Computerized Estimates of Potential Occupational Health Risk Due to Chemical Exposure

Estimating the potential health risk encountered by workers due to their exposure to various chemicals is enormously complex, since many chemicals may be involved and each may have multiple toxic effects. As an aid to this estimation process, a computer program, or model, which computes index numbers expressing the relative health risk of occupational groups due to their potential chemical exposures was developed at the National Institute for Occupational Safety and Health (NIOSH). This model considers an inventory of the chemicals to which specific occupational groups are potentially exposed, the published information regarding the toxic effects of each chemical, and the conditions of occupational exposure. The system then develops indices of potential occupational group health risk by considering weighted combinations of eight distinct health effects. No direct comparison with external occupational risk indices is currently possible, but internal testing of the model reveals no obvious inconsistencies.     

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.     

“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.     

Advances on a Decision Analytic Approach to Exposure-Based Chemical Prioritization

The volume and variety of manufactured chemicals is increasing, although little is known about the risks associated with the frequency and extent of human exposure to most chemicals. The EPA and the recent signing of the Lautenberg Act have both signaled the need for high-throughput methods to characterize and screen chemicals based on exposure potential, such that more comprehensive toxicity research can be informed. Prior work of Mitchell et al. using multicriteria decision analysis tools to prioritize chemicals for further research is enhanced here, resulting in a high-level chemical prioritization tool for risk-based screening. Reliable exposure information is a key gap in currently available engineering analytics to support predictive environmental and health risk assessments. An elicitation with 32 experts informed relative prioritization of risks from chemical properties and human use factors, and the values for each chemical associated with each metric were approximated with data from EPA's CP_CAT database. Three different versions of the model were evaluated using distinct weight profiles, resulting in three different ranked chemical prioritizations with only a small degree of variation across weight profiles. Future work will aim to include greater input from human factors experts and better define qualitative metrics.     

Assessments of Direct Human Exposure—The Approach of EU Risk Assessments Compared to Scenario-Based Risk Assessment

The awareness of potential risks emerging from the use of chemicals in all parts of daily life has increased the need for risk assessments that are able to cover a high number of exposure situations and thereby ensure the safety of workers and consumers. In the European Union (EU), the practice of risk assessments for chemicals is laid down in a Technical Guidance Document; it is designed to consider environmental and human occupational and residential exposure. Almost 70 EU risk assessment reports (RARs) have been finalized for high-production-volume chemicals during the last decade. In the present study, we analyze the assessment of occupational and consumer exposure to trichloroethylene and phthalates presented in six EU RARs. Exposure scenarios in these six RARs were compared to scenarios used in applications of the scenario-based risk assessment approach to the same set of chemicals. We find that scenarios used in the selected EU RARs to represent typical exposure situations in occupational or private use of chemicals and products do not necessarily represent worst-case conditions. This can be due to the use of outdated information on technical equipment and conditions in workplaces or omission of pathways that can cause consumer exposure. Considering the need for exposure and risk assessments under the new chemicals legislation of the EU, we suggest that a transparent process of collecting data on exposure situations and of generating representative exposure scenarios is implemented to improve the accuracy of risk assessments. Also, the data sets used to assess human exposure should be harmonized, summarized in a transparent fashion, and made accessible for all risk assessors and the public.     

Parameter Uncertainty and Variability In Evaluative Fate and Exposure Models

The human toxicity potential, a weighting scheme used to evaluate toxic emissions for life cycle assessment and toxics release inventories, is based on potential dose calculations and toxicity factors. This paper evaluates the variance in potential dose calculations that can be attributed to the uncertainty in chemical-specific input parameters as well as the variability in exposure factors and landscape parameters. A knowledge of the uncertainty allows us to assess the robustness of a decision based on the toxicity potential; a knowledge of the sources of uncertainty allows us to focus our resources if we want to reduce the uncertainty. The potential dose of 236 chemicals was assessed. The chemicals were grouped by dominant exposure route, and a Monte Carlo analysis was conducted for one representative chemical in each group. The variance is typically one to two orders of magnitude. For comparison, the point estimates in potential dose for 236 chemicals span ten orders of magnitude. Most of the variance in the potential dose is due to chemical-specific input parameters, especially half-lives, although exposure factors such as fish intake and the source of drinking water can be important for chemicals whose dominant exposure is through indirect routes. Landscape characteristics are generally of minor importance.     

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.     

