bluuebunny/crossref_metadata_2025 huggingface dataset:
A General Guideline for Management of Risk from Carcinogens1
Authors: Milvy Paul
Published: May 2006

A simple relationship is formulated that helps to discriminate between acceptable and unacceptable individual lifetime risks (RL) to populations that are exposed to chemical carcinogens. The relationship is an empirical one and is developed using objective risk data as well as subjective risk levels that have found substantial acceptance among those concerned with carcinogenic risk assessment issues. The expression sets acceptable levels of lifetime carcinogenic risk and is a function of the total population exposed to the carcinogen. Its use in risk assessment and risk management provides guidance in distinguishing those carcinogens that should be regulated because of the health hazard they pose from those whose regulation may not be needed.
Risk Homeostasis Theory and Traffic Accident Data
Authors: Evans Leonard
Published: May 2006

The risk homeostasis theory posits, in essence, that a control mechanism analogous to the thermal homeostatic system in warm‐blooded animals tends to keep risk per unit time constant, and, as a consequence, the number of traffic accidents per unit time of driving also tends to remain constant, essentially independent of changes in the traffic safety system. It is the purpose of the present research to examine the validity of this claim using a wide variety of traffic accident data. All the data examined are found to be incompatible with the risk homeostasis theory. The only specific field accident data offered in the literature to support the risk homeostasis theory are found to, in fact, refute the theory. The accident data provide evidence that a rich variety of user responses occur. While it is possible for users to collectively respond in such a way that safety benefits are completely cancelled, such a response is not particularly common; it is certainly not universally occurring, as suggested by the risk homeostasis theory. It is concluded that the risk homeostasis theory should be rejected because there is no convincing evidence supporting it and much evidence refuting it.
Asbestos Lung Cancer Risks: Comparison of Animal and Human Extrapolations1
Authors: Rowe James N. , Springer Janet A.
Published: May 2006

Using the most comprehensive inhalation study available, (Wagner, et al., 1974), the dose‐response effects of the four major types of asbestos fibers (amosite, anthophyllite, crocidolite, and chrysotile: Canadian, Rhodesian) for lung cancer have been determined. From linear regression analysis of the animal data and five human epidemiology studies giving a wide range of risk estimates, slopes of the curves have been determined and lifetime risk estimates made. Projected risks for rats are presented with and without surface area (s.a.) conversion factors. On the basis of cumulative exposure, the geometric mean of the point estimates for the human studies (0.0146) is quite close to the geometric mean of the animal data (0.0179 without s.a.; 0.0122 with s.a. calculations). These values also match quite well if one of the studies (McDonald, et al.) is eliminated (geometric mean = 0.031) due to qualitatively different exposure considerations (mining and milling vs. industrial environments). Animal risks based on a concentration per day basis (assuming an average 70‐year lifespan for humans) are below the lowest human estimate but within 5–6 fold (less) of the projected risk from nonsmoking asbestos workers (2.2time10‐3) using the Hammond et al. study.
New Approaches in Risk Assessment for Carcinogens
Authors: Perera Frederica
Published: May 2006

Methods are needed to improve the ability of biomonitoring and epidemiological studies to identify potential carcinogenic hazards and to quantify human risk. The limitations of pharmacokinetic models can be mitigated by the direct measurement of molecular markers of biologically effective dose of carcinogen. Parallel animal and human studies are recommended as a means of validating these markers.
The Spread of a PCB Spill on a Soil Surface
Authors: Eschenroeder Alan Q.
Published: May 2006

Determining the fate of an oil spill on soil is often the first step in analyzing the risks of human exposure to hazardous viscous liquids such as PCBs. The special surface properties of rigidity and porosity are not among the boundary conditions in previous analyses of spills on water. The present work solves the expressions of mass and momentum conservation using a perturbation approach. Using the example of an Aroclor 1254 spill to illustrate the approach, we find that the radius at the halt of spreading is roughly proportional to spill volume for large spills. Spreading halts when the infiltration equals the spill volume. The radial distribution of infiltration decreases gradually from its central maximum, but falls suddenly to zero approaching the outer edge. Sample results are plotted for Aroclor 1254 spills from 4 to 21 liters in volume.
Judgment and Analysis in Oil Spill Risk Assessment
Authors: Stewart Thomas R. , Leschine Thomas M.
Published: May 2006

The risk of oil spills is a major environmental issue in the siting of proposed coastal refineries, oil terminals, deepwater ports, and in the leasing of offshore lands for oil exploration and development. As with any kind of risk, oil spill risk assessment is inherently judgmental and no analytic method can eliminate the need for judgment. This paper compares representative examples of oil spill risk assessments with regard to decisions about data, variables, functional relations, and uncertainty. The comparison emphasizes the judgmental basis of analytic methods.
Benefit Analysis for Natural Hazards
Authors: Smith V. Kerry
Published: May 2006

