Framework for Human Health Risk Assessment

The views expressed in this paper are those of the authors and do not necessarily reflect the views or policies of the USEPA. The U.S. Government has the right to retain a nonexclusive royalty-free license in and to any copyright covering this article. The U.S. Environmental Protection Agency has recognized the need to develop a framework for human health risk assessment that puts a perspective on the approaches in practice throughout the Agency. In response, the USEPA's Risk Assessment Forum has begun the process of developing a framework for human health risk assessment. This paper provides some additional background to the previous review of the framework efforts and notes the Agency's extramural efforts to begin the process of integrating and harmonizing risk assessment approaches for all human health endpoints.     

Framework for the Integration of Health and Ecological Risk Assessment

The World Health Organization's International Programme on Chemical Safety (IPCS), the Organization for Economic Cooperation and Development (OECD), and the U.S. Environmental Protection Agency have developed a collaborative partnership to foster integration of assessment approaches for human health and ecological risks. This paper presents the framework developed by that group. Integration provides coherent expressions of assessment results, incorporates the interdependence of humans and the environment, uses sentinel organisms, and improves the efficiency and quality of assessments relative to independent human health and ecological risk assessments. The paper describes how integration can occur within each component of risk assessment, and communicates the benefits of integration at each point. The goal of this effort is to promote the use of this internationally accepted guidance as a basis for harmonization of risk assessment.     

生态风险评价研究进展

20多年来,生态风险评价研究经历了从环境风险到生态风险到区域生态风险评价的发展历程,风险源由单一风险源扩展到多风险源,风险受体由单一受体发展到多受体,评价范围由局地扩展到区域景观水平.区域生态风险评价就是大尺度上研究复杂环境背景下包含多风险源、多风险受体的综合风险研究.目前,区域生态风险评价的理论框架已经搭建起来,统计方法多采用相对评价法.区域生态风险评价未来的发展方向为继续加强实验和野外调查,进一步减小不确定性,逐步解决尺度推移问题.区域生态风险评价必须与经济、社会、文化相结合,才能充分发挥它在管理决策中的作用.     

Approaches for Integrated Risk Assessment

Recognizing the need to enhance the effectiveness and efficiency of risk assessments globally, the World Health Organization's International Programme on Chemical Safety, the U.S. Environmental Protection Agency, the European Commission, and the Organization for Economic Cooperation and Development developed a collaborative partnership to foster integration of assessment approaches used to evaluate human health and ecological risks. The objectives of this effort included: improving understanding of the benefits of integration, identifying obstacles to the integration process, and engaging key agencies, organizations, and scientific societies to promote integration. A framework with supporting documentation was developed to describe an approach for integration. Four case studies were constructed to illustrate how integrated risk assessments might be conducted for chemical and nonchemical stressors. The concepts and approaches developed in the project were evaluated in an international workshop. The goal of this effort was international acceptance of guidance for integrated risk assessment.     

The Chesapeake Bay Program: An Example of Ecological Risk Assessment

Ecological risk assessment grew from earlier efforts of federalagencies to protect human health from chemical releases. Overthe past several years, the U.S. Environmental Protection Agency(U.S. EPA) adapted the human health paradigm for use in protectingecological end-points, including ecosystems such as the ChesapeakeBay. The Bay restoration effort may be seen as an ecologicalrisk assessment in the sense that the program participants followedthe paradigm developed by U.S. EPA. This analysis of the programand risk assessment process provides an additional perspectiveon the success and efficacy of the Bay restoration efforts.Early efforts to determine the problems in the Bay system targetedhypoxia, habitat deterioration and natural resource degradationfor corrective actions. Additional monitoring and data gatheringrefined and focused program efforts on hypoxia caused by nutrientenrichment. Thus far, the ecological risk paradigm has beeneffectively applied to the Bay clean-up in a general sense.Recent research demonstrates that detailed application of anarrow risk approach will likely fail to include important biologicaleffects or processes     

