Mesothelioma Among Brake Mechanics: An Expanded Analysis of a Case-Control Study

The U.S. Environmental Protection Agency has begun discussions to consider its assessment of asbestos toxicity related to mineral form and fiber size. Brake workers are typically exposed to short chrysotile fibers. To explore the mesothelioma risk among brake workers, considering other occupational exposures to asbestos, data from a study that was published previously were obtained and the analysis was extended. The National Cancer Institute provided data from a case-control study of mesothelioma. Because many participants with a history of brake work also had employment in other asbestos-related occupations, mesothelioma cases and controls were compared for a history of brake work, controlling for employment in eight occupations with potential asbestos exposure. A stratified analysis was also performed excluding those with any of the eight occupations. Possible interactions between brake work and other occupational exposures related to risk of mesothelioma were also examined. The odds ratio (OR) for employment in brake installation or repair was 0.71 (95% CI: 0.30-1.60) when controlled for insulation or shipbuilding. When a history of employment in any of the eight occupations with potential asbestos exposure was controlled, the OR was 0.82 (95% CI: 0.36-1.80). ORs did not increase with increasing duration of brake work. Exclusion of those with any of the eight exposures resulted in an OR of 0.62 (95% CI: 0.01-4.71) for occupational brake work. There was no evidence of an interaction between brake work and other occupational exposures. These latter analyses were based on small numbers of exposed cases. The results are consistent with the existing literature indicating that brake work does not increase the risk of mesothelioma and adds to the evidence that fiber type and size are important determinants of mesothelioma risk.     

Ambient Asbestos Fiber Concentrations and Long‐Term Trends in Pleural Mesothelioma Incidence between Urban and Rural Areas in the United States (1973–2012)

Over the past 40 years, measured ambient asbestos concentrations in the United States have been higher in urban versus rural areas. The purpose of this study was to determine whether variations in ambient asbestos concentrations have influenced pleural mesothelioma risk in females (who generally lacked historic occupational asbestos exposure relative to males). Male pleural mesothelioma incidence trends were analyzed to provide perspective for female trends. Annual age‐adjusted incidence rates from 1973 to 2012 were obtained from the SEER 9, 13, and 18 databases for urban and rural locations, and standardized rate ratios were calculated. Female rural rates exceeded urban rates in almost half of the years analyzed, although the increases were not statistically significant, which is in line with expectations if there was no observable increased risk for urban locations. In contrast, male urban rates were elevated over rural rates for nearly all years examined and were statistically significantly elevated for 22 of the 40 years. Trend analyses demonstrated that trends for females remained relatively constant over time, whereas male urban and rural incidence increased into the 1980s and 1990s, followed by a decrease/leveling off. Annual female urban and rural incidence rates remained approximately five‐ to six‐fold lower than male urban and rural incidence rates on average, consistent with the comparatively increased historical occupational asbestos exposure for males. The results suggest that differences in ambient asbestos concentrations, which have been reported to be 10‐fold or greater across regions in the United States, have not influenced the risk of pleural mesothelioma.     

Assessment of Health Risk from Historical Use of Cosmetic Talcum Powder

This study's objective is to assess the risk of asbestos‐related disease being contracted by past users of cosmetic talcum powder.  To our knowledge, no risk assessment studies using exposure data from historical exposures or chamber simulations have been published. We conducted activity‐based sampling with cosmetic talcum powder samples from five opened and previously used containers that are believed to have been first manufactured and sold in the 1960s and 1970s.  These samples had been subject to conflicting claims of asbestos content; samples with the highest claimed asbestos content were tested.  The tests were conducted in simulated‐bathroom controlled chambers with volunteers who were talc users.  Air sampling filters were prepared by direct preparation techniques and analyzed by phase contrast microscopy (PCM), transmission electron microscopy (TEM) with energy‐dispersive x‐ray (EDX) spectra, and selective area diffraction (SAED).  TEM analysis for asbestos resulted in no confirmed asbestos fibers and only a single fiber classified as “ambiguous.”  Hypothetical treatment of this fiber as if it were asbestos yields a risk of 9.6 × 10^?7 (under one in one million) for a lifetime user of this cosmetic talcum powder.  The exposure levels associated with these results range from zero to levels far below those identified in the epidemiology literature as posing a risk for asbestos‐related disease, and substantially below published historical environmental background levels.  The approaches used for this study have potential application to exposure evaluations of other talc or asbestos‐containing materials and consumer products.     

