bluuebunny/crossref_metadata_2025 huggingface dataset:
A Physiologically Based Model for Gastrointestinal Absorption and Excretion of Chemicals Carried by Lipids
Authors: Roth William L. , Freeman Raymond A. , Wilson Alan G. E.
Published: May 2006

Pharmacokinetic models which incorporate independently measured anatomical characteristics and physiological flows have been widely used to predict the pharmacokinetic behavior of drugs, anesthetics, and other chemicals. Models appearing in the literature have included as many as 18,(1) or as few as 5 tissue compartments.(2) With the exception of the multiple‐compartment delay trains used by Bischoff(3) to model the delays inherent to the appearance of drug metabolites in bile and segments of the intestinal lumen, very little effort has been made to incorporate the available information on gastrointestinal anatomy and physiology into more accurate gastrointestinal absorption/enterohepatic recirculation submodels. Since several authors have shown that the lymphatic system is the most significant route of absorption for highly lipophilic chemicals, we have constructed a model of gastrointestinal absorption that emphasizes chylomicron production and transport as the most significant route of absorption for nonvolatile, lipophilic chemicals. The absorption and distribution of hexachlorobenzene after intravenous vs. oral dosing are used to demonstrate features of this model.
Dimensions of Risk Perception for Financial and Health Risks
Authors: Holtgrave David R. , Weber Elke U.
Published: May 2006

This study of 29 MBA students compares two models of risk perception for both financial and health risk stimuli. The first, inspired by Luce and Weber's Conjoint Expected Risk (CER) model, uses five dimensions: probability of gain, loss and status quo, and expected benefit and harm. The second, inspired by the Sovic et al. psychometric model, employs seven dimensions: voluntariness, dread, control, knowledge, catastrophic potential, novelty, and equity. The CER‐type model provided a better fit for most subjects and stimuli. Adding the psychological risk dimensions from the Slovic et al. model explained only modestly more variance. Relationships between the dimensions of the two models are described and the construction of a hybrid model explored.
Effects of the Mechanism of Receptor‐Mediated Gene Expression on the Shape of the Dose‐Response Curve
Authors: Kohn Michael C. , Portier Christopher J.
Published: May 2006

A mathematical model of receptor‐mediated gene expression that includes receptor binding of natural and xenobiotic ligands, protein synthesis and degradation, and metabolism of the xenobiotic ligand was created to identify the determinants of the shape of the dose‐response profile. Values of the model's parameters were varied to reflect alternative mechanisms of expression of the protein. These assumptions had dramatic effects on the computed response to a bolus dose of the xenobiotic ligand. If all processes in the model exhibit hyperbolic kinetics, the dose‐response curves can appear sigmoidal but actually be linear with a positive slope at low doses. The slope of the curve only approached zero at low dose, indicative of a threshold for response, if binding of the xenobiotic ligand to the receptor exhibited positive cooperativity (ligand binding at one site increases the affinity for ligand at another binding site on the receptor). Positive cooperativity in the rate‐limiting step of protein synthesis produced dose‐response curves which were “U‐shaped” at low doses, also indicative of a threshold. Positive cooperativity in the metabolism of the xenobiotic ligand produced dose‐response curves that increased more rapidly than linearly with increasing dose. The model illustrates the fact that response cannot be predicted from qualitative mechanistic arguments alone; any assessment of risk to health from xenobiotic chemicals must be based on a detailed quantitative examination of the kinetic behavior of each chemical species individually.
An Overview of the Report: Correlation Between Carcinogenic Potency and the Maximum Tolerated Dose: Implications for Risk Assessment
Authors: Krewski D. , Gaylor D .W. , Soms A. P. , Szyszkowicz M.
Published: May 2006

Current practice in carcinogen bioassay calls for exposure of experimental animals at doses up to and including the maximum tolerated dose (MTD). Such studies have been used to compute measures of carcinogenic potency such as the TD50 as well as unit risk factors such as q1* for predicting low‐dose risks. Recent studies have indicated that these measures of carcinogenic potency are highly correlated with the MTD. Carcinogenic potency has also been shown to be correlated with indicators of mutagenicity and toxicity. Correlation of the MTDs for rats and mice implies a corresponding correlation in TD50 values for these two species. The implications of these results for cancer risk assessment are examined in light of the large variation in potency among chemicals known to induce tumors in rodents.
Politics and Scientific Expertise: Scientists, Risk Perception, and Nuclear Waste Policy
Authors: Barke Richard P. , Jenkins‐Smith Hank C.
Published: May 2006

