Search

Chitosan, alginate, and chitosan-alginate (50:50) mixed hydrogels were prepared by freeze casting, freeze-drying, and subsequent physical cross-linking. Chitosan was cross-linked with citrate and alginate with calcium ions, while the mixed gels were cross-linked with both cross-linking agents. Both cryogels and xerogels were obtained by lyophilization and drying of the hydrogels. We investigated the effect of the chemical composition and the physical state of gels on the gel structure and sorption of model dyes. Alginate and mixed gels cross-linked with Ca 2+ ions sorbed 80-95% of cationic dye from the solutions. The chitosan gels are primarily capable of adsorbing anionic dyes, but at near-neutral pH, their capacity is lower than that of alginate gels, showing 50-60% dye sorption. In the case of alginate gels, the dye sorption capacity of xerogels, cryogels, and hydrogels was the same, but for chitosan gels, the hydrogels adsorbed slightly less dye than the dried gels.

Carbon disulfide (CS 2 ) is one of the sulfur components that are naturally present in petroleum fractions. Its presence causes corrosion issues in the fuel facilities and deactivates the catalysts in the petrochemical processes. It is a hazardous component that negatively impacts the environment and public health due to its toxicity. This study used zinc-carbon (ZC) composite as a CS 2 adsorbent from the gasoline fraction model component. The carbon is derived from date stone biomass. The ZC composite was prepared via a homogenous precipitation process by urea hydrolysis. The physicochemical properties of the prepared adsorbent are characterized using different techniques. The results confirm the loading of zinc oxide/hydroxide carbonate and urea-derived species on the carbon surface. The results were compared by the parent samples, raw carbon, and zinc hydroxide prepared by conventional and homogeneous precipitation. The CS 2 adsorption process was performed using a batch system at atmospheric pressure. The effects of adsorbent dosage and adsorption temperatures have been examined. The results indicate that ZC has the highest CS 2 adsorption capacity (124.3 mg.g -1 at 30 °C) compared to the parent adsorbents and the previously reported data. The kinetics and thermodynamic calculation results indicate the spontaneity and feasibility of the CS 2 adsorption process., (© 2023. The Author(s).)

We here report chemical characteristics relevant to the fate and transport of the recently discovered environmental toxicant 6PPD-quinone (2-((4-methylpentan-2-yl)amino)-5-(phenylamino)cyclohexa-2,5-diene-1,4-dione or "6PPDQ"). 6PPDQ is a transformation product of the tire rubber antioxidant 6PPD that is ubiquitous in roadway environments, including atmospheric particulate matter, soils, runoff, and receiving waters, after dispersal from tire rubber use and wear on roadways. The aqueous solubility and octanol-water partitioning coefficient ( i.e. log  K OW ) for 6PPDQ were measured to be 38 ± 10 μg L -1 and 4.30 ± 0.02, respectively. Within the context of analytical measurement and laboratory processing, sorption to various laboratory materials was evaluated, indicating that glass was largely inert but loss of 6PPDQ to other materials was common. Aqueous leaching simulations from tire tread wear particles (TWPs) indicated short term release of ∼5.2 μg 6PPDQ per gram TWP over 6 h under flow-through conditions. Aqueous stability tests observed a slight-to-moderate loss of 6PPDQ over 47 days (26 ± 3% loss) for pH 5, 7 and 9. These measured physicochemical properties suggest that 6PPDQ is generally poorly soluble but fairly stable over short time periods in simple aqueous systems. 6PPDQ can also leach readily from TWPs for subsequent environmental transport, posing high potential for adverse effects in local aquatic environments.

Cancer, the second largest human disease, has become a major public health problem. The prediction of chemicals' carcinogenicity before their synthesis is crucial. In this paper, seven machine learning algorithms (i.e., Random Forest (RF), Logistic Regression (LR), Support Vector Machines (SVM), Complement Naive Bayes (CNB), K-Nearest Neighbor (KNN), XGBoost, and Multilayer Perceptron (MLP)) were used to construct the carcinogenicity triple classification prediction (TCP) model (i.e., 1A, 1B, Category 2). A total of 1444 descriptors of 118 hazardous organic chemicals were calculated by Discovery Studio 2020, Sybyl X-2.0 and PaDEL-Descriptor software. The constructed carcinogenicity TCP model was evaluated through five model evaluation indicators (i.e., Accuracy, Precision, Recall, F1 Score and AUC). The model evaluation results show that Accuracy, Precision, Recall, F1 Score and AUC evaluation indicators meet requirements (greater than 0.6). The accuracy of RF, LR, XGBoost, and MLP models for predicting carcinogenicity of Category 2 is 91.67%, 79.17%, 100%, and 100%, respectively. In addition, the constructed machine learning model in this study has potential for error correction. Taking XGBoost model as an example, the predicted carcinogenicity level of 1,2,3-Trichloropropane (96-18-4) is Category 2, but the actual carcinogenicity level is 1B. But the difference between Category 2 and 1B is only 0.004, indicating that the XGBoost is one optimum model of the seven constructed machine learning models. Besides, results showed that functional groups like chlorine and benzene ring might influence the prediction of carcinogenic classification. Therefore, considering functional group characteristics of chemicals before constructing the carcinogenicity prediction model of organic chemicals is recommended. The predicted carcinogenicity of the organic chemicals using the optimum machine leaning model (i.e., XGBoost) was also evaluated and verified by the toxicokinetics. The RF and XGBoost TCP models constructed in this paper can be used for carcinogenicity detection before synthesizing new organic substances. It also provides technical support for the subsequent management of organic chemicals., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Manufacturing and functionalizing materials at the nanoscale has led to the generation of a whole array of nanoforms (NFs) of substances varying in size, morphology, and surface characteristics. Due to financial, time, and ethical considerations, testing every unique NF for adverse effects is virtually impossible. Use of hypothesis-driven grouping and read-across approaches, as supported by the GRACIOUS Framework, represents a promising alternative to case-by-case testing that will make the risk assessment process more efficient. Through application of appropriate grouping hypotheses, the Framework facilitates the assessment of similarity between NFs, thereby supporting grouping and read-across of information, minimizing the need for new testing, and aligning with the 3R principles of replacement, reduction, and refinement of animals in toxicology studies. For each grouping hypothesis an integrated approach to testing and assessment (IATA) guides the user in data gathering and acquisition to test the hypothesis, following a structured format to facilitate efficient decision-making. Here we present the template used to generate the GRACIOUS grouping hypotheses encompassing information relevant to “Lifecycle, environmental release, and human exposure”, “What they are: physicochemical characteristics”, “Where they go: environmental fate, uptake, and toxicokinetics”, and “What they do: human and environmental toxicity”. A summary of the template-derived hypotheses focusing on human health is provided, along with an overview of the IATAs generated by the GRACIOUS project. We discuss the application and flexibility of the template, providing the opportunity to expand the application of grouping and read-across in a logical, evidence-based manner to a wider range of NFs and substances.

