival 

• Characteristics that affect growth 

• Life stage 

• Viability 

• Infectivity and incubation period 

Environment • Medium (e.g., food, water, soil, air) 

• Characteristics of the medium (e.g., acidity, presence of 

other microorganisms) 

• Temperature 

• Time, season 

Human Host • Age 

• Gender 

• Nutritional status 

• Immune status 

• Pre-existing disease 

• Susceptibility to the specific microbial pathogen 

• Range of health outcomes 

• Severity of outcomes 

• Proximity and behaviors of infected and susceptible 

populations 

Relationships between • Virulence of the microbe 

the Pathogen, Host and • Host specificity

Environment • Environmental conditions that contribute to exposure 

• Mechanisms of infection 

• Secondary spread 

Modeling • Adequacy of conceptual framework 

• Ability to characterize all aspects of the framework 

• Static vs. dynamic models 

• Characterization of the dose-response relationship 

Sources of Uncertainty 

and Variability 

• Data quality 

• Measurement 

• Assumptions 

Model Validation • Availability of data 

3.2.8. Sources of Data 

Accessing appropriate data for MRAs involves many issues. Sources may include 

research and clinical data, epidemiological and human exposure data, as well as environmental 

or food monitoring data. Examples of issues to consider follow: 

41 
•	 Not all sources of data are readily accessible—particularly human health data that may 

require institutional review board clearance to protect human research subjects. Other 

types of data may not be in the public domain or available to persons outside of the 

organization that collected the data. 

•	 Many data sources have limitations in scope, timeliness, and relevance to the pathogen 

and/or population of concern. 

•	 Sources may not be accurate or precise. For example, pathogen recovery rates and the 

proportion of infective microorganisms detected in an environmental sample are typically 

fraught with sampling and analytic limitations. Sampling pathogens in drinking water is 

known to have significant field limitations; furthermore, distinguishing the infective 

strains of pathogens is often impossible. 

Disease outbreak data may provide insights about the potential for secondary and tertiary 

disease transmission, the magnitude and severity of infection and illness, and other 

characteristics of disease dynamics. While some modelers assume that outbreak or surveillance 

data are sufficient to use in MRAs to assess microbial-related health effects (e.g., Soller et al., 

1999), others have noted important limitations of surveillance and outbreak data and have 

questioned the value of these data for modeling microbial pathogen risks (Makri et al., 2004; 

Flint et al., 2005). In the absence of better data, however, surveillance and outbreak data⎯with 

all of their potential flaws⎯may be the best data sources available. When necessary, outbreak 

data is used with explicit recognition of their limitations. In some instances, it may be possible to 

adjust reported surveillance or outbreak data and estimate the number of all actual cases (i.e., 

both the reported and non-reported cases) (Flint et al., 2005). 

42
 
4. MICROBIAL RISK ASSESSMENT FRAMEWORKS 

Currently, four fundamental types of microbial risk assessment frameworks exist. One 

type uses the chemical risk assessment framework described in section 2.1.1 (NRC, 1983); 

another type uses a modified NRC framework, in which the two middle steps are sometimes 

reversed; a third framework builds on the NRC approach by adding a problem definition step 

(e.g., part of planning and scoping, or problem formulation) (U.S. EPA, 2005a, 2004b, 1989); the 

final type of framework was developed by ILSI (2000). 

Table 3. Categories of microbial risk assessment frameworks with MRA examples 

1. NRC, 1983 

• WHO, 1995 • Pouillot et al., 2004 

• Haas et al., 1999 • U.S. EPA, 2004a 

• Lindqvist and Westöö, 2000 • Coburn et al., 2005 

• Hill et al., 2003 • EFSA, 2006a, 2006b, 2006c and 

2006d 

• EFSA, 2006a • U.S. EPA, 2006b 

• NZFSA, 2004 

2. Modified NRC, 1983 without an explicit problem definition step 

• Sobsey et al., 1993 • USDA, 2001 

• ACDP, 1996 • FAO/WHO, 2003b 

• Medical Research Council Institute 

for Environment and Health, 2000 

3. Modified NRC, 1983 with problem definition 

• ECFS, 1997 • OECD/WHO, 2003 

• Codex, 1999 • NHMRC-NRMMC, 2004 

• WHO, 1999, 2004b, 2005 and 2006a • Nauta et al., 2005 

• U.S. FDA, 2001 and U.S. 

FDA/CFSAN, 2005 

• USDA, 2005a and 2005b 

4. ILSI, 2000 

The approach that Sobsey and colleagues (1993) proposed is an example of a modified 

NRC framework that is a risk-based conceptual framework for microbial risk assessment based 

on a model presented in an EPA research strategy report (cited in Sobsey et al., 1993). The flowdiagram model began with “microbial hazard identification” and moved into two parallel 

components titled “exposure assessment” and “effects assessment.” These components 

combined into “risk assessment and characterization,” which in turn led to “risk management,” 

which involved microbial indicators and HACCP concepts. Data from microbial assays, human 

populations, organism-host interactions, and relative risks also contributed to the framework. The 

authors stated that their approach was designed to systematically identify, analyze, quantify, and 

characterize microbial risks; compare them to chemical risks; and develop and implement a risk 

43
 
 

management plan. Furthermore, they claimed that their model would help scientists and 

decision-makers identify key issues, information gaps, and research needs. 

The following sections describe the frameworks that different organizations are using 

around the world to conduct microbial risk assessments. 

4.1. UNITED STATES 

4.1.1. Department of Agriculture 

To date, the U.S. Department of Agriculture (USDA) has completed a limited number of 

MRAs; however, no policy document was found describing the agency’s risk assessment 

methods. The Risk Assessment Division of the Office of Public Health and Science has 

described its process steps as: developing the conceptual model,14 collecting and analyzing data, 

identifying data gaps, modeling the pathogen-related risk, and analyzing uncertainty and 

variability (USDA, 2005a). 

Four MRAs posted on the agency’s website were reviewed to assess the agency’s 

approach: three for salmonella, and one for E. coli. Two were conducted in closer alignment 

with the NRC (1983) approach than the other two, but all MRAs revealed very thorough 

strategies for assessing exposures. 

Although researchers conducted earlier quantitative MRAs, the USDA’s Food Safety and 

Inspection Service (FSIS) was the first U.S. regulatory agency to publish a formal quantitative 

microbial risk assessment (on Salmonella enteriditis in eggs and egg products) (USDA, 1998). 

Two years earlier, other units within the USDA and other government agencies, including the 

FDA, had begun to provide input for this risk assessment. The product pathogen pathway 

analysis—from farm to fork—did not explicitly follow the traditional risk assessment paradigm, 

but it did present a comprehensive evaluation of the many steps in moving food products from 

the field to the consumer. The exposure assessment included five modules and sixteen pathways 

in conceptual and mathematical models. The modules were 

• Egg production 

14 A conceptual model is a written or visual representation of predicted relationships between pathogens 

and exposed populations. It may be based on working hypotheses, supported by preliminary data and information, 

and used to organize the conduct of a MRA. The model depicts the purpose, scope, and scale of the MRA; identifies 

variables and data needed to conduct the MRA; and serves as a preliminary or exploratory risk assessment (U.S. 

EPA, 2005a). 

44
 
 

 

 

• Shell egg processing and distribution 

• Egg products and distribution 

• Preparation and consumption 

• Public health outcomes 

As in most risk assessments, the MRA process helped FSIS identify important data gaps 

and research needs to improve the risk estimates. The MRA also gave risk managers a way to 

evaluate mitigation and strategic options for controlling salmonella in eggs and egg products.15 

In its more recent salmonella MRAs, USDA extensively described two sets of modules 

for shell eggs and egg products (USDA, 2005b). Table 4 shows the modules used in these 

paradigms. 

Table 4. USDA salmonella MRA modules for shell eggs and egg products 

Shell Eggs Egg Products 

• Farm • Breaking 

• Storage 1 

• Pasteurization • Pasteurization 

• Storage 2 • Storage and Preparation 

• Preparation 

• Cooking • Cooking 

USDA has also conducted an MRA to examine the impact of lethality standards on 

salmonellosis from ready-to-eat meat and poultry products (USDA, 2005a). The risk assessment 

stages (or modules) that the exposure assessment section of the paper identifies and describes are 

• Raw material pathogen burden 

• Lethality impact16 

• Compliance-level impact 

15 See also WHO, 2002a. 

16 Note that “impact” refers to the change in pathogen concentration in the raw materials, processed or 

prepared foods, or food products as they move through the farm-to-fork process. Changes in concentration may 

occur due to the effects of heating and cooling, storage, pasteurization, cross-contamination, etc. 

45
 
 

• Thermal process safety factor impact 

• Storage and growth impact 

• Reheating impact 

• Risk of illness 

FSIS asked the National Academy of Sciences to review its risk assessment of E. coli in 

ground beef (USDA, 2001). In this case, the agency more clearly organized the MRA in 

alignment with the NRC’s risk assessment components: hazard identification, exposure 

assessment, hazard characterization (dose-response), and risk characterization (NRC, 1983). 

However, the FSIS expanded the exposure assessment component with three farm-to-fork 

modules: 1) production, 2) slaughter, and 3) preparation. 

Although the Academy reviewers praised FSIS for its thorough and comprehensive 

MRA, the committee’s final report noted the impacts of limited data and the use of assumptions, 

such as the “typical individual.” The Academy recommended that USDA provide clearer 

documentation of its assumptions and detailed methods to enhance the MRA’s transparency 

(NRC, 2002). 

4.1.2. Food and Drug Administration 

FDA defines risk assessment as both a process and a product and describes several forms 

of risk assessment models. It uses its assessments to rank risks, analyze product pathways, 

evaluate risk-risk tradeoffs, and assess geographically bounded risks (U.S. FDA/CFSAN, 2002). 

The agency’s MRA components and concepts are basically the same as those used by USDA, but 

FDA gives different names to its concepts and conducts its steps in a different order. 

Nonetheless, FDA tends to use modifications of the chemical risk assessment framework for 

food-related MRAs. 

4.1.2.1. Center for Food Safety and Applied Nutrition 

Center for Food Safety and Applied Nutrition (CSFAN) researchers described the 

purposes of MRA as determining what can go wrong, how it can happen, and what the 

consequences would be (Dennis et al., 2001–2002). Their “generally accepted framework” has 

five steps: statement of the problem, hazard identification, exposure assessment, dose-response 

(or hazard characterization), and risk characterization. 

46
 
A report of the CFSAN Risk Analysis Working Group described the risk assessment as 

including: hazard identification, exposure assessment, dose-response assessment (or hazard 

characterization), and risk characterization (U.S. FDA/CFSAN, 2002). The report also briefly 

described four goals for risk assessment: 

•	 Risk ranking (comparison of risks among several hazards or foods) 

•	 Product pathway analyses (assessment of factors that influence the risk from farm to 

consumption) 

•	 Risk-risk (evaluation of risk tradeoffs) 

•	 Geographical (focused on factors that limit or foster the scope of a risk occurrence) 

Later in the report, the group described four programmatic steps for initiating risk 

assessments: 

•	 Concept generation (a list of potential MRAs, including their purpose, scope, 

importance, needs, and potential use) 

•	 Problem identification (classification of the proposed MRA according to whether it 

should or should not be conducted or whether additional information is needed to 

determine the classification) 

•	 Data feasibility determination (evaluation and recommendation as to whether 

qualitative or quantitative risk assessment, risk management, or research would be 

appropriate) 

•	 Disposition (selection of MRAs to be conducted in the coming year based on 

technical merit, data feasibility, resource availability, and other factors) 

The report also presented the means to conduct risk assessment processes (e.g., assemble 

the risk assessment team). 

CFSAN’s extensive risk assessment of Listeria monocytogenes in ready-to-eat foods used 

the four components of hazard identification, exposure assessment, hazard characterization (or 

dose-response) and risk characterization (U.S. FDA/CFSAN and USDA/FSIS and CDC, 2003), 

although earlier versions reversed the middle two steps (U.S. FDA/CFSAN and UDSA/FSIS and 

CDC, 2003; U.S. FDA/CFSAN and USDA FSIS and CDC, 2001). The primary components of 

47
 
 

 

the 2003 assessment (which focused on deli meats) were the exposure assessment and doseresponse steps.17 Two important advances in this MRA were the use of a dynamic Monte Carlo 

model to estimate levels of contamination as the product moved through the food processing 

system, and a comprehensive exposure pathway for deli meats that was linked to a dose-response 

model. The exposure assessment step included assessed contaminant levels from retail to the 

table and involved distinct mathematical models for estimating 

• L. monocytogenes levels in retail foods 

• Growth between retail and consumption 

• Impacts of the interaction between storage times and temperature 

• Impacts of thermal inactivation (for selected foods) 

This innovative MRA organized food products into categories to put them in rank order 

(e.g., seafood included smoked seafood, raw seafood, preserved fish, and cooked ready-to-eat 

crustaceans). Models were then used to estimate levels of individual and public health risks for 

each category, such as the number of cases of listeriosis per year and the predicted relative risk 

rankings for listeriosis in three subpopulations (perinatal, elderly, and intermediate age). 

In the FDA’s MRA for Vibrio parahaemolyticus in raw oysters, the agency used a U.S. 

step18 to list the risk management objectives, define the geographic and seasonal dimensions of 

the MRA, and identify data sources before implementing the traditional NRC risk assessment 

steps (U.S. FDA/CFSAN, 2005). The modules used to assess the conditions and dynamics from 

the point of harvest to consumption were 

• Harvest 

• Post harvest 

17 FDA and Exponent, Inc. developed FARE MicrobialTM software for conducting probabilistic microbial 

risk assessment (Exponent, Inc., 2002). The two modules included in the package are for Contamination and 

Growth, and Exposure. The first tracks contamination levels through a 20-stage farm-to-fork process and generates 

distributions of contamination at the time of food consumption. The second module produces distributions of 

pathogen exposure, as Colony Forming Units per food unit, based on demographic and national survey data on food 

consumption. The output of this module can be used as the input for FDA’s dose-response model. 18 This “scoping” step included many of the elements of EPA’s “problem formulation” step (U.S. EPA, 

2004b; U.S. EPA, 2005a). 

48
 
 

• Consumption 

The 2001 draft of this MRA used the sequence of hazard identification, exposure 

assessment, hazard characterization, and risk characterization (U.S. FDA/CFSAN, 2001). The 

assessment separately modeled six oyster harvesting regions and four seasons of harvesting. In 

this earlier version of the exposure assessment step, three modules were used to organize the 

complexity: harvest, post harvest, and public health. 

CFSAN has also used MRA to address food-related bioterrorism concerns. In this case, 

the modeling components were: hazard identification, hazard characterization, exposure 

assessment, and risk characterization (U.S. FDA, 2003). 

FDA has defined risk communication as the open exchange of information and ideas, and 

the agency has identified risk communication as a part of the risk analysis process with a status 

equal to that of risk assessment (U.S. FDA/CFSAN, 2002). Although FDA has little mention of 

risk communication in its risk assessments, the agency does prepare and web-post interpretative 

summaries of its MRAs for general public use and technical reports for more detailed-oriented 

readers (U.S. FDA/CFSAN, 2005). 

4.1.2.2. Center for Veterinary Medicine 

This FDA unit conducted a risk assessment of fluoroquinolone-resistant campylobacter in 

chickens (U.S. FDA, 2001). This MRA is not a full risk assessment (in the traditional NRC 

framework) and does not model the “farm-to-fork” pathway typical of most FDA risk 

assessments. Instead, this MRA uses a quantitative model to link the prevalence of resistant 

campylobacter in chicken with the prevalence of resistant infections in the U.S. human 

population due to the chicken consumption. The model outcomes are presented as the percentage 

of infections among the U.S. population and three subpopulations. The model depends on 

observational data and requires fewer assumptions than a fully implemented MRA, but it meets 

the Center’s purpose: to assess the impacts of various risk management options. Transparency, 

consistency of results, and flexibility for examining a variety of conditions were important 

considerations when the Center for Veterinary Medicine developed this approach. 

4.1.3. Environmental Protection Agency 

EPA addresses microbial hazards in drinking water and other environmental contexts, 

such as cleanup sites, wastewater, biopesticides, biosolids/manure, and recreational water. 

49
 
 

4.1.3.1. Office of Pesticide Programs 

Under section 408(p) of the Federal Food, Drug and Cosmetics Act, as amended in 1996 

(U.S. FDA, 1996), EPA is required to screen pesticides and other active ingredients for their 

potential impacts on human health. The Office of Pesticide Programs conducts risk assessments 

of modified organisms intended for pesticidal use. The assessments follow the 1983 NRC risk 

assessment framework and vary in detail according to the scientific information available. 

