Comprehensive Realism's Weight-of-Evidence Based Distributional Dose-Response Characterization

Challenges to low-dose linearity and other default assumptions in cancer risk assessment and the limitations associated with NOAELs, LOAELs, and constant uncertainty factor values in the evaluation of noncancer health effects have stimulated the continued evolution of risk assessment methodologies. The increasing need for more realistic estimates of the dose-response relationship, better uncertainty characterization, and greater utilization of cost-benefit analyses have also contributed to this evolution. “Comprehensive Realism” is an emerging quantitative weight-of-evidence based risk assessment methodology for both cancer and noncancer health effects which utilizes probability distributions and decision analysis techniques to reflect more of the relevant human exposure data, more of the available and pertinent human and animal dose-response data, and the current state of knowledge about the relative plausibility of alternative dose-response analyses. A tree (like a decision tree and a probability tree) is used to decompose the dose-response assessment into component factors, to provide a structure for explicitly considering multiple alternatives for each factor, and to explicitly incorporate the current state of knowledge about the relative plausibility of these alternatives. Groundbreaking work has demonstrated the feasibility of weight-of-evidence based distributional characterizations, and provided initial examples. Computer software implementations are also available.     

Harmonization: Developing Consistent Guidelines for Applying Mode of Action and Dosimetry Information to Cancer and Noncancer Risk Assessment

The 1983 book, Risk Assessment in the Federal Government: Managing the Process, recommended developing consistent inference guidelines for cancer risk assessment. Over the last 15 years, extensive guidance have been provided for hazard assessment for cancer and other endpoints. However, as noted in several recent reports, much less progress has occurred in developing consistent guidelines for quantitative dose response assessment methodologies. This paper proposes an approach for dose response assessment guided by consideration of mode of action (pharmacodynamics) and tissue dosimetry (pharmacokinetics). As articulated here, this systematic process involves eight steps in which available information is integrated, leading first to quantitative analyses of dose response behaviors in the test species followed by quantitative analyses of relevant human exposures. The process should be equally appropriate for both cancer and noncancer endpoints. The eight steps describe the necessary procedures for incorporating mechanistic data and provide multiple options based upon the mode of action by which the chemical causes the toxicity. Given the range of issues involved in developing such a procedure, we have simply sketched the process, focusing on major approaches for using toxicological data and on major options; many details remain to be filled in. However, consistent with the revised carcinogen risk assessment guidance (USEPA, 1996c), we propose a process that would ultimately utilize biologically based or chemical specific pharmacokinetic and pharmacodynamic models as the backbone of these analyses. In the nearer term, these approaches will be combined with analysis of data using more empirical models including options intended for use in the absence of detailed information. A major emphasis in developing any harmonized process is distinguishing policy decisions from those decisions that are affected by the quality and quantity of toxicological data. Identification of data limitations also identifies areas where further study should reduce uncertainty in the final risk evaluations. A flexible dose response assessment procedure is needed to insure that sound toxicological study results are appropriately used to influence risk management decision-making and to encourage the conduct of toxicological studies oriented toward application for dose response assessments.     

Probabilistic Environmental Risk Assessment for Dibutylphthalate (DBP)

In the risk assessment methods for new and existing chemicals in the European Union (EU), environmental “risk” is characterized by the deterministic quotient of exposure and effects (PEC/PNEC). From a scientific viewpoint, the uncertainty in the risk quotient should be accounted for explicitly in the decision making, which can be done in a probabilistic risk framework. To demonstrate the feasibility and benefits of such a framework, a sample risk assessment for an existing chemical (dibutylphthalate, DBP) is presented in this paper. The example shows a probabilistic framework to be feasible with relatively little extra effort; such a framework also provides more relevant information. The deterministic risk quotients turned out to be worst cases at generally higher than the 95th percentile of the probability distributions. Sensitivity analysis proves to be a powerful tool in identifying the main sources of uncertainty and thus will be effective for efficient further testing. The distributions assigned to the assess ment factors (derivation of the PNEC) dominate the total uncertainty in the risk assessment; uncertainties in the release estimates come second. Large uncertainties are an inherent part of risk assessment that we have to deal with quantitatively. However, the most appropriate way to characterise effects and risks requires further attention. Recommendations for further study are identified.     