Current Perspectives on Issues in Risk Assessment Methods

The Office of Research and Development (ORD) of the U.S. Environmental Protection Agency was reorganized in 1995 to follow the risk assessment paradigm developed by the National Research Council. With the reorganization, a number of different research strategies and plans were developed on problem-driven topics (e.g., arsenic, particulate matter, and microbial pathogens/disinfectant byproducts) as well as on core research (e.g., ecological research, human health risk assessment research, and pollution prevention research). The human health risk assessments research strategy, which is currently under development, addresses a variety of issues which affect all human health risk assessments. These include mechanism of action, variation in response, aggregate risk, and effect on public health. While all of the issues that have been identified are important, the challenge to ORD is to identify which will have the greatest impact on improving risk assessment so that resources can be most strategically applied.     

Genomics: Applications,Challenges, and Opportunities for the U.S. Environmental Protection Agency

Genomics information has great potential to enhance assessment of risks to human health and the environment. Although understanding genomic responses with respect to adverse ecological and human health outcomes is not, as yet, established, it is important to consider the likely future impacts of genomics technologies on risk assessment and decision-making. Four areas are identified as those likely to be influenced by the generation of genomics information within, and the submission of such information to, the U.S. Environmental Protection Agency (USEPA): risk assessment, prioritization of contaminants and contaminated sites, monitoring, and reporting provisions. For each of these risk assessment and regulatory applications, representative activities are presented to illustrate the application. Three major challenges for the USEPA associated with genomics are also identified in the areas of research, technical development, and capacity. The USEPA's initial activities to address these challenges are discussed. The Agency recognizes it must be prepared to use genomics information, and that many scientific, policy, ethical, and legal concerns will need to be addressed. The USEPA also recognizes it is essential to continue to collaborate with other federal agencies, academia, the regulated community, and other stakeholders in order to benefit from ongoing advances in genomics in the wider scientific and regulatory communities.     

美国、加拿大环境和健康风险管理方法

对目前美国和加拿大多个部门使用的风险评价与风险管理方法进行了全面回顾和综合分析,论述各种不同方法的特征,深入探讨各种管理方法的基础、利弊、使用经验,辨识环境、人类健康和职业健康风险综合方法中应该包含的要素,阐述风险管理目标的确定方法,以期为中国的环境风险管理提供经验。     

Integrated Human and Ecological Risk Assessment: A Case Study of Organophosphorous Pesticides in the Environment

This study was chosen as an example of integrated risk assessment because organophosphorous esters (OPs) share exposure characteristics for different species, including human beings and because a common mechanism of action can be identified. The “Framework for the integration of health and ecological risk assessment” is being tested against a deterministic integrated environmental health risk assessment for OPs used in a typical farming community. It is argued that the integrated approach helps both the risk manager and the risk assessor in formulating a more holistic approach toward the risk of the use of OP-esters. It avoids conclusions based on incomplete assessments or on separate assessments. The database available can be expanded and results can be expressed in a more coherent manner. In the integrated exposure assessment of OPs, the risk assessments for human beings and the environment share many communalities with regards to sources and emissions, distribution routes and exposure scenarios. The site of action of OPs, acetylcholinesterase, has been established in a vast array of species, including humans. It follows that in the integrated approach the effects assessment for various species will show communalities in reported effects and standard setting approaches. In the risk characterization, a common set of evidence, common criteria, and common interpretations of those criteria are used to determine the cause of human and ecological effects that co-occur or are apparently associated with exposure to OPs. Results of health and ecological risk assessments are presented in a common format that facilitates comparison of results. It avoids acceptable risk conclusions with regard to the environment, which are unacceptable with regard to human risk and vice versa. Risk managers will be prompted to a more balanced judgement and understanding and acceptance of risk reduction measures will be facilitated.     

