Advancing the science of a read-across framework for evaluation of data-poor chemicals incorporating systematic and new approach methods.

The assessment of human health hazards posed by chemicals traditionally relies on toxicity studies in experimental animals. However, most chemicals currently in commerce do not meet the minimum data requirements for hazard identification and dose-response analysis in human health risk assessment. Previously, we introduced a read-across framework designed to address data gaps for screening-level assessment of chemicals with insufficient in vivo toxicity information (Wang et al., 2012). It relies on inference by analogy from suitably tested source analogues to a target chemical, based on structural, toxicokinetic, and toxicodynamic similarity. This approach has been used for dose-response assessment of data-poor chemicals relevant to the U.S. EPA's Superfund program. We present herein, case studies of the application of this framework, highlighting specific examples of the use of biological similarity for chemical grouping and quantitative read-across. Based on practical knowledge and technological advances in the fields of read-across and predictive toxicology, we propose a revised framework. It includes important considerations for problem formulation, systematic review, target chemical analysis, analogue identification, analogue evaluation, and incorporation of new approach methods. This work emphasizes the integration of systematic methods and alternative toxicity testing data and tools in chemical risk assessment to inform regulatory decision-making.

Clearly weighing the evidence in read-across can improve assessments of data-poor chemicals.

This paper provides a systematic weight-of-evidence method for read-across analyses of data-poor chemicals. The read-across technique extrapolates toxicity from analogous chemicals for which suitable test data are available to a target chemical. To determine that a candidate analogue is the 'best' and is sufficiently similar, the evidence for similarity of each candidate analogue to the target is weighed. We present a systematic weight of evidence method that provides transparency and imposes a consistent and rigorous inferential process. The method assembles relevant information concerning structure, physicochemical attributes, toxicokinetics, and toxicodynamics of the target and analogues. The information is then organized by evidence types and subtypes and weighted in terms of properties: relevance, strength, and reliability into weight levels, expressed as symbols. After evidence types are weighted, the bodies of evidence are weighted for collective properties: number, diversity, and coherence. Finally, the weights for the types and bodies of evidence are weighed for each analogue, and, if the overall weight of evidence is sufficient for one or more analogues, the analogue with the greatest weight is used to estimate the endpoint effect. We illustrate this WoE approach with a read-across analysis for screening the organochlorine contaminant, p,p'-dichlorodiphenyldichloroethane (DDD), for noncancer oral toxicity.

Adequacy of sample size for estimating a value from field observational data.

In 2011, the U.S. EPA Office of Research and Development released a field-based method for deriving aquatic life benchmarks for conductivity. Since its release, it has been verified, validated, and corroborated by the authors, reviewers, and independent researchers. However, the method and published results have been recently challenged as being artifacts of small sample sizes, prompting this re-evaluation. This paper supplements prior causal analyses by weighing evidence that specifically addresses the hypothesis that the benchmark is a statistical artifact. Four types of evidence are presented: (1) Permutation analyses show that the data sets are able to reliably estimate the extirpation of 5% of genera. (2) Analyses show that 25 occurrences of a genus are sufficient to estimate extirpation. (3) Coherent ecological explanations show that the claimed influence of sample size is actually a result of community ecology. (4) A review of relevant independent studies supports the benchmark. The permutation test is a useful test of the adequacy of field data sets. Furthermore, this weight-of-evidence approach and the individual types of evidence can be a model for analysis of other field-based benchmark values.

Assessing background levels of specific conductivity using weight of evidence.

There are many ways to estimate background levels, and many types of evidence may contribute to determining whether a water, air, or soil is at background. As a result, it is important to define background in each case and to weigh the available evidence to determine the best estimate of background. A weight-of-evidence approach is demonstrated that assesses whether the background SC is sufficiently similar in streams of Ecoregion 70 in West Virginia and Ohio. During planning, five relevant considerations were identified to assess background SC: physical properties, measured SC, spatial distribution of low SC sites, biological properties, and data relevance and reliability. For each consideration, diverse types of evidence were generated, evaluated, and synthesized using weight of evidence. In the example, evidence was weighed for the hypothesis that background SC is similar in two areas in Ecoregion 70, the Western Allegheny Plateau in the eastern United States. Where, as in this case, background is not well characterized by measurements, because data sets are small or sampling designs or anthropogenic inputs may influence estimates of background, it is suggested that information about regional properties, related to and affected by SC, may be used to determine whether SC in the less characterized area is sufficiently similar to a well characterized area.