Microbial aerosol generation during laboratory accidents and subsequent risk assessment

AIM: To quantify microbial aerosols generated by a series of laboratory accidents and to use these data in risk assessment. METHODS AND RESULTS: A series of laboratory accident scenarios have been devised and the microbial aerosol generated by them has been measured using a range of microbial air samplers. The accident scenarios generating the highest aerosol concentrations were, dropping a fungal plate, dropping a large bottle, centrifuge rotor leaks and a blocked syringe filter. Many of these accidents generated low particle size aerosols, which would be inhaled into the lungs of any exposed laboratory staff. Spray factors (SFs) have been calculated using the results of these experiments as an indicator of the potential for accidents to generate microbial aerosols. Model risk assessments have been described using the SF data. CONCLUSIONS: Quantitative risk assessment of laboratory accidents can provide data that can aid the design of containment laboratories and the response to laboratory accidents. SIGNIFICANCE AND IMPACT OF THE STUDY: A methodology has been described and supporting data provided to allow microbiological safety officers to carry out quantitative risk assessment of laboratory accidents.     

Types of Integration in Risk Assessment and Management,And Why They Are Needed

Risk-based decision making requires that the decision makers and stakeholders are informed of all risks that are potentially significant and relevant to the decision. The International Programme on Chemical Safety of the World Health Organization has developed a framework for integrating the assessment of human health and ecological risks. However, other types of integration are needed to support particular environmental decisions. They are integration of exposure and effects, of multiple chemicals and other hazardous agents, of multiple routes of exposure, of multiple endpoints, multiple receptors, multiple spatial and temporal scales, a product's life cycle, management alternatives, and socioeconomics with risk assessment. Inclusion of all these factors in an integrated assessment could lead to paralysis by analysis. Therefore, it is important that assessors be cognizant of the decision process and that decision makers and those who will influence the decision (stakeholders) be involved in planning the assessment to ensure that the degree of integration is necessary and sufficient.     

How to evaluate the environmental safety of microbial plant protection products: A proposal

Plant protection products with active micro-organisms are allegedly less hazardous to the environment and wildlife than synthetic chemical pesticides. Nevertheless, they need a proper pre-marketing environmental safety evaluation because of their potential toxicity and pathogenicity. Scientific and technical guidance on such a safety evaluation for regulatory purposes is scarce. Therefore, a risk decision tree is proposed to provide such guidance and to discern the acceptable from the unacceptable environmental risks. The decision tree is based on the risk criteria of the European Union. It takes integrally into account the characterisation, identification and efficacy and also emission, exposure, environmental effects and, finally, the environmental risk assessment. Case by case expert judgement remains necessary in view of limited knowledge of microbial ecology, limited experience with regulatory test protocols and taxonomic difficulties in relation to the indigenousness of active micro-organisms. The decision tree offers regulatory guidance on the environmental safety evaluation of microbial plant protection products.     

A simple way to unify multicriteria decision analysis (MCDA) and stochastic multicriteria acceptability analysis (SMAA) using a Dirichlet distribution in benefit–risk assessment

Quantitative methodologies have been proposed to support decision making in drug development and monitoring. In particular, multicriteria decision analysis (MCDA) and stochastic multicriteria acceptability analysis (SMAA) are useful tools to assess the benefit–risk ratio of medicines according to the performances of the treatments on several criteria, accounting for the preferences of the decision makers regarding the relative importance of these criteria. However, even in its probabilistic form, MCDA requires the exact elicitations of the weights of the criteria by the decision makers, which may be difficult to achieve in practice. SMAA allows for more flexibility and can be used with unknown or partially known preferences, but it is less popular due to its increased complexity and the high degree of uncertainty in its results. In this paper, we propose a simple model as a generalization of MCDA and SMAA, by applying a Dirichlet distribution to the weights of the criteria and by making its parameters vary. This unique model permits to fit both MCDA and SMAA, and allows for a more extended exploration of the benefit–risk assessment of treatments. The precision of its results depends on the precision parameter of the Dirichlet distribution, which could be naturally interpreted as the strength of confidence of the decision makers in their elicitation of preferences.     