To study the homogeneity and influences on scientists’perspectives of environmental risks, we have examined similarities and differences in risk perceptions, particularly regarding nuclear wastes, and policy preferences among 1011 scientists and engineers. We found significant differences (p0.05)in the patterns of beliefs among scientists from different fields of research. In contrast to physicists, chemists, and engineers, life scientists tend to: (a)perceive the greatest risks from nuclear energy and nuclear waste management; (b)perceive higher levels of overall environmental risk; (c)strongly oppose imposing risks on unconsenting individuals; and (d)prefer stronger requirements for environmental management. On some issues related to priorities among public problems and calls for government action, there are significant variations among life scientists or physical scientists. We also found that–independently of field of research–perceptions of risk and its correlates are significantly associated with the type of institution in which the scientist is employed. Scientists in universities or state and local governments tend to see the risks of nuclear energy and wastes as greater than scientists who work as business consultants, for federal organizations, or for private research laboratories. Significant differences also are found in priority given to environmental risks, the perceived proximity of environmental disaster, willingness to impose risks on an unconsenting population, and the necessity of accepting risks and sacrifices.
Uncertainty in Cancer Risk Estimates
Authors: Gaylor David W. , Chen James J. , Sheehan Daniel M.
Published: May 2006

Several existing databases compiled by Gold et al.(1–3) for carcinogenesis bioassays are examined to obtain estimates of the reproducibility of cancer rates across experiments, strains, and rodent species. A measure of carcinogenic potency is given by the TD50 (daily dose that causes a tumor type in 50% of the exposed animals that otherwise would not develop the tumor in a standard lifetime). The lognormal distribution can be used to model the uncertainty of the estimates of potency (TD50) and the ratio of TD50's between two species. For near‐replicate bioassays, approximately 95% of the TD50's are estimated to be within a factor of 4 of the mean. Between strains, about 95% of the TD50's are estimated to be within a factor of 11 of their mean, and the pure genetic component of variability is accounted for by a factor of 6.8. Between rats and mice, about 95% of the TD50's are estimated to be within a factor of 32 of the mean, while between humans and experimental animals the factor is 110 for 20 chemicals reported by Allen et al.(4) The common practice of basing cancer risk estimates on the most sensitive rodent species‐strain‐sex and using interspecies dose scaling based on body surface area appears to overestimate cancer rates for these 20 human carcinogens by about one order of magnitude on the average. Hence, for chemicals where the dose‐response is nearly linear below experimental doses, cancer risk estimates based on animal data are not necessarily conservative and may range from a factor of 10 too low for human carcinogens up to a factor of 1000 too high for approximately 95% of the chemicals tested to date. These limits may need to be modified for specific chemicals where additional mechanistic or pharmacokinetic information may suggest alterations or where particularly sensitive subpopu‐lations may be exposed. Supralinearity could lead to anticonservative estimates of cancer risk. Underestimating cancer risk by a specific factor has a much larger impact on the actual number of cancer cases than overestimates of smaller risks by the same factor. This paper does not address the uncertainties in high to low dose extrapolation. If the dose‐response is sufficiently nonlinear at low doses to produce cancer risks near zero, then low‐dose risk estimates based on linear extrapolation are likely to overestimate risk and the limits of uncertainty cannot be established.
Learning from the Piper Alpha Accident: A Postmortem Analysis of Technical and Organizational Factors
Authors: Paté‐Cornell M. Elisabeth
Published: May 2006

The accident that occurred on board the offshore platform Piper Alpha in July 1988 killed 167 people and cost billions of dollars in property damage. It was caused by a massive fire, which was not the result of an unpredictable “act of God” but of an accumulation of errors and questionable decisions. Most of them were rooted in the organization, its structure, procedures, and culture. This paper analyzes the accident scenario using the risk analysis framework, determines which human decision and actions influenced the occurrence of the basic events, and then identifies the organizational roots of these decisions and actions. These organizational factors are generalizable to other industries and engineering systems. They include flaws in the design guidelines and design practices (e.g., tight physical couplings or insufficient redundancies), misguided priorities in the management of the tradeoff between productivity and safety, mistakes in the management of the personnel on board, and errors of judgment in the process by which financial pressures are applied on the production sector (i.e., the oil companies' definition of profit centers) resulting in deficiencies in inspection and maintenance operations. This analytical approach allows identification of risk management measures that go beyond the purely technical (e.g., add redundancies to a safety system) and also include improvements of management practices.
Risk Knowledge and Risk Attitudes Regarding Nuclear Energy Sources in Space
Authors: Maharik Michael , Fischhoff Baruch
Published: May 2006

