The Use of Human Experience Data in the EU Risk Assessment Process

The incorporation of human experience data (HD) into the risk assessment process is encouraged by various authorities with the aim of improving the robustness of the subsequent findings. HD, however, can present in many forms, ranging from epidemiological studies to the accumulated experiences from poison centers. This diversity of the human experience, combined with the manner in which it may (or may not) present, creates several challenges for risk assessors if they are to give available HD due weight in the RA process. An evaluation was made of how HD has been cited and used within the 64 human health RAs published by the EU to the end of 2005. In all RAs, HD had been cited to some degree. But there was no consistency between how cited data had subsequently been taken forward and used in the evaluation of different endpoints, either between the RAs authored by the same or different EU Member States. The lack of any accepted guidance for addressing the role that HD can play within the RA process appears to lead to this situation. Recommendations are provided on the scope and focus such guidance could usefully be expected to take.     

Quantifying Uncertainty in a Risk Assessment Using Human Data

A call for risk assessment approaches that better characterize and quantify uncertainty has been made by the scientific and regulatory community. This paper responds to that call by demonstrating a distributional approach that draws upon human data to derive potency estimates and to identify and quantify important sources of uncertainty. The approach is rooted in the science of decision analysis and employs an influence diagram, a decision tree, probabilistic weights, and a distribution of point estimates of carcinogenic potency. Its results estimate the likelihood of different carcinogenic risks (potencies) for a chemical under a specific scenario. For this exercise, human data on formaldehyde were employed to demonstrate the approach. Sensitivity analyses were performed to determine the relative impact of specific levels and alternatives on the potency distribution. The resulting potency estimates are compared with the results of an exercise using animal data on formaldehyde. The paper demonstrates that distributional risk assessment is readily adapted to situations in which epidemiologic data serve as the basis for potency estimates. Strengths and weaknesses of the distributional approach are discussed. Areas for further application and research are recommended.     

A Bayesian Method to Mine Spatial Data Sets to Evaluate the Vulnerability of Human Beings to Catastrophic Risk

Vulnerability of human beings exposed to a catastrophic disaster is affected by multiple factors that include hazard intensity, environment, and individual characteristics. The traditional approach to vulnerability assessment, based on the aggregate‐area method and unsupervised learning, cannot incorporate spatial information; thus, vulnerability can be only roughly assessed. In this article, we propose Bayesian network (BN) and spatial analysis techniques to mine spatial data sets to evaluate the vulnerability of human beings. In our approach, spatial analysis is leveraged to preprocess the data; for example, kernel density analysis (KDA) and accumulative road cost surface modeling (ARCSM) are employed to quantify the influence of geofeatures on vulnerability and relate such influence to spatial distance. The knowledge‐ and data‐based BN provides a consistent platform to integrate a variety of factors, including those extracted by KDA and ARCSM to model vulnerability uncertainty. We also consider the model's uncertainty and use the Bayesian model average and Occam's Window to average the multiple models obtained by our approach to robust prediction of the risk and vulnerability. We compare our approach with other probabilistic models in the case study of seismic risk and conclude that our approach is a good means to mining spatial data sets for evaluating vulnerability.     

Estimation of the Leukemia Risk in Human Populations Exposed to Benzene from Tobacco Smoke Using Epidemiological Data

Several epidemiological studies have demonstrated an association between occupational benzene exposure and increased leukemia risk, in particular acute myeloid leukemia (AML). However, there is still uncertainty as to the risk to the general population from exposure to lower environmental levels of benzene. To estimate the excess risk of leukemia from low‐dose benzene exposure, various methods for incorporating epidemiological data in quantitative risk assessment were utilized. Tobacco smoke was identified as one of the main potential sources of benzene exposure and was the focus of this exposure assessment, allowing further investigation of the role of benzene in smoking‐induced leukemia. Potency estimates for benzene were generated from individual occupational studies and meta‐analysis data, and an exposure assessment for two smoking subgroups (light and heavy smokers) carried out. Subsequently, various techniques, including life‐table analysis, were then used to evaluate both the excess lifetime risk and the contribution of benzene to smoking‐induced leukemia and AML. The excess lifetime risk for smokers was estimated at between two and six additional leukemia deaths in 10,000 and one to three additional AML deaths in 10,000. The contribution of benzene to smoking‐induced leukemia was estimated at between 9% and 24% (U_pperCL 14–31%). For AML this contribution was estimated as 11–30% (U_pperCL 22–60%). From the assessments carried out here, it appears there is an increased risk of leukemia from low‐level exposure to benzene and that benzene may contribute up to a third of smoking‐induced leukemia. Comparable results from using methods with varying degrees of complexity were generated.     

