Thyroid Cancer Risk from Exposure to Ionizing Radiation: A Case Study in the Comparative Potency Model

Considerable controversy exists about the relative risk of thyroid cancer following exposure to external radiation compared to the risk after exposure to internally deposited 131I. The human epidemiological data are equivocal, and studies are not directly comparable owing to differing ages at exposure, dose ranges, and periods of follow-up. Limited experimental data at low dose ranges support the hypothesis of equal potency in animals. This report utilizes a relative potency model to reconcile data from different sources, and to provide an estimate of thyroid cancer risk following human exposure to 131I. We utilize data from epidemiological studies of external radiation and 131I exposure in humans and data from an experimental animal study. This analysis shows that the data provide no compelling evidence to suggest that the risks accompanying external radiation or 131I exposure are different.     

Quantitative Assessment of the Risk of Lung Cancer Associated with Occupational Exposure to Refractory Ceramic Fibers

We present the results of a quantitative assessment of the lung cancer risk associated with occupational exposure to refractory ceramic fibers (RCF). The primary sources of data for our risk assessment were two long-term oncogenicity studies in male Fischer rats conducted to assess the potential pathogenic effects associated with prolonged inhalation of RCF. An interesting feature of the data was the availability of the temporal profile of fiber burden in the lungs of experimental animals. Because of this information, we were able to conduct both exposure–response and dose–response analyses. Our risk assessment was conducted within the framework of a biologically based model for carcinogenesis, the two-stage clonal expansion model, which allows for the explicit incorporation of the concepts of initiation and promotion in the analyses. We found that a model positing that RCF was an initiator had the highest likelihood. We proposed an approach based on biological considerations for the extrapolation of risk to humans. This approach requires estimation of human lung burdens for specific exposure scenarios, which we did by using an extension of a model due to Yu. Our approach acknowledges that the risk associated with exposure to RCF depends on exposure to other lung carcinogens. We present estimates of risk in two populations: (1) a population of nonsmokers and (2) an occupational cohort of steelworkers not exposed to coke oven emissions, a mixed population that includes both smokers and nonsmokers.     

Cancer Risk Estimation of Genotoxic Chemicals Based on Target Dose and a Multiplicative Model

A mechanistic model and associated procedures are proposed for cancer risk assessment of genotoxic chemicals. As previously shown for ionizing radiation, a linear multiplicative model was found to be compatible with published experimental data for ethylene oxide, acrylamide, and butadiene. The validity of this model was anticipated in view of the multiplicative interaction of mutation with inherited and acquired growth-promoting conditions. Concurrent analysis led to rejection of an additive model (i.e. the model commonly applied for cancer risk assessment). A reanalysis of data for radiogenic cancer in mouse, dog and man shows that the relative risk coefficient is approximately the same (0.4 to 0.5 percent per rad) for tumours induced in the three species.Doses in vivo, defined as the time-integrated concentrations of ultimate mutagens, expressed in millimol × kg^–1 × h (mMh) are, like radiation doses given in Gy or rad, proportional to frequencies of potentially mutagenic events. The radiation dose equivalents of chemical doses are, calculated by multiplying chemical doses (in mMh) with the relative genotoxic potencies (in rad × mMh^–1) determined in vitro. In this way the relative cancer incidence increments in rats and mice exposed to ethylene oxide were shown to be about 0.4 percent per rad-equivalent, in agreement with the data for radiogenic cancer.Our analyses suggest that values of the relative risk coefficients for genotoxic chemicals are independent of species and that relative cancer risks determined in animal tests apply also to humans. If reliable animal test data are not available, cancer risks may be estimated by the relative potency. In both cases exposure dose/target dose relationships, the latter via macromolecule adducts, should be determined.     

Chloroform Exposure and the Health Risk Associated with Multiple Uses of Chlorinated Tap Water

Recently, showers have been suspected to be an important source of indoor exposure to volatile organic compounds (VOC). The chloroform dose to an individual from showering was determined based on exhaled breath analysis. The postexposure chloroform breath concentration ranged from 6.0-21 micrograms/m3, while all corresponding background breath concentrations were less than 0.86 micrograms/m3. The internal dose from showering (inhalation plus dermal) was comparable to estimates of the dose from daily water ingestion. The risk associated with a single, 10-min shower was estimated to be 1.22 x 10(-4), while the estimated risk from daily ingestion of tap water ranged from 0.130 x 10(-4) to 1.80 x 10(-4) for 0.15 and 2.0 L, respectively. Since the estimates of chloroform risk from domestic water use for the three exposure routes--ingestion, inhalation, and dermal--are similar, all routes must be used to calculate the total risk when making policy decisions regarding the quality of the municipal water supply.     