Emergency response planning guideline values are used to protect the public when there has been a short-term chemical release. These values serve the purpose of identifying areas where a hazard exists if the concentration of hazardous chemicals is exceeded for the specified exposure duration. This paper focuses on carbonyl chlorides, a class of highly irritant/corrosive chemical intermediates characterized by the reactive moiety R-COCl. Despite their unifying property of reacting with nucleophilic biopolymers/peptides lining the airways of the respiratory tract, their adverse outcome pathway (AOP), in addition to surface area dose, appears to be dominated by their site(s) of major deposition (liquid) or retention (gas) within the respiratory tract. Thus, the physicochemical properties "phase" and "lipophilicity" become more decisive for the AOP than the chemical structure. This complicates the grouping of portal-of-entry irritant chemicals for the read-across prediction of chemicals, especially those with semivolatile properties. Phosgene (COCl 2 ) served as a template to predict emergency response planning levels 2 (non-incapacitating, reversible injury) and 3 (nonlethal) for related chemicals such as SOCl 2 , formates, and acid chlorides. A rationale and guide to the systematic characterization of uncertainties associated with the lung region, water solubility of the vapor phase, and chemical specificity is given. The approach described in this paper highlights the regional differences and outcomes that are phenotypically described as irritation of the respiratory tract. Especially for such a data-lean group of chemicals, reliable read-across predictions could reduce the uncertainty associated with the derivation of values used for emergency-related risk assessment and management. Likewise, the approach suggested could improve the grouping and categorization of such chemicals, providing a means to reduce animal testing with potentially corrosive chemicals. Overall, the course taken for read-across predictions provided valid estimates as long as emphasis was directed to the physicochemical properties determining the most critical regional injury within the respiratory tract., (Copyright © 2022 Covestro Deutschland AG. Published by Elsevier Inc. All rights reserved.)

Different groups of synthetic dyes might lead to environmental pollution. The binding affinity among hazardous materials with biomolecules necessitates a detailed understanding of their binding properties. Malachite Green might induce a change in the iron transfer by Apo-transferrin. Spectroscopic studies showed malachite green oxalate (MGO) could form the apo-transferrin-MGO complex and change the Accessible Surface Area (ASA) of the key amino acids for iron transfer. According to the ASA results the accessible surface area of Tyrosine, Aspartate, and Histidine of apo-transferrin significantly were changed, which can be considered as a convincing reason for changing the iron transfer. Moreover, based on the fluorescence data MGO could quench the fluorescence intensity of apo-transferrin in a static quenching mechanism. The experimental and Molecular Dynamic simulation results represented that the binding process led to micro environmental changes, around tryptophan residues and altered the tertiary structure of apo-transferrin. The Circular Dichroism (CD) spectra result represented a decrease in the amount of the α-Helix, as well as, increase in the β-sheet volumes of the apo-transferrin structure. Moreover, FTIR spectroscopy results showed a hypochromic shift in the peaks of amide I and II. Molecular docking and MD simulation confirmed all the computational findings., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Commercial chemicals are used extensively across urban centres worldwide 1 , posing a potential exposure risk to 4.2 billion people 2 . Harmful chemicals are often assessed on the basis of their environmental persistence, accumulation in biological organisms and toxic properties, under international and national initiatives such as the Stockholm Convention 3 . However, existing regulatory frameworks rely largely upon knowledge of the properties of the parent chemicals, with minimal consideration given to the products of their transformation in the atmosphere. This is mainly due to a dearth of experimental data, as identifying transformation products in complex mixtures of airborne chemicals is an immense analytical challenge 4 . Here we develop a new framework-combining laboratory and field experiments, advanced techniques for screening suspect chemicals, and in silico modelling-to assess the risks of airborne chemicals, while accounting for atmospheric chemical reactions. By applying this framework to organophosphate flame retardants, as representative chemicals of emerging concern 5 , we find that their transformation products are globally distributed across 18 megacities, representing a previously unrecognized exposure risk for the world's urban populations. More importantly, individual transformation products can be more toxic and up to an order-of-magnitude more persistent than the parent chemicals, such that the overall risks associated with the mixture of transformation products are also higher than those of the parent flame retardants. Together our results highlight the need to consider atmospheric transformations when assessing the risks of commercial chemicals., (© 2021. Crown.)

A system to differentiate and quantify liquid and headspace vapor leaks from closed system drug-transfer devices (CSTDs) is presented. CSTDs are designed to reduce or eliminate hazardous drug (HD) exposure risk when compounding and administering HDs. CSTDs may leak liquid, headspace, or a mixture of the two. The amount of HD contained in liquid and headspace leaks may be substantially different. Use of a test solution containing two VOCs with differences in ratios of VOC concentrations in the headspace and liquid enables source apportionment of leaked material. SIFT-MS was used to detect VOCs from liquid and headspace leaks in the vapor phase. Included in this report is a novel method to determine the origin and magnitude of leaks from CSTDs. A limit of leak detection of 24 μL of headspace vapor and 0.14 μL of test liquid were found using Selected Ion Flow Tube Mass Spectrometry (SIFT-MS)., Competing Interests: The authors have declared that no competing interests exist.

A decision-scheme outlining the steps for identifying the appropriate chemical category and subsequently appropriate tested source analog(s) for data gap filling of a target chemical by read-across is described. The primary features used in the grouping of the target chemical with source analogues within a database of 10,039 discrete organic substances include reactivity mechanisms associated with protein interactions and specific-acute-oral-toxicity-related mechanisms (e.g., mitochondrial uncoupling). Additionally, the grouping of chemicals making use of the in vivo rat metabolic simulator and neutral hydrolysis. Subsequently, a series of structure-based profilers are used to narrow the group to the most similar analogues. The scheme is implemented in the OECD QSAR Toolbox, so it automatically predicts acute oral toxicity as the rat oral LD50 value in log [1/mol/kg]. It was demonstrated that due to the inherent variability in experimental data, classification distribution should be employed as more adequate in comparison to the exact classification. It was proved that the predictions falling in the adjacent GSH categories to the experimentally-stated ones are acceptable given the variation in experimental data. The model performance estimated by adjacent accuracy was found to be 0.89 and 0.54 while based on R 2 . The mechanistic and predictive coverages were >0.85., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The approach to reproductive health and safety in academic laboratories requires increased focus and a shift in paradigm. Our analysis of the current guidance from more than 100 academic institutions' Chemical Hygiene Plans (CHPs) indicates that the burden to implement laboratory reproductive health and safety practices is often placed on those already pregnant or planning conception. We also found inconsistencies in the classification of potential reproductive toxins by resources generally considered to be authoritative, adding further confusion. In the interest of human health and safe laboratory practice, we suggest straightforward changes that institutions and individual laboratories can make to address these present deficiencies: Provide consistent and clear information to laboratory researchers about reproductive health and normalize the discussion of reproductive health among all researchers. Doing so will promote safer and more inclusive laboratory environments.

Nitroaromatic compounds (NACs) are ubiquitous in the environment due to their extensive industrial applications. The recalcitrance of NACs causes their arduous degradation, subsequently bringing about potential threats to human health and environmental safety. The problem of how to effectively predict the toxicity of NACs has drawn public concern over time. Quantitative structure-activity relationship (QSAR) is introduced as a cost-effective tool to quantitatively predict the toxicity of toxicants. Both OECD (Organization for Economic Co-operation and Development) and REACH (Registration, Evaluation and Authorization of Chemicals) legislation have promoted the use of QSAR as it can significantly reduce living animal testing. Although numerous QSAR studies have been conducted to evaluate the toxicity of NACs, systematic reviews related to the QSAR modeling of NACs toxicity are less reported. The purpose of this review is to provide a thorough summary of recent QSAR studies on the toxic effects of NACs according to the corresponding classes of toxic response endpoints.

