bluuebunny/crossref_metadata_2025 huggingface dataset:
Postnatal Handling Does Not Attenuate Hypothalamic‐Pituitary‐Adrenal Hyperresponsiveness After Prenatal Ethanol Exposure
Authors: Gabriel Kara I. , Yu Wayne , Ellis Linda , Weinberg Joanne
Published: May 2006

Background:

Prenatal ethanol exposure results in hypothalamic‐pituitary‐adrenal (HPA) hyperresponsiveness to stress in the adult animal. In contrast, an early environmental manipulation, termed “postnatal handling,'’has been shown to result in decreased and/or less prolonged HPA activity in response to moderate stressors throughout the lifespan of the animal. The effects of both prenatal ethanol exposure and postnatal handling on HPA activity may be mediated by altered feedback regulation of the HPA axis. The present study tested the hypothesis that postnatal handling could attenuate the impact of prenatal ethanol exposure on hormonal responses to stressors.

Methods:

Male and female Sprague Dawley® rats from prenatal ethanol (E), pair‐fed (PF), and ad libitum‐fed control (C) groups were either handled (H) or nonhandled (NH) during the preweaning period and were tested at 4 to 5 months of age. Animals were subjected to a 60 min restraint stress, 3 hr after intraperitoneal injection with either saline (SAL) or a synthetic glucocorticoid, dexamethasone‐21‐phosphate (DEX), in order to examine HPA responsiveness after DEX blockade of endogenous HPA activity. Blood samples were collected via jugular cannulae immediately before restraint (0 min), during restraint (10, 30, and 60 min), and 30 min after the termination of restraint (90 min).

Results:

For both males and females, DEX administration significantly reduced plasma adrenocorticotropic hormone (ACTH) and corticosterone (CORT) concentrations compared with SAL administration. H animals showed greater suppression of HPA activity (i.e., lower ACTH and/or CORT levels) than NH animals regardless of prenatal group. In addition, E females from both the H and NH treatments showed elevated ACTH and CORT after both SAL and DEX administration, whereas H and NH E males showed elevations in ACTH and CORT only after SAL, compared with their PF and C counterparts.

Conclusions:

These data extend results from previous studies that demonstrated HPA hyperresponsiveness in E animals. The finding that E females but not males exhibit elevated ACTH and CORT after DEX administration suggests that prenatal ethanol exposure results in sex‐specific alterations of HPA feedback. Consistent with previous data, handling in itself reduced the HPA response to restraint stress. However, handling did not attenuate either HPA hyperresponsiveness or feedback deficits in E animals.
Parent Ratings of Behavior in Children with Heavy Prenatal Alcohol Exposure and IQ‐Matched Controls
Authors: Mattson Sarah N. , Riley Edward P.
Published: May 2006

Background:

Behavioral disturbances are well documented in children with heavy prenatal alcohol exposure. However, the degree to which these disturbances are related to factors other than alcohol, such as general intellectual functioning or socioeconomic status, is not known.

Methods:

Using the Child Behavior Checklist, parent‐rated behaviors of children with histories of heavy prenatal alcohol exposure were compared with those of a control group matched by age, sex, socioeconomic status, ethnicity, and verbal IQ score. Using this same questionnaire, children with fetal alcohol syndrome were compared with children with heavy prenatal alcohol exposure that did not meet the criteria for fetal alcohol syndrome classification.

Results:

Data were analyzed by multivariate analyses of covariance. In the comparison of children with and without a history of prenatal alcohol exposure, significant differences were found on the competence, problem, and summary scales (all p < 0.05). For the secondary comparison between the fetal alcohol syndrome and the heavy prenatal alcohol exposure groups, there were no significant differences on any of the scales (all p > 0.10).

Conclusions:

These results suggest that prenatal alcohol exposure results in the significant and profound impairment of parent‐rated behaviors and that these deficits are not explained entirely by the presence or absence of facial dysmorphology, general intellectual functioning, or demographic factors.
Autoimmune Responses Against Oxidant Stress and Acetaldehyde‐Derived Epitopes in Human Alcohol Consumers
Authors: Viitala Katja , Makkonen Kati , Israel Yedy , Lehtimäki Terho , Jaakkola Olli , Koivula Timo , Blake Joan E. , Niemelä Onni
Published: May 2006

Background: Studies in experimental animals have indicated that chronic ethanol ingestion triggers the formation of antibodies directed against proteins modified with reactive metabolites of ethanol and products of lipid peroxidation. However, the nature and prevalence of such antibodies have not been compared previously in alcoholic patients.

Methods: Autoantibodies against adducts with acetaldehyde‐ (AA), malondialdehyde‐ (MDA), and oxidized epitopes (Ox) were examined from sera of 54 alcohol consumers with (n= 28) or without (n= 26) liver disease, and from 20 nondrinking controls.