Potential Airborne Asbestos Exposure and Risk Associated with the Historical Use of Cosmetic Talcum Powder Products

Over time, concerns have been raised regarding the potential for human exposure and risk from asbestos in cosmetic‐talc–containing consumer products. In 1985, the U.S. Food and Drug Administration (FDA) conducted a risk assessment evaluating the potential inhalation asbestos exposure associated with the cosmetic talc consumer use scenario of powdering an infant during diapering, and found that risks were below levels associated with background asbestos exposures and risk. However, given the scope and age of the FDA's assessment, it was unknown whether the agency's conclusions remained relevant to current risk assessment practices, talc application scenarios, and exposure data. This analysis updates the previous FDA assessment by incorporating the current published exposure literature associated with consumer use of talcum powder and using the current U.S. Environmental Protection Agency's (EPA) nonoccupational asbestos risk assessment approach to estimate potential cumulative asbestos exposure and risk for four use scenarios: (1) infant exposure during diapering; (2) adult exposure from infant diapering; (3) adult exposure from face powdering; and (4) adult exposure from body powdering. The estimated range of cumulative asbestos exposure potential for all scenarios (assuming an asbestos content of 0.1%) ranged from 0.0000021 to 0.0096 f/cc‐yr and resulted in risk estimates that were within or below EPA's acceptable target risk levels. Consistent with the original FDA findings, exposure and corresponding health risk in this range were orders of magnitude below upper‐bound estimates of cumulative asbestos exposure and risk at ambient levels, which have not been associated with increased incidence of asbestos‐related disease.     

Evaluation of Take‐Home Exposure and Risk Associated with the Handling of Clothing Contaminated with Chrysotile Asbestos

The potential for para‐occupational (or take‐home) exposures from contaminated clothing has been recognized for the past 60 years. To better characterize the take‐home asbestos exposure pathway, a study was performed to measure the relationship between airborne chrysotile concentrations in the workplace, the contamination of work clothing, and take‐home exposures and risks. The study included air sampling during two activities: (1) contamination of work clothing by airborne chrysotile (i.e., loading the clothing), and (2) handling and shaking out of the clothes. The clothes were contaminated at three different target airborne chrysotile concentrations (0–0.1 fibers per cubic centimeter [f/cc], 1–2 f/cc, and 2–4 f/cc; two events each for 31–43 minutes; six events total). Arithmetic mean concentrations for the three target loading levels were 0.01 f/cc, 1.65 f/cc, and 2.84 f/cc (National Institute of Occupational Health and Safety [NIOSH] 7402). Following the loading events, six matched 30‐minute clothes‐handling and shake‐out events were conducted, each including 15 minutes of active handling (15‐minute means; 0.014–0.097 f/cc) and 15 additional minutes of no handling (30‐minute means; 0.006–0.063 f/cc). Percentages of personal clothes‐handling TWAs relative to clothes‐loading TWAs were calculated for event pairs to characterize exposure potential during daily versus weekly clothes‐handling activity. Airborne concentrations for the clothes handler were 0.2–1.4% (eight‐hour TWA or daily ratio) and 0.03–0.27% (40‐hour TWA or weekly ratio) of loading TWAs. Cumulative chrysotile doses for clothes handling at airborne concentrations tested were estimated to be consistent with lifetime cumulative chrysotile doses associated with ambient air exposure (range for take‐home or ambient doses: 0.00044–0.105 f/cc year).     

