Development of a rapid screening method utilizing 2D LC for effect-directed analysis in the identification of environmental toxicants.

Effect-directed analysis (EDA) is a crucial tool in environmental toxicology, effectively integrating toxicity testing with chemical analysis. The conventional EDA approach, however, presents challenges such as significant solvent consumption, extended analysis time, labor intensity, and potential contamination risks. In response, we introduce an innovative alternative to the conventional EDA. This method utilizes the MTT bioassay and online two-dimensional liquid chromatography (2D LC) coupled with high-resolution mass spectrometry (HR-MS), significantly reducing the fractionation steps and leveraging the enhanced sensitivity of the bioassay and automated chemical analysis. In the chemical analysis phase, a switching valve interface is employed for comprehensive analysis. We tested the performance of both the conventional and our online 2D LC-based methods using a household product. Both methods identified the same number of toxicants in the sample. Our alternative EDA is 22.5 times faster than the conventional method, fully automated, and substantially reduces solvent consumption. This novel approach offers ease, cost-effectiveness, and represents a paradigm shift in EDA methodologies. By integrating a sensitive bioassay with online 2D LC, it not only enhances efficiency but also addresses the challenges associated with traditional methods, marking a significant advancement in environmental toxicology research.

Bio-QSARs 2.0: Unlocking a new level of predictive power for machine learning-based ecotoxicity predictions by exploiting chemical and biological information.

Practical, legal, and ethical reasons necessitate the development of methods to replace animal experiments. Computational techniques to acquire information that traditionally relied on animal testing are considered a crucial pillar among these so-called new approach methodologies. In this light, we recently introduced the Bio-QSAR concept for multispecies aquatic toxicity regression tasks. These machine learning models, trained on both chemical and biological information, are capable of both cross-chemical and cross-species predictions. Here, we significantly extend these models' applicability. This was realized by increasing the quantity of training data by a factor of approximately 20, accomplished by considering both additional chemicals and aquatic organisms. Additionally, variable test durations and associated random effects were accommodated by employing a machine learning algorithm that combines tree-boosting with mixed-effects modeling (i.e., Gaussian Process Boosting). We also explored various biological descriptors including Dynamic Energy Budget model parameters, taxonomic distances, as well as genus-specific traits and investigated the inclusion of mode-of-action information. Through these efforts, we developed Bio-QSARs for fish and aquatic invertebrates with exceptional predictive power (R squared of up to 0.92 on independent test sets). Moreover, we made considerable strides to make models applicable for a range of use cases in environmental risk assessment as well as research and development of chemicals. Models were made fully explainable by implementing an algorithmic multicollinearity correction combined with SHapley Additive exPlanations. Furthermore, we devised novel approaches for applicability domain construction that take feature importance into account. We are hence confident these models, which are available via open access, will make a significant contribution towards the implementation of new approach methodologies and ultimately have the potential to support "Green Chemistry" and "Green Toxicology".

Ecotoxicological assessment of biomass-derived furan platform chemicals using aquatic and terrestrial bioassays.

An environmental toxicological assessment of fourteen furanic compounds serving as valuable building blocks produced from biomass was performed. The molecules selected included well studied compounds serving as control examples to compare the toxicity exerted against a variety of highly novel furans which have been additionally targeted as potential or current alternatives to biofuels, building blocks and polymer monomers. The impact of the furan platform chemicals targeted on widely applied ecotoxicity model organisms was determined employing the marine bioluminescent bacterium Aliivibrio fischeri and the freshwater green microalgae Raphidocelis subcapitata, while their ecotoxicity effects on plants were assessed using dicotyledonous plants Sinapis alba and Lepidium sativum. Regarding the specific endpoints evaluated, the furans tested were slightly toxic or practically nontoxic for A. fischeri following 5 and 15 min of exposure. Moreover, most of the building blocks did not affect the growth of L. sativum and S. alba at 150 mg L-1 for 72 h of exposure. Specifically, 9 and 11 out of the 14 furan platform chemicals tested were non-effective or stimulant for L. sativum and S. alba respectively. Given that furans comprise common inhibitors in biorefinery fermentations, the growth inhibition of the specific building blocks was studied using the industrial workhorse yeast Saccharomyces cerevisiae, demonstrating insignificant inhibition on eukaryotic cell growth following 6, 12 and 16 h of exposure at a concentration of 500 mg L-1. The study provides baseline information to unravel the ecotoxic effects and to confirm the green aspects of a range of versatile biobased platform molecules.

