Science and Decisions: Advancing Risk Assessment

At the request of the U.S. Environmental Protection Agency (EPA), the National Research Council (NRC) recently completed a major report, Science and Decisions: Advancing Risk Assessment, that is intended to strengthen the scientific basis, credibility, and effectiveness of risk assessment practices and subsequent risk management decisions. The report describes the challenges faced by risk assessment and the need to consider improvements in both the technical analyses of risk assessments (i.e., the development and use of scientific information to improve risk characterization) and the utility of risk assessments (i.e., making assessments more relevant and useful for risk management decisions). The report tackles a number of topics relating to improvements in the process, including the design and framing of risk assessments, uncertainty and variability characterization, selection and use of defaults, unification of cancer and noncancer dose‐response assessment, cumulative risk assessment, and the need to increase EPA's capacity to address these improvements. This article describes and summarizes the NRC report, with an eye toward its implications for risk assessment practices at EPA.     

Foundational Issues in Risk Assessment and Risk Management

This is a perspective article on foundational issues in risk assessment and management. The aim is to discuss the needs, obstacles, and challenges for the establishment of a renewed, strong scientific foundation for risk assessment and risk management suited for the current and future technological challenges. The focus is on (i) reviewing and discussing the present situation and (ii) identifying how to best proceed in the future, to develop the risk discipline in the directions needed. The article provides some reflections on the interpretation and understanding of the concept of “foundations of risk assessment and risk management” and the challenges therein. One main recommendation is that different arenas and moments for discussion are needed to specifically address foundational issues in a way that embraces the many disciplinary communities involved (from social scientists to engineers, from behavioral scientists to statisticians, from health physicists to lawyers, etc.). One such opportunity is sought in the constitution of a novel specialty group of the Society of Risk Analysis.     

Implications of Developmental Toxicity Study Design for Quantitative Risk Assessment

Standard experimental designs for conducting developmental toxicity studies typically include three- or four-dose levels in addition to a control group. Some researchers have suggested that designs with more exposure groups would improve dose-response characterization and risk estimation. Such proposals have not, however, been supported by the results of simulation studies, which instead back the use of fewer dose levels. This discrepancy is partly due to using a known dose–response pattern to generate data, making model choice obvious. While the carcinogenicity literature has explored implications of different study designs, little attention has been given to the role of design in developmental toxicity risk assessment (or noncancer toxicology in general). In this research, we explore the implications of various experimental designs for developmental toxicity by resampling data from a large study of 2,4,5-trichlorophenoxyacetic acid in mice. We compare the properties of benchmark dose (BMD) estimation for different design strategies by randomly selecting animals within particular dose groups from the entire 2,4,5-T database of over 77,000 birth outcomes to create smaller "pseudo-studies" that are representative of standard bioassay sample sizes. Our results show that experimental designs which include more dose levels have advantages in terms of risk characterization and estimation.     

Incorporating Risk Assessment and Benefit-Cost Analysis in Environmental Management1

Using data from interviews with a key set of individuals at the U.S. Environmental Protection Agency, this study examines intraagency views about the incorporation of risk assessment and benefit-cost analysis in environment management.     

Subsea Release of Oil from a Riser: An Ecological Risk Assessment

This study illustrates a newly developed methodology, as a part of the U.S. EPA ecological risk assessment (ERA) framework, to predict exposure concentrations in a marine environment due to underwater release of oil and gas. It combines the hydrodynamics of underwater blowout, weathering algorithms, and multimedia fate and transport to measure the exposure concentration. Naphthalene and methane are used as surrogate compounds for oil and gas, respectively. Uncertainties are accounted for in multimedia input parameters in the analysis. The 95th percentile of the exposure concentration (EC_95%) is taken as the representative exposure concentration for the risk estimation. A bootstrapping method is utilized to characterize EC_95% and associated uncertainty. The toxicity data of 19 species available in the literature are used to calculate the 5th percentile of the predicted no observed effect concentration (PNEC_5%) by employing the bootstrapping method. The risk is characterized by transforming the risk quotient (RQ), which is the ratio of EC_95% to PNEC_5%, into a cumulative risk distribution. This article describes a probabilistic basis for the ERA, which is essential from risk management and decision‐making viewpoints. Two case studies of underwater oil and gas mixture release, and oil release with no gaseous mixture are used to show the systematic implementation of the methodology, elements of ERA, and the probabilistic method in assessing and characterizing the risk.     

