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Uncertainty Factors (uncertainty + factor)

Distribution by Scientific Domains

Medical Sciences	45%
Engineering	18%

Selected Abstracts

Impact of inter-individual differences in drug metabolism and pharmacokinetics on safety evaluation

FUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 6 2004
J.L.C.M. Dorne
Abstract Safety evaluation aims to assess the dose,response relationship to determine a dose/level of exposure for food contaminants below which no deleterious effect is measurable that is ,without appreciable health risk' when consumed daily over a lifetime. These safe levels, such as the acceptable daily intake (ADI) have been derived from animal studies using surrogates for the threshold such as the no-observed-adverse-effect-level (NOAEL). The extrapolation from the NOAEL to the human safe intake uses a 100-fold uncertainty factor, defined as the product of two 10-fold factors allowing for human variability and interspecies differences. The 10-fold factor for human variability has been further subdivided into two factors of 100.5 (3.16) to cover toxicokinetics and toxicodynamics and this subdivsion allows for the replacement of an uncertainty factor with a chemical-specific adjustment factor (CSAF) when compound-specific data are available. Recently, an analysis of human variability in pharmacokinetics for phase I metabolism (CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4, hydrolysis, alcohol dehydrogenase), phase II metabolism (N-acetyltransferase, glucuronidation, glycine conjugation, sulphation) and renal excretion was used to derive pathway-related uncertainty factors in subgroups of the human population (healthy adults, effects of ethnicity and age). Overall, the pathway-related uncertainty factors (99th centile) were above the toxicokinetic uncertainty factor for healthy adults exposed to xenobiotics handled by polymorphic metabolic pathways (and assuming the parent compound was the proximate toxicant) such as CYP2D6 poor metabolizers (26), CYP2C19 poor metabolizers (52) and NAT-2 slow acetylators (5.2). Neonates were the most susceptible subgroup of the population for pathways with available data [CYP1A2 and glucuronidation (12), CYP3A4 (14), glycine conjugation (28)]. Data for polymorphic pathways were not available in neonates but uncertainty factors of up to 45 and 9 would allow for the variability observed in children for CYP2D6 and CYP2C19 metabolism, respectively. This review presents an overview on the history of uncertainty factors, the main conclusions drawn from the analysis of inter-individual differences in metabolism and pharmacokinetics, the development of pathway-related uncertainty factors and their use in chemical risk assessment. [source]

Survey of methodologies for developing media screening values for ecological risk assessment

INTEGRATED ENVIRONMENTAL ASSESSMENT AND MANAGEMENT, Issue 4 2005
Mace G. Barron
Abstract This review evaluates the methodologies of 13 screening value (SV) compilations that have been commonly used in ecological risk assessment (ERA), including compilations from state and U.S. federal agencies, the Oak Ridge National Laboratory (ORNL), Canada, The Netherlands, and Australia. The majority of surfacewater SVs were primarily derived for the protection of aquatic organisms using 2 approaches: (1) a statistical assessment of toxicity values by species groupings, such as "ambient water quality criteria," or (2) extrapolation of a lowest observed adverse effect level determined from limited toxicity data using an uncertainty factor. Sediment SVs were primarily derived for the protection of benthic invertebrates using 2 approaches: (1) statistical interpretations of databases on the incidence of biological effects and chemical concentrations in sediment, or (2) values derived from equilibrium partitioning based on a surfacewater SV. Soil SVs were derived using a diversity of approaches and were usually based on the lowest value determined from soil toxicity to terrestrial plants or invertebrates and, less frequently, from modeled, incidental soil ingestion or chemical accumulation in terrestrial organisms. The various SV compilations and methodologies had varying levels of conservatism and were not consistent in the pathways and receptors considered in the SV derivation. Many SVs were derived from other compilations and were based on outdated values, or they relied on only older toxicity data. Risk assessors involved in ERA should carefully evaluate the technical basis of SVs and consider the uncertainty in any value used to determine the presence or absence of risk and the need for further assessment. [source]

Asbestos fiber concentration in the area surrounding a former asbestos cement plant and excess mesothelioma deaths in residents

