A Risk Assessment Framework for Waterborne Pathogens and Requirements for Producing a Complete Protocol

The U.S. Environmental Protection Agency (USEPA), Office of Water, is developing a risk assessment protocol for determining microbiological pathogen risks in water (drinking, recreational, waste waters, etc.). This effort has been conducted in collaboration with the International Life Sciences Institute. A microbiological risk assessment framework was prepared and has been peer reviewed in the open literature and vetted at the USEPA and other federal government risk assessment venues. Some goals in development of the Framework were to make it comprehensive, easy to understand and to use, since it is recognized that improvements to the framework structure and instructional material would facilitate its use. The USEPA's Office of Water wishes to develop improved tools, methods, and approaches for conducting the analysis phase for risk assessments and would like to evaluate its efficacy for a broad range of waterborne pathogens in water/wastewater media. Improved understanding of microbiological survival, infectivity, and virulence factors is needed, especially at the genomic and proteomic levels to accurately assess the occurrence and fate of pathogens in water and to predict what intrinsic factors allow pathogens to be invasive and virulent. Development of improved dose-response models (including animal models) for pathogen exposures focusing on the dynamic circumstances of immunity, secondary spread, and sensitive subpopulations, would be useful additions to the Framework. In the future, USEPA may consider establishing comprehensive pathogen risk assessment guidelines that all its program offices can use.     

Assessing Children's Exposures and Risks to Drinking Water Contaminants: A Manganese Case Study

Background: Compared to adults, children maybe more highly exposed to toxic substances in drinking water because they consume more water per unit of body weight. The U.S. Environmental Protection Agency (USEPA) has developed new guidance for selecting age groups and age-specific exposure factors for assessing children's exposures and risks to environmental contaminants. Research Aim: To demonstrate the application and importance of applying age-specific drinking water intake rates, health reference values, and exposure scenarios when assessing drinking water exposures because these approaches illustrate the potential for greater potential for adverse health effects among children. Methods: manganese, an essential nutrient and neurotoxicant, was selected as a case study and chemical of potential concern for children's health. A screening-level risk assessment was performed using age-specific drinking water intake rates and manganese concentrations from U.S. public drinking water systems. Results: When age-specific drinking water intake rates are used to calculate dose, formula-fed infants receive the highest dose of manganese from drinking water compared to all other age groups. Estimated hazard quotients suggest adverse health effects are possible. Use of USEPA's standardized childhood age groups and childhood exposure factors significantly improves the understanding of childhood exposure and risks.     

Adult:Child Differences in the Intraspecies Uncertainty Factor: A Case Study Using Lead

Adults and children differ in their susceptibility to the toxic effects of lead. Lead was therefore used as a case study to evaluate intraspecies differences by comparing the adult and child minimal Lowest Observed Adverse Effect Level (LOAEL) or the No Observed Adverse Effect Level (NOAEL), allowing an evaluation of the ten-fold intraspecies uncertainty factor (UF). The lead intakes (in µg/kg/d) necessary to achieve target blood lead (PbB) levels reflecting the minimal LOAEL or NOAEL were determined using biokinetic slope factors (BKSFs), which relate lead uptake to PbB levels. The analyses assumed chronic, low-level oral exposure to lead, and the response of a typical adult and child. Child analyses used a target geometric mean (GM) PbB of 4.6?µg/dL (95% of population <10?µg/dL), resulting in lead intakes of 1.9?µg/kg/day (assuming 100% soluble lead) and 4.9?µg/kg/day (assuming 25% soluble lead and 75 % soil lead). Adult analyses assumed intake of 100 % soluble lead, and used target GM PbB levels of 4.2?µg/dL (95% of population <11.1 µg/dL) and 11.4?µg/dL (95% of population <30?µg/dL), resulting in lead intakes of 1.9?µg/kg/day and 5.1?µg/kg/day, respectively. The results indicate that despite the greater vulnerability of young children to the effects of lead as compared to adults, the minimal LOAEL or NOAEL for lead is remarkably similar between children and adults. In this case, the application of a tenfold intraspecies uncertainty factor to adjust the adult minimal LOAEL or NOAEL for a child would be unnecessary, despite the well-established vulnerability of children to lead.     