Cross-Species Extrapolation of Biological Data to Guide the Environmental Safety Assessment of Pharmaceuticals-The State of the Art and Future Priorities.

The extrapolation of biological data across species is a key aspect of biomedical research and drug development. In this context, comparative biology considerations are applied with the goal of understanding human disease and guiding the development of effective and safe medicines. However, the widespread occurrence of pharmaceuticals in the environment and the need to assess the risk posed to wildlife have prompted a renewed interest in the extrapolation of pharmacological and toxicological data across the entire tree of life. To address this challenge, a biological "read-across" approach, based on the use of mammalian data to inform toxicity predictions in wildlife species, has been proposed as an effective way to streamline the environmental safety assessment of pharmaceuticals. Yet, how effective has this approach been, and are we any closer to being able to accurately predict environmental risk based on known human risk? We discuss the main theoretical and experimental advancements achieved in the last 10 years of research in this field. We propose that a better understanding of the functional conservation of drug targets across species and of the quantitative relationship between target modulation and adverse effects should be considered as future research priorities. This pharmacodynamic focus should be complemented with the application of higher-throughput experimental and computational approaches to accelerate the prediction of internal exposure dynamics. The translation of comparative (eco)toxicology research into real-world applications, however, relies on the (limited) availability of experts with the skill set needed to navigate the complexity of the problem; hence, we also call for synergistic multistakeholder efforts to support and strengthen comparative toxicology research and education at a global level. Environ Toxicol Chem 2024;43:513-525. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Editorial trend: adverse outcome pathway (AOP) and computational strategy - towards new perspectives in ecotoxicology.

The adverse outcome pathway (AOP) has been conceptualized in 2010 as an analytical construct to describe a sequential chain of causal links between key events, from a molecular initiating event leading to an adverse outcome (AO), considering several levels of biological organization. An AOP aims to identify and organize available knowledge about toxic effects of chemicals and drugs, either in ecotoxicology or toxicology, and it can be helpful in both basic and applied research and serve as a decision-making tool in support of regulatory risk assessment. The AOP concept has evolved since its introduction, and recent research in toxicology, based on integrative systems biology and artificial intelligence, gave it a new dimension. This innovative in silico strategy can help to decipher mechanisms of action and AOP and offers new perspectives in AOP development. However, to date, this strategy has not yet been applied to ecotoxicology. In this context, the main objective of this short article is to discuss the relevance and feasibility of transferring this strategy to ecotoxicology. One of the challenges to be discussed is the level of organisation that is relevant to address for the AO (population/community). This strategy also offers many advantages that could be fruitful in ecotoxicology and overcome the lack of time, such as the rapid identification of data available at a time t, or the identification of "data gaps". Finally, this article proposes a step forward with suggested priority topics in ecotoxicology that could benefit from this strategy.

Reporting and reproducibility: Proteomics of fish models in environmental toxicology and ecotoxicology.

Environmental toxicology and ecotoxicology research efforts are employing proteomics with fish models as New Approach Methodologies, along with in silico, in vitro and other omics techniques to elucidate hazards of toxicants and toxins. We performed a critical review of toxicology studies with fish models using proteomics and reported fundamental parameters across experimental design, sample preparation, mass spectrometry, and bioinformatics of fish, which represent alternative vertebrate models in environmental toxicology, and routinely studied animals in ecotoxicology. We observed inconsistencies in reporting and methodologies among experimental designs, sample preparations, data acquisitions and bioinformatics, which can affect reproducibility of experimental results. We identified a distinct need to develop reporting guidelines for proteomics use in environmental toxicology and ecotoxicology, increased QA/QC throughout studies, and method optimization with an emphasis on reducing inconsistencies among studies. Several recommendations are offered as logical steps to advance development and application of this emerging research area to understand chemical hazards to public health and the environment.

Methods for estimating no-effect toxicity concentrations in ecotoxicology.

A range of new statistical approaches is being developed and/or adopted in ecotoxicology that, when combined, can greatly improve the estimation of no-effect toxicity values from concentration-response (CR) experimental data. In particular, we compare the existing no-effect-concentration (NEC) threshold-based toxicity metric with an alternative no-significant-effect-concentration (NSEC) metric suitable for when CR data do not show evidence of a threshold effect. Using a model-averaging approach, these metrics can be combined to yield estimates of N(S)EC and of their uncertainty within a single analysis framework. The outcome is a framework for CR analysis that is robust to uncertainty in the model formulation, and for which resulting estimates can be confidently integrated into risk assessment frameworks, such as the species sensitivity distribution (SSD). Integr Environ Assess Manag 2024;20:279-293. © 2023 Commonwealth of Australia and The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Big Question to Developing Solutions: A Decade of Progress in the Development of Aquatic New Approach Methodologies from 2012 to 2022.