A series of four studies examined the relationship between how much people know about the risks of using nuclear energy sources in space and how they feel about the technology. We found that the more people know, the more favorable they are—except for two groups of people selected from organizations with strong pro‐industry or pro‐environment positions. These results suggest that a technology will get a more favorable hearing if it can get its message out—providing that it has a legitimate story to tell and that the situation has not become too polarized already. The limits to these conclusions are discussed.
Incorporating Structural Models into Research on the Social Amplification of Risk: Implications for Theory Construction and Decision Making
Authors: Burns William J. , Slovic Paul , Kasperson Roger E. , Kasperson Jeanne X. , Renn Ortwin , Emani Srinivas
Published: May 2006

A comprehensive approach to managing risk must draw on both the descriptive insights of the behavioral sciences and the prescriptive clarity of the management sciences. On the descriptive side, this study develops structural models to explain how the impact upon society of an accident or other unfortunate event is influenced by the physical consequences of the event, perceived risk, media coverage, and public response. Our findings indicate that the media and public response play crucial roles in determining the impact of an unfortunate event. Public response appears to be determined by perceptions that the event was caused by managerial incompetence and is a signal of future risk. On the prescriptive side, we briefly discuss how these findings based upon structural models can be incorporated into a decision‐analytic procedure known as an influence diagram.
Social Equity and Environmental Risk1
Authors: Zimmerman Rae
Published: May 2006

Social equity has become an important concern of the environmental movement over the past decade. The equity issue is analyzed here for practically all of the inactive hazardous waste disposal sites on the National Priorities List (NPL) regulated under the Comprehensive Response Compensation and Liability Act and its 1986 Superfund Amendments and Reauthorization Act (CERCLA/ SARA). Two dimensions of equity are emphasized, namely, site location relative to the location of minority populations and the distribution of cleanup plans or Records of Decision (ROD) across communities with NPL sites that have different socioeconomic characteristics. With respect to site location, the percentage of Blacks and Hispanics aggregated at the Census Place or MCD level in communities with NPL sites was greater than is typical nationwide (largely attributable to the concentration of minority populations in a few large urban areas with NPL sites). In contrast, the percentage of the population below the poverty line in communities with NPL sites largely matched that of the nation as a whole. With respect to site cleanup, communities with relatively higher percentages of racial minority populations have fewer cleanup plans (Records of Decision signed) than other communities with NPL sites. Whether a ROD exists is influenced by when the site was designated for the NPL: sites designated earlier (prior to the SARA amendments of 1986) are more likely to have RODs, and also less likely to have high proportions of racial minority populations than sites designated later. This implies that initially the designation process may have resulted in NPL sites being located disproportionately in minority areas, but this pattern seems to be reversing itself in more recently designated sites. As with any statistical analysis, these findings are findings of association and not causality. Thus, racial and ethnic disproportionalities with respect to inactive hazardous waste site location seem to be concentrated in a relatively few areas. Disproportionalities with respect to cleanup do exist, but appear to be more a function of the nature of the process of designation of NPL sites in the early 1980s rather than a result of actions connected with cleanup plans per se. Further investigations are needed at alternative geographic scales to discern the sensitivity of patterns of inequity to distance from the sites.
Leukemia Risk Associated with Benzene Exposure in the Pliofilm Cohort: I. Mortality Update and Exposure Distribution
Authors: Paxton Mary B. , Chinchilli Vernon M. , Brett Susan M. , Rodricks Joseph V.
Published: May 2006

The National Institute of Occupational Safety and Health (NIOSH) recently completed a vital status update adding 6 years of observation on the rubber workers known as the Pliofilm cohort. Using traditional standardized mortality ratio (SMR) analysis, we investigate the impact of the additional information gathered in the NIOSH update. We also compare the effect of using three sets of job‐, plant‐, and year‐specific exposure estimates on the evaluation of benzene's leukemogenicity. The lack of any additional cases of multiple myeloma does not support trends toward elevated risks for this endpoint (as had been observed earlier), and there is no indication of increased incidences of solid tumors (as predicted by animal studies). Qualitatively, which exposure estimates are used does not alter the conclusions. The data added in the update did not greatly modify the estimated relative risk of leukemia associated with benzene exposure, but did confirm previous findings that occupational exposure to high concentrations had leukemogenic potential. The fact that leukemia has not been observed in any individual who started employment in Pliofilm production after 1950 suggests that the observed leukemia cases could be a response to very high levels of benzene exposure that occurred during the early years of this manufacturing process.
A Hint of Risk: Tradeoffs Between Quantitative and Qualitative Risk Factors
Authors: Gregory Robin , Lichtenstein Sarah
Published: May 2006