The objective of this paper is to develop the ex ante perspective for benefit analysis with natural hazards. It defines an ex ante evaluation of the economic benefits that arise from policies designed to reduce either the risk of or the detrimental effects associated with a natural hazard. In the process the paper compares the ex ante and ex post perspectives and discusses the prospects for implementing the framework by measuring the valuation concepts that are developed.
Assigned Shares in Compensation for Radiation‐Related Cancers
Authors: Lagakos Stephen W. , Mosteller Frederick
Published: May 2006

At the request of Congress, a Working Group of the National Institutes of Health prepared radioepidemiologic tables which estimate the likelihood that cancer victims previously exposed to a dose of radiation developed their cancer as a result of this exposure. The ultimate purpose of the tables is to provide a scientific basis for determining compensation for such victims, and their use would represent a marked departure from the current tort system for deciding compensation. The preparation of radioepidemiologic tables requires extensive mathematical modeling because matters such as sex, size of dose, age at exposure, type of cancer, and age at diagnosis must be taken into account. The limited data require many assumptions about the quantitative relationship between radiation dose and the age‐specific incidence rate of cancer. After partitioning a population into reference sets based on age at exposure, size of dose, type of cancer, etc., an assigned share is computed for each reference set and then assigned to all of its members. The assigned share represents the fraction of the cancer cases in the reference set that are attributed to the radiation dose. Because the population can be partitioned in many ways, each individual's assigned share depends on the partition used and will change with different partitions. Options for modeling and limitations in epidemiologic data lead to considerable uncertainties in estimates of assigned shares that have been scientifically evaluated for the Working Group's tables. In contest, the uncertainties associated with the current approach for determining the likelihood that a claimant's cancer was caused by radiation have not been appraised, but are likely to be even greater than those associated with the Working Group's tables. One issue is how to use such tables to compensate victims. Some among many possibilities are: (i) to use them together with a compensation formula to determine the fraction of a standard award to be given; (ii) to use them as a starting value for the fraction, to be modified by an authority on the basis of additional information supplied by the claimant and defendant; and (iii) to use them as input to the present compensation system.
Tolerance for Environmental Health Risks: The Influence of Knowledge, Benefits, Voluntariness, and Environmental Attitudes
Authors: Baird Brian N. R.
Published: May 2006

This study examined factors affecting risk estimates and tolerance among persons directly exposed to environmental health risks. Data were gathered from questionnaires distributed at public hearings regarding proposed air pollution standards for an arsenic emitting copper smelter located in Tacoma, Washington. Approximately 80% of the area residents who attended the hearings completed the questionnaires, and the responses of 347 subjects were analyzed. Results indicated that informal risk estimates and risk tolerance were closely associated with judged benefits of the hazard source, acceptance or denial of vulnerability, judgments of exposure voluntariness, and environmental attitudes. Neither factual knowledge of formal risk estimates and proposed standards nor residential distance from the smelter was found to be closely related to risk tolerance or informal risk estimates. Implications of the results are discussed in relation to past and future studies of reactions to risk, and in relation to risk management policy and practice.
The Assessment of Probability Distributions from Expert Opinions with an Application to Seismic Fragility Curves
Authors: Mosleh Ali , Apostolakis George
Published: May 2006

A method is developed for estimating a probability distribution using estimates of its percentiles provided by experts. The analyst's judgment concerning the credibility of these expert opinions is quantified in the likelihood function of Bayes’Theorem. The model considers explicitly the random variability of each expert estimate, the dependencies among the estimates of each expert, the dependencies among experts, and potential systematic biases. The relation between the results of the formal methods of this paper and methods used in practice is explored. A series of sensitivity studies provides insights into the significance of the parameters of the model. The methodology is applied to the problem of estimation of seismic fragility curves (i.e., the conditional probability of equipment failure given a seismically induced stress).
Human Variability in Susceptibility to Toxic Chemicals— A Preliminary Analysis of Pharmacokinetic Data from Normal Volunteers
Authors: Hattis Dale , Erdreich Linda , Ballew Mary
Published: May 2006