A Bayesian Model and Stochastic Exposure (Dose) Estimation for Relative Exposure Risk Comparison Involving Asbestos‐Containing Dropped Ceiling Panel Installation and Maintenance Tasks

Assessing exposures to hazards in order to characterize risk is at the core of occupational hygiene. Our study examined dropped ceiling systems commonly used in schools and commercial buildings and lay‐in ceiling panels that may have contained asbestos prior to the mid to late 1970s. However, most ceiling panels and tiles do not contain asbestos. Since asbestos risk relates to dose, we estimated the distribution of eight‐hour TWA concentrations and one‐year exposures (a one‐year dose equivalent) to asbestos fibers (asbestos f/cc‐years) for five groups of workers who may encounter dropped ceilings: specialists, generalists, maintenance workers, nonprofessional do‐it‐yourself (DIY) persons, and other tradespersons who are bystanders to ceiling work. Concentration data (asbestos f/cc) were obtained through two exposure assessment studies in the field and one chamber study. Bayesian and stochastic models were applied to estimate distributions of eight‐hour TWAs and annual exposures (dose). The eight‐hour TWAs for all work categories were below current and historic occupational exposure limits (OELs). Exposures to asbestos fibers from dropped ceiling work would be categorized as “highly controlled” for maintenance workers and “well controlled” for remaining work categories, according to the American Industrial Hygiene Association exposure control rating system. Annual exposures (dose) were found to be greatest for specialists, followed by maintenance workers, generalists, bystanders, and DIY. On a comparative basis, modeled dose and thus risk from dropped ceilings for all work categories were orders of magnitude lower than published exposures for other sources of banned friable asbestos‐containing building material commonly encountered in construction trades.     

Comparative Risks of Cancer from Drywall Finishing Based on Stochastic Modeling of Cumulative Exposures to Respirable Dusts and Chrysotile Asbestos Fibers

Sanding joint compounds is a dusty activity and exposures are not well characterized. Until the mid 1970s, asbestos‐containing joint compounds were used by some people such that sanding could emit dust and asbestos fibers. We estimated the distribution of 8‐h TWA concentrations and cumulative exposures to respirable dusts and chrysotile asbestos fibers for four worker groups: (1) drywall specialists, (2) generalists, (3) tradespersons who are bystanders to drywall finishing, and (4) do‐it‐yourselfers (DIYers). Data collected through a survey of experienced contractors, direct field observations, and literature were used to develop prototypical exposure scenarios for each worker group. To these exposure scenarios, we applied a previously developed semi‐empirical mathematical model that predicts area as well as personal breathing zone respirable dust concentrations. An empirical factor was used to estimate chrysotile fiber concentrations from respirable dust concentrations. On a task basis, we found mean 8‐h TWA concentrations of respirable dust and chrysotile fibers are numerically highest for specialists, followed by generalists, DIYers, and bystander tradespersons; these concentrations are estimated to be in excess of the respective current but not historical Threshold Limit Values. Due to differences in frequency of activities, annual cumulative exposures are highest for specialists, followed by generalists, bystander tradespersons, and DIYers. Cumulative exposure estimates for chrysotile fibers from drywall finishing are expected to result in few, if any, mesothelioma or excess lung cancer deaths according to recently published risk assessments. Given the dustiness of drywall finishing, we recommend diligence in the use of readily available source controls.     

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.     