Derivation of Risk Management Criteria for Chemicals of Unknown Toxic Potency at Contaminated Sites

Environmental investigations of former industrial sites often detect the presence of chemicals for which no soil criteria exist and for which regulatory agencies have not derived estimates of toxic potency. This poses a considerable problem for making informed risk management decisions involving sites where such chemicals are present. As a result, a methodology has been developed for making risk-based decisions for chemicals of unknown toxic potency in soil at contaminated sites. The method is based on principles and procedures used by the US Food and Drug Administration (USFDA), the US Environmental Protection Agency (USEPA) and the Canadian Council of Ministers of the Environment (CCME). After analyzing the data on hundreds of carcinogenic and non-carcinogenic substances, the USFDA and other leading researchers have concluded that, if no toxicological data is available on a chemical, exposures less than 1.5?µg/person/day (i.e., 0.02?µg/kg body weight/day) are unlikely to result in appreciable health risks even if the substance was later found to be a carcinogen. To develop maximum soil concentrations that will be protective of human health (i.e., Risk Management Criteria or RMC), the above exposure limit of 0.02?µg/kg body weight/day has been assumed to be protective of risks from exposure to chemicals lacking toxicological data. Using a stochastic risk assessment model for estimating exposures to chemicals from contaminated sites, our analyses indicate that a soil concentration of 2?µg/g would be protective of human health for land uses that include residential, commercial, and industrial development provided no major indirect pathways exist at the site. If indirect pathways exists (e.g., vapor infiltration of soil gases, uptake of chemicals into garden produce, etc.), alternate RMC could be developed, that include such indirect pathways, using the methodology provided in this paper. Used by experienced risk assessors, the approach is a scientifically defensible screening method that will preclude many chemicals from unnecessary evaluation, while allowing risk assessors to focus efforts on chemicals of greater concern and make informed risk management decisions.     

Environmental Risks at Finnish Shooting Ranges—A Case Study

We studied three Finnish shooting ranges in order to define the extent of the risks associated with elevated environmental concentrations of metals and PAHs. A scoring system revealed that lead, arsenic, and antimony were the most critical contaminants. On Site 3, the concentration of lead in groundwater exceeded the drinking water standard indicating evident health risks. For the remaining two sites we calculated Acceptable Daily Doses (ADD) based on the Reasonable Maximum Exposure (RME) approach and compared them with safe exposure levels. We also used a pharmacokinetic model to determine blood lead levels (PbBs). Risks to biota were assessed using ecological benchmarks and exposure and accumulation models. Prediction of leaching was based on laboratory tests and a distribution model. The health risk assessment for lead resulted in the maximum hazard quotient (HQ) of 1.2 whereas the HQs of As and Sb remained less than 1. Some exposure scenarios produced PbB estimates exceeding 10 μ g dl^?1 but based on the uncertainty analysis we expect the health risks to remain insignificant. However, leaching of contaminants presents a risk to groundwater quality. At site 1 the ecotoxicity-based HQs demonstrate high risks to soil biota, small mammals, terrestrial plants and aquatic organisms.     

A Quantitative Ecological Risk Assessment of the Toxicological Risks from Exxon Valdez Subsurface Oil Residues to Sea Otters at Northern Knight Island,Prince William Sound,Alaska

A comprehensive, quantitative risk assessment is presented of the toxicological risks from buried Exxon Valdez subsurface oil residues (SSOR) to a subpopulation of sea otters (Enhydra lutris) at Northern Knight Island (NKI) in Prince William Sound, Alaska, as it has been asserted that this subpopulation of sea otters may be experiencing adverse effects from the SSOR. The central questions in this study are: could the risk to NKI sea otters from exposure to polycyclic aromatic hydrocarbons (PAHs) in SSOR, as characterized in 2001–2003, result in individual health effects, and, if so, could that exposure cause subpopulation-level effects? We follow the U.S. Environmental Protection Agency (USEPA) risk paradigm by: (a) identifying potential routes of exposure to PAHs from SSOR; (b) developing a quantitative simulation model of exposures using the best available scientific information; (c) developing scenarios based on calculated probabilities of sea otter exposures to SSOR; (d) simulating exposures for 500,000 modeled sea otters and extracting the 99.9% quantile most highly exposed individuals; and (e) comparing projected exposures to chronic toxicity reference values. Results indicate that, even under conservative assumptions in the model, maximum-exposed sea otters would not receive a dose of PAHs sufficient to cause any health effects; consequently, no plausible toxicological risk exists from SSOR to the sea otter subpopulation at NKI.     

