Integrated testing and intelligent assessment—new challenges under REACH

BACKGROUND, AIM AND SCOPE: Due to a number of drawbacks associated with the previous regime for the assessment of new and existing chemicals, the European Union established a new regulation concerning the registration, evaluation, authorisation and restriction of chemicals (REACH). All relevant industrial chemicals must now be assessed. Instead of the authorities, industry itself is responsible for the risk assessment. To achieve better and more efficient assessments while reducing animal testing, all information-standard, non-standard and non-testing-has to be used in an integrated manner. To meet these challenges, the current technical guidance documents for risk assessment of new and existing chemicals had to be updated and extended considerably. This was done by experts in a number of REACH Implementation Projects. This paper presents the most relevant results of the expert Endpoint Working Group on Aquatic Toxicity in order to illustrate the change of paradigm in the future assessment of hazards to the aquatic environment by chemical substances. MAIN FEATURES AND CHALLENGES: REACH sets certain minimum data requirements in order to achieve a high level of protection for human health and the environment. It encourages the assessor to use alternative information instead of or in addition to standard one. This information has to be equivalent to the standard information requirement and adequate to draw overall conclusions with respect to the regulatory endpoints classification and labelling, persistent, bioaccumulative and toxic (PBT) assessment and predicted no-effect concentrations (PNEC) derivation. The main task of the expert working group was to develop guidance on how to evaluate the toxicity of a substance based on integration of information from different sources and of various degrees of uncertainty in a weight of evidence approach. INTEGRATED TESTING AND INTELLIGENT ASSESSMENT: In order to verify the equivalence and adequacy of different types of information, a flexible sequence of steps was proposed, covering characterisation of the substance, analysis of modes of action, identification of possible analogues, evaluation of existing in vivo and in vitro testing data as well as of QSAR results. Finally, all available data from the different steps have to be integrated to come to an overall conclusion on the toxicity of the substance. This weight of evidence approach is the basis for the development of integrated testing strategies (ITS), in that the available evidence can help to determine subsequent testing steps and is essential for an optimal assessment. Its flexibility helps to meet the different requirements for drawing conclusions on the endpoints classification and labelling, PNEC derivation as well as PBT assessment. The integration of all kinds of additional information in a multi-criteria assessment reduces the uncertainties involved with extrapolation to the ecosystem level. The weight of evidence approach is illustrated by practical examples. CONCLUSIONS AND PERSPECTIVES: REACH leads to higher challenges in order to make sound decisions with fewer resources, i.e. to move away from extensive standard testing to an intelligent substance-tailored approach. Expert judgement and integrated thinking are key elements of the weight of evidence concept and ITS, potentially leading to better risk assessments. Important sub-lethal effects such as endocrine disruption, which are not covered by the current procedure, can be considered. Conclusions have to be fully substantiated: Risk communication will be an important aspect of future assessments.     

Apparatus for Simultaneous Size-Differentiated Sampling of Optical and Suboptical Aerosols: Application to Analysis of Nitrates and Sulfates

In recent years, the EPA has moved toward a risk assessment/risk reduction framework for making regulatory decisions. The Agency has taken a number of steps to assure the quality and consistency of the risk assessment component of those decisions. The first, and perhaps most important of these steps, is the development of Agency-wide risk assessment guidelines. Five guidelines have been published. They are: carcinogenicity, mutagenicity, developmental toxicity, chemical mixtures, and exposure. The provisions of the five guidelines are discussed in the context of the four components of risk assessment. Other activities designed to assure quality and consistency in risk assessments, reduce uncertainty in risk assessment, ensure a more efficient information exchange about risk and risk assessment, and develop the appropriate oversight mechanisms are also discussed. These include additional guidelines, the Risk Assessment Forum, risk assessment research, the Integrated Risk Information System, the Hazard Assessment Notification System, and the Risk Assessment Council.     