Human Health Risks Associated with Asbestos Abatement

Upperbound lifetime excess cancer risks were calculated for activities associated with asbestos abatement using a risk assessment framework developed for EPA's Superfund program. It was found that removals were associated with cancer risks to workers which were often greater than the commonly accepted cancer risk of 1 x 10(-6), although lower than occupational exposure limits associated with risks of 1 x 10(-3). Removals had little effect in reducing risk to school populations. Risks to teachers and students in school buildings containing asbestos were approximately the same as risks associated with exposure to ambient asbestos by the general public and were below the levels typically of concern to regulatory agencies. During abatement, however, there were increased risks to both workers and nearby individuals. Careless, everyday building maintenance generated the greatest risk to workers followed by removals and encapsulation. If asbestos abatement was judged by the risk criteria applied to EPA's Superfund program, the no-action alternative would likely be selected in preference to removal in a majority of cases. These conclusions should only be interpreted within the context of an overall asbestos risk management program, which includes consideration of specific fiber types and sizes, sampling and analytical limitations, physical condition of asbestos-containing material, episodic peak exposures, and the number of people potentially exposed.     

Characterizing and Communicating Risk with Exposure Reconstruction and Bayesian Analysis: Historical Locomotive Maintenance/Repair Associated with Asbestos Woven Tape Pipe Lagging

Our reconstructed historical work scenarios incorporating a vintage 1950s locomotive can assist in better understanding the historical asbestos exposures associated with past maintenance and repairs and fill a literature data gap. Air sampling data collected during the exposure scenarios and analyzed by NIOSH 7400 (PCM) and 7402 (PCME) methodologies show personal breathing zone asbestiform fiber exposures were below the current OSHA exposure limits for the eight‐hour TWA permissible exposure limit (PEL) of 0.1 f/cc (range <0.007–0.064 PCME f/cc) and the 30‐minute short‐term excursion limit (EL) of 1.0 f/cc (range <0.045–0.32 PCME f/cc) and orders of magnitude below historic OSHA PEL and ACGIH TLVs. Bayesian decision analysis (BDA) results demonstrate that the 95th percentile point estimate falls into an AIHA exposure category 3 or 4 as compared to the current PEL and category 1 when compared to the historic PEL. BDA results demonstrate that bystander exposures would be classified as category 0. Our findings were also significantly below the published calcium magnesium insulations exposure range of 2.5 to 7.5 f/cc reported for historic work activities of pipefitters, mechanics, and boilermakers. Diesel‐electric locomotive pipe systems were typically insulated with a woven tape lagging that may have been chrysotile asbestos and handled, removed, and reinstalled during repair and maintenance activities. We reconstructed historical work scenarios containing asbestos woven tape pipe lagging that have not been characterized in the published literature. The historical work scenarios were conducted by a retired railroad pipefitter with 37 years of experience working with materials and locomotives.     

Apples to Apples: The Origin and Magnitude of Differences in Asbestos Cancer Risk Estimates Derived Using Varying Protocols

Given that new protocols for assessing asbestos‐related cancer risk have recently been published, questions arise concerning how they compare to the “IRIS” protocol currently used by regulators. The newest protocols incorporate findings from 20 additional years of literature. Thus, differences between the IRIS and newer Berman and Crump protocols are examined to evaluate whether these protocols can be reconciled. Risks estimated by applying these protocols to real exposure data from both laboratory and field studies are also compared to assess the relative health protectiveness of each protocol. The reliability of risks estimated using the two protocols are compared by evaluating the degree with which each potentially reproduces the known epidemiology study risks. Results indicate that the IRIS and Berman and Crump protocols can be reconciled; while environment‐specific variation within fiber type is apparently due primarily to size effects (not addressed by IRIS), the 10‐fold (average) difference between amphibole asbestos risks estimated using each protocol is attributable to an arbitrary selection of the lowest of available mesothelioma potency factors in the IRIS protocol. Thus, the IRIS protocol may substantially underestimate risk when exposure is primarily to amphibole asbestos. Moreover, while the Berman and Crump protocol is more reliable than the IRIS protocol overall (especially for predicting amphibole risk), evidence is presented suggesting a new fiber‐size‐related adjustment to the Berman and Crump protocol may ultimately succeed in reconciling the entire epidemiology database. However, additional data need to be developed before the performance of the adjusted protocol can be fully validated.     

