VCCEP Pilot: Progress on Evaluating Children''s Risks and Data Needs

The Voluntary Children's Chemical Evaluation Program (VCCEP) is designed to provide information to the public on children's potential health risks associated with chemical exposures. The key question of the VCCEP is whether the potential hazards, exposures, and risks to children have been adequately characterized, and, if not, what additional data are necessary. To answer this question, manufacturers or importers of 23 chemicals were asked by the U. S. Environmental Protection Agency (U.S. EPA) to sponsor their chemicals in the first tier of a pilot program. These chemicals were selected for evaluation because they have been found as contaminants in human tissue or fluids (adipose tissue, blood, breath, breast milk, or urine); food and water children may eat and drink; or air children may breathe (including residential or school air). Under the VCCEP framework, sponsoring companies agree to prepare Tier 1 hazard, exposure, and risk assessments on the individual chemicals, and identify the need for additional data. These assessment documents are submitted to the U.S. EPA and subsequently undergo review by experts in an independent peer consultation meeting that is open to the public. Following this peer consultation process, the U.S. EPA reviews each submission and makes a data-needs determination, which may include requesting further data collection or generation by the sponsor. Sponsoring companies then decide whether to volunteer for the next tier and collect or generate the requested data. The purpose of this article is to describe the VCCEP process and to review and present the key findings from the first set of chemicals that have been fully or partially evaluated under the pilot program (vinylidene chloride, decabromodiphenyl ether, pentabromodiphenyl ether, octabromodiphenyl ether, acetone, methyl ethyl ketone, decane, undecane, and dodecane). Specifically, we provide a brief summary of the sponsors' submissions, the peer consultation panels' discussions, and the U.S. EPA's data-needs decisions. Although we do not attempt to conduct independent analyses of the underlying data, we do identify a number of common themes that have emerged during implementation of the pilot program and discuss several key issues that could become important in the future. The information presented here should be useful for various parties interested in the progress of the VCCEP and the results of the initial (Tier 1) children's assessments.     

Tiered Chemical Testing: A Value of Information Approach

In December 2000 the EPA initiated the Voluntary Children's Chemical Evaluation Program (VCCEP) by asking manufacturers to voluntarily sponsor toxicological testing in a tiered process for 23 chemicals selected for the pilot phase. The tiered nature of the VCCEP pilot program creates the need for clearly defined criteria for determining when information is sufficient to assess the potential risks to children. This raises questions about how to determine the "adequacy" of the existing information and assess the need to undertake efforts to reduce uncertainty (through further testing). This article applies a value of information analysis approach to determine adequacy by modeling how toxicological and exposure data collected through the VCCEP may be used to inform risk management decisions. The analysis demonstrates the importance of information about the exposure level and control costs in making decisions regarding further toxicological testing. This article accounts for the cost of delaying control action and identifies the optimal testing strategy for a constrained decisionmaker who, absent applicable human data, cannot regulate without bioassay data on a specific chemical. It also quantifies the differences in optimal testing strategy for three decision criteria: maximizing societal net benefits, ensuring maximum exposure control while net benefits are positive (i.e., benefits outweigh costs), and controlling to the maximum extent technologically feasible while the lifetime risk of cancer exceeds a specific level of risk. Finally, this article shows the large differences that exist in net benefits between the three criteria for the range of exposure levels where the optimal actions differ.     

A Conceptual Framework to Assess the Risks of Human Disease Following Exposure to Pathogens

Currently, risk assessments of the potential human health effects associated with exposure to pathogens are utilizing the conceptual framework that was developed to assess risks associated with chemical exposures. However, the applicability of the chemical framework is problematic due to many issues that are unique to assessing risks associated with pathogens. These include, but are not limited to, an assessment of pathogen/host interactions, consideration of secondary spread, consideration of short- and long-term immunity, and an assessment of conditions that allow the microorganism to propagate. To address this concern, a working group was convened to develop a conceptual framework to assess the risks of human disease associated with exposure to pathogenic microorganisms. The framework that was developed consists of three phases: problem formulation, analysis (which includes characterization of exposure and human health effects), and risk characterization. The framework emphasizes the dynamic and iterative nature of the risk assessment process, and allows wide latitude for planning and conducting risk assessments in diverse situations, each based on the common principles discussed in the framework.     