Reducing Risk in Hazardous Waste Management

Over the past several years, the Environmental Protection Agency has attempted to institutionalize an approach to its activities that is characterized by an active attempt to separate risk assessment from risk management activities. This approach, while not new in concept, has only been evolving at EPA for about four years. The Office of Research and Development, or ORD, has organized its research planning activities around this risk assessment-risk management concept. In order for the approach to succeed, it is necessary to develop the data and methodology necessary to undertake risk assessments both in the area of human health and ecology, and to develop methods to reduce those risks. Accordingly, we have organized our research planning into four major areas: Human Health Risk, Environmental or Ecological Risk, Exposure Assessment, and Risk Reduction. What I would like to do is outline briefly the breadth and diversity of EPA’s research program and the Agency’s research needs.     

Evaluation of EU risk assessments existing chemicals (EC Regulation 793/93)

An evaluation was performed on the first group (41) of completed risk assessments for chemicals of the EU priority lists (Existing Chemicals; EC Regulation 793/93). The evaluation focussed on the conclusions of the risk assessments. The EU risk assessment process detected a high number of substances of concern. Furthermore priority chemicals may pose potential risks to the whole range of protection goals of the risk assessment. The predictability of the risk assessments for priority chemicals was investigated. Our a priori knowledge on possible risks of priority chemicals is found to be poor, especially for consumers. Both for environment and human health the potential risks were linked with a broad spectrum of use patterns. It is concluded that no industry category can in advance be excluded from performing risk assessments. For a great number of chemicals, additional testing was found to be needed to finalize the risk assessment. This evokes questions about the completeness of the current base-set, but also about the suitability of some of the submitted human health tests that should initially fulfil the base-set needs. The results of this evaluation are useful for ongoing discussions on risk assessment processes for chemicals.     

Reporting and evaluation criteria as means towards a transparent use of ecotoxicity data for environmental risk assessment of pharmaceuticals

Ecotoxicity data with high reliability and relevance are needed to guarantee the scientific quality of environmental risk assessments of pharmaceuticals. The main advantages of a more structured approach to data evaluation include increased transparency and predictability of the risk assessment process, and the possibility to use non-standard data.In this collaboration, between the research project MistraPharma and the German Federal Environment Agency, a new set of reporting and evaluation criteria is presented and discussed. The new criteria are based on the approaches in the literature and the OECD reporting requirements, and have been further developed to include both reliability and relevance of test data.Intended users are risk assessors and researchers performing ecotoxicological experiments, but the criteria can also be used for education purposes and in the peer-review process for scientific papers. This approach intends to bridge the gap between the regulator and the scientist’s needs and way of work.     

A new dose model for assessment of health risk due to contaminants in air

The problem of making quantitative assessments of the risks associated with human exposure to toxic contaminants in the environment is a pressing one. This study demonstrates the capability of a new computational technique involving the use of fuzzy logic and neural networks to produce realistic risk assessments. The systematic analysis of human exposure involves the use of measurements and models, the results of which are sometimes used in regulatory decisions or in the drafting of legislation. Because of limited scientific understanding, however, interpretation of models often involves substantial uncertainty. Extensive measurement programs can be very expensive. The high complexity and inherent heterogeneity of exposure analysis is still a major challenge. The approach to this challenge tested here is to use a new model incorporating sophisticated artificial intelligence algorithms. Exposure assessment often requires that a number of factors be evaluated, including exposure concentrations, intake rates, exposure times, and frequencies. These factors are incorporated into a system that can "learn" the relevant relationships based on a known data set. The results can then be applied to new data sets and thus be applied widely without the need for extensive measurements. In this analysis, an example is developed for human health risk through inhalation exposure to benzene from vehicular emissions in the cities of Auckland and Christchurch, New Zealand. Risk factors considered were inhaled contaminant concentration, age, body weight, and activity patterns of humans. Three major variables affecting the inhaled contaminant concentration were emissions (mainly from motor vehicles), meteorology (wind speed, temperature, and atmospheric stability), and site factors (hilly, flat, etc.). The results are preliminary and used principally to demonstrate the technique, but they are very encouraging.     