Results: Anti‐AA‐adduct IgA and IgG antibodies were elevated in 64% and 31% of patients with biopsy‐proven alcoholic liver disease (ALD, n= 28), respectively. The IgA titers were significantly higher than those from nondrinking controls (p < 0.001), or heavy drinkers without significant liver disease (p < 0.001). Anti‐MDA adduct titers (IgG) were elevated in 70% of the ALD patients. These titers were significantly higher (p < 0.001) than those from nondrinking controls, or heavy drinkers without liver disease. Antibodies (IgG) against Ox epitopes occurred in 43% of ALD patients, and the titers also were significantly higher (p < 0.05) than those from nondrinking controls. The anti‐AA and anti‐MDA adduct titers in ALD patients correlated significantly with the combined clinical and laboratory index (CCLI) of liver disease severity (rs= 0.449, p < 0.05; rs= 0.566, p < 0.01, respectively), the highest prevalences of anti‐AA‐adducts (73%) and anti‐MDA‐adducts (76%) occurring in ALD patients with cirrhosis.

Conclusions: The present results indicated that autoantibodies against several distinct types of protein modifications are generated in ALD patients showing an association with the severity of liver disease.
Dopaminergic Neurons in the Ventral Tegmental Area of C57BL/6J and DBA/2J Mice Differ in Sensitivity to Ethanol Excitation
Authors: Brodie Mark S. , Appel Sarah B.
Published: May 2006

Background: The mesolimbic dopamine pathway that originates in the ventral tegmental area (VTA) is important for the rewarding effects of ethanol. Ethanol has been shown to excite dopaminergic neurons of the VTA, both in vivo and in vitro, in rats. Behavioral differences in the rewarding effects of ethanol have been observed between C57BL/6J and DBA/2J mice. The present electrophysiological study examined the effect of ethanol on individual dopaminergic VTA neurons from these two inbred mouse strains.

Methods: Extracellular single unit recordings of spontaneous action potentials were made from dopaminergic VTA neurons in brain slices from either C57BL/6J or DBA/2J mice. Ethanol (10 to 160 mM) was administered in the superfusate and the mean change in firing rate produced by ethanol was measured.

Results: There was no significant difference in basal spontaneous firing rate of dopaminergic VTA neurons between these two mouse strains. Ethanol caused a concentration‐dependent increase in the firing rate of neurons from both mouse strains. Ethanol excited dopaminergic VTA neurons from DBA/2J mice more potently than those from C57BL/6J mice.

Conclusions: The difference in sensitivity to ethanol excitation of dopaminergic VTA neurons in C57BL/6J and DBA/2J mice may contribute to differences in their behavioral response to ethanol. The fact that a given concentration of ethanol causes greater excitation of dopaminergic VTA (reward) neurons in DBA/2J mice than in C57BL/6J mice could explain why DBA/2J mice show much stronger place preference conditioning with ethanol. The higher voluntary intake of ethanol by C57BL/6J mice may be partly due to the insensitivity of their dopaminergic VTA neurons that requires them to drink a lot of ethanol to achieve sufficient excitation of reward neurons, whereas DBA/2J mice avoid oral ingestion of ethanol, despite its rewarding effect, because of their aversion to its taste.
Reduction of Perforin, Granzyme B, and Cytokine Interferon γ by Ethanol in Male Fischer 344 Rats
Authors: Dokur Madhavi , Boyadjieva Nadka I. , Sarkar Dipak K.
Published: May 2006

Background: Chronic alcohol consumption can impair the immune system and predispose individuals to an increased risk of cancer and infection. Natural killer (NK) cells are the first line of defense against viral, bacterial, and fungal infections and play an important role in cellular resistance to malignancy and tumor metastasis. We have shown previously that ethanol administration suppresses NK cell cytolytic activity in male Fischer rats. This study analyzed the effects of ethanol on perforin, granzyme B, and the cytokine interferon (IFN)‐γ, factors that modulate NK cell cytolytic activity, to understand the molecular mechanism involved in ethanol's suppression of NK cell activity.

Methods: A group of male Fischer rats was fed an ethanol‐containing diet (8.7% v/v), whereas a control group was pair‐fed an isocaloric diet. At the end of 2 weeks, animals were decapitated, and spleen tissues were immediately removed and used for analysis of NK cell cytolytic activity, perforin, granzyme B, and IFN‐γ messenger RNA (mRNA) or protein levels. The mRNA levels of perforin, granzyme B, and IFN‐γ were evaluated by quantitative real‐time polymerase chain reaction, and protein levels of these factors were analyzed by Western blot, enzyme‐linked immunosorbent assay, or enzymatic activity assay.

Results: Ethanol reduced the NK cell cytolytic activity and decreased the mRNA expression of perforin, granzyme B, and IFN‐γ in ethanol‐fed animals when compared with pair‐fed animals. Ethanol also significantly reduced the protein levels of perforin and IFN‐γ and the enzyme activity of granzyme B in alcohol‐fed animals as compared with pair‐fed animals.

Conclusions: These data suggest that chronic ethanol consumption may suppress NK cell cytolytic activity in male Fischer rats by decreasing the production, activity, or both of granzyme B, perforin, and IFN‐γ.
Developmental Binge Exposure to Ethanol and Artificial Rearing Do Not Affect the Social Transfer of Diet Preference
Authors: Girard T. A. , Hung V. , Patel S. , Ward G. R. , Wainwright P. E.
Published: May 2006

Background: A previous study reported no effect of binge exposure to ethanol during the brain growth spurt on the social acquisition of enhanced diet preference in male rats. The objective of this study was to replicate this finding by using the artificial rearing technique and to investigate whether delay‐dependent mnemonic deficits previously observed in the water maze would extend to social memory of diet preference. We also addressed whether this naturalistic behavior was dependent on the presentation of diet odor in the context of a rat‐produced component in ethanol‐exposed rats, as it is in normal controls.

