Harmful effects of metal(loid) oxide nanoparticles.

The incorporation of nanomaterials (NMs), including metal(loid) oxide (MOx) nanoparticles (NPs), in the most diversified consumer products, has grown enormously in recent decades. Consequently, the contact between humans and these materials increased, as well as their presence in the environment. This fact has raised concerns and uncertainties about the possible risks of NMs to human health and the adverse effects on the environment. These concerns underline the need and importance of assessing its nanosecurity. The present review focuses on the main mechanisms underlying the MOx NPs toxicity, illustrated with different biological models: release of toxic ions, cellular uptake of NPs, oxidative stress, shading effect on photosynthetic microorganisms, physical restrain and damage of cell wall. Additionally, the biological models used to evaluate the potential hazardous of nanomaterials are briefly presented, with particular emphasis on the yeast Saccharomyces cerevisiae, as an alternative model in nanotoxicology. An overview containing recent scientific advances on cellular responses (toxic symptoms exhibited by yeasts) resulting from the interaction with MOx NPs (inhibition of cell proliferation, cell wall damage, alteration of function and morphology of organelles, presence of oxidative stress bio-indicators, gene expression changes, genotoxicity and cell dead) is critically presented. The elucidation of the toxic modes of action of MOx NPs in yeast cells can be very useful in providing additional clues about the impact of NPs on the physiology and metabolism of the eukaryotic cell. Current and future trends of MOx NPs toxicity, regarding their possible impacts on the environment and human health, are discussed. KEY POINTS: • The potential hazardous effects of MOx NPs are critically reviewed. • An overview of the main mechanisms associated with MOx NPs toxicity is presented. • Scientific advances about yeast cell responses to MOx NPs are updated and discussed.

Extrapolation of imidacloprid toxicity between soils by exposing Folsomia candida in soil pore water.

Soil properties like organic matter (OM) content show great variation, making it hard to predict the fate and effects of a chemical in different soils. We therefore addressed the question: can we remove the complexity of the soil matrix and yet accurately predict soil toxicity from porewater exposures? Folsomia candida was exposed to imidacloprid in natural (LUFA 2.2 [4.02% OM], Grassland [12.6% OM]) and artificial soils (OECD 5 [6.61% OM], OECD 10 [10.8% OM]), in pore water extracted from spiked LUFA 2.2 soil and in water. Toxicity decreased with increasing OM content except for Grassland soil, which had the highest OM content but the lowest clay content, suggesting a role of clay minerals in the binding of imidacloprid. Distribution coefficients for imidacloprid based on toxicity (Toxicity-Kd) were derived by comparing effect concentrations in LUFA 2.2 soil and in water. Using these Toxicity-Kds to recalculate soil LC50s/EC50s to porewater concentrations, the differences in LC50/EC50s almost disappeared. The recalculated porewater LC50s did not differ by more than a factor of 0.55-1.43 from the LC50 obtained upon water exposure. This similarity suggests that the toxicity in the soil is dependent on porewater concentrations and can be obtained from water exposure. The porewater test and the corresponding "pore-water extrapolation concept" developed in this study may be used to predict the toxicity of chemicals in the soil and extrapolate among different soils.

Predicting Hydrocarbon Primary Biodegradation in Soil and Sediment Systems Using System Parameterization and Machine Learning.

Technical complexity associated with biodegradation testing, particularly for substances of unknown or variable composition, complex reaction products, or biological materials (UVCB), necessitates the advancement of non-testing methods such as quantitative structure-property relationships (QSPRs). Models for describing the biodegradation of petroleum hydrocarbons (HCs) have been previously developed. A critical limitation of available models is their inability to capture the variability in biodegradation rates associated with variable test systems and environmental conditions. Recently, the Hydrocarbon Biodegradation System Integrated Model (HC-BioSIM) was developed to characterize the biodegradation of HCs in aquatic systems with the inclusion of key test system variables. The present study further expands the HC-BioSIM methodology to soil and sediment systems using a database of 2195 half-life (i.e., degradation time [DT]50) entries for HCs in soil and sediment. Relevance and reliability criteria were defined based on similarity to standard testing guidelines for biodegradation testing and applied to all entries in the database. The HC-BioSIM soil and sediment models significantly outperformed the existing biodegradation HC half-life (BioHCWin) and virtual evaluation of chemical properties and toxicities (VEGA) quantitative Mario Negri Institute for Pharmacological Research (IRFMN) models in soil and sediment. Average errors in predicted DT50s were reduced by up to 6.3- and 8.7-fold for soil and sediment, respectively. No significant bias as a function of HC class, carbon number, or test system parameters was observed. Model diagnostics demonstrated low variability in performance and high consistency of parameter usage/importance and rule structure, supporting the generalizability and stability of the models for application to external data sets. The HC-BioSIM provides improved accuracy of Persistence categorization, with correct classification rates of 83.9%, and 90.6% for soil and sediment, respectively, demonstrating a significant improvement over the existing BioHCWin (70.7% and 58.6%) and VEGA (59.5% and 18.5%) models. Environ Toxicol Chem 2024;43:1352-1363. © 2024 Concawe. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