Risk‐perception research plays an active role in discussions of risk‐management alternatives. However, little guidance is provided regarding how public concerns should be weighed against other sources of cost and benefits. This paper reports the results of two experiments that measure tradeoffs among cost (in dollars), a quantitative risk measure (number of deaths or injuries), and several qualitative characteristics associated with perceived risk. Most subjects were willing to make the requested trade. However, the perceived risk information led others to reject the proposed technology.
Biological Models of Carcinogenesis and Quantitative Cancer Risk Assessment
Authors: Moolgavkar Suresh H.
Published: May 2006

Biologically‐based models of carcinogenesis were originally developed to explain certain quanti‐tative phenomena associated with carcinogenesis, and to provide a framework within which questions regarding the process could be addressed. Some limitations in the use of these models for quantitative cancer risk assessment are discussed.
The Risks of “Putting the Numbers in Context”: A Cautionary Tale
Authors: Freudenburg William R. , Rursch Julie A.
Published: May 2006

Despite the warnings of risk communication specialists, members of the technical community often urge that technological risks should be “put in context” by comparisons against risks that are more familiar. Little quantitative evidence is available on the actual behavioral consequences of such risk comparison efforts. In the present study, subjects were presented with two types of information about a hazardous waste incinerator–a simplified statistical summary and a comparison of incinerator risks against the risks of smoking. Statistical information led to a modest increase in the reported willingness to vote in favor of the incinerator in a community referendum, but the comparison against cigarettes led to a slight decrease in support; the difference between the two messages is statistically significant (p <.001). In combination with other results, this study's findings suggest that an implicit assumption of risk comparisons is in error: Opposition to controversial technologies may have little to do with citizens’ levels of information about technology, having more to do with citizens’ levels of trust in governmental and industrial actors.
Adjusting Triangular Distributions for Judgmental Bias
Authors: Hudak David G.
Published: May 2006

The common problem in risk analysis of correctly specifying a probability distribution about an estimate in situations when few data are available is examined. In the absence of data, experts are sometimes used to give a lowest and highest conceivable estimate. Triangular distributions are well suited for these situations when only a low, high, and most likely estimate are given. A problem, however, exists from the failure to adjust for biases when estimating extreme values. Various types of biases, which narrow the range of extreme estimates, are explored. A method is suggested for accounting for these biases by placing extreme estimates at specified percentile points rather than endpoints of a triangular distribution. Since most Monte Carlo models require end points of a triangular distribution, a closed‐form expression for identifying the end points given two percentile points and a most likely point is derived. This method has been used extensively in developing cost risk estimates for the Ballistic Missile Defense Organization (BMDO).
Multistage Models of Carcinogenesis: An Approximation for the Size and Number Distribution of Late‐Stage Clones
Authors: Sherman Claire D. , Portier Christopher J. , Kopp‐Schneider Annette
Published: May 2006

Multistage models have become the basic paradigm for modeling carcinogenesis. One model, the two‐stage model of carcinogenesis, is now routinely used in the analysis of cancer risks from exposure to environmental chemicals. In its most general form, this model has two states, an initiated state and a neoplastic state, which allow for growth of cells via a simple linear birth‐death process. In all analyses done with this model, researchers have assumed that tumor incidence is equivalent to the formation of a single neoplastic cell and the growth kinetics in the neoplastic state have been ignored. Some researchers have discussed the impact of this assumption on their analyses, but no formal methods were available for a more rigorous application of the birth‐death process. In this paper, an approximation is introduced which allows for the application of growth kinetics in the neoplastic state. The adequacy of the approximation against simulated data is evaluated and methods are developed for implementing the approximation using data on the number and size of neoplastic clones.
A Psychological Study of the Inverse Relationship Between Perceived Risk and Perceived Benefit
Authors: Alhakami Ali Siddiq , Slovic Paul
Published: May 2006

Judgments of risk and judgments of benefit have been found to be inversely related. Activities or technologies that are judged high in risk tend to be judged low in benefit, and vice versa. In the present study, we examine this inverse relationship in detail, using two measures of relationship between risk and benefit. We find that the inverse relationship is robust and indicative of a confounding of risk and benefit in people's minds. This confounding is linked to a person's overall evaluation of an activity or technology. Theoretical and practical implications of this risk‐benefit confounding are discussed.
Exposure Assessment: Then, Now, and Quantum Leaps in the Future
Authors: Keenan Russell E. , Finley Brent L. , Price Paul S.
Published: May 2006