The tenfold “uncertainty” factor traditionally used to guard against human interindividual differences in susceptibility to toxicity is not based on human observations. To begin to build a basis for quantifying an important component of overall variability in susceptibility to toxicity, a data base has been constructed of individual measurements of key pharmacokinetic parameters for specific substances (mostly drugs) in groups of at least five healthy adults. 72 of the 101 data sets studied were positively skewed, indicating that the distributions are generally closer to expectations for log‐normal distributions than for normal distributions. Measurements of interindividual variability in elimination half‐lives, maximal blood concentrations, and AUC (area under the curve of blood concentration by time) have median values of log10 geometric standard deviations in the range of 0.11–0.145. For the median chemical, therefore, a tenfold difference in these pharmacokinetic parameters would correspond to 7–9 standard deviations in populations of normal healthy adults. For one relatively lipophilic chemical, however, interindividual variability in maximual blood concentration and AUC was 0.4—implying that a tenfold difference would correspond to only about 2.5 standard deviations for those parameters in the human population. The parameters studied to date are only components of overall susceptibility to toxic agents, and do not include contributions from variability in exposure‐ and response‐determining parameters. The current study also implicitly excludes most human interindividual variability from age and illness. When these other sources of variability are included in an overall analysis of variability in susceptibility, it is likely that a tenfold difference will correspond to fewer standard deviations in the overall population, and correspondingly greater numbers of people at risk of toxicity.
Use of Risk Assessment Methods in the Certification of Decontaminated Buildings
Authors: Seiler Fritz A. , Davis Herbert T. , Kominsky John R. , Ronan Richard J. , Kowka Christopher D.
Published: May 2006

Accidental events such as fires, explosions, and leaks often result in large‐scale contaminations of buildings with toxic chemicals. After decontamination, the certification for original use requires testing for residual contamination. The two basic kinds of sampling plans in use up to recently both fall short of the required performance. Their deficiencies are analyzed in terms of the scientific questions implicit in both the sampling plan and the subsequent statistical evaluation. A sampling strategy of a new kind is proposed and discussed in the same context. It is motivated by concern for the long‐term safety of the building's occupants and is, therefore, based on factors important in risk assessment. Three different sampling plans are derived in the framework of this methodology, two of which have already been used in actual certification proceedings.
Error Propagation for Large Errors
Authors: Seiler Fritz A.
Published: May 2006

An essential facet of a risk assessment is the correct evaluation of uncertainties inherent in the numerical results. If the calculation is based on an explicit algebraic expression, an analytical treatment of error propagation is possible, usually as an approximation valid for small errors. In many instances, however, the errors are large and uncertain. It is the purpose of this paper to demonstrate that despite large errors, an analytical treatment is possible in many instances. These cases can be identified by an analysis of the algebraic structure and a detailed examination of the errors in input parameters and mathematical models. From a general formula, explicit formulas for some simple algebraic structures that occur often in risk assessments are derived and applied to practical problems.
Graphical Communication of Uncertain Quantities to Nontechnical People
Authors: Ibrekk Harald , Morgan M. Granger
Published: May 2006

Nine pictorial displays for communicating quantitative information about the value of an uncertain quantity, x, were evaluated for their ability to communicate x̄, p(x > a) and p(b > x > a) to well‐educated semi‐and nontechnical subjects. Different displays performed best in different applications. Cumulative distribution functions alone can severely mislead some subjects in estimating the mean. A “rusty” knowledge of statistics did not improve performance, and even people with a good basic knowledge of statistics did not perform as well as one would like. Until further experiments are performed, the authors recommend the use of a cumulative distribution function plotted directly above a probability density function with the same horizontal scale, and with the location of the mean clearly marked on both curves.
Risk Analysis of Terrorist Attacks
Authors: Martz Harry F. , Johnson Mark E.
Published: May 2006

A quantitative probabilistic/systems analysis model is described which is useful for allocating resources to safeguard valuable documents or materials in either a fixed‐site facility or a moving convoy against an overt terrorist attack. The model is also useful for ranking the sensitive areas at a site according to their survivability of a given hypothesized terrorist attempt. To compare various defense strategies and security configurations, the probability of a successful terrorist activity is computed based on event tree models of the site/security configuration. This calculation incorporates a realistic engagement model (in the event a guard force engages the terrorists prior to completion of their objective) and information on barrier penetration times (for example, distribution of the time to defeat a chain link fence or vault door, traverse an open area, and so forth). Two security analyses are described to illustrate the methodology. One example considers a terrorist attack on a convoy transporting a missile from a storage to a launch facility. The second example involves an attack on a munitions storage facility.
Risk—Its Priority and Probability: The Analytic Hierarchy Process
Authors: Saaty Thomas L.
Published: May 2006

Risk estimation involves priorities and probabilities which are themselves a form of priority of natural alternatives. This paper provides illustrations of how one can deal with risk and uncertainty using the Analytic Hierarchy Process, a new approach to measurement by ratio scales. The paper also includes a discussion of how to deal with risk strategies involving interdependence. Particular emphasis is made on the siting of nuclear power plants.
An Analysis of the Portfolio of Sites to Characterize for Selecting a Nuclear Repository
Authors: Keeney Ralph L.
Published: May 2006