Ecosystem services as assessment endpoints for ecological risk assessment.

Ecosystem services are defined as the outputs of ecological processes that contribute to human welfare or have the potential to do so in the future. Those outputs include food and drinking water, clean air and water, and pollinated crops. The need to protect the services provided by natural systems has been recognized previously, but ecosystem services have not been formally incorporated into ecological risk assessment practice in a general way in the United States. Endpoints used conventionally in ecological risk assessment, derived directly from the state of the ecosystem (e.g., biophysical structure and processes), and endpoints based on ecosystem services serve different purposes. Conventional endpoints are ecologically important and susceptible entities and attributes that are protected under US laws and regulations. Ecosystem service endpoints are a conceptual and analytical step beyond conventional endpoints and are intended to complement conventional endpoints by linking and extending endpoints to goods and services with more obvious benefit to humans. Conventional endpoints can be related to ecosystem services even when the latter are not considered explicitly during problem formulation. To advance the use of ecosystem service endpoints in ecological risk assessment, the US Environmental Protection Agency's Risk Assessment Forum has added generic endpoints based on ecosystem services (ES-GEAE) to the original 2003 set of generic ecological assessment endpoints (GEAEs). Like conventional GEAEs, ES-GEAEs are defined by an entity and an attribute. Also like conventional GEAEs, ES-GEAEs are broadly described and will need to be made specific when applied to individual assessments. Adoption of ecosystem services as a type of assessment endpoint is intended to improve the value of risk assessment to environmental decision making, linking ecological risk to human well-being, and providing an improved means of communicating those risks. Integr Environ Assess Manag 2016;12:522-528. Published 2015 SETAC. This article is a US Government work and, as such, is in the public domain in the USA.

An integrated framework for health and ecological risk assessment.

The World Health Organization's (WHO's) International Program for Chemical Safety has developed a framework for performing risk assessments that integrate the assessment of risks to human health and risks to nonhuman organisms and ecosystems. The WHO's framework recognizes that stakeholders and risk managers have their own processes that are parallel to the scientific process of risk assessment and may interact with the risk assessment at various points, depending on the context. Integration of health and ecology provides consistent expressions of assessment results, incorporates the interdependence of humans and the environment, uses sentinel organisms, and improves the efficiency and quality of assessments relative to independent human health and ecological risk assessments. The advantage of the framework to toxicologists lies in the opportunity to use understanding of toxicokinetics and toxicodynamics to inform the integrated assessment of all exposed species.

Why care about aquatic insects: uses, benefits, and services.

Aquatic insects are common subjects of ecological research and environmental monitoring and assessment. However, their important role in protecting and restoring aquatic ecosystems is often challenged because their benefits and services to humans are not obvious to decision makers or the public. Insects are food for fish, amphibians, and wildlife. They are important contributors to energy and nutrient processing, including capturing nutrients and returning them to terrestrial ecosystems and purifying water. They provide recreation to fishermen and nature lovers and are cultural symbols. Monetary benefits to fishermen can be quantified, but most other benefits have been described qualitatively. Integr Environ Assess Manag 2015;11:188-194.

Bottom-up and top-down integration of human and ecological risk assessment.

The World Health Organization has published a framework for integrating human health and ecological risk assessments, and many others have argued for greater integration of health and environmental concerns in assessments. However, those who argue for integration do not agree on the expected benefits. This article provides a conceptual organization of the rationale for integration. The bottom-up line of argument begins with the premise that the mechanisms of transport, fate, exposure, and effects of chemicals on humans and nonhuman organisms are largely common. Therefore, integrated assessment should be more efficient and should employ the highest quality of science. The top-down line of argument begins with the premise that humans are organisms that reside in ecosystems. Therefore, changes in the environment imply changes in human health and welfare. These include changes in the many services of nature that contribute to human health, such as air and water purification, sentinel functions, and provision of recreation and food supplies. They also include the direct health benefits that have been associated with exposure of humans to plants, animals, and natural ecosystems. Integration should proceed from both the top and bottom.

A methodology for inferring the causes of observed impairments in aquatic ecosystems.