Health risk assessments have become so widely accepted in the United States that their conclusions are a major factor in many environmental decisions. Although the risk assessment paradigm is 10 years old, the basic risk assessment process has been used by certain regulatory agencies for nearly 40 years. Each of the four components of the paradigm has undergone significant refinements, particularly during the last 5 years. A recent step in the development of the exposure assessment component can be found in the 1992 EPA Guidelines for Exposure Assessment. Rather than assuming worst‐case or hypothetical maximum exposures, these guidelines are designed to lead to an accurate characterization, making use of a number of scientific advances. Many exposure parameters have become better defined, and more sensitive techniques now exist for measuring concentrations of contaminants in the environnment. Statistical procedures for characterizing variability, using Monte Carlo or similar approaches, eliminate the need to select point estimates for all individual exposure parameters. These probabilistic models can more accurately characterize the full range of exposures that may potentially be encountered by a given population at a particular site, reducing the need to select highly conservative values to account for this form of uncertainty in the exposure estimate. Lastly, our awareness of the uncertainties in the exposure assessment as well as our knowledge as to how best to characterize them will almost certainly provide evaluations that will be more credible and, therein, more useful to risk managers. If these refinements are incorporated into future exposure assessments, it is likely that our resources will be devoted to problems that, when resolved, will yield the largest improvement in public health.
Issues in Ecological Risk Assessment: The CRAM Perspective
Authors: Barnthouse Lawrence W.
Published: May 2006

In 1989, a Committee on Risk Assessment Methodology (CRAM) was convened by the National Research Council (NRC) to identify and investigate important scientific issues in risk assessment. One of the first issues considered by the committee was the development of a conceptual framework for ecological risk assessment, defined as “the characterization of the adverse ecological effects of environmental exposures to hazards imposed by human activities.” Adverse ecological effects include all biological and nonbiological environmental changes that society perceives as undesirable. The committee's opinion was that a general framework is needed to define the relationship of ecological risk assessment to environmental management and to facilitate the development of uniform technical guidelines. The framework for human health risk assessment proposed by the NRC in 1983 was adopted as a starting point for discussion. CRAM concluded that, although ecological risk assessment and human health risk assessment differ substantially in terms of scientific disciplines and technical problems, the underlying decision process is the same for both. Therefore, CRAM recommended that the 1983 risk assessment framework be modified to accommodate both human health and ecological risk assessment. CRAM defined an integrated health/ ecological risk assessment framework consisting of the four components: Hazard Identification, Exposure Assessment, Exposure‐Response Assessment, and Risk Characterization. CRAM further provided recommendations on the scope of issues to be addressed in ecological risk assessment, critical research needs, and mechanisms for providing more detailed guidance on the scientific content of ecological risk assessments.
Analysis of the Multistep Process of Carcinogenesis Using Human Fibroblasts
Authors: McCormick J. Justin , Maher Veronica M.
Published: May 2006

Normal human cells in culture have never been neoplastically transformed by carcinogen exposure. One possible explanation is that the life span of such cells is too short for them to acquire the necessary changes. To test this hypothesis, we needed normal human cells with a greatly extended or an infinite life span. We transfected the v‐myc gene and a selectable marker into normal human fibroblasts, identified a drug‐resistant clone expressing v‐myc protein, and passaged the progeny of the clone until they senesced. A few cells continued to proliferate and gave rise to a diploid, infinite life span cell strain, MSU‐1.0, that has normal growth control and is nontumorigenic in athymic mice. Analysis showed that one more genetic change, in addition to unregulated expression of the v‐myc gene, was involved in generating MSU‐1.0 cells. They spontaneously gave rise to a variant strain, designated MSU‐1.1, that grows more rapidly and is less dependent on exogenous growth factors. Analysis showed that at least two additional changes were involved in generating this cell strain. It has a stable karyotype composed of 45 chromosomes, including two markers. Transfection of specific oncogenes was used to determine the number and nature of additional changes required to transform MSU‐1.1 cells into malignant cells. Analysis indicated that two changes were involved, but no change in karyotype. Exposure of MSU‐1.1 cells to a single carcinogen treatment, followed by selection for cells with the characteristics of oncogene‐trans‐formed MSU‐1.1 cells also yielded malignant human cells. We conclude that malignant transformation of normal human fibroblasts requires six or seven genetic changes, some of which involve suppressor genes.
Risk Communication in Environmental Restoration Programs
Authors: Bradbury Judith A.
Published: May 2006

The author advocates adoption of a convergence model in place of the traditional source‐receiver model of communication for communicating with members of the public who have a stake in remediation of a nearby site. The source‐receiver model conceives of communication as the transmission of a message from a risk management agency (sender) to a target audience of the public (receivers). The underlying theme is that the sender intends to change the perception of the receiver of either the issue or the sender of information. The author draws on her experience at a Department of Energy (DoE) site undergoing remediation to illustrate why the convergence model is more appropriate in the context of cleanup. This alternative model focuses on the Latin derivation of communication as sharing or making common to many (i.e., as involving a relationship between participants who engage in a process of communication). The focus appears to be consistent with recently issued DoE policy that calls for involving the public in identifying issues and problems and in formulating and evaluating decision alternatives in cleanup. By emphasizing context, process, and participants, as opposed to senders and receivers, the model identifies key issues to address in facilitating consensus concerning the risks of cleanup. Similarities between the institutional context of DoE and Department of Defense (DoD) suggest that a convergence model may also prove to be an appropriate conceptual foundation for risk communication at contaminated DoD sites.
Applications of Multinomial Dose‐Response Models in Developmental Toxicity Risk Assessment
Authors: Krewski D. , Zhu Y.
Published: May 2006