Predicted Infant Exposure to Tetrachloroethene in Human Breastmilk

Based on a variety of maternal occupational and residential inhalation exposure scenarios, estimates of infant exposure to the dry-cleaning solvent tetrachlorothylene (perchloroethylene, PCE) in breastmilk were made. Physiologically based pharmacokinetic (PBPK) modeling indicates that infants may be exposed to elevated levels of PCE in breastmilk due to their mothers' inhalation of PCE. The PBPK-predicted breastmilk PCE concentrations agree very well with measured concentrations, where available. Based on this analysis, infants may be exposed to this workplace chemical via breastmilk at doses corresponding to rather high levels of risk. Predicted breastmilk doses provide the infant with little margin of exposure to doses associated with adverse health effects. In addition, the estimated increased cancer risks associated with these infant exposures are large under certain exposure scenarios. The actual concentrations of PCE in breastmilk of exposed mothers can only be known with certainty if monitoring is conducted. Due to the widespread exposure potential, monitoring studies should be undertaken so that the appropriate risk management alternatives can be better evaluated.     

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.     

The Application of Bioassays in Risk Assessment of Environmental Pollution

Increased contamination of the environment by toxic chemicals has resulted in the need for sensitive assays to be used in risk assessment of polluted sites. Traditional tests are useful to detect and measure concentrations of chemicals in the environment and in tissues. However, physicochemical assays possess deficiencies that impair their use in evaluating complex environmental contamination. We have developed cytogenetic procedures, including chromosomal, micronucleus, and flow cytometric assays, to assess the mutagenic damage of petrochemicals and low-level radioactivity on indigenous terrestrial and aquatic wildlife populations. These procedures are sensitive to the perturbation of DNA that results from exposure to mutagenic contaminants in both field and laboratory studies. The use of natural populations of animals in biomonitoring, combined with traditional chemical assays, will ultimately provide sufficient information to estimate the risk to human health and environmental quality from anthropogenic pollution.     

Life cycle impact assessment: a challenge for risk analysts.

Modern technology, together with an advanced economy, can provide a good or service in myriad ways, giving us choices on what to produce and how to produce it. To make those choices more intelligently, society needs to know not only the market price of each alternative, but the associated health and environmental consequences. A fair comparison requires evaluating the consequences across the whole "life cycle"--from the extraction of raw materials and processing to manufacture/construction, use, and end-of-life--of each alternative. Focusing on only one stage (e.g., manufacture) of the life cycle is often misleading. Unfortunately, analysts and researchers still have only rudimentary tools to quantify the materials and energy inputs and the resulting damage to health and the environment. Life cycle assessment (LCA) provides an overall framework for identifying and evaluating these implications. Since the 1960s, considerable progress has been made in developing methods for LCA, especially in characterizing, qualitatively and quantitatively, environmental discharges. However, few of these analyses have attempted to assess the quantitative impact on the environment and health of material inputs and environmental discharges Risk analysis and LCA are connected closely. While risk analysis has characterized and quantified the health risks of exposure to a toxicant, the policy implications have not been clear. Inferring that an occupational or public health exposure carries a nontrivial risk is only the first step in formulating a policy response. A broader framework, including LCA, is needed to see which response is likely to lower the risk without creating high risks elsewhere. Even more important, LCA has floundered at the stage of translating an inventory of environmental discharges into estimates of impact on health and the environment. Without the impact analysis, policymakers must revert to some simple rule, such as that all discharges, regardless of which chemical, which medium, and where they are discharged, are equally toxic. Thus, risk analysts should seek LCA guidance in translating a risk analysis into policy conclusions or even advice to those at risk. LCA needs the help of RA to go beyond simplistic assumptions about the implications of a discharge inventory. We demonstrate the need and rationale for LCA, present a brief history of LCA, present examples of the application of this tool, note the limitations of LCA models, and present several methods for incorporating risk assessment into LCA. However, we warn the reader not to expect too much. A comprehensive comparison of the health and environmental implications of alternatives is beyond the state of the art. LCA is currently not able to provide risk analysts with detailed information on the chemical form and location of the environmental discharges that would allow detailed estimation of the risks to individuals due to toxicants. For example, a challenge for risk analysts is to estimate health and other risks where the location and chemical speciation are not characterized precisely. Providing valuable information to decisionmakers requires advances in both LCA and risk analysis. These two disciplines should be closely linked, since each has much to contribute to the other.     