4.1.3.2. Office of Water 

In the past decade, EPA has begun efforts to transfer FDA’s and others’ experience with 

foodborne pathogens to the drinking water experience. In the mid-1990s, EPA’s Office of Water 

and the International Life Sciences Institute (ILSI) convened a workshop of experts to design a 

conceptual framework for assessing risks associated with waterborne microbial pathogens. 

Building on chemical and ecological risk assessment methods and lessons learned, the workshop 

participants designed a four-component process that was organized into three steps: (1) problem 

formulation, (2) problem analysis (with two sub-steps for exposure and human health effects), 

and (3) risk characterization (ILSI, 1996). 

The first step (problem formulation) states the fundamental questions to be addressed, 

defines the scope and scale of the assessment, and identifies the necessary variables and data. 

Risk assessors, managers, and stakeholders consider these issues collaboratively to ensure that 

the end users’ needs will be met. The second step (analysis) characterizes the independent and 

related variations in the organism, host, and environment; discusses the impacts of the variations; 

and decides the nature of the dose-response relationship. For example, subpopulations are 

identified, specific pathogen-host relationships are considered, exposure pathways are 

determined, the impacts of dose variability are evaluated, and uncertainties in the field and 

laboratory data are examined. The final step (risk characterization) integrates the exposure and 

health findings; reviews the biological plausibility of the estimated effects; conducts the 

sensitivity analyses; documents uncertainties and assumptions; analyzes management options 

(including the use of surrogates and indicators in monitoring programs); and considers the use of 

measures of effectiveness (such as disability adjusted life years [DALYs]) (ILSI, 2000). 

This model has been tested in two case studies, one for cryptosporidium (Teunis and 

Havelaar, 1999) and one for rotavirus (Soller et al., 1999). The case studies identified modeling 

issues, information limitations, and data needs, and were used to review and revise the initial 

50
 
pathogen risk assessment paradigm. The results led to a reorganization of some elements of the 

model and enhancements and clarifications of several other elements (ILSI, 2000) (Figure 3). 

Figure 3. Components of a microbial risk assessment. 

Source: Adapted from ILSI, 2000 

Problem 

Formulation 

Analysis 

Risk 

Characterization Pathogen 

Characterization 

Pathogen 

Occurrence 

Exposure 

Analysis 

Exposure 

Profile 

Host 

Characterization 

Health 

Effects 

Dose-Response 

Analysis 

Host-Pathogen 

Profile 

Exposure 

Characterization 

Human Health 

Effects 

Characterization 

Risk 

Estimation 

Risk 

Description 

51
 
 

 

The ILSI paradigm is similar to chemical and ecological risk assessment approaches 

(U.S. EPA, 1998; NRC, 1983) with adaptations to account for the unique characteristics of 

living, microbial hazards and the dynamics that occur in the environment and human populations 

in the presence of these pathogens. The ILSI paradigm explicitly addresses these unique issues 

(e.g., pathogens’ capacity to grow and remain viable in a variety of environmental media, agenthost specificity, and secondary or person-to-person spread of disease). Another issue is that 

specific strains of microbial pathogens typically behave differently in humans than in animals. 

Unlike chemical risk assessment, MRA cannot rely heavily on animal data. 

The ILSI framework is sound, but a great deal of research is needed for many 

microorganisms to fill data gaps and reduce MRA uncertainty, such as the biological 

mechanisms that cause progression from infection to disease. In addition, data are needed to 

clarify the distribution of pathogens, the probability of infection following ingestion of 

organisms at a specific dose, the nature of dose-response relationships, the determinants of 

illness following infection, as well as the impact of factors such as immune status, prior 

exposures, and medical conditions (ILSI, 2000). 

The ILSI documentation (2000) also notes that risk communication is an important aspect 

of MRA, and calls for the development of this component in MRAs.19 

EPA’s guidance on risk characterization (U.S. EPA, 1995) indicates that the standard 

four-compartment risk assessment framework (NRC, 1983) be used. In 2005, the Office of 

Drinking Water conducted an economic analysis for the LT2 Final Rule and based it on a risk 

assessment of cryptosporidium in surface and finished water (See section 5.2 in U.S. EPA, 

2005b). This risk assessment was conducted in alignment with EPA’s risk assessment principles 

and policies; its purpose was to estimate the pre-LT2 (baseline) annual incidence of pathogenrelated illness and death and to compare the estimates to those that would result from 

implementing different treatment options. The pathogen and related public health concerns were 

described with attention to subpopulation issues and the quality of available human health data 

(see section 2.4 in U.S. EPA, 2005b). Following a hazard identification step, the dose-response 

step included three subcomponents: infectivity dose-response, the risk of illness given infection, 

and the risk of mortality given illness. The exposure assessment step relied on both individual 

and population scale data to estimate human exposures to infectious oocysts. The final step, risk 

characterization, used Monte Carlo methods to combine the results of the dose-response and 

19 Note that in EPA’s recent genomics guidelines, the need for partnerships and translating technical 

information for general audiences was noted (U.S. EPA, 2006a). 

52
 
 

 

 

exposure assessments for estimating the annual individual and population-scale risks of illness 

and death. The population scale estimates were made including estimates of secondary spread of 

disease.20 The impacts of uncertainty and variability throughout the MRA were analyzed 

extensively. While considerable attention was given to sensitive subpopulations, data were not 

available and/or sufficient for estimating their risks. 

4.1.3.3. National Center for Environmental Assessment 

In 1996, the amended Safe Drinking Water Act (SDWA) required EPA to publish a list of 

contaminants, which became known as the Contaminant Candidate List. In the 1998 and 2005 

versions of the list, several cyanobacteria were listed; the later list was based in part on the 

results of a 2001 EPA-hosted meeting of experts, who identified algal toxins as potential human 

health concerns. The National Center for Environmental Assessment has produced a series of 

publications to support the Office of Water’s decision-making about such toxins. EPA risk 

assessment guidelines and the NRC (1983) framework has been used as the structural basis for 

these publications. The focus of these documents, however, has been on compiling and 

integrating information for the hazard identification and dose-response assessment steps. 

4.1.3.4. National Homeland Security Research Center 

Risk assessment models are important tools for predicting and prioritizing hazards that 

may be caused intentionally. Center staff members have described the value of a microbial risk 

assessment framework for biological contamination incidents (Nichols et al., 2006). Both 

strategic and tactical applications of MRA are envisioned and described across a planningpreparing-responding spectrum of activities. Prior to an incident, MRA can be used to identify 

and characterize pathogens, assess potential exposures, prioritize hazards based on probabilities 

and consequences, and develop threat scenarios and mitigation options. During an incident, 

specific information can help characterize the exposure and population characteristics resulting 

in more precise estimates of microbial risks. Following an incident, additional site information 

can help refine the MRA results, identify appropriate levels for decontamination of affected sites, 

and assess related hazards. 

The Center’s preliminary MRA framework for bioagent incidence response is based on a 

compendium of MRA studies and methods published between 1994 and 2004. The framework is 

comprised of three tiers: 

20 Key considerations related to interpreting evidence of secondary spread are noted in U.S. EPA, 2005b. 

53
 
•	 Tier I: Site/Incident Assessment 

•	 Tier II: Exposure Assessment conducted simultaneously with Hazard Assessment 

•	 Tier III: Risk Characterization 

At the time of this review, the framework was being evaluated using hypothetical 

scenarios to characterize risks associated with a range of agents and incidents. 

The key components of the framework are comparable to the ILSI (2000) approach; 

however, the elements within the tiers have been modified to suit incident response needs 

(Nichols et al., 2006). For example, the exposure assessment step requires 

•	 Characterization of the release (e.g., identification of the organism, time and duration 

of release; number and location of release points; and mode, mechanism, and medium 

of release) 

•	 Definition of the contaminated area (derived from modeling the initial zone of 

release) 

•	 Definition of the exposed population (including their activity patterns and probable 

exposure scenarios) 

•	 Development and execution of an environmental sampling plan (based on scenario 

and population data) 

•	 Estimation and prediction of exposure concentrations (define the boundaries of the 

contaminated area, and estimate exposure levels) 

•	 Estimation of intakes (select exposure models, determine values of exposure factors, 

and characterize uncertainty and variability) 

In the Center’s framework, hazard assessment involves identifying the hazard and 

predicting the health hazards using dose-response modeling, while risk characterization 

combines the results of the health hazard predictions with the exposure estimates for each 

exposure scenario. 

Each of these tiers poses unique challenges that ought to be addressed to fully implement 

the framework. Some of the challenges relate to 

54
 
•	 Technical and laboratory limitations (e.g., false positives, delays in diagnostics) 

•	 Constraints due to the nature of the bioagent and host populations, environmental 

conditions, and exposure characteristics (e.g., health effects related to the organism 

that mimic common conditions such as influenza, lack of relevant and available 

information or MRAs, multiple routes of exposure, re-aerosolization and transport of 

bioagents) 

•	 Modeling complexities (e.g., dynamic disease transmission modeling) 

•	 The need to use defaults (e.g., virulence factor activity assessments or infectivity 

biomarkers) 

These and other gaps in MRA methodologies need to be addressed to support homeland 

security objectives. 

4.1.4. Department of Defense 

The U.S. Army’s Center for Health Promotion and Preventive Medicine has developed a 

MRA framework (CHPPM, 2006), which builds on the traditional chemical risk assessment 

approach (NRC, 1983). The focus is on supporting decision-makers in determining “How clean 

is safe?” The Center’s framework has been designed for predictive and not incident response 

purposes. The four-step approach includes 

•	 Planning and Problem Formulation 

•	 Release Assessment 

•	 Exposure and Infectivity Assessment 

•	 Characterization of Health Impact 

Assumptions made and uncertainties noted throughout the application of the framework 

are described in a table at the end of the MRA. 

The first step entails identification of the microbial pathogen and receptor population(s), 

health endpoints, and development of the analysis plan and risk management options. 

Assumptions for conducting the assessment are explicitly stated. A substep, Threat 

55
 
Identification, involves examining the interactions that occur between the pathogen and human 

populations in a variety of environments. 

Release Assessment describes the mechanism by which the pathogen is released and 

distributed and estimates the rates of release, in order to estimate exposure point concentrations 

(e.g., the environmental concentrations which receptor populations would experience). This 

estimation process may be completed for several scenarios, and addresses the range of 

environmental factors in this fate-and-transport modeling step. Sources of uncertainty are 

described. 

Exposure Assessment estimates exposures among the receptor populations, considering 

characteristics of the host, pathogen, and environment. Important factors include inhalation rate, 

exposure time, and internal biological deposition and clearance. The output of this step, with 

uncertainties described, is a set of estimates of the pathogen concentration within the human 

receptor. 

Another component of the third step of the framework is Infectivity Assessment. This 

step parallels the traditional dose-response step (NRC, 1983); it evaluates the impacts of the 

pathogen level in the target organ, considering variability and the sources of uncertainty involved 

in modeling the pathogen-response relationship. Pathogen factors are more influential in the 

Infectivity Assessment component of the framework, while host characteristics are the focus in 

Exposure Assessment. Literature is reviewed, debates noted about infectivity values, and 

rationales for the choices made are documented. A reference value is calculated, with 

uncertainties stated, and then used to estimate the risk from exposure to the pathogen. This value 

is one of the inputs to the next step of the framework. 

The last step, Characterization of the Health Impact, integrates the prior steps’ outputs by 

comparing the estimated health impacts to the Infectivity Assessment reference value. The 

estimates may be expressed in a qualitative manner, rather than quantitative estimates, but 

uncertainties are described. One qualitative format is a matrix of estimates by hazard probability 

and hazard severity. This matrix provides decision-makers with a succinct presentation of the 

range of risks, thereby facilitating their decisions. Decision-makers are further aided by a table of 

assumptions and uncertainties, allowing them to interpret the matrix with greater insight. 

56
 
 

 

 

 

 

 

4.2. CANADA 

4.2.1. Health Canada 

Health Canada published and adopted its risk assessment framework in 2000 (Health 

Canada, 2000). The framework is based on the U.S. Presidential/Congressional Commission’s 

work (P/C, 1997)21, because it used an iterative, integrated approach that reflected the 

interrelationships of actual decision processes (Health Canada, 2000). Health Canada’s 

framework includes a problem formulation step, uses a public health approach, and is intended to 

address all potential human health risks including microbial pathogens (Jardine et al., 2003). 

Health Canada uses a flexible, six-step framework for developing drinking water 

guidelines, including those for addressing microbial pathogens (Krewski et al., 2004). Although 

both the traditional four-compartment model (NRC, 1983) and the ILSI, 2000 model are 

described, neither is pointed to as the preferred approach in implementing Health Canada’s 

paradigm. The six steps are 

•	 Identification (determination as to whether a contaminant should be considered for 

guideline22 development) 

•	 Assessment (a science-based risk assessment of potential health risks) 

•	 Evaluation (examination of the feasibility of implementing the recommended 

guidelines) 

•	 Decision-making and approval (governmental entities approve the decision to set or 

revise guidelines) 

•	 Announcement and publication (public release of the guidelines) 

•	 Re-evaluation (to be conducted as needed) 

21 Jardine et al. (2003) pointed out that Health Canada’s framework is based on the P/C (1997) approach. 

While no MRA framework reviewed for this paper explicitly cited P/C (1997) as its basis, other MRAs did reflect or 

use key P/C principles: iteration, inclusion of stakeholders, protection of public health, scientific bases, and risk 

assessment within a comprehensive risk management approach. WHO has based its recent public health policy 

guidance on P/C’s principles and framework (McLaughlin Centre for Population Health Risk Assessment, 

University of Ottawa, and World Health Organization, 2005). 22 In North America and Europe, guidelines typically do not have the same regulatory or enforcement 

implications as standards. Guidelines are usually developed to improve the quality and consistency of products (such 

as risk assessments), and are therefore recommended as “best practices.” However, standards are requirements that 

must be met to avoid enforcement actions. WHO (2001) has stated that guidelines provide a scientific rationale on 

which nations can build standards in their own social, economic, and environmental contexts. In Canada, guidelines 

are used to provide “a flexible process that must accommodate the diverse needs of various jurisdictions (Health 

Canada, 1999a),” as cited by Krewski et al. (2004). 

57
 
Additionally, the paradigm stresses communication throughout the process that public 

consultations be included as early as the first step (identification). Public input in evaluation is 

seen as particularly important. 

4.2.2. Public Health Agency of Canada 

Lammerding (2006) of the Public Health Agency of Canada has described MRA as 

systematic, structured, and integrative. It is a “modular process” that builds on steps in a chain, 

such as a food production process; the output of one module serves as the input for the next 

module in the chain. She provides examples of modular MRAs and discusses different modeling 

approaches. She also states that it is important to ensure that the MRA level matches the risk 

management needs. Lammerding’s review of microbial risk assessment methods and modeling is 

an excellent summary, but it does not indicate whether the Public Health Agency of Canada 

prefers any particular approaches or has adopted a specific framework as policy. 

4.3. AUSTRALIA AND NEW ZEALAND 

Australia and New Zealand have defined “risk assessment” as “the overall process of 

using available information to predict how often hazards or specific events may occur 

(likelihood) and the magnitude of their consequences (adapted from AS/NZS 4360:1999)” 

(NRMMC, 2006). The purpose of risk assessment is “to distinguish between very high and very 

low risks so that priorities for risk management can be established” (NHMRC-NRMMC, 2004). 

The fundamental approach is based on the traditional four-step chemical risk assessment 

paradigm (NRC, 1983). 

4.3.1. Australia 

Risk assessments are conducted within a larger risk management framework, based on 

HACCP principles (Codex, 1997); systems such as ISO 9001 (AS/NZS, 2000); and WHO’s 

unified risk management approach for drinking water, recreational water, and recycled water 

(WHO, 2001). This framework is described in Australia’s Drinking Water Guidelines (NHMRCNRMMC, 2004) and WHO’s Guidelines for Drinking Water Quality (WHO, 2004b). Australia’s 

risk management framework has 12 steps (or elements), which are organized into four 

components: 

58
 
• Commitment to responsible use and management (Element 1) 

• Systems analysis and management (Elements 2-6) 

• Supporting requirements (Elements 7-10) 

• Review (Elements 11-12) 

The Systems component contains the risk assessment process (Element 2). However, in 

the Commitment component, a risk management framework, conceptual model, and plans are 

developed before the risk assessment process is initiated; this is essentially a planning and 

scoping step (Element 1). (Figure 4). 

Commitment to Management 

System Analysis and 

Management 

(includes Risk Assessment) Supporting Requirements 

Review 

Figure 4. Australia’s risk management framework including risk assessment. 