The Benefits of Probabilistic Exposure Assessment: Three Case Studies Involving Contaminated Air,Water, and Soil1

Probabilistic risk assessments are enjoying increasing popularity as a tool to characterize the health hazards associated with exposure to chemicals in the environment. Because probabilistic analyses provide much more information to the risk manager than standard “point” risk estimates, this approach has generally been heralded as one which could significantly improve the conduct of health risk assessments. The primary obstacles to replacing point estimates with probabilistic techniques include a general lack of familiarity with the approach and a lack of regulatory policy and guidance. This paper discusses some of the advantages and disadvantages of the point estimate vs. probabilistic approach. Three case studies are presented which contrast and compare the results of each. The first addresses the risks associated with household exposure to volatile chemicals in tapwater. The second evaluates airborne dioxin emissions which can enter the food-chain. The third illustrates how to derive health-based cleanup levels for dioxin in soil. It is shown that, based on the results of Monte Carlo analyses of probability density functions (PDFs), the point estimate approach required by most regulatory agencies will nearly always overpredict the risk for the 95^th percentile person by a factor of up to 5. When the assessment requires consideration of 10 or more exposure variables, the point estimate approach will often predict risks representative of the 99.9^th percentile person rather than the 50^th or 95^th percentile person. This paper recommends a number of data distributions for various exposure variables that we believe are now sufficiently well understood to be used with confidence in most exposure assessments. A list of exposure variables that may require additional research before adequate data distributions can be developed are also discussed.     

Assessments of Direct Human Exposure—The Approach of EU Risk Assessments Compared to Scenario-Based Risk Assessment

The awareness of potential risks emerging from the use of chemicals in all parts of daily life has increased the need for risk assessments that are able to cover a high number of exposure situations and thereby ensure the safety of workers and consumers. In the European Union (EU), the practice of risk assessments for chemicals is laid down in a Technical Guidance Document; it is designed to consider environmental and human occupational and residential exposure. Almost 70 EU risk assessment reports (RARs) have been finalized for high-production-volume chemicals during the last decade. In the present study, we analyze the assessment of occupational and consumer exposure to trichloroethylene and phthalates presented in six EU RARs. Exposure scenarios in these six RARs were compared to scenarios used in applications of the scenario-based risk assessment approach to the same set of chemicals. We find that scenarios used in the selected EU RARs to represent typical exposure situations in occupational or private use of chemicals and products do not necessarily represent worst-case conditions. This can be due to the use of outdated information on technical equipment and conditions in workplaces or omission of pathways that can cause consumer exposure. Considering the need for exposure and risk assessments under the new chemicals legislation of the EU, we suggest that a transparent process of collecting data on exposure situations and of generating representative exposure scenarios is implemented to improve the accuracy of risk assessments. Also, the data sets used to assess human exposure should be harmonized, summarized in a transparent fashion, and made accessible for all risk assessors and the public.     

Risk Assessment and Alternatives Assessment: Comparing Two Methodologies

The selection and use of chemicals and materials with less hazardous profiles reflects a paradigm shift from reliance on risk minimization through exposure controls to hazard avoidance. This article introduces risk assessment and alternatives assessment frameworks in order to clarify a misconception that alternatives assessment is a less effective tool to guide decision making, discusses factors promoting the use of each framework, and also identifies how and when application of each framework is most effective. As part of an assessor's decision process to select one framework over the other, it is critical to recognize that each framework is intended to perform different functions. Although the two frameworks share a number of similarities (such as identifying hazards and assessing exposure), an alternatives assessment provides a more realistic framework with which to select environmentally preferable chemicals because of its primary reliance on assessing hazards and secondary reliance on exposure assessment. Relevant to other life cycle impacts, the hazard of a chemical is inherent, and although it may be possible to minimize exposure (and subsequently reduce risk), it is challenging to assess such exposures through a chemical's life cycle. Through increased use of alternatives assessments at the initial stage of material or product design, there will be less reliance on post facto risk‐based assessment techniques because the potential for harm is significantly reduced, if not avoided, negating the need for assessing risk in the first place.     

A Tiered Approach for Risk‐Benefit Assessment of Foods

Risk‐benefit analyses are introduced as a new paradigm for old problems. However, in many cases it is not always necessary to perform a full comprehensive and expensive quantitative risk‐benefit assessment to solve the problem, nor is it always possible, given the lack of required date. The choice to continue from a more qualitative to a full quantitative risk‐benefit assessment can be made using a tiered approach. In this article, this tiered approach for risk‐benefit assessment will be addressed using a decision tree. The tiered approach described uses the same four steps as the risk assessment paradigm: hazard and benefit identification, hazard and benefit characterization, exposure assessment, and risk‐benefit characterization, albeit in a different order. For the purpose of this approach, the exposure assessment has been moved upward and the dose‐response modeling (part of hazard and benefit characterization) is moved to a later stage. The decision tree includes several stop moments, depending on the situation where the gathered information is sufficient to answer the initial risk‐benefit question. The approach has been tested for two food ingredients. The decision tree presented in this article is useful to assist on a case‐by‐case basis a risk‐benefit assessor and policymaker in making informed choices when to stop or continue with a risk‐benefit assessment.     