Methodology for conducting screening-level ecological risk assessments for hazardous waste sites. Part II: grouping ecological components

Screening-level ecological risk assessments are commonly conducted to identify those contaminants and receptors on which to focus future phases or tiers of the ecological risk assessment process. Most screening assessments are performed using a suite of individual species subjected to intensive evaluation of exposure (endpoint species) and selected for their appropriateness for serving as representatives or 'indicators' for all other species. As site complexity and the number of contaminants of concern increase, it becomes more difficult to assure with confidence that the potential for significant effects has been adequately assessed through an appropriate choice of endpoint species. As an alternative, functional groups demonstrating biological similarity and similar potential for contaminant exposure were developed for INEEL screening-level ecological risk assessments using taxonomic, trophic and habitat parameters. Data for individual species within each group are then integrated to address the potential for risk of adverse effects from contaminant exposure for the group as a whole.     

A risk assessment tool for contaminated sites in low-permeability fractured media

A risk assessment tool for contaminated sites in low-permeability fractured media is developed, based on simple transient and steady-state analytical solutions. The discrete fracture (DF) tool, which explicitly accounts for the transport along fractures, covers different source geometries and history (including secondary sources) and can be applied to a wide range of compounds. The tool successfully simulates published data from short duration column and field experiments. The use for risk assessment is illustrated by three typical risk assessment case studies, involving pesticides, chlorinated solvents, benzene and MTBE. The model is compared with field data and with results from a simpler approach based on an Equivalent Porous Media (EPM). Risk assessment conclusions of the DF and EPM approaches are very different due to the early breakthrough, long term tailing, and lower attenuation due to degradation associated with fractured media. While the DF tool simulates the field data, it is difficult to conclude that the DF model is superior to an EPM model because of a lack of long term monitoring data. However, better agreement with existing field data by the DF model using observed physical fracture parameters favors the use of this model over the EPM model for risk assessments.     

Development of risk-based air quality management strategies under impacts of climate change

Climate change is forecast to adversely affect air quality through perturbations in meteorological conditions, photochemical reactions, and precursor emissions. To protect the environment and human health from air pollution, there is an increasing recognition of the necessity of developing effective air quality management strategies under the impacts of climate change. This paper presents a framework for developing risk-based air quality management strategies that can help policy makers improve their decision-making processes in response to current and future climate change about 30-50 years from now. Development of air quality management strategies under the impacts of climate change is fundamentally a risk assessment and risk management process involving four steps: (1) assessment of the impacts of climate change and associated uncertainties; (2) determination of air quality targets; (3) selections of potential air quality management options; and (4) identification of preferred air quality management strategies that minimize control costs, maximize benefits, or limit the adverse effects of climate change on air quality when considering the scarcity of resources. The main challenge relates to the level of uncertainties associated with climate change forecasts and advancements in future control measures, since they will significantly affect the risk assessment results and development of effective air quality management plans. The concept presented in this paper can help decision makers make appropriate responses to climate change, since it provides an integrated approach for climate risk assessment and management when developing air quality management strategies. Implications: Development of climate-responsive air quality management strategies is fundamentally a risk assessment and risk management process. The risk assessment process includes quantification of climate change impacts on air quality and associated uncertainties. Risk management for air quality under the impacts of climate change includes determination of air quality targets, selections of potential management options, and identification of effective air quality management strategies through decision-making models. The risk-based decision-making framework can also be applied to develop climate-responsive management strategies for the other environmental dimensions and assess costs and benefits of future environmental management policies.     