Reproductive and developmental anomalies induced by toxic chemicals may be identified using laboratory experiments with small mammalian species such as rats, mice, and rabbits. In this paper, dose‐response models for correlated multinomial data arising in studies of developmental toxicity are discussed. These models provide a joint characterization of dose‐response relationships for both embryolethality and teratogenicity. Generalized estimating equations are used for model fitting, incorporating overdispersion relative to the multinomial variation due to correlation among littermates. The fitted dose‐response models are used to estimate benchmark doses in a series of experiments conducted by the U.S. National Toxicology Program. Joint analysis of prenatal death and fetal malformation using an extended Dirichlet‐trinomial covariance function to characterize overdispersion appears to have statistical and computational advantages over separate analysis of these two end points. Benchmark doses based on overall toxicity are below the minimum of those for prenatal death and fetal malformation and may, thus, be preferred for risk assessment purposes.
Perception of Risks From Electromagnetic Fields: A Psychometric Evaluation of a Risk‐Communication Approach
Authors: MacGregor Donald G. , Slovic Paul , Morgan M. Granger
Published: May 2006

Potential health risks from exposure to power‐frequency electromagnetic fields (EMF) have become an issue of significant public concern. This study evaluates a brochure designed to communicate EMF health risks from a scientific perspective. The study utilized a pretest‐posttest design in which respondents judged various sources of EMF (and other) health and safety risks, both before reading the brochure and after. Respondents assessed risks on dimensions similar to those utilized in previous studies of risk perception. In addition, detailed ratings were made that probed respondents’ beliefs about the possible causal effects of EMF exposure. The findings suggest that naive beliefs about the potential of EMF exposure to cause harm were highly influenced by specific content elements of the brochure. The implications for using risk‐communication approaches based on communicating scientific uncertainty are discussed.
Point Estimates of Cancer Risk at Low Doses
Authors: Gaylor David W. , Kodell Ralph L. , Chen James J. , Springer Janet A. , Lorentzen Ronald J. , Scheuplein Robert J.
Published: May 2006

There has been considerable discussion regarding the conservativeness of low‐dose cancer risk estimates based upon linear extrapolation from upper confidence limits. Various groups have expressed a need for best (point) estimates of cancer risk in order to improve risk/benefit decisions. Point estimates of carcinogenic potency obtained from maximum likelihood estimates of low‐dose slope may be highly unstable, being sensitive both to the choice of the dose–response model and possibly to minimal perturbations of the data. For carcinogens that augment background carcinogenic processes and/or for mutagenic carcinogens, at low doses the tumor incidence versus target tissue dose is expected to be linear. Pharmacokinetic data may be needed to identify and adjust for exposure‐dose nonlinearities. Based on the assumption that the dose response is linear over low doses, a stable point estimate for low‐dose cancer risk is proposed. Since various models give similar estimates of risk down to levels of 1%, a stable estimate of the low‐dose cancer slope is provided by ŝ= 0.01/ED01, where ED01 is the dose corresponding to an excess cancer risk of 1%. Thus, low‐dose estimates of cancer risk are obtained by, risk =ŝ× dose. The proposed procedure is similar to one which has been utilized in the past by the Center for Food Safety and Applied Nutrition, Food and Drug Administration. The upper confidence limit, s, corresponding to this point estimate of low‐dose slope is similar to the upper limit, q1 obtained from the generalized multistage model. The advantage of the proposed procedure is that ŝ provides stable estimates of low‐dose carcinogenic potency, which are not unduly influenced by small perturbations of the tumor incidence rates, unlike q̂1.
A Simple Data Transformation for Estimating Benchmark Doses in Developmental Toxicity Experiments
Authors: Krewski D. , Zhu Y.
Published: May 2006