Stochastic Estimates of Exposure and Cancer Risk from Carbon Tetrachloride Released to the Air from the Rocky Flats Plant

Carbon tetrachloride is a degreasing agent that was used at the Rocky Flats Plant (RFP) in Colorado to clean product components and equipment. The chemical is considered a volatile organic compound and a probable human carcinogen. During the time the plant operated (1953-1989), most of the carbon tetrachloride was released to the atmosphere through building exhaust ducts. A smaller amount was released to the air via evaporation from open-air burn pits and ground-surface discharge points. Airborne releases from the plant were conservatively estimated to be equivalent to the amount of carbon tetrachloride consumed annually by the plant, which was estimated to be between 3.6 and 180 Mg per year. This assumption was supported by calculations that showed that most of the carbon tetrachloride discharged to the ground surface would subsequently be released to the atmosphere. Atmospheric transport of carbon tetrachloride from the plant to the surrounding community was estimated using a Gaussian Puff dispersion model (RATCHET). Time-integrated concentrations were estimated for nine hypothetical but realistic exposure scenarios that considered variation in lifestyle, location, age, and gender. Uncertainty distributions were developed for cancer slope factors and atmospheric dispersion factors. These uncertainties were propagated through to the final risk estimate using Monte Carlo techniques. The geometric mean risk estimates varied from 5.2 x 10(-6) for a hypothetical rancher or laborer working near the RFP to 3.4 x 10(-9) for an infant scenario. The distribution of incremental lifetime cancer incidence risk for the hypothetical rancher was between 1.3 x 10(-6) (5% value) and 2.1 x 10(-5) (95% value). These estimates are similar to or exceed estimated cancer risks posed by releases of radionuclides from the site.     

Estimating the National Public Health Burden Associated with Exposure to Ambient PM2.5 and Ozone

Ground‐level ozone (O₃) and fine particulate matter (PM_2.5) are associated with increased risk of mortality. We quantify the burden of modeled 2005 concentrations of O₃ and PM_2.5 on health in the United States. We use the photochemical Community Multiscale Air Quality (CMAQ) model in conjunction with ambient monitored data to create fused surfaces of summer season average 8‐hour ozone and annual mean PM_2.5 levels at a 12 km grid resolution across the continental United States. Employing spatially resolved demographic and concentration data, we assess the spatial and age distribution of air‐pollution‐related mortality and morbidity. For both PM_2.5 and O₃ we also estimate: the percentage of total deaths due to each pollutant; the reduction in life years and life expectancy; and the deaths avoided according to hypothetical air quality improvements. Using PM_2.5 and O₃ mortality risk coefficients drawn from the long‐term American Cancer Society (ACS) cohort study and National Mortality and Morbidity Air Pollution Study (NMMAPS), respectively, we estimate 130,000 PM_2.5‐related deaths and 4,700 ozone‐related deaths to result from 2005 air quality levels. Among populations aged 65–99, we estimate nearly 1.1 million life years lost from PM_2.5 exposure and approximately 36,000 life years lost from ozone exposure. Among the 10 most populous counties, the percentage of deaths attributable to PM_2.5 and ozone ranges from 3.5% in San Jose to 10% in Los Angeles. These results show that despite significant improvements in air quality in recent decades, recent levels of PM_2.5 and ozone still pose a nontrivial risk to public health.     

Applying a Health Behavior Theory to Explore the Influence of Information and Experience on Arsenic Risk Representations, Policy Beliefs, and Protective Behavior

The common sense model (CSM) shows how people process information to construct representations, or mental models, that guide responses to health threats. We applied the CSM to understand how people responded to information about arsenic-contaminated well water. Constructs included external information (arsenic level and information use), experience (perceived water quality and arsenic-related health effects), representations, safety judgments, opinions about policies to mitigate environmental arsenic, and protective behavior. Of 649 surveys mailed to private well users with arsenic levels exceeding the maximum contaminant level, 545 (84%) were analyzed. Structural equation modeling quantified CSM relationships. Both external information and experience had substantial effects on behavior. Participants who identified a water problem were more likely to reduce exposure to arsenic. However, about 60% perceived good water quality and 60% safe water. Participants with higher arsenic levels selected higher personal safety thresholds and 20% reported a lower arsenic level than indicated by their well test. These beliefs would support judgments of safe water. A variety of psychological and contextual factors may explain judgments of safe water when information suggested otherwise. Information use had an indirect effect on policy beliefs through understanding environmental causes of arsenic. People need concrete information about environmental risk at both personal and environmental-systems levels to promote a comprehensive understanding and response. The CSM explained responses to arsenic information and may have application to other environmental risks.     