Potential Impact on Standards for Toxic Air Contaminants

Since the Bhopal incident, the public has placed pressure on regulatory agencies to set community exposure limits for the dozens of chemicals that may be released by manufacturing facilities. More or less objective limits can be established for the vast majority of these chemicals through the use of risk assessment. However, each step of the risk assessment process (i.e., hazard identification, dose-response assessment, exposure assessment, and risk characterization) contains a number of pitfalls that scientists need to avoid to ensure that valid limits are established. For example, in the hazard identification step there has been little discrimination among animal carcinogens with respect to mechanism of action or the epidemiology experience. In the dose-response portion, rarely is the range of “plausible” estimated risks presented. Physiologically based pharmacokinetic (PB-PK) models should be used to understand the difference between the tissue doses and the administered dose, as well as the difference in target tissue concentrations of the toxicant between rodents and humans. Biologically-based models like the Moolgavkar-Knudson-Venzon (MKV) should be developed and used, when appropriate. The exposure assessment step can be significantly improved by using more sensitive and specific sampling and analytical methods, more accurate exposure parameters, and computer models that can account for complex environmental factors. Whenever possible, model predictions of exposure and uptake should be validated by biological monitoring of exposed persons (urine, blood, adipose) or by field measurements of plants, soil, fish, air, or water. In each portion of an assessment, the weight of evidence approach should be used to identify the most defensible value. In the risk characterization, the best estimate of the potential risk as well as the highest plausible risk should be presented. Future assessments would be much improved if quantitative uncertainty analyses were conducted. Procedures are currently available for making future assessments. By correcting some of these shortcomings in how health risk assessments have been conducted, scientists and risk managers should be better able to identify scientifically appropriate ambient air standards and emission limits.     

The current practice of health risk assessment: potential impact on standards for toxic air contaminants

Since the Bhopal incident, the public has placed pressure on regulatory agencies to set community exposure limits for the dozens of chemicals that may be released by manufacturing facilities. More or less objective limits can be established for the vast majority of these chemicals through the use of risk assessment. However, each step of the risk assessment process (i.e., hazard identification, dose-response assessment, exposure assessment, and risk characterization) contains a number of pitfalls that scientists need to avoid to ensure that valid limits are established. For example, in the hazard identification step there has been little discrimination among animal carcinogens with respect to mechanism of action or the epidemiology experience. In the dose-response portion, rarely is the range of "plausible" estimated risks presented. Physiologically based pharmacokinetic (PB-PK) models should be used to understand the difference between the tissue doses and the administered dose, as well as the difference in target tissue concentrations of the toxicant between rodents and humans. Biologically-based models like the Moolgavkar-Knudson-Venzon (MKV) should be developed and used, when appropriate. The exposure assessment step can be significantly improved by using more sensitive and specific sampling and analytical methods, more accurate exposure parameters, and computer models that can account for complex environmental factors. Whenever possible, model predictions of exposure and uptake should be validated by biological monitoring of exposed persons (urine, blood, adipose) or by field measurements of plants, soil, fish, air, or water. In each portion of an assessment, the weight of evidence approach should be used to identify the most defensible value. In the risk characterization, the best estimate of the potential risk as well as the highest plausible risk should be presented. Future assessments would be much improved if quantitative uncertainty analyses were conducted. Procedures are currently available for making future assessments. By correcting some of these shortcomings in how health risk assessments have been conducted, scientists and risk managers should be better able to identify scientifically appropriate ambient air standards and emission limits.     

Environmental risk assessment of phosphonates,used in domestic laundry and cleaning agents in The Netherlands

In the long-term cooperative project Voluntary Plan of Action (1990) between the Dutch Soap and Detergent Association (NVZ) and the Dutch Ministry of Housing, Spatial Planning and the Environment (VROM) environmental risk assessments of several main components of laundry cleaning formulations were completed. As a part of that project the environmental risk assessment of HEDP, ATMP, EDTMP and DTPMP phosphonates used in detergent applications has been carried out according to the EU Technical Guidance Document for Environmental Risk Assessment for New and Existing Chemicals. All PEC/PNEC ratios were well below 1. Results of this assessment based on the total industry volumes from 1995 and 1998 indicate that the environmental risk of these phosphonates is low in The Netherlands with properly functioning sewage treatment plants.     

