Bypassing the Identification: MS2Quant for Concentration Estimations of Chemicals Detected with Nontarget LC-HRMS from MS2 Data.

Nontarget analysis by liquid chromatography-high-resolution mass spectrometry (LC-HRMS) is now widely used to detect pollutants in the environment. Shifting away from targeted methods has led to detection of previously unseen chemicals, and assessing the risk posed by these newly detected chemicals is an important challenge. Assessing exposure and toxicity of chemicals detected with nontarget HRMS is highly dependent on the knowledge of the structure of the chemical. However, the majority of features detected in nontarget screening remain unidentified and therefore the risk assessment with conventional tools is hampered. Here, we developed MS2Quant, a machine learning model that enables prediction of concentration from fragmentation (MS2) spectra of detected, but unidentified chemicals. MS2Quant is an xgbTree algorithm-based regression model developed using ionization efficiency data for 1191 unique chemicals that spans 8 orders of magnitude. The ionization efficiency values are predicted from structural fingerprints that can be computed from the SMILES notation of the identified chemicals or from MS2 spectra of unidentified chemicals using SIRIUS+CSI:FingerID software. The root mean square errors of the training and test sets were 0.55 (3.5×) and 0.80 (6.3×) log-units, respectively. In comparison, ionization efficiency prediction approaches that depend on assigning an unequivocal structure typically yield errors from 2× to 6×. The MS2Quant quantification model was validated on a set of 39 environmental pollutants and resulted in a mean prediction error of 7.4×, a geometric mean of 4.5×, and a median of 4.0×. For comparison, a model based on PaDEL descriptors that depends on unequivocal structural assignment was developed using the same dataset. The latter approach yielded a comparable mean prediction error of 9.5×, a geometric mean of 5.6×, and a median of 5.2× on the validation set chemicals when the top structural assignment was used as input. This confirms that MS2Quant enables to extract exposure information for unidentified chemicals which, although detected, have thus far been disregarded due to lack of accurate tools for quantification. The MS2Quant model is available as an R-package in GitHub for improving discovery and monitoring of potentially hazardous environmental pollutants with nontarget screening.

Scenario-based modelling of changes in chemical intake fraction in Sweden and the Baltic Sea under global change.

The climate in Europe is warming twice as fast as it is across the rest of the globe, and in Sweden annual mean temperatures are forecast to increase by up to 3-6 °C by 2100, with increasing frequency and magnitude of floods, heatwaves, and other extreme weather. These climate change-related environmental factors and the response of humans at the individual and collective level will affect the mobilization and transport of and human exposure to chemical pollutants in the environment. We conducted a literature review of possible future impacts of global change in response to a changing climate on chemical pollutants in the environment and human exposure, with a focus on drivers of change in exposure of the Swedish population to chemicals in the indoor and outdoor environment. Based on the literature review, we formulated three alternative exposure scenarios that are inspired by three of the shared socioeconomic pathways (SSPs). We then conducted scenario-based exposure modelling of the >3000 organic chemicals in the USEtox® 2.0 chemical library, and further selected three chemicals (terbuthylazine, benzo[a]pyrene, PCB-155) from the USEtox library that are archetypical pollutants of drinking water and food as illustrative examples. We focus our modelling on changes in the population intake fraction of chemicals, which is calculated as the fraction of a chemical emitted to the environment that is ingested via food uptake or inhaled by the Swedish population. Our results demonstrate that changes of intake fractions of chemicals are possible by up to twofold increases or decreases under different development scenarios. Changes in intake fraction in the most optimistic SSP1 scenario are mostly attributable to a shift by the population towards a more plant-based diet, while changes in the pessimistic SSP5 scenario are driven by environmental changes such as rain fall and runoff rates.

Berlin statement on legacy and emerging contaminants in polar regions.

