Avian Influenza Risk Perception and Live Poultry Purchase in Guangzhou, China, 2006

Human H5N1 highly pathogenic avian influenza (HPAI) infection is associated with intimate exposure to live poultry. Perceptions of risk can modify behaviors, influencing actual exposure. However, greater hazard is not necessarily followed by perception of greater risk and more precautionary behavior because self-serving cognitive biases modulate precautionary and hazardous behaviors. We examined risk perception associated with avian influenza. A total of 1,550 face-to-face within-household interviews and 1,760 telephone interviews were derived to study avian influenza risk perception and live poultry use in Guangzhou and Hong Kong, respectively. Chi-square and Mann-Whitney tests assessed bivariate associations and risk distributions, respectively, and fully adjusted multivariate logistic models determined independent risk associations. Relative to Hong Kong, perceived "generalized" risk from buying live poultry (GZ, 58%, 95% confidence interval 55–60% vs. HK, 41%, 39–43%; χ²= 86.95, df  = 1, p < 0.001) and perceived self/family risk from buying ( z  =−2.092, p  = 0.036) were higher in Guangzhou. Higher perceived "generalized" risk was associated with not buying live poultry (OR = 0.65, 0.49–0.85), consistent with the pattern seen in Hong Kong, while perceived higher self/family risk was associated with buying ("likely/very likely/certain" OR = 1.74, 1.18–2.59); no such association was seen in Hong Kong. Multivariate adjustment indicated older age was associated with buying live poultry in Guangzhou (OR = 2.91, 1.36–6.25). Guangzhou respondents perceived greater risk relative to Hong Kong. Buying live poultry was associated with perceptions of less "generalized" risk but more self/family risk. Higher generalized risk was associated with fewer live poultry purchases, suggesting generalized risk may be a useful indicator of precautionary HPAI risk behavior.     

Physiologically-Based Pharmacokinetic Model for Trichloroethylene Considering Enterohepatic Recirculation of Major Metabolites

Trichloroacetic acid (TCA) is major metabolite of trichloroethylene (TRI) thought to contribute to its hepatocarcinogenic effects in mice. Recent studies have shown that peak blood concentrations of TCA in rats do not occur until approximately 12 hours following an oral dose of TRI. However, blood concentrations of TRI reach maximum within an hour and are nondetectable after 2 hours.⁽¹⁾ The results of study which examined the enterohepatic recirculation (EHC) of the principle TRI metabolited⁽²⁾ was used to develop physiologically-based pharmacokinetic model for TRI, which includes enterohepatic recirculation of its metabolites. The model quantitatively predicts the uptake, distribution and elimination of TRI, trichloroethanol, trichloroethanol-glucuronide, and TCA and includes production of metabolites through the enterohepatic recirculation pathway. Physiologic parameters used in the model were obtained from the literature.^(3.4) Parameters for TRI metabolism were taken from Fisher et al.⁽⁵⁾ Other kinetic parameters were found in the literature or estimated from experimental data.⁽²⁾ The model was calibrated to data from experiments of an earlier study where TRI was orally administered⁽²⁾ Verification of the model was conducted using data on the enterohepatic recirculation of TCEOH and TCA⁽²⁾ chloral hydrate data (infusion doses) from Merdink,⁽¹⁾ and TRI data from Templin(l) and Larson and Bull.⁽¹⁾     

What Do We Know About Making Risk Comparisons?

The risks of unfamiliar technologies are often evaluated by comparing them with the risks of more familiar ones. Such risk comparisons have been criticized for neglecting critical dimensions of risky decisions. In a guide written for the Chemical Manufacturers Association, Covello et al. (¹) have summarized these critiques and developed a taxonomy that characterizes possible risk comparisons in terms of their acceptability (or objectionableness). We asked four diverse groups of subjects to judge the acceptability of 14 statements produced by Covello et al. as examples of their categories. We found no correlation between the judgments of acceptability produced by our subjects and those predicted by Covello et al. .     