Aligning Chemical Assessment Tools Across the Hazard-Risk Continuum

With the growing number and diversity of hazard and risk assessment algorithms, models, databases, and frameworks for chemicals and their applications, risk assessors and managers are challenged to select the appropriate tool for a given need or decision. Some decisions require relatively simple tools to evaluate chemical hazards (e.g., toxicity), such as labeling for safe occupational handling and transport of chemicals. Others require assessment tools that provide relative comparisons among chemical properties, such as selecting the optimum chemical for a particular use among a group of candidates. Still other needs warrant full risk characterization, coupling both hazard and exposure considerations. Examples of these include new chemical evaluations for commercialization, evaluations of existing chemicals for novel uses, and assessments of the adequacy of risk management provisions. Even well-validated tools can be inappropriately applied, with consequences as severe as misguided chemical management, compromised credibility of the tool and its developers and users, and squandered resources. This article describes seven discrete categories of tools based on their information content, function, and the type of outputs produced. It proposes a systematic framework to assist users in selecting hazard and risk assessment tools for given applications. This analysis illustrates the importance of careful selection of assessment tools to achieve responsible chemical assessment communication and sound risk management.     

Peak Exposures in Epidemiologic Studies and Cancer Risks: Considerations for Regulatory Risk Assessment

We review approaches for characterizing “peak” exposures in epidemiologic studies and methods for incorporating peak exposure metrics in dose–response assessments that contribute to risk assessment. The focus was on potential etiologic relations between environmental chemical exposures and cancer risks. We searched the epidemiologic literature on environmental chemicals classified as carcinogens in which cancer risks were described in relation to “peak” exposures. These articles were evaluated to identify some of the challenges associated with defining and describing cancer risks in relation to peak exposures. We found that definitions of peak exposure varied considerably across studies. Of nine chemical agents included in our review of peak exposure, six had epidemiologic data used by the U.S. Environmental Protection Agency (US EPA) in dose–response assessments to derive inhalation unit risk values. These were benzene, formaldehyde, styrene, trichloroethylene, acrylonitrile, and ethylene oxide. All derived unit risks relied on cumulative exposure for dose–response estimation and none, to our knowledge, considered peak exposure metrics. This is not surprising, given the historical linear no‐threshold default model (generally based on cumulative exposure) used in regulatory risk assessments. With newly proposed US EPA rule language, fuller consideration of alternative exposure and dose–response metrics will be supported. “Peak” exposure has not been consistently defined and rarely has been evaluated in epidemiologic studies of cancer risks. We recommend developing uniform definitions of “peak” exposure to facilitate fuller evaluation of dose response for environmental chemicals and cancer risks, especially where mechanistic understanding indicates that the dose response is unlikely linear and that short‐term high‐intensity exposures increase risk.     

The Architecture of Chemical Alternatives Assessment

Chemical alternatives assessment is a method rapidly developing for use by businesses, governments, and nongovernment organizations seeking to substitute chemicals of concern in production processes and products. Chemical alternatives assessment is defined as a process for identifying, comparing, and selecting safer alternatives to chemicals of concern (including those in materials, processes, or technologies) on the basis of their hazards, performance, and economic viability. The process is intended to provide guidance for assuring that chemicals of concern are replaced with safer alternatives that are not likely to be later regretted. Conceptually, the assessment methods are developed from a set of three foundational pillars and five common principles. Based on a number of emerging alternatives assessment initiatives, in this commentary, we outline a chemical alternatives assessment blueprint structured around three broad steps: Scope, Assessment, and Selection and Implementation. Specific tasks and tools are identified for each of these three steps. While it is recognized that on‐going practice will further refine and develop the method and tools, it is important that the structure of the assessment process remain flexible, adaptive, and focused on the substitution of chemicals of concern with safer alternatives.     