The U.S. Department of Energy has selected three sites, from five nominated, to characterize for a nuclear repository to permanently dispose of nuclear waste. This decision was made without the benefit of an analysis of this “portfolio” problem. This paper analyzes different portfolios of three sites for simultaneous characterization and strategies for sequential characterization. Characterization of each site, which involves significant subsurface excavation, is now estimated to cost $1 billion. Mainly because of the high characterization costs, sequential characterization strategies are identified which are the equivalent of $1.7–2.0 billion less expensive than the selected DOE simultaneous characterization of the three sites. If three sites are simultaneously characterized, one portfolio is estimated to be the equivalent of $100–400 million better than the selected DOE portfolio. Because of these potential savings and several other complicating factors that may influence the relative desirability of characterization strategies, a thorough analysis of characterization strategies that addresses the likelihood of finding disqualifying conditions during site characterization, uncertainties, and dependencies in forecast site repository costs, preclosure and postclosure health and safety impacts, potential delays of both sequential and simultaneous characterization strategies, and the environmental, socioeconomic, and health and safety impacts of characterization activities is recommended.
Multiobjective Risk‐Impact Analysis Method
Authors: Leach Mark R. , Haimes Yacov Y.
Published: May 2006

This paper integrates two methodologies of risk and impact analysis—the partitioned multiobjective risk method (PMRM) and the multiobjective, multistage impact analysis method (MMIAM). The PMRM, in an effort to overcome the difficulties created by commensurating extreme events that have catastrophic impacts with those that have more frequent but less harmful consequences, introduces the use of conditional expectations for different regimes of probabilities and damages. The MMIAM is a multiobjective decisionmaking method for impact analysis which explicitly develops trade‐offs among different objectives at different stages or periods. Decision makers who must act under conditions of extreme risk and uncertainty often find that they are more interested in knowing “what not to do” than they are in optimizing their current objectives (the more traditional aim of decision‐making methodologies). This paper focuses on a way to answer their needs, in which major elements of both the PMRM and the MMIAM are combined in a new, integrated methodology, termed here the multiobjective risk‐impact analysis method (MRIAM). The new methodology incorporates risk and impact analysis within a dynamic multiobjective decision‐making framework. To demonstrate the usefulness of the integrated methodology, an example problem concerning the environmental effects of pollutant emissions over a number of years is formulated, solved, and analyzed.
Frequency‐Cost Curves and Derivative Risk Profiles
Authors: Reid Stuart G.
Published: May 2006

Frequency‐cost curves (used to describe risks and to prescribe limits on “acceptable risks”) are examined with regard to their information content. Frequency density functions, expected cost density functions and cumulative expected cost distribution functions (analogous to probability distribution functions) are proposed to describe explicitly the distributions of frequency and expected cost which are implicit in frequency‐cost curves. It is shown that frequency‐cost curves can conceal rare catastrophic events that are critically important with regard to expected costs. Therefore, curves of frequency density, expected cost density, and cumulative expected cost are recommended (instead of frequency‐cost curves) for the description of risks.
Risk Estimators for Radiation‐Induced Bone Marrow Syndrome Lethality in Humans
Authors: Scott Bobby R. , Hahn Fletcher F. , McClellan Roger O. , Seiler Fritz A.
Published: May 2006

This manuscript provides risk estimators for acute lethality from radiation‐induced injury to the bone marrow of humans after uniform total‐body exposure to low linear energy transfer (LET) radiation. The risk estimators are needed for nuclear disaster risk assessment. The approach used is based on the dose X, in units of D50 (i.e., the dose required for 50% lethality). Using animal data, it is demonstrated that the use of dose in units of D50 eliminates most of the variability associated with mammalian species, type of low‐LET radiation, and low‐LET dose rate. Animal data are used to determine the shape of the dose‐effect curve for marrow‐syndrome lethality in man and to develop a functional relationship for the dependence of the D50 on dose rate. The functional relationship is used, along with the Weibull model, to develop acute lethality risk estimators for complex temporal patterns of continuous exposure to low‐LET radiation. Animal data are used to test model predictions.
Incorporating Risk Assessment and Benefit‐Cost Analysis in Environmental Management1
Authors: Rycroft Robert W. , Regens James L. , Dietz Thomas
Published: May 2006

Using data from interviews with a key set of individuals at the U.S. Environmental Protection Agency, this study examines intraagency views about the incorporation of risk assessment and benefit‐cost analysis in environment management.
Issues in Qualitative and Quantitative Risk Analysis for Developmental Toxicology1
Authors: Kimmel Carole A. , Gaylor David W.
Published: May 2006