Appraisal of Individual Radiation Risk in the Context of Probabilistic Exposures

There exists a growing desire to base safety criteria in different fields on the same principles. The current approach by the international Commission on Radiological Protection (ICRP) to control radiation exposure touches many aspects such as social, psychological, or economic factors that are important for such principles. This paper attempts to further explore possible ways of defining a common basis for dealing with radiation risks and other safety problems. Specifically, it introduces the following issues: (1) different types of risk are judged differently. To account for this, the concept of risk categories is introduced. (2) The dimension of time may play an important role. There is a difference between an immediate death and a death occurring 20 years after exposure to radiation. Effects such as reduced quality of life after exposure and reduction of lifetime expectancy are discussed. The paper suggests to introduce an individual risk equivalent which allows to compare risks as defined in various fields. Furthermore, it suggests the use of risk acceptance criteria which depend on the different categories of risk.     

Issues in Ecological Risk Assessment: The CRAM Perspective

In 1989, a Committee on Risk Assessment Methodology (CRAM) was convened by the National Research Council (NRC) to identify and investigate important scientific issues in risk assessment. One of the first issues considered by the committee was the development of a conceptual framework for ecological risk assessment, defined as "the characterization of the adverse ecological effects of environmental exposures to hazards imposed by human activities." Adverse ecological effects include all biological and nonbiological environmental changes that society perceives as undesirable. The committee's opinion was that a general framework is needed to define the relationship of ecological risk assessment to environmental management and to facilitate the development of uniform technical guidelines. The framework for human health risk assessment proposed by the NRC in 1983 was adopted as a starting point for discussion. CRAM concluded that, although ecological risk assessment and human health risk assessment differ substantially in terms of scientific disciplines and technical problems, the underlying decision process is the same for both. Therefore, CRAM recommended that the 1983 risk assessment framework be modified to accommodate both human health and ecological risk assessment. CRAM defined an integrated health/ ecological risk assessment framework consisting of the four components: Hazard Identification, Exposure Assessment, Exposure-Response Assessment, and Risk Characterization. CRAM further provided recommendations on the scope of issues to be addressed in ecological risk assessment, critical research needs, and mechanisms for providing more detailed guidance on the scientific content of ecological risk assessments.     

Risk Analysis and Risk Management: An Historical Perspective

This paper reviews the history of risk analysis and risk management, giving special emphasis to the neglected period prior to the 20th century. The overall objective of the paper is to: (1) dampen the prevailing tendency to view present-day concerns about risk in an ahistorical context; (2) shed light on the intellectual antecedents of current thinking about risk; (3) clarify how contemporary ideas about risk analysis and societal risk management differ significantly from the past; and (4) provide a basis for anticipating future directions in risk analysis and management.     

Quantitative Risk Assessment for Developmental Neurotoxic Effects

Developmental neurotoxicity concerns the adverse health effects of exogenous agents acting on neurodevelopment. Because human brain development is a delicate process involving many cellular events, the developing fetus is rather susceptible to compounds that can alter the structure and function of the brain. Today, there is clear evidence that early exposure to many neurotoxicants can severely damage the developing nervous system. Although in recent years, there has been much attention given to model development and risk assessment procedures for developmental toxicants, the area of developmental neurotoxicity has been largely ignored. Here, we consider the problem of risk estimation for developmental neurotoxicants from animal bioassay data. Since most responses from developmental neurotoxicity experiments are nonquantal in nature, an adverse health effect will be defined as a response that occurs with very small probability in unexposed animals. Using a two-stage hierarchical normal dose-response model, upper confidence limits on the excess risk due to a given level of added exposure are derived. Equivalently, the model is used to obtain lower confidence limits on dose for a small negligible level of risk. Our method is based on the asymptotic distribution of the likelihood ratio statistic (cf. Crump, 1995). An example is used to provide further illustration.     

Summary of the Workshop on Issues in Risk Assessment: Quantitative Methods for Developmental Toxicology

This report summarizes the proceedings of a conference on quantitative methods for assessing the risks of developmental toxicants. The conference was planned by a subcommittee of the National Research Council's Committee on Risk Assessment Methodology ⁴ in conjunction with staff from several federal agencies, including the U.S. Environmental Protection Agency, U.S. Food and Drug Administration, U.S. Consumer Products Safety Commission, and Health and Welfare Canada. Issues discussed at the workshop included computerized techniques for hazard identification, use of human and animal data for defining risks in a clinical setting, relationships between end points in developmental toxicity testing, reference dose calculations for developmental toxicology, analysis of quantitative dose-response data, mechanisms of developmental toxicity, physiologically based pharmacokinetic models, and structure-activity relationships. Although a formal consensus was not sought, many participants favored the evolution of quantitative techniques for developmental toxicology risk assessment, including the replacement of lowest observed adverse effect levels (LOAELs) and no observed adverse effect levels (NOAELs) with the benchmark dose methodology.     

