The Risk Screening for Indoor Air Pollution Chemicals in Japan

In recent years, public health problems caused by indoor air pollution have been drawing strong public concern in Japan. After conducting extensive exposure assessment, governmental agencies have taken effective measures to solve the problem; for instance, "Guidelines for indoor air quality (IAQ)" of 13 chemicals, for example, formaldehyde, toluene, and xylene, has been established. Thousands of chemicals have been identified in the indoor environment. Priority rating of those chemicals, however, was not based on the health risk level. We developed a risk-screening scheme for indoor air pollution chemicals and analyzed the current status of the risk levels of those chemicals in Japan. We researched scientific knowledge of health hazards and exposure surveys of indoor air pollution chemicals in Japan, and classified those chemicals based on the health risk level estimated from the scheme. The risk levels of 93 chemicals were characterized and six chemicals (formaldehyde, acrolein, 1,4-dichlorobenzene, benzene, tetrachloroethylene, and benzo(a)pyrene) were classified in the highest risk category.     

Estimation of the Leukemia Risk in Human Populations Exposed to Benzene from Tobacco Smoke Using Epidemiological Data

Several epidemiological studies have demonstrated an association between occupational benzene exposure and increased leukemia risk, in particular acute myeloid leukemia (AML). However, there is still uncertainty as to the risk to the general population from exposure to lower environmental levels of benzene. To estimate the excess risk of leukemia from low‐dose benzene exposure, various methods for incorporating epidemiological data in quantitative risk assessment were utilized. Tobacco smoke was identified as one of the main potential sources of benzene exposure and was the focus of this exposure assessment, allowing further investigation of the role of benzene in smoking‐induced leukemia. Potency estimates for benzene were generated from individual occupational studies and meta‐analysis data, and an exposure assessment for two smoking subgroups (light and heavy smokers) carried out. Subsequently, various techniques, including life‐table analysis, were then used to evaluate both the excess lifetime risk and the contribution of benzene to smoking‐induced leukemia and AML. The excess lifetime risk for smokers was estimated at between two and six additional leukemia deaths in 10,000 and one to three additional AML deaths in 10,000. The contribution of benzene to smoking‐induced leukemia was estimated at between 9% and 24% (U_pperCL 14–31%). For AML this contribution was estimated as 11–30% (U_pperCL 22–60%). From the assessments carried out here, it appears there is an increased risk of leukemia from low‐level exposure to benzene and that benzene may contribute up to a third of smoking‐induced leukemia. Comparable results from using methods with varying degrees of complexity were generated.     

A Quantitative Estimate of Leukemia Mortality Associated with Occupational Exposure to Benzene3

In 1980, the U.S. Supreme Court vacated a revised occupational standard for benzene, stating that the Occupational Safety and Health Administration (OSHA) had failed to demonstrate that significant health risks existed under the current standard. This decision has been interpreted by OSHA as requiring the consideration of quantitative risk assessments, whenever possible, in the development of regulations for occupational carcinogens. In light of this decision, the available epidemiologic evidence was used to generate a quantitative risk assessment for benzene. Uncertainties regarding the levels and lengths of benzene exposure for the studied cohorts were incorporated into the analysis. Based on the one-hit model, the assessment indicates that a working lifetime exposure to benzene at the current permissible exposure level (10 ppm) poses a substantial excess risk of death from leukemia. This report discusses the calculation of the risk estimates, the basis for relying on certain assumptions, and the inherent limitations of using epidemiologic studies to quantify cancer risks.     

Consideration of Background Exposures in the Management of Hazardous Waste Sites: A New Approach to Risk Assessment

The current approach to health risk assessment of toxic waste sites in the U.S. may lead to considerable expenditure of resources without any meaningful reduction in population exposure. Risk assessment methods used generally ignore background exposures and consider only incremental risk estimates for maximally exposed individuals. Such risk estimates do not address true public health risks to which background exposures also contribute. The purpose of this paper is to recommend a new approach to risk assessment and risk management concerning toxic waste sites. Under this new approach, which we have called public health risk assessment, chemical substances would be classified into a level of concern based on the potential health risks associated with typical national and regional background exposures. Site assessment would then be based on the level of concern for the particular pollutants involved and the potential contribution of site contaminants to typical background human exposures. While various problems can be foreseen with this approach, the key advantage is that resources would be allocated to reduce the most important sources of human exposure, and site remediation decisions could be simplified by focussing on exposure assessment rather than questionable risk extrapolations.     

