Materials design for hypersonics.

Hypersonic vehicles must withstand extreme conditions during flights that exceed five times the speed of sound. These systems have the potential to facilitate rapid access to space, bolster defense capabilities, and create a new paradigm for transcontinental earth-to-earth travel. However, extreme aerothermal environments create significant challenges for vehicle materials and structures. This work addresses the critical need to develop resilient refractory alloys, composites, and ceramics. We will highlight key design principles for critical vehicle areas such as primary structures, thermal protection, and propulsion systems; the role of theory and computation; and strategies for advancing laboratory-scale materials to manufacturable flight-ready components.

Noninvasive Stratification of Colon Cancer by Multiplex PET Imaging.

PURPOSE: The current approach for molecular subtyping of colon cancer relies on gene expression profiling, which is invasive and has limited ability to reveal dynamics and spatial heterogeneity. Molecular imaging techniques, such as PET, present a noninvasive alternative for visualizing biological information from tumors. However, the factors influencing PET imaging phenotype, the suitable PET radiotracers for differentiating tumor subtypes, and the relationship between PET phenotypes and tumor genotype or gene expression-based subtyping remain unknown. EXPERIMENTAL DESIGN: In this study, we conducted 126 PET scans using four different metabolic PET tracers, [18F]fluorodeoxy-D-glucose ([18F]FDG), O-(2-[18F]fluoroethyl)-l-tyrosine ([18F]FET), 3'-deoxy-3'-[18F]fluorothymidine ([18F]FLT), and [11C]acetate ([11C]ACE), using a spectrum of five preclinical colon cancer models with varying genetics (BMT, AKPN, AK, AKPT, KPN), at three sites (subcutaneous, orthograft, autochthonous) and at two tumor stages (primary vs. metastatic). RESULTS: The results demonstrate that imaging signatures are influenced by genotype, tumor environment, and stage. PET imaging signatures exhibited significant heterogeneity, with each cancer model displaying distinct radiotracer profiles. Oncogenic Kras and Apc loss showed the most distinctive imaging features, with [18F]FLT and [18F]FET being particularly effective, respectively. The tissue environment notably impacted [18F]FDG uptake, and in a metastatic model, [18F]FET demonstrated higher uptake. CONCLUSIONS: By examining factors contributing to PET-imaging phenotype, this study establishes the feasibility of noninvasive molecular stratification using multiplex radiotracer PET. It lays the foundation for further exploration of PET-based subtyping in human cancer, thereby facilitating noninvasive molecular diagnosis.

Assessing the relevance of environmental exposure data sets.

Environmental exposure data are used by decision-makers to assess environmental risks and implement actions to mitigate risks from contaminants. The first article in this series summarized the available evaluation schemes for environmental exposure data, of which there are few compared to those available for environmental hazard data. The second article covered the assessment of the reliability of environmental exposure data sets under the Criteria for the Reporting and Evaluation of Exposure Data (CREED). The aim of this article is to provide an overview and practical guidance on the relevance assessment in the context of the CREED approach for evaluating exposure monitoring data sets. Systematically considering relevance is critical for both evaluating existing data sets and for optimizing the design of new monitoring studies. Relevance is defined here as the degree of suitability or appropriateness of a data set to address a specific purpose or to answer the questions that have been defined by the assessor or for those generating exposure data. The purpose definition will be the foundation for the relevance assessment, to clarify how the assessor should rate the assessment criteria (fully met, partly met, not met/inappropriate, not reported, not applicable). This will provide transparency for anyone reviewing the outcomes. An explicit gap analysis (i.e., an articulation of the data set limitations for the stated purpose) is an important outcome of the relevance assessment. The relevance evaluation approach is demonstrated with three case studies, all relating to the freshwater aquatic environment, where the data sets are scored as relevant with or without restrictions, not relevant, or not assignable. The case studies represent both organic and inorganic constituents, and have different data characteristics (e.g., percentage of censored data, sampling frequencies, relation to supporting parameters). Integr Environ Assess Manag 2024;00:1-15. © 2023 SETAC.

Validation of Nickel Bioavailability Models for Algae, Invertebrates, and Fish in Chinese Surface Waters.