Quantitative Assessment of the Risk of Lung Cancer Associated with Occupational Exposure to Refractory Ceramic Fibers

We present the results of a quantitative assessment of the lung cancer risk associated with occupational exposure to refractory ceramic fibers (RCF). The primary sources of data for our risk assessment were two long-term oncogenicity studies in male Fischer rats conducted to assess the potential pathogenic effects associated with prolonged inhalation of RCF. An interesting feature of the data was the availability of the temporal profile of fiber burden in the lungs of experimental animals. Because of this information, we were able to conduct both exposure–response and dose–response analyses. Our risk assessment was conducted within the framework of a biologically based model for carcinogenesis, the two-stage clonal expansion model, which allows for the explicit incorporation of the concepts of initiation and promotion in the analyses. We found that a model positing that RCF was an initiator had the highest likelihood. We proposed an approach based on biological considerations for the extrapolation of risk to humans. This approach requires estimation of human lung burdens for specific exposure scenarios, which we did by using an extension of a model due to Yu. Our approach acknowledges that the risk associated with exposure to RCF depends on exposure to other lung carcinogens. We present estimates of risk in two populations: (1) a population of nonsmokers and (2) an occupational cohort of steelworkers not exposed to coke oven emissions, a mixed population that includes both smokers and nonsmokers.     

Chronic Health Risks from Aggregate Exposures to Ionizing Radiation and Chemicals: Scientific Basis for an Assessment Framework

Very little quantitative analysis is currently available on the cumulative effects of exposure to multiple hazardous agents that have either similar or different mechanisms of action. Over the past several years, efforts have been made to develop the methodologies for risk assessment of chemical mixtures, but mixed exposures to two or more dissimilar agents such as radiation and one or more chemical agents have not yet been addressed in any substantive way. This article reviews the current understanding of the health risks arising from mixed exposures to ionizing radiation and specific chemicals. Specifically discussed is how mixed radiation/chemical exposures, when evaluated in aggregation, were linked to chronic health endpoints such as cancer and intermediate health outcomes such as chromosomal aberrations. Also considered is the extent to which the current practices are consistent with the scientific understanding of the health risks associated with mixed-agent exposures. From this the discussion moves to the research needs for assessing the cumulative health risks from aggregate exposures to ionizing radiation and chemicals. The evaluation indicates that essentially no guidance has been provided for conducting risk assessment for two agents with different mechanisms of action (i.e., energy deposition from ionizing radiation versus DNA interactions with chemicals) but similar biological endpoints (i.e., chromosomal aberrations, mutations, and cancer). The literature review also reveals the problems caused by the absence of both the basic science and an appropriate evaluation framework for the combined effects of mixed-agent exposures. This makes it difficult to determine whether there is truly no interaction or somehow the interaction is masked by the scale of effect observation or inappropriate dose-response assumptions.     

Bounding Analysis of Drinking Water Health Risks from a Spill of Hydraulic Fracturing Flowback Water

A bounding risk assessment is presented that evaluates possible human health risk from a hypothetical scenario involving a 10,000‐gallon release of flowback water from horizontal fracturing of Marcellus Shale. The water is assumed to be spilled on the ground, infiltrates into groundwater that is a source of drinking water, and an adult and child located downgradient drink the groundwater. Key uncertainties in estimating risk are given explicit quantitative treatment using Monte Carlo analysis. Chemicals that contribute significantly to estimated health risks are identified, as are key uncertainties and variables to which risk estimates are sensitive. The results show that hypothetical exposure via drinking water impacted by chemicals in Marcellus Shale flowback water, assumed to be spilled onto the ground surface, results in predicted bounds between 10⁻¹⁰ and 10⁻⁶ (for both adult and child receptors) for excess lifetime cancer risk. Cumulative hazard indices (HI_CUMULATIVE) resulting from these hypothetical exposures have predicted bounds (5th to 95th percentile) between 0.02 and 35 for assumed adult receptors and 0.1 and 146 for assumed child receptors. Predicted health risks are dominated by noncancer endpoints related to ingestion of barium and lithium in impacted groundwater. Hazard indices above unity are largely related to exposure to lithium. Salinity taste thresholds are likely to be exceeded before drinking water exposures result in adverse health effects. The findings provide focus for policy discussions concerning flowback water risk management. They also indicate ways to improve the ability to estimate health risks from drinking water impacted by a flowback water spill (i.e., reducing uncertainty).     