Methods: Male rat pups were reared artificially from postnatal days 5 to 18, during which (postnatal days 6–9) they were fed either 6.5 g/kg/day of ethanol in a binge model or an isocaloric maltose‐dextrin solution (gastrostomy controls). A third suckled control group was reared normally. These test rats were allowed to interact with conspecifics that had previously consumed a distinctive diet, X. Subsequently, the experimental rats were provided a choice between two novel diets, one of which was X, after delays of 0 hr (experiment 1), 24 hr, and 4 weeks (experiment 2). In experiment 3, the rats were again given the two‐choice preference test, but after exposure to the diet odor alone.

Results: All groups demonstrated a significant preference for the socially cued diet in experiments 1 and 2, and the strength of this inclination remained consistent across the 0‐hr, 24‐hr, and 4‐week retention intervals. Moreover, all groups demonstrated sensitivity to the social context of this task, as shown by a lesser preference for the diet exposed alone in experiment 3.

Conclusions: Intact performance on the ethologically meaningful diet‐preference test supports specificity in the cognitive/behavioral effects of developmental exposure to ethanol. Interestingly, early isolation, as experienced in the artificial‐rearing procedure, also did not impair performance on this social task.
Prenatal Ethanol Exposure Alters the Responsiveness of the Rat Hypothalamic‐Pituitary‐Adrenal Axis to Nitric Oxide
Authors: Lee Soon , Blanton Cynthia A. , Rivier Catherine
Published: May 2006

Background: Prenatal alcohol exposure is known to cause hyperactivity of the mature offspring's hypothalamic‐pituitary‐adrenal (HPA) axis. We have recently shown that hypothalamic neurons that produce corticotropin‐releasing factor (CRF), the peptide that represents the major adrenocorticotropin hormone (ACTH) secretagogue, display increased responses to various stimuli in prenatal alcohol‐exposed (E), compared to control (C) rats. CRF‐producing perikarya are regulated, in part, by nitric oxide (NO), a signaling molecule whose function is also modified by prenatal alcohol exposure. The present investigation was therefore undertaken to test the hypothesis that prenatal alcohol exposure is associated with alterations in NO‐stimulated ACTH secretion.

Methods: Adult male and female Sprague‐Dawley rats exposed to alcohol in utero were injected intracerebroventricularly (icv) with the vehicle or the NO donor 3‐morpholino‐sydnonimine (SIN‐1; 20 or 50 μg). ACTH levels were measured in blood samples collected from indwelling jugular cannulae at 15, 30 and 45 min following injection. Brains were obtained 45 and 90 min after SIN‐1 injection and processed for in situ hybridization.

Results: Compared to males, both C and E females exhibited a significantly (p < 0.01) larger ACTH response to SIN‐1 (20 μg). Prenatal alcohol treatment enhanced SIN‐1‐induced ACTH release in all E animals, but this difference only reached statistical significance (p < 0.01) in males. This prenatal influence was also observed in the significantly (p < 0.01) larger SIN‐1‐induced increase in transcripts for the immediate early gene nerve growth factor induced protein B (NGFI‐B) in the paraventricular nucleus (PVN) of the males', but not females' hypothalamus.

Conclusions: The ability of increased brain NO levels to release ACTH and stimulate PVN neuronal activity is enhanced in adult male rats exposed to alcohol prenatally. These data support the hypothesis that alterations in HPA axis activity in adult offspring of alcohol‐exposed dams may be related to changes in hypothalamic responsiveness to NO.
Induction of CYP3A by Ethanol in Multiple In Vitro and In Vivo Models
Authors: Feierman Dennis E. , Melinkov Zoya , Nanji Amin A.
Published: May 2006

Background: Cytochrome P‐450 3A (CYP3A) is responsible for the metabolism of numerous therapeutic agents. The content of CYP3A seems to be affected by ethanol ingestion. Because ethanol is used widely, its potential interaction with CYP3A is of great interest. The effects of ethanol on CYP3A content and activity were assessed in different in vivo and in vitro models.

Methods: Rats fed either the Lieber‐DeCarli ethanol‐containing diet or an ethanol and liquid diet via the intragastric tube feeding method were used. Additionally, HepG2 cell lines that constitutively and stably express human CYP3A4 were constructed to study ethanol interactions with CYP3A4.

Results: In all models tested, ethanol induced CYP3A activity and content, as assessed by the metabolism of fentanyl, a sensitive and specific CYP3A substrate, and Western blot analysis, respectively. In the CYP3A4‐expressing HepG2 cell line, incubation with ethanol caused a dose‐dependent increase in CYP3A4 activity. Ethanol also increased messenger RNA levels of CYP3A4. In the HepG2‐CYP3A4 line, incubation with cycloheximide caused a decrease in fentanyl metabolism secondary to a decrease in CYP3A4 levels; this decrease was prevented by coincubation of cycloheximide with ethanol.