Integrating Uncertainty and Interindividual Variability in Environmental Risk Assessment

An integrated, quantitative approach to incorporating both uncertainty and interindividual variability into risk prediction models is described. Individual risk R is treated as a variable distributed in both an uncertainty dimension and a variability dimension, whereas population risk I (the number of additional cases caused by R) is purely uncertain. I is shown to follow a compound Poisson-binomial distribution, which in low-level risk contexts can often be approximated well by a corresponding compound Poisson distribution. The proposed analytic framework is illustrated with an application to cancer risk assessment for a California population exposed to 1,2-dibromo-3-chloropropane from ground water.     

Characterizing Environmental Harm: Developments in an Approach to Strategic Risk Assessment and Risk Management

Environmental policymakers and regulators are often in the position of having to prioritize their actions across a diverse range of environmental pressures to secure environmental protection and improvements. Information on environmental issues to inform this type of strategic analysis can be disparate; it may be too voluminous or even absent. Data on a range of issues are rarely presented in a common format that allows easy analysis and comparison. Nevertheless, judgments are required on the significance of various environmental pressures and on the inherent uncertainties to inform strategic assessments such as “state of the environment” reports. How can decisionmakers go about this type of strategic and comparative risk analysis? In an attempt to provide practical tools for the analysis of environmental risks at a strategic level, the Environment Agency of England and Wales has conducted a program of developmental research on strategic risk assessment since 1996. The tools developed under this program use the concept of “environmental harm” as a common metric, viewed from technical, social, and economic perspectives, to analyze impacts from a range of environmental pressures. Critical to an informed debate on the relative importance of these perspectives is an understanding and analysis of the various characteristics of harm (spatial and temporal extent, reversibility, latency, etc.) and of the social response to actual or potential environmental harm from a range of hazards. Recent developments in our approach, described herein, allow a presentation of the analysis in a structured fashion so as to better inform risk‐management decisions.     

Risk Assessment and Risk Governance of Liquefied Natural Gas Development in Gladstone,Australia

This article is a retrospective analysis of liquefied natural gas development (LNG) in Gladstone, Australia by using the structure of the risk governance framework developed by the International Risk Governance Council (IRGC). Since 2010 the port of Gladstone has undergone extensive expansion to facilitate the increasing coal export as well as the new development of three recently completed LNG facilities. Significant environmental and socio‐economic impacts and concerns have occurred as a result of these developments. The overall aim of the article, therefore, is to identify the risk governance deficits that arose and to formulate processes capable of improving similar decision‐making problems in the future. The structure of the IRGC framework is followed because it represents a broad analytical approach for considering risk assessment and risk governance in Gladstone in ways that include, but also go beyond, the risk approach of the ISO 31000:2009 standard that was employed at the time. The IRGC risk framework is argued to be a consistent and comprehensive risk governance framework that integrates scientific, economic, social, and cultural aspects and advocates the notion of inclusive risk governance through stakeholder communication and involvement. Key aspects related to risk preassessment, risk appraisal, risk tolerability and acceptability, risk management, and stakeholder communication and involvement are considered. The results indicate that the risk governance deficits include aspects related to (i) the risk matrix methodology, (ii) reflecting uncertainties, (iii) cumulative risks, (iv) the regulatory process, and (v) stakeholder communication and involvement.     

Uncertainty and Sensitivity Analysis in Assessment of the Thyroid Cancer Risk Related to Chernobyl Fallout in Eastern France

The increase in the thyroid cancer incidence in France observed over the last 20 years has raised public concern about its association with the 1986 nuclear power plant accident at Chernobyl. At the request of French authorities, a first study sought to quantify the possible risk of thyroid cancer associated with the Chernobyl fallout in France. This study suffered from two limitations. The first involved the lack of knowledge of spontaneous thyroid cancer incidence rates (in the absence of exposure), which was especially necessary to take their trends into account for projections over time; the second was the failure to consider the uncertainties. The aim of this article is to enhance the initial thyroid cancer risk assessment for the period 1991-2007 in the area of France most exposed to the fallout (i.e., eastern France) and thereby mitigate these limitations. We consider the changes over time in the incidence of spontaneous thyroid cancer and conduct both uncertainty and sensitivity analyses. The number of spontaneous thyroid cancers was estimated from French cancer registries on the basis of two scenarios: one with a constant incidence, the other using the trend observed. Thyroid doses were estimated from all available data about contamination in France from Chernobyl fallout. Results from a 1995 pooled analysis published by Ron et al. were used to determine the dose-response relation. Depending on the scenario, the number of spontaneous thyroid cancer cases ranges from 894 (90% CI: 869-920) to 1,716 (90% CI: 1,691-1,741). The number of excess thyroid cancer cases predicted ranges from 5 (90% UI: 1-15) to 63 (90% UI: 12-180). All of the assumptions underlying the thyroid cancer risk assessment are discussed.     