A Chronic Aquatic Hazard Assessment for the Perfume Raw Material Octahydro-tetramethyl-naphthalenyl-ethanone.

Octahydro-tetramethyl-naphthalenyl-ethanone (OTNE) is a high-production volume fragrance material used in various down-the-drain consumer products. To assess aquatic risk, the Research Institute for Fragrance Materials (RIFM) uses a tiered data-driven framework to determine a risk characterization ratio, where the ratio of the predicted-environmental concentration to the predicted-no-effect concentration (PNEC) of <1 indicates an acceptable level of risk. Owing to its high production volume and the conservative nature of the RIFM framework, RIFM identified the need to utilize a species sensitivity distribution (SSD) approach to reduce the PNEC uncertainty for OTNE. Adding to the existing Daphnia magna, Danio rerio, and Desmodesmus subspicatus chronic studies, eight new chronic toxicity studies were conducted on the following species: Navicula pelliculosa, Chironomus riparius, Lemna gibba, Ceriodaphnia dubia, Hyalella azteca, Pimephales promelas, Anabaena flos-aquae, and Daphnia pulex. All toxicity data were summarized as chronic 10% effect concentration estimates using the most sensitive biological response. Daphnia magna was the most sensitive (0.032 mg/L), and D. subspicatus was the least sensitive (>2.6 mg/L, the OTNE solubility limit). The 5th percentile hazardous concentration (HC5) derived from the cumulative probability distribution of the chronic toxicity values for the 11 species was determined to be 0.0498 mg/L (95% confidence interval 0.0097-0.1159 mg/L). A series of "leave-one-out" and "add-one-in" simulations indicated the SSD was stable and robust. Add-one-in simulations determined that the probability of finding a species sensitive enough to lower the HC5 two- or threefold was 1/504 and 1/15,300, respectively. Given the high statistical confidence in this robust SSD, an additional application factor protection is likely not necessary. Nevertheless, to further ensure the protection of the environment, an application factor of 2 to the HC5, resulting in a PNEC of 0.0249 mg/L, is recommended. When combined with environmental exposure information, the overall hazard assessment is suitable for a probabilistic environmental risk assessment. Environ Toxicol Chem 2024;43:1378-1389. © 2024 SETAC.

Characterizing Freshwater Ecotoxicity of More Than 9000 Chemicals by Combining Different Levels of Available Measured Test Data with In Silico Predictions.

Ecotoxicological impacts of chemicals released into the environment are characterized by combining fate, exposure, and effects. For characterizing effects, species sensitivity distributions (SSDs) estimate toxic pressures of chemicals as the potentially affected fraction of species. Life cycle assessment (LCA) uses SSDs to identify products with lowest ecotoxicological impacts. To reflect ambient concentrations, the Global Life Cycle Impact Assessment Method (GLAM) ecotoxicity task force recently recommended deriving SSDs for LCA based on chronic EC10s (10% effect concentration, for a life-history trait) and using the 20th percentile of an EC10-based SSD as a working point. However, because we lacked measured effect concentrations, impacts of only few chemicals were assessed, underlining data limitations for decision support. The aims of this paper were therefore to derive and validate freshwater SSDs by combining measured effect concentrations with in silico methods. Freshwater effect factors (EFs) and uncertainty estimates for use in GLAM-consistent life cycle impact assessment were then derived by combining three elements: (1) using intraspecies extrapolating effect data to estimate EC10s, (2) using interspecies quantitative structure-activity relationships, or (3) assuming a constant slope of 0.7 to derive SSDs. Species sensitivity distributions, associated EFs, and EF confidence intervals for 9862 chemicals, including data-poor ones, were estimated based on these elements. Intraspecies extrapolations and the fixed slope approach were most often applied. The resulting EFs were consistent with EFs derived from SSD-EC50 models, implying a similar chemical ecotoxicity rank order and method robustness. Our approach is an important step toward considering the potential ecotoxic impacts of chemicals currently neglected in assessment frameworks due to limited test data. Environ Toxicol Chem 2024;00:1-14. © 2024 The Author(s). Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Towards Precision Ecotoxicology: Leveraging Evolutionary Conservation of Pharmaceutical and Personal Care Product Targets to Understand Adverse Outcomes Across Species and Life Stages.