In 2012, 20 key questions related to hazard and exposure assessment and environmental and health risks of pharmaceuticals and personal care products in the natural environment were identified. A decade later, this article examines the current level of knowledge around one of the lowest-ranking questions at that time, number 19: "Can nonanimal testing methods be developed that will provide equivalent or better hazard data compared with current in vivo methods?" The inclusion of alternative methods that replace, reduce, or refine animal testing within the regulatory context of risk and hazard assessment of chemicals generally faces many hurdles, although this varies both by organism (human-centric vs. other), sector, and geographical region or country. Focusing on the past 10 years, only works that might reasonably be considered to contribute to advancements in the field of aquatic environmental risk assessment are highlighted. Particular attention is paid to methods of contemporary interest and importance, representing progress in (1) the development of methods which provide equivalent or better data compared with current in vivo methods such as bioaccumulation, (2) weight of evidence, or (3) -omic-based applications. Evolution and convergence of these risk assessment areas offer the basis for fundamental frameshifts in how data are collated and used for the protection of taxa across the breadth of the aquatic environment. Looking to the future, we are at a tipping point, with a need for a global and inclusive approach to establish consensus. Bringing together these methods (both new and old) for regulatory assessment and decision-making will require a concerted effort and orchestration. Environ Toxicol Chem 2024;43:559-574. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Second Fundão Dam Rupture Science Meeting: Updating the science.

The second Fundão Dam Rupture Science Meeting was held in Ouro Preto, Minas Gerais, Brazil, on 21 and 22 September 2022. A total of 100 delegates attended the meeting, which featured high-quality oral presentations and posters over the two days and lively discussions of the science presented. The meeting resulted in nine papers being published in this special series. In the discussion, it was commented that the first meeting had been more a meeting of competitive perspectives but that the second meeting featured a more collaborative sharing of knowledge. Also, there had been substantial improvement in ways to deal with the lack of pre-event data and account for other stressors in the system, and as a result, stronger conclusions regarding the recovery rates of the system were able to be made. Importantly, there was no evidence for a feasible "time bomb" of a future catastrophic release of contaminants, but it was agreed that different scenarios continue to be researched. Integr Environ Assess Manag 2024;20:70-73. © 2023 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Cryptic Species in Ecotoxicology.

The advent of genetic methods has led to the discovery of an increasing number of species that previously could not be distinguished from each other on the basis of morphological characteristics. Even though there has been an exponential growth of publications on cryptic species, such species are rarely considered in ecotoxicology. Thus, the particular question of ecological differentiation and the sensitivity of closely related cryptic species is rarely addressed. Tackling this question, however, is of key importance for evolutionary ecology, conservation biology, and, in particular, regulatory ecotoxicology. At the same time, the use of species with (known or unknown) cryptic diversity might be a reason for the lack of reproducibility of ecotoxicological experiments and implies a false extrapolation of the findings. Our critical review includes a database and literature search through which we investigated how many of the species most frequently used in ecotoxicological assessments show evidence of cryptic diversity. We found a high proportion of reports indicating overlooked species diversity, especially in invertebrates. In terrestrial and aquatic realms, at least 67% and 54% of commonly used species, respectively, were identified as cryptic species complexes. The issue is less prominent in vertebrates, in which we found evidence for cryptic species complexes in 27% of aquatic and 6.7% of terrestrial vertebrates. We further exemplified why different evolutionary histories may significantly determine cryptic species' ecology and sensitivity to pollutants. This in turn may have a major impact on the results of ecotoxicological tests and, consequently, the outcome of environmental risk assessments. Finally, we provide a brief guideline on how to deal practically with cryptic diversity in ecotoxicological studies in general and its implementation in risk assessment procedures in particular. Environ Toxicol Chem 2023;42:1889-1914. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Antidepressant pharmaceuticals in aquatic systems, individual-level ecotoxicological effects: growth, survival and behavior.

