Recommended updates to the USEPA Framework for Metals Risk Assessment: Aquatic ecosystems.

In 2007, the USEPA issued its "Framework for Metals Risk Assessment." The framework provides technical guidance to risk assessors and regulators when performing human health and environmental risk assessments of metals. This article focuses on advances in the science including assessing bioavailability in aquatic ecosystems, short- and long-term fate of metals in aquatic ecosystems, and advances in risk assessment of metals in sediments. Notable advances have occurred in the development of bioavailability models for assessing toxicity as a function of water chemistry in freshwater ecosystems. The biotic ligand model (BLM), the multiple linear regression model, and multimetal BLM now exist for most of the common mono- and divalent metals. Species sensitivity distributions for many metals exist, making it possible for many jurisdictions to develop or update their water quality criteria or guidelines. The understanding of the fate of metals in the environment has undergone significant scrutiny over the past 20 years. Transport and toxicity models have evolved including the Unit World Model allowing for estimation of concentrations of metals in various compartments as a function of loading and time. There has been significant focus on the transformation of metals in sediments into forms that are less bioavailable and on understanding conditions that result in resolubilization or redistribution of metals in and from sediments. Methods for spiking sediments have advanced such that the resulting chemistry in the laboratory mimics that in natural systems. Sediment bioavailability models are emerging including models that allow for prediction of toxicity in sediments for copper and nickel. Biodynamic models have been developed for several organisms and many metals. The models allow for estimates of transport of metals from sediments to organisms via their diet as well as their water exposure. All these advances expand the tool set available to risk assessors. Integr Environ Assess Manag 2023;00:1-28. © 2023 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Environmental risk of nickel in aquatic Arctic ecosystems.

The Arctic faces many environmental challenges, including the continued exploitation of its mineral resources such as nickel (Ni). The responsible development of Ni mining in the Arctic requires establishing a risk assessment framework that accounts for the specificities of this unique region. We set out to conduct preliminary assessments of Ni exposure and effects in aquatic Arctic ecosystems. Our analysis of Ni source and transport processes in the Arctic suggests that fresh, estuarine, coastal, and marine waters are potential Ni-receiving environments, with both pelagic and benthic communities being at risk of exposure. Environmental concentrations of Ni show that sites with elevated Ni concentrations are located near Ni mining operations in freshwater environments, but there is a lack of data for coastal and estuarine environments near such operations. Nickel bioavailability in Arctic freshwaters seems to be mainly driven by dissolved organic carbon (DOC) concentrations with bioavailability being the highest in the High Arctic, where DOC levels are the lowest. However, this assessment is based on bioavailability models developed from non-Arctic species. At present, the lack of chronic Ni toxicity data on Arctic species constitutes the greatest hurdle toward the development of Ni quality standards in this region. Although there are some indications that polar organisms may not be more sensitive to contaminants than non-Arctic species, biological adaptations necessary for life in polar environments may have led to differences in species sensitivities, and this must be addressed in risk assessment frameworks. Finally, Ni polar risk assessment is further complicated by climate change, which affects the Arctic at a faster rate than the rest of the world. Herein we discuss the source, fate, and toxicity of Ni in Arctic aquatic environments, and discuss how climate change effects (e.g., permafrost thawing, increased precipitation, and warming) will influence risk assessments of Ni in the Arctic.

Development of a bioavailability-based risk assessment framework for nickel in Southeast Asia and Melanesia.

Nickel laterite ore deposits are becoming increasingly important sources of Ni for the global marketplace and are found mainly in tropical and subtropical regions, including Indonesia, the Philippines, Papua New Guinea, Cuba, and New Caledonia. There are few legislatively derived standards or guidelines for the protection of aquatic life for Ni in many of these tropical regions, and bioavailability-based environmental risk assessment (ERA) approaches for metals have mainly been developed and tested in temperate regions, such as the United States and Europe. This paper reports on a multi-institutional, 5-y testing program to evaluate Ni exposure, effects, and risk characterization in the Southeast Asia and Melanesia (SEAM) region, which includes New Caledonia, Papua New Guinea, the Philippines, and Indonesia. Further, we have developed an approach to determine if the individual components of classical ERA, including effects assessments, exposure assessments, and risk characterization methodologies (which include bioavailability normalization), are applicable in this region. A main conclusion of this research program is that although ecosystems and exposures may be different in tropical systems, ERA paradigms are constant. A large chronic ecotoxicity data set for Ni is now available for tropical species, and the data developed suggest that tropical ecosystems are not uniquely sensitive to Ni exposure; hence, scientific support exists for combining tropical and temperate data sets to develop tropical environmental quality standards (EQSs). The generic tropical database and tropical exposure scenarios generated can be used as a starting point to examine the unique biotic and abiotic characteristics of specific tropical ecosystems in the SEAM region. Integr Environ Assess Manag 2021;17:802-813. © 2021 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Acute and chronic toxicity of nickel on freshwater and marine tropical aquatic organisms.