Assessing the environmental fate of chemicals of emerging concern: a case study of the polybrominated diphenyl ethers

It is suggested that assessments of chemicals of emerging concern can be rationally structured around a multistage process in which fate and risk are evaluated with increasing accuracy as new data become available. An initial tentative and approximate assessment of fate and risk can identify key data gaps and justify and direct further investigations, which progressively improve the reliability of the assessment. This approach is demonstrated for a class of chemicals, the polybrominated diphenyl ethers (PBDEs), which is of increasing concern, but about which there is presently a lack of comprehensive data on properties, sources, fate and effects. Specifically, 20 PBDE congeners are investigated using the suggested approach and research needs are identified.     

A framework for risk characterization of environmental pollutants.

Risk characterization is defined by both the U.S. National Academy of Sciences and the U.S. EPA as the estimation of human health risk due to harmful (i.e., toxic or carcinogenic) substances or organisms. Risk characterization studies are accomplished by integrating quantitative exposure estimates and dose-response relationships with the qualitative results of hazard identification. A Risk Characterization Framework has been developed to encourage a systematic approach for analysis and presentation of risk estimates. This methodology subdivides the four common components of the risk assessment process into ten elements. Each of these elements is based on a term in a predictive risk equation. The equation allows independent computations of exposure, dose, lifetime individual risk, and risk to affected populations. All key assumptions in the predictive risk equation can be explicitly shown. This is important to understand the basis and inherent uncertainties of the risk estimation process. The systematic treatment of each of the ten elements in this framework aids in the difficult job of comparing risk estimates by different researchers using different methodologies. The Risk Characterization Framework has been applied to various indoor and outdoor air pollutants of a carcinogenic nature. With further development, it also promises to be applicable to noncarcinogenic effects.     

Policy and Science Implications of the Framing and Qualities of Uncertainty in Risks: Toxic and Beneficial Fish from the Baltic Sea

Policy and research issues in the framing and qualities of uncertainties in risks are analyzed, based on the assessments of dioxin-like compounds (DLCs) and other ingredients in Baltic Sea fish, a high-profile case of governance. Risks are framed broadly, to then focus on dioxins and beneficial fatty acids, fish consumption, human health, and science-management links. Hierarchies of uncertainty (data, model, decision rule, and epistemic) and ambiguity (of values) are used to identify issues of scientific and policy contestation and opportunities for resolving them. The associated complexity of risks is illustrated by risk–benefit analyses of fish consumption and by evaluations of guideline values, highlighting value contents and policy factors in presumably scientific decision criteria, and arguments used in multi-dimensional risk and benefit comparisons. These comparisons pose challenges to narrow assessments centered, for e.g., on toxicants or on food benefits, and to more many-sided and balanced risk communication and management. It is shown that structured and contextualized treatment of uncertainties and ambiguities in a reflexive approach can inform balances between wide and narrow focus, detail and generality, and evidence and precaution.     

AMEG: the new SETAC advisory group on aquatic macrophyte ecotoxicology

Introduction and background

Primary producers play critical structural and functional roles in aquatic ecosystems; therefore, it is imperative that the potential risks of toxicants to aquatic plants are adequately assessed in the risk assessment of chemicals. The standard required macrophyte test species is the floating (non-sediment-rooted) duckweed Lemna spp. This macrophyte species might not be representative of all floating, rooted, emergent, and submerged macrophyte species because of differences in the duration and mode of exposure; sensitivity to the specific toxic mode of action of the chemical; and species-specific traits (e.g., duckweed's very short generation time).

Discussion and perspectives

These topics were addressed during the workshop entitled “Aquatic Macrophyte Risk Assessment for Pesticides” (AMRAP) where a risk assessment scheme for aquatic macrophytes was proposed. Four working groups evolved from this workshop and were charged with the task of developing Tier 1 and higher-tier aquatic macrophyte risk assessment procedures. Subsequently, a SETAC Advisory Group, the Macrophyte Ecotoxicology Group (AMEG) was formed as an umbrella organization for various macrophyte working groups. The purpose of AMEG is to provide scientifically based guidance in all aspects of aquatic macrophyte testing in the laboratory and field, including prospective as well as retrospective risk assessments for chemicals. As AMEG expands, it will begin to address new topics including bioremediation and sustainable management of aquatic macrophytes in the context of ecosystem services.     