Sources: Adapted from NHMRC-NRMMC, 2004; NRMMC, 2006 

The risk assessment follows the traditional four steps: hazard identification (including a 

preliminary or screening risk assessment); dose-response; exposure assessment; and risk 

characterization (labeled risk assessment). The output of the risk assessment process is one or 

more risk estimates, which may be expressed quantitatively or qualitatively. Qualitative risk 

estimates (from low to high) may be communicated in a matrix of likelihood and consequence 

levels. An initial, screening-level risk assessment may be conducted to distinguish between high 

and low risks. Guidelines and criteria for estimating risks are available for specific sources and 

end uses (e.g., as in for recycled water in NRMMC, 2006). These guidance materials also 

indicate that uncertainty, variability, and limitations of the risk assessment need to be discussed 

and documented (NRMMC, 2006; NHMRC-NRMMC, 2004). Quantitative estimates of the 

59
 
 

 

likelihood of illness are expressed in DALYs to convey the magnitude of disease burden and to 

provide a benchmark for “tolerable risk.” 

Other components (Elements 1, 6, and 8) of the framework address risk communication 

issues; including identification and engagement of stakeholders (1), management of incidents 

and emergencies through communication and incident response protocols and strategies (6), and 

two-way forms of community involvement to address longer-term risks (8) (e.g., NRMMC, 

2006). These three sections of the guidelines describe general principles for ensuring appropriate 

types of communication with related agencies, employees, contractors, the mass media, 

stakeholders, the general public or consumers. 

4.3.1.1. Drinking Water 

The specific issues associated with conducting a risk assessment for categories of 

pathogens (e.g., bacteria, viruses) are described in broad terms. The probability of community 

outbreaks relates, for example, to the virulence of the pathogen, consumption rates of consumers, 

infectious dose of the specific pathogen, and incidence of the infection in the community. 

Susceptible subpopulations—such as very young, immunosuppressed, sick and elderly people— 

are considered in microbial risk assessments. Subgroups also include people who have had recent 

surgery, injury or burns (e.g., groups with compromised defense mechanisms) (NHMRCNRMMC, 2004). 

4.3.1.2. Recycled Water 

Australia’s guidelines for managing risks associated with the use of recycled water 

address both environmental and health hazards (NRMMC, 2006). Human health risk assessment 

explicitly deals with multiple microbial pathogen-related risks; risk characterization is described 

in detail in Appendix 2 of Australia’s guidelines (NRMMC, 2006). Susceptible subpopulations 

are defined using a range of characteristics and thereby are considered in the risk assessment. 

Tolerable levels of risk are expressed in terms of DALYS (disability adjusted life years) per 

person per year. Both deterministic and stochastic analyses are considered, and health-based 

performance targets are calculated. 

4.3.2. New Zealand 

The New Zealand Food Safety Authority has completed a risk profile, or qualitative 

assessment, to screen the risks associated with salmonella in whole and pieced poultry (NZFSA, 

60
 
 

 

2004). The framework used to conduct this MRA complied with Codex principles (1999) and 

followed the order of hazard identification, hazard characterization (dose-response), exposure 

assessment, and risk characterization. 

In the New Zealand risk management framework, risk communication and consultation 

encircle risk assessment (NZFSA, 2004), but the MRA text does not indicate how these activities 

are to be conducted. 

4.4. FRANCE 

Quantitative microbial risk assessments have been conducted by the French Food Safety 

Agency (Agence Francaise de Sécurité Sanitaire des Aliments). The authors of a quantitative 

risk assessment of waterborne cryptosporidiosis stated that WHO’s recommendations and 

framework (FAO/WHO, 2002a) were the basis for their work (Pouillot, et al., 2004). 

WHO’s “global risk assessment model” is presented in the following order: hazard 

identification, consumption, pathogen emission, exposure, and effect. These components were 

examined at the individual level. Over 20 assumptions were made to design and implement the 

model; the impacts of many of these are discussed. The results for C. parvum infection are 

presented on two levels, daily and annual risk estimates, for immunocompetent and 

immunodeficient populations. 

4.5. THE NETHERLANDS 

Using a modular process risk model approach, Nauta et al. (2005) conducted a 

quantitative microbial risk assessment of campylobacter transmitted through several routes of 

exposure: raw and undercooked foods, pet and farm animals, and recreational and drinking 

water. The guiding framework for this assessment was a “farm-to-fork” chain, with an exposure 

module at the “fork” end. The output of this chain became the input for a dose-response model 

for predicting the annual number of cases of infection and illness in the Dutch population. The 

authors noted that a qualitative outcome based on the quantitative results may be more 

appropriate for public health decision-making processes. 

4.6. SWEDEN 

The National Food Administration of Sweden follows the four-step risk assessment 

framework, originated by the NRC (1983) and supported by Codex (1999). This framework has 

been used to conduct a quantitative risk assessment of the exposure and risk of developing 

61
 
listeriosis from consumption of contaminated ready-to-eat foods, particularly gravad or smoked 

salmon and rainbow trout (Lindqvist and Westöö, 2000). 

4.7. UNITED KINGDOM 

Due to increasing sociological, political, scientific, and economic needs, the United 

Kingdom has been examining microbial risk assessment approaches and applications since the 

late 1980s (ACDP, 1996). The Advisory Committee on Dangerous Pathogens has defined MRA 

as “a formal structured procedure for identifying and characterizing microbial hazard and 

determining the risk associated with it” (ACDP, 1996). Although some of the basic principles 

are the same, UK experts have stated that MRA involves issues not found in chemical risk 

assessment. 

The committee also laid out an eight-stage approach to MRA, in which Stage 1 requires a 

problem statement, Stage 2 involves the conduct of the MRA, and Stage 7 addresses risk 

communication needs (ACDP, 1996). Stage 2 is ordered in a manner similar to the NRC (1983) 

paradigm. The approach identified host, environment, and pathogen factors that influence the 

conduct of MRA and noted the importance of principles underlying HACCP and HAZOP 

(Hazards and Operability) processes. The Committee also described computational models 

available to conduct portions of MRAs, such as the food micromodel for common food 

poisoning bacteria. The need to clearly state sources of uncertainty and their impacts on MRA 

results was noted. 

4.8. EUROPEAN UNION 

The European Commission has undertaken a number of activities to address and advance 

MRA issues. Several organizations within the European Union (EU) have published documents 

describing the framework and bases for microbial risk assessment. Harmonization of risk 

assessment procedures for quantitative microbiological risk assessment was initiated in the 1990s 

and culminated in a report (EC, 2000) that serves as the basis for continuing work (e.g., EC, 

2003). This report of the Scientific Steering Committee’s Working Group on Harmonisation of 

Risk Assessment Procedures adopted the NRC (1983) paradigm, with a preceding problem 

definition step. This step included formulation of the risk assessment questions and conduct of a 

preliminary assessment for planning and scoping purposes. The report also recommended the 

development of quantitative risk assessment guidelines and common exposure models and 

scenarios, noted the importance of using epidemiological approaches, and established a Working 

62
 
 

Group on Risk Assessment as Applied to Biological Materials, which has focused on bacterial 

pathogens in foods. The report briefly discussed the four traditional steps of risk assessment as 

they applied to microbial pathogens, noting that some aspects of pathogen exposures required 

different approaches. 

Another product of the Working Group was a report on quantitative methodologies for 

exposure assessment23 in foodborne pathogen risk assessments, which adopted the modular 

process risk model to represent six basic steps within the farm-to-fork pathway (EC, 2003). The 

EU’s Steering Committee also carries out MRAs on specific topics (e.g., bovine spongiform 

encephalopathy), with input from several working groups (EFSA, 2005c). 

The following two EU organizations have documents describing the framework and 

bases for microbial risk assessment. 

4.8.1. European Commission on Food Safety 

The European Commission on Food Safety (ECFS) published MRA principles that 

adopted the chemical risk assessment steps (hazard identification, hazard characterization, 

exposure assessment, and risk characterization), but acknowledged that these steps did not have 

to be completed in a rigid order, because the order be designed to suit the purposes of the risk 

assessment (ECFS, 1997). The ECFS also adopted a step focused on formulating a statement of 

purpose as a precursor to implementing the four MRA steps. In another forward-thinking 

statement, the agency said that the dynamics of both the microbial pathogen (and related toxins) 

and the host population must be considered in MRA. Risk communication is not explicitly 

addressed in this document, but a publicly available, clear, transparent, fully documented, and 

systematically organized report is expected as the final product. 

4.8.2. European Food Safety Authority 

In an EU workshop conducted in 2000, experts stated that the basic formal steps for 

MRA include identification/characterization, analysis, and assessment, but that the conduct of 

each step is heavily dependent on regulatory and cultural contexts (Jardine et al., 2003). The 

European Food Safety Authority (EFSA) has subsequently published a guidance document 

relevant for microbial risk assessments (EFSA, 2006b). This manual describes the steps of risk 

assessment as hazard identification, hazard characterization, exposure assessment, and risk 

23 The definition of exposure assessment used here is “an estimate of how likely it is that an individual or a 

population will be exposed to a microbial hazard and what numbers of organisms are likely to be ingested” 

(Lammerding and Fazil, 2000). 

63
 
 

characterization. These steps have been implemented in an EU opinion on Ochratoxin A in food 

(EFSA, 2006c). 

EFSA’s guidance for risk assessment of genetically modified plants presented the MRA 

as the traditional NRC (1983) framework, and noted this approach aligns with prior European 

Commission and Codex policies (EFSA, 2006a; 2006b; 2006c). The guidance includes extended 

discussion about the characteristics and issues that need to be considered in the hazard 

identification and hazard characterization steps. Some of the information needed relates to the 

traits and characteristics that have been modified in the plant, derived food, or feed; details of the 

genetic insertion or deletion; expression of the genetic insert; genetic stability of the genetically 

modified plant; information on any toxic, allergenic, or other harmful effects on human or animal 

health, etc. The exposure assessment step requires information to describe the pathways by 

which genetically modified plants may be modified in the environment and interact with 

components of the environment and/or with humans. The risk characterization step considers the 

genetically modified plant’s molecular character compared with naturally occurring varieties, as 

well as food and feed safety issues and environmental impacts. Although this guidance builds 

from the traditional NRC framework, it requires the integration of a wide range of ecological and 

human health concerns.24 

EFSA guidance on genetically modified plants defines risk communication as “the 

interactive exchange of information and opinions throughout the risk analysis process as regards 

hazards and risks, risk-related factors and risk perceptions among risk assessors, risk managers, 

consumers, feed and food businesses, the academic community and other interested parties, 

including explanation of risk assessment findings and the basis for risk management decisions” 

(EFSA, 2006d). 

In a separate guidance document issued for transparency in risk assessments, EFSA 

distinguished between “institutional” and “civil society” stakeholders on the basis that the 

agency has different legal and legitimate responsibilities to each (EFSA, 2006b). EFSA stated 

that wide stakeholder involvement, active dialogue, and collaboration are important, but that predetermined criteria are needed to identify when stakeholders should be involved and on what 

topics. 

24 This is in alignment with the integrated framework recommended by Suter et al. (2005). 

64 
 

 

4.9. UNITED NATIONS 

Risk assessments for five microbial pathogens have been posted on United Nationsrelated websites; in some cases, multiple, evolving versions are posted. The pathogens examined 

to date are 

• Campylobacter in chickens and seafood 

• Enterobacter in infant formula 

• Listeria in ready-to-eat foods 

• Salmonella in eggs and broiler chickens 

• Vibrio in raw oysters 

All of these MRAs start with a distinct hazard identification step and end with risk 

characterization, while some include a scoping step. Some document the exposure assessment 

step before the hazard characterization (e.g., chickens in WHO, 2002) and others do not (e.g., 

seafood in WHO, 2002). There was no obvious reason why this inconsistency should be the 

case, given that Codex has adopted a risk assessment framework with exposure assessment 

preceding hazard characterization (Codex, 1999). 

The joint initiative between the Food and Agriculture Organization of the United Nations 

(FAO) and WHO and Codex has defined “risk communication” as an interactive exchange of 

information and opinions about risk among risk managers, risk assessors, and stakeholders 

(Codex, 1999; FAO/WHO, 1995). While a few UN agency MRA guidance documents have 

discussed risk communication (e.g., WHO, 2004b), to date, none of the MRAs completed by 

United Nations entities have included discussions about risk communication. 

4.9.1. Joint FAO/WHO 

FAO/WHO have jointly defined MRA as “an objective, systematic evaluation of relevant 

scientific knowledge to help the risk manager make an informed decision about how to reduce 

risk posed by a food safety issue,” and dynamic and predictive modeling methods are used to 

estimate public health risks (FAO/WHO, 2006). 

Joint initiatives, convened at the request of Codex, have played a crucial role in 

developing, standardizing, and informing MRA and related guidelines on an international scale. 

The 1995 Joint Consultation experts recommended that Codex adopt a four-compartment model 

for biological agents in foods, similar to the NRC approach used for chemical risk assessment 

65
 
(FAO/WHO, 1995). The steps in MRA were identified as: hazard identification, hazard 

characterization (including dose-response), exposure assessment, and risk characterization. The 

FAO/WHO model emphasizes sound scientific bases, as much quantification as possible, clearly 

stated outcomes, and HACCP-based options for MRA. However, the Consultation recognized 

that more knowledge and information and a different application of the four-compartment model 

would be needed to adequately address microbial risks. In the risk evaluation step, prior to risk 

assessment, the food safety problem is identified and ranked, and the policies needed to conduct 

the risk assessment are defined; this is equivalent to some scoping and planning steps of other 

agencies (FAO/WHO, 2000). Sound scientific bases, as much quantification as possible, clearly 

stated outcomes, and HACCP-based options are noted as the foundations of MRA. 

The Joint FAO/WHO Expert Consultation on the Application of Risk Analysis to Food 

Standards Issues was held in 1995 to provide Codex, FAO, and WHO with advice on practical 

approaches to risk analysis for food issues, and to promote consistency and transparency in 

related Codex standards and guidelines. In a later Joint Expert Meeting, it was noted that public 

health goals (such as appropriate levels of protection) can be achieved when MRAs inspire the 

public and governments to take appropriate actions. This is more likely to occur when the public 

and officials have been engaged as stakeholders in the process (FAO/WHO, 2006). 

Risk assessment and risk communication, along with risk management, are the three 

major components of the United Nations’ approach to risk analysis (FAO/WHO, 1999). In 1998, 

a Joint FAO/WHO Expert Consultation addressed risk communication for food-related matters 

(FAO/WHO, 1999). The convener noted that risk communication occurs throughout the risk 

assessment and management processes, among all parties involved (including the public), and 

requires different types and tiers of communication. The consultation produced a list of risk 

communication goals, such as to promote awareness and understanding of risk analysis issues, 

contribute to effective information and education programs, involve all interested parties, and 

strengthen working and mutually respectful relationships. Principles noted to be fundamental to 

risk communication are transparency and consistency. The Consultation affirmed the importance 

of pursuing risk communication through a systematic approach, and recommended a number of 

issues to be considered in planning for crisis and non-crisis conditions. Furthermore, FAO/WHO 

documentation states that risk assessment results should be made public and communicated to 

relevant and interested parties (FAO/WHO, 2003b). 

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4.9.2. Codex Alimentarius Commission 

The primary purposes of this intergovernmental organization are to protect human health 

and ensure fair practices in food trade (FAO/WHO, 1997). Codex is a subsidiary body of the 

FAO and WHO; it provides an annual forum for dialogue and debate about major, international 

food safety issues. Through the work of its committees, the Commission establishes international 

food safety standards and guidelines, develops principles for using risk assessment to identify 

such standards, and has risk management responsibilities for food in international trade. The 

World Trade Organization considers Codex opinions representative of international consensus 

regarding foodborne health risks and controls. Codex initiated a survey of risk assessment 

methods in 1993, provided guidance for risk analyses of foods in 1994, and has conducted a 

series of expert consultations on MRA since 1995 (EC, 2000). 

The committee that primarily addresses MRA principles, approaches, and related issues 

is the Codex Committee on Food Hygiene. Codex describes risk analysis as having three major 

parts: risk assessment, risk management, and risk communication. Codex has adopted a modified 

form of the chemical risk assessment framework for food-related MRA and incorporated 

HACCP concepts. The four components in the Codex framework are: hazard identification, 

hazard characterization, exposure assessment, and risk characterization (WHO, 1999). Like the 

European Commission on Food Safety, Codex has clearly stated that the dynamics of microbial 

pathogens (growth, survival, and death) must be accounted for in microbial risk assessments of 

foods. 