Compliance Versus Risk in Assessing Occupational Exposures

Assessments of occupational exposures to chemicals are generally based upon the practice of compliance testing in which the probability of compliance is related to the exceedance [γ, the likelihood that any measurement would exceed an occupational exposure limit (OEL)] and the number of measurements obtained. On the other hand, workers’ chronic health risks generally depend upon cumulative lifetime exposures which are not directly related to the probability of compliance. In this paper we define the probability of “overexposure” (θ) as the likelihood that individual risk (a function of cumulative exposure) exceeds the risk inherent in the OEL (a function of the OEL and duration of exposure). We regard θ as a relevant measure of individual risk for chemicals, such as carcinogens, which produce chronic effects after long-term exposures but not necessarily for acutely-toxic substances which can produce effects relatively quickly. We apply a random-effects model to data from 179 groups of workers, exposed to a variety of chemical agents, and obtain parameter estimates for the group mean exposure and the within- and between-worker components of variance. These estimates are then combined with OELs to generate estimates of γ and θ. We show that compliance testing can significantly underestimate the health risk when sample sizes are small. That is, there can be large probabilities of compliance with typical sample sizes, despite the fact that large proportions of the working population have individual risks greater than the risk inherent in the OEL. We demonstrate further that, because the relationship between θ and γ depends upon the within- and between-worker components of variance, it cannot be assumed a priori that exceedance is a conservative surrogate for overexposure. Thus, we conclude that assessment practices which focus upon either compliance or exceedance are problematic and recommend that employers evaluate exposures relative to the probabilities of overexposure.     

Dose‐Response Modeling for Inhalational Anthrax in Rabbits Following Single or Multiple Exposures

There is a need to advance our ability to characterize the risk of inhalational anthrax following a low‐dose exposure. The exposure scenario most often considered is a single exposure that occurs during an attack. However, long‐term daily low‐dose exposures also represent a realistic exposure scenario, such as what may be encountered by people occupying areas for longer periods. Given this, the objective of the current work was to model two rabbit inhalational anthrax dose‐response data sets. One data set was from single exposures to aerosolized Bacillus anthracis Ames spores. The second data set exposed rabbits repeatedly to aerosols of B. anthracis Ames spores. For the multiple exposure data the cumulative dose (i.e., the sum of the individual daily doses) was used for the model. Lethality was the response for both. Modeling was performed using Benchmark Dose Software evaluating six models: logprobit, loglogistic, Weibull, exponential, gamma, and dichotomous‐Hill. All models produced acceptable fits to either data set. The exponential model was identified as the best fitting model for both data sets. Statistical tests suggested there was no significant difference between the single exposure exponential model results and the multiple exposure exponential model results, which suggests the risk of disease is similar between the two data sets. The dose expected to cause 10% lethality was 15,600 inhaled spores and 18,200 inhaled spores for the single exposure and multiple exposure exponential dose‐response model, respectively, and the 95% lower confidence intervals were 9,800 inhaled spores and 9,200 inhaled spores, respectively.     

Projections of Cancer Risks Attributable to Future Exposure to Asbestos

To assess the maximum possible impact of further government regulation of asbestos exposure, projections were made of the use of asbestos in nine product categories for the years 1985-2000. A life table risk assessment model was then developed to estimate the excess cases of cancer and lost person-years of life likely to occur among those occupationally and nonoccupationally exposed to the nine asbestos product categories manufactured in 1985-2000. These estimates were made under the assumption that government regulation remains at its 1985 level. Use of asbestos in the nine product categories was predicted to decline in all cases except for friction products. The risk assessment results show that, although the cancer risks from future exposure to asbestos are significantly less than those from past exposures, in the absence of more stringent regulations, a health risk remains.     