Conclusions: Ethanol induced CYP3A activity and content both in vitro and in vivo. There may be multiple mechanisms of induction of CYP3A4 by ethanol, including stabilization of messenger RNA and protein. Ethanol‐induced increases in both the protein level and activity of CYP3A4 may play a role that might be of pathophysiological or clinical significance.
Dilinoleoylphosphatidylcholine Reproduces the Antiapoptotic Actions of Polyenylphosphatidylcholine Against Ethanol‐Induced Hepatocyte Apoptosis
Authors: Mak Ki M. , Wen Kefeng , Ren Chaoling , Lieber Charles S.
Published: May 2006

Background: Polyenylphosphatidylcholine (PPC), a mixture of polyunsaturated phosphatidylcholines extracted from soybeans, attenuates hepatocyte apoptosis induced by ethanol feeding of rats. Our aims were to evaluate whether dilinoleoylphosphatidylcholine (DLPC), the main component of PPC, reproduces the antiapoptotic actions of PPC against alcohol‐induced apoptosis and to identify the apoptotic proteins that are affected by PPC and DLPC.

Methods: Rats were fed Lieber‐DeCarli liquid diets containing ethanol (35% of energy) or an isocaloric amount of carbohydrate for 4 weeks. Another group of rats were given the ethanol diet supplemented with PPC (3 g/liter) or DLPC (1.5 and 3 g/liter). Hepatocyte apoptosis was assessed by terminal transferase‐mediated dUTP nick end labeling staining and by caspase 3 enzyme activity. Activity of caspases 3 and 9 was assayed by using fluorogenic peptide substrates. Cytochrome c was quantified by enzyme‐linked immunosorbent assay. The protein contents of cytochrome c, procaspase 3, caspase 3, Bcl‐xL, and Bax were analyzed by Western blot and quantified by densitometry. Lobular localization of active caspase 3 was examined by immunoperoxidase staining.

Results: PPC and DLPC decreased ethanol‐induced increases in hepatocyte apoptosis, cytosolic cytochrome c, and caspase 3 content and its activity. Caspase 3 activity correlated with the number of apoptotic hepatocytes. Active caspase 3 was present predominantly in perivenular hepatocytes, and ethanol feeding extended it to lobular hepatocytes; this ethanol effect was reduced by PPC and DLPC. Ethanol significantly decreased Bcl‐xL in homogenate, mitochondria, and cytosol, and there was a trend for increased Bcl‐xL in these fractions after PPC and DLPC supplementation. Microsomal Bcl‐xL did not differ between treatment groups. Bax was detected in homogenate and cytosol, and its level was not affected by ethanol.

Conclusions: DLPC, at a dose contained in PPC, reproduces the antiapoptotic actions of PPC through a reduction in cytosolic cytochrome c concentration and caspase 3 activity, possibly in association with up‐regulation of Bcl‐xL expression. Because DLPC is a pure and well defined compound, it may be more suitable than PPC for intervention against alcohol‐induced apoptosis.
Risk Analysis: Understanding “How Safe is Safe Enough?“
Authors: Derby Stephen L. , Keeney Ralph L.
Published: May 2006

The basic characteristics of determining acceptable risk are discussed. Technical, political, and social aspects of the problem add much complexity. The appropriate manner to reach responsible decisions regarding acceptable risk is suggested. This explicitly addresses the alternatives, the objectives, the uncertainty, and the values which constitute the information necessary to arrive at any solution. The inappropriateness of many “solutions” currently in use or “suggested” is exposed.
Cognitive Components of Risk Ratings
Authors: von Winterfeldt Detlof , John Richard S. , Borcherding Katrin
Published: May 2006

This study examined what lay people mean when they judge the “risk” of activities that involve the potential for accidental fatalities (e.g., hang gliding, living near a nuclear reactor). A sample of German and American students rated the “overall risk” of 14 such activities and provided 3 fatality estimates: the number of fatalities in an “average year,” the individual yearly fatality probability (or odds), and the number of fatalities in a “disastrous accident.” Subjects' fatality estimates were reasonably accurate and only moderately influenced by attitudes towards nuclear energy. Individual fatality probability correlated most highly with intuitive risk ratings. Disaster estimates correlated positively with risk ratings for those activities that had a low fatality probability and a relatively high disaster potential. Annual average fatality rates did not correlate with risk ratings at all. These findings were interpreted in terms of a two‐dimensional cognitive structure. Subjective notions of risk were determined primarily by the personal chance of death; for some activities, “disaster potential” played a secondary role in shaping risk perception.
Quasiextinction Probabilities as a Measure of Impact on Population Growth
Authors: Ginzburg Lev R. , Slobodkin Lawrence B. , Johnson Keith , Bindman Andrew G.
Published: May 2006

A probabilistic language based on stochastic models of population growth is proposed for a standard language to be used in environmental assessment. Environmental impact on a population is measured by the probability of quasiextinction. Density‐dependent and independent models are discussed. A review of one‐dimensional stochastic population growth models, the implications of environmental autocorrelation, finite versus “infinite” time results, age‐structured models, and Monte Carlo simulations are included. The finite time probability of quasiextinction is presented for the logistic model. The sensitivity of the result with respect to the mean growth rate and the amplitude of environmental fluctuations are examined. Stochastic models of population growth form a basis for formulating reasonable criteria for environmental impact estimates.
The Multistage Model with a Time‐Dependent Dose Pattern: Applications to Carcinogenic Risk Assessment1
Authors: Clump Kenny S. , Howe Richard B.
Published: May 2006