Translation of environmental science to the practice aims to protect biodiversity and ecosystem services, and our future ability to do so relies on the development of a precision ecotoxicology approach wherein we leverage the genetics and informatics of species to better understand and manage the risks of global pollution. A little over a decade ago, a workshop focusing on the risks of pharmaceuticals and personal care products (PPCPs) in the environment identified a priority research question, "What can be learned about the evolutionary conservation of PPCP targets across species and life stages in the context of potential adverse outcomes and effects?" We review the activities in this area over the past decade, consider prospects of more recent developments, and identify future research needs to develop next-generation approaches for PPCPs and other global chemicals and waste challenges. Environ Toxicol Chem 2024;43:526-536. © 2023 SETAC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

A Comparison of In Vitro Metabolic Clearance of Various Regulatory Fish Species Using Hepatic S9 Fractions.

Bioaccumulation predictions can be substantially improved by combining in vitro metabolic rate measurements derived from rainbow trout hepatocytes and/or hepatic S9 fractions with quantitative structure-activity relationship (QSAR) modeling approaches. Compared with in vivo testing guidelines Organisation for Economic Co-operation and Development (OECD) 305 and Office of Chemical Safety and Pollution Prevention (OCSPP; an office of the US Environmental Protection Agency) 850.1730, the recently adopted OECD test guidelines 319A and 319B are in vitro approaches that have the potential to provide a time- and cost-efficient, humane solution, reducing animal use while addressing uncertainties in bioaccumulation across species. The present study compares the hepatic clearance of the S9 subcellular fraction of rainbow trout, bluegill, common carp, fathead minnow, and largemouth bass, discerning potential differences in metabolism between different warm- and cold-water species. With refinements to the in vitro metabolic S9 assay for high-throughput analysis, we measured in vitro clearance rates of seven chemicals crossing multiple classes of chemistry and modes of action. We confirmed that data from rainbow trout liver S9 fraction metabolic rates can be utilized to predict rainbow trout bioconcentration factors using an in vitro to in vivo extrapolation model, as intended in the OECD 319B applicability domain per the bioaccumulation prediction. Also, we determined that OECD 319B can be applied to other species, modified according to their habitat, adaptations to feeding behavior, and environmental conditions (e.g., temperature). Once toxicokinetics for each species is better understood and appropriate models are developed, this method can be an excellent tool to determine hepatic clearance and potential bioaccumulation across species. The present study could be leveraged prior to or in place of initiating in vivo bioconcentration studies, thus optimizing selection of appropriate fish species. Environ Toxicol Chem 2024;43:1390-1405. © 2024 SETAC.

Toxicity of Coumaphos Residues in Beeswax Foundation to the Honey Bee Brood.

Coumaphos is one of the most frequently detected pesticides in recycled beeswax. The objective was to assess the maximal level of coumaphos in foundation sheets that could exist without lethal effects on the honey bee larvae. Brood development was followed in cells drawn on foundation squares containing coumaphos ranging from 0 to 132 mg/kg. Furthermore, larval exposure was determined by measuring the coumaphos level in the drawn cells. Coumaphos levels in the initial foundation sheets up to 62 mg/kg did not increase brood mortality because the emergence rates of bees raised on these foundation squares were similar to controls (median of 51%). After a single brood cycle, coumaphos levels in the drawn cells were up to three times lower than the initial levels in foundation sheets. Hence, coumaphos levels of 62 mg/kg in the initial foundation sheets, almost the highest exposures, resulted in levels of 21 mg/kg in drawn cells. A significantly reduced emergence rate (median of 14%) was observed for bees raised on foundation sheets with initial coumaphos levels of 132 mg/kg, indicating increased brood mortality. Such levels resulted in coumaphos concentrations of 51 mg/kg in drawn cells, which is close to the median lethal concentration (LC50) as determined in previous in vitro experiments. In conclusion, brood mortality was increased on wax foundation sheets with initial coumaphos levels of 132 mg/kg, while no elevated mortality was observed for levels up to 62 mg/kg. Environ Toxicol Chem 2023;42:1816-1822. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Application of Ion Mobility Spectrometry-Mass Spectrometry for Compositional Characterization and Fingerprinting of a Library of Diverse Crude Oil Samples.