Comparing Toxicologic and Epidemiologic Studies: Methylene Chloride-A Case Study

Exposure to methylene chloride induces lung and liver cancers in mice. The mouse bioassay data have been used as the basis for several cancer risk assessments. ^(1,2) The results from epidemiologic studies of workers exposed to methylene chloride have been mixed with respect to demonstrating an increased cancer risk. The results from a negative epidemiologic study of Kodak workers have been used by two groups of investigators to test the predictions from the EPA risk assessment models.^(3,4) These two groups used very different approaches to this problem, which resulted in opposite conclusions regarding the consistency between the animal model predictions and the Kodak study results. The results from the Kodak study are used to test the predictions from OSHA's multistage models of liver and lung cancer risk. Confidence intervals for the standardized mortality ratios (SMRs) from the Kodak study are compared with the predicted confidence intervals derived from OSHA's risk assessment models. Adjustments for the "healthy worker effect," differences in length of follow-up, and dosimetry between animals and humans were incorporated into these comparisons. Based on these comparisons, we conclude that the negative results from the Kodak study are not inconsistent with the predictions from OSHA's risk assessment model.     

The Possibility for "Natural" Generation of Chlorinated Organic Compounds

There is continuing concern for the exposure of persons to various chlorinated organics via the environment, for example, chlorinated disinfection byproducts in drinking water.⁽¹⁾ Some of these may be carcinogenic,⁽²⁾ although the evidence is far from strong.⁽³⁾ There is an accumulating body of evidence that one of the normal human immunological responses to foreign agents is the generation of hypochlorous acid. This evidence will be summarized. The possibility that this HOCl generated in vivo could result in the formation of organo-chlorine compounds does not appear to have been seriously considered. Based on best available information, the amount of such byproduct formation will be estimated.     

Cancer Risk Estimation for Mixtures of Coal Tars

Two-year chronic bioassays were conducted by using B6C3F1 female mice fed several concentrations of two different mixtures of coal tars from manufactured gas waste sites or benzo(a)pyrene (BaP). The purpose of the study was to obtain estimates of cancer potency of coal tar mixtures, by using conventional regulatory methods, for use in manufactured gas waste site remediation. A secondary purpose was to investigate the validity of using the concentration of a single potent carcinogen, in this case benzo(a)pyrene, to estimate the relative risk for a coal tar mixture. The study has shown that BaP dominates the cancer risk when its concentration is greater than 6,300 ppm in the coal tar mixture. In this case the most sensitive tissue site is the forestomach. Using low-dose linear extrapolation, the lifetime cancer risk for humans is estimated to be: Risk < 1.03 × 10⁻⁴ (ppm coal tar in total diet) + 240 × 10⁻⁴ (ppm BaP in total diet), based on forestomach tumors. If the BaP concentration in the coal tar mixture is less than 6,300 ppm, the more likely case, then lung tumors provide the largest estimated upper limit of risk, Risk < 2.55 × 10⁻⁴ (ppm coal tar in total diet), with no contribution of BaP to lung tumors. The upper limit of the cancer potency (slope factor) for lifetime oral exposure to benzo(a)pyrene is 1.2 × 10⁻³ per μg per kg body weight per day from this Good Laboratory Practice (GLP) study compared with the current value of 7.3 × 10⁻³ per μg per kg body weight per day listed in the U.S. EPA Integrated Risk Information System.     

Evaluating the Simplified Conjoint Expected Risk Model: Comparing the Use of Objective and Subjective Information

The simplified Conjoint Expected Risk (CER) model by Holtgrave and Weber posits that perceived risk is a linear combination of the subjective judgments of the probabilities of harm, benefit, and status quo, and the expected harm and benefit of an activity. It modifies Luce and Weber's original CER model—that uses objective information to evaluate financial gambles—to accommodate activities such as health/technology activities where values of the model variables are subjective. If the simplified model is a valid modification of the original model, its performance should not be sensitive to the use of subjective information. However, because people may evaluate information differently when objective information is provided to them than when they generate information on their own, the performance of the simplified CER model may not be robust to the source of model-variable information. We compared the use of objective and subjective information, and results indicate that the estimates of the simplified CER model parameters and the proportion of variance in risk judgments accounted for by the model are similar under these two conditions. Thus, the simplified CER model is viable with activities for which harm and benefit information is subjective.     