Empirical Bayes and Adjusted Estimates Approach to Estimating the Relation of Mortality to Exposure of PM10

Forward Links to Citing Articles Retraction . Risk Analysis 25: 6, 1683
In the framework of the APHEIS program (Air Pollution and Health: A European Information System), a health impact assessment of air pollution in 26 European cities was performed for particles of an aerodynamic diameter less than or equal to 10 μm (PM₁₀). For short-term effects, it was based on overall estimates from the APHEA-2 project (Air Pollution and Health: A European Approach). These city-specific risk assessments require city-specific concentration-response functions, raising the question of which concentration-response is most appropriate. Estimates from city-specific models are more specific, but have greater uncertainty than those provided from multicity analyses. We compared several estimates derived from the city-specific analyses in cities that were part of the APHEA-2 project, as well as in a city that was not included in APHEA-2 but was part of the APHEIS project. These estimates were: the estimates from a local regression model, the adjusted estimates based on two significant effect modifiers identified through meta-regression models, and the city-specific empirical Bayes (shrunken) estimates and their underlying distribution. The shrunken and adjusted estimates were used to improve the estimation of city-specific concentration-response function. From these different estimates, attributable numbers of deaths per year were calculated. The advantages and limits of the different approaches are discussed through real data and in a simulation study.     

Assessment of the Effect of Population and Diary Sampling Methods on Estimation of School‐Age Children Exposure to Fine Particles

Population and diary sampling methods are employed in exposure models to sample simulated individuals and their daily activity on each simulation day. Different sampling methods may lead to variations in estimated human exposure. In this study, two population sampling methods (stratified‐random and random‐random) and three diary sampling methods (random resampling, diversity and autocorrelation, and Markov‐chain cluster [MCC]) are evaluated. Their impacts on estimated children's exposure to ambient fine particulate matter (PM_2.5) are quantified via case studies for children in Wake County, NC for July 2002. The estimated mean daily average exposure is 12.9 μg/m³ for simulated children using the stratified population sampling method, and 12.2 μg/m³ using the random sampling method. These minor differences are caused by the random sampling among ages within census tracts. Among the three diary sampling methods, there are differences in the estimated number of individuals with multiple days of exposures exceeding a benchmark of concern of 25 μg/m³ due to differences in how multiday longitudinal diaries are estimated. The MCC method is relatively more conservative. In case studies evaluated here, the MCC method led to 10% higher estimation of the number of individuals with repeated exposures exceeding the benchmark. The comparisons help to identify and contrast the capabilities of each method and to offer insight regarding implications of method choice. Exposure simulation results are robust to the two population sampling methods evaluated, and are sensitive to the choice of method for simulating longitudinal diaries, particularly when analyzing results for specific microenvironments or for exposures exceeding a benchmark of concern.     

考虑石油替代品和关税配额政策的石油储备模型研究

石油储备在国民经济的发展和国家经济安全中起着极为重要的作用,文章构建了具有石油替代品和关税配额政策影响的石油储备模型,分析了石油替代品和关税配额政策对石油储备规模、补仓速率和释放速率等一些储备策略的影响机理,并设置了三种不同的情景对模型进行了数值分析。结果表明:石油替代能力的减小将会导致国家最优石油储备规模的增大和石油释放速率的减小;石油进口配额的减小将会引起国家最优石油储备规模的增大、石油补仓速率的急剧减小和石油释放速率的小幅下降。     

A Framework for Measuring the Importance of Variables with Applications to Management Research and Decision Models*

In many disciplines, including various management science fields, researchers have shown interest in assigning relative importance weights to a set of explanatory variables in multivariable statistical analysis. This paper provides a synthesis of the relative importance measures scattered in the statistics, psychometrics, and management science literature. These measures are computed by averaging the partial contributions of each variable over all orderings of the explanatory variables. We define an Analysis of Importance (ANIMP) framework that reflects two desirable properties for the relative importance measures discussed in the literature: additive separability and order independence. We also provide a formal justification and generalization of the “averaging over all orderings” procedure based on the Maximum Entropy Principle. We then examine the question of relative importance in management research within the framework of the “contingency theory of organizational design” and provide an example of the use of relative importance measures in an actual management decision situation. Contrasts are drawn between the consequences of use of statistical significance, which is an inappropriate indicator of relative importance and the results of the appropriate ANIMP measures.