Toxicologists face several challenges when communicating with the public about the potential risks of chemical substances in consumer products. However, based on the consumers' scepticism and detachment from the use of chemical substances in the manufacturing of consumer goods, evidence is needed on how this communication can be improved. Hence, the goal of this study was to experimentally check the effect of an informational video on consumers' acceptance of trace chemicals in consumer products, their willingness to purchase and finally, their perception of the dose-response mechanism. For this, an informational video was developed and evaluated in a pre-post online study with a sample of South Korean consumers (N = 600). The results suggest that providing information on toxicological principles increases people's acceptance of trace chemicals in consumer products and their willingness to purchase a consumer product containing trace chemicals. Within the article, implications for practice and ideas for new research avenues are presented., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Water pollution originating from organic dyes is endangering the survival and development of society; however, adsorbents with high capacity (>5000 mg g -1 ) for the fast removal (≤30 min) of Congo Red (CR) in aqueous solution have been not reported to date. In the present work, an acid-base stably layered MOF, [Cd(H 2 L)(BS) 2 ] n ·2nH 2 O (L-MOF-1, H 2 L = N1,N2-bis(pyridin-3-ylmethyl)ethane-1,2-diamine, BS = benzenesulfonate), was hydrothermally prepared. L-MOF-1 exhibited high-performance adsorption of CR in aqueous solution at room temperature. The experimental adsorption capacity of the L-MOF-1 adsorbent towards CR reached up to about 12 000 mg g -1 in 20 min in the pH range of 2.2-4.7, which is the best adsorbent with the highest capacity and fastest adsorption of CR to date. The spontaneous adsorption process can be described by the pseudo-second-order kinetic and Langmuir isotherm models. Meanwhile, the L-MOF-1 absorbent possessed a highly positive zeta potential in acid condition (even at pH = 2.2, zeta potential = 36.2 mV). Its good adsorption performance mainly originates from its strong electrostatic attraction with CR in acidic condition, together with diverse hydrogen bonds and ππ stacking interactions. Furthermore, the L-MOF-1 absorbent exhibited good selectivity and could be reused five times through simply washing, where its adsorption efficiency was hardly affected. Therefore, L-MOF-1 is a potential absorbent for effectively removing CR from dye wastewater.

Due to the large amount of chemical substances on the market, fast and reproducible screening is essential to prioritize chemicals for further evaluation according to highest concern. We here evaluate the performance of structural similarity models that are developed to identify potential substances of very high concern (SVHC) based on structural similarity to known SVHCs. These models were developed following a systematic analysis of the performance of 112 different similarity measures for varying SVHC-subgroups. The final models consist of the best combinations of fingerprint, similarity coefficient and similarity threshold, and suggested a high predictive performance (≥80%) on an internal dataset consisting of SVHC and non-SVHC substances. However, the application performance on an external dataset was not evaluated. Here, we evaluated the application performance of the developed similarity models with a 'pseudo-external assessment' on a set of substances (n = 60-100 for the varying SVHC-subgroups) that were putatively assessed as SVHC or non-SVHC based upon consensus scoring using expert elicitations (n = 30 experts). Expert scores were direct evaluations based on structural similarity to the most similar SVHCs according to the similarity models, and did not consider an extensive evaluation of available data. The use of expert opinions is particularly suitable as this is exactly the intended purpose of the chemical similarity models: a quick, reproducible and automated screening tool that mimics the expert judgement that is frequently applied in various screening applications. In addition, model predictions were analyzed via qualitative approaches and discussed via specific examples, to identify the model's strengths and limitations. The results indicate a good statistical performance for carcinogenic, mutagenic or reprotoxic (CMR) and endocrine disrupting (ED) substances, whereas a moderate performance was observed for (very) persistent, (very) bioaccumulative and toxic (PBT/vPvB) substances when compared to expert opinions. For the PBT/vPvB model, particularly false positive substances were identified, indicating the necessity of outcome interpretation. The developed similarity models are made available as a freely-accessible online tool. In general, the structural similarity models showed great potential for screening and prioritization purposes. The models proved to be effective in identifying groups of substances of potential concern, and could be used to identify follow-up directions for substances of potential concern., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Photosafety evaluations of chemicals used in consumer products, such as pharmaceuticals and cosmetics, are very important. Currently, two non-animal tests for photosafety evaluations, the in vitro 3T3 neutral red uptake phototoxicity test (NRU PT) and the reactive oxygen species (ROS) assay, are used to detect photoreactive chemicals. However, these two tests are difficult to apply to hydrophobic chemicals. In the present study, we attempted to develop a new photosafety test method, named the electron spin resonance-based photosafety test (ESR-PT), that would be applicable even to hydrophobic chemicals based on the detection of singlet oxygen generation after irradiation using ESR spectroscopy with 4-hydroxy-2,2,6,6-tetramethyl-piperidine as a spin trap reagent. To achieve a quantitative evaluation, the singlet oxygen formation (SOF) value, which can be calculated as the increment in relative intensity after irradiation of the test mixture normalized by the increment in relative intensity after irradiation of the vehicle control solution, was calculated. The performance of the ESR-PT was evaluated by testing all the proficiency chemicals of the ROS assay plus additional chemicals, including hydrophobic chemicals and chemicals that tested false negative in the 3T3-NRU PT and ROS assay. SOF values were successfully calculated for all the chemicals tested including the hydrophobic chemicals, and the accuracy of the ESR-PT using a tentative cutoff value of 2.8 against the photosafety information was 100%. Therefore, the SOF value could be an effective parameter for photosafety evaluations, suggesting that the newly developed ESR-PT is a promising non-animal test applicable even to hydrophobic chemicals., (© 2020 John Wiley & Sons, Ltd.)

One of the most challenging areas in regulatory science is assessment of the substances known as UVCB (unknown or variable composition, complex reaction products and biological materials). Because the inherent complexity and variability of UVCBs present considerable challenges for establishing sufficient substance similarity based on chemical characteristics or other data, we hypothesized that new approach methodologies (NAMs), including in vitro test-derived biological activity signatures to characterize substance similarity, could be used to support grouping of UVCBs. We tested 141 petroleum substances as representative UVCBs in a compendium of 15 human cell types representing a variety of tissues. Petroleum substances were assayed in dilution series to derive point of departure estimates for each cell type and phenotype. Extensive quality control measures were taken to ensure that only high-confidence in vitro data were used to determine whether current groupings of these petroleum substances, based largely on the manufacturing process and physico-chemical properties, are justifiable. We found that bioactivity data-based groupings of petroleum substances were generally consistent with the manufacturing class-based categories. We also showed that these data, especially bioactivity from human induced pluripotent stem cell (iPSC)-derived and primary cells, can be used to rank substances in a manner highly concordant with their expected in vivo hazard potential based on their chemical compositional profile. Overall, this study demonstrates that NAMs can be used to inform groupings of UVCBs, to assist in identification of repre­sentative substances in each group for testing when needed, and to fill data gaps by read-across.

Tattooing entails a high amount of tattoo colorants that is injected into skin. Tattoo colorants usually contain various substances of which the colouring component is the major ingredient that can be assigned to two different groups. Firstly, amorphous carbon particles (carbon black) are almost exclusively found in black tattoos. Secondly, tattooists use azo and polycyclic pigments to create nearly all colours of the visible spectrum. Due to their different but frequently complex chemistry, tattoo colorants usually contain various compounds like by-products and impurities which may exhibit health concerns. Professional tattooists inject that mixture into skin using the solid needles of tattoo machines. It is known that part of injected tattoo colorants is predominantly transported away from skin via lymphatic system. In addition to tattooing, exposure of tattooed skin to solar radiation or laser light may cause decomposition of pigment molecules leading to new and potential hazard chemical compounds. In light of the various hazard substances in the tattoo colorants and its decomposition products, tattooing might pose a health risk not only to skin but also to other organs of humans., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

A sampling, modulation, and separation (SMS) unit was tested for detection of hazardous chemicals. The SMS unit, designed and developed for on-site sampling and analysis, consists of a dynamic inlet system coupled with a fast, miniaturized gas chromatograph (GC). Feasibility of the SMS unit was evaluated together with a hazardous chemical vapor generator. The performance of the SMS unit was tested with automated thermal desorption after SMS to collect samples for GC-mass spectrometry (GC-MS) measurements. Detection of sarin nerve agent was verified. Additionally, the vapor generator was connected to the SMS unit, which was hyphenated with a photoionization detector (PID), thus creating a fast GC-PID system. This system gave a positive response for degradation products of sulfur mustard, thereby indicating suitability of the SMS-PID unit for field drone applications.