A cancer risk assessment methodology based upon the Armitage–Doll multistage model of cancer is applied to animal bioassay data. The method utilizes the exact time‐dependent dose pattern used in a bioassay rather than some single measure of dose such as average dose rate or cumulative dose. The methodology can be used to predict risks from arbitrary exposure patterns including, for example, intermittent exposure and short‐term exposure occurring at an arbitrary age. The methodology is illustrated by applying it to a National Cancer Institute bioassay of ethylene dibromide in which dose rates were modified several times during the course of the experiment.
Learning from Nuclear Accident Experience
Authors: Vaurio Jussi K.
Published: May 2006

Statistical procedures are developed to estimate accident occurrence rates from historical event records, to predict future rates and trends, and to estimate the accuracy of the rate estimates and predictions. Maximum likelihood estimation is applied to several learning models and results are compared to earlier graphical and analytical estimates. The models are based on (1) the cumulative number of operating years, (2) the cumulative number of plants built, and (3) accidents (explicitly), with the accident rate distinctly different before and after an accident. The statistical accuracies of the parameters estimated are obtained in analytical form using the Fisher information matrix. Using data on core damage accidents in electricity producing plants, it is estimated that the probability for a plant to have a serious flaw has decreased from 0.1 to 0.01 during the developmental phase of the nuclear industry. At the same time the equivalent frequency of accidents has decreased from 0.04 per reactor year to 0.0004 per reactor year, partly due to the increasing population of plants.
Ethics, Decision Analysis, and Public Risk
Authors: Keeney Ralph L.
Published: May 2006

In any analysis of a decision problem involving public risks, ethical implications are introduced. In some cases, these ethical implications may be introduced simply because an analysis is being done. Additional ethical implications may be inherently part of the methodology being utilized or introduced into the specific analysis of the decision problem. In this paper, we investigate where and how ethical implications enter when using the methodology of decision analysis to examine problems involving public risks. We conclude that the methodology of decision analysis is sufficiently robust to allow for numerous different ethical viewpoints to be accounted for in any specific analysis. Stated alternatively, decision analyses of public risks can be conducted in a manner consistent with utilitarianism, deontological theories, libertarianism, egalitarianism, and so forth. However, any specific analysis has embedded within it numerous ethical implications. This suggests that the careful ethical scrutiny of analyses involving the methodology of decision analysis should be placed on the specific application and not on the methodology per se or on the fact that an analysis is undertaken.
Do Drivers of Small Cars Take Less Risk in Everyday Driving?
Authors: Wasielewski Paul , Evans Leonard
Published: May 2006

Previously reported observed data on risky everyday driving are brought together and reanalyzed in order to focus on the relation between risky driving and the size of the car being driven, as indicated by car mass. The measures of risky driving include separation between vehicles in heavy freeway traffic and speed on a two lane road. Observed seat belt use provides a third measure of driver risk. Confounding effects arising from the observed association between car mass and driver age are taken into account by segmenting the data into three driver age groups. Driver risk taking is found to increase with increasing car mass for each of these three aspects of everyday driving. The implications of these results with respect to driver fatality rates are discussed in terms of a simple model relating observed risky driving to the likelihood of involvement in a severe crash.
Risk Assessment of Laboratory Rats and Mice Chronically Exposed to Formaldehyde Vapors
Authors: Brown Kenneth G.
Published: May 2006

Experimental data from the Chemical Industry Institute of Toxicology (CIIT) are used to estimate the risk of squamous cell carcinoma of the nasal cavity in Fischer 344 (F344) rats over a range of ambient air concentrations of formaldehyde that includes current exposure guidelines for the workplace and home. These values are presented as a best estimate envelope obtained from five mathematical dose‐response formulations. The response of Sprague‐Dawley (SD) rats dosed at 15 ppm in a separate study at New York University is consistent with the predicted lifetime response for F344 rats at a slightly lower concentration (13–14 ppm). A dose‐related mortality effect beyond what is attributable to the occurrence of nasal carcinomas is found in F344 rats at all CIIT exposure levels (2, 6, and 15 ppm). There is no evidence of a mortality effect in B6C3F1 mice of the CIIT study, and data for SD rats of the NYU experiment are inconclusive. In the CIIT study, rats exposed to 15 ppm exhibited a high incidence of nasal cavity squamous cell carcinomas and polypoid adenomas. Polypoid adenomas were also observed with increased incidences at 2 ppm and 6 ppm. Statistical comparisons with matched controls, and the low historical rate of spontaneous occurrence both suggest that polypoid adenomas may be a risk to F344 rats at exposure levels below the current Occupational Safety and Health Administration (OSHA) standard of 3 ppm. Squamous cell carcinomas were observed in two mice exposed to 15 ppm. This finding may be biologically significant since this tumor is rare and has not been previously reported in 4932 untreated B6C3F1 mice from recent National Toxicology Program (NTP) feeding studies.
The Promise of Molecular Epidemiology for Quantitative Risk Assessment
Authors: Hattis Dale B.
Published: May 2006