Potential Airborne Asbestos Exposure and Risk Associated with the Historical Use of Cosmetic Talcum Powder Products

Over time, concerns have been raised regarding the potential for human exposure and risk from asbestos in cosmetic‐talc–containing consumer products. In 1985, the U.S. Food and Drug Administration (FDA) conducted a risk assessment evaluating the potential inhalation asbestos exposure associated with the cosmetic talc consumer use scenario of powdering an infant during diapering, and found that risks were below levels associated with background asbestos exposures and risk. However, given the scope and age of the FDA's assessment, it was unknown whether the agency's conclusions remained relevant to current risk assessment practices, talc application scenarios, and exposure data. This analysis updates the previous FDA assessment by incorporating the current published exposure literature associated with consumer use of talcum powder and using the current U.S. Environmental Protection Agency's (EPA) nonoccupational asbestos risk assessment approach to estimate potential cumulative asbestos exposure and risk for four use scenarios: (1) infant exposure during diapering; (2) adult exposure from infant diapering; (3) adult exposure from face powdering; and (4) adult exposure from body powdering. The estimated range of cumulative asbestos exposure potential for all scenarios (assuming an asbestos content of 0.1%) ranged from 0.0000021 to 0.0096 f/cc‐yr and resulted in risk estimates that were within or below EPA's acceptable target risk levels. Consistent with the original FDA findings, exposure and corresponding health risk in this range were orders of magnitude below upper‐bound estimates of cumulative asbestos exposure and risk at ambient levels, which have not been associated with increased incidence of asbestos‐related disease.     

A Pharmacokinetic Study of Occupational and Environmental Benzene Exposure with Regard to Gender

Using physiologically-based pharmacokinetic (PBPK) modeling, occupational, personal, and environmental benzene exposure scenarios are simulated for adult men and women. This research identifies differences in internal exposure due to physiological and biochemical gender differences. Physiological and chemical-specific model parameters were obtained from other studies reported in the literature and medical texts for the subjects of interest. Women were found to have a higher blood/air partition coefficient and maximum velocity of metabolism for benzene than men (the two most sensitive parameters affecting gender-specific differences). Additionally, women generally have a higher body fat percentage than men. These factors influence the internal exposure incurred by the subjects and should be considered when conducting a risk assessment. Results demonstrated that physicochemical gender differences result in women metabolizing 23–26% more benzene than men when subject to the same exposure scenario even though benzene blood concentration levels are generally higher in men. These results suggest that women may be at significantly higher risk for certain effects of benzene exposure. Thus, exposure standards based on data from male subjects may not be protective for the female population.     

Exposure Assessment: Then, Now, and Quantum Leaps in the Future

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.     

Peak Exposures in Epidemiologic Studies and Cancer Risks: Considerations for Regulatory Risk Assessment

We review approaches for characterizing “peak” exposures in epidemiologic studies and methods for incorporating peak exposure metrics in dose–response assessments that contribute to risk assessment. The focus was on potential etiologic relations between environmental chemical exposures and cancer risks. We searched the epidemiologic literature on environmental chemicals classified as carcinogens in which cancer risks were described in relation to “peak” exposures. These articles were evaluated to identify some of the challenges associated with defining and describing cancer risks in relation to peak exposures. We found that definitions of peak exposure varied considerably across studies. Of nine chemical agents included in our review of peak exposure, six had epidemiologic data used by the U.S. Environmental Protection Agency (US EPA) in dose–response assessments to derive inhalation unit risk values. These were benzene, formaldehyde, styrene, trichloroethylene, acrylonitrile, and ethylene oxide. All derived unit risks relied on cumulative exposure for dose–response estimation and none, to our knowledge, considered peak exposure metrics. This is not surprising, given the historical linear no‐threshold default model (generally based on cumulative exposure) used in regulatory risk assessments. With newly proposed US EPA rule language, fuller consideration of alternative exposure and dose–response metrics will be supported. “Peak” exposure has not been consistently defined and rarely has been evaluated in epidemiologic studies of cancer risks. We recommend developing uniform definitions of “peak” exposure to facilitate fuller evaluation of dose response for environmental chemicals and cancer risks, especially where mechanistic understanding indicates that the dose response is unlikely linear and that short‐term high‐intensity exposures increase risk.     

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 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.     

Building a Human Health Risk Assessment Ontology (RsO): A Proposed Framework

Over the last decade the health and environmental research communities have made significant progress in collecting and improving access to genomic, toxicology, exposure, health, and disease data useful to health risk assessment. One of the barriers to applying these growing volumes of information in fields such as risk assessment is the lack of informatics tools to organize, curate, and evaluate thousands of journal publications and hundreds of databases to provide new insights on relationships among exposure, hazard, and disease burden. Many fields are developing ontologies as a way of organizing and analyzing large amounts of complex information from multiple scientific disciplines. Ontologies include a vocabulary of terms and concepts with defined logical relationships to each other. Building from the recently published exposure ontology and other relevant health and environmental ontologies, this article proposes an ontology for health risk assessment (RsO) that provides a structural framework for organizing risk assessment information and methods. The RsO is anchored by eight major concepts that were either identified by exploratory curations of the risk literature or the exposure‐ontology working group as key for describing the risk assessment domain. These concepts are: (1) stressor, (2) receptor, (3) outcome, (4) exposure event, (5) dose‐response approach, (6) dose‐response metric, (7) uncertainty, and (8) measure of risk. We illustrate the utility of these concepts for the RsO with example curations of published risk assessments for ionizing radiation, arsenic in drinking water, and persistent pollutants in salmon.     