Accumulation of cyanobacterial toxins in freshwater "seafood" and its consequences for public health: a review

This review summarizes and discusses the current understanding of human exposure to cyanobacterial toxins in "seafood" collected from freshwater and coastal areas. The review consists of three parts: (a) the existing literature on concentrations of cyanobacterial toxins in seafood is reviewed, and the likelihood of bioaccumulation discussed; (b) we derive cyanotoxin doses likely to occur through seafood consumption and propose guideline values for seafood and compare these to guidelines for drinking water; and (c) we discuss means to assess, control or mitigate the risks of exposure to cyanotoxins through seafood consumption. This is discussed in the context of two specific procedures, the food specific HACCP-approach and the water-specific Water Safety Plan approach by the WHO. Risks of exposure to cyanotoxins in food are sometimes underestimated. Risk assessments should acknowledge this and investigate the partitioning of exposure between drinking-water and food, which may vary depending on local circumstances.     

A Framework for Risk Characterization of Environmental Pollutants

Risk characterization is defined by both the U.S. National Academy of Sciences and the U.S. EPA as the estimation of human health risk due to harmful (i.e., toxic or carcinogenic) substances or organisms. Risk characterization studies are accomplished by integrating quantitative exposure estimates and dose-response relationships with the qualitative results of hazard identification.

A Risk Characterization Framework has been developed to encourage a systematic approach for analysis and presentation of risk estimates. This methodology subdivides the four common components of the risk assessment process into ten elements. Each of these elements is based on a term in a predictive risk equation. The equation allows independent computations of exposure, dose, lifetime individual risk, and risk to affected populations. All key assumptions in the predictive risk equation can be explicitly shown. This is important to understand the basis and inherent uncertainties of the risk estimation process.

The systematic treatment of each of the ten elements in this framework aids in the difficult job of comparing risk estimates by different researchers using different methodologies. The Risk Characterization Framework has been applied to various indoor and outdoor air pollutants of a carcinogenic nature. With further development, it also promises to be applicable to noncarcinogenic effects.     

Water resources development and impact assessment in the Mekong Basin: which way to go?

The Mekong River Basin is facing rapid changes, including intensive plans for water development. While the different development projects are considered to be important for economic development, the negative impacts that they are likely to cause for ecosystems and livelihoods are estimated to be remarkable. Yet, existing impact assessment processes seem in many cases to be inadequate to capture even the actual magnitude of the impacts at different levels. This article looks at the different impact assessment processes and their challenges in the basin. It is argued that impact assessment in this kind of dynamic and complex setting requires better coordination between assessments at different levels. Basinwide impact assessment would benefit from a more adaptive, multilevel approach that makes better use of assessments from local levels up to the regional level and builds on more participatory and interdisciplinary methods. Successful impact assessment also requires the recognition of the highly political nature of water development and related planning processes.     

Risk assessment approaches for ecosystem responses to transient pollution events in urban receiving waters

Alternative risk assessment approaches are reviewed for the evaluation of the ecological status and health of urban receiving waters subject to intermittent pollution events. Performance-based criteria founded on exceedance probabilities and related to the end-of-pipe discharge of chemical-specific substances comprise the conventional basis for setting regulatory standards in both North America and Europe. The difficulties and limitations of this approach, particularly in identifying realistic chronic, sub-lethal toxic risks arising from complex effluents are discussed. The potential role of Toxicity Based Criteria (TBC) for setting ecological consent limits for stormwater effluents is considered and the capabilities and limitations of Direct Toxicity Assessment (DTA) are identified. The inability of DTA procedures to satisfactorily evaluate chronic, sub-lethal risks has led to increasing interest in the potential use of in-situ biomarker techniques for the fingerprinting of stress-response properties as a means of diagnosing risk assessment for integrated urban runoff management.