Use of Advances in Technology for Maritime Risk Assessment

The maritime industry is moving toward a "goal-setting" risk-based regime. This opens the way to safety engineers to explore and exploit flexible and advanced risk modeling and decision-making approaches in the design and operation processes. In this article, following a brief review of the current status of maritime risk assessment, a design/operation selection framework and a design/operation optimization framework are outlined. A general discussion of control engineering techniques and their application to risk modeling and decision making is given. Four novel risk modeling and decision-making approaches are then outlined with illustrative examples to demonstrate their use. Such approaches may be used as alternatives to facilitate risk modeling and decision making in situations where conventional techniques cannot be appropriately applied. Finally, recommendations on further exploitation of advances in general engineering and technology are suggested with respect to risk modeling and decision making.     

Radiological Risk Assessment by Convergence Methodology Model in RDD Scenarios

A radiological dispersal device (RDD) is a simple weapon capable of causing human harm, environmental contamination, disruption, area denial, and economic cost. It can affect small, large, or long areas depending on atmospheric stability. The risk of developing a radio‐induced cancer depends on exposure, and an effective response depends upon available timely guidance. This article proposes and demonstrates a convergence of three different capabilities to assess risk and support rapid safe resource efficient response. The three capabilities that are integrated are Hotspot for dispersion, RERF for epidemiological risk, and RESRAD‐RDD for response guidance. The combined methodology supports decisions on risk reduction and resource allocation through work schedules, the designation and composition of response teams, and siting for operations. In the illustrative RDD scenario, the contamination area for sheltering, evacuation, and long‐term public concern was greatest for calm atmospheric conditions, whilst close‐quarter responders faced highest dose rates for neutral atmospheric conditions. Generally, the risks to women responders were found to be significantly greater than for men, and the risks to 20‐year‐old responders were three times that of their 60‐year‐old counterparts for similar exposure.     

Predicting Future Excess Events in Risk Assessment

Risk characterization in a study population relies on cases of disease or death that are causally related to the exposure under study. The number of such cases, so-called "excess" cases, is not just an indicator of the impact of the risk factor in the study population, but also an important determinant of statistical power for assessing aspects of risk such as age-time trends and susceptible subgroups. In determining how large a population to study and/or how long to follow a study population to accumulate sufficient excess cases, it is necessary to predict future risk. In this study, focusing on models involving excess risk with possible effect modification, we describe a method for predicting the expected magnitude of numbers of excess cases and assess the uncertainty in those predictions. We do this by extending Bayesian APC models for rate projection to include exposure-related excess risk with possible effect modification by, e.g., age at exposure and attained age. The method is illustrated using the follow-up study of Japanese Atomic-Bomb Survivors, one of the primary bases for determining long-term health effects of radiation exposure and assessment of risk for radiation protection purposes. Using models selected by a predictive-performance measure obtained on test data reserved for cross-validation, we project excess counts due to radiation exposure and lifetime risk measures (risk of exposure-induced deaths (REID) and loss of life expectancy (LLE)) associated with cancer and noncancer disease deaths in the A-Bomb survivor cohort.     

Incorporation of Pharmacokinetics in Noncancer Risk Assessment: Example with Chloropentafluorobenzene

Noncancer risk assessment traditionally relies on applied dose measures, such as concentration in inhaled air or in drinking water, to characterize no-effect levels or low-effect levels in animal experiments. Safety factors are then incorporated to address the uncertainties associated with extrapolating across species, dose levels, and routes of exposure, as well as to account for the potential impact of variability of human response. A risk assessment for chloropentafluorobenzene (CPFB) was performed in which a physiologically based pharmacokinetic model was employed to calculate an internal measure of effective tissue dose appropriate to each toxic endpoint. The model accurately describes the kinetics of CPFB in both rodents and primates. The model calculations of internal dose at the no-effect and low-effect levels in animals were compared with those calculated for potential human exposure scenarios. These calculations were then used in place of default interspecies and route-to-route safety factors to determine safe human exposure conditions. Estimates of the impact of model parameter uncertainty, as estimated by a Monte Carlo technique, also were incorporated into the assessment. The approach used for CPFB is recommended as a general methodology for noncancer risk assessment whenever the necessary pharmacokinetic data can be obtained.