Polar regions should be given greater consideration with respect to the monitoring, risk assessment, and management of potentially harmful chemicals, consistent with requirements of the precautionary principle. Protecting the vulnerable polar environments requires (i) raising political and public awareness and (ii) restricting and preventing global emissions of harmful chemicals at their sources. The Berlin Statement is the outcome of an international workshop with representatives of the European Commission, the Arctic Council, the Antarctic Treaty Consultative Meeting, the Stockholm Convention on Persistent Organic Pollutants (POPs), environmental specimen banks, and data centers, as well as scientists from various international research institutions. The statement addresses urgent chemical pollution issues in the polar regions and provides recommendations for improving screening, monitoring, risk assessment, research cooperation, and open data sharing to provide environmental policy makers and chemicals management decision-makers with relevant and reliable contaminant data to better protect the polar environments. The consensus reached at the workshop can be summarized in just two words: "Act now!" Specifically, "Act now!" to reduce the presence and impact of anthropogenic chemical pollution in polar regions by. •Establishing participatory co-development frameworks in a permanent multi-disciplinary platform for Arctic-Antarctic collaborations and establishing exchanges between the Arctic Monitoring and Assessment Program (AMAP) of the Arctic Council and the Antarctic Monitoring and Assessment Program (AnMAP) of the Scientific Committee on Antarctic Research (SCAR) to increase the visibility and exchange of contaminant data and to support the development of harmonized monitoring programs. •Integrating environmental specimen banking, innovative screening approaches and archiving systems, to provide opportunities for improved assessment of contaminants to protect polar regions.

Assessing and managing environmental hazards of polymers: historical development, science advances and policy options.

Polymers are the main constituents of many materials and products in our modern world. However, their environmental safety is not assessed with the same level of detail as done for non-polymeric chemical substances. Moreover, the fundamentals of contemporary regulatory approaches for polymers were developed in the early 1990s, with little change occurring since then. Currently, the European Commission is working on a proposal to initiate registration of polymers under the European Union's (EU) chemicals legislation REACH. This provides a unique opportunity for regulation to catch up on recent scientific advances. To inform this process, we here critically appraise the suggested regulatory approaches to the environmental assessment and management of polymers against the latest scientific findings regarding their environmental fate, exposure, and effects, and identify the remaining critical knowledge gaps. While we use the EU draft proposal as an example, our findings are broadly applicable to other polymer legislations worldwide, due to the similarity of polymer assessment criteria being used. We emphasize four major aspects that require more attention in the regulation of polymers: (i) increased transparency about chemical identities, physical characteristics and grouping approaches for in-use polymers; (ii) improved understanding of the environmental fate of polymers and materials composed of polymers across size and density categories and exposure profiles; (iii) comprehensive assessment of the environmental hazards of polymers, considering the effects of degradation and weathering and taking into account the actual uptake, long-term toxicity, and geophysical impacts; and (iv) consideration of the production volume and use/release patterns in determining regulatory data and testing requirements. Transitioning toward a toxic-free and sustainable circular economy will likely require additional policy instruments that will reduce the overall complexity and diversity of in-use polymers and polymeric materials.

Computational models to confront the complex pollution footprint of plastic in the environment.

The threat posed by plastic in the environment is poorly characterized due to uncertainties and unknowns about sources, transport, transformation and removal processes, and the properties of the plastic pollution itself. Plastic creates a footprint of particulate pollution with a diversity of composition, size and shape, and a halo of chemicals. In this Perspective, we argue that process-based mass-balance models could provide a platform to synthesize knowledge about plastic pollution as a function of its measurable intrinsic properties.

MS2Tox Machine Learning Tool for Predicting the Ecotoxicity of Unidentified Chemicals in Water by Nontarget LC-HRMS.

