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Insect cell lines are finding utility in many areas of biology, but their application as an in vitro tool for ecotoxicity testing has been given less attention. Our study aimed to demonstrate the utility and sensitivity of Sf21 cells to commonly used fungicides: Propiconazole and CuSO4, as well as dimethyl sulphoxide (DMSO) an industrial solvent. Sf21 cells were readily cultured from frozen stocks in 3-4 days and showed utility as an invertebrate in vitro acute toxicity test. The data showed the threshold levels of cell survivability against propiconazole and CuSO4. The EC50 values were 135.1 µM and 3.31 mM respectively. The LOAEL (lowest observed adverse effect level) was ≈ 1 µM for propiconazole and ≈ 10 µM for CuSO4. Culturing of Sf21 cells in media containing the solvent DMSO showed that 0.5% DMSO concentration did not effect cell viability. Sf21 cells are sensitive and useful as a robust ecologically relevant screening tool for acute toxicity testing.
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Exposure to metal(loid)s can cause adverse health effects. This study evaluated the concentrations of aluminum, arsenic, cadmium, chromium, mercury, nickel, and lead in particulate matter <10 µm (PM10) and in the urine of 100 participants from urban residential areas in Iran. A total of 100 residential buildings (one adult from each household) in six cities across Iran were recruited for this study. The levels of metal(loid)s in PM10 and the urine of participants were measured using acid digestion followed by inductively coupled plasma mass spectrometry (ICP-MS). The average (±SE) PM10 concentration in the buildings was 51.7 ± 3.46 µg/m3. Aluminum and cadmium had the highest and lowest concentrations among the metal(loid)s, averaging 3.74 ± 1.26 µg/m3 and 0.01 ± 0.001 µg/m3, respectively. In 85 % of the samples, the concentration of metal(loid)s in indoor air exceeded WHO air quality standards. Cadmium and lead had the highest and lowest numbers of indoor air samples exceeding the recommended standards, respectively. A significant correlation was found between the concentration of metal(loid)s in urine samples and indoor PM10 levels, as well as the wealth index of participants. There was also a significant direct relationship between the concentrations of nickel, arsenic, lead, and mercury in urine and the age of participants. Factors such as building location, type of cooling systems, use of printers at home, and natural ventilation influenced the concentration and types of metal(loid)s in the indoor air.
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Contaminantes Atmosféricos , Contaminación del Aire Interior , Monitoreo Biológico , Exposición a Riesgos Ambientales , Contaminación del Aire Interior/análisis , Contaminación del Aire Interior/estadística & datos numéricos , Irán , Humanos , Contaminantes Atmosféricos/análisis , Exposición a Riesgos Ambientales/análisis , Exposición a Riesgos Ambientales/estadística & datos numéricos , Adulto , Material Particulado/análisis , Ciudades , Metales/análisis , Metales/orina , Masculino , Monitoreo del Ambiente/métodos , Femenino , Arsénico/análisis , Persona de Mediana EdadRESUMEN
In the natural ecosystem, aquatic organisms are exposed to a cocktail of chemicals that may result in toxicological responses differing from those of individual chemicals. In the present study, mussels were exposed using a semi-static and triplicated design to either control (no added metal), 50 µg l-1 (Hg alone), 50 µg l-1 (Cd alone), or 50 µg l-1 Hg plus 50 µg l-1 Cd (Hg + Cd) mixture for 14 days. Tissues were collected on days 0, 2, 4, 8, and 14 for metal analysis and sub-lethal responses using a suite of assays. Tissue metal concentrations were not significantly different in the single metal (Hg or Cd) compared to the Hg plus Cd mixture treatment for all tissues, apart from the gill of the Cd alone treatment. At the end of the experiment, the gill Cd concentration was significantly increased in the Hg plus Cd mixture compared to the Cd alone treatment, suggesting the influence of Hg on Cd uptake. The percentage increases of the Hg plus Cd mixture compared to the arithmetic sum of the individual metals were (â¯%): 20.2, 9.3, 25.1, 23.8, 10.7, and 12.4 for adductor muscle, digestive gland, gill, gonad, remaining soft tissue, and haemolymph, respectively. There were no observed treatment effects on total haemocyte count, haemolymph protein, or glucose concentration in the cell-free haemolymph. Neither was there any treatment effect on osmotic pressure, ions in the tissues, or in the cell-free haemolymph. At the end of the experiment, Hg-mediated oxidative damage, as an increase of thiobarbituric reactive substances (TBARS) and apparent depletion of total glutathione. This was observed in the gill and digestive gland of the Hg alone and Hg plus Cd mixture. Histopathology examination showed similar pathology in the Hg alone and the Hg plus Cd treatment. In conclusion, despite some oxidative stress and pathology during metal exposure, the accumulation of metals and effects on mussel health were similar between single exposures and a mixture of Hg plus Cd. In terms of risk assessment, regulations for the individual metals should suffice to protect against the mixture of Hg plus Cd, at least for adult M. edulis in full-strength seawater.
