Ecological risk assessors face increasing demands to assess more chemicals, with greater speed and accuracy, and to do so using fewer resources and experimental animals. New approaches in biological and computational sciences may be able to generate mechanistic information that could help in meeting these challenges. However, to use mechanistic data to support chemical assessments, there is a need for effective translation of this information into endpoints meaningful to ecological risk-effects on survival, development, and reproduction in individual organisms and, by extension, impacts on populations. Here we discuss a framework designed for this purpose, the adverse outcome pathway (AOP). An AOP is a conceptual construct that portrays existing knowledge concerning the linkage between a direct molecular initiating event and an adverse outcome at a biological level of organization relevant to risk assessment. The practical utility of AOPs for ecological risk assessment of chemicals is illustrated using five case examples. The examples demonstrate how the AOP concept can focus toxicity testing in terms of species and endpoint selection, enhance across-chemical extrapolation, and support prediction of mixture effects. The examples also show how AOPs facilitate use of molecular or biochemical endpoints (sometimes referred to as biomarkers) for forecasting chemical impacts on individuals and populations. In the concluding sections of the paper, we discuss how AOPs can help to guide research that supports chemical risk assessments and advocate for the incorporation of this approach into a broader systems biology framework.

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Abstract-Toxicity of fresh waters with high total dissolved solids has been shown to be dependent on the specific ionic composition of the water. To provide a predictive tool to assess toxicity attributable to major ions, we tested the toxicity of over 2,900 ion solutions using the daphnids, Ceriodaphnia dubia and Daphnia magna, and fathead minnows (Pimephales promelas). Multiple logistic regression was used to relate ion composition to survival for each of the three test species. In general, relative ion toxicity was K ϩ Ͼ ഠ Mg 2ϩ Ͼ Cl Ϫ Ͼ ; Na ϩ and Ca 2ϩ were not significant variables in the regressions, suggesting that the toxicityof Na ϩ and Ca 2ϩ salts was primarily attributable to the corresponding anion. For C. dubia and D. magna, toxicity of Cl Ϫ , , 2 Ϫ SO 4 and K ϩ was reduced in solutions enriched with more than one cation. Final regression models showed a good quality of fit to the data (R 2 ϭ 0.767-0.861). Preliminary applications of these models to field-collected samples indicated a high degree of accuracy for the C. dubia model, while the D. magna and fathead minnow models tended to overpredict ion toxicity.

The ions Na , K , Ca , Mg , Cl , SO , and HCO /CO (referred to in the present study as "major ions") are present in all freshwaters and physiologically required by aquatic organisms but can increase to harmful levels from a variety of anthropogenic activities. It is also known that the toxicities of major ion salts can vary depending on the concentrations of other ions, and understanding these relationships is key to establishing appropriate environmental limits. The authors present a series of experiments with Ceriodaphnia dubia to evaluate the acute toxicity of 12 major ion salts and to determine how toxicity of these salts varies as a function of background water chemistry. All salts except CaSO and CaCO were acutely toxic below saturation, with the lowest median lethal concentrations found for K salts. All 10 salts that showed toxicity also showed some degree of reduced toxicity as the ionic content of the background water increased. Experiments that independently varied Ca:Mg ratio, Na:K ratio, Cl:SO ratio, and alkalinity/pH demonstrated that Ca concentration was the primary factor influencing the toxicities of Na and Mg salts, whereas the toxicities of K salts were primarily influenced by the concentration of Na. These experiments also indicated multiple mechanisms of toxicity and suggested important aspects of dosimetry; the toxicities of K, Mg, and Ca salts were best related to the chemical activity of the cation, whereas the toxicities of Na salts also reflected an influence of the anions and were well correlated with osmolarity. Understanding these relationships between major ion toxicity and background water chemistry should aid in the development of sensible risk-assessments and regulatory standards. Environ Toxicol Chem 2016;35:3039-3057. Published 2016 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.