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.     

Annual Burden of Occupationally‐Acquired Influenza Infections in Hospitals and Emergency Departments in the United States

Infections among health‐care personnel (HCP) occur as a result of providing care to patients with infectious diseases, but surveillance is limited to a few diseases. The objective of this study is to determine the annual number of influenza infections acquired by HCP as a result of occupational exposures to influenza patients in hospitals and emergency departments (EDs) in the United States. A risk analysis approach was taken. A compartmental model was used to estimate the influenza dose received in a single exposure, and a dose–response function applied to calculate the probability of infection. A three‐step algorithm tabulated the total number of influenza infections based on: the total number of occupational exposures (tabulated in previous work), the total number of HCP with occupational exposures, and the probability of infection in an occupational exposure. Estimated influenza infections were highly dependent upon the dose–response function. Given current compliance with infection control precautions, we estimated 151,300 and 34,150 influenza infections annually with two dose–response functions (annual incidence proportions of 9.3% and 2.1%, respectively). Greater reductions in infectious were achieved by full compliance with vaccination and IC precautions than with patient isolation. The burden of occupationally‐acquired influenza among HCP in hospitals and EDs in the United States is not trivial, and can be reduced through improved compliance with vaccination and preventive measures, including engineering and administrative controls.     

Some Limitations of Aggregate Exposure Metrics

Aggregate exposure metrics based on sums or weighted averages of component exposures are widely used in risk assessments of complex mixtures, such as asbestos-associated dusts and fibers. Allowed exposure levels based on total particle or fiber counts and estimated ambient concentrations of such mixtures may be used to make costly risk-management decisions intended to protect human health and to remediate hazardous environments. We show that, in general, aggregate exposure information alone may be inherently unable to guide rational risk-management decisions when the components of the mixture differ significantly in potency and when the percentage compositions of the mixture exposures differ significantly across locations. Under these conditions, which are not uncommon in practice, aggregate exposure metrics may be "worse than useless," in that risk-management decisions based on them are less effective than decisions that ignore the aggregate exposure information and select risk-management actions at random. The potential practical significance of these results is illustrated by a case study of 27 exposure scenarios in El Dorado Hills, California, where applying an aggregate unit risk factor (from EPA's IRIS database) to aggregate exposure metrics produces average risk estimates about 25 times greater - and of uncertain predictive validity - compared to risk estimates based on specific components of the mixture that have been hypothesized to pose risks of human lung cancer and mesothelioma.     

Interpretation of Airborne Asbestos Measurements

Transmission electron microscopy (TEM) is the preferred method of measuring airborne asbestos in buildings, but TEM measurements cannot be used directly in the existing equations relating risk to exposure because the equations are based on measurements made with a different technique--phase contrast microscopy (PCM). Comparison between measurements made by different methods is not simple because the methods differ in the size of particles they can detect, and the relationship between exposure and disease is thought to depend on, among other things, asbestos fiber size. Previous suggestions for converting TEM measurements to PCM equivalents lack generality because they fail to take into account the size distribution of the asbestos particles and the expectation that fiber-size distributions in current nonoccupational environments could differ from the workplaces of the past on which the risk equations are based. A mathematical model is presented for investigating the conversion of airborne asbestos measurements made by one method to an equivalent measurement made by another method. "Equivalent" means having the same potential to cause disease. The model clarifies the issues of concern and suggests approaches for obtaining meaningful conversion factors that will allow TEM measurements to be used in PCM-based risk equations.     