Nickel (Ni) is used primarily in the production of alloys like stainless steel and is increasingly being used in the production of batteries for the electric vehicle market. Exposure of Ni to ecosystems is of concern because Ni can be toxic to aquatic organisms. The influence of water chemistry constituents (e.g., hardness, pH, dissolved organic carbon) on the toxicity of Ni has prompted the development and use of bioavailability models, such as biotic ligand models (BLMs), which have been demonstrated to accurately predict Ni toxicity in broadly different ecosystems, including Europe, North America, and Australia. China, a leading producer of Ni, is considering bioavailability-based approaches for regulating Ni emissions. Adoption of bioavailability-based approaches in China requires information to demonstrate the validity of bioavailability models for the local water chemistry conditions. The present study investigates the toxicity of Ni to three standard test species (Daphnia magna, Pseudokirchneriella subcapitata, and Danio rerio) in field-collected natural waters that are broadly representative of the range of water chemistries and bioavailabilities encountered in Chinese lakes and rivers. All experimental data are within a factor of 3 of the BLM predicted values for all tests with all species. For D. magna, six of seven waters were predicted within a factor of 2 of the experimental result. Comparison of experimental data against BLM predictions shows that the existing Ni bioavailability models are able to explain the differences in toxicity that result from water chemistry conditions in China. Validation of bioavailability models to water chemistries and bioavailability ranges within China provides technical support for the derivation of site-specific Ni water quality criteria in China. Environ Toxicol Chem 2023;42:1257-1265. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Following the evidence and using the appropriate regulatory tools: A European-wide risk assessment of copper in freshwaters.

The ecological risks of copper (Cu) in freshwaters have been the focus of regulatory assessments for several decades. Recently, it has been suggested by the European Commission that Cu represents a continent-wide risk to freshwaters. We assessed to what extent this suggestion is supported by the available evidence if Cu bioavailability is considered in the assessment of risk. We used several evidence-driven metrics to assess the continental-wide risks of Cu to European freshwaters. Such an approach is recommended and readily applicable where comprehensive data sets are available. We confirmed the validity of a bioavailability-based Environmental Quality Standard of 1 µg L-1 for Cu and used this to characterize the risks of Cu in 286 185 regulatory monitoring samples from 17 307 sites across 19 European countries between 2006 and 2021. These data show that risks, based on site averages and accounting for bioavailability, were identified in only two countries (Spain and Portugal). Investigation of these risks showed them to be highly localized to a single region in Spain and not reflective of the country-wide risks for either country. The 95th percentile of all the risk quotients for the continent-wide data set is 0.35. The relatively low levels of risk associated with Cu are supported by long-term trend data from sites on two large European rivers (Rhine and Meuse), where highly significant (p < 0.001) decreases in Cu concentrations over the last 40 years can be observed. We conclude that it is critical to consider metal bioavailability in both effects and exposures in assessments of potential risk to ensure ecological relevance. Integr Environ Assess Manag 2023;19:1570-1580. © 2023 WCA Environment Ltd. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Updating the Chronic Freshwater Ecotoxicity Database and Biotic Ligand Model for Nickel for Regulatory Applications in Europe.

Bioavailability has been taken into account in the regulation of nickel in freshwater ecosystems in Europe for over a decade; during that time a significant amount of new information has become available covering both the sensitivity of aquatic organisms to nickel toxicity and bioavailability normalization. The ecotoxicity database for chronic nickel toxicity to freshwater organisms has been updated and now includes 358 individual data points covering a total of 53 different species, all of which are suitable for bioavailability normalization to different water chemistry conditions. The bioavailability normalization procedure has also been updated to include updates to the bioavailability models that enable more sensitive water chemistry conditions to be covered by the model predictions. The updated database and bioavailability normalization procedure are applicable to more than 95% of regulated European surface water conditions and have been used to calculate site-specific criteria for a variety of different water chemistry scenarios, to provide an indication of how the sensitivity to nickel varies between different water types. The hazardous concentration for 5% of a species (HC5) values for this diverse selection of water types range from 1.6 to 36 µg L-1 , clearly demonstrating the importance of accounting for nickel bioavailability in freshwaters. This updated database and bioavailability normalization procedure provide a robust basis for the derivation of regulatory thresholds for chronic nickel toxicity in freshwaters such as predicted no-effect concentrations and Environmental Quality Standards and are protective of the results of several mesocosm studies. Environ Toxicol Chem 2023;42:566-580. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Evaluating the Protectiveness of a Bioavailability-Based Environmental Quality Standard for the Protection of Aquatic Communities from Zinc Toxicity Based on Field Evidence.