An Analysis of the Health Benefits Associated with the Use of MTBE Reformulated Gasoline and Oxygenated Fuels in Reducing Atmospheric Concentrations of Selected Volatile Organic Compounds

To assess the health benefits gained from the use of cleaner burning gasoline, an analysis was conducted of changes in the atmospheric concentration of eight VOCs: acetaldehyde, benzene, 1,3-butadiene, ethylbenzene, formaldehyde, POM, toluene, and xylenes resulting from the use of reformulated gasoline and oxyfuel containing the additive MTBE. Modeled ambient air concentrations of VOCs were used to assess three seasonally-based scenarios: baseline gasoline compared to (a) summer MTBE:RFG, (b) winter MTBE:RFG, and (c) MTBE oxyfuel. The model predicts that the addition of MTBE to RFG or oxyfuel will decrease acetaldehyde, benzene, 1,3-butadiene and POM, but increase formaldehyde tailpipe emissions. The increased formaldehyde emissions, however, will be offset by the reduction of formaldehyde formation in the atmosphere from other VOCs. Using a range of plausible risk estimates, the analysis predicts a positive health benefit, i.e., a decline in cancer incidence associated with use of MTBE:RFG and MTBE oxyfuel. Using EPA cancer risk estimates, reduction in 1,3-butadiene exposure accounts for the greatest health benefit while reduction of benzene exposure accounts for the greatest health benefits based on alternative risk estimates. An analysis of microenvironment monitoring data indicates that most exposures to VOCs are significantly below levels of concern based on established margin-of-safety standards. The analysis does suggest, however, that health effects associated with short-term exposures to acetaldehyde and benzene may warrant further investigation.     

A Conceptual Framework to Assess the Risks of Human Disease Following Exposure to Pathogens

Currently, risk assessments of the potential human health effects associated with exposure to pathogens are utilizing the conceptual framework that was developed to assess risks associated with chemical exposures. However, the applicability of the chemical framework is problematic due to many issues that are unique to assessing risks associated with pathogens. These include, but are not limited to, an assessment of pathogen/host interactions, consideration of secondary spread, consideration of short- and long-term immunity, and an assessment of conditions that allow the microorganism to propagate. To address this concern, a working group was convened to develop a conceptual framework to assess the risks of human disease associated with exposure to pathogenic microorganisms. The framework that was developed consists of three phases: problem formulation, analysis (which includes characterization of exposure and human health effects), and risk characterization. The framework emphasizes the dynamic and iterative nature of the risk assessment process, and allows wide latitude for planning and conducting risk assessments in diverse situations, each based on the common principles discussed in the framework.     

Vero-Cytotoxigenic Escherichia coli O157 in Pasteurized Milk Containers at the Point of Retail: A Qualitative Approach to Exposure Assessment

Dairies within the United Kingdom are classified into two groups, namely, off-farm and on-farm dairies (the latter often being small scale). We propose a model for the probability of milk sold as pasteurized reaching the point of retail contaminated with Vero-cytotoxigenic Escherichia coli (VTEC) O157 from each of these two pathways. We evaluate qualitatively the exposures inherent in each, and compare and contrast the two situations. The model framework is generic, in that it can in principle be used, with the relevant data modifications, to provide a qualitative assessment of the likely exposure from milk sold as pasteurized to any potentially milk-borne pathogenic organism. Furthermore, the methodological approaches presented are widely applicable in the microbial risk assessment field. The specific example presented will be of particular interest to the UK dairy and public health communities: we conclude that the exposure potential per liter consumed from milk processed in off-farm dairies is negligible, whereas the exposure potential per liter consumed from milk processed on-farm is low, but not sufficiently small to be regarded as negligible. We also identify areas of data sparsity, which need to be addressed for quantitative risk assessment to proceed, and highlight the critical points in the pasteurized milk production chain, which, in the event of a breakdown, have the potential to increase the risk to the consumer.     