The Importance of Biological Realism in Dioxin Risk Assessment Models Michael

Mechanistic mathematical models of hepatocarcinogenesis in the female rat were constructed to investigate possible relationships among the Ah, estrogen, and EGF receptors in TCDD hepato-carcinogenicity. Each model generates dose-response curves for the expression of biomarker liver proteins CYP1A1, CYP1A2, and residual plasma membrane EGF receptor consequent to exposure to TCDD. The shapes of the response curves were strongly dependent on the assumed mechanisms of constitutive expression of these proteins. Assuming a constant level of the hepatic Ah receptor, a sigmoidal dose-response of hepatic CYP1A1 to total liver TCDD was computed. However, inclusion of induction of the Ah receptor by TCDD in a physiologically realistic dosimetric model produced a linear low-dose response of CYP1A1. This behavior was computed to arise from the net effect of sublinear response of CYP1A1 mRNA to the concentration of the Ah-TCDD complex and supralinear response of the protein concentration to the mRNA level, illustrating the importance of biological realism in dose-response modeling. The dosimetric model also computed effects of TCDD on the hepatic estradiol concentration and consequent effects on the binding capacity of the EGF receptor and suggests plausible mechanisms for tumor promotion by TCDD. Setting circulating estradiol levels in the model to values typical of the male rat indicated possible sources of the differences in the responses of the EGF receptor and in development of tumors in the two sexes.     

Importance of Distributional Form in Characterizing Inputs to Monte Carlo Risk Assessments

The selection among distributional forms for inputs into uncertainty and variability (e.g., Monte Carlo) analyses is an important task. This paper considers the importance of distributional selection by examining the overall and tail behavior of the lognormal, Weibull, gamma, and inverse gaussian distributions. It is concluded that at low relative standard deviation (below 1), there is less of a difference between upper tail behavior among the distributions than at higher RSD values. Sample sizes in excess of 200 are required to reliably distinguish between distributional forms at the higher RSD values. The likelihood statistic appears to offer a reasonable approach to distributional discrimination, and it, or a similar approach, should be incorporated into distributional fitting procedures used in risk analysis.     

Risk Assessment for Aflatoxin: II. Implications of Human Epidemiology Data

A review of epidemiology literature revealed that only studies conducted in Africa and Asia included data adequate to permit quantitative assessment of the dose-response relationship between aflatoxin exposure levels and liver cancer rates. Although these studies were judged adequate, their direct use to predict risks in U.S. populations may be questioned since hepatitis B virus (HBV) infections are far more common in the studied areas than in the U.S. Recent research indicates that, if aflatoxin contributes to the development of liver cancer, it almost always does so in the presence of HBV infection. The African/Asian data do not permit us to estimate the potency of aflatoxin in the absence of HBV. Recognizing this, these data can only be used to establish upper limits for the predicted excess lifetime risk for liver cancer in the U.S. When used in conjunction with aflatoxin exposure estimates for the Southeast U.S., these data predict a liver cancer rate, due to aflatoxin alone, far above that actually observed due to all causes; this provides an indication of the conservatism of this approach. Data from the Southeast U.S. may be used to estimate an excess lifetime risk for liver cancer of 2.17 x 10(-6) x (aflatoxin intake, ng/kg/day).     

The Importance of Multiple Performance Criteria for Understanding Trust in Risk Managers

Effective risk management requires balancing several, sometimes competing, goals, such as protecting public health and ensuring cost control. Research examining public trust of risk managers has largely focused on trust that is unspecified or for a single goal. Yet it can be reasonable to have a high level of trust in one aspect of a target's performance but not another. Two studies involving redevelopment of contaminated land (Study 1) and drinking water standards (Study 2) present preliminary evidence on the value of distinguishing between performance criteria for understanding of trust. Study 1 assessed perceptions of several trust targets (councilors, developers, scientists, residents) on their competence (capacity to achieve goals) and willingness to take action under uncertainty for four criteria. Study 2 assessed competence, willingness, and trust for five criteria regarding a single government agency. In both studies overall trust in each target was significantly better explained by considering perceptions of their performance on multiple criteria than on the single criterion of public health. In Study 1, the influence of criteria also varied plausibly across trust targets (e.g., willingness to act under uncertainty increased trust in developers on cost control and councilors on local economic improvement, but decreased it for both targets on environmental protection). Study 2 showed that explained variance in trust increased with both dimension‐ and trust‐based measures of criteria. Further conceptual and methodological development of the notion of multiple trust criteria could benefit our understanding of stated trust judgments.     

中国金融机构的系统重要性及系统性风险传染机制分析——基于复杂网络的视角

采用最小生成树(MST)和平面极大过滤图(PMFG)方法构建和分析金融市场网络可以动态识别金融网络中节点的系统重要性,而利用最小生成树的唯一性可以全面而直观地显示系统性风险的传导机制。我们通过对银行间同业拆借市场进行的实证分析证明了该方法的有效性和稳健性,特别是最小生成树方法对系统性风险传导潜在路径的识别以及系统性风险的宏观审慎监管提供了直观而有效的手段。     

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.     