Children's health risk assessment: incorporating a lifestage approach into the risk assessment process

This overview paper provides the historical context for the incorporation of lifestage‐specific concerns in human health risk assessment, briefly explains the process employed in a lifestage framework for risk assessment, and discusses the scientific rationale for how utilizing lifestage data will strengthen the overall risk assessment process. This risk assessment approach will add value by: (1) providing a more complete evaluation of the potential for vulnerability at different lifestages, including a focus on the underlying biological events and incorporation of mode of action information related to different critical developmental periods; (2) evaluating the potential for toxicity during all lifestages after early lifestage exposure; (3) reviewing the importance of integrating exposure information and adverse health effects across lifestages; and (4) serving as a basis to extend some aspects of the children's health risk assessment framework to all lifestages. Birth Defects Res (Part B), 2008. © 2008 Wiley‐Liss, Inc.     

Pharmaceuticals in the environment: scientific evidence of risks and its regulation

During the past two decades scientists, regulatory agencies and the European Commission have acknowledged pharmaceuticals to be an emerging environmental problem. In parallel, a regulatory framework for environmental risk assessment (ERA) of pharmaceutical products has been developed. Since the regulatory guidelines came into force the German Federal Agency (UBA) has been evaluating ERAs for human and veterinary pharmaceutical products before they are marketed. The results show that approximately 10% of pharmaceutical products are of note regarding their potential environmental risk. For human medicinal products, hormones, antibiotics, analgesics, antidepressants and antineoplastics indicated an environmental risk. For veterinary products, hormones, antibiotics and parasiticides were most often discussed as being environmentally relevant. These results are in good correlation with the results within the open scientific literature of prioritization approaches for pharmaceuticals in the environment. UBA results revealed that prospective approaches, such as ERA of pharmaceuticals, play an important role in minimizing problems caused by pharmaceuticals in the environment. However, the regulatory ERA framework could be improved by (i) inclusion of the environment in the risk–benefit analysis for human pharmaceuticals, (ii) improvement of risk management options, (iii) generation of data on existing pharmaceuticals, and (iv) improving the availability of ERA data. In addition, more general and integrative steps of regulation, legislation and research have been developed and are presented in this article. In order to minimize the quantity of pharmaceuticals in the environment these should aim to (i) improve the existing legislation for pharmaceuticals, (ii) prioritize pharmaceuticals in the environment and (iii) improve the availability and collection of pharmaceutical data.     

基于近海健康评价现有体系的我国普适海洋健康评价“双核”新框架的构建

海洋生态环境保持健康状态是人类可持续开发利用海洋资源环境的基础,而近海海洋生态环境的健康状况综合评价可为海洋生态环境良性发展以及社会经济决策提供科学依据。首先对国际上3种代表性的海洋环境健康综合评价方法的应用特点进行了对比分析,并归纳了我国海洋生态环境健康评价的状况,在此基础上,以指标体系法重构了一个双核结构的综合评价框架,其中内核评价以海洋生态系统的自身状态为主,外核评价则主要反映海洋之于人类经济社会的贡献,以期能够科学、准确、全面的评价我国近海海洋环境健康状况。     

Reduction,refinement and replacement: putting the immune system to work

Many chemicals are known to be, or have been implicated as, contact allergens, and allergic contact dermatitis is an important occupational and environmental health issue. It is the responsibility of toxicologists to identify those chemicals that have the potential to induce skin sensitisation, and to assess the conditions under which there will exist a risk to human health. This article describes progress that has been made in the development of new approaches to the toxicological evaluation of skin sensitisation, and the benefits to animal welfare that such developments have already produced, and are likely to produce in the future. In this context, the local lymph node assay is described with regard to hazard identification and risk assessment, and possible strategies for the development of in vitro approaches to safety assessment are discussed.     