Midvale Community Lead Study

Abstract

The primary objective of this study was to ascertain whether children living in close proximity to mill tailings and a former lead smelter site were currently exhibiting elevated blood lead (PbB) concentrations. To address this issue, the mean PbB for community children and the relationship between PbB and the proximity of the child's residence to the site was estimated. A secondary objective was to identify and quantify accessible lead (Pb) and arsenic (As) in the environment (e.g. Pb in soil, dust, paint and water or As in soil and dust). A third objective was to test for association between specific sources of environmental Pb and PbB and to estimate the relative contribution of these proximate sources of lead to the children's PbB. The data analytic methods allowed estimation of both direct and indirect impact of environmentally accessible Pb. The average PbB level of all children screened in Midvale was 5.2 μg dL^?1. Three percent exceeded 15 μg dL^?1; 12.7% exceeded 10 μg dL^?1. Pb-based house paint and Pb contaminated soil were identified as principal contributors to PbB. PbB was found to increase 1.25 μg dL^?1 per 1,000 ppm increase in lead in soil. Proximity of residence to the mill and smelter site was found to be a strong predictor of Pb in soil, and therefore indirectly related to increases in PbB.     

Methyl Ethyl Ketone Safety Characterization for Infants and Children: Assessment in the USEPA Voluntary Children's Chemical Evaluation Program

A safety characterization specific to children was performed for methyl ethyl ketone (MEK) according to the guidelines of the Voluntary Children's Chemical Evaluation Program (VCCEP). The characterization indicates that MEK exposures are not expected to pose an acute or chronic risk to children. Hazard information, summarized as per the VCCEP Tier structure, indicated no need for additional studies. All exposure pathways potentially relevant to children were considered, including child contact with environmental media, food, drinking water, parental transfer to child (human milk or dermal contact), direct consumer product use, and presence during product use. The assessment found that exposures from anthropogenic sources that children may encounter on a daily basis are very low, and in particular well below the chronic inhalation and oral health benchmarks (RfC and RfD) derived by the U.S. Environmental Protection Agency (USEPA). Indoor uses of consumer products can result in higher acute exposures, but these are short-lived and also fall below chronic benchmarks adjusted to an acute timeframe. In addition, MEK is rapidly metabolized and excreted, thus acute exposures do not lead to an increase in body burden over time. The USEPA concluded the VCCEP submission sufficiently characterized potential risks to children, and that no additional toxicity tests were needed for MEK.     

A Conceptual Framework for the Interpretation of Biological Markers for Environmental Exposure Assessment

Human exposure to environmental contaminants occurs via air, water, soil, dust, food, and other environmental media. Given this multitude of sources, environmental exposure assessment is moving away from single route exposure assessment to more integrated measures of exposure. Biological markers are frequently advocated as appropriate exposure assessment tools since they provide a measure of internal dose integrated over all routes of exposure. However, contributing sources may be difficult to identify through use of biological markers, and thus, have had limited utility in the regulatory community. To explore the different perspectives on the use and application of biological markers for exposure assessors, epidemiologists, and regulatory personnel, we have developed a biological marker conceptual framework. This framework is developed as a paradigm for the interpretation of biological markers for environmental exposure assessment linking the exposure assessment and the health effects assessment perspectives regarding biological markers. Further, it incorporates issues of source-specific exposures, aggregate exposure assessment, route-specific contributions, and biological variation in response to exposure. This structure provides an approach to explore the current constraints in using biological markers to evaluate source-specific exposures. This framework is discussed in the context of currently available biological markers for lead, carbon monoxide, and toluene. Biological markers represent a complex tool to assess human exposures to environmental contaminants; the biological marker framework presents a structure for their interpretation recognizing that many of the determinants of exposure, bioavailablity, and toxicokinetics are still being evaluated. The conceptual framework presented here provides another tool for the researcher in assessing the utility of biological markers in exposure assessment and epidemiology.     