Codex defines risk communication as “the interactive exchange of information and 

opinions concerning risk and risk management among risk assessors, risk managers, consumers 

and other interested parties” (Codex, 1999). One of the goals of risk communication in Codex 

processes is to increase the credibility and public acceptability of risk assessment outcomes. 

4.9.3. International Office of Epizootics 

Aligned with the SPS Agreement and its World Trade Organization responsibilities, this 

office has addressed MRA related to animals used for foods, and has incorporated risk analysis 

guidelines in the International Health Code. These guidelines address and provide underlying 

principles for risk assessment (EC, 2000). 

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4.9.4. World Health Organization 

The WHO Environmental Health Criteria Programme was established in 1973, in followup to the UN’s Conference on the Human Environment in the prior year. The work conducted by 

this office contributed to chemical risk assessment strategies, and monographs on the assessment 

of contaminants in food (EC, 2000). 

WHO approaches MRA as part of an overall risk management problem (Codex, 1999). 

MRA serves a crucial role in risk management paradigms; it is pivotal to ensuring that the 

quality of synthesized information is high, and that related management options provided to 

decision-makers are as complete as possible and relevant to the originally defined problem and 

scope. Several agencies have described generic risk management frameworks (e.g., P/C, 1997; 

CSA, 1997), but only one has been specific to microbial risks (WHO, 2003a). 

WHO’s four components for managing microbial pathogens are 

• Preliminary risk management activities 

• Evaluation of risk management options 

• Implementation of the risk management decision 

• Monitoring and review 

The first step, preliminary risk management, includes the MRA process. Although a 

problem formulation component may be added (OECD/WHO, 2003), WHO typically uses the 

traditional four-compartment approach to MRA: hazard identification, hazard characterization, 

exposure assessment, and risk characterization. A preliminary step—statement of the problem— 

appears in some WHO guidelines (e.g., WHO, 1999), and the middle two steps (exposure 

assessment and hazard characterization) are sometimes reversed (see chickens in WHO, 2002b) 

or are shown as concurrent activities (e.g., WHO, 2002a). The agency’s steps to conduct MRA 

involve (FAO/WHO, 2002a) 

1. Identifying the food safety issue 

2. Initiating immediate interim decisions 

3. Determining the risk profile to enable additional decisions 

4. Making the initial risk management decisions 

5. Defining the purpose and scope of the MRA 

6. Establishing policies for the MRA 

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7. Commissioning the MRA 

8. Interacting during the MRA 

9. Presenting the results of the MRA 

10. Considering the MRA results 

Steps 1 through 4 involve programmatic activities that lay the foundation for the MRA 

conducted in step 5. Once the food safety issue has been identified (step 1), immediate actions 

may be necessary to protect the public’s health (step 2). An initial risk profile involves a 

systematic collection of information, which is evaluated to determine what other actions 

(including MRA) and resources may be needed (step 3). If MRA is required, then the risk 

manager defines the scope, purpose, and operational policies for its conduct (step 4). In step 5, 

the risk managers and assessors clarify the MRA goals and specific questions. The questions 

posed depend on the scope of the problem, specific contexts of the microbial risk issue (e.g., the 

agent, food and exposure pathways involved), and the intended use of the MRA results. 

Ensuring that the MRA is conducted in a systematic, transparent, and well-documented manner 

is essential to step 6. Policies that apply generally to MRA and specifically to the problem to be 

addressed are identified in this step. When the decision-makers call for MRA, (step 7), the 

mandate and outcome measures—as well as the roles and responsibilities of risk assessors and 

managers—are clearly laid out. Although assessors and managers communicate during the 

MRA (step 8), this communication should be objective and limited to necessary technical 

information, not policy decisions. Risk assessors are responsible for ensuring that the MRA 

results are provided in a manner that is relevant, useful, and informative to decision-makers 

(steps 9 and 10). 

In its 2002 assessment of S. enteriditis in eggs, egg products, and broiler chickens (WHO, 

2002a), WHO used an innovative modification of the MRA component of the ten-step process. 

By sharing the first two steps of the MRA framework but separating the third where key 

conditions and issues were different, the joint WHO/FAO assessment gained efficiencies and 

produced outputs relevant for both foods. 

69
 
Hazard Identification 

Hazard Characterization 

Exposure Assessment 

Eggs and Egg Products Broiler Chickens 

• Production • Slaughterhouse 

•	 Processing eggs • Storage and transport 

•	 Distribution • Distribution 

•	 Processing egg • Preparation 

products • Consumption 

•	 Preparation 

•	 Consumption 

Risk Characterization 

For Eggs 

Risk Characterization 

For Chickens 

 

 

Figure 5. WHO approach to the risk assessment of Salmonella enteriditis 

in eggs and broiler chickens 

Source: WHO, 2002a 

The 2004 Drinking Water Guidelines (WHO, 2004b) discusses risk communication as an 

essential part of each step in risk assessment. WHO’s stated risk communication goals include 

raising public knowledge and awareness about issues, and empowering people to participate in 

decision-making processes and take effective actions. An additional point that is rarely made in 

MRAs is that understanding the diversity of views is necessary to meet community needs. 

70
 
 

5. COMPARISON OF FRAMEWORKS 

To elucidate the similarities and differences between governments’ and agencies’ MRA 

approaches, at the time of this review, the most recently completed and available MRA for each 

nation, or agency, when there was more than one completed MRA per government, was selected 

for study. This review evaluates the type of MRA framework used and the components included 

in the framework for each MRA. MRAs were found for pathogens in air, drinking water, 

recreational water, foods (both fresh and processed), biosolids, modified organisms, and 

intentional uses of microbes. 

The purpose of this section is to briefly present and compare completed microbial risk 

assessments. The analytic focus of this project centered on 12 recently published, governmentsponsored MRAs, and one series of EPA MRAs—for biopesticides. Because of the similarities 

of the MRAs in this series, each set of MRAs was treated as a single MRA approach. Therefore, 

the unit of comparison in this section is 13 MRA frameworks. 

The MRAs compared for this project were 

•	 Cryptosporidium in drinking water (WHO, 2006a) 

•	 Cryptosporidium in drinking water in France (Pouillot et al., 2004) 

•	 Salmonella (non-typhoidal) in poultry (whole and pieces) in New Zealand (NZFSA, 

2004) 

•	 S. enteriditis in shell eggs and egg products in the United States (USDA, 2005b) 

•	 S. typhimurium in three sets of pig-meat products in the United Kingdom (Hill et al. 

2003) 

•	 V. vulnificus in raw oysters (WHO, 2005) 

•	 V. parahaemolyticus in raw oysters in the United States (U.S. FDA, 2005) 

•	 Campylobacter in broiler meat in The Netherlands (Nauta et al., 2005) 

•	 L. monocytogenes in fish in Sweden (Lindqvist and Westöö, 2000) 

•	 Eight microbial pathogens in processed wild game in the United Kingdom (Coburn et 

al., 2005) 

•	 Ochratoxin A in foods (EFSA, 2006c) 

71
 
 

 

•	 The MRA portion of the economic analysis for the final Long Term 2 Enhanced 

Surface Water Rule (EPA, 2005b) 

An example of the U.S. biopesticides series 

•	 Streptomyces lydicus WYEC 108 (U.S. EPA, 2004a) 

Note that although other governmental documents have been prepared to initiate MRAs 

(e.g., the cyanobacterial toxin series produced by the EPA’s National Center for Environmental 

Assessment [NCEA]), these are not complete MRAs and thus did not qualify for evaluation in 

this review (U.S. EPA, 2006b). The NCEA reviews focus on toxicology, and complete only the 

hazard identification and dose-response steps of traditional risk assessment. 

5.1. OVERALL FRAMEWORK STRUCTURE 

Microbial risk assessments involve many factors and complex relationships, including the 

dynamic aspects of pathogens and hosts and their environment. Such complex systems have 

networks of factors, feedback loops, and agents that are self-organizing under simple rules. One 

of the key issues in MRA is how to develop both conceptual and mathematical modeling 

methods that are sufficient, but not overly complex to address the MRA scope and risk 

management problem. 

“Systems thinking”25 characterizes complex, dynamic relationships and focuses on 

emerging and unpredictable outcomes; this approach seems well suited to applications in MRA. 

Even though increasingly complex MRAs are being conducted, the application of systems 

thinking to MRA has not yet been explicitly described. One method that can facilitate systems 

thinking is concept mapping (Trochim et al., 2006), which may be particularly useful in the 

problem formulation stage of MRA. In concept mapping, multi-disciplinary teams (individually 

or collectively) brainstorm about what the problem is, what factors affect the problem, and what 

the boundaries of the problem system are. After participants’ ideas are sorted into groups of 

similar concepts, the team rates each concept group for its relative importance to the problem. 

25 As stated in a recent article, “Systems thinking is a general conceptual orientation concerned with the 

interrelationships between parts and their relationships to a functioning whole, often understood within the context 

of an even greater whole” (Trochim et al., 2006). Ecologists use such system-oriented approaches when they define 

the conceptual model for an ecological risk assessment. In this case, systems thinking involves identifying and 

characterizing the relationships between the many stressors and endpoints in an ecosystem (i.e., a biotic community 

and its abiotic environment) (U.S. EPA, 1998). 

72
 
 

 

 

Through iterations of the data and participants’ input, the problem system is mapped into a 

structured diagram that helps teams identify remaining issues, gaps, and challenges in addressing 

the problem. 

Tools such as risk assessment frameworks and modules26 help risk assessors organize the 

complex microbial risk conditions and model dynamic relationships. MRA frameworks provide a 

broad template to guide the organization of many factors into a series of technical steps and to 

identify data gaps and appropriate computational methods. Risk assessment frameworks can be 

constructed on several levels—moving from least to most complex—and applied at the level 

needed to address the problem. In one analysis of risk assessment frameworks, a broad 

agreement was found on the three essential parts in risk assessment: identification and possible 

estimation of the hazard, exposure and/or vulnerability assessment, and risk estimation (IRGC, 

2005). 

The most basic decision-making model has been described by Drucker (2001) as 

including three phases: problem definition, analysis, and interpretation. Two of these three 

components are apparent in both the chemical and microbial risk assessment paradigms (see 

Table 5). The phase that clearly receives the least attention in MRA frameworks is problem 

definition. If the generic decision model is used as the benchmark to evaluate the completeness 

of MRA frameworks, most MRA approaches come up short. They are lacking the first step, 

which arguably is the most important because it defines what and how the remaining MRA steps 

are to be conducted. 

26 Although no explicit definition for “module” was found in the MRAs reviewed, WHO has referred to 

modules in food safety risk assessment guidance as “different areas along the food chain” (FAO/WHO, 2002a). In 

MRAs, module tends to refer to self-contained units that perform a specific task or function within an overall 

problem system. Typically, a module is both a distinct conceptual and mathematically modeled unit that produces an 

output (e.g., pathogen concentration distribution), which is then used in later steps, such as the exposure assessment, 

of an MRA (e.g., USDA, 2005b). 

73
 
 

 

 

 

 

 

 

 

Table 5. Microbial risk assessment framework structures compared with the basic 

decision-making model 

Frameworks 

Steps in the NRC Modified NRC Modified NRC with ILSI 

Basic Decision- without explicit a form of problem 

Making Model problem 

definition27 

definition 

Problem Included as problem Problem formulation 

Definition formulation, problem 

statement, or scoping 

step 

Analysis • Hazard 

identification 

• Hazard 

characterization 

• Exposure 

• Hazard 

identification 

• Hazard 

characterization 

• Exposure 

• Hazard 

identification 

• Hazard 

characterization 

• Exposure 

Analysis 

• Exposure 

characterization 

• Human health effects 

characterization 

assessment assessment assessment 

Interpretation Risk 

characterization 

Risk characterization Risk characterization Risk characterization 

Sources 

Drucker, 2000 NRC, 1983 

WHO, 1995 

Haas et al., 1999 

Lindqvist and 

Sobsey et al., 1993 

Medical Research 

Council Institute for 

Environment and 

ECFS, 1997 

Codex, 1999 

WHO, 1999, 2004, 

2005, and 2006a 

ILSI, 2000 

Westöö, 2000 

U.S. EPA, 2004a 

NZFSA, 2004 

U.S. EPA, 2005b 

EFSA, 2006c 

Health, 2000 

USDA, 2001 

FAO/WHO, 2003b 

U.S. FDA, 2001 

U.S. FDA/CFSAN 

2005 

OECD/WHO, 2003 

Pouillot et al., 2004 

Nauta et al., 2005 

USDA, 2005a and 

2005b 

NRMMC, 2006 

Note that Coburn et al. (2005) could not be classified due to the limitations of the documentation. It is likely that 

this MRA was a modified NRC framework with a problem statement. 

Most MRAs do not acknowledge problem formulation (“problem definition” in the basic 

decision-making model) as a step in the assessment process, but do have a section that states the 

purpose of the assessment 28 before describing the first recognized step—hazard identification. 

The purpose may also include comments about the scope of the problem (time, place) or 

questions to be addressed. Similar to EPA’s ecological risk assessment framework (U.S. EPA, 

1992), the components of problem formulation in MRA may include characteristics of the 

27 Problem definition (the generic decision-making term) may include problem formulation (U.S. EPA, 

2005a), scope or focus, a statement of purpose, a list of risk managers’ questions, goals, objectives, plan for 

conducting the MRA, regulatory or other contextual material, major factors or issues to consider, assessment 

endpoints, and/or a conceptual model. 28 Note that problem formulation and statement of the problem are not the same thing. Problem formulation 

often encompasses more insightful tasks, such as planning and conceptual modeling, than does developing a 

problem statement. However, problem formulations do not always have the same components, and are not 

conducted in a uniform manner (EPA, 2003). 

74
 
pathogen, adverse health effects, endpoints of the MRA, and the conceptual model to guide the 

MRA. 

Elements of hazard identification fit either in “problem definition” or “analysis,” but the 

hazard characterization and exposure assessment steps are clearly within the analytic step of 

basic decision-making frameworks, and the interpretation step is the same as risk 

characterization. 

The ILSI model follows the basic decision-making model more closely than does the 

traditional risk assessment approach. In the case of the ILSI model, “problem definition” is 

labeled “problem formulation”; “analysis” has the same name (with two major subcomponents: 

characterization of exposure and characterization of human health effects); and “interpretation” 

is identified as “risk characterization.” 

Each MRA is publicly available and is supported by technical documentation with 

varying levels of detail (Table 6). The discussion of the similarities and differences among the 

frameworks and components used in the MRAs below is based on the publicly available 

documentation. 

Most MRAs had some form of a problem definition. However, two (NZFSA, 2004; 

Coburn et al., 2005) were qualitative risk assessments. They had particularly general statements 

of purpose (to provide contextual and background information for decision-makers) and 

identified the food safety issue (the first step in “risk evaluation”) before the NRC framework 

was used on a screening level. In the NZFSA framework, risk evaluation includes the following 

sub-steps, with the first sub-step preceding the preliminary MRA: 

•	 Identification of the food safety issue 

•	 Establishment of a risk profile (conduct of the preliminary MRA) 

•	 Ranking of the food safety issue for risk management 

•	 Establishment of risk assessment policy 

•	 Commissioning of a risk assessment (conduct of a full MRA, to the extent that 

appropriate data and information are available) 

•	 Consideration of the results of the risk assessment 

75
 
All MRAs used the traditional risk assessment steps (NRC, 1983), but in different orders 

to suit their particular risk management needs. The structural and component similarities and 

differences among these MRAs are described in section 5.2. 