Risk Assessment and Life-Cycle Impact Assessment (LCIA) for Human Health Cancerous and Noncancerous Emissions: Integrated and Complementary with Consistency within the USEPA

The historical parallels, complementary roles, and potential for integration of human health risk assessment (RA) and Life-Cycle Impact Assessment (LCIA) are explored. Previous authors have considered the comparison of LCA and risk assessment recognizing the inherent differences in LCA and risk assessment (e.g., LCA's focus on the functional unit, and the differences in perspective of LCA and risk assessment), and also the commonalities (e.g., the basis for the modeling). Until this time, however, no one has proposed a coordinated approach for conducting LCA and risk assessment using models consistent with the U.S. Environmental Protection Agency's (USEPA's) handbooks, policies, and guidelines. The current status of LCIA methodology development can be compared to the early days of human health RA when practitioners were overwhelmed with the model choices, assumptions, lack of data, and poor data quality. Although methodology developers can build on the shoulders of the giant, LCIA requires more innovation to deal with more impact categories, more life-cycle stages, and less data for a greater number of stressors. For certain impact categories, LCIA can use many of the guidelines, methodologies, and default parameters that have been developed for human health RA, in conjunction with sensitivity and uncertainty analysis to determine the level of detail necessary for various applications. LCIA can then identify “hot spots” that require the additional detail and level of certainty provided by RA. A comparison of the USEPA's Tool for the Reduction and Assessment of Chemical and other environmental Impacts (TRACI) and the USEPA's Risk-Screening Environmental Indicators (RSEI) will be explored.     

Unraveling the Chimera: A Corporate View of the Precautionary Principle

Current controversy regarding how and when the precautionary principle should be applied to the introduction of new technology has created a false dichotomy, a dichotomy between conventional, risk-based decision making and an alternative paradigm that seemingly denounces risk assessment. As we compare views of the precautionary principle relative to our own operating standards for ensuring human and environmental safety, we perceive no irreconcilable conflict. Due precaution is entirely consistent with sound, cost-effective management of the risks and uncertainties inherent in new technologies. The principle guides prudent risk management actions under a prescribed set of circumstances, i.e., potentially serious or irreversible risks, or incomplete characterization (high uncertainty). In order to enable technological innovation toward a more sustainable future, it is critical that any preventative measures taken under these circumstances be provisional in nature, pending adequate risk characterization. As with all risk management decisions, we contend that the principle requires consideration of a suite of factors beyond risk assessment, including political, social, legal and cultural considerations to tailor the measures proportionately to the risk at hand. Overall, we are encouraged to find relatively broad agreement in this interpretation with a number of key multinational governmental and trade institutions.     

Climate change vulnerability for species—Assessing the assessments

Climate change vulnerability assessments are commonly used to identify species at risk from global climate change, but the wide range of methodologies available makes it difficult for end users, such as conservation practitioners or policymakers, to decide which method to use as a basis for decision‐making. In this study, we evaluate whether different assessments consistently assign species to the same risk categories and whether any of the existing methodologies perform well at identifying climate‐threatened species. We compare the outputs of 12 climate change vulnerability assessment methodologies, using both real and simulated species, and validate the methods using historic data for British birds and butterflies (i.e. using historical data to assign risks and more recent data for validation). Our results show that the different vulnerability assessment methods are not consistent with one another; different risk categories are assigned for both the real and simulated sets of species. Validation of the different vulnerability assessments suggests that methods incorporating historic trend data into the assessment perform best at predicting distribution trends in subsequent time periods. This study demonstrates that climate change vulnerability assessments should not be used interchangeably due to the poor overall agreement between methods when considering the same species. The results of our validation provide more support for the use of trend‐based rather than purely trait‐based approaches, although further validation will be required as data become available.     