Relative Contributions of Four Exposure Pathways to Influenza Infection Risk

The relative contribution of four influenza virus exposure pathways—(1) virus-contaminated hand contact with facial membranes, (2) inhalation of respirable cough particles, (3) inhalation of inspirable cough particles, and (4) spray of cough droplets onto facial membranes—must be quantified to determine the potential efficacy of nonpharmaceutical interventions of transmission. We used a mathematical model to estimate the relative contributions of the four pathways to infection risk in the context of a person attending a bed-ridden family member ill with influenza. Considering the uncertainties in the sparse human subject influenza dose-response data, we assumed alternative ratios of 3,200:1 and 1:1 for the infectivity of inhaled respirable virus to intranasally instilled virus. For the 3,200:1 ratio, pathways (1), (2), and (4) contribute substantially to influenza risk: at a virus saliva concentration of 10⁶ mL⁻¹, pathways (1), (2), (3), and (4) contribute, respectively, 31%, 17%, 0.52%, and 52% of the infection risk. With increasing virus concentrations, pathway (2) increases in importance, while pathway (4) decreases in importance. In contrast, for the 1:1 infectivity ratio, pathway (1) is the most important overall: at a virus saliva concentration of 10⁶ mL⁻¹, pathways (1), (2), (3), and (4) contribute, respectively, 93%, 0.037%, 3.3%, and 3.7% of the infection risk. With increasing virus concentrations, pathway (3) increases in importance, while pathway (4) decreases in importance. Given the sparse knowledge concerning influenza dose and infectivity via different exposure pathways, nonpharmaceutical interventions for influenza should simultaneously address potential exposure via hand contact to the face, inhalation, and droplet spray.     

On the Relationship Between Carcinogenicity and Acute Toxicity

Parodi et al. ⁽¹⁾ and Zeise et al. ⁽²⁾ found a surprising statistical correlation (or association) between acute toxicity and carcinogenic potency. In order to shed light on the questions of whether or not it is a causal correlation, and whether or not it is a statistical or tautological artifact, we have compared the correlations for the NCI/NTP data set with those for chemicals not in this set. Carcinogenic potencies were taken from the Gold et al. database. We find a weak correlation with an average value of TD₅₀/LD₅₀= 0.04 for the non-NCI data set, compared with TD₅₀/LD₅₀= 0.15 for the NCI data set. We conclude that it is not easy to distinguish types of carcinogens on the basis of whether or not they are acutely toxic.     

Bounding Estimates for Critical Events When Directly Disposing Highly Enriched Spent Nuclear Fuel in Unsaturated Tuff

This paper examines the possibility of criticality in a nuclear waste repository. The estimated probabilities are rough bounds and do not entirely dismiss the possibility of a critical condition; however, they do point to the difficulty of creating conditions under which a critical mass could be assembled (i.e., corrosion of containers, separation of neutron absorbers from the fissile material, and collapse or precipitation of the fissile material). In addition, should a criticality occur in or near a container, the bounding consequence calculations showed that fissions from one critical event are quite small (<˜10²⁰ fissions, if similar to aqueous and metal accidents and experiments). Furthermore, a reasonable upper bound of total critical events of 10²⁸ fissions corresponds to only 0.1% of the number of fissions represented by the spent nuclear fuel inventory in a repository containing 70,000 metric tons of heavy metal (MTHM) (the expected size for the proposed repository at Yucca Mountain, Nevada).     

On the Effect of Probability Distributions of Input Variables in Public Health Risk Assessment

A central part of probabilistic public health risk assessment is the selection of probability distributions for the uncertain input variables. In this paper, we apply the first-order reliability method (FORM)^(1–3) as a probabilistic tool to assess the effect of probability distributions of the input random variables on the probability that risk exceeds a threshold level (termed the probability of failure) and on the relevant probabilistic sensitivities. The analysis was applied to a case study given by Thompson et al. ⁽⁴⁾ on cancer risk caused by the ingestion of benzene contaminated soil. Normal, lognormal, and uniform distributions were used in the analysis. The results show that the selection of a probability distribution function for the uncertain variables in this case study had a moderate impact on the probability that values would fall above a given threshold risk when the threshold risk is at the 50th percentile of the original distribution given by Thompson et al. ⁽⁴⁾ The impact was much greater when the threshold risk level was at the 95th percentile. The impact on uncertainty sensitivity, however, showed a reversed trend, where the impact was more appreciable for the 50th percentile of the original distribution of risk given by Thompson et al. ⁴ than for the 95th percentile. Nevertheless, the choice of distribution shape did not alter the order of probabilistic sensitivity of the basic uncertain variables.     