76
 
Table 6. Type and level of component detail available for government-sponsored MRAs 

Problem Definition 

Analysis Inter

Author, Date, and Environmental Category 

Type of Framework 

Problem Formulation 

Hazard Identification 

Hazard Characterization 

Exposure Assessment 

Risk Cha

Lindqvist and Westöö, 2000 Processed food 

Modified NRC with problem definition 

Brief statement of objective 

Brief description Moderate detail, 

including susceptible subgroups 

Brief section Brie

illnenum

Hill et al. 2003 Processed food 

NRC Brief statement of 

purpose 

Brief description Moderate description Extensive detail Estim

annucase

EPA, 2004 Modified organisms 

NRC General 

description 

Moderate description 

Noted by each route of exposure 

Conducted by each route of exposure 

Brieeach expo

NZFSA, 2004 Processed foods 

Modified NRC with problem definition 

Identification of the issue, preliminary MRA, planning steps 

Descriptions of pathogen and food matrix 

Brief section Focused on 

pathway of exposure 

Desceffecqualof ri

Pouillot et al., 2004 Drinking water 

Modified NRC with problem definition 

Statement of purpose 

Moderate description 

Discussion for both immunocompetent and immunodeficient populations 

Moderate description 

Probinfecillneannu

Coburn et al., 2005 Processed food 

Unclassifiable due to limited documentation 

General question stated 

Not included Not included Focus of the 

brief article 

Qualrisk micr

EPA, 2005b Drinking water 

NRC Discussion of 

purpose, scenarios and approaches 

Description of adverse health effects related to the pathogen, subpopulations, water systems 

Extensive description and bases for doseresponse with three components 

Extensive descriptions of pathogen distribution, water consumption, and populations affected 

Quanestimannudeath indivpopusecodiscu

FDA, 2005 Processed foods 

Modified NRC with problem definition 

Brief scope, context, objectives, and MRA questions 

Description of pathogen, at risk populations, related health effects, etc. with data sources 

Fairly brief but includes data limitations and assumption sections, also a very detailed appendix 

Diagram of modular approach, and data selection and criteria (with tables) 

Descoutpsensand 

77
 
Problem 

Definition 

Analysis Inter

Author, Date, and Environmental Category 

Type of Framework 

Problem Formulation 

Hazard Identification 

Hazard Characterization 

Exposure Assessment 

Risk Cha

Nauta et al., 2005 Processed food 

Modified NRC with problem definition 

Problem description 

Moderate description 

Fairly brief section Extensive 

“farm-to-fork” 

Briefocuinter

USDA, 2005b Processed foods 

Modified NRC with problem definition 

Purpose, scope, list of risk managers’ questions 

Brief descriptions of pathogen and related disease 

Describes data sources, dose response, and estimates for a range of effect severity 

Extensive sections for shell eggs and egg products 

Extefor sprodincluand 

WHO, 2005 Processed foods 

Modified NRC with problem definition 

Scope, context, and objectives presented 

Brief description Focused on doseresponse and public 

health focus, additional material in an appendix 

Three module structure, simulations, model validation, and appendix 

Brie

EFSA, 2006c Foods 

NRC General 

description 

Moderate discussion 

Extensive toxicological review 

Moderate description with data 

Briemenand 

WHO, 2006a Drinking water 

Modified NRC with problem definition 

Detailed formulation conducted after Hazard Identification 

Detailed description of the pathogen and its infectivity 

Detailed doseresponse in the Effect Assessment step 

Detailed consideration of detection and monitoring; less detail about consumption 

Novdesccase demMRAvalu

78
 
5.2. INDIVIDUAL FRAMEWORK COMPONENTS 

Each MRA step may develop concepts and implement quantitative models to varying levels of 

depth, depending on the MRA objective and the availability of data to support detailed mathematical 

models. In the more detailed cases, MRA documentation is more likely to refer to modules, particularly 

in the exposure assessment step. In this step, more complex modeling is more commonly being seen, 

and dynamic functions between agents and hosts are mathematically modeled. 

Before exploring the similarities and differences among the MRAs, descriptions of each 

component of the MRA frameworks follow (primarily based on definitions listed in EPA, 2005a). The 

components are scope and framework, problem formulation/statement, feasibility, conceptual model, 

analytic plan, plus the four traditional components that are associated with the NRC model: hazard 

identification, hazard characterization, exposure assessment, and risk characterization. The final 

component is risk communication. 

While the European Commission, Codex, and WHO also require a statement of purpose and 

most U.S. MRAs include a statement of the scope, it is important to note that these scoping concepts are 

not the same. A statement of purpose is usually limited to the overriding goal that risk managers want to 

achieve (e.g., rank ordering a set of risks). A statement of scope includes both the managers’ questions 

and the physical, geographic scale of the issue. Codex uses a risk profile step that includes analysis to 

describe the microbial food safety problem, its scenario (processing, handling, etc.), its contexts (social, 

cultural, economic, etc.), and a feasibility assessment. If the MRA scope is clear and the MRA is 

feasible, a conceptual model and management plan need to be in place before the first MRA step— 

hazard identification—is attempted. In some cases (e.g., WHO, 2006a), scoping is completed as part of 

or after the hazard identification step. 

Risk assessors often use the concepts of problem formulation and problem statement 

interchangeably, but as the science evolves, problem formulation is increasingly taking on a broader 

meaning—and often encompasses the problem statement. In a specialty workshop, problem formulation 

in MRA was defined as “a systematic planning step that identifies the goals, breadth, and focus of the 

microbial risk assessment, the regulatory and policy context of the assessment, and the major factors that 

will need to be addressed for the assessment” (ILSI, 2000). Among definitions for the initial stage of 

risk assessment (U.S. EPA, 2005a), problem formulation is the most comprehensive concept. MRA 

problem formulation was described in an EPA workshop (EPA, 2003) as involving several sub-steps, 

requiring consideration and description of 

79
 
• Concerns that brought the issue to attention 

• Risk management activities 

o Problem statement 

o Objective of the MRA 

o Questions to be addressed 

• Risk assessment feasibility 

o Preliminary analysis 

• Development of the conceptual model and narrative 

• Development of an analytic plan 

Problem formulation entails both the fundamental questions to be addressed and a preliminary 

assessment as to whether a relevant MRA can be conducted. The ILSI model (2000) is the only MRA 

framework that explicitly calls for a problem formulation step. As problem statements have been more 

commonly used in microbial risk assessments, this review will also use that terminology, although the 

methodology appears to be evolving to adopt the broader concept of problem formulation. 

1) Problem statement. While the ECFS has called for the routine use of problem statements, 

FDA and WHO have sometimes explicitly included the “statement of the problem” in their guidelines 

(Dennis et al., 2001–2002; WHO, 1999). Clear description of the MRA objectives and the risk 

management questions to be addressed are important parts of defining and scoping the MRA. 

Additionally, identification of the population and/or subpopulations of concern is essential. Specific 

groups may be of interest because they could have higher or more frequent exposures, genetic or other 

predisposing risk factors, or behaviors that would increase the likelihood for their contact with the 

pathogen. 

2) Feasibility. Conducting a preliminary analysis can help the risk assessor identify data and 

resource needs to implement a quantitative MRA. A preliminary analysis may identify logistical issues, 

including clarification of roles, responsibilities, and communication procedures. 

3) Conceptual model. A conceptual model is a written or visual representation of the predicted 

relationships between pathogens and exposed populations. It may be based on working hypotheses, 

supported by preliminary data and information, and used to organize the way the MRA is conducted. 

The model depicts the purpose, scope, and scale of the MRA; identifies variables and data needed to 

80
 
conduct the MRA; and can serve as a preliminary or exploratory risk assessment. When comprehensive 

problem formulation is used, the development of a conceptual model can provide new insights for the 

risk assessment team, allowing them to understand issues, contributing factors, and data sources beyond 

their expertise and experience. A systems approach to developing the model (Trochim et al., 2006) can 

more readily identify gaps in knowledge and information and recognize the feasibility of implementing a 

full MRA more rapidly. 

A conceptual model (e.g., a source-pathway-receptor or “farm-to-fork” model) is developed 

early in the process, but only to the level necessary to address the MRA’s purpose. The model should 

guide risk assessors in 

• Ensuring that all possible exposure routes have been considered and explicitly described 

• Identifying the types and sources of data needed to conduct the MRA 

• Ensuring that the right questions are being asked 

• Communicating effectively with risk managers 

• Ensuring transparency of the MRA process and bases 

An example of a simple conceptual model is presented in the upper portion of Figure 6. 

4) Analytic plan. The risk manager develops this plan after a feasibility assessment and before a 

full MRA is conducted. Risk managers determine whether the MRA is needed, required resources are 

available, and data and information needed to conduct the MRA are accessible. Once these decisions are 

made, a plan is laid out for the conduct and outcome of the MRA. An analysis plan may include a list of 

the risk managers’ questions to be addressed, goals, objectives, deliverable products, and timelines, as 

well as policy and operational guidance. 

81
 
Pathway Model 

Source Pathway Exposure Dose Response 

MRA Steps 

Hazard 

Identification 

Exposure Assessment Hazard Characterization 

Figure 6. Source-to-response paradigm aligned with relevant MRA steps based 

on the NRC framework. 

The four fundamental steps of traditional risk assessment (NRC, 1983) are commonly used in 

MRA frameworks. Briefly, the steps are 

1) Hazard identification. This term refers to the process used for determining whether a 

microbial pathogen can cause adverse health effects in humans and what those effects might be. 

Sometimes characteristics of the pathogen are placed in this MRA step. 

2) Hazard characterization. This step describes the potential adverse health effects attributable 

to a specific pathogen; the mechanisms by which the pathogen exerts its effects; and the associated dose, 

route, duration, and timing of exposure. This step often includes calculating the dose-response 

relationship between pathogen exposures and the extent of adverse outcomes among the exposed 

population. 

3) Exposure assessment. This step is used to identify the pathways by which pathogens may 

reach individuals, estimate the extent of pathogen exposure among humans, and estimate the likely 

number of persons exposed. A simple pathway model is presented in the upper portion of Figure 6. The 

output of this step is typically the estimate of the magnitude and/or probability of human exposure to the 

pathogen or microbial toxin of concern. 

4) Risk characterization. The final step of risk assessment is an integrative step that involves the 

“estimation of the likelihood of adverse human health effects occurring as a result of a defined exposure 

to a microbial contaminant or medium” (ILSI, 2000). This step is universally used as the last step in risk 

82
 
assessments. Descriptions of the modeling assumptions, uncertainties, and variability, along with 

possible risk management options, are also included in this step. 

5) Risk communication. Risk communication as a part of risk analysis is widely recognized as 

the open, interactive exchange of information and ideas about risk. When conducted effectively, risk 

communication is a strategic component of risk analysis, clearly based on knowledge, not guesses, about 

stakeholders’ interests and priorities (CSA, 1997). Few MRAs presented in this review mentioned risk 

communication issues. 

5.3. SIMILARITIES AMONG MICROBIAL RISK ASSESSMENTS 

5.3.1. Scope and Framework 

Scope. The scope of most MRAs conducted to date has been focused on specific places (e.g., 

Soller et al., 2003), foods (e.g., U.S. FDA, 2005), or pathogens in a limited number of foods (e.g., 

USDA, 2005b). Among the 13 MRAs reviewed in depth, all but one focused on a specific pathogen 

(e.g., salmonella, vibrio, cryptosporidium). Several MRAs investigated the impacts of a variety of 

environmental conditions (e.g., U.S. FDA, 2005) or a variety of foods (e.g., Coburn et al., 2005; USDA, 

2005a). 

Framework. Most organizations that have published MRAs have used the framework of the 

traditional chemical risk assessment paradigm (NRC, 1983). For food-related MRAs, organizations 

including USDA, FDA, ECFS, WHO, and Codex tend to use a modification of the chemical risk 

assessment framework (e.g., U.S. FDA, 2003a; WHO, 2002). In implementing the framework, teams 

have developed increasingly complex mathematical models. 

Among the MRAs studied in depth in this report, five (U.S. EPA, 2005b; U.S. FDA, 2005; U.S. 

EPA, 2004a; NZFSA, 2004; Hill et al., 2003) followed the same order as the traditional NRC (1983) 

framework: hazard identification, hazard characterization, exposure assessment, and risk 

characterization. Six (EFSA, 2006c; WHO, 2005; Nauta et al., 2005; USDA, 2005b; Pouillot et al., 

2004; Lindqvist and Westöö, 2000) reversed the middle two steps in this framework, and one (WHO, 

2006a) conducted the steps in a unique manner, as described in section 5.4.2. The incomplete 

documentation in Coburn et al. (2005) made the application of the full framework indeterminable. 

83
 
5.3.2. Components 

FDA and WHO have described the essential parts of each MRA step, shown in Table 7 (U.S. 

FDA, 2003a; WHO, 2002). Codex and ILSI have captured most of the important elements needed to 

conduct MRAs (see Appendix 7 of Yoe, 2003), but have not always been clear about the details of how 

to implement their approaches. 

Table 7. Steps in the FDA and WHO frameworks 

1. Statement of the problem 

a. State clearly the specific problem and scope to be addressed 

b. Define the nature and form of the MRA output and output 

alternatives 

c. Create a preliminary model “from farm to fork” 

2. Hazard identification 

a. Identify the microorganisms or microbial toxins of concern 

b. Determine relevant sources of data (such as clinical studies, 

epidemiological studies or surveillance, laboratory studies, etc.) 

c. Gather evidence about the pathogen, its presence in foods, and the 

adverse health effects (including severity and subpopulations at 

risk) associated with human consumption of contaminated foods 

3. Exposure assessment 

a. Define the actual or expected extent of human exposure 

b. Determine the scope and frequency of food contamination based 

on factors such as the microbial ecology of the foods (or matrices) 

of concern, potential for cross-contamination from contaminated to 

uncontaminated objects, sanitation and controls in production 

processes, methods of food handling and packaging, temperatures 

during storage and preparation, etc. 

c. Assess characteristics of consumers (e.g., demographics, 

behaviors, knowledge, perceptions of food hazards, prior illness, 

etc.) 

d. Examine patterns of consumption by seasonality, region, etc. 

e. Describe clearly the pathway from production to consumption 

f. Consider using scenarios to identify variations in exposures 

g. Estimate the level of pathogens and the probability of their 

occurrence in foods at the time of consumption 

4. Hazard characterization 

a. Determine the severity and duration of adverse health effects 

b. Examine potentially important characteristics of the microbe of 

concern (e.g., its ability to replicate, virulence and infectivity, 

potential for secondary and tertiary spread among hosts, time 

course from infection to the range of illness outcomes, impact of 

food attributes on the pathogenicity of the microorganism) 

c. Evaluate the importance of host characteristics (e.g., integrity of 

84
 
physiological barriers, factors that influence susceptibility and time 

course from infection to illness, population characteristics) 

d. Estimate the dose-response relationship, clearly noting the 

endpoints used for response (e.g., infection, illness) 

e. Examine the shape of the dose-response relationship and validate 

with real world data when possible 

f. Consider the importance of severity and duration of disease 

5. Risk characterization 

a. Integrate the prior three steps using conceptual and computational 

models to develop a risk estimate 

b. Estimate the likelihood and severity of adverse heath effects in a 

given population 

c. Describe the impacts of the assumptions and sources of uncertainty 

and variability embedded in the estimate 

d. Critically evaluate the strengths and weaknesses of the data used 

(e.g., comment on the weight of the evidence integrated) 

The data in this table were merged from numerous sources, cited in the Reference section and in Parkin (2007). 

The following component-specific observations are derived from the 13 MRAs examined in 

detail for this project: 

1) Problem statement. Nine of the 13 MRAs (see Table 6) included some type of problem 

statement. Most included a statement of purpose, and three included a section to describe the scope of 

the MRA. 

2) Feasibility. All of these MRAs omitted documentation of any feasibility assessment that was 

done prior to conducting the MRA. Little mention was given to issues of data access and availability, 

although some like EPA (2005b) discussed data sources and their strengths and weaknesses. Some noted 

data quality issues that limited the nature of the MRA; e.g., the Coburn et al (2005) MRA was 

qualitative due to the lack of quantitative data. 

3) Conceptual model. More detailed MRAs (e.g., U.S. EPA, 2005b; Nauta et al., 2005; USDA, 

2005a; Hill et al., 2003) provided extensive documentation of the modeling approaches, components, 

and underlying concepts. These multi-step models were made up of a series of mathematical models that 

fed outputs into the next module. 

4) Analytic plan. Analytic plans for the MRAs reviewed for this project typically were not 

presented in the publicly available documentation. 

A comparison of the traditional risk assessment steps yielded the following observations: 

1) Hazard identification. Among the MRAs reviewed, this step showed the least variation in 

content. The assessors consistently characterized aspects of the pathogen, its traits, and transmission 

85
 
 

routes that make it infective to humans. Typically, this step notes the pathogen’s life cycle, virulence, 

and factors that influenced the pathogen’s infectivity. 

2) Hazard characterization. All MRAs described host characteristics and disease outcomes, and 

modeled the dose-response pathogen-host relationship in this step. Most that conducted quantitative 

MRAs used the beta-Poisson model to calculate the probability of adverse health outcomes (e.g., WHO, 

2006). EPA (2005b) used an Exponential Dose Response Model that resulted from combining two 

probability functions (a Poisson probability distribution of infection given pathogen ingestion and a 

binomially distributed probability of infection given the dose ingested). Additionally, the step included 

all described pathogen characteristics that were particularly significant to implementing the model (e.g., 

Nauta et al., 2005). 

In this step, the MRAs that examined processed foods discussed characteristics of food matrices 

that could influence the shape of the dose-response curve (e.g., U.S. FDA, 2005; USDA, 2005b; WHO, 

2005). 