This review aims to elucidate the current knowledge and future research needs regarding the hazard potential of nanocellulose to human health. Growing interest from research and industry alike has led to increasing likelihood of human contact to the material via various exposure routes. Although a number of comprehensive reviews on human health hazards of nanocellulose have been conducted, this paper brings new insights as it systematically analyzes and quantitatively assesses the results of in vivo and in vitro tests in terms of investigated endpoints, tested concentration ranges, physicochemical properties, surface modifications and source of the tested nanocellulose, exposure route, and cell lines used. The quality of the studies is further inspected based on various established criteria. Considering the rapid development of nanocellulose-based products and the novelty of the material, human health studies remain scarce. By assessing those that have been conducted, patterns and gaps were identified that will be helpful to guide future research. The results show that there are still significant uncertainties remaining, particularly regarding in vivo testing, with pulmonary exposure showing some cause for concern. Although a substantial number of in vitro studies have been undertaken, results are often conflicting. The detected effects could not be directly attributed to size of nanoparticles, cell lines, surface modifications or tested concentrations. This may also be linked to the varying quality of the studies. This review ends by identifying key gaps to help pave the way for future research and ensure the safe development and use of nanocellulose.

In the event of a chemical, biological, radiological, or nuclear (CBRN) hazard release, emergency responders rely on respiratory protection to prevent inhalation of these hazards. The National Institute for Occupational Safety and Health's (NIOSH) CBRN Statement of Standard calls for CBRN respirator canisters to be challenged with 11 different chemical test representative agents (TRAs) during certification testing, which represent hazards from 7 distinct Chemical Families; these 11 TRAs were identified during the original 2001 CBRN hazard assessment. CBRN hazards are constantly evolving in type, intent of use, and ways of dissemination. Thus, new and emerging hazards must be identified to ensure CBRN canisters continue to provide protection to emergency responders against all hazards that would most likely be used in an intentional or unintentional event. The objectives are to: (1) update the CBRN list of hazards to ensure NIOSH-approved CBRN canisters continue to provide adequate protection capabilities from newly emerging chemical and radiological hazards and (2) identify the need to update NIOSH TRAs to ensure testing conditions represent relevant hazards. These objectives were accomplished by reviewing recent hazard assessments to identify a list of chemical and radiological respiratory hazards, evaluate chemical/physical properties and filtration behavior for these hazards, group the hazards based on NIOSH's current Chemical Families, and finally compare the hazards to the current TRAs based on anticipated filtration behavior, among other criteria. Upon completion of the evaluation process, 237 hazards were identified and compared to NIOSH's current CBRN TRAs. Of these 237 hazards, 203 were able to be categorized into one of NIOSH's current seven Chemical Families. Five were identified for further evaluation. Based on reviewing key chemical/physical properties of each hazard, NIOSH's current 11 TRAs remain representative of the identified respiratory CBRN hazards to emergency responders and should continue to be used during NIOSH certification testing. Thus, NIOSH's CBRN Statement of Standard remains unchanged. The process developed standardizes a methodology for future hazard evaluations.

While the etiology of non-familial Parkinson's disease (PD) remains unclear, there is evidence that increased levels of tissue iron may be a contributing factor. Moreover, exposure to some environmental toxicants is considered an additional risk factor. Therefore, brain-targeted iron chelators are of interest as antidotes for poisoning with dopaminergic toxicants, and as potential treatment of PD. We, therefore, designed a series of small molecules with high affinity for ferric iron and containing structural elements to allow their transport to the brain via the neutral amino acid transporter, LAT1 (SLC7A5). Five candidate molecules were synthesized and initially characterized for protection from ferroptosis in human neurons. The promising hydroxypyridinone SK4 was characterized further. Selective iron chelation within the physiological range of pH values and uptake by LAT1 were confirmed. Concentrations of 10-20 µM blocked neurite loss and cell demise triggered by the parkinsonian neurotoxicants, methyl-phenyl-pyridinium (MPP + ) and 6-hydroxydopamine (6-OHDA) in human dopaminergic neuronal cultures (LUHMES cells). Rescue was also observed when chelators were given after the toxicant. SK4 derivatives that either lacked LAT1 affinity or had reduced iron chelation potency showed altered activity in our assay panel, as expected. Thus, an iron chelator was developed that revealed neuroprotective properties, as assessed in several models. The data strongly support the role of iron in dopaminergic neurotoxicity and suggests further exploration of the proposed design strategy for improving brain iron chelation.

Read-across based on only structural similarity is considered to have a risk of error in chemical risk assessment. Under these circumstances, considering biological similarity based on adverse outcome pathways using in vitro omics technologies is expected to enhance the accuracy and robustness of conclusions in read-across. However, due to a lack of practical case studies, key considerations and use of these technologies for data gap filling are not well discussed. Here we extracted and compared the potential mechanisms for hepatotoxicity for structural analogs of p-dialkoxy chlorobenzenes including 1,4-dichloro-2,5-dimethoxybenzene (DDMB), 2,5-dichloro-1,4-diethoxybenzene (DDEB), 2-chloro-1,4-dimethoxybenzene (CDMB), and 1-chloro-2,5-diethoxybenzene (CDEB) using in vitro omics technologies for read-across. To reveal the potential mechanisms for hepatotoxicity, we conducted microarray analysis with rat primary hepatocytes. The results showed that three (DDMB, DDEB, CDEB) of the four chemicals affected similar biological pathways such as peroxisome proliferation, oxidative stress, and mitochondrial dysfunction. Furthermore, these biological pathways are consistent with in vivo hepatotoxicity in the source chemical, DDMB. In contrast, CDMB did not affect a specific toxicological pathway. Taken together, these data show the potential mechanisms for hepatotoxicity for three chemicals (DDMB, DDEB, CDEB) and provide novel insights into grouping chemicals using in vitro toxicogenomics for read-across., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

At the 2019 annual meeting of the European Environmental Mutagen and Genomics Society a workshop session related to the use of read across concepts in toxicology was held. The goal of this session was to provide the audience an overview of general read-across concepts. From ECHA's read across assessment framework, the starting point is chemical similarity. There are several approaches and algorithms available for calculating chemical similarity based on molecular descriptors, distance/similarity measures and weighting schemata for specific endpoints. Therefore, algorithms that adapt themselves to the data (endpoint/s) and provide a good ability to distinguish between structural similar and not similar molecules regarding specific endpoints are needed and their use discussed. Toxico-dynamic end points are usually in the focus of read across cases. However, without appropriate attention to kinetics and metabolism such cases are unlikely to be successful. To further enhance the quality of read across cases new approach methods can be very useful. Examples based on a biological approach using plasma metabolomics in rats are given. Finally, with the availability of large data sets of structure activity relationships, in silico tools have been developed which provide hitherto undiscovered information. Automated process is now able to assess the chemical - activity space around the molecule target substance and examples are given demonstrating a high predictivity for certain endpoints of toxicity. Thus, this session provides not only current state of the art criteria for good read across, but also indicates how read-across can be further developed in the near future., (Copyright © 2020 Elsevier B.V. All rights reserved.)