The qualitative and quantitative evaluation of risk in developmental toxicology has been discussed in several recent publications.(1–3) A number of issues still are to be resolved in this area. The qualitative evaluation and interpretation of end points in developmental toxicology depends on an understanding of the biological events leading to the end points observed, the relationships among end points, and their relationship to dose and to maternal toxicity. The interpretation of these end points is also affected by the statistical power of the experiments used for detecting the various end points observed. The quantitative risk assessment attempts to estimate human risk for developmental toxicity as a function of dose. The current approach is to apply safety (uncertainty) factors to die no observed effect level (NOEL). An alternative presented and discussed here is to model the experimental data and apply a safety factor to an estimated risk level to achieve an “acceptable” level of risk. In cases where the dose‐response curves upward, this approach provides a conservative estimate of risk. This procedure does not preclude the existence of a threshold dose. More research is needed to develop appropriate dose‐response models that can provide better estimates for low‐dose extrapolation of developmental effects.
Quantification of the Genetic Risk of Environmental Mutagens
Authors: Ehling U. H.
Published: May 2006

Screening methods are used for hazard identification. Assays for heritable mutations in mammals are used for the confirmation of short‐term test results and for the quantification of the genetic risk. There are two main approaches in making genetic risk estimates. One of these, termed the direct method, expresses risk in terms of the expected frequency of genetic changes induced per unit dose. The other, referred to as the doubling dose method or the indirect method, expresses risk in relation to the observed incidence of genetic disorders now present in man. The indirect method uses experimental data only for the calculation of the doubling dose. The quality of the risk estimation depends on the assumption of persistence of the induced mutations and the ability to determine the current incidence of genetic diseases. The difficulties of improving the estimates of current incidences of genetic diseases or the persistence of the genes in the population led us to the development of an alternative method, the direct estimation of the genetic risk. The direct estimation uses experimental data for the induced frequency for dominant mutations in mice. For the verification of these quantifications one can use the data of Hiroshima and Nagasaki. According to the estimation with the direct method, one would expect less than 1 radiation‐induced dominant cataract in 19,000 children with one or both parents exposed. The expected overall frequency of dominant mutations in the first generation would be 20–25, based on radiation‐induced dominant cataract mutations. It is estimated that 10 times more recessive than dominant mutations are induced. The same approaches can be used to determine the impact of chemical mutagens.
A Cellular Dynamics Model of Experimental Bladder Cancer: Analysis of the Effect of Sodium Saccharin in the Rat
Authors: Ellwein Leon B. , Cohen Samuel M.
Published: May 2006

To make the methodology of risk assessment more consistent with the realities of biological processes, a computer‐based model of the carcinogenic process may be used. A previously developed probabilistic model, which is based on a two‐stage theory of carcinogenesis, represents urinary bladder carcinogenesis at the cellular level with emphasis on quantification of cell dynamics: cell mitotic rates, cell loss and birth rates, and irreversible cellular transitions from normal to initiated to transformed states are explicitly accounted for. Analyses demonstrate the sensitivity of tumor incidence to the timing and magnitude of changes to these cellular variables. It is demonstrated that response in rats following administration of nongenotoxic compounds, such as sodium saccharin, can be explained entirely on the basis of cytotoxicity and consequent hyperplasia alone.
Estimation of Human Exposure from Fish Contaminated with Dioxins and Furans Emitted by a Resource‐Recovery Facility
Authors: Goeden Helen M. , Smith Allan H.
Published: May 2006

Ingestion of contaminated fish can be an important human exposure pathway for dioxins and furans emitted from waste incineration plants. A new method for calculating fish contamination resulting from dioxin and furan emissions has been developed to overcome some of the problems of those currently used. The method is based on evidence that the major determinant of fish dioxin and furan uptake is sediment concentrations. Only two steps are necessary to calculate fish tissue levels. Step 1: Calculation of the concentration of dioxins and furans in particulate matter entering the lake or pond, and hence, the resulting sediment concentration. Step 2: Calculation of fish concentrations utilizing fish‐to‐sediment ratios for the various dioxin and furan isomers.
Nuclear Safety in Ontario: A Critical Review of Quantitative Analyses
Authors: Oxman A.D. , Shannon H.S. , Garland W.J. , Torrance G.W.
Published: May 2006

In this article quantitative analyses of CANDU nuclear generating stations are evaluated using an explicit set of criteria derived from a decision‐analytic framework. A systematic search was made for relevant analyses, including both risk assessments and economic analyses. Only a small number of scientifically sound quantitative analyses that are being used to make decisions about specific safety measures or projects were located. The availability of scientifically sound quantitative data for making major energy policy decisions is even more limited, and what is available has major shortcomings. The province of Ontario is now heavily dependent on nuclear energy. Given the uncertainties surrounding the health, environmental, economic, and social consequences of nuclear energy, there is a need to assemble the information that is available within a comprehensive decision‐making framework, and to decide future energy policies for the province in a public forum from a societal perspective.
The Ocean Ranger Oil Rig Disaster: A Risk Analysis
Authors: Heising Carolyn D. , Grenzebach William S.
Published: May 2006