To achieve water quality objectives of the zero pollution action plan in Europe, rapid methods are needed to identify the presence of toxic substances in complex water samples. However, only a small fraction of chemicals detected with nontarget high-resolution mass spectrometry can be identified, and fewer have ecotoxicological data available. We hypothesized that ecotoxicological data could be predicted for unknown molecular features in data-rich high-resolution mass spectrometry (HRMS) spectra, thereby circumventing time-consuming steps of molecular identification and rapidly flagging molecules of potentially high toxicity in complex samples. Here, we present MS2Tox, a machine learning method, to predict the toxicity of unidentified chemicals based on high-resolution accurate mass tandem mass spectra (MS2). The MS2Tox model for fish toxicity was trained and tested on 647 lethal concentration (LC50) values from the CompTox database and validated for 219 chemicals and 420 MS2 spectra from MassBank. The root mean square error (RMSE) of MS2Tox predictions was below 0.89 log-mM, while the experimental repeatability of LC50 values in CompTox was 0.44 log-mM. MS2Tox allowed accurate prediction of fish LC50 values for 22 chemicals detected in water samples, and empirical evidence suggested the right directionality for another 68 chemicals. Moreover, by incorporating structural information, e.g., the presence of carbonyl-benzene, amide moieties, or hydroxyl groups, MS2Tox outperforms baseline models that use only the exact mass or log KOW.

The Path to UVCB Ecological Risk Assessment: Grappling with Substance Characterization.

Substances of unknown or variable composition, complex reaction products, and biological materials (UVCBs) pose a unique challenge to regulators and to product registrants, who are required to characterize their fate, exposure, hazard, and potential risks to human health and the environment. To address these challenges and ensure an efficient and fit-for-purpose process, it is proposed that the ecological risks of UVCBs be assessed following a tiered strategy. The development of this approach required exploring how substance composition ties into hazard and exposure information and determining the extent to which a UVCB needs to be characterized to ensure a robust risk assessment. The present study highlights the key aspects of this new method. It presents how a tiered substance characterization approach can be integrated into broader UVCB risk-assessment schemes to encourage an examination of data needs before a full substance characterization is performed. The first tier of the characterization process, Tier 0, is a fundamental step that includes data from basic, lower-resolution compositional analyses. Tier 0 assessments can be used to inform hazard and exposure for any substance of interest. The need for more sophisticated, higher-tier characterization is determined by the level of uncertainty of the risk assessment. The next step will integrate a tiered exposure assessment into the characterization scheme featured in the present study, to create a more complete risk-assessment framework. Environ Toxicol Chem 2022;41:2649-2657. © 2022 Her Majesty the Queen in Right of Canada, Health and Environmental Sciences Institute and The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC. Reproduced with the permission of the Minister of Environment and Climate Change Canada.

Fate-directed risk assessment of chemical mixtures: a case study for cedarwood essential oil.

The environmental risk assessment of UVCBs (i.e., substances of unknown or variable composition, complex reaction products, or biological materials) is challenging due to their inherent complexity. A particular problem is that UVCBs can contain constituents with unidentified chemical structures and/or have variable composition of constituents from batch to batch. Moreover, the composition of a UVCB in the environment is not the same as that of the UVCB in a product, meaning that a risk assessment based on environmental exposure to the UVCB in a product does not represent the actual environmental risk. Here we propose an in silico fate-directed risk assessment framework for UVCBs using cedarwood oil as a case study. The framework uses Monte Carlo simulations and the mass-balance models SimpleTreat and RAIDAR to provide quantitative information on whether unidentified constituents within the physical-chemical property space of a UVCB can be the decisive factor for the environmental risk of the entire UVCB. Thereby the framework provides a robust decision tool to evaluate if a UVCB risk assessment requires additional tests or if the data on known constituents is representative for the risk of the entire UVCB. In the case of cedarwood oil, it could be shown that a risk assessment based on the known constituents (representing around 70% of the overall UVCB by weight) is representative for the environmental risk of the entire UVCB - reducing the need for additional testing and test animals.

Enabling forecasts of environmental exposure to chemicals in European agriculture under global change.