Water quality guidelines and ecological risk assessment of chemical substances like nickel (Ni) in tropical regions such as South East Asia and Melanesia are often based on temperate information as a result of fewer Ni ecotoxicity data available for tropical species. This leaves an unknown margin of uncertainty in the risk assessment in the tropics. In order to fill this data gap, this study was designed to conduct standard toxicity tests on Ni with two freshwater species (acute tests) and three marine species (acute and chronic tests) originated from tropical Hong Kong. All tests were carried out using measured concentrations of Ni with control mortality below 15%. The median lethal concentrations (LC50s) were determined as 2520 (95% confidence interval: 2210, 2860) and 426 (351, 515) µg Ni L-1 for the freshwater gastropods Pomacea lineata (48 h) and Sulcospira hainanensis (96 h), respectively, while 96 h LC50s of 4300 (3610, 5090), 18,200 (6470, 51,200), 62,400 (56,800, 68,500), and 71,700 (68,200, 75,400) µg Ni L-1 were derived for the marine copepod Tigriopus japonicus, the gastropod Monodonta labio, juvenile and adult of the marine fish Oryzias melastigma, respectively. The chronic effect concentration of 10% (EC10) based on the intrinsic rate of increase of the population of T. japonicus was 29 (12, 69) µg Ni L-1. In terms of growth inhibition, the chronic EC10 for M. labio was 34 (17, 67) µg Ni L-1. The results also indicated that T. japonicus in maturation stage (LC10: 484 (349, 919) µg Ni L-1) was less sensitive than its nauplii stage (LC10: 44 (27, 72) µg Ni L-1). This study represents an important addition of high-quality toxicity data to the tropical Ni toxicity database which can be used for future ecological risk assessment of Ni and derivation of its water quality guidelines in tropical regions.

Deriving a Chronic Guideline Value for Nickel in Tropical and Temperate Marine Waters.

The absence of chronic toxicity data for tropical marine waters has limited our ability to derive appropriate water quality guideline values for metals in tropical regions. To aid environmental management, temperate data are usually extrapolated to other climatic (e.g., tropical) regions. However, differences in climate, water chemistry, and endemic biota between temperate and tropical systems make such extrapolations uncertain. Chronic nickel (Ni) toxicity data were compiled for temperate (24 species) and tropical (16 species) marine biota and their sensitivities to Ni compared. Concentrations to cause a 10% effect for temperate biota ranged from 2.9 to 20 300 µg Ni/L, with sea urchin larval development being the most sensitive endpoint. Values for tropical data ranged from 5.5 to 3700 µg Ni/L, with copepod early-life stage development being the most sensitive test. There was little difference in temperate and tropical marine sensitivities to Ni, with 5% hazardous concentrations (95% confidence interval) of 4.4 (1.8-17), 9.6 (1.7-26), and 5.8 (2.8-15) µg Ni/L for temperate, tropical, and combined temperate and tropical species, respectively. To ensure greater taxonomic coverage and based on guidance provided in Australia and New Zealand, it is recommended that the combined data set be used as the basis to generate a jurisdiction-specific water quality guideline of 6 µg Ni/L for 95% species protection applicable to both temperate and tropical marine environments. Environ Toxicol Chem 2020;39:2540-2551. © 2020 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Toxicity of Nanoparticulate Nickel to Aquatic Organisms: Review and Recommendations for Improvement of Toxicity Tests.