This paper analyzes quantitatively the design of the Ocean Ranger off‐shore oil drilling rig that capsized and sank on February 15, 1982 off the coast of Canada. A review of the actual disaster is also included based on evidence gathered by the Canadian Royal Commission. The risk analysis includes the construction of a failure modes and effects analysis (FMEA) table, a fault tree, and a quantitative evaluation including common cause failure of the rig components. In the case of the Ocean Ranger ballast control system, it was shown that the analysis was able both to successfully model the catastrophic system failure of the portholes, the actual system failure mode, and identify a common cause failure mode of the pump system. This study represents an application of reliability and risk techniques to the oil services industry.
Decentralizing Risk Analysis in Large Engineered Systems: An Approach to Articulating Technical and Socioorganizational Dimensions of System Performance1
Authors: Mays Claire M. , Poumadère Marc
Published: May 2006

Nuclear power production in France, as the domain of one national utility and one reactor builder, has a standardized profile of technical installations, safety procedures, and personnel qualifications. Despite this relative homogeneity, discrepancies are observed from one production unit to another, notably in the area of worker‐safety performance. There is a strong implication for risk analysis: varying performance cannot be attributed solely to the technical dimensions of equipment, procedures, and human skills. The authors retain as a working hypothesis that safety performance is an outcome of interactions between technical and organizational factors. Traditional risk analysis appears to be underequipped to represent such interactions. The notion of decentralized risk analysis (DRA) is introduced as a means of achieving this goal. A program of applied research carried out in a NPP facility is presented. It aims at increasing, across plant work structure, knowledge and control of these interactions specific to the given context. Systematic measurements and feedback of social representations are performed, using a three‐dimensional factor space of individual and organizational values. Direct involvement of the total plant population, transfer of analytic tools, methodological continuity, interactive elaboration of data, coordination of different levels of findings with operations, follow‐up and feedback of measured change, are the main features of this DRA process. In the case cited, improvement observed in safety performance parallels changes in measured social representations. The value of DRA for articulating technical and organizational dimensions of risk, and for integrating information into decision‐making, is argued.
Limitations on the Usefulness of Risk Assessment
Authors: Roberts Lewis E. J. , Hayns Michael R.
Published: May 2006

Quantitative risk assessment (QRA) is now regarded as an essential component in the analysis of risks arising from installations classified as major hazards. The purpose of this paper is to discuss the value of the results in decision‐making in practical situations. The use made of QRA in three contrasting cases which came to extensive public attention in the U.K. is examined. The first concerned an extension of domestic development near a chemical factory; the second an extension to a large petrochemical complex; and the third to a proposal to build a pressurized water reactor. The two public inquiries concerned with the chemical industry accepted standards of individual risk which were comparable to the risks from everyday accidents; the evidence of societal risk that could arise from major accidents at the petrochemical complex was compared with that of a local natural hazard — flooding. Higher standards of individual safety were set in the inquiry into the PWR proposal, and the definition of societal risk was debated at length. The QRA results were analyzed to show that risks arising from accidents were lower than those from normal operations, but they were used explicitly as a check on the overall safety of the design and of the operational and licensing organization. Such qualitative examination will always be required in addition to QRA. All these inquiries were faced with considerable technical argument. There is a need for the full details of risk calculations to be clear. The usefulness of QRA as an input to decision‐making would be much enhanced if the technical points at issue could be clarified outside a formal public inquiry. In addition, there are some technical questions which apply to many installations. There should be better mechanisms of technical debate to achieve a measure of agreement on the optimum methods of calculation in these cases, and some possibilities are explored.
Dermal Uptake of Organic Chemicals from a Soil Matrix
Authors: McKone Thomas E.
Published: May 2006

Uptake of chemicals from soil on human skin is considered. Based on a review of literature on the structure of human skin, the processes by which chemicals pass through this boundary, and experiments that reveal the rate and magnitude of this transport process; a two‐layer model is presented for estimating how chemical uptake through the stratum corneum depends on chemical properties, skin properties, soil properties and exposure conditions. The model is applied to two limiting scenarios—(1) continuous deposition and removal of soil on the skin surface and (2) a one‐time deposition of soil onto the skin surface. The fraction of soil‐bound chemical that passes through the stratum corneum is dependent on the skin‐soil layer thickness; the dimensionless Henry's law constant, Kh and the octanol‐water partition coefficient, Kow of the soil‐bound chemical. The nature of this dependence is discussed.
Comparison of the Cancer Risk of Methylene Chloride Predicted from Animal Bioassay Data with the Epidemiologic Evidence
Authors: Tollefson Linda , Lorentzen Ronald J. , Brown Robert N. , Springer Janet A.
Published: May 2006