In the long run, molecular epidemiological techniques (1) can provide important insights for understanding a wide variety of important issues in current risk assessment and (2) are applicable across a broad spectrum of adverse effects in addition to carcinogenesis. Unfortunately, current risk assessment practices make very little use of the kind of detailed mechanistic information that molecular epidemiology can provide. Eventually, there is reason to hope that the availability of mechanistic insights provided in part by molecular epidemiology can produce some of the “essential tension” required to reform paradigms for the formulation of quantitative risk assessment models in general.
On Criteria of Insignificant Difference Between Two Risks
Authors: Goodman Julius
Published: May 2006

The comparison and ranking of risks is very important for safety and cost‐benefit analysis. Most formats present risks in the form of probability distribution. Different ranking criteria for probability distributions are considered. It is demonstrated that significantly overlapping distributions lead to ambiguous results. For this reason, criteria of insignificant overlapping distributions are proposed. The first criterion uses the information theory approach; and the second criterion uses the statistical tests approach. Both approaches can be applied to decision theory to avoid questionable decisions based on statistically insignificant differences between two risks.
Perceived Acceptability of Risk Analysis as a Decision‐Making Approach
Authors: MacGregor Donald , Slovic Paul
Published: May 2006

Three methods for making a consumer product safety decision were evaluated on scales relating to their perceived acceptability, logical soundness, completeness, and sensitivity to moral and ethical concerns. Two of the methods were formalized techniques: cost‐benefit analysis and risk analysis. The third method involved abiding by standard industry practices. Other factors in the decision‐making context were also varied. The results indicated that formalized techniques were preferred over the standard practices method. Within the formalized methods, cost‐benefit analysis was judged less acceptable than a comparable method that did not involve making explicit value tradeoffs. All methods were judged more acceptable when they led to improved product safety. Knowledge of consequences did not exert direct effect on judgments, though it did interact significantly with other variables. The results are discussed in terms of judgmental processes that people apply when evaluating decision methods.
A Methodology for Estimating Time‐of‐Day Variations in the Size of a Population Exposed to Risk
Authors: Glickman Theodore S.
Published: May 2006

Consequence models for the risk assessment of man‐made or natural disasters do not ordinarily take into account time‐of‐day variations in the size of the exposed population. Residential census population statistics are used instead. This paper proposes and illustrates a methodology for using metropolitan travel survey data to estimate the variations in question. Variations are computed from the Washington, D.C. area sample survey statistics on the number of trips taken in and out of different census tracts throughout each workday. Four principal patterns of population variation are identified, corresponding to four types of land use: (a) commercial, (b) residential, (c) shopping/entertainment, and (d) mixed use. Some general implications for consequence analysis are discussed.
Cost‐Effectiveness of Risk‐Reduction Measures from a National Viewpoint: A Case Study of the Angra Nuclear Plant in Brazil
Authors: de Oliveira Luiz Fernando Seixas , da Motta Barros Edson Benigno , Fleming Paulo Victor , Rosa Luiz Pinguelli
Published: May 2006

In this paper a systemic or national approach to cost‐effectiveness analysis of risk‐reduction measures is reviewed, and its advantages and limitations are discussed. The method is applied to the problem of the cost‐effectiveness of increasing the Angra 3 NPP containment wall thickness from the present 60 cm to 180 cm thick in order to prevent damage to the reactor core in case of a direct commercial aircraft crash on it. It is concluded that this measure is not cost‐effective if the referred approach is considered.
Chemical Health Effects Assessment Methodology for Airborne Contaminants
Authors: Brown Halina Szejnwald , West Carol Rowan , Bishop Donna R.
Published: May 2006

Chemical Health Effects Assessment Methodology (CHEM) is a new procedure for assessing hazardous properties of airborne toxic contaminants. CHEM evaluates substances for four major health effect categories: carcinogenicity, mutagenicity, reproductive/developmental toxicity, and toxic effects other than the first three. Three elements are considered in the assessment: weight of evidence, potency, and severity of effect. This approach produces a profile of toxic properties of chemicals which preserves their unique multidimensional character and highlights data gaps.
Issues Concerning the Estimation of the TD50
Authors: Portier Christopher J. , Hoel David G.
Published: May 2006

The TD50 (or tumorigenic dose rate 50) is a generally accepted measure of the carcinogenic potency of a chemical in a particular strain of animal. This paper discusses error in the estimation of the TD50 caused by intercurrent mortality and error resulting from consideration of only significant TD50's. Using computer simulations, we found that treatment‐related toxicity had only a small effect on estimating the TD50, with errors seldom exceeding 5%. The TD50 is sensitive to changes in tumor lethality with errors ranging to as high as 50%. Many of these errors were significantly different from zero and the results suggest that potency estimation could be improved by basing the estimates upon the tumor incidence rate rather than upon the tumor death rate when an estimate of tumor lethality is obtainable.
A Matrix‐Based Approach to Uncertainty and Sensitivity Analysis for Fault Trees1
Authors: Iman Ronald L.
Published: May 2006