Actual and perceived collision risk for bird strikes at Namibian airports

At Namibia’s two major airports, Hosea Kutako International and Eros (domestic), 117 bird strike collision incidents were recorded between 2006 and 2010. A risk assessment, which included a proposed risk weighting methodology, was conducted at Hosea Kutako and Eros airports, which estimated the probability of an accident/collision as well as the consequence of such a collision. The assessment included surveys of bird occurrence frequencies as well as pilot interviews. The results of the risk assessments were compared with actual bird strike incidences for each species, frequency of occurrence of birds and pilot perceptions of species risk, in order to find whether risk assessment and pilot perception are reliable measures of potential bird strike incidence. White-backed Vulture Gyps africanus and Helmeted Guineafowl Numida meleagris were the highest risk species at both airports. They were also, after Crowned Lapwing Vanellus coronatus, the species most often observed by pilots. Bird strike records showed that Crowned Lapwing and Helmeted Guineafowl were also the most frequently struck birds at both airports. The study illustrates how combining risk assessment, pilot perception and bird strike history can benefit bird strike minimisation plans at airports through the rapid identification of priority bird species.     

Integrating life cycle cost analysis and LCA

The private sector decision making situations which LCA addresses mustalso eventually take theeconomic consequences of alternative products or product designs into account. However, neither the internal nor external economic aspects of the decisions are within the scope of developed LCA methodology, nor are they properly addressed by existing LCA tools. This traditional separation of life cycle environmental assessment from economic analysis has limited the influence and relevance of LCA for decision-making, and left uncharacterized the important relationships and trade-offs between the economic and life cycle environmental performance of alternative product design decision scenarios. Still standard methods of LCA can and have been tightly, logically, and practically integrated with standard methods for cost accounting, life cycle cost analysis, and scenario-based economic risk modeling. The result is an ability to take both economic and environmental performance — and their tradeoff relationships — into account in product/process design decision making.     

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。     

The Concept of Data Utility in Health Risk Assessment: A Multi-Disciplinary Perspective

Human and ecological health risk assessments and the decisions that stem from them require the acquisition and analysis of data. In agencies that are responsible for health risk decision-making, data (and/or opinions/judgments) are obtained from sources such as scientific literature, analytical and process measurements, expert elicitation, inspection findings, and public and private research institutions. Although the particulars of conducting health risk assessments of given disciplines may be dramatically different, a common concern is the subjective nature of judging data utility. Often risk assessors are limited to available data that may not be completely appropriate to address the question being asked. Data utility refers to the ability of available data to support a risk-based decision for a particular risk assessment. This article familiarizes the audience with the concept of data utility and is intended to raise the awareness of data collectors (e.g., researchers), risk assessors, and risk managers to data utility issues in health risk assessments so data collection and use will be improved. In order to emphasize the cross-cutting nature of data utility, the discussion has not been organized into a classical partitioning of risk assessment concerns as being either human health- or ecological health-oriented, as per the U.S. Environmental Protection Agency's Superfund Program.     

ENVIRONMENTAL RISK ASSESSMENT: TASKS AND OBLIGATIONS

Synthesizing, characterizing, and communicating the risk science information used in environmental decision-making depends in the first instance on the nature and quality of the technical analysis. At the same time, other important features of the risk analysis, features that require special attention to provide context for the analysis as a whole, are frequently overlooked in practice or in presentation. Now, as the field expands to meet new challenges and to include new participants, all practitioners — government, academics, industry, and interest groups — must give renewed emphasis to certain hall marks of sound risk assessment: identifying incomplete information and its influence on the risk assessment process, articulating alternative assumptions and the scientific or policy reasons for choices made among alternatives, describing process considerations and limitations as well as numerical results, and fully informing decision makers, the press, and the interested public. The resulting greater clarity and transparency in the scientific analyses that under lie environmental decision making can enhance credibility and public confidence in the scientific foundation for those decisions.     

Assessing Risks of Plant-Based Pharmaceuticals: II. Non-Target Organism Exposure

Plant-based pharmaceuticals potentially offer a cleaner method of producing a protein for drug manufacturing than traditional methods because plants are free of mammalian infectious agents. However, in the open environment they have the potential for intra-and inter-species gene flow, protein exposure to the public and non-target organisms, and they also have the potential to contaminate livestock feed. This study used probabilistic approaches to quantify the non-target organism risks associated with three pharmaceutical proteins produced in field-grown maize. The risk assessment for plant-based pharmaceuticals was conducted for four receptor species used as surrogates for a wider range of species. Body weights and maize consumption rates for each species were modeled from currently available information and used to calculate the exposure based on expression levels of three proteins. The acute dietary exposure for the receptor species was a single-day event in which the total maize consumption came from the recombinant maize. The non-target organism risk assessment demonstrated that risks will vary between species and between proteins, based primarily on differences in toxic endpoint and consumption rates. It also shows the utility of probabilistic, quantitative risk assessment methodologies and the importance of assessing risks from plant-based pharmaceuticals on a case-by-case basis.     