We investigated the responses of microRNAs (miRNAs) using mouse embryonic stem cells (mESCs) exposed to nine chemicals (bis(2-ethylhexyl)phthalate, p-cresol, p-dichlorobenzene, phenol, pyrocatecol, chloroform, tri-n-butyl phosphate, trichloroethylene, and benzene), which are listed as "Class I Designated Chemical Substances" from the Japan Pollutant Release and Transfer Register. Using deep sequencing analysis (RNA-seq), several miRNAs were identified that show a substantial response to general chemical toxicity (i.e., to these nine chemicals considered as a group) and several miRNA biomarkers that show a substantial and specific response to benzene. The functions of the identified miRNAs were investigated in accordance with Gene Ontology terms of their predicted target genes, indicating regulation of cellular processes. We compared the results with those for the long non-coding RNAs (ncRNAs) and mRNAs reported in our previous studies in addition to previously identified miRNAs that are either up- or down-regulated in response to the benzene as stimuli. We also observed that the changes in expression of miRNAs were smaller than those for long ncRNAs and mRNAs. Taken together the current and previous results revealed that toxic chemical stimuli regulate the expression of miRNAs. We believe that the use of miRNAs, including the thus identified miRNAs, as biomarkers contribute to predicting the potential toxicity of particular chemicals or identifying human individuals that have been exposed to chemical hazards., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The determination of Cd, Co, Cr, Cu, Fe, Na, Zn, and Pb by inductively coupled plasma-optical emission spectrometry (ICP OES) was performed on dry matter and decoctions of the medicinal plants Cordia salicifolia , Chiococca alba (L.) Hitchc., and Echites peltata used as an appetite suppressant and diuretic in Brazil. The accuracy of the measurements was analyzed by the spike recovery test. Results showed that the concentration of these seven metals (Cd, Co, Cr, Cu, Fe, Na, and Zn) in dry plant samples is below the oral concentration of elemental impurities established by the United States Pharmacopoeia Convention (USP). However, there are no concentration limits for Fe, Na, and Zn established by the USP in drug substances and excipients. Levels higher than the recommended value by the USP were observed for Pb and the lowest for Cd, Co, Cr, and Cu, both in dried plant samples and their decoctions. In the decoctions prepared from these plants were found elements such as Cd, Co, Cr, Cu, Fe, Na, Zn, and Pb. In the decoction prepared from 40 g C. salicifolia leaves and 40 g C. alba wood, the content of Cd is above the oral daily exposure value set by the USP. Hazard index (HI) for decoctions prepared from these plants exceeded the threshold (1). Given the uncertainties associated with the estimates of toxicity values and exposure factors, futures researches should address the possible toxicity in humans. Uncontrolled selling and long-term ingestion of medicinal plants can cause toxicity and interfere with the effect of drugs. Limited knowledge on the interaction potential of medicinal plants poses a challenge and public health problem in Brazil and other countries., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 Paula F. S. Tschinkel et al.)

Ionizable organic chemicals (IOCs) such as organic acids and bases are an important substance class requiring aquatic hazard evaluation. Although the aquatic toxicity of IOCs is highly dependent on the water pH, many toxicity studies in the literature cannot be interpreted because pH was not reported or not kept constant during the experiment, calling for an adaptation and improvement of testing guidelines. The modulating influence of pH on toxicity is mainly caused by pH-dependent uptake and bioaccumulation of IOCs, which can be described by ion-trapping and toxicokinetic models. The internal effect concentrations of IOCs were found to be independent of the external pH because of organisms' and cells' ability to maintain a stable internal pH milieu. If the external pH is close to the internal pH, existing quantitative structure-activity relationships (QSARs) for neutral organics can be adapted by substituting the octanol-water partition coefficient by the ionization-corrected liposome-water distribution ratio as the hydrophobicity descriptor, demonstrated by modification of the target lipid model. Charged, zwitterionic and neutral species of an IOC can all contribute to observed toxicity, either through concentration-additive mixture effects or by interaction of different species, as is the case for uncoupling of mitochondrial respiration. For specifically acting IOCs, we recommend a 2-step screening procedure with ion-trapping/QSAR models used to predict the baseline toxicity, followed by adjustment using the toxic ratio derived from in vitro systems. Receptor- or plasma-binding models also show promise for elucidating IOC toxicity. The present review is intended to help demystify the ecotoxicity of IOCs and provide recommendations for their hazard and risk assessment. Environ Toxicol Chem 2020;39:269-286. © 2019 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC., (© 2019 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC.)

The main source of nitroaromatic compounds in nature is anthropogenic activities. In the present report, a facile and green method was employed to fabricate highly efficient catalyst to turn toxic nitrophenols to more safe aminophenols. The Fe 3 O 4 /Ag@Ca-Al LDH hybrid (FAL hybrid) was synthesized by the Fe 3 O 4 and Ag nanoparticles supported on layer double hydroxide (LDH) and the bionanocomposite (BNC) of this hybrid and starch was prepared via an in situ growth method. The FAL hybrid and BNC were characterized by different techniques. The reduction reaction of 4-nitrophenol in the presence of these catalysts indicated that both of them have high catalytic activity due to their large numbers of hydroxyl groups as capping agent. The comparison rate kinetics study between 4-nitrophenol and 2-nitrophenol showed that the FALS-BNC has higher potential in the case of the para derivative. Also, catalysts were recovered without difficulty and reused after completion of the reduction reaction., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Understanding the physicochemical characteristics of oil-based cuttings (OBCs) is an important foundation for subsequent treatment and management. The macro- and microscopic properties of white oil-based cuttings (WOBCs) and diesel-based cuttings (DBCs) after the different pretreatment steps have been assessed using scanning electron microscopy. The organic and inorganic compositions of OBCs have been analyzed using X-ray diffraction, Fourier-transform infrared spectrometry, and gas chromatography-mass spectrometry. Inorganic matter (SiO 2 , BaSO 4 , and CaCO 3 ), alkanes, aromatic compounds, and water were the main components of OBCs. The organic content (26.14%) and alkane content of the WOBCs were higher than that of the DBCs, whereas for the inorganic content (70.87%), the reverse was true. The macro- and micromorphologies of OBCs were quite different because their oil and water contents were different. The oil contents of OBCs decreased in the order A1 (14.64%) > A3 (12.67%) > A2 (11.06%) and B1 (9.19%) > B3 (8.94%) > B2 (4.66%); the water contents decreased in the order A1 (2.99%) > A3 (2.19%) > A2 (1.09%) and B1 (2.30%) > B3 (1.87%) > B2 (1.09%). Moreover, a skid-mounted treatment technology for OBCs was proposed. The results can be a scientific guidance for the treatment and management of OBCs.

Read-across (RAX) is a popular data-gap filling technique that uses category and analogue approaches to predict toxicological endpoints for a target. Despite its increasing relevance, RAX relies on human expert judgement and lacks a reproducible and automated protocol. It also only relies on structural similarity for identifying the analogues, while other aspects are often neglected. In this paper, we propose an automated procedure for the selection of analogues for data gap-filling. Analogues were identified with a decision algorithm that integrates three similarity metrics, each considering different toxicologically relevant aspects (i.e., structural, biological and metabolic similarity). Structural filters based on the presence of maximum common substructures (MCS) and common functional groups were applied to narrow the chemical space for the analogues search. The procedure has been implemented as a workflow in KNIME and is freely available. The workflow provides informative tabular and graphical outputs to support toxicologists and risk assessors in drawing conclusion based on the RAX approach. The procedure has been validated for its predictive power on two datasets related to high-tier in vivo toxicological endpoints, i.e. human hepatotoxicity and drug-induced liver injury (DILI). The validation results gave good accuracy values (i.e., up to 0.79 for the binary hepatotoxicity classification and up to 0.67 for the three-class DILI classification) that were higher than those returned by RAX based on the sole use of structural similarity. Results confirmed the suitability of the procedure as a source of data to support regulatory decision-making.