Environmental quality standards (EQS) are typically derived from the results of laboratory studies on single species. There is always uncertainty surrounding the protectiveness of an EQS when applied to real ecosystems containing a multitude of chemical and physical stressors. Quantile regression was used with field biological data on invertebrates in United Kingdom waters to identify taxa that are responsive to bioavailable zinc exposures. A threshold based on the total abundance of eight responsive taxa is used as an indicator of the overall ecosystem sensitivity. The inclusion of some responsive but insensitive taxa in this ecological metric could bias the results toward a higher threshold. The least responsive species were progressively removed from the collective ecological metric, basing the analysis on a progressively smaller number of the more responsive species. Quantile regression analysis at the 95th quantile for the three most responsive taxa resulted in a 10% effect concentration of 14.8 µg L-1 bioavailable zinc, suggesting that the EQS of 10.9 µg L-1 bioavailable zinc is sufficiently protective of sensitive members of the invertebrate community. There is a compromise between the robustness of the analysis and the sensitivity of the subcommunity that it is based on. Analyses based on fewer taxa provide a more sensitive result. This approach assessed real ecosystem data and evaluated the uncertainty associated with the protectiveness of the EQS for zinc. The zinc EQS is sufficiently protective of sensitive members of benthic macroinvertebrate communities under real environmental conditions, including a mix of multiple substances. Environ Toxicol Chem 2023;42:1010-1021. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Sources of copper into the European aquatic environment.

Chemical contamination from point source discharges in developed (resource-rich) countries has been widely regulated and studied for decades; however, diffuse sources are largely unregulated and widespread. In the European Union (EU), large dischargers report releases of some chemicals, yet little is known of total emissions (point and diffuse) and their relative significance. We estimated copper loadings from all significant sources including industry, sewage treatment plants, surface runoff (from traffic, architecture, and atmospheric deposition), septic tanks, agriculture, mariculture, marine transport (antifoulant leaching), and natural processes. A combination of European datasets, literature, and industry data were used to generate export coefficients. These were then multiplied by activity rates to derive loads. A total of approximately 8 kt of copper per annum (ktpa) is estimated to enter freshwaters in the EU, and another 3.5 ktpa enters transitional and coastal waters. The main inputs to freshwater are natural processes (3.7 ktpa), agriculture (1.8 ktpa), and runoff (1.8 ktpa). Agricultural emissions are dominated by copper-based plant protection products and farmyard manure. Urban runoff is influenced by copper use in architecture and by vehicle brake linings. Antifoulant leaching from boats (3.2 ktpa) dominates saline water loads of copper. It is noteworthy that most of the emissions originate in a limited number of copper uses where environmental exposure and pathways exist, compared with the bulk of copper use within electrical and electronic equipment and infrastructure that has no environmental pathway during its use. A sensitivity analysis indicated significant uncertainty in data from abandoned mines and urban runoff load estimates. This study provided for the first time a methodology and comprehensive metal load apportionment to European aquatic systems, identifying data gaps and uncertainties, which may be refined over time. Source apportionments using this methodology can inform more cost-effective environmental risk assessment and management. Integr Environ Assess Manag 2023;19:1031-1047. © 2022 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Assessing the Extent of Environmental Risks From Nickel in European Freshwaters: A Critical Reflection of the European Commission's Current Approach.

Nickel (Ni) has a been a Priority Substance under the European Water Framework Directive since 2008. As such it is deemed to present an European Union-wide risk to surface waters. Since 2013, the Ni Environmental Quality Standard (EQS) has been bioavailability-based, and new European Guidance supports accounting for bioavailability in assessing Ni compliance with the EQS. The European Commission has developed an approach to determine whether Priority Substances present a sufficient European Union-wide risk to justify an ongoing statutory monitoring programme, effectively to deselect a substance. This is a key step to ensure that finite monitoring resources are targeted at delivering environmental benefit, when there is an ever-growing burden of determinands to measure for all regulators. When the European Commission performed this exercise for Ni without accounting for bioavailability, they concluded that Ni should not be deselected, and Ni is an European Union-wide risk. Performing this same exercise with the same methodology, using regulatory monitoring data for over 300 000 samples, from more than 19 000 sites across Europe, and accounting for bioavailability, as detailed in the Directive, >99% of sites comply with the Ni EQS. Nickel shows very low risks for all of the criteria identified by the European Commission that need to be met for deselection. Accounting for bioavailability is key in the assessment of Ni risks in surface waters to deliver ecologically relevant outcomes. Environ Toxicol Chem 2022;41:1604-1612. © 2022 NiPERA. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Variation in chronic nickel toxicity to Daphnia magna among Japanese river waters and performance evaluation of bioavailability models in predicting the toxicity.