Presenting Uncertainty in Health Risk Assessment: Initial Studies of Its Effects on Risk Perception and Trust

Some analysts suggest that discussing uncertainties in health risk assessments might reduce citizens'perceptions of risk and increase their respect for the risk-assessing agency. We tested this assumption with simulated news stories varying simple displays of uncertainty (e.g., a range of risk estimates, with and without graphics). Subjects from Eugene, Oregon, read one story each, and then answered a questionnaire. Three studies tested between 180 and 272 subjects each. Two focus groups obtained more detailed responses to these stories. The results suggested that (1) people are unfamiliar with uncertainty in risk assessments and in science; (2) people may recognize uncertainty when it is presented simply; (3) graphics may help people recognize uncertainty; (4) reactions to the environmental problems in the stories seemed affected less by presentation of uncertainty than by general risk attitudes and perceptions; (5) agency discussion of uncertainty in risk estimates may signal agency honesty and agency incompetence for some people; and (6) people seem to see lower risk estimates (10^-6, as opposed to 10^-3) as less credible. These findings, if confirmed, would have important implications for risk communication.     

A Method for Computing the Fraction of Attributable Risk Related to Climate Damages

The recent decision of the U.S. Supreme Court on the regulation of CO₂ emissions from new motor vehicles^{( 1 )} shows the need for a robust methodology to evaluate the fraction of attributable risk from such emissions. The methodology must enable decisionmakers to reach practically relevant conclusions on the basis of expert assessments the decisionmakers see as an expression of research in progress, rather than as knowledge consolidated beyond any reasonable doubt.^{( 2,3,4 )} This article presents such a methodology and demonstrates its use for the Alpine heat wave of 2003. In a Bayesian setting, different expert assessments on temperature trends and volatility can be formalized as probability distributions, with initial weights (priors) attached to them. By Bayesian learning, these weights can be adjusted in the light of data. The fraction of heat wave risk attributable to anthropogenic climate change can then be computed from the posterior distribution. We show that very different priors consistently lead to the result that anthropogenic climate change has contributed more than 90% to the probability of the Alpine summer heat wave in 2003. The present method can be extended to a wide range of applications where conclusions must be drawn from divergent assessments under uncertainty.     

Source Attribution of Food-Borne Zoonoses in New Zealand: A Modified Hald Model

A Bayesian approach was developed by Hald et al .^{( 1 )} to estimate the contribution of different food sources to the burden of human salmonellosis in Denmark. This article describes the development of several modifications that can be used to adapt the model to different countries and pathogens. Our modified Hald model has several advantages over the original approach, which include the introduction of uncertainty in the estimates of source prevalence and an improved strategy for identifiability. We have applied our modified model to the two major food-borne zoonoses in New Zealand, namely, campylobacteriosis and salmonellosis. Major challenges were the data quality for salmonellosis and the inclusion of environmental sources of campylobacteriosis. We conclude that by modifying the Hald model we have improved its identifiability, made it more applicable to countries with less intensive surveillance, and feasible for other pathogens, in particular with respect to the inclusion of nonfood sources. The wider application and better understanding of this approach is of particular importance due to the value of the model for decision making and risk management.     

A Physiologically Based Model for Gastrointestinal Absorption and Excretion of Chemicals Carried by Lipids

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.     

On the Correlation Coefficient Between the TD50 and the MTD

The existence of correlation between the carcinogenic potency and the maximum tolerated dose has been the subject of many investigations in recent years. Several attempts have been made to quantify this correlation in different bioassay experiments. By using some distributional assumptions, Krewski et al .⁽¹⁾ derive an analytic expression for the coefficient of correlation between the carcinogenic potency TD₅₀ and the maximum tolerated dose. Here, we discuss the deviation that may result in using their analytical expression. By taking a more general approach we derive an expression for the correlation coefficient which includes the result of Krewski et al .⁽¹⁾ as a special case, and show that their expression may overestimate the correlation in some instances and yet underestimate the correlation in other instances. The proposed method is illustrated by application to a real dataset.     