Harmonization: Developing Consistent Guidelines for Applying Mode of Action and Dosimetry Information to Cancer and Noncancer Risk Assessment

The 1983 book, Risk Assessment in the Federal Government: Managing the Process, recommended developing consistent inference guidelines for cancer risk assessment. Over the last 15 years, extensive guidance have been provided for hazard assessment for cancer and other endpoints. However, as noted in several recent reports, much less progress has occurred in developing consistent guidelines for quantitative dose response assessment methodologies. This paper proposes an approach for dose response assessment guided by consideration of mode of action (pharmacodynamics) and tissue dosimetry (pharmacokinetics). As articulated here, this systematic process involves eight steps in which available information is integrated, leading first to quantitative analyses of dose response behaviors in the test species followed by quantitative analyses of relevant human exposures. The process should be equally appropriate for both cancer and noncancer endpoints. The eight steps describe the necessary procedures for incorporating mechanistic data and provide multiple options based upon the mode of action by which the chemical causes the toxicity. Given the range of issues involved in developing such a procedure, we have simply sketched the process, focusing on major approaches for using toxicological data and on major options; many details remain to be filled in. However, consistent with the revised carcinogen risk assessment guidance (USEPA, 1996c), we propose a process that would ultimately utilize biologically based or chemical specific pharmacokinetic and pharmacodynamic models as the backbone of these analyses. In the nearer term, these approaches will be combined with analysis of data using more empirical models including options intended for use in the absence of detailed information. A major emphasis in developing any harmonized process is distinguishing policy decisions from those decisions that are affected by the quality and quantity of toxicological data. Identification of data limitations also identifies areas where further study should reduce uncertainty in the final risk evaluations. A flexible dose response assessment procedure is needed to insure that sound toxicological study results are appropriately used to influence risk management decision-making and to encourage the conduct of toxicological studies oriented toward application for dose response assessments.     

Health Risk Assessment of Lead in the Republic of Korea

The purpose of this study was to estimate the daily exposure to lead due to food ingestion, air inhalation, and soil ingestion in the Republic of Korea's general population, and to evaluate the level of risk associated with the current lead exposure level using the proportional daily dose (3–4 μg/kg body weight/day) corresponding to the Provisional Tolerable Weekly Intake (PTWI) suggested by the Joint FAO/WHO Expert Committee on Food Additives as the toxicological tolerance level. The estimation of the daily exposure to lead via three pathways including food, soil ingestion and air inhalation was conducted as a chronic exposure assessment. For the lead exposure assessment through dietary intake, 1,389 lead residue data for 45 commodities investigated by the Korea Food and Drug Administration during the period 1995–2000 were utilized (KFDA 1996, 1997, 1998). Six hundred seventy-two air monitoring data from 7 major cities during the period 1993–2000 and 4,500 soil residue data at 1,500 sites during the period 1999–2001 were considered for the lead exposure assessment involving air inhalation and soil ingestion, respectively. The total daily exposure to lead was estimated by combining dietary intake, inhaled amount and soil intake corresponding to the typical activity of the general population, which was treated as a group of adults with a body weight of 60 kg. For risk characterization, the daily exposure to lead was compared with the toxicological tolerance level. The level of risk due to lead exposure was calculated using the hazard ratio (HR). The dietary intake of lead was 9.71 × 10_?4 mg/kg/day and the total daily exposure level, including air inhalation and soil ingestion, was 9.97 × 10_?4 mg/kg/day. The exposure contributions of foods, air and soil induced from the percentage of each media to the total daily exposure were 97.4%, 2.1% and 0.5%, respectively. Of the different commodity groups, the highest contribution to the total exposure came from grain, which represented 47.7% of the total. Additional exposure to lead occurs in certain population groups due to the use of tobacco, alcoholic beverages, and the intake of other foods, all factors not considered in this study. Through the comparison of the daily exposure to lead with the tolerance level based on the PTWI, the hazard ratio was estimated as being 0.25–0.33. This value implies that no increase in blood lead level is to be expected in the general population at the current lead exposure levels.     