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Bioaccumulation test procedures using the oligochaete Lumbriculus variegatus have been developed as a means of evaluating the accumulation of chemicals from freshwater sediments. To avoid including chemicals associated with gut contents as part of the measured tissue residue, a 24‐h period of purging in clean water after the uptake phase of the test has been recommended. While purging acts to reduce bias from gut contents, it also has the potential to introduce bias caused by depuration of chemicals from tissues. In this paper, a series of model calculations are used to assess the expected sensitivity of measured residues of nonionic organic chemicals to the presence of sediment in the gut and to varying lengths of purging. If organisms are not purged, the predicted influence of gut contents on measured residue is not large (generally <20%) when a biota‐sediment accumulation factor (BSAF) of one is assumed. However, if BSAFs substantially less than one apply, projected errors increase to 30‐fold or more. To derive a better estimate of the time required for L. variegatus to clear the gut of sediment, a sediment purging experiment was conducted; results indicate that >98% of sediment had cleared the gut in 6 h (half‐life = 0.98 h). Based on these results and model analyses, a much shorter purging period of 6 h, rather than 24 h, is suggested as a reasonable guideline for many test applications.

Many human activities increase concentrations of major geochemical ions (Na , K , Ca , Mg , Cl , SO , and HCO /CO ) in freshwater systems, and can thereby adversely affect aquatic life. Such effects involve several toxicants, multiple toxicity mechanisms, various ion interactions, and widely varying ion compositions across different water bodies. Previous studies of individual salt toxicities have defined some useful relationships; however, adding single salts to waters results in atypical compositions and does not fully address mixture toxicity. To better understand mechanisms and interactions for major ion toxicity, 29 binary mixture experiments, each consisting of 7 to 8 toxicity tests, were conducted on the acute toxicity of major ion salts and mannitol to Ceriodaphnia dubia. These tests showed multiple mechanisms of toxicity, including: 1) nonspecific ion toxicity, correlated with osmolarity and to which all ions contribute; and 2) cation-dependent toxicities for potassium (K), magnesium (Mg), and calcium (Ca) best related to their chemical activities. These mechanisms primarily operate independently, except for additive toxicity of Mg-dependent and Ca-dependent toxicities. These mixture studies confirmed ameliorative effects of Ca on sodium (Na) and Mg salt toxicities and of Na on K salt toxicity, and further indicated lesser ameliorative effects of Ca on K salt toxicity and Mg on Na salt toxicity. These results provide a stronger basis for assessing risks from the complex mixtures of ions found in surface waters. Environ Toxicol Chem 2017;36:1525-1537. Published 2016 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.

Abstract-Globally, estimated costs to manage (i.e., remediate and monitor) contaminated sediments are in the billions of U.S. dollars. Biologically based approaches for assessing the contaminated sediments which pose the greatest ecological risk range from toxicity testing to benthic community analysis. In addition, chemically based sediment quality guidelines (SQGs) provide a relatively inexpensive line of evidence for supporting these assessments. The present study summarizes a mechanistic SQG based on equilibrium partitioning (EqP), which uses the dissolved concentrations of contaminants in sediment interstitial waters as a surrogate for bioavailable contaminant concentrations. The EqP-based mechanistic SQGs are called equilibrium partitioning sediment benchmarks (ESBs). Sediment concentrations less than or equal to the ESB values are not expected to result in adverse effects and benthic organisms should be protected, while sediment concentrations above the ESB values may result in adverse effects to benthic organisms. In the present study, ESB values are reported for 34 polycyclic aromatic hydrocarbon, 32 other organic contaminants, and seven metals (cadmium, chromium, copper, nickel, lead, silver, zinc). Also included is an overview of EqP theory, ESB derivation, examples of applying ESB values, and considerations when using ESBs. The ESBs are intended as a complement to existing sediment-assessment tools, to assist in determining the extent of sediment contamination, to help identify chemicals causing toxicity, and to serve as targets for pollutant loading control measures. Environ. Toxicol. Chem. 2013;32:102-114. # 2012 SETAC