Summary of the Workshop on Issues in Risk Assessment: Quantitative Methods for Developmental Toxicology

This report summarizes the proceedings of a conference on quantitative methods for assessing the risks of developmental toxicants. The conference was planned by a subcommittee of the National Research Council's Committee on Risk Assessment Methodology ⁴ in conjunction with staff from several federal agencies, including the U.S. Environmental Protection Agency, U.S. Food and Drug Administration, U.S. Consumer Products Safety Commission, and Health and Welfare Canada. Issues discussed at the workshop included computerized techniques for hazard identification, use of human and animal data for defining risks in a clinical setting, relationships between end points in developmental toxicity testing, reference dose calculations for developmental toxicology, analysis of quantitative dose-response data, mechanisms of developmental toxicity, physiologically based pharmacokinetic models, and structure-activity relationships. Although a formal consensus was not sought, many participants favored the evolution of quantitative techniques for developmental toxicology risk assessment, including the replacement of lowest observed adverse effect levels (LOAELs) and no observed adverse effect levels (NOAELs) with the benchmark dose methodology.     

Book Reviews

Books are reviewed in this article:
Corporate Management of Health and Safety Hazards: A Comparison Current Practice By Roger E. Kasperson, Jeanne X. Kasperson
Risk Assessment of Hazardous Chemical Systems in Developing Countries By Kirk R. Smith, Richard A. Carpenter, and M. Susanne Faulstich (with contributions from Loren Habegger, F. Dewolfe Miller, and David Weinstein
Risk Assessment and Risk Management of Industrial and Environmental Chemicals, Volume 15, Advances in Modern Environmental Toxicology Edited by C. Richard Cothern, Myron A. Mehlman, and William L. Marcus Princeton
Advances in Air Sampling (Second Printing) American Conference of Governmental Industrial Hygienists Chelsea
Living in a Chemical World: Occupational and Environmental Significance of Industrial Carcinogens Edited by Cesare Maltoni and Irving J. Selikoff
Rural Groundwater Contamination (Second Printing) Edited by Frank M. D'Itri and Lois G. Wolfson Chelsea
Risk Assessment and Management: Emergency Planning Perspectives Edited by Larry R.G. Martin and Gilbert Lafond Waterloo
Banbury Report 31: Carcinogen Risk Assessment: New Directions in the Qualitative and Quantitative Aspects Edited by Ronald W. Hart and Fred D. Hoerger
Toxic Air Pollutant Guidelines: Review of Recent Progress and Problems Edited by Paul J. Lioy and Morton Lippmann
The Risk Ranking Technique in Decision Making ² By John C. Chicken and Michael R. Hayns     

Evacuation Risks: A Tentative Approach for Quantification

This study tries to assess the risk of deaths and injuries from motor vehicle accidents associated with an evacuation of population groups in case of nuclear plant accidents. The risk per person–km is evaluated using: (a) data from previous evacuation: information from Soufriere evacuation (Guadeloupe Island 1976) and Mississauga (1979), added to Hans and Sell's data: no road accident occurred for a sample of 1,500,000 persons; (b) national recording system for motor vehicle accident: the rates of 2.2 10 ^-8 deaths per person–km and 32 10^-8 injuries per person–km is calculated as an average. These last rates in France overestimate the number of casualties. A reasonable hypothesis is to assume that the probability of road accident occurrence follows a Poisson distribution, as these events are independent and unfrequent, as no accident was observed in a sample of 1,500,000 persons the probability is between 0 and an upper value of 0.24 10^-8 deaths per person-km and 3.29 10^-8 injuries per person–km. The average and maximum population involved within different radii around French and U.S. Nuclear power sites are taken as a sample size in order to study the total risk of deaths and injuries in the hypothesis of an evacuation being necessary to protect the populations.     

An Evaluation of Alternative Safety Criteria for Nuclear Power Plants

Safety criteria for frequency of nuclear-reactor accidents and for reactor-induced risk to individuals and to society are evaluated on the basis of their comprehensiveness, clarity, recognition of uncertainty, practicability, defensibility, simplicity, and internal consistency. Many criteria were found to be comprehensive and practicable; few completely satisfied the other evaluation standards. A consensus inferred from the most favorably evaluated criteria would allow between 1.0time10^-4 and 1.0time10^-3 core melts per reactor year, between 1.0time10^-6 and 2.0time10^-5 fatalities per reactor year per individual, and a total exposure in the United States of between 1000 and 10,000 person rems per reactor year. This consensus is consistent with the criteria proposed in NUREG0880.