System unavailabilities for large complex systems such as nuclear power plants are often evaluated through use of fault tree analysis. The system unavailability is obtained from a Boolean representation of a system fault tree. Even after truncation of higher order terms these expressions can be quite large, involving thousands of terms. A general matrix notation is proposed for the representation of Boolean expressions which facilitates uncertainty and sensitivity analysis calculations.
Estimating Fatality Reductions from Increased Safety Belt Use
Authors: Evans Leonard
Published: May 2006

Fatality reductions from increases in safety belt use are estimated taking into account that drivers who change from being nonusers to being users have lower accident involvement rates than the remaining nonusers, a process referred to as “selective recruitment.” Analytical functions are derived which express expected fatality reductions in terms of changes in safety belt use rates from an initial rate. The function parameters are determined by requiring that computed average crash rates for nonusers be 53% higher than the rates for users, a recently determined empirical value. These functions show that, depending on the initial use rate and use rate increase, selective recruitment may increase or decrease expected fatality reductions. However, effects are relatively small, in no case exceeding ±5.3%.
Radon Risk Information and Voluntary Protection: Evidence from a Natural Experiment
Authors: Johnson F. Reed , Luken Ralph A.
Published: May 2006

This study examines the perceived risks and mitigating behavior of Maine households who received new information on their exposures to significant health risks from indoor radon. The observed responses of these households illustrate conceptual issues related to designing an effective risk information program. Despite the involvement of generally well‐motivated homeowners and well‐intentioned researchers and government officials, we conclude that the risk information approach used in Maine failed to induce appropriate, cost‐effective voluntary protection. The results indicate that, after receiving radon test results, information on associated health risks, and suggestions on how to reduce exposures: (1) perceived risks tended to understate objective risks by orders of magnitude, and (2) there was no statistically significant relationship between mitigating behavior and objective risks. These results suggest that the formation of risk perceptions and subsequent behavioral adjustments involve complex interactions among information, contextual, socioeconomic, and psychological variables. Therefore, government programs that seek to reduce health and safety risks with information programs, instead of using more conventional enforced standards, must be crafted very carefully to accommodate this complex process.
Public Values in Risk Debates
Authors: Edwards Ward , von Winterfeldt Detlof
Published: May 2006

Both the issues inherent in regulation of specific risks and the contexts in which such regulatory processes occur are often characterized by confusion and controversy. Tools based on multiattribute utility measurement (MAUT) can help to clarify public values in risk debates and thus to facilitate option invention and decision making. Stakeholder group representatives, in interaction with an analyst, structure their values relevant to the problem into a value tree. The analyst prepares a common tree, iterating until all stakeholder representatives accept it. Stakeholders express their values as weights on the common tree. This provides a basis for option invention and negotiation. The paper presents three illustrative applications.
A Review of the High‐Level Nuclear Waste Repository Siting Analysis
Authors: Gregory Robin , Lichtenstein Sarah
Published: May 2006

We critique two 1986 Department of Energy reports concerning the selection of sites for characterization as the nation's first high‐level nuclear waste repository. We find that the multiattribute utility analysis of the five nominated sites was well done, although we express concern about the assessed probabilities, question the construction of two important attribute scales, and disagree with some of the value tradeoffs that were used. In contrast, we find the logic of the recommendations report to be weak and unconvincing.
Emissions from Mass Burn Resource Recovery Facilities
Authors: Marcus Jerry Z. , Mills Ronald J.
Published: May 2006

Recent resource recovery facility stack tests have increased the available pool of data on emissions from these facilities. This has led to more accurate predictions of emissions from proposed facilities. The source, type, and rate of emissions presented are based upon a review of the literature, theoretical approaches, stack test data from existing facilities, permit levels of other facilities, and discussions with equipment manufacturers. The pollutants selected for study are those regulated by United States Environmental Protection Agency (USEPA) Prevention of Significant Deterioration (PSD) regulations and other pollutants of concern. The pollutants studied are particulate matter, sulfur dioxide, nitrogen oxides, carbon monoxide, nonmethane hydrocarbons, hydrogen sulfide, reduced sulfide, reduced sulfur compounds, total reduced sulfur, lead, mercury, beryllium, arsenic, cadmium, chromium, chromium +6, copper, manganese, nickel, vanadium, zinc, hydrogen chloride, fluorides, sulfuric acid mist, polynuclear aromatic hydrocarbons, polychlorinated biphenyls, vinyl chloride, dioxins, furans, formaldehyde, and asbestos.
Concentrating on the Worst Performers
Authors: Lewis H. W.
Published: May 2006

There is a substantial variation in the quality of operators of nuclear power plants, and it is therefore widely believed that regulatory attention is best directed at the worst performers. What is not immediately apparent is a strategy for the optimal allocation of regulatory resources. We study a simple model for this problem, and find that, under reasonable assumptions, the optimal allocation does indeed behave as expected. The proper degree of unbalance, however, depends upon the effectiveness of regulation itself and on the variation among performers, ineffective regulation leading to more concentration on the bottom of the list and a net reduction in attention to the top. Not surprisingly, the optimal strategy is to press toward parity in risk, even if it means allowing some plants to become riskier. This strategy leads to a minimized net probability of accident anywhere.
Taxonomic Analysis of Perceived Risk: Modeling Individual and Group Perceptions Within Homogeneous Hazard Domains
Authors: Kraus Nancy Nighswonger , Slovic Paul
Published: May 2006