AMERICAN JOURNAL OF INDUSTRIAL MEDICINE, Issue 10 2009
Shinji Kumagai D Eng
Abstract Background Many persons who had lived near a former asbestos cement plant (AC plant) died from mesothelioma in Amagasaki city, Japan. Methods Asbestos fiber concentration in the area surrounding the AC plant was estimated so that the female mesothelioma death number predicted by a mathematical model was the same as the observed excess death number. We used the estimated asbestos fiber concentration to predict the excess mesothelioma deaths from 1970 to 2049. Results In a grid just south of the AC plant, the fiber concentration was estimated to be more than 3,f/ml for KM (asbestos potency factor for mesothelioma) of 7.75,×,10,9. An uncertainty factor of five yields a KM range 1.55,×,10,9 to 38.8,×,10,9; these in turn correspond to fiber concentrations of 15 and 0.6,f/ml. For KM,=,7.75,×,10,9, grid units with higher fiber concentrations than 0.01,f/ml were estimated to extend 4.1,km (95% CI: 3.8,4.4,km) south-southwest of the plant. Over the 80-year study period (1970 to 2049), we predicted that the exposure under study will cause 346 excess mesothelioma deaths with range of 296 to 382 deaths. Conclusions This prediction suggests that considerable medical resources will be needed through 2049 as a result of past asbestos exposure in this region. Am. J. Ind. Med. 52:790,798, 2009. © 2009 Wiley-Liss, Inc. [source]

A Grid-enabled problem-solving environment for advanced reservoir uncertainty analysis

CONCURRENCY AND COMPUTATION: PRACTICE & EXPERIENCE, Issue 18 2008
Zhou Lei
Abstract Uncertainty analysis is critical for conducting reservoir performance prediction. However, it is challenging because it relies on (1) massive modeling-related, geographically distributed, terabyte, or even petabyte scale data sets (geoscience and engineering data), (2) needs to rapidly perform hundreds or thousands of flow simulations, being identical runs with different models calculating the impacts of various uncertainty factors, (3) an integrated, secure, and easy-to-use problem-solving toolkit to assist uncertainty analysis. We leverage Grid computing technologies to address these challenges. We design and implement an integrated problem-solving environment ResGrid to effectively improve reservoir uncertainty analysis. The ResGrid consists of data management, execution management, and a Grid portal. Data Grid tools, such as metadata, replica, and transfer services, are used to meet massive size and geographically distributed characteristics of data sets. Workflow, task farming, and resource allocation are used to support large-scale computation. A Grid portal integrates the data management and the computation solution into a unified easy-to-use interface, enabling reservoir engineers to specify uncertainty factors of interest and perform large-scale reservoir studies through a web browser. The ResGrid has been used in petroleum engineering. Copyright © 2008 John Wiley & Sons, Ltd. [source]

Principles of risk assessment for determining the safety of chemicals: Recent assessment of residual solvents in drugs and di(2-ethylhexyl) phthalate

CONGENITAL ANOMALIES, Issue 2 2004
Ryuichi Hasegawa
ABSTRACT Risk assessment of chemicals is essential for the estimation of chemical safety, and animal toxicity data are typically used in the evaluation process, which consists of hazard identification, dose,response assessment, exposure assessment, and risk characterization. Hazard identification entails the collection of all available toxicity data and assessment of toxicity endpoints based on findings for repeated dose toxicity, carcinogenicity or genotoxicity and species-specificity. Once a review is compiled, the allowable lifetime exposure level of a chemical is estimated from a dose,response assessment based on several measures. For non-carcinogens and non-genotoxic carcinogens, the no-observed-adverse-effect-level (NOAEL) is divided by uncertainty factors (e.g. with environmental pollutants) or safety factors (e.g. with food additives) to derive a tolerable daily intake (TDI) or acceptable daily intake (ADI), respectively. These factors include interspecies and individual differences, duration of exposure, quality of data, and nature of toxicity such as carcinogenicity or neurotoxicity. For genotoxic carcinogens, low dose extrapolation is accomplished with mathematical modeling (e.g. linearized multistage model) from the point of departure to obtain exposure levels that will be associated with an excess lifetime cancer risk of a certain level. Data for levels of chemicals in food, water and air, are routinely used for exposure assessment. Finally, risk characterization is performed to ensure that the established ,safe' level of exposure exceeds the estimated level of actual exposure. These principles have led to the evaluation of several existing chemicals. To establish a guideline for residual solvents in medicine, the permitted daily exposure (PDE), equivalent to TDI, of N,N-dimethylformamide was derived on the basis of developmental toxicity (malformation) and of N-methylpyrrolidone on the basis of the developmental neurotoxicity. A TDI for di(2-ethylhexyl)phthalate was derived from assessment of testicular toxicity. [source]