The growing consumption of antidepressant pharmaceuticals has resulted in their widespread occurrence in the environment, particularly in waterways with a typical concentration range from ng L-1 to µg L-1. An increasing number of studies have confirmed the ecotoxic potency of antidepressants, not only at high concentrations but also at environmentally relevant levels. The present review covers literature from the last decade on the individual-level ecotoxicological effects of the most commonly used antidepressants, including their impact on behavior, growth, and survival. We focus on the relationship between antidepressants physico-chemical properties and dynamics in the environment. Furthermore, we discuss the advantages of considering behavioral changes as sensitive endpoints in ecotoxicology, as well as some current methodological shortcomings in the field, including low standardization, reproducibility and context-dependency.

Ecotoxicological Methodologies to Evaluate Biomarkers at Different Scales in Neotropical Anurans.

The new questions in ecotoxicology highlight the importance of applying a battery of biomarkers, as this results in ecotoxicological predictions that improve not only the interpretation of the effects of environmental stressors on organisms but also the determination of their possible impact. It is well known that the use of ecotoxicological biomarkers at different levels of organization allows for the prediction of the biological responses of organisms to environmental stressors, which is useful in environmental risk assessment. Nevertheless, it is necessary to consider the optimization of basic procedures, to generate historical data in control groups, and to employ specific bioassays to evaluate responses in organs and tissues in order to elucidate the nature and variation of the effects observed. Therefore, the present work aims to describe several ecotoxicological methodologies employed in all stages of neotropical anurans at different ecological levels and to validate them as useful biomarkers to be used both in wildlife and in laboratory conditions. In this work, these biomarkers were applied at the individual/organismic level (body condition index), histological/physiological level (histopathology, histometric, and pigmentary analyses), biochemical level (oxidative stress enzymes), and genetic level (direct and oxidative damage in DNA by comet assay). Although these methodologies have small variations or modifications depending on the species, these techniques provide effective biomarkers for evaluating the effect of xenobiotics on anurans, which possess certain characteristics that make them useful indicator species of aquatic and terrestrial ecosystems. In conclusion, the battery of biomarkers employed in the present study has proven to be adequate for estimating toxic responses in Neotropical anurans and can be further recommended as bioindicators for identifying the impact of pollutants on the aquatic ecosystems of the region. Finally, it is recommended to achieve the standardization of these important biomarkers for anurans in specific regions as well as to possibly include them in risk assessments and decision-making.

Chemical Mixtures and Multiple Stressors: Same but Different?

Ecosystems are strongly influenced by multiple anthropogenic stressors, including a wide range of chemicals and their mixtures. Studies on the effects of multiple stressors have largely focussed on nonchemical stressors, whereas studies on chemical mixtures have largely ignored other stressors. However, both research areas face similar challenges and require similar tools and methods to predict the joint effects of chemicals or nonchemical stressors, and frameworks to integrate multiple chemical and nonchemical stressors are missing. We provide an overview of the research paradigms, tools, and methods commonly used in multiple stressor and chemical mixture research and discuss potential domains of cross-fertilization and joint challenges. First, we compare the general paradigms of ecotoxicology and (applied) ecology to explain the historical divide. Subsequently, we compare methods and approaches for the identification of interactions, stressor characterization, and designing experiments. We suggest that both multiple stressor and chemical mixture research are too focused on interactions and would benefit from integration regarding null model selection. Stressor characterization is typically more costly for chemical mixtures. While for chemical mixtures comprehensive classification systems at suborganismal level have been developed, recent classification systems for multiple stressors account for environmental context. Both research areas suffer from rather simplified experimental designs that focus on only a limited number of stressors, chemicals, and treatments. We discuss concepts that can guide more realistic designs capturing spatiotemporal stressor dynamics. We suggest that process-based and data-driven models are particularly promising to tackle the challenge of prediction of effects of chemical mixtures and nonchemical stressors on (meta-)communities and (meta-)food webs. We propose a framework to integrate the assessment of effects for multiple stressors and chemical mixtures. Environ Toxicol Chem 2023;42:1915-1936. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Introducing the No-Significant-Effect Concentration.