基于故障树方法的非计划再次手术风险评估

目的 探索一种适合于在过程复杂、环境多变、风险多样的手术治疗系统中,对术前准备、术中操作、术后医疗护理及管理等贯穿围手术期全过程进行风险评估的方法。方法 通过危险事件的风险影响因子识别、定性分析与定量分析、基本事件综合风险等级评价,绘制具有实践操作意义的风险矩阵图,全面识别手术治疗系统风险、科学分析危险事件与风险影响因子,有效评价风险等级与可容忍度。结果 构建包括7个中间事件、29个基本事件、9个逻辑或门和1个逻辑与门的非计划再次手术故障树模型,故障树由8个一阶割集和104个二阶割集组成。当所有最小割集均存在时,被调查医院非计划再次手术的发生概率为0.950 10,同时确定25个基本事件在该医院的综合风险重要性等级,并根据绘制的风险图谱进一步确定风险应对的优先顺序。结论 基于故障树的手术治疗系统风险评估方法,可以全面识别手术治疗系统风险,科学分析风险影响因子,有效评价风险等级。     

The role of human factor in maritime environment risk assessment: A practical application on Ballast Water Treatment (BWT) system in ship

The role of human factor plays a critical role in the safe and clean operation of maritime industry. Human error prediction can be beneficial to assess risk in maritime industry since shipping activities can pose potential hazards to human life and maritime ecology. The aim of this paper is to propose a risk assessment tool by considering the role of human factor. Hence, the desired safety control level in maritime transportation activities can be ascertained. In the proposed approach, a Success Likelihood Index Method (SLIM) extended with fuzzy logic is used to calculate human error probability (HEP). Severity of consequences are adopted in the proposed approach to assess risk. The quantitative risk assessment approach under fuzzy SLIM methodology will be applied to a very specific case on-board ship: Ballast Water Treatment (BWT) system. In order to improve consistency of research and minimize subjectivity of experts' judgments, the paper adopts the dominance factor which is used to adjust the impact level of experts' judgments in the aggregation stage of the methodology. The paper aims at not only highlighting the importance of human factor in maritime risk assessment but also enhancing safety control level and minimizing potential environmental impacts to marine ecology.     

Probabilistic risk assessment of inhalation of nickel-rich soil particulates on Jeju Island,Korea

The soils of Jeju Island contain naturally abundant nickel originating from prehistoric volcanic activity. Nickel is a known human carcinogen via inhalation exposure. A risk assessment of soil particle inhalation was conducted for the first time in Korea through the analysis of soil and air data obtained from agricultural sites. Sixteen sites in Jeju were selected—13 farms, 2 citrus orchards, and 1 ranch. Forty-four soil samples were taken from these sites and analyzed for nickel content. Total suspended solids (TSP) and particulate matter up to 10 µm in size (PM10) were measured directly from the agricultural sites, and nickel concentrations in TSP and PM10 were quantified for use in the inhalation risk assessment. We conducted a probabilistic inhalation risk analysis using monitoring data obtained from the 16 sites on Jeju Island. Risk assessment procedures followed both the Korean Ministry of Environment and the U.S. Environmental Protection Agency (USEPA) risk assessment methodologies. The cancer risk associated with inhalation followed by application of the Korean risk assessment approach ranged from 4.98 × 10^?9 to 3.43 × 10^?7, whereas the cancer risk associated with inhalation followed by application of the USEPA risk assessment approach ranged from 3.40 × 10^?9 to 3.74 × 10^?7. This study demonstrates that no carcinogenic risk is associated with inhalation in Jeju, based on a lower cancer risk limit of 10^?6.