European agricultural development in the 21st century will be affected by a host of global changes, including climate change, changes in agricultural technologies and practices, and a shift towards a circular economy. The type and quantity of chemicals used, emitted, and cycled through agricultural systems in Europe will change, driven by shifts in the use patterns of pesticides, veterinary pharmaceuticals, reclaimed wastewater used for irrigation, and biosolids. Climate change will also impact the chemical persistence, fate, and transport processes that dictate environmental exposure. Here, we review the literature to identify research that will enable scenario-based forecasting of environmental exposures to organic chemicals in European agriculture under global change. Enabling exposure forecasts requires understanding current and possible future 1.) emissions, 2.) persistence and transformation, and 3.) fate and transport of agricultural chemicals. We discuss current knowledge in these three areas, the impact global change drivers may have on them, and we identify knowledge and data gaps that must be overcome to enable predictive scenario-based forecasts of environmental exposure under global change. Key research gaps identified are: improved understanding of relationships between global change and chemical emissions in agricultural settings; better understanding of environment-microbe interactions in the context of chemical degradation under future conditions; and better methods for downscaling climate change-driven intense precipitation events for chemical fate and transport modelling. We introduce a set of narrative Agricultural Chemical Exposure (ACE) scenarios - augmenting the IPCC's Shared Socio-economic Pathways (SSPs) - as a framework for forecasting chemical exposure in European agriculture. The proposed ACE scenarios cover a plausible range of optimistic to pessimistic 21st century development pathways. Filling the knowledge and data gaps identified within this study and using the ACE scenario approach for chemical exposure forecasting will support stakeholder planning and regulatory intervention strategies to ensure European agricultural practices develop in a sustainable manner.

Outside the Safe Operating Space of the Planetary Boundary for Novel Entities.

We submit that the safe operating space of the planetary boundary of novel entities is exceeded since annual production and releases are increasing at a pace that outstrips the global capacity for assessment and monitoring. The novel entities boundary in the planetary boundaries framework refers to entities that are novel in a geological sense and that could have large-scale impacts that threaten the integrity of Earth system processes. We review the scientific literature relevant to quantifying the boundary for novel entities and highlight plastic pollution as a particular aspect of high concern. An impact pathway from production of novel entities to impacts on Earth system processes is presented. We define and apply three criteria for assessment of the suitability of control variables for the boundary: feasibility, relevance, and comprehensiveness. We propose several complementary control variables to capture the complexity of this boundary, while acknowledging major data limitations. We conclude that humanity is currently operating outside the planetary boundary based on the weight-of-evidence for several of these control variables. The increasing rate of production and releases of larger volumes and higher numbers of novel entities with diverse risk potentials exceed societies' ability to conduct safety related assessments and monitoring. We recommend taking urgent action to reduce the harm associated with exceeding the boundary by reducing the production and releases of novel entities, noting that even so, the persistence of many novel entities and/or their associated effects will continue to pose a threat.

The global threat from plastic pollution.

Plastic pollution accumulating in an area of the environment is considered "poorly reversible" if natural mineralization processes occurring there are slow and engineered remediation solutions are improbable. Should negative outcomes in these areas arise as a consequence of plastic pollution, they will be practically irreversible. Potential impacts from poorly reversible plastic pollution include changes to carbon and nutrient cycles; habitat changes within soils, sediments, and aquatic ecosystems; co-occurring biological impacts on endangered or keystone species; ecotoxicity; and related societal impacts. The rational response to the global threat posed by accumulating and poorly reversible plastic pollution is to rapidly reduce plastic emissions through reductions in consumption of virgin plastic materials, along with internationally coordinated strategies for waste management.

Combining Headspace Solid-Phase Microextraction with Internal Benchmarking to Determine the Elimination Kinetics of Hydrophobic UVCBs.