Biological surveys have become a common technique for determining whether aquatic communities have been injured. However, their results are not useful for identifying management options until the causes of apparent injuries have been identified. Techniques for determining causation have been largely informal and ad hoc. This paper presents a logical system for causal inference. It begins by analyzing the available information to generate causal evidence; available information may include spatial or temporal associations of potential cause and effect, field or laboratory experimental results, and diagnostic evidence from the affected organisms. It then uses a series of three alternative methods to infer the cause: Elimination of causes, diagnostic protocols, and analysis of the strength of evidence. If the cause cannot be identified with sufficient confidence, the reality of the effects is examined, and if the effects are determined to be real, more information is obtained to reiterate the process.

Determining the causes of impairments in the Little Scioto River, Ohio, USA: part 2. Characterization of causes.

Two stream reaches in the Little Scioto River (OH, USA) were characterized for the causes of impairments measured at two locations. By inductive inference, six candidate causes were winnowed down to three and five candidate causes for each of the two stream reaches. Using a formal strength-of-evidence process, a single cause was determined. At the most upstream location, habitat alterations, including fine-textured substrates and low DO, were characterized as the probable causes for an increased percentage of anomalies of fish, a decreased percentage of mayflies, and an increased percentage of tolerant macroinvertebrates. An increase in the relative weight of fish was attributed to an artificially narrow, deepened channel. Approximately 2 km downstream, polycyclic aromatic hydrocarbon (PAH)-contaminated sediments were identified as the cause for both fish and macroinvertebrate impairments. Causal characterization using first elimination and then a strength-of-evidence approach narrowed and defined the causes of ecological impairment even in this situation, where many complex and interacting candidate causes existed. Applying a formal method highlighted types of data and associations that can strengthen and present a more convincing determination of the causes of impairment.

Determining probable causes of ecological impairment in the Little Scioto River, Ohio, USA: part 1. Listing candidate causes and analyzing evidence.

The Little Scioto River in north-central Ohio, USA, is considered to be biologically impaired based on the results of fish and invertebrate surveys. The causes for these impairments were evaluated by means of a formal method. Two of the impairments identified on the stream reach were characterized in detail to support the causal assessment. A list of six candidate causes was developed that included habitat alteration, polycyclic aromatic hydrocarbon contamination, metals contamination, low dissolved oxygen, ammonia toxicity, and nutrient enrichment. Evidence for the causal evaluation was developed with data from the site that associated each candidate cause with the biological responses. Evidence was also developed that drew on data from other locations and laboratory studies, including comparisons of site exposures with screening values and criteria. The formal method increased the transparency of the assessment; candidate causes were clearly listed and the pathways by which they may have produced effects were shown. Analysis of the evidence maximized the utility of available data, which were collected as part of monitoring and research programs rather than to specifically support a causal assessment. This case study illustrates how the stressor identification method can be used to draw conclusions from available data about the most likely causes of impairment and to show what additional studies would be useful.

Water quality guidelines for chemicals: learning lessons to deliver meaningful environmental metrics.

Many jurisdictions around the globe have well-developed regulatory frameworks for the derivation and implementation of water quality guidelines (WQGs) or their equivalent (e.g. environmental quality standards, criteria, objectives or limits). However, a great many more still do not have such frameworks and are looking to introduce practical methods to manage chemical exposures in aquatic ecosystems. There is a potential opportunity for learning and sharing of data and information between experts from different jurisdictions in order to deliver efficient and effective methods to manage potential aquatic risks, including the considerable reduction in the need for aquatic toxicity testing and the rapid identification of common challenges. This paper reports the outputs of an international workshop with representatives from 14 countries held in Hong Kong in December 2011. The aim of the workshop and this paper was to identify 'good practice' in the development of WQGs to deliver to a range of environmental management goals. However, it is important to broaden this consideration to cover often overlooked facets of implementable WQGs, such as demonstrable field validation (i.e. does the WQG protect what it is supposed to?), fit for purpose of monitoring frameworks (often an on-going cost) and finally how are these monitoring data used to support management decisions in a manner that is transparent and understandable to stakeholders. It is clear that regulators and the regulated community have numerous pressures and constraints on their resources. Therefore, the final section of this paper addresses potential areas of collaboration and harmonisation. Such approaches could deliver a consistent foundation from which to assess potential chemical aquatic risks, including, for example, the adoption of bioavailability-based approaches for metals, whilst reducing administrative and technical burdens in jurisdictions.