Nickel (Ni) ecotoxicity is dictated by water chemistry characteristics such as pH, water hardness, and amount of dissolved organic carbon. Bioavailability models have been developed to predict Ni toxicity and validated for European, Australian, and US natural waters. In this study, chronic toxicity tests in Ni-spiked Japanese river waters were conducted on a strain of Daphnia magna to test whether the chronic toxicity differs among Japanese natural waters with different water chemistries. Based on the results of chronic Ni toxicity tests, we assessed the performance of existing D. magna bioavailability models, which were developed in artificial waters (Model 1) and calibrated in European natural waters (Model 2), in terms of the accuracy and the bias of model predictions. Furthermore, we also calibrated the two models by using toxicity test results to develop a bioavailability model for Ni chronic toxicity to the strain of D. magna in Japanese river waters. The 10%, 20%, and 50% effect concentrations (EC10, EC20, and EC50) of dissolved Ni on reproduction of the D. magna strain were within ranges from 8.1 to 44.9 µg/L, 9.0 to 57.1 µg/L, and 10.9 to 86.1 µg/L, respectively. Results indicate that differences in water chemistry among Japanese river waters influenced chronic Ni toxicity to the model organism. Model 1predicted 43% of the observed EC10, EC20, and EC50 values within a factor of 2 and 100%, 100%, and 43% within a factor of 3, respectively. Model 2 predicted 14%, 14%, and 29% of the observed EC10, EC20, and EC50 values within a factor of 2 and 43% within a factor of 3. The values of model bias based on the geometric mean of ratios of EC10, EC20 and EC50 values predicted by each of the two models and observed EC10, EC20, and EC50 values were 0.71, 0.65, and 0.62 for Model 1 and 0.27, 0.26, and 0.29 for Model 2, respectively. After calibrating two models using the results of toxicity tests, refined Model 1 predicted 71%, 57%, and 57% of observed EC10, EC20, and EC50 values within a factor of 2 and 100%, 86%, and 100% within a factor of 3; refined Model 2 predicted 71% of observed EC10, EC20, and EC50 values within a factor 2 and 100%, 86%, and 86% within a factor of 3, respectively. Our results indicate that calibrating the Ni bioavailability models in Japanese natural waters increased their predictive capacity by a factor of up to approximately five.

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).

Empirical Bioavailability Corrections for Nickel in Freshwaters for Australia and New Zealand Water Quality Guideline Development.

Bioavailability-based approaches have been developed for the regulation of metals in freshwaters in several countries. Empirical multiple linear regression (MLR) models have been developed for nickel that can be applied to aquatic organisms. The MLR models have been compared against the use of previously developed biotic ligand models (BLMs) for the normalization of an ecotoxicity dataset compiled for the derivation of a water quality guideline value that could be applied in Australia and New Zealand. The MLR models were developed from data for a number of specific species and were validated independently to confirm their reliability. An MLR modeling approach using different models for algae, plants, invertebrates, and vertebrates performed better than either a pooled MLR model for all taxa or the BLMs, in terms of its ability to correctly predict the results of the tests in the ecotoxicity database based on their water chemistry and a fitted species-specific sensitivity parameter. The present study demonstrates that MLR approaches can be developed and validated to predict chronic nickel toxicity to freshwater ecosystems from existing datasets. The MLR approaches provide a viable alternative to the use of BLMs for taking account of nickel bioavailability in freshwaters for regulatory purposes. Environ Toxicol Chem 2021;40:113-126. © 2020 SETAC.

Application of Bioavailability Models to Derive Chronic Guideline Values for Nickel in Freshwaters of Australia and New Zealand.

There has been an increased emphasis on incorporating bioavailability-based approaches into freshwater guideline value derivations for metals in the Australian and New Zealand water quality guidelines. Four bioavailability models were compared: the existing European biotic ligand model (European Union BLM) and a softwater BLM, together with 2 newly developed multiple linear regressions (MLRs)-a trophic level-specific MLR and a pooled MLR. Each of the 4 models was used to normalize a nickel ecotoxicity dataset (combined tropical and temperate data) to an index condition of pH 7.5, 6 mg Ca/L, 4 mg Mg/L, (i.e., approximately 30 mg CaCO3 /L hardness), and 0.5 mg DOC/L. The trophic level-specific MLR outperformed the other 3 models, with 79% of the predicted 10% effect concentration (EC10) values within a factor of 2 of the observed EC10 values. All 4 models gave similar normalized species sensitivity distributions and similar estimates of protective concentrations (PCs). Based on the index condition water chemistry proposed as the basis of the national guideline value, a protective concentration for 95% of species (PC95) of 3 µg Ni/L was derived. This guideline value can be adjusted up and down to account for site-specific water chemistries. Predictions of PC95 values for 20 different typical water chemistries for Australia and New Zealand varied by >40-fold, which confirmed that correction for nickel bioavailability is critical for the derivation of site-specific guideline values. Environ Toxicol Chem 2021;40:100-112. © 2020 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Deriving a bioavailability-based zinc environmental quality standard for France.