Notably, three MRAs provided appendices detailing their dose-response procedures and 

outcomes; FDA’s provides the most detail of all MRAs reviewed (U.S. EPA, 2005b; U.S. FDA, 2005; 

WHO, 2005). 

Coburn et al. (2005) did not include this step in their brief MRA article. 

3) Exposure assessment. In 10 of the MRAs, this step was the most extensively documented. 

Risk assessors used this step to effectively identify and model the complexity of the pathogen pathway 

and routes of exposure. For example, in the WHO (2005) risk assessment of V. vulnificus in raw oysters, 

the microbe’s ecological conditions, growth, and survival characteristics were discussed. EPA (2004) 

was the only MRA that presented data for numerous routes of exposure. In most cases, numerous 

factors could affect the outcome of the exposure assessment step, and considerable data needs had to be 

met. 

In most of the MRAs, the exposure assessment presented and described data on the human 

consumption of water or foods that conveyed pathogens of concern. Distributions of consumption were 

typically provided and when data were available, differences in consumption patterns were described. 

The data in this step are essential to characterizing the pathogen-host interface and to producing a useful 

outcome for risk characterization. Graphing pathways and constructing models for modules within those 

pathways facilitated organization of the complexities (e.g., USDA, 2005b). 

One MRA (Lindqvist and Westöö, 2000) did not provide much detail for this step. 

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4) Risk characterization. All of the MRAs described their modeling approaches and outputs in 

this section. Furthermore, although there are differences in level of detail, all agencies used this step to 

present, describe, and interpret their modeling results. Risk management options were also noted, but in 

different ways. 

It is in this step that most MRAs evaluated and described the sources of uncertainty and 

variability that affect the final MRA estimate of illness. Uncertainty is the result of unknown and 

unknowable errors in the data used in the MRA. Variability is the result of inherent heterogeneity in the 

data inputs (WHO, 2006a). 

5) Risk communication. The MRAs reviewed had little, if anything, to say about risk 

communication. 

5.4. DIFFERENCES AMONG MICROBIAL RISK ASSESSMENTS 

5.4.1. Scope and Framework 

Scope. The MRAs reviewed handled scoping issues in different ways—in statements of purpose, 

risk profiles, or problem formulation steps. The 13 MRAs reviewed typically had a national scope, but 

few addressed place and time explicitly. Furthermore, few addressed the risks to susceptible 

subpopulations (e.g., EFSA, 2006c; U.S. EPA, 2005b; Pouillot et al., 2004). 

Framework. While most organizations have adopted the traditional chemical risk assessment 

framework or a modification of it for microbial risks, the EPA National Homeland Security Research 

Center office has used the ILSI (2000) paradigm as the basis for its incident response assessments 

(Nichols et al., 2006). Their process begins with problem formulation and ends with risk 

characterization; the differences appear in the analytical phase. The Center’s exposure assessment and 

hazard assessment steps involve many of the elements that appear in the analysis phase of the ILSI 

paradigm. Elements within each of these steps, however, have been aligned differently than in the 

exposure characterization and human health effects characterization steps of the ILSI framework. 

Additionally, exposure assessment requires a conceptual model that is generally similar to sourcepathway-receptor approaches, but includes sampling for incident response contexts. 

Among the MRAs studied in detail, WHO (2006a) modified the traditional NRC steps in a 

unique manner: problem formulation was documented after hazard identification. 

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5.4.2. Components 

ILSI (2000) and Codex (1999) have listed many elements that need to be considered in MRA 

steps. These elements have been reviewed and compared by Yoe (2003); there are many similarities in 

what elements to include, but terminology varies. Codex is more inclusive in the hazard 

characterization step (e.g., regional, behavioral, and ethnic concerns are more developed), while ILSI 

includes more elements for dose-response (e.g., specificity of the organism strain and virulence and use 

of surveillance and outbreak data). Yoe and others have noted that elements are repeated in several 

steps in the ILSI framework, potentially causing confusion for some risk assessors. Others have seen 

this redundancy as supporting flexibility in implementation, or demonstrating an ad hoc approach to 

MRA (Buchanan et al., 2000). 

Components within general MRA frameworks are not typically defined, but may be revealed by 

examining MRAs published by agencies. For example, elements of problem formulation were identified 

in some steps (e.g., hazard identification), but generally the MRAs reviewed did not include problem 

formulation. These differences reflect the current ad hoc application of frameworks for MRAs (Yoe, 

2003).. 

The following component-specific observations are derived from the MRAs examined in detail 

for this project: 

1) Problem statement. The cryptosporidium MRA (WHO, 2006a) was the only one that included 

an explicitly identified problem formulation step; this comprehensive step followed the hazard 

identification step. After describing the pathogen’s characteristics that make it infective to humans, the 

problem formulation focused on describing events and disease outbreaks in which waterborne 

cryptosporidium resulted in adverse human health events. This MRA also examined data from sanitary 

surveys and historical monitoring systems to describe features of specific sites that contributed to 

hazardous events and outbreaks. 

2) Feasibility. Some consideration of the populations of interest was given early in MRA 

articles and reports. While the hazard characterization step usually described characteristics of at-risk 

populations (e.g., U.S. EPA, 2005b; WHO, 2005), the exposure assessment step noted factors and 

behaviors that could contribute to increased risks. These populations were usually described in 

qualitative, rather than quantitative terms. A few MRAs included data for subpopulations (e.g., Pouillot 

et al., 2004; Lindqvist and Westöö, 2000). 

88
 
 

3) Conceptual model. Several of the MRAs presented modular schematics that helped organize 

and explain the assessment’s components, contributing factors, and calculations (U.S. FDA, 2005; Nauta 

et al., 2005; USDA, 2005b; WHO, 2005). USDA offered a schematic early in the documentation 

(Figure 1-1 on page 11 of USDA, 2005b) that showed the MRA steps and the factors to be addressed in 

each step. More detailed schematics are presented and discussed in each of USDA’s MRA steps. Both 

FDA and USDA described their modules extensively, although USDA does not use “module” in 

reference to the compartments or separate mathematical models in its MRA. These modules are 

described further in section 5.5.2. 

WHO’s raw oyster MRA (WHO, 2005) presented a conceptual model with three modules— 

Harvest, Post-Harvest, and Public Health. This schematic (Figure 1 on page 22 of WHO, 2005) is 

offered in the Interpretative Summary, as well as in the exposure assessment step. In both cases, it helps 

the reader follow the text and grasp the impact of the many factors considered in modeling the health 

risk. 

Lindqvist and Westöö (2000) provided a schematic of their conceptual model, with some 

equations linking components of the model. 

4) Analytic plan. Although some of the MRAs generally described their approach (e.g., U.S. 

FDA, 2005), only one provided an explicitly labeled “modeling plan”; this was a detailed description for 

a probabilistic analysis of shell eggs (USDA, 2005b). The plan described the components of the model 

(see section 5.2); the inputs for assessing pathogen concentrations throughout the model; the means to 

handle uncertainty; and other aspects of modeling. 

Observations about the differences in application of the four steps in the traditional risk 

assessment framework follow: 

1) Hazard identification. In this step, some of the MRAs (e.g., NZFSA, 2004; WHO, 2004b; 

WHO, 2006a) identified hazards. These and three more MRAs (U.S. EPA, 2004a; U.S. FDA, 2004; 

EFSA, 2006a) described pathogen pathways in different foods, processes, and/or geographical regions. 

FDA (2005) provided the most extensive description of the possible sources of contamination in 

this step. 

In one drinking water MRA (WHO, 2006a), a detailed hazard identification step described the 

pathogen’s characteristics (e.g., life cycle, prevalence, and routes of transmission), ability to be 

transmitted in water (e.g., environmental sources, resistance to chemical treatment and filtration by 

89
 
water systems, persistence in drinking water), and the characteristics that make it pathogenic to humans 

(e.g., infectivity, shedding). 

2) Hazard characterization. The WHO raw oyster MRA (2005) presented its Public Health 

module (including dose-response calculations) in the hazard characterization step, which followed 

exposure assessment in the documentation. The step described the pathogen’s virulence, host 

susceptibility factors, health behaviors, characteristics of oysters as food matrix, and adverse health 

outcomes. The dose-response relationship was modeled using a beta-Poisson approach. Furthermore, 

impacts of modeling assumptions, uncertainty, and variability were analyzed and described here, rather 

than in the risk characterization step. 

EPA (2005b) presented an analysis of several dose-response models, and compared them to 

determine which approach was most suitable. The description of these models and their relative merits 

for the MRA purpose is extensive and informative. Furthermore, this MRA used data on infectivity from 

numerous published studies to estimate a probability distribution for infectivity and used morbidity and 

mortality factors to estimate, respectively, the risks of illness given infection and the risks of death given 

illness. 

3) Exposure assessment. Three of the MRAs (U.S. FDA, 2005; Nauta et al., 2005; USDA, 

2005b) presented detailed modules, subcomponents, schematics, and mathematical models to 

characterize the changes in pathogen concentrations as the microorganisms moved through source-tohost pathways. The most complex set of modules was developed in the USDA (2005b) MRA of 

salmonella in shell eggs and egg products. The complexity resulted in part because these two types of 

foods do not have the same farm-to-fork pathway; consequently, each had to be described, modeled, and 

discussed separately. For example, the farm-to-fork model described in this step had eight modules that 

were mathematically modeled (See section 5.5.2.) 

The WHO MRA of raw oyster risks (2005) modeled harvest and post-harvest processes; 

included simulations of differing source, environmental, and handling conditions; and preserved data for 

the purpose of validating the model. 

WHO’s MRA (2006a) detailed assessments of exposures and effects presented in two separate 

steps. This MRA also provides insights into how to obtain data necessary to conduct MRAs. First, the 

exposure assessment section presents data for and describes the methods by which cryptosporidium is 

detected in water, monitored in treated and untreated drinking water supplies, and removed by treatment 

processes. Limitations of treatment, monitoring, and laboratory methods are discussed. Patterns and a 

90
 
statistical distribution for human consumption of drinking water are also detailed. Second, in the effect 

assessment step, the host characteristics (including susceptibility factors) are presented, adverse heath 

effects described, and the dose-response relationships for four strains of cryptosporidium (IOWA, 

TAMU, UCP, and Moredun) are determined. The evidence basis for effects assessment includes human 

feeding trials, theories, evidence about host and pathogen factors, and factors that affect the probability 

of illness following infection. This last issue is important because not all infections lead to clinically 

diagnosed illness, while some infections (e.g., C. jejuni) can result in long-term sequelae. 

EPA’s exposure assessment of cryptosporidium in drinking water relied on the distribution of the 

pathogen in finished water, distribution of individual consumption of drinking water and days of 

exposure, and estimated numbers of the populations served by affected water systems (U.S. EPA, 

2005b). 

4) Risk characterization. In this step, most MRAs (e.g., U.S. EPA, 2005b; U.S. FDA, 2005: 

USDA, 2005b) discussed uncertainty and variability, some conducted sensitivity and scenario analyses, 

and some interpreted the impacts of uncertainty and variability on the MRA outputs. As noted below, 

however, FDA’s detailed appendices provided additional valuable information for understanding how 

these issues were examined and interpreted (U.S. FDA, 2005). 

In risk characterization, WHO (2005) used seasonal variations in water temperature to calculate 

the annual variation in risk from V. vulnificus in raw oysters, and to predict the annual number of 

illnesses that would result. Additionally, this step presented data describing the impacts of a variety of 

geographic settings and public health interventions to reduce these risks. 

Like most MRAs, based on the outcomes of all prior steps, WHO’s drinking water MRA (2006a) 

presented an integrated assessment of the risk from waterborne cryptosporidium. However, this 

document provides additional value to decision-makers by describing a tiered approach to risk 

management; it provides three cases to demonstrate how to apply their MRA framework to meet 

different risk management needs. The cases focus on prioritizing risk management options, evaluating 

risk scenarios, and considering health-based targets. 

In its V. parahaemolyticus MRA, FDA presented the most extensive risk characterization, 

including a thorough assessment of both uncertainty and variability (U.S. FDA, 2005). The considerable 

depth and excellent organization of the related appendices are commendable. An additional strength of 

this MRA is its validation of the MRA output. 

91
 
 

 

5) Risk communication. Three agencies prepared and web-posted interpretative summaries for 

readers with less of a technical background (U.S. FDA, 2005; USDA, 2005b; WHO, 2005). One had a 

very brief summary (NZFSA, 2004), and one did not include a summary (WHO, 2006a). Some of the 

MRAs included extensive, technical appendices (e.g., U.S. FDA, 2005) and some did not (e.g., NZFSA, 

2004). 

One relevant and outstanding feature of the FDA (2005) MRA, however, was its tiered 

construction—a summary for general audiences, a report for readers who wish to know more, and the 

inclusion of numerous appendices that provided detail for the most technically oriented readers. This 

approach to providing information on differing levels often meets the widest possible range of 

stakeholder needs. Furthermore, FDA included specific sections describing the criteria and selection 

procedures for data used in each step of their MRA. The assessment used tables in these sections to 

highlight the results of the criteria used. An additional feature that strengthened the FDA MRA was the 

inclusion of specific sections describing assumptions made, and the data sources used in each step of the 

framework. Overall, the FDA (2005) MRA is highly readable, informative, and innovative in the 

construction and presentation of its text and graphics. 

5.5. KEY ISSUES IN COMPARING MICROBIAL RISK ASSESSMENTS 

While the frameworks used in the 13 MRAs were quite similar (some form of problem 

description preceded the four traditional risk assessment steps), they differed in the implementation and 

depth of the framework components. Flexibility in applying MRA frameworks is essential for meeting 

urgent and emerging needs. However, it is striking that no agency to date has conducted and evaluated 

an MRA using the ILSI (2000) paradigm.29 In this reviewer’s opinion, this framework provides a 

comprehensive structure and set of individual components that are better suited to MRA than does a 

modified chemical risk assessment approach. One strength of the ILSI paradigm is its explicit calling out 

of the many unique factors that influence pathogen-host relationships. Assuring that these and all routes 

of exposure are considered are important contributions of the ILSI approach. 

A recent and key contribution to MRA is the development of a modular approach, particularly to 

exposure assessments’ pathway analyses. The complexity of these pathways can be extraordinary, but 

the ability to identify self-contained elements that can be modeled effectively is an important 

29 It is noted, however, the two evaluations of the ILSI (1996) paradigm were completed by Teunis and Havelaar and 

Soller et al., (both in 1999), as bases for the 1999 ILSI workshop that redesigned the original MRA framework. 

92
 
advancement. In this reviewer’s opinion, this approach to implementing MRAs should be more widely 

applied, and risk assessors should share the lessons learned from using this approach. 

Many scientific questions remain to be addressed; all of the MRAs noted research and data 

needs. Data are insufficient to implement many of the desired MRA models (Yoe, 2003). For example, 

data are needed on strain virulence factors, dose-response relationships, exposure characteristics, 

subpopulation characteristics, dynamics of disease spread in populations, animal model extrapolations, 

and illnesses due to toxins generated by microorganisms (Krewski et al., 2004). While significant data 

deficiencies exist, MRA methods, pathogen test protocols, and sampling schemes need to be advanced 

as well (Gardner, 2004). 

Currently, the extent of missing or insufficient data is much greater in most MRAs than in 

chemical risk assessments, resulting in a greater degree of uncertainty. Additionally, the extent to which 

MRA components vary is largely unknown, making the steps to understand the sources of variability as 

well as uncertainty in the final modeling results more important. The value of conducting sensitivity 

and probabilistic analyses to reveal the impacts of variations in MRA components cannot be 

overestimated. The insights gained will not only be useful for the specific MRA being conducted, but 

will also contribute to the body of knowledge about microbial pathogens, factors that influence their 

impacts on human health, and factors that affect MRA methods and results. 

Most importantly, understanding the sources of uncertainty and variability remains crucial for 

ensuring informed decision-making and selection of appropriate risk management options. While 

methods exist to assess and describe uncertainty and variability impacts on MRA outputs, more needs to 

be done to enhance comprehension of the rich information embodied in graphic displays of quantitative 

distributions. Furthermore, the explicit identification of assumptions used in MRA models is essential; 

en excellent example is demonstrated in the FDA (2005) MRA for raw oysters. 

The ability to conduct an effective MRA may be constrained by several factors, including the 

lack of skilled personnel to fully implement the analytic steps. An incomplete understanding of sourcepathway-receptor elements and linkages also limits the conduct of MRAs (Godfrey and Smith, 2005). 

Important gaps in knowledge about disease processes and microbial pathogen lifecycles require 

assumptions and uncertainty analysis (Parkin, 2002). 