Developmental anomalies induced by toxic chemicals may be identified using laboratory experiments with rats, mice or rabbits. Multinomial responses of fetuses from the same mother are often positively correlated, resulting in overdispersion relative to multinomial variation. In this article, a simple data transformation based on the concept of generalized design effects due to Rao‐Scott is proposed for dose‐response modeling of developmental toxicity. After scaling the original multinomial data using the average design effect, standard methods for analysis of uncorrected multinomial data can be applied. Benchmark doses derived using this approach are comparable to those obtained using generalized estimating equations with an extended Dirichlet‐trinomial covariance function to describe the dispersion of the original data. This empirical agreement, coupled with a large sample theoretical justification of the Rao‐Scott transformation, confirms the applicability of the statistical methods proposed in this article for developmental toxicity risk assessment.
Results of a National Symposium on Risk Communication: Next Steps for Government Agencies
Authors: Chess Caron , Salomone Kandice L. , Hance Billie Jo , Saville Alex
Published: May 2006

A national symposium of risk communication practitioners and researchers was held in 1994 to discuss next steps to improve government agencies’risk communication practices. The symposium focused on three issues which a survey of researchers and practitioners indicated were priorities for risk communication research: integrating outside concerns into agency decision‐making; communicating with communities of different races, ethnic backgrounds and incomes; and evaluation of risk communication. There are indications that the working assumptions underlying these issues are shifting in several distinctive ways. For example, a shift from simply communicating risk to forging partnerships with communities was clearly evident throughout the symposium. Communicating with different social, ethnic, and racial groups gained recognition as a vital component of the risk communication research agenda. Agencies themselves should be the subject of study, according to many symposium participants who were concerned less about the so‐called irrationality of the public and more about the reluctance of agencies to encourage risk communication.
Improving Risk Communication in Government: Research Priorities
Authors: Chess Caron , Salomone Kandice L. , Hance Billie Jo
Published: May 2006

Despite the increased interest in risk communication among government agencies, there is evidence that agencies’risk communication practices lag. We conducted a study to explore which risk communication research would be most important to improve government agencies’risk communication practices. Qualitative interviews and a survey of 145 risk communication experts based in academic institutions and government agencies explored how important research on each of 48 topics would be to improving agencies’risk communication efforts. Respondents identified topics within three areas as priorities for further research: 1) involving communities in agency decisionmaking; 2) communicating with communities of different races, ethnic backgrounds, and incomes; and 3) evaluating risk communication. Both practitioners and researchers responded to additional statements about agencies’risk communication practices with reservations about staff and managers’commitment to effective communication about environmental issues. We discuss the implications of these findings.
Ecological Risk Assessment Case Study: Impacts to Aquatic Receptors at a Former Metals Mining Superfund Site
Authors: Hattemer‐Frey Holly A. , Quinlan Robert E. , Krieger Gary R.
Published: May 2006

An ecological risk assessment (ERA) was conducted as part of the Baseline Risk Assessment of the Remedial Investigation (RI) for the Baxter Springs/Treece subsites, Cherokee County, Kansas Superfund site, a former metals mining site. Chemicals of potential concern were heavy metals associated with mine wastes and with base metal ore deposits that were characteristic of this area. An EPA‐approved method was used to developed site‐specific ambient water quality criteria. Ecological impacts were assessed using three complimentary approaches. First, potential chronic impacts were assessed by applying the toxicity quotient approach (i.e., a comparison of the measured concentration of site‐related metals in surface water with calculated site‐specific health‐based criteria). Secondly, semi‐quantitative comparative ecology data were used to provide a direct measure of impacts to key species. Finally, data on other factors (e.g., acclimation and tolerance evolution) that may affect the bioavailability and toxicity of site‐related metals were also considered. Information from these three sources were used to obtain a realistic picture of actual and potential population‐ and community‐level effects associated with exposure to mining‐related metals.
Improving the Regulation of Carcinogens by Expediting Cancer Potency Estimation1
Authors: Hoover Sara M. , Zeise Lauren , Pease William S. , Lee Louise E. , Hennig Mark P. , Weiss Laura B. , Cranor Carl
Published: May 2006

The statutory language of the Safe Drinking Water and Toxic Enforcement Act of 1986 (Proposition 65; California Health and Safety Code 25249.5 et seq.) encourages rapid adoption of “no significant risk levels” (NSRLs), intakes associated with estimated cancer risks of no more than 1 in 100,000. Derivation of an NSRL for a carcinogen listed under Proposition 65 requires the development of a cancer potency value. This paper discusses the methodology for the derivation of cancer potencies using an expedited procedure, and provides potency estimates for a number of agents listed as carcinogens under Proposition 65. To derive expedited potency values, default risk assessment methods are applied to data sets selected from an extensive tabulation of animal cancer bioassays according to criteria used by regulatory agencies. A subset of these expedited values is compared to values previously developed by regulatory agencies using conventional quantitative risk assessment and found to be in good agreement. Specific regulatory activities which could be facilitated by adopting similar expedited procedures are identified.
Perceived Nuclear Risk, Organizational Commitment, and Appraisals of Management: A Study of Nuclear Power Plant Personnel
Authors: Kivimäki Mika , Kalimo Raija , Salminen Simo
Published: May 2006