National Environmental Quality Standards (EQS) for zinc used for the assessment of ecological status in freshwaters have been shown to vary by over two orders of magnitude across 25 European countries. Such variability is unlikely to reflect consistent ecological protection or environmental relevance. Recent European technical guidance on EQS derivation gives an opportunity to derive protective metrics for zinc that are relevant to national water chemistry conditions. To derive a zinc EQS relevant to national water chemistry conditions and account for bioavailability, the new technical guidance requires high-quality spatial and temporal monitoring data. These data must be of water samples with concurrent measures of pH, dissolved organic carbon (DOC) and calcium, the parameters that most influence zinc bioavailability in freshwaters. A national bioavailability-based zinc EQS for France has been derived from Biotic Ligand Model calculations undertaken for freshwaters samples from 4645 sites (22,000 samples with concurrent measures of pH, DOC, calcium) in 96 regions. An EQS of 11.3 µg Zn L-1 was derived based on sensitive waters from the Bretagne region typically of circumneutral pH and relatively low DOC and low dissolved calcium. The least sensitive waters to zinc exposures in France are found in the Hauts-De-France, higher pH values than those in Bretagne, similar dissolved organic carbon and higher dissolved calcium. An indicative assessment of compliance showed that across France, 2% of the sites would exceed this bioavailability-based EQS.

Perspectives on Relevancy Assessment for Non-Standard Ecotoxicity Data in Environment Quality Standard derivation: Examples for Diclofenac.

A key step in deriving an Environmental Quality Standard (EQS) is assessing the reliability and relevance of the underpinning ecotoxicity data. While the assessment of data reliability is relatively well established, the detailed evaluation of data relevancy is a more recent development. We applied broadly accepted relevancy criteria to a series of non-standard ecotoxicity studies on diclofenac, focusing on some aspects that should be accounted for in studies used in EQS derivation. Specific relevancy issues include potential experimental bias, claimed 'significant effects' that are indistinguishable from controls, or within the range of normal, and lack of environmental applicability. We highlight that rigorous, comprehensive and, where necessary, specialist assessment of data relevancy for studies potentially applicable for EQS setting is critical if studies are to be appropriately used regulatory decision-making. We provide recommendations for researchers and environmental practitioners to ensure robust accounting of relevancy in non-standard studies is undertaken.

Demonstrating the Reliability of bio-met for Determining Compliance with Environmental Quality Standards for Metals in Europe.

The importance of considering the bioavailability of metals in understanding and assessing their toxicity in freshwaters has been recognized for many years. Currently, biotic ligand models (BLMs) are being applied for the derivation and implementation of environmental quality standards (EQS) for metals under the Water Framework Directive in Europe. bio-met is a simplified tool that was developed for implementing bioavailability-based EQS for metals in European freshwaters. We demonstrate the reliability of the relationship between the full BLM predictions and the thresholds (hazardous concentration affecting 5% of species [HC5] values) predicted by bio-met in 3 stages, for the metals copper, nickel, and zinc. First, ecotoxicity data for specific species from laboratory tests in natural waters are compared with predictions by the individual species BLMs included in the full BLMs. Second, the site-specific HC5 values predicted by bio-met for the natural waters used for ecotoxicity testing are compared with those provided by the full BLMs. The reliability of both relationships is demonstrated for all 3 metals, with more than 80% of individual species BLM predictions being within a factor of 3 of the experimental results, and 99% of bio-met local HC5 predictions being within a factor of 2 of the full BLM result. Third, using a larger set of European natural waters in addition demonstrates the reliability of bio-met over a broad range of water chemistry conditions. bio-met is therefore an appropriate tool for performing compliance assessments against EQS values in Europe, due to the demonstrated consistency with the toxicity test data. Environ Toxicol Chem 2020;39:2361-2377. © 2020 SETAC.