The effect of essentiality on risk assessment

Metals are ubiquitous in the human environment, making exposure inevitable and requiring scientifically sound risk assessment methodology to ensure adequate health protection. Within this area, as part of its ongoing efforts to improve and harmonize internationally approaches to risk assessments, the International Program on Chemical Safety (IPCS) has initiated work to improve the risk assessment procedures for essential trace elements (ETEs). Zn, Cu, Se, Cr, and MO are ETEs for humans, with increasing evidence of an essential role for boron (B). For ETEs, there is a range of daily intake within which the organism maintains homeostasis. At intakes below this range, there is an increased risk from deficiency, and at intakes above the range toxicity may develop. Obviously, for ETEs one cannot assume zero exposure is without risk. Adequate health protection will require the cooperative effort of scientists in nutrition and toxicology to develop the limits of the accepted range for ETEs considering such unique properties of metals as bioavailability, speciation, interactions, and biokinetics. Based on previous work by other groups and the recommendations of an IPCS consultation, a scientific monograph will be completed by IPCS. It will examine present risk assessment methodology for ETEs, and develop scientific principles supporting use of a homeostatic model for the development of dietary reference values and tolerable daily intakes. The objective is to develop an internationally accepted methodology for assessing ETEs as part of the IPCS effort to harmonize approaches to risk assessment worldwide. A recent IPCS Task Group on Zn highlighted some of the scientific issues that require resolution to avoid an overlap of the recommended daily intake based on nutritional needs with that based on toxicity and will serve as a case study.     

A Risk Assessment Framework for Waterborne Pathogens and Requirements for Producing a Complete Protocol

The U.S. Environmental Protection Agency (USEPA), Office of Water, is developing a risk assessment protocol for determining microbiological pathogen risks in water (drinking, recreational, waste waters, etc.). This effort has been conducted in collaboration with the International Life Sciences Institute. A microbiological risk assessment framework was prepared and has been peer reviewed in the open literature and vetted at the USEPA and other federal government risk assessment venues. Some goals in development of the Framework were to make it comprehensive, easy to understand and to use, since it is recognized that improvements to the framework structure and instructional material would facilitate its use. The USEPA's Office of Water wishes to develop improved tools, methods, and approaches for conducting the analysis phase for risk assessments and would like to evaluate its efficacy for a broad range of waterborne pathogens in water/wastewater media. Improved understanding of microbiological survival, infectivity, and virulence factors is needed, especially at the genomic and proteomic levels to accurately assess the occurrence and fate of pathogens in water and to predict what intrinsic factors allow pathogens to be invasive and virulent. Development of improved dose-response models (including animal models) for pathogen exposures focusing on the dynamic circumstances of immunity, secondary spread, and sensitive subpopulations, would be useful additions to the Framework. In the future, USEPA may consider establishing comprehensive pathogen risk assessment guidelines that all its program offices can use.     

Use of the reference dose in risk characterization of drinking water contaminants

Regulatory decisions should be made in the most expert and informed way since they are precipitated by real and perceived threats to public health, under the glare of public scrutiny. The development of environmental regulations require a three‐step paradigm, collectively called risk analysis. This paper will address the risk assessment practices required under the Safe Drinking Water Act (SDWA) Amendments of 1986 to determine a Maximum Contaminant Level Goal (MCLG, nonenforceable health goal) which should result in no known or anticipated health effects, and allows adequate margin of safety. The end product of this risk assessment, risk characterization, and risk management encompassing control options and nonrisk analysis are combined to derive the Maximum Contaminant Level (MCL, enforceable standard). Furthermore, this paper discusses the U.S. Environmental Protection Agency's efforts in exploring new and improved noncancer risk assessment approaches providing the basis for MCLGs for the protection of human health.     

An Integrated Framework for Risk Management and Population Health

The traditional medical model of health and health policy development has focused on individuals and the role of medical care in preventing and treating disease and injury. Recent attention to health inequities and social determinants of health has raised the profile of population heath and evidence-based strategies for improving the health of whole populations. At the same time, risk science has emerged as an important new discipline for the assessment and management of risks to health. This article reviews historical developments in the fields of risk management and population health and proposes a joint population health risk management framework that integrates the key elements of both fields. Applying this integrated approach to managing population health risks will facilitate the development of evidence-based health policy. It will encourage a more systematic and comprehensive evaluation of population health issues and promote the use of a broader suite of interventions to reduce health risks and enhance population health status.     