Exposure characterization of crude oils, especially in time-sensitive circumstances such as spills and disasters, is a well-known analytical chemistry challenge. Gas chromatography-mass spectrometry is commonly used for "fingerprinting" and origin tracing in oil spills; however, this method is both time-consuming and lacks the resolving power to separate co-eluting compounds. Recent advances in methodologies to analyze petroleum substances using high-resolution analytical techniques have demonstrated both improved resolving power and higher throughput. One such method, ion mobility spectrometry-mass spectrometry (IMS-MS), is especially promising because it is both rapid and high-throughput, with the ability to discern among highly homologous hydrocarbon molecules. Previous applications of IMS-MS to crude oil analyses included a limited number of samples and did not provide detailed characterization of chemical constituents. We analyzed a diverse library of 195 crude oil samples using IMS-MS and applied a computational workflow to assign molecular formulas to individual features. The oils were from 12 groups based on geographical and geological origins: non-US (1 group), US onshore (3), and US Gulf of Mexico offshore (8). We hypothesized that information acquired through IMS-MS data would provide a more confident grouping and yield additional fingerprint information. Chemical composition data from IMS-MS was used for unsupervised hierarchical clustering, as well as machine learning-based supervised analysis to predict geographic and source rock categories for each sample; the latter also yielded several novel prospective biomarkers for fingerprinting of crude oils. We found that IMS-MS data have complementary advantages for fingerprinting and characterization of diverse crude oils and that proposed polycyclic aromatic hydrocarbon biomarkers can be used for rapid exposure characterization. Environ Toxicol Chem 2023;42:2336-2349. © 2023 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.

Assessment of the Potential Ecotoxicological Effects of Pharmaceuticals in the World's Rivers.

During their production, use, and disposal, active pharmaceutical ingredients (APIs) are released into aquatic systems. Because they are biologically active molecules, APIs have the potential to adversely affect nontarget organisms. We used the results of a global monitoring study of 61 APIs alongside available ecotoxicological and pharmacological data to assess the potential ecotoxicological effects of APIs in rivers across the world. Approximately 43.5% (461 sites) of the 1052 sampling locations monitored across 104 countries in a recent global study had concentrations of APIs of concern based on apical, nonapical, and mode of action-related endpoints. Approximately 34.1% of the 137 sampling campaigns had at least one location where concentrations were of ecotoxicological concern. Twenty-three APIs occurred at concentrations exceeding "safe" concentrations, including substances from the antidepressant, antimicrobial, antihistamine, ß-blocker, anticonvulsant, antihyperglycemic, antimalarial, antifungal, calcium channel blocker, benzodiazepine, painkiller, progestin, and lifestyle compound classes. At the most polluted sites, effects are predicted on different trophic levels and on different endpoint types. Overall, the results show that API pollution is a global problem that is likely negatively affecting the health of the world's rivers. To meet the United Nations' Sustainable Development Goals, work is urgently needed to tackle the problem and bring concentrations down to an acceptable level. Environ Toxicol Chem 2022;41:2008-2020. © 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Trout and Human Plasma Protein Binding of Selected Pharmaceuticals Informs the Fish Plasma Model.