United States Pharmacopeia Chapter <800>, concerned with the handling of hazardous drugs in healthcare settings, requires that any entity handling such drugs maintain a hazardous drug list. While this list must include any drug found on the latest NIOSH List of Antineoplastic and Other Hazardous Drugs in Health Settings, entities are expected to include other drugs and substances of concern. The intent of this article is to provide concrete information concerning articles of personal protective equipment, as well as guidance as to where and how they should be donned, used, and removed. This information will cover every aspect of handling hazardous drugs from receipt to disposal, most certainly including both sterile and nonsterile compounding., (Copyright© by International Journal of Pharmaceutical Compounding, Inc.)

Silver nanoparticles (AgNPs) have been widely used for a multitude of applications without full comprehensive knowledge regarding their safety. In particular, lack of data on hazard characterization may lead to uncertainties regarding potential human health risk. To provide the foundation for human health risk assessment of AgNPs, this study evaluates existing hazard characterization data, including reported pharmacokinetics, symptoms, and their corresponding dose-response relationships. Human equivalent relationships are also provided by extrapolation from animal dose-response relationships. From the data analyzed, it appears that AgNPs may persist for long periods (from days to years) in the human body. It was found that AgNP toxicity on traditional major targets of exogenous substances were generally underestimated. Some omissions of toxicity on sensitive systems in the AgNP toxicity assessment require attention, such as reprotoxicity and neurotoxicity. The necessity of the establishment of toxicity tests specifically for nanomaterials is highlighted. The scientific basis of a toxicity testing strategy is advised by this study, which paves the way for the monitoring and regulation of the ENP utilization in various industries.

Advancements on analytical strategies to determine the chemicals present in treated wastewater are necessary to clearly link their occurrence with the ecotoxicity of such effluents. This study describes the development of an integrated screening approach to determine the highest number of pharmaceutical transformation products (TPs) in a single run. The identification of TPs was based on the comparison of detected features with literature sources, compound prediction tools, in-house libraries and reference standards using high-resolution mass spectrometry (HRMS). This integrated approach allowed a better estimation (in silico) of the ecotoxicological contribution of the individual TPs identified. As a proof of concept, this methodology was applied for identification of the TPs generated from metoprolol and its main human metabolite (metoprolol acid) in pure water, hospital wastewater and industrial wastewater treated by UV/H 2 O 2 . Twenty-four TPs with potential ecotoxicological implications were identified and their presence was pinpointed as a function of the treated wastewater. An integrated screening approach has been developed using four different screening methodologies in the same run. Additionally, the metabolite MTPA has been considered as a target pollutant in UV/H 2 O 2 experiments., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Alkylation reaction catalyzed by concentrated H 2 SO 4 generates hazardous waste H 2 SO 4 containing a large amount of organic pollutants. This study focused on effective utilization and treatment of the waste H 2 SO 4 for simultaneous consumption of H 2 SO 4 and deep oxidative degradation of the organics. The waste H 2 SO 4 could completely react with magnesium oxide ore to prepare crude MgSO 4 solution, and the organic pollutants in the solution were deeply degraded and mainly mineralized to H 2 O and CO 2 with H 2 O 2 as oxidant and sugarcane bagasse citrate (SBC), a kind of lignocellulose ester, as catalyst. The total amount of acidic groups of SBC significantly affected its catalytic activity, attributing to that these oxygen-containing functional groups adsorbed and immobilized metal ions on SBC to form catalytic active sites, which could activate and catalyze H 2 O 2 to generate •OH and HO 2 • radicals for effective degradation of the organics. The resulting purified MgSO 4 solution with color removal of 93.71% and total organic carbon removal of 85.89% under optimum catalytic reaction conditions was used to produce qualified MgSO 4 ∙7H 2 O product. These results highlighted the feasibility of using lignocellulose ester as effective catalyst for deep oxidative degradation of hazardous organic pollutants., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Mixed matrix membranes (MMMs) provide a unique pathway to treat hazardous industrial effluents. MMMs containing zeolitic imidazolate framework-8 (ZIF-8) as filler in polydimethoxysilane (PDMS) matrix were synthesized. ZIF-8 was prepared using a modified recipe and characterized by different techniques to evaluate its morphology, thermal stability, surface area, pore volume, and other characteristics. The performance of membranes was evaluated for their application in industrial dye-stuff wastewater treatment and solvent-resistant nanofiltration. The results demonstrated that increase in the percentage of ZIF-8 loading in PDMS led to simultaneous increase in the solvent permeability as well as solute rejection from wastewater. The permeability of MMMs increased up to 32% as compared with neat PDMS membrane. The organic dye rejection was achieved more than 87% with MMMs incorporated with 20% loading of nanofillers. Rejection of MMMs was 22% higher than that of unfilled PDMS membrane due to the effect of reduced polymer swelling and size exclusion of the nanofillers. Membrane swelling tests with toluene and isopropanol demonstrated that nanofiller amount has inverse relation with membrane swelling, which implied that nanofillers were in good interaction with polymer and allowed defect free membranes with higher solute rejections and reduced membrane swelling.

Metallothioneins are peculiar cysteine rich, heat resistant, small cellular plasma proteins expressed through almost all life forms. The currently established biological functions of metallothioneins are the homeostasis of essential metals and protection against toxic transitional metals (TM) alongside defence from oxidative stress by direct scavenging of reactive oxygen and nitrogen species (ROS and RNS). In mammals, among the four main evolutionary conserved forms, only the ubiquitously expressed metallothionein 1 and 2 (here abbreviated as MT) are inducible by TM, oxidative stress, glucocorticoids and starvation among various other stimuli. However, more than sixty years after being discovered, metallothioneins still bear unresolved issues about their possible physiological function and regulation. The biological function of MTs has still not been associated with the in vitro-demonstrated capacity of MT interaction with cellular molecules glutathione (GSH) or adenosine triphosphate (ATP), or with the possibility of direct iron-MT binding in the reducing intracellular environment of some organelles, e.g. lysosomes. Iron as the most abundant cellular TM is also one of the main physiological sources of ROS. Moreover, iron exhibits strain, sex and age differences that reflected ROS generation and MT induction in (patho)physiology and toxicology studies. A recent study showed that iron sex differences follows expression of both ferritin and MT leading to wide implications from essential TM interconnectivity to aging. This review places emphasis on biochemically proven but physiologically ignored interactions of MT with iron to stimulate advanced research for establishing a wide frame of the biological roles of MTs important for health and longevity.

The control of permeation is vital not only for the topical application of lotions, creams, and ointments but also for the toxicological and risk assessment of materials from environmental and occupational hazards. To understand the effects of physicochemical properties of a variety of 211 compounds on skin permeability, we developed a three-dimensional quantitative structure-property relationship (3 D-QSPR) model. Alignment free GRid-INdependent Descriptors (GRINDs), which were derived from molecular interaction fields (MIFs) contributed to the regression models. Kennard-Stone algorithm was employed to split data set to a training set of 159 molecules and a test set of 52 molecules. Fractional factorial design (FFD), genetic algorithm (GA) and successive projection algorithm (SPA) were applied to select the most relevant 3 D molecular descriptors. The descriptors selected using various feature selection were correlated with skin permeability constants by partial least squares (PLS) and support vector machine (SVM). SPA-SVM model gave prominent statistical values with the correlation coefficient of [Formula: see text]= 0.96, Q 2 = 0.73 and R 2 pred =0.76. According to the analysis results, the hydrogen bonding donor and acceptor properties of the investigated compounds can influence the penetration into the human skin. Furthermore, it was found that permeability was enhanced by increasing the hydrophobicity and was diminished by increasing the molecular weight. In addition, the presence of hydrophobic groups in the target molecule, as well as their shape and position, can affect the skin permeability.