The no-effect concentration (NEC) is the preferred threshold metric for single-species toxicity tests applied to derive safe concentration thresholds for contaminants in the environment for use in species sensitivity distributions. However, the NEC is only suitable when concentration-response (C-R) data exhibit a threshold response. We describe an alternative toxicity estimate, the no-significant-effect concentration (NSEC), which is better suited to C-R data for which the response is a monotonically decreasing function of concentration and no threshold effects are evident. We use a flexible, three-parameter sigmoidal function to describe the C-R relationship and detail both Bayesian and frequentist approaches to estimation and inference for the NSEC. While the NSEC is conceptually linked to the traditional no-observed-effect concentration (NOEC), it is a substantial improvement over the NOEC because it decouples the estimate from being directly dependent on the placement of treatment concentrations as well as admitting statements of precision of the resulting toxicity estimate. Environ Toxicol Chem 2023;42:2019-2028. © 2023 Commonwealth of Australia and The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Genes-to-Pathways Species Conservation Analysis: Enabling the Exploration of Conservation of Biological Pathways and Processes Across Species.

The last two decades have witnessed a strong momentum toward integration of cell-based and computational approaches in safety assessments. This is fueling a global regulatory paradigm shift toward reduction and replacement of the use of animals in toxicity tests while promoting the use of new approach methodologies. The understanding of conservation of molecular targets and pathways provides an opportunity to extrapolate effects across species and ultimately to determine the taxonomic applicability domain of assays and biological effects. Despite the wealth of genome-linked data available, there is a compelling need for improved accessibility, while ensuring that it reflects the underpinning biology. We present the novel pipeline Genes-to-Pathways Species Conservation Analysis (G2P-SCAN) to further support understanding on cross-species extrapolation of biological processes. This R package extracts, synthetizes, and structures the data available from different databases, that is, gene orthologs, protein families, entities, and reactions, linked to human genes and respective pathways across six relevant model species. The use of G2P-SCAN enables the overall analysis of orthology and functional families to substantiate the identification of conservation and susceptibility at the pathway level. In the present study we discuss five case studies, demonstrating the validity of the developed pipeline and its potential use as species extrapolation support. We foresee this pipeline will provide valuable biological insights and create space for the use of mechanistically based data to inform potential species susceptibility for research and safety decision purposes. Environ Toxicol Chem 2023;42:1152-1166. © 2023 UNILEVER GLOBAL IP LTD. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

A Quantitative Structure-Activity Relationship Approach to Determine Biotoxicity of Amide Herbicides for Ecotoxicological Risk Assessment.

Amide herbicides have been widely applied in agriculture and found to be widespread and affect nontarget organisms in the environment. To better understand the biotoxicity mechanisms and determine the toxicity to the nontarget organisms for the hazard and risk assessment, five QSAR models were developed for the biotoxicity prediction of amide herbicides toward five aquatic and terrestrial organisms (including algae, daphnia, fish, earthworm and avian species), based on toxicity concentration and quantitative molecular descriptors. The results showed that the developed models complied with OECD principles for QSAR validation and presented excellent performances in predictive ability. In combination, the investigated QSAR relationship led to the toxicity mechanisms that eleven electrical descriptors (EHOMO, ELUMO, αxx, αyy, αzz, µ, qN-, Qxx, Qyy, qH+, and q-), four thermodynamic descriptors (Cv, Sθ, Hθ, and ZPVE), and one steric descriptor (Vm) were strongly associated with the biotoxicity of amide herbicides. Electrical descriptors showed the greatest impacts on the toxicity of amide herbicides, followed by thermodynamic and steric descriptors.

Current testing programs for pesticides adequately capture endocrine activity and adversity for protection of vertebrate wildlife.

The toxicity and ecotoxicity of pesticide active ingredients are evaluated by a number of standardized test methods using vertebrate animals. These standard test methods are required under various regulatory programs for the registration of pesticides. Over the past two decades, additional test methods have been developed with endpoints that are responsive to endocrine activity and subsequent adverse effects. This article examines the available test methods and their endpoints that are relevant to an assessment of endocrine-disrupting properties of pesticides. Furthermore, the article highlights how weight-of-evidence approaches should be applied to determine whether an adverse response in (eco)toxicity tests is caused by an endocrine mechanism of action. The large number of endpoints in the current testing paradigms for pesticides make it unlikely that endocrine activity and adversity is being overlooked. Integr Environ Assess Manag 2023;19:1089-1109. © 2023 Bayer CropScience and The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

An innovative methodological path to attribute the hazard property HP14 "ecotoxic" to waste using a weight of evidence approach.