Methylene chloride has been shown to be a lung and liver carcinogen in the mouse; yet, the current epidemiologic data show no adverse health effects associated with chronic exposure to this compound. Hearne et al.(1) have compared the results of a large mortality study on occupational exposure to methylene chloride to the human risk predictions based on the rodent bioassay to point out the inconsistency between the animal toxicologie and human epidemiologic data. The maximum number of lung and liver cancers predicted due to methylene chloride exposure based on the rodent bioassay data was 24 compared to 14 deaths from these cancers actually observed in the Hearne et al.(1) epidemiology study. We assess the minimum risk detectable by the human study in order to calculate the upperbound potency of methylene chloride and compare it to the potency derived from the bioassay data. Results from the epidemiology study imply an upperbound potency of 1.5 × 10−2 per ppm, compared to 1.4 × 10−2 per ppm calculated using the most conservative analysis of the animal data. We conclude that the negative epidemiology study of Hearne et al. is not sufficiently powerful to show that the risk is inconsistent with the human risk estimated by modeling the rodent bioassay data. Specifically, the doses to which the workers were exposed, the population studied, and the latency period were not adequate to determine that the risks are outside the bounds of the risk estimates predicted by low‐dose modeling of the animal data.
Uncertainties in Pharmacokinetic Modeling for Perchloroethylene. I. Comparison of Model Structure, Parameters, and Predictions for Low‐Dose Metabolism Rates for Models Derived by Different Authors
Authors: Hattis Dale , White Paul , Marmorstein Laura , Koch Paul
Published: May 2006

In recent years physiologically based pharmacokinetic models have come to play an increasingly important role in risk assessment for carcinogens. The hope is that they can help open the black box between external exposure and carcinogenic effects to experimental observations, and improve both high‐dose to low‐dose and interspecies projections of risk. However, to date, there have been only relatively preliminary efforts to assess the uncertainties in current modeling results. In this paper we compare the physiologically based pharmacokinetic models (and model predictions of risk‐related overall metabolism) that have been produced by seven different sets of authors for perchloroethylene (tetrachloroethylene). The most striking conclusion from the data is that most of the differences in risk‐related model predictions are attributable to the choice of the data sets used for calibrating the metabolic parameters. Second, it is clear that the bottom‐line differences among the model predictions are appreciable. Overall, the ratios of low‐dose human to bioassay rodent metabolism spanned a 30‐fold range for the six available human/rat comparisons, and the seven predicted ratios of low‐dose human to bioassay mouse metabolism spanned a 13‐fold range. (The greater range for the rat/human comparison is attributable to a structural assumption by one author group of competing linear and saturable pathways, and their conclusion that the dangerous saturable pathway constitutes a minor fraction of metabolism in rats.) It is clear that there are a number of opportunities for modelers to make different choices of model structure, interpretive assumptions, and calibrating data in the process of constructing pharmacokinetic models for use in estimating “delivered” or “biologically effective” dose for carcinogenesis risk assessments. We believe that in presenting the results of such modeling studies, it is important for researchers to explore the results of alternative, reasonably likely approaches for interpreting the available data—and either show that any conclusions they make are relatively insensitive to particular interpretive choices, or to acknowledge the differences in conclusions that would result from plausible alternative views of the world.
Distribution Analyzer and Risk Evaluator (DARE) Using Fault Trees
Authors: Tulsiani Vijay , Haimes Yacov Y. , Li Duan
Published: May 2006

Risk and uncertainty are integral parts of modern technology, and they must be managed effectively to allow the development of reliable, high‐quality products. Because so many facets of technology and society involve risk and uncertainty, it is essential that risk management be handled in a systematic manner. Fault‐tree analysis is one of the principal methods used in the analysis of systems’safety. Its detailed and systematic deductive structure makes it a valuable tool for design and diagnostic purposes. Point probability and the minimization of the expected failure probability have, until recently, dominated fault‐tree analysis. A methodology that incorporates uncertainty analysis, conditional expected risk, and multiple objectives with fault‐tree analysis is presented. A computer software package termed the “Distribution Analyzer and Risk Evaluator (DARE) Using Fault Trees,” which translates the new methodology into a working decision‐support system, is developed. DARE Using Fault Trees is a flexible computer code that is capable of analyzing the risk of the overall system in terms of the probability density function of failure probability. Emphasis is placed on the uncertainty and risk of extreme events. A comparative study between existing codes for fault‐tree analysis and DARE demonstrates the strengths of the methodology. A case study for NASA's solid rocket booster is used to perform the comparative analysis.
Exposure Assessment: Methods of Analysis for Environmental Carcinogens1
Authors: Jayanty R.K.M. , Peterson Max R. , Naugle Dennis F. , Berry Michael A.
Published: May 2006