We reviewed the literature on toxicity of nanoparticulate nickel (nano-Ni) to aquatic organisms, from the perspective of relevance and reliability in a regulatory framework. Our main findings were 1) much of the published nano-Ni toxicity data is of low or medium quality in terms of reporting key physical-chemical properties, methodologies, and results, compared with published dissolved nickel studies; and 2) based on the available information, some common findings about nanoparticle (NP) toxicity are not supported for nano-Ni. First, we concluded that nanoparticulate elemental nickel and nickel oxide, which differ in chemical composition, generally did not differ in their toxicity. Second, there is no evidence that the toxicity of nano-Ni increases as the size of the NPs decreases. Third, for most organisms tested, nano-Ni was not more toxic on a mass-concentration basis than dissolved Ni. Fourth, there is conflicting evidence about whether the toxicity is directly caused by the NPs or by the dissolved fraction released from the NPs. However, no evidence suggests that any of the molecular, physiological, and structural mechanisms of nano-Ni toxicity differ from the general pattern for many metal-based nanomaterials, wherein oxidative stress underlies the observed effects. Physical-chemical factors in the design and conduct of nano-Ni toxicity tests are important, but often they are not adequately reported (e.g., characteristics of dry nano-Ni particles and of wetted particles in exposure waters; exposure-water chemistry). Environ Toxicol Chem 2020;39:1861-1883 © 2020 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

A Mystery Tale: Nickel Is Fickle When Snails Fail-Investigating the Variability in Ni Toxicity to the Great Pond Snail.

Dissolved Ni concentrations inhibiting the growth of juvenile great pond snails (Lymnaea stagnalis) have been documented to vary from about 1 to 200 µg L-1 Ni. This variability makes L. stagnalis either a moderately sensitive or the most sensitive freshwater species to chronic Ni exposure tested to date. Given the role of sensitive species in environmental risk assessment frameworks, it is particularly important to understand this variability, i.e., to characterize the factors that modulate Ni toxicity and that may confound toxicity test outcomes when uncontrolled. In the present study, we tested if this variability was due to analytical (growth calculation: biomass versus growth rate), environmental (water quality), lab-specific practices, and/or snail population differences among earlier studies. Specifically, we reanalyzed previously published Ni toxicity data and conducted additional measurements of Ni aqueous speciation, short-term Ni uptake, and chronic Ni toxicity with test waters and snail cultures used in previous studies. Corrections for Ni bioavailability and growth calculations explained a large degree of variability in the published literature. However, a residual 16-fold difference remained puzzling between 2 studies: Niyogi et al. (2014) (low ECxs) and Crémazy et al. (2018) (high ECxs). Indeed, differences in metal bioavailability due to water chemistry, lab-specific practices, and snail population sensitivity could not explain the large variation in Ni toxicity in these 2 very similar studies. Other potentially important toxicity-modifying factors were not directly evaluated in the present work: test duration, diet, snail holding conditions, and snail age at onset of testing. The present analysis highlights the need for further studies to elucidate 1) the mechanisms of growth inhibition in Ni-exposed L. stagnalis and 2) the important abiotic and biotic factors affecting this biological response. Until these processes are understood, substantial uncertainties will remain about inclusion of this species in Ni environmental risk assessment. Integr Environ Assess Manag 2020;16:983-997. © 2020 SETAC.

Validation of Bioavailability-Based Toxicity Models for Metals.

Regulatory jurisdictions worldwide are increasingly incorporating bioavailability-based toxicity models into development of protective values (PVALs) for freshwater and saltwater aquatic life (e.g., water quality criteria, standards, and/or guidelines) for metals. Use of such models for regulatory purposes should be contingent on their ability to meet performance criteria as specified through a model-validation process. Model validation generally involves an assessment of a model's appropriateness, relevance, and accuracy. We review existing guidance for validation of bioavailability-based toxicity models, recommend questions that should be addressed in model-validation studies, discuss model study type and design considerations, present several new ways to evaluate model performance in validation studies, and suggest a framework for use of model validation in PVAL development. We conclude that model validation should be rigorous but flexible enough to fit the user's purpose. Although a model can never be fully validated to a level of zero uncertainty, it can be sufficiently validated to fit a specific purpose. Therefore, support (or lack of support) for a model should be presented in such a way that users can choose their own level of acceptability. We recommend that models be validated using experimental designs and endpoints consistent with the data sets that were used to parameterize and calibrate the model and validated across a broad range of geographically and ecologically relevant water types. Environ Toxicol Chem 2019;39:101-117. © 2019 SETAC.

Toxicity of nickel to tropical freshwater and sediment biota: A critical literature review and gap analysis.