Tiered Approach to Resilience Assessment

Regulatory agencies have long adopted a three‐tier framework for risk assessment. We build on this structure to propose a tiered approach for resilience assessment that can be integrated into the existing regulatory processes. Comprehensive approaches to assessing resilience at appropriate and operational scales, reconciling analytical complexity as needed with stakeholder needs and resources available, and ultimately creating actionable recommendations to enhance resilience are still lacking. Our proposed framework consists of tiers by which analysts can select resilience assessment and decision support tools to inform associated management actions relative to the scope and urgency of the risk and the capacity of resource managers to improve system resilience. The resilience management framework proposed is not intended to supplant either risk management or the many existing efforts of resilience quantification method development, but instead provide a guide to selecting tools that are appropriate for the given analytic need. The goal of this tiered approach is to intentionally parallel the tiered approach used in regulatory contexts so that resilience assessment might be more easily and quickly integrated into existing structures and with existing policies.     

Assessing Health Risks Associated with DDT Residues in Soils in California: A Proposition 65 Case Study

Population growth in California has increased the pressure to convert agricultural land to commercial, industrial, or residential uses. In the ensuing property transactions, buyers and sellers must address the presence of toxic materials in soils such as pesticides, several of which are known to the State of California to cause cancer under Proposition 65. While this statute does not specifically address soil contaminants, the potential scope of its enforcement is sufficiently broad that owners of former agricultural properties may be obliged to provide warning of exposure to potential buyers, occupants, or construction workers about exposure to residues in soil from pesticide applications. However, Proposition 65 provides no guidance on how to assess exposures to chemicals in soil. The U.S. EPA Risk Assessment Guidance for Superfund (RAGS) provides a method for assessing soil-related exposure pathways that is consistent with the intent of Proposition 65. Using this approach, we have calculated the lifetime average concentrations of DDT in soil corresponding to the no-significant-risk level stipulated under Proposition 65 (1 × 10⁻⁵) for a hypothetical residential exposure scenario. The concentration of DDT in soil corresponding to a no-significant-risk ranges from 7.9-18.8 mg/kg, depending upon which exposure pathways are deemed to be complete for residential land use. It is argued that Proposition 65 forces the assessment and possible cleanup of such a situation through the threat of creating a health risk perception that could affect the market value of a property.     

Do Interactions Between Environmental Chemicals and the Human Microbiome Need to Be Considered in Risk Assessments?

One of the most dynamic and fruitful areas of current health‐related research concerns the various roles of the human microbiome in disease. Evidence is accumulating that interactions between substances in the environment and the microbiome can affect risks of disease, in both beneficial and adverse ways. Although most of the research has concerned the roles of diet and certain pharmaceutical agents, there is increasing interest in the possible roles of environmental chemicals. Chemical risk assessment has, to date, not included consideration of the influence of the microbiome. We suggest that failure to consider the possible roles of the microbiome could lead to significant error in risk assessment results. Our purpose in this commentary is to summarize some of the evidence supporting our hypothesis and to urge the risk assessment community to begin considering and influencing how results from microbiome‐related research could be incorporated into chemical risk assessments. An additional emphasis in our commentary concerns the distinct possibility that research on chemical–microbiome interactions will also reduce some of the significant uncertainties that accompany current risk assessments. Of particular interest is evidence suggesting that the microbiome has an influence on variability in disease risk across populations and (of particular interest to chemical risk) in animal and human responses to chemical exposure. The possible explanatory power of the microbiome regarding sources of variability could reduce what might be the most significant source of uncertainty in chemical risk assessment.     

Significance of the Dermal Route of Exposure to Risk Assessment

The skin is a route of exposure that needs to be considered when conducting a risk assessment. It is necessary to identify the potential for dermal penetration by a chemical as well as to determine the overall importance of the dermal route of exposure as compared with inhalation or oral routes of exposure. The physical state of the chemical, vapor or liquid, the concentration, neat or dilute, and the vehicle, lipid or aqueous, is also important. Dermal risk is related to the product of the amounts of penetration and toxicity. Toxicity involves local effects on the skin itself and the potential for systemic effects. Dermal penetration is described in large part by the permeability constant. When permeability constants are not known, partition coefficients can be used to estimate a chemical's potential to permeate the skin. With these concepts in mind, a tiered approach is proposed for dermal risk assessment. A key first step is the determination of a skin-to-air or skin-to-medium partition coefficient to estimate a potential for dermal absorption. Building a physiologically-based pharmacokinetic (PBPK) model is another step in the tiered approach and is useful prior to classical in vivo toxicity tests. A PBPK model can be used to determine a permeability constant for a chemical as well as to show the distribution of the chemical systemically. A detailed understanding of species differences in the structure and function of the skin and how they relate to differences in penetration rates is necessary in order to extrapolate animal data from PBPK models to the human. A study is in progress to examine anatomical differences for four species.     