Substances classified as unknown or variable composition, complex reaction products or biological origin (UVCB) present a challenge for environmental hazard and risk assessment. Here, we present a novel approach for whole-substance bioconcentration testing applied to cedarwood oil-an essential oil composed of volatile, hydrophobic organic chemicals. The method yields whole-body elimination rate constants for a mixture of constituents. Our approach combines in vivo dietary fish exposure with internal benchmarking and headspace solid-phase microextraction (HS-SPME) equilibrium sampling followed by suspect-screening analysis. We quantified depuration rate constants of 13 individual cedarwood oil constituents based on relative peak areas using gas chromatography (GC) coupled with Orbitrap-mass spectrometry (MS) and GC triple-quadrupole (QqQ)-MS. For seven constituents with available analytical standards, we compared the rate constants to the results obtained from solvent extraction, clean-up, and targeted GC-MS analysis. The HS-SPME sampling approach allowed for automated sample extraction and analyte enrichment while minimizing evaporative losses of the volatile target analytes and reducing matrix interferences from low-volatility organics. The suspect-screening analysis enabled the quantification of constituents without available analytical standards, while the internal benchmarking significantly reduced variability from differences in delivered dose and analytical variability between the samples.

Variability in Toxicity of Plastic Leachates as a Function of Weathering and Polymer Type: A Screening Study with the Copepod Nitocra spinipes.

AbstractThe production and use of plastic over many decades has resulted in its accumulation in the world's oceans. Plastic debris poses a range of potential risks to the marine environment and its biota. Especially, the potential hazards of small plastic debris and chemicals associated with plastic have not been extensively studied. When buoyant plastic is exposed to ultraviolet radiation, it will slowly degrade and leach chemicals into surrounding waters. These leachates can include additives, sorbed organic pollutants, and degradation products of the plastic polymers. While most hazard assessments have focused on studying adverse effects due to the uptake of plastic, toxicity studies of the leachates of plastics are less common. To begin to address this knowledge gap, we studied the acute toxicity of leachates from diverse plastics in the harpacticoid copepod Nitocra spinipes. Our results show that leachates caused a higher toxicity after plastic was exposed to ultraviolet light compared to leaching in darkness. We observed differences in toxicity for different polymer types: polyvinyl chloride and polypropylene resulted in the most toxic leachates, while polystyrene and poly[ethylene terephthalate] were least toxic. Furthermore, we observed increased toxicity of leachates from some plastics that had been weathered in the real marine environment compared to matching new materials. Our results indicate that both weathering condition and polymer type influence the toxicity of plastic leachates.

Weathering Plastics as a Planetary Boundary Threat: Exposure, Fate, and Hazards.

We described in 2017 how weathering plastic litter in the marine environment fulfils two of three criteria to impose a planetary boundary threat related to "chemical pollution and the release of novel entities": (1) planetary-scale exposure, which (2) is not readily reversible. Whether marine plastics meet the third criterion, (3) eliciting a disruptive impact on vital earth system processes, was uncertain. Since then, several important discoveries have been made to motivate a re-evaluation. A key issue is if weathering macroplastics, microplastics, nanoplastics, and their leachates have an inherently higher potential to elicit adverse effects than natural particles of the same size. We summarize novel findings related to weathering plastic in the context of the planetary boundary threat criteria that demonstrate (1) increasing exposure, (2) fate processes leading to poorly reversible pollution, and (3) (eco)toxicological hazards and their thresholds. We provide evidence that the third criterion could be fulfilled for weathering plastics in sensitive environments and therefore conclude that weathering plastics pose a planetary boundary threat. We suggest future research priorities to better understand (eco)toxicological hazards modulated by increasing exposure and continuous weathering processes, to better parametrize the planetary boundary threshold for plastic pollution.

Bioconcentration of cedarwood oil constituents in rainbow trout.

Cedarwood oil is an essential oil used as a fragrance material and insect repellent. Its main constituents are sesquiterpenes which are potentially bioaccumulative according to the REACH screening criteria. Cedarwood oil is a complex mixture of hydrophobic and volatile organic chemicals. The volatility and limited water solubility of its constituents are a challenge for standard bioconcentration factor (BCF) test methods using aqueous exposure. We used an abbreviated dietary exposure in vivo testing protocol with internal benchmark substances as "internal standards" to derive the BCF of cedarwood oil constituents using rainbow trout (Oncorhynchus mykiss). Internal benchmarking proved to be a useful tool to control for inter-individual variability, enabling us to calculate the BCF for all major cedarwood oil constituents as a mixture. We found that the BCF of two out of six analysed cedarwood oil constituents exceed a BCF of 5000 and two others exceed a BCF of 2000 (90% confidence level) even though we found evidence for biotransformation for individual constituents. The results of this study indicate that more work is warranted to study the bioaccumulation of essential oils and highlights the utility of internal benchmarking in in vivo dietary exposure BCF tests to increase robustness and allow for the BCF measurement of complex mixtures.

