Human Health Risk Assessment: Required Reading

Over the past 30 years, risk assessment has developed into a scientific discipline. It is critical that the next generation of risk assessors understand the history of our field, and recognize the numerous successes and failures that have taken place. This short Perspective identifies and describes specific books, monographs, and reports that are required reading for any nascent risk assessor.     

Toxicological Considerations of Contaminants in the Terrestrial Environment for Ecological Risk Assessment

The terrestrial environment acts as a “sink” for contaminants that have been purposely or accidentally released into the environment. Science and policy that support protective measures for terrestrial ecosystems have run behind those of aquatic toxicology and water quality concerns. As a result ecological risk assessment (ERA) involving terrestrial environments tends to be conducted at a simplistic level, relying on numeric targets (soil quality criteria) as a basis for decision-making. However, soil criteria for ecological receptors are somewhat deficient in terms of the numbers available and the data that supports these numbers. Direct toxicity assessments (DTA) for terrestrial environments, such as those used for water quality evaluations, can provide additional useful information about the toxicity and bioavailability of mixtures of contaminants present in soils. This article outlines the approaches used for assessing the toxicity of soil contaminants in terrestrial environments and critiques their advantages and pitfalls.     

Ten Years of the Relative Risk Model and Regional Scale Ecological Risk Assessment

It has been 10 years since the publication of the relative risk model (RRM) for regional scale ecological risk assessment. The approach has since been used successfully for a variety of freshwater, marine, and terrestrial environments in North America, South America, and Australia. During this period the types of stressors have been expanded to include more than contaminants. Invasive species, habitat loss, stream alteration and blockage, temperature, change in land use, and climate have been incorporated into the assessments. Major developments in the RRM have included the extensive use of geographical information systems, uncertainty analysis using Monte Carlo techniques, and its application to retrospective assessments to determine causation. The future uses of the RRM include assessments for forestry and conservation management, an increasing use in invasive species evaluation, and in sustainability. Developments in risk communication, the use of Bayesian approaches, and in uncertainty analyses are on the horizon.     

Improving Risk Assessment: Toxicological Research Needs

A workshop convened to define research needs in toxicology identified several deficiencies in data and methods currently applied in risk assessment. The workshop panel noted that improving the link between chemical exposure and toxicological response requires a better understanding of the biological basis for inter-and intra-human variability and susceptibility. This understanding will not be complete unless all life stages are taken into consideration. Because animal studies serve as a foundation for toxicological assessment, proper accounting for cross-species extrapolation is essential. To achieve this, adjustments for dose-rate effects must be improved, which will aid in extrapolating toxicological responses to low doses and from short-term exposures. Success depends on greater use of validated biologically based dose-response models that include pharmacokinetic and pharmacodynamic data. Research in these areas will help define uncertainty factors and reduce reliance on underlying default assumptions. Throughout the workshop the panel recognized that biomedical science and toxicology in particular is on the verge of a revolution because of advances in genomics and proteomics. Data from these high-output technologies are anticipated to greatly improve risk assessment by enabling scientists to better define and model the elements of the relationship between exposure to biological hazards and health risks in populations with differing susceptibilities.     

Risk Assessment and Safety Evaluation Using Probabilistic Fault Tree Analysis

Risk assessment is an essential prelude to the development of accident prevention strategies in any chemical or petrochemical industry. Many techniques and methodologies such as HAZOP, failure mode effect analysis, fault tree analysis, preliminary hazard analysis, quantitative risk assessment and probabilistic safety analysis are available to conduct qualitative, quantitative, and probabilistic risk assessment. However, these methodologies are limited by: extensive data requirements, the length of study, results are not directly interpretable for decision making, simulation is often difficult, and they are applicable only at the operation or late design stage. Khan et al. (2001a) recently proposed a detailed methodology for risk assessment and safety evaluation. This methodology is simple, yet it is effective in safety and design-related decision making, and it has been applied successfully to many case studies. It is named SCAP, where S stands for safety, C and A stand for credible accident respectively, and P stands for probabilistic fault tree analysis. This paper recapitulates the SCAP methodology and demonstrates its application to a petrochemical plant.     