The Toxicity Reference Database (ToxRefDB) structures information from over 5000 in vivo toxicity studies, conducted largely to guidelines or specifications from the US Environmental Protection Agency and the National Toxicology Program, into a public resource for training and validation of predictive models. Herein, ToxRefDB version 2.0 (ToxRefDBv2) development is described. Endpoints were annotated (e.g. required, not required) according to guidelines for subacute, subchronic, chronic, developmental, and multigenerational reproductive designs, distinguishing negative responses from untested. Quantitative data were extracted, and dose-response modeling for nearly 28,000 datasets from nearly 400 endpoints using Benchmark Dose (BMD) Modeling Software were generated and stored. Implementation of controlled vocabulary improved data quality; standardization to guideline requirements and cross-referencing with United Medical Language System (UMLS) connects ToxRefDBv2 observations to vocabularies linked to UMLS, including PubMed medical subject headings. ToxRefDBv2 allows for increased connections to other resources and has greatly enhanced quantitative and qualitative utility for predictive toxicology., (Copyright © 2019. Published by Elsevier Inc.)

The Hg-C bond of MeHgCl, a ubiquitous environmental toxicant, is notoriously inert and exceedingly difficult to cleave. The cleavage of the Hg-C bond of MeHgCl at low temperature, therefore, is of significant importance for human health. Among various bis(imidazole)-2-selones L n Se (n=1-4, or 6), the three-spacer L 3 Se shows extraordinarily high reactivity in the degradation of various mercury alkyls including MeHgCl because of its unique ability to coordinate through κ 2 -fashion, in which both the Se atoms simultaneously attack the Hg center of mercury alkyls for facile Hg-C bond cleavage. It has the highest softness (σ) parameter and the lowest HOMO(L n Se)-LUMO(MeHgX) energy gap and, thus, L 3 Se is the most reactive among L n Se towards MeHgX (X=Cl or I). L 3 Se is highly efficient, more than L 1 Se, in restoring the activity of antioxidant enzyme glutathione reductase (GR) that is completely inhibited by MeHgCl; 80 % GR activity is recovered by L 3 Se relative to 50 % by L 1 Se. It shows an excellent cytoprotective effect in liver cells against MeHgCl-induced oxidative stress by protecting vital antioxidant enzymes from inhibition caused by MeHgCl and, thus, does not allow to increase the intracellular reactive oxygen species (ROS) levels. Furthermore, it protects the mitochondrial membrane potential (ΔΨ m ) from perturbation by MeHgCl. Major Hg-responsive genes analyses demonstrate that L 3 Se plays a significant role in MeHg + detoxification in liver cells., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

An extension of the transformation/dissolution protocol (T/DP) was developed and evaluated as a tool to measure the removal of metals from the water column for chronic aquatic hazard classification. The T/DP extension (T/DP-E) consists of 2 parts: T/DP-E part 1, to measure metal removal from the water column via binding of metals to a substrate and subsequent settling, and T/DP-E part 2, to assess the potential for remobilization of metals following resuspension. The T/DP-E methodology (672-h [28-d] removal period, 1-h resuspension event, and 96-h resettling period) was tested using Cu, Co, and Sr solutions in the presence of a substrate. The metal removal rates varied from rapid removal for Cu to slower rates of removal for Co and Sr. The resuspension event did not trigger any increase in dissolved Cu, Co, or Sr. Additional 96-h experiments were conducted using dissolved Ni, Pb, Zn, and Ag and supported the conclusion that the T/DP-E is sufficiently robust to distinguish removal rates between metals with a wide range of reactivities. The proposed method provides a means to quantify the rate of metal removal from the water column and evaluate remobilization potential in a standardized and reliable way. Environ Toxicol Chem 2019;38:2032-2042. © 2019 SETAC., (© 2019 SETAC.)

Consumer goods and building materials present in the preschool environment can be important sources of hazardous chemicals, such as plasticizers, bisphenols, organophosphorus and brominated flame retardants, poly- and perfluoroalkyl substances, which may pose a health risk to children. Even though exposure occurs via many different pathways, such as food intake, inhalation, dermal exposure, mouthing of toys etc., dust has been identified as a valuable indicator for indoor exposure. In the present study, we evaluate the efficiency of product substitution actions taken in 20 Swedish preschools from the Stockholm area to reduce the presence of hazardous substances in indoor environments. Dust samples were collected from elevated surfaces in rooms where children have their everyday activities, and the concentrations found were compared to the levels from a previous study conducted in 2015 at the same preschools. It was possible to lower levels of hazardous substances in dust, but their continued presence in the everyday environment of children was confirmed since bisphenol A, restricted phthalates and organophosphate esters were still detectable in all preschools. Also, an increase in the levels of some of the substitutes for the nowadays restricted substances was noted; some of the alternative plasticizers to phthalates, such as DEHA and DEHT, were found with increased concentrations. DINP was the dominant plasticizer in preschool dust with a median concentration of 389 μg/g, while its level was significantly (p = 0.012) higher at 716 μg/g in preschools with polyvinyl chloride (PVC) flooring. PBDEs were now less frequently detected in dust and their levels decreased 20% to 30%. This was one of the few times that PFAS were analyzed in preschool dust, where 6:2 diPAP was found to be most abundant with a median concentration of 1140 ng/g, followed by 6:2 PAP 151 ng/g, 8:2 diPAP 36 ng/g, N-Et-FOSAA 18 ng/g, PFOS 12 ng/g, PFOA 7.7 ng/g and PFNA 1.1 ng/g. In addition, fluorotelomer alcohols were detected in 65-90% of the samples. Children's exposure via dust ingestion was evaluated using intermediate and high daily intake rates of the targeted chemicals and established health limit values. In each case, the hazard quotients (HQs) were < 1, and the risk for children to have adverse health effects from the hazardous chemicals analyzed in this study via dust ingestion was even lower after the product substitution actions were taken in preschools., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Read-across has become a primary approach to fill data gaps for chemical safety assessments. Chemical similarity based on structure, reactivity, and physic-chemical property information is a traditional approach applied for read-across toxicity studies. However, toxicity mechanisms are usually complicated in a biological system, so only using chemical similarity to perform the read-across for new compounds was not satisfactory for most toxicity endpoints, especially when the chemically similar compounds show dissimilar toxicities. This study aims to develop an enhanced read-across method for chemical toxicity predictions. To this end, we used two large toxicity datasets for read-across purposes. One consists of 3979 compounds with Ames mutagenicity data, and the other contains 7332 compounds with rat acute oral toxicity data. First, biological data for all compounds in these two datasets were obtained by querying thousands of PubChem bioassays. The PubChem bioassays with at least five compounds from either of these two datasets showing active responses were selected to generate comprehensive bioprofiles. The read-across studies were performed by using chemical similarity search only and also by using a hybrid similarity search based on both chemical descriptors and bioprofiles. Compared to traditional read-across based on chemical similarity, the hybrid read-across approach showed improved accuracy of predictions for both Ames mutagenicity and acute oral toxicity. Furthermore, we could illustrate potential toxicity mechanisms by analyzing the bioprofiles used for this hybrid read-across study. The results of this study indicate that the new hybrid read-across approach could be an applicable computational tool for chemical toxicity predictions. In this way, the bottleneck of traditional read-across studies can be overcome by introducing public biological data into the traditional process. The incorporation of bioprofiles generated from the additional biological data for compounds can partially solve the "activity cliff" issue and reveal their potential toxicity mechanisms. This study leads to a promising direction to utilize data-driven approaches for computational toxicology studies in the big data era., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Red mud is a solid waste of bauxite processing by Bayer process which involves caustic digestion of Al-containing mineral for alumina production. The global inventory of red mud waste reached an estimated amount of 4 billion tons in 2015, increasing at an approximate rate of 120 million tons per year. Therefore, its management is becoming a global environmental issue for the protection of environment, and the need for awareness in this regard is becoming crucial. Although red mud is not considered as a hazardous material in many countries, its high alkalinity and fine particle size may pose significant environmental threat, and it is found to be an interesting material for environmental remediation purposes due to rich iron content. This paper provides a review of possible remedial applications of red mud in various environmental compartments. Modification of red mud creates novel opportunities for cost-effective and efficient removal of metal ions, inorganic anions, dyes, and phenols from wastewater and acid mine drainage. Re-vegetation of red mud disposal sites, treatment of metal-contaminated acidic soils presents the usefulness of this material but less research has been done so far to investigate its use in the stabilization of polluted sediments. On the other hand, leaching and eco-toxicological tests have also revealed that red mud does not pose high toxicity to the environment making it suitable for the treatment of contaminated media. Nevertheless, neutralization of red mud is recommended for its safe disposal and secure application in any environmental media.