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Bioacumulación , Cadmio , Branquias , Mercurio , Mytilus edulis , Contaminantes Químicos del Agua , Animales , Contaminantes Químicos del Agua/toxicidad , Cadmio/toxicidad , Mytilus edulis/efectos de los fármacos , Mercurio/toxicidad , Branquias/efectos de los fármacos , Branquias/metabolismoRESUMEN
The present research assessed, for the first time, toxicity of ZIF-8 (1 mg/L) and the building blocks (0.1 mg/L Zn2+ and 0.4 mg/L 2-methylimidazole (2-MIm)), besides that of AgNPs@ZIF-8 (0.25, 0.5, and 1 mg/L) and AgNO3 (0.1 mg/L) to aquatic organisms. Two consecutive generations (F0 & F1) of Artemia salina were exposed to these chemicals. All of the chemical treatments considerably caused mortality in F0, especially AgNPs@ZIF-8 and AgNO3, whereas F1 displayed notable tolerance and survived comparable to the control group, except in the case of AgNO3 treatment. Similarly, growth indices (weight, mainly in ZIF-8, Zn2+, and 2-MIm; length, in Ag-doped ZIF-8 and AgNO3) were significantly retarded in F0 and especially F1 of all treatments, and 2-MIm caused the greatest length retardation in F0. AgNPs@ZIF-8 (0.5 and 1 mg/L), 2-MIm, and AgNO3 postponed the ovary emergence in about 40%-60% of the exposed F0, and ZIF-8 delayed this phenomenon in some individuals of F0 and F1 up to 6 days. This temporal disturbance was also observed in time to first brood of almost all experimental F0 and F1 groups, with being over 80% of F1 exposed to ZIF-8, 2-MIm, and Zn2+, as well as about 50% of F0 treated with 2-MIm, and Zn2+. The highest neonate number was recorded for F0 and F1 exposed to AgNO3 and Zn2+, while ZIF-8 and, importantly, 2-MIm decreased the reproductivity to the lowest levels in both generations. Generally, the reproductive frequency was significantly decreased in all F0 and F1 treatments, especially 2-MIm, ZIF-8, AgNPs@ZIF-8 (0.25 & 1 mg/L). This study highlighted the neglected importance of 2-MIm in assessing overall toxicity of ZIF-8, and even other organic ligands of MOFs, and also filled a gap in the literature by investigating the potential effect of additives such as AgNPs on the toxicity of ZIF-8 and other MOFs.