Ecological Risk Assessment and Ecological Epidemiology for Contaminated Sites

After 20 years of development, ecological risk assessment is widely accepted. However, it is evolving in response to a variety of technical and societal pressures. First, pressure for greater simplicity and standardization arise from the expectation that risk assessments should require little time and resources but be defensible. Second, the advance of the environmental sciences and increasing awareness of the complexity of ecological responses generate pressure for greater realism. Third, the dominance of human health risk assessment generates a pressure to integrate ecological risk assessment with that dominant field. Fourth, the demand for cost-benefit analysis creates pressure for integration with environmental economics. Finally, the need to connect the practice of ecological epidemiology with risk-based decision-making creates a pressure of the formation of a single integrated ecological assessment practice.     

羊肚菌食品毒理学安全性评价

本文研究了羊肚菌子实体的食品毒理学安全性,结果表明羊肚菌小鼠经口服LD50＞10g/kg.BW,属无毒级;鼠伤寒沙门氏菌/哺乳动物微粒体酶试验、骨髓微核试验及小鼠精子畸变试验表明该样品无致突变作用、对雄性生殖细胞无遗传毒性;30天喂养试验结果表明对动物最大毒理学无作用剂量大于3.0g/kg·BW/d.可以作保健食品的原料.     

Approaches for Integrated Risk Assessment

Recognizing the need to enhance the effectiveness and efficiency of risk assessments globally, the World Health Organization's International Programme on Chemical Safety, the U.S. Environmental Protection Agency, the European Commission, and the Organization for Economic Cooperation and Development developed a collaborative partnership to foster integration of assessment approaches used to evaluate human health and ecological risks. The objectives of this effort included: improving understanding of the benefits of integration, identifying obstacles to the integration process, and engaging key agencies, organizations, and scientific societies to promote integration. A framework with supporting documentation was developed to describe an approach for integration. Four case studies were constructed to illustrate how integrated risk assessments might be conducted for chemical and nonchemical stressors. The concepts and approaches developed in the project were evaluated in an international workshop. The goal of this effort was international acceptance of guidance for integrated risk assessment.     

Role of Ecological Risk Assessment Findings in Agency Decision-Making Regarding Oyster Restoration in Chesapeake Bay

Failure of on-going management programs to restore oyster populations in Chesapeake Bay, USA, prompted state and federal agencies to consider the introduction of the non-native Asian oyster (Crassostrea ariakensis). An ecological risk assessment (ERA) of the proposed introduction was an essential element in preparation of a programmatic environmental impact statement (PEIS). The ERA had to assess risks of not only the proposed action (Asian oyster introduction) but also of the eight alternatives evaluated in the PEIS. The ERA suggested that the risk that the Asian oyster would not provide ecosystem services similar to those afforded by the native Eastern oyster was low, but there was moderate uncertainty associated with that conclusion. There was a non-zero risk of self-sustaining Asian oyster populations becoming established even if aquaculture with triploid, purportedly sterile Asian oysters were to be permitted. Nearly all of the risk conclusions had associated moderate to high uncertainty, not providing the level of proof that the agencies felt sufficient to justify proceeding with any action involving the Asian oyster. The irreversible nature of an introduction of the species bolstered that decision. Maryland and Virginia agencies have implemented numerous actions focused on the native oyster, but the outcome of these on-going actions is not yet known.     

复合生物杀菌剂F6-11的安全性毒理学研究

目的：为研究复合生物杀菌剂F6．11毒性,采用动物实验法进行毒理学评价。方法：对复合生物杀菌剂F6-11进行小鼠急性毒性试验、小鼠骨髓嗜多染红细胞微核试验、亚急性毒性试验、家兔多次完整皮肤刺激试验、急性眼刺激试验、豚鼠皮肤变态反应试验、鱼类延长毒性14天试验。结果：复合生物杀菌剂F6—11对小鼠急性毒性LD50〉5000mg／kg．bw,属于实际无毒级物质;小鼠微核试验该杀菌剂各剂量组与阴性对照组比较,微核率无显著性差异（P〉0．05）;亚急性毒性试验动物血常规、生化指标及各脏器均未发现异常;对家兔多次完整皮肤及眼刺激反应积分均为0,均属无刺激性;对豚鼠皮肤变态反应试验组动物与阴性对照组无可见不同．试验组动物皮肤致敏反应积分为0,无致敏作用;鱼类延长毒性14天试验无异常。结论：毒理学研究表明,复合生物杀菌剂F6．11具有良好的使用安全性。     