More than two-thirds of the world's nickel (Ni) lateritic deposits are in tropical regions, and just less than half are within South East Asia and Melanesia (SEAM). With increasing Ni mining and processing in SEAM, environmental risk assessment tools are required to ensure sustainable development. Currently, there are no tropical-specific water or sediment quality guideline values for Ni, and the appropriateness of applying guideline values derived for temperate systems (e.g., Europe) to tropical ecosystems is unknown. Databases of Ni toxicity and toxicity tests for tropical freshwater and sediment species were compiled. Nickel toxicity data were ranked, using a quality assessment, identifying data to potentially use to derive tropical-specific Ni guideline values. There were no data for Ni toxicity in tropical freshwater sediments. For tropical freshwaters, of 163 Ni toxicity values for 40 different species, high-quality chronic data, based on measured Ni concentrations, were found for just 4 species (1 microalga, 2 macrophytes, and 1 cnidarian), all of which were relevant to SEAM. These data were insufficient to calculate tropical-specific guideline values for long-term aquatic ecosystem protection in tropical regions. For derivation of high-reliability tropical- or SEAM-specific water and sediment quality guideline values, additional research effort is required. Using gap analysis, we recommend how research gaps could be filled. Environ Toxicol Chem 2018;37:293-317. © 2017 SETAC.

The mechanisms of nickel toxicity in aquatic environments: An adverse outcome pathway analysis.

Current ecological risk assessment and water quality regulations for nickel (Ni) use mechanistically based, predictive tools such as biotic ligand models (BLMs). However, despite many detailed studies, the precise mechanism(s) of Ni toxicity to aquatic organisms remains elusive. This uncertainty in the mechanism(s) of action for Ni has led to concern over the use of tools like the BLM in some regulatory settings. To address this knowledge gap, the authors used an adverse outcome pathway (AOP) analysis, the first AOP for a metal, to identify multiple potential mechanisms of Ni toxicity and their interactions with freshwater aquatic organisms. The analysis considered potential mechanisms of action based on data from a wide range of organisms in aquatic and terrestrial environments on the premise that molecular initiating events for an essential metal would potentially be conserved across taxa. Through this analysis the authors identified 5 potential molecular initiating events by which Ni may exert toxicity on aquatic organisms: disruption of Ca2+ homeostasis, disruption of Mg2+ homeostasis, disruption of Fe2+/3+ homeostasis, reactive oxygen species-induced oxidative damage, and an allergic-type response of respiratory epithelia. At the organ level of biological organization, these 5 potential molecular initiating events collapse into 3 potential pathways: reduced Ca2+ availability to support formation of exoskeleton, shell, and bone for growth; impaired respiration; and cytotoxicity and tumor formation. At the level of the whole organism, the organ-level responses contribute to potential reductions in growth and reproduction and/or alterations in energy metabolism, with several potential feedback loops between each of the pathways. Overall, the present AOP analysis provides a robust framework for future directed studies on the mechanisms of Ni toxicity and for developing AOPs for other metals. Environ Toxicol Chem 2017;36:1128-1137. © 2016 SETAC.

A review of nickel toxicity to marine and estuarine tropical biota with particular reference to the South East Asian and Melanesian region.

The South East Asian Melanesian (SEAM) region contains the world's largest deposits of nickel lateritic ores. Environmental impacts may occur if mining operations are not adequately managed. Effects data for tropical ecosystems are required to assess risks of contaminant exposure and to derive water quality guidelines (WQG) to manage these risks. Currently, risk assessment tools and WQGs for the tropics are limited due to the sparse research on how contaminants impact tropical biota. As part of a larger project to develop appropriate risk assessment tools to ensure sustainable nickel production in SEAM, nickel effects data were required. The aim of this review was to compile data on the effects of nickel on tropical marine, estuarine, pelagic and benthic species, with a particular focus on SEAM. There were limited high quality chronic nickel toxicity data for tropical marine species, and even fewer for those relevant to SEAM. Of the data available, the most sensitive SEAM species to nickel were a sea urchin, copepod and anemone. There is a significant lack of high quality chronic data for several ecologically important taxonomic groups including cnidarians, molluscs, crustaceans, echinoderms, macroalgae and fish. No high quality chronic nickel toxicity data were available for estuarine waters or marine and estuarine sediments. The very sparse toxicity data for tropical species limits our ability to conduct robust ecological risk assessment and may require additional data generation or read-across from similar species in other databases (e.g. temperate) to fill data gaps. Recommendations on testing priorities to fill these data gaps are presented.

Development of a bioavailability-based risk assessment approach for nickel in freshwater sediments.