Consumption of Fish and Shrimp from Southeast Louisiana Poses No Unacceptable Lifetime Cancer Risks Attributable to High‐Priority Polycyclic Aromatic Hydrocarbons

Following oil spills such as the Deepwater Horizon accident (DWH), contamination of seafood resources and possible increased health risks attributable to consumption of seafood in spill areas are major concerns. In this study, locally harvested finfish and shrimp were collected from research participants in southeast Louisiana and analyzed for polycyclic aromatic hydrocarbons (PAHs). PAHs are some of the most important chemicals of concern regarding oil‐spill‐contaminated seafood resources during and following oil spills. Some PAHs are considered carcinogens for risk assessment purposes, and currently, seven of these can be combined in lifetime cancer risk assessments using EPA approaches. Most PAHs were not detected in these samples (minimum detection limits ranged from 1.2 to 2.1 PPB) and of those that were detected, they were generally below 10 PPB. The pattern of detected PAHs suggested that the source of these chemicals in these seafood samples was not a result of direct contact with crude oil. Lifetime cancer risks were assessed using conservative assumptions and models in a probabilistic framework for the seven carcinogenic PAHs. Lifetime health risks modeled using this framework did not exceed a 1/10,000 cancer risk threshold. Conservative, health‐protective deterministic estimates of the levels of concern for PAH chemical concentration and seafood intake rates were above the concentrations and intake rates modeled under this probabilistic framework. Taken together, consumption of finfish and shrimp harvested from southeast Louisiana following the DWH does not pose unacceptable lifetime cancer risks from these seven carcinogenic PAHs even for the heaviest possible consumers.     

Uncertainty and Variation in Indirect Exposure Assessments: An Analysis of Exposure to Tetrachlorodibenzo-p-Dioxin from a Beef Consumption Pathway

Indirect exposures to 2,3,7,8-tetrachlorodibenzo- p -dioxin (TCDD) and other toxic materials released in incinerator emissions have been identified as a significant concern for human health. As a result, regulatory agencies and researchers have developed specific approaches for evaluating exposures from indirect pathways. This paper presents a quantitative assessment of the effect of uncertainty and variation in exposure parameters on the resulting estimates of TCDD dose rates received by individuals indirectly exposed to incinerator emissions through the consumption of home-grown beef. The assessment uses a nested Monte Carlo model that separately characterizes uncertainty and variation in dose rate estimates. Uncertainty resulting from limited data on the fate and transport of TCDD are evaluated, and variations in estimated dose rates in the exposed population that result from location-specific parameters and individuals'behaviors are characterized. The analysis indicates that lifetime average daily dose rates for individuals living within 10 km of a hypothetical incinerator range over three orders of magnitude. In contrast, the uncertainty in the dose rate distribution appears to vary by less than one order of magnitude, based on the sources of uncertainty included in this analysis. Current guidance for predicting exposures from indirect exposure pathways was found to overestimate the intakes for typical and high-end individuals.     

Assessing human health response in life cycle assessment using ED10s and DALYs: part 1--Cancer effects.

Life cycle assessment (LCA) is a framework for comparing products according to their total estimated environmental impact, summed over all chemical emissions and activities associated with a product at all stages in its life cycle (from raw material acquisition, manufacturing, use, to final disposal). For each chemical involved, the exposure associated with the mass released into the environment, integrated over time and space, is multiplied by a toxicological measure to estimate the likelihood of effects and their potential consequences. In this article, we explore the use of quantitative methods drawn from conventional single-chemical regulatory risk assessments to create a procedure for the estimation of the cancer effect measure in the impact phase of LCA. The approach is based on the maximum likelihood estimate of the effect dose inducing a 10% response over background, ED10, and default linear low-dose extrapolation using the slope betaED10 (0.1/ED10). The calculated effects may correspond to residual risks below current regulatory compliance requirements that occur over multiple generations and at multiple locations; but at the very least they represent a "using up" of some portion of the human population's ability to accommodate emissions. Preliminary comparisons are performed with existing measures, such as the U.S. Environmental Protection Agency's (U.S. EPA's) slope factor measure q1*. By analyzing bioassay data for 44 chemicals drawn from the EPA's Integrated Risk Information System (IRIS) database, we explore estimating ED10 from more readily available information such as the median tumor dose rate TD50 and the median single lethal dose LD50. Based on the TD50, we then estimate the ED10 for more than 600 chemicals. Differences in potential consequences, or severity, are addressed by combining betaED10 with the measure disability adjusted life years per affected person, DALYp. Most of the variation among chemicals for cancer effects is found to be due to differences in the slope factors (betaED10) ranging from 10(-4) up to 10(4) (risk of cancer/mg/kg-day).     