Applying USEPA Risk Assessment Guidance in the 90s

Over the past decade, risk assessment has become increasingly relied upon for helping to make environmental management decisions. This trend has been accompanied by research and refinements in basic risk assessment methodologies to improve our ability to understand and evaluate the human health risks associated with chemical exposures.Despite this progress, significant uncertainties continue to be associated with the risk assessment process. These uncertainties typically derive from gaps in available data regarding chemical toxicity, and from difficulties in reliably estimating the magnitude of chemical exposures. Given these limitations, risk assessment is generally most valuable in evaluating relative risk; for example, when comparing alternatives to achieving a specified goal, setting priorities for protecting human health, or establishing procedures for properly allocating resources. Risk assessment can also be useful for developing regulatory benchmarks such as permit limits for air or water. In many cases, however, the limitations of the risk assessment process make it difficult (if not impossible) to reliably estimate an absolute level of risk, especially for a specific individual in an exposed population. In such cases, risk assessment can be seriously misapplied, and its results misinterpreted.This paper discusses some of the challenges that have been faced by the field of risk assessment during the 1990s. Current trends in risk assessment, and its use by regulatory agencies in making risk management decisions, are also described.     

The Fox River Risk Assessment Teaching Tool

In 1999 and 2000, two environmental consulting companies independently prepared risk assessments of the Lower Fox River waste site in Wisconsin. Because the two assessments produced somewhat different risk characterizations, the Association for Environmental Health & Sciences was asked by the site's Potentially Responsible Party to form a peer review panel to critique and compare the two assessments. The panel found interesting differences between the two risk assessments and recommended that their observations, together with the two risk assessments, be made available as a Teaching Tool for persons interested in conducting human and ecological risk assessments. An accompanying CD contains these and other materials useful for teaching purposes.     

An Evaluation of Risk Drivers from a Sample of Risk Assessments Conducted for the U.S. Army

We evaluate risk drivers at selected U.S. Army installations by developing a database containing contaminant-pathway-receptor combinations that exceed regulatory thresholds for ecological (toxicity quotient greater than one), human health cancer risk (predicted incremental lifetime cancer risk greater than one in ten thousand), and noncancer human health (hazard index greater than one). We compare the risk drivers from the database to reported corrective action objectives from available decision documents. For noncancer hazards, explosives (particularly in ground water) dominate the reported exceedances of regulatory thresholds in the database. PAHs in home-grown produce show the highest number of exceedances of regulatory thresholds for cancer risk. For ecological risks, PAHs in both terrestrial and aquatic environments dominate the exceedances of regulatory thresholds. All available cleanup levels were derived based on human health exposures rather than ecological exposures, except for one site. In general, ecological risks were considered to be “more uncertain,” and that was used as a basis for not relying on backcalculated target levels on the basis of ecological risk. The reverse was true for human health risks: the “conservative” assumptions incorporated into the modeling provided the justification for backcalculating health-protective target levels.     

Ecological Risk Assessment of Tebuthiuron Following Application on Tropical Australian Wetlands

