Reproductive and Developmental Risks from Ethylene Oxide: A Probabilistic Characterization of Possible Regulatory Thresholds

Ethylene oxide is a gas produced in large quantities in the United States that is used primarily as a chemical intermediate in the production of ethylene glycol, propylene glycol, non-ionic surfactants, ethanolamines, glycol ethers, and other chemicals. It has been well established that ethylene oxide can induce cancer, genetic, reproductive and developmental, and acute health effects in animals. The U.S. Environmental Protection Agency is currently developing both a cancer potency factor and a reference concentration (RfC) for ethylene oxide. This study used the rich database on the reproductive and developmental effects of ethylene oxide to develop a probabilistic characterization of possible regulatory thresholds for ethylene oxide. This analysis was based on the standard regulatory approach for noncancer risk assessment, but involved several innovative elements, such as: (1) the use of advanced statistical methods to account for correlations in developmental outcomes among littermates and allow for simultaneous control of covariates (such as litter size); (2) the application of a probabilistic approach for characterizing the uncertainty in extrapolating the animal results to humans; and (3) the use of a quantitative approach to account for the variation in heterogeneity among the human population. This article presents several classes of results, including: (1) probabilistic characterizations of ED10s for two quantal reproductive outcomes-resorption and fetal death, (2) probabilistic characterizations of one developmental outcome-the dose expected to yield a 5% reduction in fetal (or pup) weight, (3) estimates of the RfCs that would result from using these values in the standard regulatory approach for noncancer risk assessment, and (4) a probabilistic characterization of the level of ethylene oxide exposure that would be expected to yield a 1/1,000 increase in the risk of reproductive or developmental outcomes in exposed human populations.     

A Weighted Composite Dose – Response Model For Human Salmonellosis

This article describes the development of a weighted composite dose – response model for human salmonellosis. Data from previously reported human challenge studies were categorized into two different groups representing low and moderately virulent/pathogenic Salmonella strains based on a disease end point. Because epidemiological data indicate that some Salmonella strains are particularly pathogenic, and in the absence of human feeding study data for such strains, Shigella dysenteriae was used as a proxy for highly virulent strains. Three single-hit dose – response models were applied to the human feeding study data and evaluated for best fit using maximum likelihood estimation: (1) the exponential (E-1pop), (2) the two-subpopulation exponential (E-2pop), and (3) the Beta-Poisson (BP). Based on the goodness-of-fit test, the E-1pop and BP were the best-fit models for low and moderately virulent/pathogenic Salmonella strains, and the E-2pop and BP models were better for highly virulent/pathogenic strains. Epistemic analysis was conducted by determining the degree of confidence associated with the selected models, which was found to be 50%/50% (E-1pop/BP) for low and moderately pathogenic Salmonella strains, and 9.8%/90.2% (E-2pop/BP) for highly virulent strains. The degree of confidence for each component model and variations in the proportion of strains within each virulence/pathogenicity category were incorporated into the overall composite model. This study describes the influence of variation in strain virulence and host susceptibility on the shape of the population dose – response relationship.     

Role of Negative Emotion in Communication about CO2 Risks

This article describes how the effectiveness of risk communication is determined by the interaction between emotional and informative elements. An experiment is described that examined the role of negative emotion in communication about CO₂ risks. This experiment was based on the elaboration likelihood model and the related heuristic systematic model of attitude formation. The results indicated that inducing fear of CO₂ risks leads to systematic processing of information about energy conservation as a risk-reducing strategy. In turn, this results in more favorable attitudes toward energy conservation if strong arguments are provided. Individual differences in concern seem to have similar effects.     

QUALITY MANAGEMENT: UNIVERSAL OR CONTEXT DEPENDENT?

Quality management has often been advocated as being universally applicable to organizations. This is in contrast with the manufacturing strategy contingency approach of Operations Management that advocates internal and external consistency between manufacturing strategy choices. This article empirically investigates whether quality management practices are contingent on a plant's manufacturing strategy context, by examining the use of process quality management practices—a critical and distinctive subset of the whole set of quality management practices—across plants representative of different manufacturing strategy contexts. The study strongly suggests that process quality management practices are contingent on a plant's manufacturing strategy, and identifies mechanisms by which this takes place.     

INTERNATIONAL DIFFUSION OF ISO 14000 CERTIFICATION

The ISO 9000 series of quality management systems standards and the more recent ISO 14000 environmental management systems standards have generated much controversy among practitioners. Although ISO 9000 has become a de facto requirement for many firms, its effects are poorly understood, and similarly the value and domain of applicability of ISO 14000 have been questioned. This paper reports on an exploratory study into the global spread of ISO 14000. We interviewed practitioners worldwide to identify factors that they believe explain differences between national ISO 14000 certification counts. We then collected quantititive data for these factors and, using regression analysis, we found that exports, environmental attitudes (combined with economic development), and ISO 9000 certification count were significant. The fact that ISO 9000 appears as an important factor explaining diffusion of ISO 14000 certifications suggests that the drivers behind the two have significant overlap. This indicates that, although ISO 14000 is an environmental standard, many of the factors driving national certification patterns are not at all environmental in nature, and that ISO 14000 therefore needs to be studied from a broader perspective than from a purely environmental point of view.     