When MRA products are needed in an emergency context, risk managers will find it difficult to 

implement all MRA framework steps effectively. In anticipation of future needs, organizations may 

want to consider developing clearer managerial processes to guide MRAs when urgency is a driver. 

93
 
Identifying the leader to convene the MRA team and the mechanism to clarify the statement of purpose 

and scope of the MRA are crucial first steps. 

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6. ENVIRONMENTAL MEDIA AND MICROBIAL RISK ASSESSMENT 

The purpose of this section is to comment on issues related to environmental media identified in various 

MRAs, including those evaluated in section 5. While the focus of the discussion here is on the modules 

used to organize the MRAs, key media-specific concerns and methods are also presented. 

6.1. AIR 

There are two general types of exposure models for airborne pathogens: one for person-person 

transmission and one for aerosol contamination of foods or other items by humans (environment-person 

contact). Liao et al. (2005) have described indoor air transmission models for three scenarios: a school, 

a hospital, and commercial airliner. This infectious disease model includes variables such as respiratory 

rate, air exchange rate, and numbers of infected and susceptible individuals. 

In den Aantrekker et al.’s (2003) study of recontamination of foods during factory processing, 

researchers identified aerosolization of cleaning chemicals as one way in which pathogens could be 

introduced into foods. They determined that bacterial residues on processing equipment formed a 

biofilm that could periodically break off and recontaminate food after pathogens in the food had been 

inactivated in the processing system. 

At the time of this review, government-sponsored airborne pathogen models were under 

development. 

6.2. DRINKING WATER 

Numerous studies of drinking water exposures to pathogens have been conducted (e.g., 

Eisenberg et al., 2005; Haas et al., 1993). It is striking that in these studies the modules considered are 

very similar. The typical sequence of MRA exposure assessment compartments is 

• Source of contamination (e.g., household sewage) 

• Raw water source (catchment, reservoir, river, well) for the drinking water supply 

• Treatment 

• Storage and distribution 

• Customer’s plumbing and point-of-use devices (least often found element) 

• Tap water 

95
 
• Consumption/exposure 

While these modules are followed by dose-response assessments, some MRAs address risk on 

the individual scale while others address the population level. In the latter case, disease transmission 

models are used and primary (environment-person), secondary (person-person), and tertiary (personenvironment-person) transmission may be included (e.g., Eisenberg et al., 2005). 

The French MRA of cryptosporidiosis provides a schematic display of their modeling approach 

(Pouillot et al. 2004). The major modules are 

• Emission 

• Consumption 

• Exposure 

• Effect 

o Dose-response 

o Infection-illness 

The diagram clearly shows that the outputs from the emission and consumption modules are 

combined to create the input for the exposure module. The result of this component is then combined 

with the results of the dose-response model to produce two effects measures: probability of infection and 

probability of illness. 

EPA’s cryptosporidium MRA for the LT2 rule economic analysis modeled infectivity, 

morbidity, and mortality. The MRA included extensive discussions of the dose-response literature and 

documented a comparative analysis of the literature. The agency laid out its model for estimating 

individual risk (Exhibit 5.11 in U.S. EPA, 2005b) as follows: 

• Pathogen occurrence 

• Source water concentration (for both baseline and LT2 reduction options) 

• Finished water concentration 

96
 
• Consumption 

• Daily dose 

• Daily risk of infection 

• Days of exposure 

• Annual risk of infection and illness 

• Risk distributions 

The final step involved a Monte Carlo model to characterize the distribution of individual risks 

of illness and death and also the population-scale levels of annual illness and death. The assessment 

extensively discussed the literature on secondary spread and described decisions as to how the data were 

used for informing the population-scale estimates. The first step of risk characterization was calculating 

the annual risk of illness, and the second step applied that result and included the impacts of secondary 

spread to estimate the population level estimate of the risks of illness and death and finally the benefits 

obtained when the various versions of the proposed rule were modeled (U.S. EPA, 2005b). 

WHO’s recently completed MRA of cryptosporidium in drinking water does not use a modular 

approach, but does provide in-depth descriptions of the pathogen and environmental factors that affect 

its infectivity and transmission to human hosts (WHO, 2006a). The report also covers the difficulties of 

accurately monitoring the pathogen in drinking water sources and treated water supplies. The hazard 

identification step in this MRA is quite detailed. Elements considered in this step include 

• The pathogen’s taxonomic position 

• Life cycle 

• Related disease 

• Prevalence of the pathogen in human excretions 

• Routes of transmission (via food and water, human-to-human and animal-to-human) 

• Resistance to chemical disinfection processes 

97
 
•	 Persistence in the environment 

•	 Impacts of the pathogen’s small size (ability to pass through water filtration systems) 

•	 Infectivity of pathogen strains 

•	 Human and livestock sources 

•	 Oocyst shedding amounts 

•	 Immediate infectivity of the oocysts upon excretion 

Furthermore, the assessment carefully considers factors that have influenced disease outbreaks 

and ways to model those factors. Considerable data are used to characterize the health risks. An 

important contribution of this MRA is its presentation of three case studies, which demonstrate the value 

of the MRA’s methods for different risk management purposes. 

Uniquely, this MRA separates exposure and effect assessment into two distinct processes. The 

level of detail provided in these two steps is important to ensuring a comprehensive approach to the 

MRA. Key elements addressed in these two steps are 

Exposure assessment 

•	 Methods of detecting Cryptosporidium in water for determining 

o	 Recovery efficiency 

o	 Viability/infectivity 

o	 Specificity 

•	 Monitoring (un)treated drinking water (meaning monitoring data for water systems presumed 

to be treated but in reality with failed or suboptimal treatment processes). 

•	 Cryptosporidium in source water and removal by treatment 

o	 Assessment of treatment efficacy 

o	 Post-treatment contamination 

•	 Consumption of drinking water (presenting data from several nations) 

Effects assessment 

•	 Host characterization 

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• Health effects 

• Dose-response analysis 

o Human feeding studies 

o Hit theory for infection (beta-Poisson modeling) 

o Pathogen factors (variations in infectivity among isolates) 

o Host factors (immunity and susceptibility to infection) 

o The spectrum of health outcomes from infection to illness 

The detailed examination of key factors in the WHO (2006a) MRA demonstrates how different 

the issues are in MRAs compared to chemical risk assessments and how important it is to identify and 

characterize these factors sufficiently to improve the utility of the MRA. The major limitation in 

implementing this level of assessment is the lack of relevant data for many waterborne pathogens and 

related health outcomes. 

6.3. RECREATIONAL WATER 

Recreational water includes both flowing and impounded water, including rivers, lakes, ponds, 

spas, hot tubs, pools, etc. In risk assessments for impounded waters (e.g., van Heerden et al., 2005), 

exposure assessments include estimating the concentration of the pathogen in the water, treatment 

efficacy, rate of pool water change, pH level, viability of the organisms recovered, and consumption. 

Two risk assessments that have investigated swimming in flowing waters used the following exposure 

assessment modules (Craig et al., 2003; Soller et al., 2003): 

• Raw wastewater 

• Source water and ambient environmental factors 

• Treatment 

• Contact/consumption (dermal and ingestion) 

Similar to drinking water, the output of this sequence of steps is sometimes linked to disease 

transmission models to estimate population risks. 

Although WHO has developed HACCP approaches to pathogens in drinking water, no complete, 

government-sponsored MRA of a pathogen in recreational water was found during this project. 

99
 
6.4. WASTEWATER 

Sewage from animal and human sources can be treated and used for a variety of purposes such as 

toilet flushing; irrigation of crops, parks, sport playing fields, and golf courses; and recharge of ground 

water supplies. It also is sometimes inadvertently introduced into recreational water supplies. 

Several MRAs have modeled the risks associated with “gray water” or water reuse applications 

(e.g., Westrell et al., 2004; Ottoson and Stenstrom, 2003). In these evaluations, exposure assessment 

sub-steps have included examinations of 

•	 Source of contamination 

•	 Transport (distance from source to treatment or point of use) and use (application to 

agricultural land) 

•	 Treatment 

•	 Post-treatment storage 

•	 Distribution and use (holding ponds or tanks, etc.) 

•	 Contact/consumption in treatment plant or public spaces 

These modules from source to contact/consumption would not apply to all cases, but can be 

tailored to the contexts of the scenario of concern. 

No government-sponsored MRA for pathogens in wastewater was found during this project. 

6.5. FOOD 

Foods vary in the degree of handling, processing, storage, preparation, and their significance and 

use among differing population groups. To reduce the conceptual and computational challenges in 

assessing pathogen risks related to foods, MRAs typically focus on subsets of foods, such as fresh 

produce, minimally processed foods, or highly processed foods. 

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6.5.1. Fresh Foods 

Fresh produce such as lettuce, fruits, and peppers have been studied for microbial contamination 

and related health risks (e.g., Stine et al., 2005; Petterson et al., 2001). Modules used in exposure 

assessments for produce that receives little or no processing include 

•	 Secondary treatment effluent used for irrigation 

•	 Distribution and use of irrigation water (holding ponds or tanks, on land, in irrigation 

systems, etc.) 

•	 Pre-harvest contamination of crops 

•	 Harvest 

•	 Post-harvest contamination 

•	 Handling and preparation of produce 

•	 Contact/consumption 

No agency-sponsored MRA for fresh food was located during the course of this project. 

6.5.2. Processed Foods 

Other foods require processing before retail sales, preparation, and consumption. However, the 

intensity of processing may vary widely, resulting in a need to consider different modules in conducting 

exposure assessments of processed foods. This section summarizes the modules used to model pathogen 

risks associated with processed foods. Nine of the 13 agency-sponsored MRAs reviewed addressed 

pathogens in foods, and thus are discussed in the following section, with more details about modules in 

Appendix 1. 

Foods that require minimal processing before retail sales include unripened cheese made from 

raw milk (Lindqvist et al., 2002), shellfish (U.S. FDA, 2005; WHO, 2005; FAO/WHO, 2002c), some 

fishery products (Ross et al., 2000; Lindqvist and Westöö, 2000), whole and pieced poultry (Nauta et al., 

2005; NZFSA, 2004; WHO, 2002; FAO/WHO, 2002c; U.S. FDA, 2001), shell eggs (USDA, 2005b; 

WHO, 2002; USDA, 1998), and beverages (Syposs et al., 2005). 

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Other food products such as egg products (USDA, 2005b; 1998); wild game products (Coburn et 

al., 2005); turkey cordon bleu (Bemrah et al., 2002); pig-meat products (Hill et al., 2003); and ready-toeat meals (USDA, 2005a; U.S. FDA, 2003a; 2004; U.S. FDA/USDA FSIS, 2001) involve more 

processing steps and therefore more opportunities for contamination (e.g., den Aantrekker et al., 2003). 

WHO’s guidelines to strengthen prevention and response systems for food safety includes a sixstep schematic of the typical food chain (WHO, 2002). The steps shown are: agricultural production and 

harvesting, storage and transport of raw commodities, processing and manufacture, storage and transport 

of processed and manufactured products, wholesale and retail distribution, and food service sector. 

Table 8 provides a summary of the modules found in the peer-reviewed and government literature. 

Appendix 1 includes additional details. 

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Table 8. Summary of exposure pathway modules used in processed food MRAs 

MODULES 

FOODS 

Source Harvest Post-harvest 

production 

Processing Transport or 

Distribution 

Storage Retail 

sale 

Consumer preparation 

C

Unripened cheese 

X X 

Storage 

Shell eggs X 

Farm 

X 

Collection 

X 

Pasteurization 

X X X 

Egg products 

X 

Break shells 

and 

Pasteurization 

X X 

Storage, 

preparation 

and cooking 

Beverages X 

Raw water 

X 

Processing, 

bottling, 

capping 

Shellfish X X Fish products 

X 

Fishery 

X X X X 

Wild game products 

X 

Live animal 

X 

Slaughter 

X X 

Broiler chickens 

X 

Farm 

X 

Slaughter 

X X X X 

Turkey products 

X 

Farm 

X 

Slaughter 

X 

Pig meat products 

X 

Farm 

X 

Slaughter 

X X X X 

Highly processed foods 

X 

Raw food 

ingredients 

X X X X X 

103
 
 

Some foods were assessed by several organizations. The opportunity to compare 

approaches for specific foods are food groups was used to look for substep variations. The 

comparisons made at this level are described below. 

6.5.2.1. Raw Oysters 

The MRAs most recently completed by FDA (2005) and WHO (2005) were conducted to 

investigate Vibrio spp. hazards associated with raw oysters. The modules and components of 

these two MRAs are shown in Table 9. Both of these MRAs included scoping steps and 

described pathogen and host characteristics in the hazard identification and hazard 

characterization steps. Both discussed characteristics of the food matrix (raw oysters) in hazard 

characterization, and used the beta-Poisson model to determine the dose-response relationship. 

Both MRAs used a modular approach in the exposure assessment step. While the first 

two modules in the MRAs were Harvest and Post-Harvest, FDA named its third module 

Consumption, while WHO named its third component Public Health. More importantly, the 

components of the modules are quite similar and in the same sequence, but the outcomes for 

these two MRAs are different. 

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Table 9. FDA and WHO raw oyster MRA modules and components 

FDA (2005) modules and components WHO (2005) modules and components 

Harvest Harvest 

• Water temperature 

o Relationship between pathogens 

in oysters and water 

temperature 

• Water temperature 

o Relationship between pathogens 

in oysters and water 

temperature 

• Concentration in oysters at time of 

harvest 

• Concentration in oysters at time of 

harvest 

o Duration of harvest 

o Time to refrigeration 

o Oyster/air temperature 

• Concentration in oysters at time of 

initial refrigeration 

o Duration of cool-down 

Post-Harvest Post-Harvest 

o Duration of harvest 

o Time to refrigeration 

o Oyster/air temperature 

• Concentration in oysters at time of 

cool-down 

o Die-off rate 

o Duration of storage 

• Concentration in oysters at time of 

initial refrigeration 

o Duration of cool-down 

o Growth rate 

• Concentrations at time of 

consumption 

o Grams per oyster 

o Number of oysters per 

serving 

• Concentration in oysters at time of 

refrigeration 

o Cold storage time 

o Die-off rate 

• Pathogenic oysters at retail 

Consumption Public Health 

• Pathogenic organisms per serving at 

consumption 

o Dose response relationship 

• Pathogen dose per serving 

o Dose-response relationship 

• Risk of illness (per serving) 

o Frequency of servings 

• Risk of illness (per serving) 

o Number of servings 

consumed by the at-risk 

population 

• Risk of illness (per annum) • Number of illnesses 

6.5.2.2. Shell Eggs and Egg Products 

USDA’s most recent MRA examined the risks associated with S. enteriditis in shell eggs 

and egg products (USDA, 2005b). In this MRA, characteristics of salmonella, factors that affect 

disease transmission, and related illness are described in the hazard identification step. In the 

exposure assessment section, separate assessments are completed for shell eggs and egg products 

105 
 

using the modular approaches listed below. Hazard characterization includes dose-response 

assessment and estimation of a range of adverse health outcome measures (illness, 

hospitalizations, deaths, and sequelae30). The MRA ended with a risk characterization with two 

sections, one for each type of food of concern. 

As Table 10 shows, the exposure assessment modules and components for shell eggs and 

egg products are similar, but they require consideration of different factors and data sources to 

implement an MRA for each. 

Table 10. USDA Exposure assessment modules and components for shell eggs and egg 

products 

Shell eggs Egg products 

Farm-to-Table Progression in Exposure 

Assessment 

Flow of Egg Products in Exposure 

Assessment 

• Farm 

o Salmonella in egg at lay 

• Breaking 

o Salmonella in serving before 

pasteurization 

• Storage 1 

o Growth in egg prior to 

processing 

• Pasteurization 

o Pasteurization factor 

• Pasteurization 

o Pasteurization factor 

• Storage 2 

o Growth in egg after 

pasteurization 

• Storage and preparation 

o Growth in serving after 

pasteurization 

• Preparation 

o Portions per contaminated egg 

• Cooking 

o Cooking effect 

o Salmonella at consumption 

• Cooking 

o Cooking effect 

6.5.2.3. Whole Chickens 

The New Zealand Food Safety Authority’s most recently sponsored MRA was for 

salmonella (non-typhoidal) in whole and pieced chicken (NZFSA, 2004). Relevant 

characteristics of the pathogen, and domestic versus imported chicken supplies were described in 

the hazard identification step, with health outcomes and dose response presented in hazard 

characterization. The ensuing exposure assessment had the following components: 

30 Sequelae noted in this MRA included adverse health outcomes with delayed onset after initial infection 

and/or illness. Sequelae were identified as: reactive arthritis, urethritis, conjunctivitis, entesopathy, myalgia, weight 

loss of over 5 kg, dactylitis, erythema nodosum, oral ulcers, myocarditis, acute anterior uveitis, iritis, cholecystitis, 

keratitis, pharyngitis, and pneumonia. 