高绩效人力资源管理系统对新产品成功影响机制研究

本文以383家中国医疗器械生产企业调研数据为依据,实证研究了新兴市场企业高绩效人力资源管理系统对新产品成功的影响机制。由于新兴市场企业产品创新机制和发达国家不完全相同,在有效控制相关影响变量后,本文发现,动态能力对高绩效人力资源管理系统和新产品成功之间的关系起到部分中介作用;环境动态性对高绩效人力资源管理系统与新产品成功直接和间接关系以及总的关系存在显著负向调节作用。本文的研究丰富了新兴市场高绩效人力资源管理系统对组织创新影响的文献内容。     

The Use of PBPK Models to Inform Human Health Risk Assessment: Case Study on Perchlorate and Radioiodide Human Lifestage Models

Physiologically‐based pharmacokinetic (PBPK) models are often submitted to or selected by agencies, such as the U.S. Environmental Protection Agency (U.S. EPA) and Agency for Toxic Substances and Disease Registry, for consideration for application in human health risk assessment (HHRA). Recently, U.S. EPA evaluated the human PBPK models for perchlorate and radioiodide for their ability to estimate the relative sensitivity of perchlorate inhibition on thyroidal radioiodide uptake for various population groups and lifestages. The most well‐defined mode of action of the environmental contaminant, perchlorate, is competitive inhibition of thyroidal iodide uptake by the sodium‐iodide symporter (NIS). In this analysis, a six‐step framework for PBPK model evaluation was followed, and with a few modifications, the models were determined to be suitable for use in HHRA to evaluate relative sensitivity among human lifestages. Relative sensitivity to perchlorate was determined by comparing the PBPK model predicted percent inhibition of thyroidal radioactive iodide uptake (RAIU) by perchlorate for different lifestages. A limited sensitivity analysis indicated that model parameters describing urinary excretion of perchlorate and iodide were particularly important in prediction of RAIU inhibition; therefore, a range of biologically plausible values available in the peer‐reviewed literature was evaluated. Using the updated PBPK models, the greatest sensitivity to RAIU inhibition was predicted to be the near‐term fetus (gestation week 40) compared to the average adult and other lifestages; however, when exposure factors were taken into account, newborns were found to be populations that need further evaluation and consideration in a risk assessment for perchlorate.     

企业报酬机制与人力资本投资

由于企业与员工双方都以自己的收益最大化为目标函数,所以当企业采取对产出按比例分成的报酬机制时,会导致双边道德风险,从而使员工实际的人力资本投资力度和工作努力程度以及企业的实际相关投入力度都低于整个社会福利最大化时的力度.如果企业能够采取另外一种报酬机制,使员工拥有完全剩余索取权,就能够使企业与员工都选择社会福利最大化时人力资本投资力度和工作努力程度以及相关投入力度.     

Fostering Risk Taking in Research and Development: The Importance of a Project's Terminal Value

Large firms face a conflict in managing a portfolio of high-risk projects. When an ongoing project is thought to have a low likelihood of success, project team members take risks to improve its chances of success. However, upper-level managers who allocate resources tend to withhold resources from a project with a low likelihood of success in favor of others in the portfolio that look more promising. Because this paucity of resources influences project team members to avoid risk, the total effect of success likelihood on risk taking is conflicted. The influence on risk taking of a project's terminal value—defined as the value that remains in the firm in the event of project failure—is unequivocally positive, because both senior management resource allocation and project team risk-taking propensity are encouraged by terminal value. Thus, firms can override the ambivalent effect of likelihood of success on project decision making by focusing attention on a project's terminal value.     

Risk Assessment Based on Financial Data: Market Response to Airline Accidents

The risk of catastrophic failures, for example in the aviation and aerospace industries, can be approached from different angles (e.g., statistics when they exist, or a detailed probabilistic analysis of the system). Each new accident carries information that has already been included in the experience base or constitutes new evidence that can be used to update a previous assessment of the risk. In this paper, we take a different approach and consider the risk and the updating from the investor's point of view. Based on the market response to past airplane accidents, we examine which ones have created a surprise response and which ones are considered part of the risk of the airline business as previously assessed. To do so, we quantify the magnitude and the timing of the observed market response to catastrophic accidents, and we compare it to an estimate of the response that would be expected based on the true actual cost of the accident including direct and indirect costs (full-cost information response). First, we develop a method based on stock market data to measure the actual market response to an accident and we construct an estimate of the full-cost information response to such an event. We then compare the two figures for the immediate and the long-term response of the market for the affected firm, as well as for the whole industry group to which the firm belongs. As an illustration, we analyze a sample of ten fatal accidents experienced by major US domestic airlines during the last seven years. In four cases, we observed an abnormal market response. In these instances, it seems that the shareholders may have updated their estimates of the probability of a future accident in the affected airlines or more generally of the firm's future business prospects. This market reaction is not always easy to explain much less to anticipate, a fact which management should bear in mind when planning a firm's response to such an event.