Pragmatism: a practical philosophy for environmental scientists.

Challenges to the credibility of the scientific community make it particularly important for environmental scientists to understand the bases for the authority of their science. We argue that pragmatism provides a defensible and effective scientific philosophy. It provides a transparent basis for justifying belief and a set of practices and concepts for inference. It makes the scientific community the author of scientific truth, which has implications for the opening of science in the age of social media and the communication of consensus positions on important issues. We describe how pragmatism acknowledges the social aspect of science without losing the scientific tradition of critical thinking.

A method for deriving water-quality benchmarks using field data.

The authors describe a methodology that characterizes effects to individual genera observed in the field and estimate the concentration at which 5% of genera are adversely affected. Ionic strength, measured as specific conductance, is used to illustrate the methodology. Assuming some resilience in the population, 95% of the genera are afforded protection. The authors selected an unambiguous effect, the presence or absence of a genus from sampling locations. The absence of a genus, extirpation, is operationally defined as the point above which only 5% of the observations of a genus occurs. The concentrations that cause extirpation of each genus are rank-ordered from least to greatest, and the benchmark is estimated at the 5th percentile of the distribution using two-point interpolation. When a full range of exposures and many taxa are included in the model of taxonomic sensitivity, the model broadly characterizes how species in general respond to a concentration gradient of the causal agent. This recognized U.S. Environmental Protection Agency methodology has many advantages. Observations from field studies include the full range of conditions, effects, species, and interactions that occur in the environment and can be used to model some causal relationships that laboratory studies cannot.

A method for assessing the potential for confounding applied to ionic strength in central Appalachian streams.

Causal relationships derived from field data are potentially confounded by variables that are correlated with both the cause and its effect. The present study presents a method for assessing the potential for confounding and applies it to the relationship between ionic strength and impairment of benthic invertebrate assemblages in central Appalachian streams. The method weighs all available evidence for and against confounding by each potential confounder. It identifies 10 types of evidence for confounding, presents a qualitative scoring system, and provides rules for applying the scores. Twelve potential confounders were evaluated: habitat, organic enrichment, nutrients, deposited sediments, pH, selenium, temperature, lack of headwaters, catchment area, settling ponds, dissolved oxygen, and metals. One potential confounder, low pH, was found to be biologically significant and eliminated by removing sites with pH < 6. Other potential confounders were eliminated based on the weight of evidence. This method was found to be useful and defensible. It could be applied to other environmental assessments that use field data to develop causal relationships, including contaminated site remediation or management of natural resources.

A method for assessing causation of field exposure-response relationships.

Because associations between agents and environmental effects are not necessarily causal, it is necessary to assess causation before using such relationships in environmental management. The authors adapted epidemiological methods to assess general causal hypotheses. General causation establishes that an agent is capable of causing an effect. The method uses all relevant and good-quality evidence in a weight-of-evidence system. The system is credible due to its explicit a priori criteria. The evidence is organized in terms of six characteristics of causation: co-occurrence, preceding causation, interaction, alteration, sufficiency, and time order. The causal assessment proceeds through six steps that generate, organize, and score evidence to determine whether causation is adequately supported by the body of evidence.

Derivation of a benchmark for freshwater ionic strength.

Because increased ionic strength has caused deleterious ecological changes in freshwater streams, thresholds for effects are needed to inform resource-management decisions. In particular, effluents from surface coal mining raise the ionic strength of receiving streams. The authors developed an aquatic life benchmark for specific conductance as a measure of ionic strength that is expected to prevent the local extirpation of 95% of species from neutral to alkaline waters containing a mixture of dissolved ions in which the mass of SO (4)2- + HCO (3)- ≥ Cl(-). Extirpation concentrations of specific conductance were estimated from the presence and absence of benthic invertebrate genera from 2,210 stream samples in West Virginia. The extirpation concentration is the 95th percentile of the distribution of the probability of occurrence of a genus with respect to specific conductance. In a region with a background of 116 µS/cm, the 5th percentile of the species sensitivity distribution of extirpation concentrations for 163 genera is 300 µS/cm. Because the benchmark is not protective of all genera and protects against extirpation rather than reduction in abundance, this level may not fully protect sensitive species or higher-quality, exceptional waters.