Human populations are exposed to environmental carcinogens in both indoor and outdoor atmospheres. Recent studies indicate that pollutant concentrations are generally higher in indoor atmospheres than in outdoor. Environmental pollutants that occur in indoor air from a variety of sources include radon, asbestos, organic and inorganic compounds, and certain particles (e.g., tobacco smoke). Some of the gases or vapors are adsorbed on suspended particulate matter, whereas others exist entirely in the gas phase or are distributed between the latter and a particle‐bound state. Because of differences in chemical and physical properties, each class of carcinogens generally requires different sampling and analytical methods. In addition, a single indoor environment may contain a wide variety of air pollutants from different sources. Unfortunately, no single best approach currently exists for the quantitative determination of such complex mixtures and, for practical reasons, only the more toxic or the more abundant pollutants are usually measured. This paper summarizes the currently available monitoring methods for selected environmental pollutants found in indoor atmospheres. In addition, some possible sources for those pollutants are identified.
The Fallacy of Ranking Possible Carcinogen Hazards Using the TD50
Authors: Wartenberg Daniel , Gallo Michael A.
Published: May 2006

Ames et al. have proposed a new model for evaluating carcinogenic hazards in the environment. They advocate ranking possible carcinogens on the basis of the TD50, the estimated dose at which 50% of the test animals would get tumors, and extrapolating that ranking to all other doses. We argue that implicit in this methodology is a simplistic and inappropriate statistical model. All carcinogens are assumed to act similarly and to have dose‐response curves of the same shape that differ only in the value of one parameter. We show by counterexample that the rank order of cancer potencies for two chemicals can change over a reasonable range of doses. Ames et al.'s use of these TD50 ranks to compare the hazards from low level exposures to contaminants in our food and environment is wholly inappropriate and inaccurate. Their dismissal of public health concern for environmental exposures, in general, based on these comparisons, is not supported by the data.
Software Listings
Authors: Moskowitz Paul D.
Published: May 2006

AIRDOS‐PC Barry Parks (702) 798–2443, U.S. Environmental Protection Agency, Office of Radiation Programs, Las Vegas Facility, P.O. Box 98517, Las Vegas, Nevada 89193‐8517.
Exposure to Formaldehyde in Indoor Air
Authors: Gammage Richard B.
Published: May 2006

Trends in formaldehyde concentrations to which residents are exposed are reviewed, as are the means for assessing these exposures. Concentrations as high as a few ppm encountered in manufactured housing during the 1970s were eliminated after the Housing and Urban Development (HUD) 1984 ruling came into effect. The pressed‐wood product industry, and its trade organizations, have made concerted efforts to comply with the ruling. Moreover, they have imposed additional voluntary product standards upon themselves intended to be applicable to a range of pressed‐wood products wider than that defined in the HUD standard. Quarterly product testing on arbitrarily selected products shows a general lowering of emission rates with only a few percent of products now being above the HUD level. Measurement of ambient indoor levels of formaldehyde has been largely replaced by testing to assure conformance to product standards. The loweremitting products on the market, if used in mobile home construction and furnishing, will expectantly produce formaldehyde levels not exceeding 0.1 ppm, except under conditions of unusually high temperature and humidity. Recent studies implicate household dust as a significant carrier of bound formaldehyde. In a few instances, old urea‐formaldehyde cavity wall insulation has become friable and particles have blown into living areas. Future health assessments might need to consider this additional pathway of potential exposure.
Quantitative Cancer Risk Estimation for Formaldehyde
Authors: Starr Thomas B.
Published: May 2006

Of primary concern are irreversible effects, such as cancer induction, that formaldehyde exposure could have on human health. Dose‐response data from human exposure situations would provide the most solid foundation for risk assessment, avoiding problematic extrapolations from the health effects seen in nonhuman species. However, epidemiologic studies of human formaldehyde exposure have provided little definitive information regarding dose‐response. Reliance must consequently be placed on laboratory animal evidence. An impressive array of data points to significantly nonlinear relationships between rodent tumor incidence and administered dose, and between target tissue dose and administered dose (the latter for both rodents and Rhesus monkeys) following exposure to formaldehyde by inhalation. Disproportionately less formaldehyde binds covalently to the DNA of nasal respiratory epithelium at low than at high airborne concentrations. Use of this internal measure of delivered dose in analyses of rodent bioassay nasal tumor response yields multistage model estimates of low‐dose risk, both point and upper bound, that are lower than equivalent estimates based upon airborne formaldehyde concentration. In addition, risk estimates obtained for Rhesus monkeys appear at least 10‐fold lower than corresponding estimates for identically exposed Fischer‐344 rats.