To assess nickel (Ni) toxicity and behavior in freshwater sediments, a large-scale laboratory and field sediment testing program was conducted. The program used an integrative testing strategy to generate scientifically based threshold values for Ni in sediments and to develop integrated equilibrium partitioning-based bioavailability models for assessing risks of Ni to benthic ecosystems. The sediment testing program was a multi-institutional collaboration that involved extensive laboratory testing, field validation of laboratory findings, characterization of Ni behavior in natural and laboratory conditions, and examination of solid phase Ni speciation in sediments. The laboratory testing initiative was conducted in 3 phases to satisfy the following objectives: 1) evaluate various methods for spiking sediments with Ni to optimize the relevance of sediment Ni exposures; 2) generate reliable ecotoxicity data by conducting standardized chronic ecotoxicity tests using 9 benthic species in sediments with low and high Ni binding capacity; and, 3) examine sediment bioavailability relationships by conducting chronic ecotoxicity testing in sediments that showed broad ranges of acid volatile sulfides, organic C, and Fe. A subset of 6 Ni-spiked sediments was deployed in the field to examine benthic colonization and community effects. The sediment testing program yielded a broad, high quality data set that was used to develop a Species Sensitivity Distribution for benthic organisms in various sediment types, a reasonable worst case predicted no-effect concentration for Ni in sediment (PNECsediment ), and predictive models for bioavailability and toxicity of Ni in freshwater sediments. A bioavailability-based approach was developed using the ecotoxicity data and bioavailability models generated through the research program. The tiered approach can be used to fulfill the outstanding obligations under the European Union (EU) Existing Substances Risk Assessment, EU Registration, Evaluation, Authorisation, and Regulation of Chemicals (REACH), and other global regulatory initiatives. Integr Environ Assess Manag 2016;12:735-746. © 2015 SETAC.

Metal mixtures modeling evaluation project: 1. Background.

Despite more than 5 decades of aquatic toxicity tests conducted with metal mixtures, there is still a need to understand how metals interact in mixtures and to predict their toxicity more accurately than what is currently done. The present study provides a background for understanding the terminology, regulatory framework, qualitative and quantitative concepts, experimental approaches, and visualization and data-analysis methods for chemical mixtures, with an emphasis on bioavailability and metal-metal interactions in mixtures of waterborne metals. In addition, a Monte Carlo-type randomization statistical approach to test for nonadditive toxicity is presented, and an example with a binary-metal toxicity data set demonstrates the challenge involved in inferring statistically significant nonadditive toxicity. This background sets the stage for the toxicity results, data analyses, and bioavailability models related to metal mixtures that are described in the remaining articles in this special section from the Metal Mixture Modeling Evaluation project and workshop. It is concluded that although qualitative terminology such as additive and nonadditive toxicity can be useful to convey general concepts, failure to expand beyond that limited perspective could impede progress in understanding and predicting metal mixture toxicity. Instead of focusing on whether a given metal mixture causes additive or nonadditive toxicity, effort should be directed to develop models that can accurately predict the toxicity of metal mixtures.

Sediment nickel bioavailability and toxicity to estuarine crustaceans of contrasting bioturbative behaviors--an evaluation of the SEM-AVS paradigm.

Robust sediment quality criteria require chemistry and toxicity data predictive of concentrations where population/community response should occur under known geochemical conditions. Understanding kinetic and geochemical effects on toxicant bioavailability is key, and these are influenced by infaunal sediment bioturbation. This study used fine-scale sediment and porewater measurement of contrasting infaunal effects on carbon-normalized SEM-AVS to evaluate safe or potentially toxic nickel concentrations in a high-binding Spartina saltmarsh sediment (4%TOC; 35-45 µmol-S2-·g(-1)). Two crustaceans producing sharply contrasting bioturbation--the copepod Amphiascus tenuiremis and amphipod Leptocheirus plumulosus--were cultured in oxic to anoxic sediments with SEM[Ni]-AVS, TOC, porewater [Ni], and porewater DOC measured weekly. From 180 to 750 µg-Ni·g(-1) sediment, amphipod bioturbation reduced [AVS] and enhanced porewater [Ni]. Significant amphipod uptake, mortality, and growth-depression occurred at the higher sediment [Ni] even when [SEM-AVS]/foc suggested acceptable risk. Less bioturbative copepods produced higher AVS and porewater DOC but exhibited net population growth despite porewater [Ni] 1.3-1.7× their aqueous [Ni] LOEC. Copepod aqueous tests with/without dissolved organic matter showed significant aqueous DOC protection, which suggests porewater DOC attenuates sediment Ni toxicity. The SEM[Ni]-AVS relationship was predictive of acceptable risk for copepods at the important population-growth level.