Aligning Chemical Assessment Tools Across the Hazard-Risk Continuum

With the growing number and diversity of hazard and risk assessment algorithms, models, databases, and frameworks for chemicals and their applications, risk assessors and managers are challenged to select the appropriate tool for a given need or decision. Some decisions require relatively simple tools to evaluate chemical hazards (e.g., toxicity), such as labeling for safe occupational handling and transport of chemicals. Others require assessment tools that provide relative comparisons among chemical properties, such as selecting the optimum chemical for a particular use among a group of candidates. Still other needs warrant full risk characterization, coupling both hazard and exposure considerations. Examples of these include new chemical evaluations for commercialization, evaluations of existing chemicals for novel uses, and assessments of the adequacy of risk management provisions. Even well-validated tools can be inappropriately applied, with consequences as severe as misguided chemical management, compromised credibility of the tool and its developers and users, and squandered resources. This article describes seven discrete categories of tools based on their information content, function, and the type of outputs produced. It proposes a systematic framework to assist users in selecting hazard and risk assessment tools for given applications. This analysis illustrates the importance of careful selection of assessment tools to achieve responsible chemical assessment communication and sound risk management.     

Assessment of Health Risk from Exposure to Contaminated Soil

The risk to human health posed by contaminated soil in a residential area depends on the potential extent of exposure to soil and on the toxic properties of the contaminants. A detailed soil exposure analysis is presented for young children, older children, and adults living in a house surrounded by contaminated soil. From this analysis, a lifetime exposure model is derived and used to assess chronic health risks.     

Risk Assessment and Alternatives Assessment: Comparing Two Methodologies

The selection and use of chemicals and materials with less hazardous profiles reflects a paradigm shift from reliance on risk minimization through exposure controls to hazard avoidance. This article introduces risk assessment and alternatives assessment frameworks in order to clarify a misconception that alternatives assessment is a less effective tool to guide decision making, discusses factors promoting the use of each framework, and also identifies how and when application of each framework is most effective. As part of an assessor's decision process to select one framework over the other, it is critical to recognize that each framework is intended to perform different functions. Although the two frameworks share a number of similarities (such as identifying hazards and assessing exposure), an alternatives assessment provides a more realistic framework with which to select environmentally preferable chemicals because of its primary reliance on assessing hazards and secondary reliance on exposure assessment. Relevant to other life cycle impacts, the hazard of a chemical is inherent, and although it may be possible to minimize exposure (and subsequently reduce risk), it is challenging to assess such exposures through a chemical's life cycle. Through increased use of alternatives assessments at the initial stage of material or product design, there will be less reliance on post facto risk‐based assessment techniques because the potential for harm is significantly reduced, if not avoided, negating the need for assessing risk in the first place.     

Assessing human health response in life cycle assessment using ED10s and DALYs: part 2--Noncancer effects.

In Part 1 of this article we developed an approach for the calculation of cancer effect measures for life cycle assessment (LCA). In this article, we propose and evaluate the method for the screening of noncancer toxicological health effects. This approach draws on the noncancer health risk assessment concept of benchmark dose, while noting important differences with regulatory applications in the objectives of an LCA study. We adopt the centraltendency estimate of the toxicological effect dose inducing a 10% response over background, ED10, to provide a consistent point of departure for default linear low-dose response estimates (betaED10). This explicit estimation of low-dose risks, while necessary in LCA, is in marked contrast to many traditional procedures for noncancer assessments. For pragmatic reasons, mechanistic thresholds and nonlinear low-dose response curves were not implemented in the presented framework. In essence, for the comparative needs of LCA, we propose that one initially screens alternative activities or products on the degree to which the associated chemical emissions erode their margins of exposure, which may or may not be manifested as increases in disease incidence. We illustrate the method here by deriving the betaED10 slope factors from bioassay data for 12 chemicals and outline some of the possibilities for extrapolation from other more readily available measures, such as the no observable adverse effect levels (NOAEL), avoiding uncertainty factors that lead to inconsistent degrees of conservatism from chemical to chemical. These extrapolations facilitated the initial calculation of slope factors for an additional 403 compounds; ranging from 10(-6) to 10(3) (risk per mg/kg-day dose). The potential consequences of the effects are taken into account in a preliminary approach by combining the betaED10 with the severity measure disability adjusted life years (DALY), providing a screening-level estimate of the potential consequences associated with exposures, integrated over time and space, to a given mass of chemical released into the environment for use in LCA.