Ebola Virus Dose Response Model for Aerosolized Exposures: Insights from Primate Data

This study develops dose–response models for Ebolavirus using previously published data sets from the open literature. Two such articles were identified in which three different species of nonhuman primates were challenged by aerosolized Ebolavirus in order to study pathology and clinical disease progression. Dose groups were combined and pooled across each study in order to facilitate modeling. The endpoint of each experiment was death. The exponential and exact beta-Poisson models were fit to the data using maximum likelihood estimation. The exact beta-Poisson was deemed the recommended model because it more closely approximated the probability of response at low doses though both models provided a good fit. Although transmission is generally considered to be dominated by person-to-person contact, aerosolization is a possible route of exposure. If possible, this route of exposure could be particularly concerning for persons in occupational roles managing contaminated liquid wastes from patients being treated for Ebola infection and the wastewater community responsible for disinfection. Therefore, this study produces a necessary mathematical relationship between exposure dose and risk of death for the inhalation route of exposure that can support quantitative microbial risk assessment aimed at informing risk mitigation strategies including personal protection policies against occupational exposures.     

Interindividual Variation in Source-Specific Doses is a Determinant of Health Impacts of Combined Chemical Exposures

All individuals are exposed to multiple chemicals from multiple sources. These combined exposures are a concern because they may cause adverse effects that would not occur from an exposure recieved from any single source. Studies of combined chemical exposures, however, have found that the risks posed by such combined exposures are almost always driven by exposures from a few chemicals and sources and frequently by a single chemical from a single source. Here, a series of computer simulations of combined exposures are used to investigate when multiple sources of chemicals drive the largest risks in a population and when a single chemical from a single source is responsible for the largest risks. The analysis found that combined exposures drive the largest risks when the interindividual variation of source-specific doses is small, moderate-to-high correlations occur between the source-specific doses, and the number of sources affecting an individual varies across individuals. These findings can be used to identify sources with the greatest potential to cause combined exposures of concern.     

Multiple Interacting Risk Factors: On Methods for Allocating Risk Factor Interactions

A persistent problem in health risk analysis where it is known that a disease may occur as a consequence of multiple risk factors with interactions is allocating the total risk of the disease among the individual risk factors. This problem, referred to here as risk apportionment, arises in various venues, including: (i) public health management, (ii) government programs for compensating injured individuals, and (iii) litigation. Two methods have been described in the risk analysis and epidemiology literature for allocating total risk among individual risk factors. One method uses weights to allocate interactions among the individual risk factors. The other method is based on risk accounting axioms and finding an optimal and unique allocation that satisfies the axioms using a procedure borrowed from game theory. Where relative risk or attributable risk is the risk measure, we find that the game‐theory‐determined allocation is the same as the allocation where risk factor interactions are apportioned to individual risk factors using equal weights. Therefore, the apportionment problem becomes one of selecting a meaningful set of weights for allocating interactions among the individual risk factors. Equal weights and weights proportional to the risks of the individual risk factors are discussed.     

Characterizing Risk for Cumulative Risk Assessments

In assessing environmental health risks, the risk characterization step synthesizes information gathered in evaluating exposures to stressors together with dose–response relationships, characteristics of the exposed population, and external environmental conditions. This article summarizes key steps of a cumulative risk assessment (CRA) followed by a discussion of considerations for characterizing cumulative risks. Cumulative risk characterizations differ considerably from single chemical‐ or single source‐based risk characterization. CRAs typically focus on a specific population instead of a pollutant or pollutant source and should include an evaluation of all relevant sources contributing to the exposures in the population and other factors that influence dose–response relationships. Second, CRAs may include influential environmental and population‐specific conditions, involving multiple chemical and nonchemical stressors. Third, a CRA could examine multiple health effects, reflecting joint toxicity and the potential for toxicological interactions. Fourth, the complexities often necessitate simplifying methods, including judgment‐based and semi‐quantitative indices that collapse disparate data into numerical scores. Fifth, because of the higher dimensionality and potentially large number of interactions, information needed to quantify risk is typically incomplete, necessitating an uncertainty analysis. Three approaches that could be used for characterizing risks in a CRA are presented: the multiroute hazard index, stressor grouping by exposure and toxicity, and indices for screening multiple factors and conditions. Other key roles of the risk characterization in CRAs are also described, mainly the translational aspect of including a characterization summary for lay readers (in addition to the technical analysis), and placing the results in the context of the likely risk‐based decisions.