Initial Risk-Based Screening of Potential Brownfield Development Sites

Brownfield redevelopment is sustainable only when it is a transparent process protective of public health. The objective of the brownfield health risk screening matrix is to provide a scientifically based, transparent process to evaluate human health risks on proposed redevelopment sites as well as a framework that can be critically evaluated by both environmentalists and the community in general. Public discussion and understanding of current health risk assessment, as well as the risks specific to each brownfield redevelopment site, are essential for an effective brownfield redevelopment program.

The Brownfields Redevelopment Program was started by the EPA in 1995 and seeks to use already contaminated sites rather than contaminate even more greenfields. Two of the biggest difficulties are making redevelopment profitable and protecting human health. Traditional human health risk assessment evaluates single chemical exposures and identifies the level below which no adverse effect will occur to the most sensitive subgroups of the population. For cancer–causing chemicals the risk must be lower than 1:1,000,000. When brownfield redevelopment sites are associated with high cost, extensive time and unmanageable uncertainty, additional greenfield sites will become contaminated and the contamination on current brownfield sites will remain un-remediated.

The citizens' advisory group addressing brownfields in a southern New York county has developed a risk matrix to evaluate the uncertainty of the available data, the toxicity of the known or suspected contaminants and the likely exposure routes for each brownfield site in the county. The matrix categorizes sites as high, medium or low risk according to exposure groups. The risk matrix complements the triad approach currently being developed by EPA to identify and manage project decision uncertainties, addresses uncertainty as well as toxicity and has the potential to reduce the cost of traditional health risk assessment at brownfield redevelopment sites.     

Evaluating Human and Ecological Impacts of a Product Life Cycle: The Complementary Roles of Life-Cycle Assessment and Risk Assessment

Life-cycle assessment (LCA) is a tool for evaluating various health and environmental impacts throughout a product's life. When used as a screening tool, LCA can potentially identify the processes and materials most likely to pose a threat to human health and the environment, and to determine where a risk assessment is warranted. The European Union has issued a ban on lead-based solder from use in electronic equipment beginning in July 2006. In response, the Lead-Free Solder Partnership, involving the U.S. Environmental Protection Agency, several electronics manufacturers, and the University of Tennessee afforded a vehicle for conducting a thorough LCA of leaded and lead-free solders used in the electronics industry. Sixteen impact categories were evaluated in the LCA, including human toxicity.

A primary conclusion of the assessment for human and aquatic toxicity, across the entire life cycle of tin-lead solder, was the potential for impacts derived from the landfilling of lead. These results, based on broad assumptions about exposure, suggest that a more detailed risk assessment of the landfilling process would assist in better understanding the potential for health and environmental risks. We believe LCA data can be used to identify the need for focused risk assessments, allowing the two tools to effectively complement one another. Use of both methods could assist in understanding the effectiveness of the European ban on lead solder and its potential to improve public health.     

Risk Assessment: Replacing Default Options with Specific Science

The history of approaches to evaluating the hazards and risks of chemicals is briefly reviewed. The role of default options (generic approaches based on general knowledge in the absence of specific knowledge to the contrary) is discussed as a part of the risk assessment paradigm advanced by the National Academy of Science/National Research Council in 1983 and 1994. Examples are given of the impact of acquiring specific science to replace default options. An argument is made for developing specific science that would reduce uncertainty in risk assessments. Research on specific science would be guided by identified sources of uncertainty in the risk assessment process. The importance of using a research strategy that builds on human data is emphasized for validating new molecular and cellular biological assessment methods. The paper closes with a discussion of the tension between a hazard-based approach versus quantitative risk assessment in guiding risk management decisions. The former requires limited data, is qualitative, and easy to communicate, while the latter requires substantial data and is difficult to communicate. However, quantitative risk assessment provides a more rational basis for decisions on the allocation of both public and private resources for actions that will effectively minimize overall health risks to the public.