“How Exposed Is Exposed Enough?” Lay Inferences About Chemical Exposure

The concept of exposure is central to chemical risk assessment and plays an important role in communicating to the public about the potential health risks of chemicals. Research on chemical risk perception has found some indication that the model lay people use to judge chemical exposure differs from that of toxicologists, thereby leading to different conclusions about chemical safety. This paper presents the results of a series of studies directed toward developing a model for understanding how lay people interpret the concept of chemical exposure. The results indicate that people's beliefs about chemical exposure (and its risks) are based on two broad categories of inferences. One category of inferences relates to the nature in which contact with a chemical has taken place, including the amount of a chemical involved and its potential health consequences. A second category of inferences about chemical exposure relates to the pragmatics of language interpretation, leading to beliefs about the motives and purposes behind chemical risk communication. Risk communicators are encouraged to consider how alternative models of exposure and language interpretation can lead to conflicting conclusions on the part of the public about chemical safety.     

Benzene Risk Estimation Using Radiation Equivalent Coefficients

We estimated benzene risk using a novel framework of risk assessment that employed the measurement of radiation dose equivalents to benzene metabolites and a PBPK model. The highest risks for 1 μg/m³ and 3.2 mg/m³ life time exposure of benzene estimated with a linear regression were 5.4 × 10⁻⁷ and 1.3 × 10⁻³, respectively. Even though these estimates were based on in vitro chromosome aberration test data, they were about one-sixth to one-fourteenth that from other studies and represent a fairly good estimate by using radiation equivalent coefficient as an "internal standard."     

The EPA Health Risk Assessment of Methylcyclopentadienyl Manganese Tricarbonyl (MMT)

This paper describes the U.S. Environmental Protection Agency's assessment of potential health risks associated with the possible widespread use of a manganese (Mn)-based fuel additive, methylcyclopentadienyl manganese tricarbonyl (MMT). This assessment was significant in several respects and may be instructive in identifying certain methodological issues of general relevance to risk assessment. A major feature of the inhalation health risk assessment was the derivation of Mn inhalation reference concentration (RfC) estimates using various statistical approaches, including benchmark dose and Bayesian analyses. The exposure assessment component used data from the Particle Total Exposure Assessment Methodology (PTEAM) study and other sources to estimate personal exposure levels of particulate Mn attributable to the permitted use of MMT in leaded gasoline in Riverside, CA, at the time of the PTEAM study; on this basis it was then possible to predict a distribution of possible future exposure levels associated with the use of MMT in all unleaded gasoline. Qualitative as well as quantitative aspects of the risk characterization are summarized, along with inherent uncertainties due to data limitations.     

Intuitive Toxicology: Expert and Lay Judgments of Chemical Risks

Human beings have always been intuitive toxicologists, relying on their senses of sight, taste, and smell to detect harmful or unsafe food, water, and air. As we have come to recognize that our senses are not adequate to assess the dangers inherent in exposure to a chemical substance, we have created the sciences of toxicology and risk assessment to perform this function. Yet despite this great effort to overcome the limitations of intuitive toxicology, it has become evident that even our best scientific methods still depend heavily on extrapolations and judgments in order to infer human health risks from animal data. Many observers have acknowledged the inherent subjectivity in the assessment of chemical risks and have indicated a need to examine the subjective or intuitive elements of expert and lay risk judgments. We have begun such an examination by surveying members of the Society of Toxicology and the lay public about basic toxicological concepts, assumptions, and interpretations. Our results demonstrate large differences between toxicologists and laypeople, as well as differences between toxicologists working in industry, academia, and government. In addition, we find that toxicologists are sharply divided in their opinions about the ability to predict a chemical's effect on human health on the basis of animal studies. We argue that these results place the problems of risk communication in a new light. Although the survey identifies misconceptions that experts should clarify for the public, it also suggests that controversies over chemical risks may be fueled as much by limitations of the science of risk assessment and disagreements among experts as by public misconceptions.     

Model Averaging Using the Kullback Information Criterion in Estimating Effective Doses for Microbial Infection and Illness

Since the National Food Safety Initiative of 1997, risk assessment has been an important issue in food safety areas. Microbial risk assessment is a systematic process for describing and quantifying a potential to cause adverse health effects associated with exposure to microorganisms. Various dose-response models for estimating microbial risks have been investigated. We have considered four two-parameter models and four three-parameter models in order to evaluate variability among the models for microbial risk assessment using infectivity and illness data from studies with human volunteers exposed to a variety of microbial pathogens. Model variability is measured in terms of estimated ED01s and ED10s, with the view that these effective dose levels correspond to the lower and upper limits of the 1% to 10% risk range generally recommended for establishing benchmark doses in risk assessment. Parameters of the statistical models are estimated using the maximum likelihood method. In this article a weighted average of effective dose estimates from eight two- and three-parameter dose-response models, with weights determined by the Kullback information criterion, is proposed to address model uncertainties in microbial risk assessment. The proposed procedures for incorporating model uncertainties and making inferences are illustrated with human infection/illness dose-response data sets.