Concerns are increasing that pharmaceuticals released into the environment pose a risk to nontarget organism such as fish. The fish plasma model is a read-across approach that uses human therapeutic blood plasma concentrations for estimating likely effects in fish. However, the fish plasma model neglects differences in plasma protein binding between fish and humans. Because binding data for fish plasma are scarce, the binding of 12 active pharmaceutical ingredients (APIs; acidic, basic, and neutral) to rainbow trout (Oncorhynchus mykiss) and human plasma was measured using solid-phase microextraction (SPME). The plasma/water distribution ratios (D plasma/w ) of neutral and basic APIs were similar for trout and human plasma, differing by no more than a factor of 2.7 for a given API. For the acidic APIs, the D plasma/w values of trout plasma were much lower than for human plasma, by up to a factor of 71 for naproxen. The lower affinity of the acidic APIs to trout plasma compared with human plasma suggests that the bioavailability of these APIs is higher in trout. Read-across approaches like the fish plasma model should account for differences in plasma protein binding to avoid over- or underestimation of effects in fish. For the acidic APIs, the effect ratio of the fish plasma model would increase by a factor of 5 to 60 if the unbound plasma concentrations were used to calculate the effect ratio. Environ Toxicol Chem 2022;41:559-568. © 2020 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Marine Debris and Human Health: An Exposure Pathway of Persistent Organic Pollutants?

Although there are not any direct studies linking persistent organic pollutants (POPs) accumulated on marine debris to human health, there are numerous studies showing human health impacts from repeated and high-level POP exposure, as well as studies showing that POPs accumulate on plastic debris in the marine environment. With this knowledge, there is a need for greater awareness of the risks of POP exposure for those who handle marine debris regularly, especially in contexts of higher exposure such as those working in marine debris-concentrated areas. Among the scientific community, understanding of the exposure risk might be high, but others who handle marine debris, for instance, citizen groups in the Global South, are not necessarily aware of this exposure pathway. Moreover, global consumers who are marketed "ocean plastics" upcycled products are also not aware of potential POP exposure. Before marine plastics are accepted into the upcycled economy, these risks warrant further examination. This is a perspectives piece that aims to draw awareness to these emergent POP exposure pathways and considerations regarding marine plastic pollution. Environ Toxicol Chem 2022;41:263-265. © 2021 SETAC.

Country-Specific Environmental Risks of Fragrance Encapsulates Used in Laundry Care Products.

Fragrance encapsulates (FEs) are designed to deliver fragrance components, notably in laundry care products. They are made of thermoset polymeric shells surrounding the fragrance content. These materials enter the environment mainly during laundry washing, but little is known about their distribution in and impact on the environment. The aim of the present study was to estimate the environmental concentrations of FE shells in freshwater, sediment, and soil compartments for 34 selected countries and to compare them with ecotoxicological effects. Probabilistic material flow analysis was used to estimate worst-case predicted environmental concentrations (PECs). The lowest freshwater PEC was predicted for Finland (0.00011 µg/L) and the highest for Belgium (0.13 µg/L). Accumulation of FE shells between 2010 and 2019 was considered for sediments and sludge-treated soils. The PECs in sediments ranged from 3.0 µg/kg (Finland) to 3400 µg/kg (Belgium). For sludge-treated soil, the concentration was estimated to be between 0 (Malta and Switzerland) and 3600 µg/kg (Vietnam). Ecotoxicological tests showed no effects for FE shells at any tested concentration (up to 2700 µg/L freshwater, 5400 µg/kg sediment, and 9100 µg/kg soil), thus not allowing derivation of a predicted-no-effect concentration (PNEC). Therefore, to characterize the environmental risks, the PEC values were compared with highest-observed-no-effect concentrations (HONECs) derived from ecotoxicological tests. The PEC/HONEC ratios were 9.3 × 10-6 , 0.13, and 0.04 for surface waters, sediments, and sludge-treated soils, respectively, which are much below 1, suggesting no environmental risk. Because the PEC values constitute an upper boundary (no fate considered) and the HONEC values represent a lower boundary (actual PNEC values based on NOECs will be higher), the current risk estimation can be considered a precautionary worst-case assessment. Environ Toxicol Chem 2022;41:905-916. © 2021 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Bioaccumulation Screening of Neutral Hydrophobic Organic Chemicals in Air-Breathing Organisms Using In Vitro Rat Liver S9 Biotransformation Assays.