Impact of inter-individual differences in drug metabolism and pharmacokinetics on safety evaluation

Optimized damage detection of steel plates from noisy impact test

INTERNATIONAL JOURNAL FOR NUMERICAL METHODS IN ENGINEERING, Issue 7 2006
G. Rus
Abstract Model-based non-destructive evaluation proceeds measuring the response after an excitation on an accessible area of the structure. The basis for processing this information has been established in recent years as an iterative scheme that minimizes the discrepancy between this experimental measurement and sequence of measurement trials predicted by a numerical model. The unknown damage that minimizes this discrepancy by means of a cost functional is to be found. The damage location and size is quantified and sought by means of a well-conditioned parametrization. The design of the magnitude to measure, its filtering for reducing noise effects and calibration, as well as the design of the cost functional and parametrization, determines the robustness of the search to combat noise and other uncertainty factors. These are key open issues to improve the sensitivity and identifiability during the information processing. Among them, a filter for the cost functional is proposed in this study for maximal sensitivity to the damage detection of steel plate under the impact loading. This filter is designed by means of a wavelet decomposition together with a selection of the measuring points, and the optimization criterion is built on an estimate of the probability of detection, using genetic algorithms. Numerical examples show that the use of the optimal filter allows to find damage of a magnitude several times smaller. Copyright © 2006 John Wiley & Sons, Ltd. [source]

Testing and Implementing the Use of Multiple Bidding Rounds in Conservation Auctions: A Case Study Application

CANADIAN JOURNAL OF AGRICULTURAL ECONOMICS, Issue 3 2009
John Rolfe
Conservation auctions are typically framed as closed, discriminatory, single round, first-price auctions, and are based on the assumption that landholders will offer bids determined by their "independent private values." Where landholders are unfamiliar with conservation tender processes and the supply of environmental services, they may find it very difficult to construct bids in this way. Bid values may be influenced by other factors, such as concerns about "winner's curse," a desire to capture economic rent, and premiums for risk and uncertainty factors. Sealed, single round auctions may exacerbate information gaps and uncertainty factors because of the limited information flows compared to traditional market exchanges and open, ascending auctions. In this paper, the cost efficiencies of a multiple bidding round auction for landholder management actions are explored with the use of field experiments and a conservation auction. The case study application is improved grazing management in a rangeland area of Australia, where landholders are unfamiliar with supplying environmental services or conservation auctions. Results suggest that multiple round auctions may be associated with efficiency gains, particularly in initial rounds. Les enchères pour la conservation sont généralement des enchères au premier prix, à un tour, discriminatoires et par offre écrite. Elles reposent sur l'hypothèque que les offres des propriétaires fonciers refléteront leur ,valeur privée,. Lorsque les propriétaires fonciers ne sont pas familiers avec les processus d'enchères pour la conservation et la prestation de services environnementaux, ils peuvent éprouver de la difficultéà attribuer une valeur à leur offre. Cette valeur peut-être influencée par d'autres facteurs, tels que la crainte de la ,malédiction du vainqueur ,, le désir de réaliser une rente économique, les primes de risque et les facteurs d'incertitude. Les enchères scellées à un tour peuvent aggraver le manque d'information et les facteurs d'incertitude étant donné que les enchérisseurs disposent de peu d'information comparativement aux enchères ascendantes ouvertes traditionnelles. Dans le présent article, nous avons examiné, à l'aide d'expériences sur le terrain et d'enchères pour la conservation, l'efficacité-coût d'une enchère à tours multiples pour des mesures de gestion de la part de propriétaires fonciers. L'exercice visait à améliorer la gestion des pâturages d'un parcours naturel en Australie, où les propriétaires fonciers ne sont pas familiers avec la prestation de services environnementaux ni avec les enchères pour la conservation. Les résultats autorisent à penser que les enchères à tours multiples pourraient offrir des gains d'efficience, particulièrement durant les premiers tours. [source]