The present study assessed the ecological risks of the herbicide tebuthiuron to freshwater fauna and flora of northern Australia's tropical wetlands. Effects characterization utilized acute and chronic toxicity data of tebuthiuron to local freshwater species (three animals and two plants) as well as toxicity data derived from northern hemisphere species. Species sensitivity distributions (SSDs) for four effects scenarios—plant chronic toxicity (NOEC data), plant chronic toxicity (EC/IC₅₀ data), invertebrate and vertebrate chronic toxicity (NOEC data), and vertebrate acute toxicity (LC₅₀ data)—were used to characterize effects and calculate 10, 5, and 1% hazardous concentrations (HCs). Tebuthiuron concentrations affecting 5% of species (i.e., HC₅s) for the earlier scenarios were 0.013, 0.093, 9.0, and 97 mg L^?1, respectively. Exposure characterization involved the use of historical field monitoring data of tebuthiuron concentrations following application of tebuthiuron to a large infestation of the wetland weed Mimosa pigra (Mimosa). Tebuthiuron concentrations in surface water ranged from below detection to 2.05 mg L^?1 and were still measurable up to 10 months following application. A breakpoint regression model was fitted to the field monitoring data, providing a time-dependent estimate of exposure to tebuthiuron. Risk characterization involved the comparison of the SSDs and associated HCs for each of the effects scenarios, with the time-dependent model of tebuthiuron exposure. Modeled tebuthiuron concentrations over the first 12 days post-application were in excess of concentrations required to cause major (i.e., 50% reductions in population numbers) effects to over 85% of freshwater plant species (based on data for phytoplankton and floating macrophytes). Beyond this period and up to 300 d post-application, 10–20% of species were still predicted to be affected. To quantify the probability of prolonged effects, the plant SSDs were compared to a cumulative probability distribution of tebuthiuron measured from 70 d to 293 d post-application. The probability of at least 5% of freshwater plant species experiencing chronic effects due to tebuthiruon at ≥70 d post-application was 58% based on NOEC data and 8% based on EC/IC₅₀ data. Overlap of the 95% confidence limits of the exposure distribution and plant SSDs indicated substantial uncertainty in the risk estimates. Risks of effects to freshwater invertebrates and vertebrates were generally < 1%. It was concluded that tebuthiuron appears to represent a significant and prolonged risk to native freshwater plant species, particularly phytoplankton and floating macrophytes, whereas the risks to freshwater invertebrates and vertebrates appear low. However, from a management perspective, the risks of tebuthiuron (and other herbicides) must be weighed against the known, serious environmental and economic impacts of the target weed, Mimosa. Overall, the outcomes of the risk assessment support the various management options that have been implemented with regard to the use of tebuthiuron to control Mimosa.     

An Assessment of Integrated Risk Assessment

In order to promote international understanding and acceptance of the integrated risk assessment process, the World Health Organization/International Programme on Chemical Safety (WHO/IPCS), in collaboration with the U.S. Environmental Protection Agency and the Organization for Economic Cooperation and Development, initiated a number of activities related to integrated risk assessment. In this project, the WHO/IPCS defines integrated risk assessment as a science-based approach that combines the processes of risk estimation for humans, biota, and natural resources in one assessment. This article explores the strengths and weaknesses of integration as identified up to this date and the degree of acceptance of this concept by the global risk assessment/risk management community. It discusses both opportunities and impediments for further development and implementation.

The major emerging opportunities for an integrated approach stem from the increasing societal and political pressure to move away from vertebrate testing leading to a demand for scientific integrated approaches to in vitro and in vivo testing, as well as to computer simulations, in so-called Intelligent Testing Strategies. In addition, by weighing the evidence from conventional mammalian toxicology, ecotoxicology, human epidemiology, and eco-epidemiology, risk assessors could better characterize mechanisms of action and the forms of the relationships of exposures to responses. It is concluded that further demonstrations of scientific, economic and regulatory benefits of an integrated approach are needed. As risk assessment is becoming more mechanistic and molecular this may create an integrated approach based on common mechanisms and a common systems-biology approach.     

The Concept of Data Utility in Health Risk Assessment: A Multi-Disciplinary Perspective

Human and ecological health risk assessments and the decisions that stem from them require the acquisition and analysis of data. In agencies that are responsible for health risk decision-making, data (and/or opinions/judgments) are obtained from sources such as scientific literature, analytical and process measurements, expert elicitation, inspection findings, and public and private research institutions. Although the particulars of conducting health risk assessments of given disciplines may be dramatically different, a common concern is the subjective nature of judging data utility. Often risk assessors are limited to available data that may not be completely appropriate to address the question being asked. Data utility refers to the ability of available data to support a risk-based decision for a particular risk assessment. This article familiarizes the audience with the concept of data utility and is intended to raise the awareness of data collectors (e.g., researchers), risk assessors, and risk managers to data utility issues in health risk assessments so data collection and use will be improved. In order to emphasize the cross-cutting nature of data utility, the discussion has not been organized into a classical partitioning of risk assessment concerns as being either human health- or ecological health-oriented, as per the U.S. Environmental Protection Agency's Superfund Program.