Application factors are routinely applied in the extrapolation of laboratory aquatic toxicity data to ensure protection from exposure to chemicals in the natural environment. The magnitude of the application factor is both a scientific and a policy decision, but in any case, it should be rooted in scientific knowledge so as to not be arbitrary. Information-rich chemicals are often subjected to species sensitivity distribution (SSD) analysis to transparently describe certain aspects of assessment uncertainty and are normally subjected to much smaller application factors than screening information data sets. We describe a new set of tools useful to assess the quality of SSDs. Twenty-two data sets and 19 chemicals representing agrochemicals, biocides, surfactants, metals, and common wastewater contaminants were compiled to demonstrate how the tools can be used. "Add-one-in" and "leave-one-out" simulations were used to investigate SSD robustness and develop quantitative evidence for the use of application factors. Theoretical new toxicity data were identified for add-one-in simulations based on the expected probabilities necessary to lower the hazardous concentration to 5% of a species (HC5) by a factor of 2, 3, 5, or 10. Simulations demonstrate the basis for application factors in the range of 1 to 5 for well-studied chemicals with high-quality SSDs. Leave-one-out simulations identify the fact that the most influential values in the SSD come from the extremes of the sensitive and tolerant toxicity values. Mesocosm and field data consistently demonstrate that HC5s are conservative, further justifying the use of small application factors for high-quality SSDs. Environ Toxicol Chem 2019;38:1526-1541. © 2019 SETAC., (© 2019 SETAC.)

We propose a framework on sample size for species sensitivity distribution (SSD) analyses, with perspectives on Bayesian, frequentist, and even nonparametric approaches to estimation. The intent of a statistical sample size analysis is to ensure that the implementation of a statistical model will satisfy a minimum performance standard when relevant conditions are met. It requires that a statistical model be fully specified and that the means of measuring its performance as a function of sample size be detailed. Defining the model conditions under which sample size is calculated is often the most difficult, and important, aspect of sample size analysis because if the model is not representative, then the sample size analysis will provide incorrect guidance. Definitive guidance on sample size requires general agreement on representative models and their performance from stakeholders in important domains such as chemical safety assessments involving government regulators and industry; the present study provides an initial framework that could be used to this end in the future. In addition, our analysis provides immediate value for understanding how well current SSD analyses perform under a few basic models, sample sizes, and quantitative performance criteria. The results confirm that many analyses are adequately sized to estimate hazardous concentration percentile values (typically the 5th percentile for chemical hazard assessments). However, on the low end of sizes seen in common practice, hazardous concentration estimates can be more than 1 order of magnitude greater than the model-defined value. Environ Toxicol Chem 2019;38:1514-1525. © 2019 SETAC., (© 2019 SETAC.)

We previously demonstrated that the Connectivity Map (CMap) (Lamb et al., 2006) concept can be successfully applied to a predictive toxicology paradigm to generate meaningful MoA-based connections between chemicals (De Abrew et al., 2016). Here we expand both the chemical and biological (cell lines) domain for the method and demonstrate two applications, both in the area of read across. In the first application we demonstrate CMap's utility as a tool for testing biological relevance of source chemicals (analogs) during a chemistry led read across exercise. In the second application we demonstrate how CMap can be used to identify functionally relevant source chemicals (analogs) for a structure of interest (SOI)/target chemical with minimal knowledge of chemical structure. Finally, we highlight four factors: promiscuity of chemical, dose, cell line and timepoint as having significant impact on the output. We discuss the biological relevance of these four factors and incorporate them into a work flow., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Predicting the diffusion rule of toxic gas plays a distinctly important role in emergency capability assessment and rescue work. Among diffusion prediction models, the traditional artificial neural network has exhibited excellent performance not only in prediction accuracy but also in calculation time. Nevertheless, with the continuous development of deep learning and data science, some new prediction models based on deep learning algorithms have been shown to be more advantageous because their structure can better discover internal laws and external connections between input data and output data. The long short-term memory (LSTM) network is a kind of deep learning neural network that has demonstrated outstanding achievements in many prediction fields. This paper applies the LSTM network directly to the prediction of toxic gas diffusion and uses the Project Prairie Grass dataset to conduct experiments. Compared with the Gaussian diffusion model, support vector machine (SVM) model, and back propagation (BP) network model, the LSTM model of deep learning has higher prediction accuracy (especially for the prediction at the point of high concentration values) while avoiding the occurrence of negative concentration values and overfitting problems found in traditional artificial neural network models.

Reduced graphene oxide (rGO) is relied upon to be the most promising candidate for high-proficiency. Hydrazine is the most conventional efficient reducing agent that has been frequently used for reduction of graphene oxide, however, it is not environmentally safe due to its toxic nature, causing unsatisfactory defects on the basal plan of GO. Therefore, employing green and efficient reducing agents from natural sources like plant extracts has become the research interest for obtaining high quality reduced graphene oxide sheets in recent years. Here a one-step, easy, cost-effective and green synthesis method based on Nettle leaves' extract has been introduced as an effective reduction method of graphene oxide compared with the toxic and harmful Hydrazine hydrate substance. In this study, GO and rGO were obtained from various methods and characterized by Raman spectroscopy, field emission scanning electron microscope, high-resolution transmission electron microscope (HR-TEM), X-ray diffraction analysis (XRD) and X-ray photon spectroscopy (XPS) analysis. Results of different analytical techniques revealed that the Nettle leaves' extract could successfully reduce GO sheets to high performance reduced graphene oxide with 79% efficiency in comparison with conventional Hydrazine hydrate. On the other side the rGO obtained by Nettle solution could scavenge the free radicals with 70% inhibition capacity at least concentration. Existence of Histamine and Serotonin and many other polyphenols as a part of Nettle leaves composition by following anti-oxidants mechanisms (H donation or electron transfer) promote the anti-oxidant functionality of Nettle leaves. So the highlighted achievement of this paper is to obtain a highly anti-oxidant green reduced graphene oxide with a wide applications i.e medical and polymer composite with UV-shielding activity., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Environmental pollution is one of the most serious problems facing mankind today, and has attracted widespread attention worldwide. The burgeoning class of crystalline porous organic framework materials, metal-organic frameworks and covalent organic frameworks present promising application potential in areas related to pollution control due to their interesting surface properties. In this review, the literature of the past five years on the adsorptive removal of various hazardous materials, mainly including heavy metal ions, harmful gases, organic dyes, pharmaceutical and personal care products, and radionuclides from the environment by using COFs and MOFs, is summarized. The adsorption mechanisms are also discussed to help understand their adsorption performance and selectivity. Additionally, some insightful suggestions are given to enhance the performance of MOFs and COFs in the adsorptive removal of various hazardous materials., (Copyright © 2019. Published by Elsevier B.V.)