Chemistry of Unsymmetrical C1-Substituted Oxabenzonorbornadienes.

Oxabenzonorbornadiene (OBD) is a useful synthetic intermediate, which can be readily activated by transition metal complexes with great face selectivity due to its dual-faced nature and intrinsic angle strain on the alkene. To date, the understanding of transition-metal catalyzed reactions of OBD itself has burgeoned; however, this has not been the case for unsymmetrical OBDs. Throughout the development of these reactions, the nature of C1-substituent has proven to have a profound effect on both the reactivity and selectivity of the outcome of the reaction. Upon substitution, different modes of reactivity arise, contributing to the possibility of multiple stereo-, regio-, and in extreme cases, constitutional isomers, which can provide unique means of constructing a variety of synthetically useful cyclic frameworks. To maximize selectivity, an understanding of bridgehead substituent effects is crucial. To that end, this review outlines hitherto reported examples of bridgehead substituent effects on the chemistry of unsymmetrical C1-substituted OBDs.

ECORISK2050: An Innovative Training Network for predicting the effects of global change on the emission, fate, effects, and risks of chemicals in aquatic ecosystems.

By 2050, the global population is predicted to reach nine billion, with almost three quarters living in cities. The road to 2050 will be marked by changes in land use, climate, and the management of water and food across the world. These global changes (GCs) will likely affect the emissions, transport, and fate of chemicals, and thus the exposure of the natural environment to chemicals. ECORISK2050 is a Marie Sklodowska-Curie Innovative Training Network that brings together an interdisciplinary consortium of academic, industry and governmental partners to deliver a new generation of scientists, with the skills required to study and manage the effects of GCs on chemical risks to the aquatic environment. The research and training goals are to: (1) assess how inputs and behaviour of chemicals from agriculture and urban environments are affected by different environmental conditions, and how different GC scenarios will drive changes in chemical risks to human and ecosystem health; (2) identify short-to-medium term adaptation and mitigation strategies, to abate unacceptable increases to risks, and (3) develop tools for use by industry and policymakers for the assessment and management of the impacts of GC-related drivers on chemical risks. This project will deliver the next generation of scientists, consultants, and industry and governmental decision-makers who have the knowledge and skillsets required to address the changing pressures associated with chemicals emitted by agricultural and urban activities, on aquatic systems on the path to 2050 and beyond.

Steady-State Mass Balance Model for Predicting Particle-Gas Concentration Ratios of PBDEs.

Assuming equilibrium partitioning between the gas and particle phases has been shown to overestimate the fraction of low-volatility chemicals in the particle phase. Here, we present a new steady-state mass balance model that includes separate compartments for fine and coarse aerosols and the gas phase and study its sensitivity to the input parameters. We apply the new model to investigate deviations from equilibrium partitioning by exploring model scenarios for seven generic aerosol scenarios representing different environments and different distributions of emissions as the gas phase, fine aerosol, and coarse aerosol. With 100% of emissions as the particle phase, the particle-gas concentration ratio in our model is similar to the equilibrium model, while differences are up to a factor of 106 with 100% of emissions as the gas phase. The particle-gas concentration ratios also depend on the particle size distributions and aerosol loadings in the different environmental scenarios. The new mass balance model can predict the particle-gas concentration ratio with more fidelity to measurements than equilibrium models. However, further laboratory-based evaluations and calibrations of the standard sampling techniques, field investigations with preferably size-resolved measurements of aerosol particle composition, together with the appropriate process modeling for low-volatility chemicals are warranted.