Previous studies of risk perception have typically focused on the mean judgments of a group of people regarding the riskiness (or safety) of a diverse set of hazardous activities, substances, and technologies. This paper reports the results of two studies that take a different path. Study 1 investigated whether models within a single technological domain were similar to previous models based on group means and diverse hazards. Study 2 created a group taxonomy of perceived risk for only one technological domain, railroads, and examined whether the structure of that taxonomy corresponded with taxonomies derived from prior studies of diverse hazards. Results from Study 1 indicated that the importance of various risk characteristics in determining perceived risk differed across individuals and across hazards, but not so much as to invalidate the results of earlier studies based on group means and diverse hazards. In Study 2, the detailed analysis of railroad hazards produced a structure that had both important similarities to, and dissimilarities from, the structure obtained in prior research with diverse hazard domains. The data also indicated that railroad hazards are really quite diverse, with some approaching nuclear reactors in their perceived seriousness. These results suggest that information about the diversity of perceptions within a single domain of hazards could provide valuable input to risk‐management decisions.
Estimation of Human Reproductive Risk from Animal Studies: Determination of Interspecies Extrapolation Factors for Steroid Hormone Effects on the Male
Authors: Meistrich Marvin L.
Published: May 2006

The problem of extrapolating effects of reproductive toxins on experimental animals to predict the doses that would produce infertility in human males is discussed using published data on effects of testosterone and estradiol on sperm production in the rat, rabbit, rhesus monkey, ram, stallion, and humans. This analysis indicates that calculation of the dose of testosterone that reduces human sperm counts by a given percentage is best done using the dose administered to laboratory animals expressed on the basis of body weight, as opposed to some other parameter such as body surface area. A survey of the available data in the literature indicates the incompleteness of the data set and the specific information needed to improve the basis for extrapolation. Nevertheless, we can predict from studies on laboratory animals the dose of testosterone necessary to reduce sperm counts in humans within a factor of 2.
Evaluation of Developmental Toxicity Data: A Discussion of Some Pertinent Factors and a Proposal
Authors: Hart William L. , Reynolds Ralph C. , Krasavage Walter J. , Ely Thomas S. , Bell R. Hays , Raleigh Robert L.
Published: May 2006

There is currently no well‐accepted standard method for evaluation of developmental toxicity data. This paper presents one approach to the evaluation of developmental toxicity data. We initially identify some pertinent factors that influence the interpretation of animal data and summarize the literature pertaining to these factors. Such factors include the quality and quantity of data and the relationship between maternal and developmental toxicity. We proceed with a discussion of quantitative assessment of data and propose schemes for qualitative and quantitative developmental hazard assessments.
Equity in Social Risk: Some Empirical Observations
Authors: Keller L. Robin , Sarin Rakesh K.
Published: May 2006

In societal risk analysis the equity of the distribution of risks is often an important consideration owing to the special nature of health risks. We empirically validate some assumptions about equity that have been discussed in the decision analytic literature. Our results show that the way fatalities are distributed throughout a society is considered along with the number of fatalities in evaluating alternative policies involving mortality risks. The concepts of ex ante equity and ex post equity are both shown to be important in judgments of fairness. We next present a decision model based on multiattribute preference theory incorporating the number of fatalities, as well as ex ante equity and ex post equity. When ex ante equity and ex post equity are positively weighted in this fair‐risk model, options with more equal risk distributions are ranked higher. Next we empirically show that the distribution of benefits has an impact on judgments of fairness. The fair‐risk model does not include information on the benefits distribution, so it would apply when benefits are distributed equally or when the decision maker wishes to not include benefits in the model. We briefly discuss how the notion of proportional equity can incorporate benefits into judgments of the fairness of risk distributions. We then include benefits in a more general model in which fair risk‐benefit combinations are those that are exchange equitable. A key implication of this envy‐free risk–benefit model is that an unequal distribution of risks may be preferred if it is accompanied by a compensatory differential in benefits consistent with peoples' preference tradeoffs between received benefits and assumed risks. Finally, we discuss how perceived deservedness may influence judgments about equity. We conclude with a discussion of the implications of research on alternative notions of equity for policy makers dealing with social risks.
Financing Liabilities Under Superfund
Authors: Anderson Dan R.
Published: May 2006

One of the more critical environmental risk areas involves the financing of cleanup costs associated with past improper disposal of hazardous wastes. These costs will run into the tens of billions of dollars. The federal Superfund program and related state programs are the driving forces for cleaning up hazardous waste. Under Superfund, the government collects taxes and coordinates cleanup strategies, and searches for potentially responsible parties (generators, disposers, transporters) to assist in financing the cleanup. To lessen the financial impact, responsible parties are looking to their liability insurers to provide coverage under old general liability insurance policies. Insurance companies contend that Superfund liabilities are not covered under liability policies. The paper examines the various financing methods and liabilities produced by Superfund. Particular emphasis is placed on developments in the courts which are resulting in a significant shift in the financial responsibilities to the insurance industry. Broad estimates of the financial impact of Superfund liabilities are developed. Finally, several public policy issues, which are raised by the topics exmained in this paper, are discussed.