To advance methods for bioaccumulation assessment of organic substances in air-breathing organisms, the present study developed an in vitro approach for screening neutral hydrophobic organic substances for their bioaccumulation potential in air-breathing organisms consisting of (1) depletion assays for chemicals in rat liver S9 subcellular fractions, (2) in vitro-in vivo extrapolation, and (3) whole-organism bioaccumulation modeling to assess the biomagnification potential of neutral organic substances in the rat. Testing of the in vitro method on 14 test chemicals of potentially biomagnifying substances showed that the bioassays could be conducted with a high level of reproducibility and that in vitro-derived elimination rate constants were in good agreement with in vivo-determined elimination rate constants in the rat. Exploring the potential of the in vitro approach for screening organic chemicals for bioaccumulation in air-breathing organisms indicated that chemical substances that exhibit a depletion rate constant in the S9 in vitro bioassay ≥0.3 h-1 are not expected to biomagnify in rats independent of their octanol-water partitioning coefficient (KOW ) or octanol-air partitioning coefficient (KOA ). The high level of reproducibility achieved in the test, combined with the good agreement between in vitro-derived and in vivo-determined depuration rates, suggests that the in vitro approach in combination with a KOA - and KOW -based screening approach has good potential for screening chemicals in commerce for their bioaccumulation potential in air-breathing organisms in a cost-effective and expedient manner, especially if the bioassay can be automated. Environ Toxicol Chem 2022;41:2565-2579. © 2022 SETAC.

Automated Counting of Daphnid Neonates, Artemia Nauplii, and Zebrafish Eggs: A Proof of Concept.

In aquatic invertebrate (e.g., daphnids and Artemia sp.) and zebrafish cultures, in ecotoxicological bioassays, or when addressing complex population-level experimental designs, the counting of an organism's progeny is often required. This counting process is laborious, repetitive, and time-consuming, potentially posing health hazards to the operators, and necessarily entailing a higher likelihood of human error. We present an experimental evaluation of a computer-based device for counting neonates (Daphnia magna, Daphnia longispina, and Ceriodaphnia sp.), nauplii (Artemia salina and Artemia franciscana), and zebrafish (Danio rerio) eggs. Manual counts by an experienced technician were compared with the corresponding automated counts achieved by the computer-based counting device. A minimum of 55 counts/species was performed, with the number of counted organisms being up to a maximum of 150 neonates of Ceriodaphnia dubia, 200 neonates of D. magna and D. longispina, 200 nauplii of A. franciscana and A. salina, and 500 zebrafish eggs. Manual and automated counts were both performed in culture medium solutions of 50 ml of volume. Automated counts showed a mean relative acccuracy of 98.9% (97.9%-99.4%) and a relative standard deviation of 1.72%. The results demonstrate that the computer-based device can be used for accurately counting these aquatic organisms. This computer-based counting might be extended to other organisms of similar size, thus facilitating reproduction and life-cycle ecotoxicity tests. Environ Toxicol Chem 2022;41:1451-1458. © 2022 SETAC.

A Framework for Utilizing High-Resolution Mass Spectrometry and Nontargeted Analysis in Rapid Response and Emergency Situations.

Unknown chemical releases constitute a large portion of the rapid response situations to which the US Environmental Protection Agency is called on to respond. Workflows used to address unknown chemical releases currently involve screening for a large array of known compounds using many different targeted methods. When matches are not found, expert analytical chemistry knowledge is used to propose possible candidates from the available data, which generally includes low-resolution mass spectra and situational clues such as the location of the release, nearby industrial operations, and other field-reported facts. The past decade has witnessed dramatic improvements in capabilities for identifying unknown compounds using high-resolution mass spectrometry (HRMS) and nontargeted analysis (NTA) approaches. Complementary developments in cheminformatics tools have further enabled an increase in NTA throughput and identification confidence. Together with the expanding availability of HRMS instrumentation in monitoring laboratories, these advancements make NTA highly relevant to rapid response scenarios. In this article, we introduce the concept of NTA as it relates to rapid response needs and describe how it can be applied to address unknown chemical releases. We advocate for the consideration of HRMS-based NTA approaches to support future rapid response scenarios. Environ Toxicol Chem 2022;41:1117-1130. Published 2021. This article is a U.S. Government work and is in the public domain in the USA.

AOP Report: Uncoupling of Oxidative Phosphorylation Leading to Growth Inhibition via Decreased Cell Proliferation.