Chronic Health Risks from Aggregate Exposures to Ionizing Radiation and Chemicals: Scientific Basis for an Assessment Framework

Very little quantitative analysis is currently available on the cumulative effects of exposure to multiple hazardous agents that have either similar or different mechanisms of action. Over the past several years, efforts have been made to develop the methodologies for risk assessment of chemical mixtures, but mixed exposures to two or more dissimilar agents such as radiation and one or more chemical agents have not yet been addressed in any substantive way. This article reviews the current understanding of the health risks arising from mixed exposures to ionizing radiation and specific chemicals. Specifically discussed is how mixed radiation/chemical exposures, when evaluated in aggregation, were linked to chronic health endpoints such as cancer and intermediate health outcomes such as chromosomal aberrations. Also considered is the extent to which the current practices are consistent with the scientific understanding of the health risks associated with mixed-agent exposures. From this the discussion moves to the research needs for assessing the cumulative health risks from aggregate exposures to ionizing radiation and chemicals. The evaluation indicates that essentially no guidance has been provided for conducting risk assessment for two agents with different mechanisms of action (i.e., energy deposition from ionizing radiation versus DNA interactions with chemicals) but similar biological endpoints (i.e., chromosomal aberrations, mutations, and cancer). The literature review also reveals the problems caused by the absence of both the basic science and an appropriate evaluation framework for the combined effects of mixed-agent exposures. This makes it difficult to determine whether there is truly no interaction or somehow the interaction is masked by the scale of effect observation or inappropriate dose-response assumptions.     

Comparative Probabilistic Assessment of Occupational Pesticide Exposures Based on Regulatory Assessments

Implementation of probabilistic analyses in exposure assessment can provide valuable insight into the risks of those at the extremes of population distributions, including more vulnerable or sensitive subgroups. Incorporation of these analyses into current regulatory methods for occupational pesticide exposure is enabled by the exposure data sets and associated data currently used in the risk assessment approach of the Environmental Protection Agency (EPA). Monte Carlo simulations were performed on exposure measurements from the Agricultural Handler Exposure Database and the Pesticide Handler Exposure Database along with data from the Exposure Factors Handbook and other sources to calculate exposure rates for three different neurotoxic compounds (azinphos methyl, acetamiprid, emamectin benzoate) across four pesticide‐handling scenarios. Probabilistic estimates of doses were compared with the no observable effect levels used in the EPA occupational risk assessments. Some percentage of workers were predicted to exceed the level of concern for all three compounds: 54% for azinphos methyl, 5% for acetamiprid, and 20% for emamectin benzoate. This finding has implications for pesticide risk assessment and offers an alternative procedure that may be more protective of those at the extremes of exposure than the current approach.     

The [R]Evolving Relationship Between Risk Assessment and Risk Management

In Science and Decisions: Advancing Risk Assessment, the National Research Council recommends improvements in the U.S. Environmental Protection Agency's approach to risk assessment. The recommendations aim to increase the utility of these assessments, embedding them within a new risk‐based decision‐making framework. The framework involves first identifying the problem and possible options for addressing it, conducting related analyses, then reviewing the results and making the risk management decision. Experience with longstanding requirements for regulatory impact analysis provides insights into the implementation of this framework. First, neither the Science and Decisions framework nor the framework for regulatory impact analysis should be viewed as a static or linear process, where each step is completed before moving on to the next. Risk management options are best evaluated through an iterative and integrative procedure. The extent to which a hazard has been previously studied will strongly influence analysts’ ability to identify options prior to conducting formal analyses, and these options will be altered and refined as the analysis progresses. Second, experience with regulatory impact analysis suggests that legal and political constraints may limit the range of options assessed, contrary to both existing guidance for regulatory impact analysis and the Science and Decisions recommendations. Analysts will need to work creatively to broaden the range of options considered. Finally, the usefulness of regulatory impact analysis has been significantly hampered by the inability to quantify many health impacts of concern, suggesting that the scientific improvements offered within Science and Decisions will fill an crucial research gap.