A human health risk assessment of heavy metals in agricultural soils of Yanqi Basin,Silk Road Economic Belt,China

A total of 195 farmland soil samples were collected in Yanqi Basin, Xinjiang, northwest China, and the concentrations of As, Cd, Cr, Cu, Ni, Pb, and Zn were analyzed for their concentrations and pollution levels using the Nemerow comprehensive index. The health risk assessment model introduced by USEPA was utilized to evaluate the human health risks of heavy metals. Results indicated that the average concentrations of these seven metals were lower than the allowed soil environmental quality standards of China, while the average concentrations of Cd, Cr, Ni, Pb and Zn exceeded the background values of irrigation soils in Xinjiang. The average contamination factor (CF) for Pb indicated the heavy pollution, whereas the CF for Cd, Zn, Ni, Cu and Cr indicated the moderate pollution. The average PLI of heavy metals indicated the low pollution. The non-carcinogenic hazard index were below the threshold values, and the total carcinogenic risks due to As and Cr were within the acceptable range for both children and adults. As and Pb were the main non-carcinogenic factors, while As was the main carcinogenic factor in the study area. Special attentions should be paid to these priority control metals in order to target the lowest threats to human health.     

The Apache Longbow–Hellfire Missile Test at Yuma Proving Ground: Introduction and Problem Formulation for a Multiple Stressor Risk Assessment

An ecological risk assessment was conducted at Yuma Proving Ground, Arizona, as a demonstration of the Military Ecological Risk Assessment Framework (MERAF). The focus of the assessment was a testing program at the Cibola Range, which involved an Apache Longbow helicopter firing Hellfire missiles at moving targets, that is, M60-A1 tanks. The problem formulation for the assessment included conceptual models for three component activities of the test, helicopter overflight, missile firing, and tracked vehicle movement, and two ecological endpoint entities, woody desert wash communities and desert mule deer (Odocoileus hemionus crooki) populations. An activity-specific risk assessment framework was available to provide guidance for assessing risks associated with aircraft overflights. Key environmental features of the assessment area include barren desert pavement and tree-lined desert washes. The primary stressors associated with helicopter overflights were sound and the view of the aircraft. The primary stressor associated with Hellfire missile firing was sound. The principal stressor associated with tracked vehicle movement was soil disturbance, and a resulting, secondary stressor was hydrological change. Water loss to desert washes and wash vegetation was expected to result from increased ponding, infiltration, and/or evaporation associated with disturbances to desert pavement. A plan for estimating integrated risks from the three military activities was included in the problem formulation.     

Assessing the Bioavailability and Risk from Metal-Contaminated Soils and Dusts

Exposure to contaminated soil and dust is an important pathway in human health risk assessment. Physical and chemical characteristics and biological factors determine the bioaccessibility/bioavailability of soil and dust contaminants. Within a single sample, contamination may arise from multiple sources of toxic elements that may exist as different species that impact bioavailability. In turn, the bioaccessibility/bioavailability of soil and dust contaminants directly impacts human health risk. Research efforts focusing on development and application of in vitro and in vivo methods to measure the bioaccessibility/bioavailability of metal-contaminated soils have advanced in recent years. The objective of this workshop was to focus on developments in assessing the bioaccessibility/bioavailability of arsenic-contaminated soils, metals’ contamination in urban Canadian residences and potential children's exposures to toxic elements in house dust, an urban community-based study (i.e., West Oakland Residential Lead Assessment), bioavailability studies of soil cadmium, chromium, nickel, and mercury and human exposures to contaminated Brownfield soils. These presentations covered issues related to human health and bioavailability along with the most recent studies on community participation in assessing metals’ contamination, studies of exposures to residential contamination, and in vitro and in vivo methods development for assessing the bioaccessibility/bioavailability of metals in soils and dusts.     