106
 
• Hazard in the New Zealand food supply 

o Salmonella in poultry meat during production and after chilling 

o Salmonella in poultry meat at retail 

o Salmonella prevalence based on a 2003–2004 New Zealand-specific survey 

• Food consumption 

• Qualitative estimation of exposure 

o Number of servings and serving sizes 

o Frequency of contamination 

o Predicted contamination at retail 

o Growth rate during storage and probable storage time 

o Heat treatment 

o Exposure summary 

• Overseas context 

o Salmonella in poultry meat, raw and ready-to-eat 

Although not as extensively detailed as Nauta et al. (2005), NZFSA provides sufficient 

detail for the reader to understand the factors that influence the level of contamination in whole 

and pieced chicken. 

Nauta et al. (2005), however, provided extensive documentation and data for the farm-tofork pathway for broiler chickens. This MRA’s model relied on the Modular Process Risk 

Model, which includes several stages: 

• Farm 

• Processing 

• Cutting 

• Storage 

• Consumer preparation 

• Ingestion/dose-response 

The model also considers multiple opportunities for cross-contamination and removal. 

The MRA provides graphic representations of the model, detailed equations, and clearly stated 

107
 
assumptions throughout. It also thoroughly examines the potential impacts of uncertainties and 

variabilities. 

6.5.2.4. Variety of Foods 

Five MRAs assessed pathogen risks associated with groups of foods: 

• Lindqvist and Westöö, 2000: Several types of cold- and hot-smoked fish 

• Hill et al. 2003: Three categories of pig-meat products 

• Coburn et al., 2005: Food types of processed wild game 

• Nauta et al., 2005: Broiler and other meats 

• EFSA, 2006c: Foods and beverages 

The least detailed qualitative MRA (Coburn et al., 2005) identified the three microbial 

pathogens that posed the greatest health risks and in which foods. 

Lindqvist and Westöö (2000) presented a schematic diagram of their model structure, 

clearly indicating how each component relates to other parts of the MRA. The primary 

compartments of the model are 

• Concentration of the pathogen in fish 

• Number of pathogens consumed 

• Dose-response 

• Probability of illness (per serving and per year) 

• Number of cases per year in Sweden 

The authors also provided data and Excel spreadsheets they used in the model, and they 

presented and discussed results from using two different dose-response models. 

Hill et al. (2003) provided extensive detail of their pig-meat products model, with the 

following major modules: 

108
 
• Farm 

• Transport and lairage 

• Slaughter and processing 

• Distribution and storage 

• Preparation and consumption 

• Human effect 

The detailed report of this MRA provides a purpose statement for each module, the data and 

equations used, modeling decisions, assumptions, and assessments of the impacts of uncertainties 

and variabilities. Several scenarios are used to assess the impacts of specific parameters. 

Limitations of the modeling approach and results are included. The model also considers 

multiple opportunities for cross-contamination and removal. The MRA provides graphic 

representations of the model, detailed equations, and clearly stated assumptions are provided 

throughout. The potential effects of uncertainties and variabilities are thoroughly examined. 

EFSA (2006c) provided detailed toxicological data for the renal, nervous, immune, and 

reproductive systems in addition to cancer. The authors also presented consumption data derived 

from three European nations. 

The modular approach used by Nauta et al (2005) is described in section 6.5.2.3. 

6.6. BIOSOLIDS 

A few risk assessments have been completed for biosolids—animal waste on pastures 

used for recreation, and biosolids used on agricultural lands (Eisenberg et al., 2004; Gerba et al., 

2002; Strachan et al., 2002). 

In these cases, the modelers used the following modules in their exposure assessments: 

• Pathogen sources and intermediate hosts 

• Pathogen fate and transport in the environment 

• Pathogen resistance to environmental conditions 

109
 
• Pathogen occurrence in biosolids 

• Pathogen survival of biosolid treatment processes 

• Use of biosolids (land applications) 

• Environment-person contact/exposure 

When secondary and tertiary transmission and population risk estimates are needed, the 

exposure assessment outcomes have been linked to disease-transmission models. 

Eisenberg et al. (2006) have proposed a dynamic modeling approach to estimating human 

health risks due to biosolid uses. Exposure scenarios and exposure pathway models 

(groundwater and aerosol) provide the statistical inputs for estimating three risk measures: 

individual single event level risk, annual individual level risk, and population level attributable 

risk. Based on the first ILSI framework (ILSI, 1996), five components—wastewater, wastewater 

treatment, sludge treatment, biosolids application, and exposure—represent the environmental 

processes that lead to human exposures. The health effects part of the framework includes 

modeling health effects (using either static or dynamic models) and characterizing risk. 

No agency-sponsored MRA of biosolids was found at the time of this review. 

6.7. GENETICALLY MODIFIED ORGANISMS 

The MRA of Streptomyces lydicus WYEC 108 (U.S. EPA, 2004a) reviewed in this 

project is an example from a series of assessments conducted on modified organisms used in 

food processing and other purposes. The emphasis in these evaluations is on toxicological 

evidence, because these organisms are not approved for use at the time of assessment. Exposure 

potentials for various routes and populations (e.g., occupational and susceptible groups) are 

considered but no pathway analyses are conducted. Risk characterizations are brief, but margins 

of exposure and uncertainty factors may be applied to protect vulnerable populations. 

The recent publication of guidelines related to genetically modified organisms (e.g., 

EFSA, 2006a; FAO/WHO, 2003b), however, suggests that MRAs for these organisms may be in 

process and published in the near future. 

110
 
6.8. INTENTIONAL USES OF MICROBES 

The U.S. Centers for Disease Control and Prevention (CDC) has selected and prioritized 

biological terrorism agents using a qualitative risk assessment approach (CDC, 2002). Based on 

judgments of each agent’s potential public health impacts, potential for widespread distribution 

among populations, public perception of each agent, and specific public health preparedness 

needs, CDC categorized pathogens into three classes (A, B, and C) to guide preparedness 

planning. 

6.8.1. Contamination 

Two estimates of human exposure and related health risks have been completed for the 

2001 postal anthrax event (Fennelly et al., 2004; Webb and Blaser, 2002). While neither study 

used a risk assessment framework, both used mathematical models to obtain exposure and risk 

estimates. Webb and Blaser simulated a series of cross-contaminations of mail using a matrix 

model, while Fennelly et al. used the Wells-Rilely model (as in Liao et al., 2005) to estimate 

ambient exposures to anthrax spores and risk of infection. Components of these models included 

both environmental and host factors, such as room air exchange rates, pulmonary ventilation 

rates, age, duration of exposure, etc. 

At the time of this review, contamination models were under development. 

6.8.2. Clean-Up 

EPA’s National Homeland Security Research Center has described an incident-response 

MRA framework (Nichols et al., 2006). The exposure assessment step requires data on the type 

of microorganism, number and locations of release points, time and duration of releases, area of 

contamination, population exposed, population behaviors, exposure scenarios, and other factors. 

The outcomes of this assessment are prediction of the area of contamination, potentially exposed 

population, potential exposure point concentrations, and exposure intakes. Presumably, these 

outcomes would be used to assist in clean-up decision-making. 

At the time of this review, clean-up models were under development. 

6.9. KEY ISSUES RELATED TO ENVIRONMENTAL MEDIA 

Media-specific factors and characteristics are important to pathogen survival, persistence, 

growth, and die-off. The significance of having a comprehensive organizational structure and 

components to characterize the pathogen’s progress from source to host cannot be 

111
 
overemphasized. Each environmental medium or matrix entails different challenges and 

opportunities for pathogens. It is easy to miss crucial factors in such complex conditions without 

the benefit of a conceptual model and systematic framework to guide the assessors’ 

consideration of the many factors and their inter-relationships. These pathways are complex, 

requiring detailed compilations of concepts and data to adequately inform and conduct MRAs. 

Furthermore, translation of the factors and relationships into tractable formulas requires 

additional technical skill and attention to detail. 

Developing broad, flexible categories of MRA elements is an important goal in module 

development. Modules should not be rigid lists of steps or elements to consider in every MRA, 

but rather groupings of characteristics to be considered in specific risk assessments. Like 

frameworks, modules could serve as guides, not cookbooks, for risk assessors. Particularly in 

the context of urgent political and/or public health scenarios, modules can help assure that 

complete and effective MRAs are implemented. 

Modules produce more transparent organization and greater description of the many 

factors that contribute to pathogen-related health risks. Modules could be constructed to assure 

that they align with functional components of the pathogen’s pathway and facilitate the design 

and conduct of mathematical models for essential inputs to the successive module and MRA 

steps. 

112
 
7. RECOMMENDATIONS 

Although similarities exist among many microbial risk assessment frameworks, the 

differences may result in important variations in MRA results. Beginning with effective 

planning and scoping, problem formulation, definitions and a sound conceptual model are 

essential to conducting a meaningful and relevant MRA. Getting the questions right early in the 

process through dialogue with risk managers is a crucial step. Developing a sound and 

comprehensive conceptual model may require several iterations, but it is suggested that 

identifying the fundamental components of the model be done early, so the model will focus on 

risk managers’ needs. 

One way to develop an effective set of risk questions and a conceptual model is to use 

systems thinking or concept-mapping approaches, as described in section 5.1 (e.g., Trochim et 

al., 2006). These methods can help set the boundaries of the MRA problem statement and scope, 

reveal valuable insights about the problem and MRA process, and facilitate more comprehensive 

and precise thinking about MRA issues. 

Furthermore, agencies responsible for specific types of MRAs (e.g., food, water) may be 

able to identify modules that they will commonly need for the MRAs within their authorities. A 

large number of the elements required for each module could be listed and organized in advance, 

and the elements could be further refined when specific applications are defined. These modules 

could be drafted within agencies and vetted among panels of peer reviewers to provide 

organizations with rapidly accessible, off-the-shelf components for MRAs. 

Assessors are encouraged to continue working toward more reader-friendly ways of 

presenting their modeling activities and results. The FDA (2005) MRA includes a number of 

innovations that may be suitable for other MRAs. Improved communication strategies for a wide 

range of stakeholders may yield important partnerships that could enable improvements in MRA 

data sources and approaches. 

Few validations of MRAs have been completed to date. It is often difficult to locate 

enough data to both run the models and to set aside enough data to use for later validation. 

When more data become available to evaluate the models, MRAs can then be revised and 

improved. There are many needs for new research and technologies to improve MRA precision 

and accuracy. Data are needed to more fully populate components of MRA paradigms; such 

research will take time and resources. 

With comprehensive paradigms to help risk assessors identify and consider the many 

potential factors involved in pathogen-related illness, MRAs will become increasingly 

113
 
informative and contribute to more effective public health interventions. Risk assessors are 

encouraged to share the lessons they learn in conducting MRAs and to continue developing 

effective, strategic approaches to MRA models and communications. 

114
 
 

 

 

 

 

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APPENDIX 1. PROCESSED FOOD MODULES 

The purpose of this appendix is to provide more specific information about exposure 

pathways modules for the MRAs summarized in section 6 and Table 8. See additional citations 

in section 6. 

Unripened cheese. 

The modules used to assess contamination in the unripened cheese were for microbial 

levels at the time of retail sale, storage, and consumption. 

Shellfish. 

For shellfish MRAs, exposure assessment modules included 

• Harvest 

• Post-harvest 

• Public health (epidemiology and consumption) 

• Consumption 

Shell eggs. 

Exposure assessments of shell eggs have included modules such as 

• Production 

• Processing, distribution, and storage 

• Preparation and consumption 

Egg products. 

For egg products, the processing step has been modified to consider the additional 

conditions involved in breaking the shell and using the egg to create egg products. 

Beverages. 

In a beverage risk assessment, the modules used were 

• Raw water 

• Water treatment 

• Use of water in production, additional processing, bottling, and capping 

125
 
 

Fish products. 

Modules used for fishery products included 

• Fishery ecology 

• Fish microbial growth factors 

• Lag times and death rates 

• Thermal inactivation (cooking) 

• Non-thermal inactivation 

• Serving 

• Consumption 

The Swedish framework used to guide the implementation of the four-stage model 

involved a series of mathematical models (Figure 1 in Lindqvist and Westöö, 2000). Each model 

generated a quantitative output that became the input for the next model in the series. The 

concentration of L. monocytogenes in a fish and serving size data were combined to obtain the 

total number of microorganisms consumed (exposure). Combined with dose-response data in 

two models (hazard characterization), this outcome was used for the risk characterization step 

(e.g., to estimate the probability of illness per serving and per year at the individual level, 

including among susceptible subpopulations). The number of listeriosis cases per year in the 

country was estimated by considering the amount of contaminated food consumed per year and 

the number of exposures per year in Sweden. Throughout the risk assessment, assumptions were 

clearly noted, and their potential impacts on the final estimates were analyzed and discussed 

along with recommendations for risk reduction strategies. Data gaps were mentioned as well 

(Lindqvist and Westöö, 2000). 

Broiler chickens. 

For broiler chickens, risk assessment modules have included 

• Farm and transport 

• Slaughter and processing 

• Transport and processing 

• Retail distribution and storage 

126
 
 

 

• Preparation 

• Consumption 

The preparation component considered cross-contamination and undercooking in 

domestic food settings. 

Wild game. 

Four types of processed wild game were examined: gamebirds, wild ducks, wild deer, 

and wild lagomorphs (Coburn et al., 2005). The risks due to eight microbial pathogens and lead 

shot were estimated qualitatively. The human exposure pathway (see Figure 1 in Coburn et al., 

2005) was laid out in four major steps: 

• Live wild animal 

• Transport and processing 

• Storage, distribution and retail 

• Preparation and consumption 

At each step health risks associated with handling were considered. The risk of illness 

associated with consumption was evaluated in the final step. 

Pig-meat products. 

Hill et al. (2003) used a framework to guide this assessment, which was a “farm to 

consumption” approach, involving five modules: 

• Farm (prevalence) 

• Transport and holding (prevalence) 

• Slaughter and processing (prevalence and concentration) 

• Distribution and storage (prevalence and concentration) 

• Preparation and consumption (prevalence and concentration) 

• Health effects 

Three sets of pig-meat products were examined: pork, mixed meat products, and bacon. 

Both fresh and chilled products, which were cooked improperly or cross-contaminated other 

foods, were considered. 

127
 
Within each module, a mathematical model of biological processes was implemented to 

characterize their impacts on pathogen prevalence and, in some cases, concentrations. 

Parameters in the farm module were varied to evaluate the impacts of various possible pathogencontrol methods. The output of the preparation and consumption module was the probability of a 

person ingesting the pathogen and the number of organisms consumed. These results became the 

inputs for the human effects (dose-response) module. 

The report presents extensive descriptions of each module, with equations and 

assumptions (Hill et al., 2003). Data gaps are noted for each component, as appropriate to the 

state of the science at the time the module was implemented. Tables and figures showing the 

results for the scenarios are presented and compared to baseline conditions. These presentations 

and the authors’ discussions offer decision-makers valuable information for understanding and 

interpreting the data as they choose among control options. 

Highly processed foods. 

The modules used for more highly processed foods (e.g., turkey products, ready-to-eat 

foods and meals) were 

• Raw food ingredients 

• Live bird contamination 

• Slaughter and processing 

• Food product processing (mincing of meat, reconstituting or mixing raw ingredients) 

• Transport and storage 

• Contamination at the point of retail sale 

• Microbial growth between sale and consumption 

• Storage, preparation, and cooking 

• Consumption 

Variety of routes of exposure. 

In The Netherlands’ risk assessment of campylobacter, various routes of exposure 

(broiler and other meats, contact with pet and farm animals, and consumption of raw and 

undercooked foods) were examined to determine which route/s had the most significant impacts 

on public health (Nauta et al., 2005). The transmission and concentrations of campylobacter in 

the broiler meat part of the MRA were modeled within modules in the “farm to fork” chain to 

obtain “units” of potentially contaminated food or animal items (e.g., on the exterior of a carcass 

or filet). The modules were designed to characterize the impacts of: bacterial processes such as 

128
 
growth and inactivation, food handling processes including partitioning, mixing, crosscontamination, and finally, removal. 

In each module, the dynamic factors and often non-linear processes that affected 

pathogen concentrations were modeled using Monte Carlo methods. Each model produced an 

output that was used as the input for the next model in the pathway. The report acknowledged 

sources of variability and uncertainty and assumptions used to design and implement the model. 

One important limitation was the lack of information for constructing model parameters and 

relationships among them. 

129