The criteria for the application of hazard property code HP14 "ecotoxicity" to waste assessment have been defined by the Council Regulation (EU) 2017/997. However, on the basis of available methodologies, its application may present some issues. Those can be referred to the preparation and representativeness of the sample to be analyzed, to the chemical evaluation by the summation method (CLP Regulation), to the toxicity thresholds of ecotoxicological tests and the evaluation of the real environmental impact of waste. In this work an integrated chemical and ecotoxicological approach, that relies on modified synthetic indices previously developed for dredging sediment management is proposed. The methodological procedure, assuming that the eluate represents the most relevant carrier of contaminant into the environment, was applied on eluates extracted from samples of 3 kinds of waste categories (car-fluff, fly-ash and sludges), introducing changes starting from the sample preparation and the targeted ecotoxicological and chemical analyses. The application of this approach allowed qualifying the sludge and part of fly-ash samples as "non ecotoxic", unlike the conventional method (CLP) under which all waste categories considered were found to be "ecotoxic". The new pathway for waste qualification, abandoning the classical tabular approach based on mere chemical concentrations and/or predetermined thresholds of toxicity (principle of the worst case), showed a greater discriminatory power among samples with different characteristics, and a more realistic and quantitative assessment of the environmental impact which can be caused by leaching of the waste.

Optimizing laboratory cultures of Gammarus fossarum (Crustacea: Amphipoda) as a study organism in environmental sciences and ecotoxicology.

Amphipods are among the most abundant macroinvertebrates in freshwater ecosystems of the Palaearctic and crucial for ecosystem functioning. Furthermore, their high sensitivity to environmental change and pollutants makes them widely used model organisms in environmental sciences and ecotoxicology. In field studies and surveys across Eurasia, species of the genus Gammarus are commonly used, yet laboratory-based studies and ecotoxicological tests are often restricted to the in most parts of the world non-native Hyalella azteca, as Gammarus is much harder to breed and maintain under laboratory conditions. However, for direct comparisons and extrapolations of results of field- vs. laboratory-based studies, the use of the same species would be desirable. Here, we investigated different settings with respect to feeding, shelter and day length to successfully increase survival, juvenile production and their respective growth and survival, and ultimately multi-generation breeding of the amphipod Gammarus fossarum. Amphipod populations persisted and reproduced successfully under optimized husbandry conditions for 12 months and were partially maintained for another year in populations up to a few hundred individuals. Specifically, supplementing diet with protein-rich food sources as well as the provisioning of shelters improved survival rate of G. fossarum significantly. However, we found no significant effect of different day length treatments on the overall relative reproductive activity or on the total amphipod abundance maintained. We conclude that G. fossarum can be kept and reared under standardized conditions. Despite the longer generation times of G. fossarum and higher effort required for maintenance compared to H. azteca, direct ecological relevance and comparability of results to natural systems may justify its future use and development as a study organism for environmental sciences and ecotoxicology.

A critical review of the application of polymer of low concern regulatory criteria to fluoropolymers II: Fluoroplastics and fluoroelastomers.

Fluoropolymers are a distinct class of per- and polyfluoroalkyl substances (PFAS), high molecular weight (MW) polymers with fluorine attached to their carbon-only backbone. Fluoropolymers possess a unique combination of properties and unmatched functional performance critical to the products and manufacturing processes they enable and are irreplaceable in many uses. Fluoropolymers have documented safety profiles; are thermally, biologically, and chemically stable, negligibly soluble in water, nonmobile, nonbioavailable, nonbioaccumulative, and nontoxic. Although fluoropolymers fit the PFAS structural definition, they have very different physical, chemical, environmental, and toxicological properties when compared with other PFAS. This study describes the composition, uses, performance properties, and functionalities of 14 fluoropolymers, including fluoroplastics and fluoroelastomers, and presents data to demonstrate that they satisfy the widely accepted polymer hazard assessment criteria to be considered polymers of low concern (PLC). The PLC criteria include physicochemical properties, such as molecular weight, which determine bioavailability and warn of potential hazard. Fluoropolymers are insoluble (e.g., water, octanol) solids too large to migrate into the cell membrane making them nonbioavailable, and therefore, of low concern from a human and environmental health standpoint. Further, the study results demonstrate that fluoropolymers are a distinct and different group of PFAS and should not be grouped with other PFAS for hazard assessment or regulatory purposes. When combined with an earlier publication by Henry et al., this study demonstrates that commercial fluoropolymers are available from the seven participating companies that meet the criteria to be considered PLC, which represent approximately 96% of the global commercial fluoropolymer market. Integr Environ Assess Manag 2023;19:326-354. © 2022 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).