污染场地土壤生态风险评估研究进展

随着我国快速城市化以及产业结构的调整,遗留下了大量的污染场地,发展和实施污染场地土壤生态风险评估是进行大规模污染场地修复行动的必要条件。本文围绕污染场地土壤生态风险评估的科学原理、框架构建及技术方法等方面的关键问题: 1)评估框架的场地实际针对性;2)概念模型的不确定性;3)土壤复合污染毒性机制;4)评估终点筛选;5)评估方法和框架构建等展开讨论,指出土壤复合污染的制毒机制,即污染物生物有效性和联合效应是污染场地土壤生态风险评估的关键科学问题。耦合美国环保局四步法和欧盟层级法的“证据-权重法”评估框架适用于野外复杂环境条件下的土壤污染生态风险评估。建议今后重点开展以下5个方面的工作: 1)污染场地土壤生态风险评估技术框架与风险管控技术框架之间的联合;2)概念模型研究;3)基于过程的场地土壤污染物反应运移模型研究;4)场地土壤复合污染生态毒理学机制研究;5)生态系统高水平生态风险评估终点研究。旨在为形成我国本土污染场地土壤生态风险评估技术指南提供理论基础和构架。     

Role of Ecological Modeling in Risk Assessment

Ecological models are useful tools for evaluating the ecological significance of observed or predicted effects of toxic chemicals on individual organisms. Current risk estimation approaches using hazard quotients for individual-level endpoints have limited utility for assessing risks at the population, ecosystem, and landscape levels, which are the most relevant indicators for environmental management. In this paper, we define different types of ecological models, summarize their input and output variables, and present examples of the role of some recommended models in chemical risk assessments. A variety of population and ecosystem models have been applied successfully to evaluate ecological risks, including population viability of endangered species, habitat fragmentation, and toxic chemical issues. In particular, population models are widely available, and their value in predicting dynamics of natural populations has been demonstrated. Although data are often limited on vital rates and doseresponse functions needed for ecological modeling, accurate prediction of ecological effects may not be needed for all assessments. Often, a comparative assessment of risk (e.g., relative to baseline or reference) is of primary interest. Ecological modeling is currently a valuable approach for addressing many chemical risk assessment issues, including screening-level evaluations.     

Application of a Probabilistic Risk Assessment Methodology to a Lead Smelter Site

Exposure of children to lead in the environment was assessed at the Murray Smelter Superfund site using both a deterministic risk assessment approach, the Integrated Exposure Uptake Biokinetic (IEUBK) model, and a probabilistic approach, the Integrated Stochastic Exposure (ISE) model. When site-specific data on lead in environmental media were input as point estimates into the IEUBK model, unacceptable risks were predicted for children living within five of eight study zones. The predicted soil cleanup goal was 550?ppm. Concentration and exposure data were then input into the ISE model as probability distribution functions and a one-dimensional Monte Carlo analysis (ID MCA) was run to predict the expected distribution of exposures and blood lead values. Uncertainty surrounding these predictions was examined in a two-dimensional Monte Carlo analysis (2-D MCA). The ISE model predicted risks that were in the same rank order as those predicted by the IEUBK model, although the probability estimates of exceeding a blood lead level of 10?µg/dl (referred to as the P10) from the ISE model were uniformly lower than those predicted by the IEUBK model. The 2-D MCA allowed evaluation of the confidence around each P10 level, and identified the main sources of both uncertainty and variability in exposure estimates. The ISE model suggested cleanup goals ranging from 1300 to 1500 ppm might be protective at this site.     

Evidence of High Tolerance to Ecologically Relevant Lead Shot Pellet Exposures by an Upland Bird

Upland birds that display grit ingestion behavior are potentially at risk of detrimental effects and death from lead poisoning at trap and skeet ranges and other areas where vast quantities of spent lead shot pellets abound. Because commonly cited force-feeding pellet exposure studies deviate from true field conditions, their results may not reflect true risks faced by upland birds. In particular, studies that use new shot pellets and administer more pellets than would be reasonably ingested, critically interfere with the understanding of actualized pellet exposures. In this study, northern bobwhites (Colinus virginianus), a frequent test species in shot pellet research, were dosed in an ecologically-relevant manner (i.e., with spent shot and with no more than three pellets). Notably, the 56-day post-dosing observation period, during which a battery of physiological measures were recorded, exceeded that of related studies. Despite a sustained suppression of a lead poisoning indicator, the data suggest upland birds can withstand spent shot pellet exposures. Data detected a survivorship ≥95%, absence of illness, demonstrated tolerance for extremely high blood lead concentrations, and unaffected blood parameters. In conjunction with ecological considerations (e.g., spatial scale and animal behavior), concern about bird population losses from the incidental ingestion of spent shot pellets is potentially overstated.