Higher Education's Role in the Dialogue on Race

The university is a logical locus for discussionof the role race has played in our society. Perhaps noAmerican institution is more committed to free andopen dialogue than the university. Higher educationcan thus provide a context for the recognition ofissues as well as a forum for the resolution ofinitiatives. To date, however, university attempts atdiversity training have often imbued recipients withself-consciousness, usurping the unity implicit in theword `university' and evoking an even greater tendencytoward separatism. The university's traditional questfor truth has been subverted by a subtle and pervasivesense that some views are more correct than others,that openness is dangerous, and that some issues mighteven be taboo. At best, such an approach to diversityleads to a fragile stalemate among self-containedenclaves. By championing President Clinton's call fora dialogue on race, the university can restore itselfas an institution that puts honesty above all else.Not only is there a resonant rationale for theuniversity's central responsibility in this debate,but there is also a pedagogical means by which itsrole can be realized. This paper proposes a model forethnic dialogue relevant to either a text-based orissues-based class. Borrowing from pedagogy developedin professional schools, we believe that the tenets ofthe `case method' can create a climate conducive tothe substantive scrutiny of race, ethnicity, andprejudice in general. We argue that this dialogueshould not be a mere add-on to college life, butintegrated into existing curricula in the socialsciences, literature, and history. Heated debate canthen occur without anger, and race/ethnicity can bediscussed without fear of recrimination.Paradoxically, the very expression of ethnicity may bethe catalyst that eventually moves multiculturalismtoward interculturalism – where differences are nolonger articulated, measurable or even discernible.     

Risk analysis of PCB exposure via the soil-food crop pathway, and alternatives for remediation at Serpukhov, Russian Federation.

A risk assessment was conducted to determine the likelihood of certain health risks resulting from exposure to soils and food crops contaminated with polychlorinated biphenyl (PCBs). PCBs have contaminated soils, river sediments, and air in the past as a result of industrial activities at a capacitor plant located in the City of Serpukhov, Russian Federation. This risk assessment and suggestions for remediation are designed to aid in decision-making efforts by a joint Russian-American research team developing a community, national, and international response to industrial contamination. Bobovnikova et al. (The Science of the Total Environment 139/140, 357-364, [1993]) have reported that PCBs are elevated in soils and sediments, breast milk, and locally grown foods in the Serpukhov area. Data from these and other investigators have been used in this risk assessment to calculate a potential cancer risk resulting from exposure to PCBs. Our assessment indicates that members of the local population may be at increased risk of cancer, and possibly other adverse health effects, as a result of PCB contamination of their environment. Because previously unassessed environmental contamination is a common problem in the former Soviet Republics, as well as many other areas of the world, we believe this type of evaluation, using known methods, can serve as a model for assessment efforts in other parts of the globe and result in remediative efforts in regions constrained by faltering economies.     

Risk Estimation and Value-of-Information Analysis for Three Proposed Genetic Screening Programs for Chronic Beryllium Disease Prevention

Genetic differences (polymorphisms) among members of a population are thought to influence susceptibility to various environmental exposures. In practice, however, this information is rarely incorporated into quantitative risk assessment and risk management. We describe an analytic framework for predicting the risk reduction and value-of-information (VOI) resulting from specific risk management applications of genetic biomarkers, and we apply the framework to the example of occupational chronic beryllium disease (CBD), an immune-mediated pulmonary granulomatous disease. One described Human Leukocyte Antigen gene variant, HLA-DP beta 1*0201, contains a substitution of glutamate for lysine at position 69 that appears to have high sensitivity (approximately 94%) but low specificity (approximately 70%) with respect to CBD among individuals occupationally exposed to respirable beryllium. The expected postintervention CBD prevalence rates for using the genetic variant (1) as a required job placement screen, (2) as a medical screen for semiannual in place of annual lymphocyte proliferation testing, or (3) as a voluntary job placement screen are 0.08%, 0.8%, and 0.6%, respectively, in a hypothetical cohort with 1% baseline CBD prevalence. VOI analysis is used to examine the reduction in total social cost, calculated as the net value of disease reduction and financial expenditures, expected for proposed CBD intervention programs based on the genetic susceptibility test. For the example cohort, the expected net VOI per beryllium worker for genetically based testing and intervention is $13,000, $1,800, and $5,100, respectively, based on a health valuation of $1.45 million per CBD case avoided. VOI results for alternative CBD evaluations are also presented. Despite large parameter uncertainty, probabilistic analysis predicts generally positive utility for each of the three evaluated programs when avoidance of a CBD case is valued at $1 million or higher. Although the utility of a proposed risk management program may be evaluated solely in terms of risk reduction and financial costs, decisions about genetic testing and program implementation must also consider serious social, legal, and ethical factors.     

Chemical and Radiation Environmental Risk Management: Differences, Commonalities, and Challenges

Driven by differing statutory mandates and programmatic separation of regulatory responsibilities between federal, state, and tribal agencies, distinct chemical and radiation risk management strategies have evolved. In the field this separation poses real challenges since many of the major environmental risk management decisions we face today require the evaluation of both types of risks. Over the last decade, federal, state, and tribal agencies have continued to discuss their different approaches and explore areas where their activities could be harmonized. The current framework for managing public exposures to chemical carcinogens has been referred to as a "bottom up approach." Risk between 10(-4) and 10(-6) is established as an upper bound goal. In contrast, a "top down" approach that sets an upper bound dose limit and couples with site specific As Low As Reasonably Achievable Principle (ALARA), is in place to manage individual exposure to radiation. While radiation risk are typically managed on a cumulative basis, exposure to chemicals is generally managed on a chemical-by-chemical, medium-by-medium basis. There are also differences in the nature and size of sites where chemical and radiation contamination is found. Such differences result in divergent management concerns. In spite of these differences, there are several common and practical concerns among radiation and chemical risk managers. They include 1) the issue of cost for site redevelopment and long-term stewardship, 2) public acceptance and involvement, and 3) the need for flexible risk management framework to address the first two issues. This article attempts to synthesize key differences, opportunities for harmonization, and challenges ahead.