This report describes a novel adverse outcome pathway (AOP) on uncoupling of oxidative phosphorylation (OXPHOS) leading to growth inhibition via decreased adenosine triphosphate (ATP) pool and cell proliferation (AOPWiki, AOP263). Oxidative phosphorylation is a major metabolic process that produces the primary form of energy (ATP) supporting various biological functions. Uncoupling of OXPHOS is a widely recognized mode of action of many chemicals and is known to affect growth via different biological processes. Capturing these events in an AOP can greatly facilitate mechanistic understanding and hazard assessment of OXPHOS uncouplers and growth regulators in eukaryotes. The four proposed key events in this AOP are intentionally generalized to cover a wide range of organisms and stressors. Three out of four events can be measured using in vitro high-throughput bioassays, whereas for most organisms, growth inhibition can also be measured in a high-throughput format using standard in vivo toxicity test protocols. The key events and key event relationships in this AOP are further assessed for weight of evidence using evolved Bradford-Hill considerations. The overall confidence levels range from moderate to high with only a few uncertainties and inconsistencies. The chemical applicability domain of the AOP mainly contains protonophores uncouplers, which can be predicated using the quantitative structure-activity relationship (QSAR) approach and validated using in vitro high-throughput bioassays. The biological domain of the AOP basically covers all eukaryotes. The AOP described in this report is part of a larger AOP network linking uncoupling of OXPHOS to growth inhibition, and is considered highly relevant and applicable to both human health and ecological risk assessments.

Estimating Environmental Hazard and Risks from Exposure to Per- and Polyfluoroalkyl Substances (PFASs): Outcome of a SETAC Focused Topic Meeting.

Per- and polyfluoroalkyl substances (PFAS) are a group of highly fluorinated synthetic chemicals that were originally developed for uses as surfactants and surface protectors. Increasingly, specific substances of this class are being found in environmental media (e.g., surface water, soils, sediments, food sources), and concerns regarding exposure to humans and environmental receptors have been described by the public, legislators, and the general population. Data suggest that some PFAS (such as certain of the long-chain ones) bioaccumulate and have long biological half-lives, particularly in humans. Toxicity data in various organisms are variable as are their toxicokinetics. A Society of Environmental Toxicology and Chemistry (SETAC) Focused Topic Meeting and workshop entitled Environmental Risk Assessment of PFAS convened during 12 to 15 August, 2019 in Durham, North Carolina (USA) and brought together experts from around the globe to highlight recent advances in research pertinent to evaluating environmental and human health risks from exposures. The objectives of the Focused Topic Meeting and workshop were: 1) to review new and emerging information on PFAS chemical classification and grouping, environmental chemistry, detection technology, fate and transport, exposure potential, human health toxicity, and ecological toxicity; and 2) to harness the expertise of attendees to discuss and formulate a roadmap to prioritize the study of specific PFAS with the goal of developing a risk assessment approach that considers mechanistic (including computational) data for extrapolating exposure and data across different species/scenarios and compounds within environmental exposure pathways. We present the key issues that were discussed. Environ Toxicol Chem 2021;40:543-549. © 2020 SETAC.

Developing Hazard Rating Calculation Methodologies for Per- and Polyfluoroalkyl Substances.

Historical and present-day use of per- and polyfluoroalkyl substances (PFAS) have been linked to environmental and human health impacts that prove challenging to address. Therefore, prioritization of PFAS management based on observed or predicted toxicological properties and environmental fate is critical in the development of effective risk management practices. Hazard rating calculations use a range of literature-derived quantitative data to identify and rank the potential risk posed by a contaminant of concern associated with an activity or land use. The present study describes the use of hazard rating calculation methodologies to evaluate PFAS at federally owned properties across Canada. The hazard rating calculations assess potential site impacts from the use of PFAS, including application of PFAS-containing aqueous film-forming foam (AFFF) at fire-fighting training areas (FFTAs). Eleven PFAS were evaluated based on their prevalence or use in AFFFs and the availability of established chemical data. The hazard rating evaluated 4 properties: human health, environmental fate, deleterious quantity, and release and impact modifier. In the present study, hazard ratings calculated for perfluorohexane sulfonate, perfluoroheptanoate, and 8:2 fluorotelomer sulfonate were greater than for the remaining evaluated PFAS. This hazard rating system is beneficial for selecting and/or developing site management or remediation strategies. The methodology supports a comprehensive, site-scale approach for prioritizing PFAS management, and can be integrated into future regulatory framework and contaminant prioritization. Environ Toxicol Chem 2021;40:937-946. © 2021 SETAC.