This study examined to what extent nuclear risk perceptions, organizational commitment (OC), and appraisals of management are associated with each other among nuclear power plant personnel. The sample consisted of 428 nuclear power plant workers who completed a questionnaire at their workplace. Perceived nuclear risk and OC were most closely related to the appraisals of the top management of the organization. As the trust in and satisfaction with the top management increased, perceived nuclear safety and acceptance of the organizational goals and values heightened. This result is discussed in the context of industrial safety management.
Eliciting and Classifying Concerns: A Methodological Critique
Authors: Webler Thomas , Rakel Horst , Renn Ortwin , Johnson Branden
Published: May 2006

Two methodological steps in the study of peoples’concerns are elicitation and classification. Elicitation of concerns through analytical methods such as surveys can be supplemented with techniques that perform more diversively. We present two examples of how this can be accomplished: one in the expert community and one in the lay community. A classification taxonomy is a subjective choice of the researcher and it can only be evaluated against the stated objectives of the research. We present a classification schema that is explicitly oriented toward diagnosing the substantive needs of public discourses about risk decision making. To illustrate how concerns can be elicited in a social setting and how this classification tool can be applied, we report on a public participation exercise in New Jersey where citizens discussed the impacts of land application of sewage sludge at an experimental farm.
Residential Air Exchange Rates in the United States: Empirical and Estimated Parametric Distributions by Season and Climatic Region
Authors: Murray Donald M. , Burmaster David E.
Published: May 2006

The purpose of this paper is to undertake a statistical analysis to specify empirical distributions and to estimate univariate parametric probability distributions for air exchange rates for residential structures in the United States. To achieve this goal, we used data compiled by the Brookhaven National Laboratory using a method known as the perfluorocarbon tracer (PFT) technique. While these data are not fully representative of all areas of the country or all housing types, they are judged to be by far the best available. The analysis is characterized by four key points: the use of data for 2,844 households; a four‐region breakdown based on heating degree days, a best available measure of climatic factors affecting air exchange rates; estimation of lognormal distributions as well as provision of empirical (frequency) distributions; and provision of these distributions for all of the data, for the data segmented by the four regions, for the data segmented by the four seasons, and for the data segmented by a 16 region by season breakdown. Except in a few cases, primarily for small sample sizes, air exchange rates were found to be well fit by lognormal distributions (adjusted R2 0.95). The empirical or lognormal distributions may be used in indoor air models or as input variables for probabilistic human health risk assessments.
An Improved Approximation to the Exact Solution of the Two‐Stage Clonal Growth Model of Cancer
Authors: Clewell III Harvey J. , Quinn Dennis W. , Andersen Melvin E. , Conolly Rory B.
Published: May 2006

Multistage clonal growth models are of interest for cancer risk assessment because they can explicitly incorporate data on cell replication. Both approximate and exact formulations of the two stage growth model have been described. The exact solution considers the conditional probability of tumors arising in previously tumor‐free animals; the approximate solution estimates total probability of tumor formation. The exact solution is much more computationally intensive when time‐dependent cell growth parameters are included. The approximate solution deviates from the exact solution at high incidences and probabilities of tumor. This report describes a computationally tractable,‘improved approximation’to the exact solution. Our improved approximation includes a correction term to adjust the unconditional expectation of intermediate cells based on the time history of formation of intermediate cells by mutation of normal cells (recruitment) or by cell division in the intermediate cell population (expansion). The improved approximation provided a much better match to the exact solution than the approximate solution for a wide range of parameter values. The correction term also appears to provide insight into the biological factors that contribute to the variance of the expectation for the number of intermediate cells over time.
A Framework for Hazardous Materials Transport Risk Assessment
Authors: Erkut Erhan , Verter Vedat
Published: May 2006

In this paper, we provide a framework for quantitative risk assessment in hazardous materials transport. We first outline a basic model where population centers are approximated by points on a plane with the assumption that in the case of an incident all residents in a population center will experience the same consequences. Different versions of this model have been used by other authors in the literature. This model may be valid if the hazardous materials route goes by small population centers. Then we extend this basic model to assess risks of shipping hazardous materials through large population centers that cannot be modeled as single points on a plane. In the extended model, large population centers are treated as two‐dimensional objects on the plane, which allows for a more accurate treatment of consequences than the basic model. To the extent of our knowledge the extended model is novel. We provide numerical examples for both the basic and the extended models, and finish by discussing limitations of the suggested risk assessment framework.