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Artemia , Nanopartículas , Humanos , Animales , Femenino , Recién Nacido , ReproducciónRESUMEN
Zinc (Zn) is an essential metal present in numerous enzymes throughout the body, playing a vital role in animal and human health. However, the increasing use of zinc oxide nanomaterials (ZnONPs) in a diverse range of products has raised concerns regarding their potential impacts on health and the environment. Despite these concerns, the toxicity of ZnONP exposure on animal health remain poorly understood. To help address this knowledge gap, we have developed a highly sensitive oxidative stress (OS) biosensor zebrafish capable of detecting cell/tissue-specific OS responses to low doses of various oxidative stressors, including Zn, in a live fish embryo. Using live-imaging analysis with this biosensor zebrafish embryo, we discovered that the olfactory sensory neurons in the brain are especially sensitive to ZnOP exposure. Furthermore, through studies monitoring neutrophil migration and neuronal activation in the embryonic brain and via behaviour analysis, we have found that sub-lethal doses of ZnONPs (ranging from 0.033 to 1 mg/L nominal concentrations), which had no visible effect on embryo growth or morphology, cause significant localised inflammation, disrupting the neurophysiology of olfactory brain tissues and ultimately impaired olfaction-mediated behaviour. Collectively, these findings establish a potent and important effect mechanism for ZnONP toxicity, indicating the olfactory sensory system as the primary target for ZnONPs as an environmental toxicant in aquatic environments. Our result also highlights that even low doses of ZnONPs can have detrimental effects on the olfactory sensory system, surpassing previous expectations. The importance of olfaction in environment sensing, sex behaviours and overall fitness across species raises concerns about the potential impact of ZnONPs on olfaction-mediated brain function and behaviour in animals and humans. Our study emphasises the need for greater consideration of the potential risks associated with these nanomaterials.
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Nanopartículas , Óxido de Zinc , Animales , Humanos , Óxido de Zinc/toxicidad , Pez Cebra , Olfato , Zinc/toxicidad , Órganos de los SentidosRESUMEN
The mechanisms of toxicity of engineered nanomaterials (ENMs) to the early life stages of freshwater fish, and the relative hazard compared to dissolved metals, is only partially understood. In the present study, zebrafish (Danio rerio) embryos were exposed to lethal concentrations of silver nitrate (AgNO3) or silver (Ag) ENMs (primary size 42.5 ± 10.2 nm). The 96 h-LC50 for AgNO3 was 32.8 ± 0.72 µg Ag L-1 (mean ± 95% CI) compared to 6.5 ± 0.4 mg L-1 of the whole material for Ag ENMs; with the ENMs being orders of magnitude less toxic than the metal salt. The EC50 for hatching success was 30.5 ± 1.4 µg Ag L-1 and 6.04 ± 0.4 mg L-1 for AgNO3 and Ag ENMs, respectively. Further sub-lethal exposures were performed with the estimated LC10 concentrations for both AgNO3 or Ag ENMs over 96 h, where about 3.7% of the total Ag as AgNO3 was internalised, as measured by Ag accumulation in the dechorionated embryos. However, for the ENM exposures, nearly all (99.8%) of the total Ag was associated with chorion; indicating the chorion as an effective barrier to protect the embryo in the short term. Calcium (Ca2+) and sodium (Na+) depletion was induced in embryos by both forms of Ag, but hyponatremia was more pronounced in the nano form. Total glutathione (tGSH) levels declined in embryos exposed to both Ag forms, but a superior depletion occurred with the nano form. Nevertheless, oxidative stress was mild as superoxide dismutase (SOD) activity stayed uniform and the sodium pump (Na+/K+-ATPase) activity had no appreciable inhibition compared to the control. In conclusion, AgNO3 was more toxic to the early life stage zebrafish than the Ag ENMs, still differences were found in the exposure and toxic mechanisms of both Ag forms.
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Nanopartículas del Metal , Nanoestructuras , Animales , Nitrato de Plata/toxicidad , Pez Cebra , Nanopartículas del Metal/toxicidad , Disponibilidad Biológica , Estrés Oxidativo , Nanoestructuras/toxicidadRESUMEN
Lead halide perovskites are promising semiconducting materials for solar energy harvesting. However, the presence of heavy-metal lead ions is problematic when considering potential harmful leakage into the environment from broken cells and also from a public acceptance point of view. Moreover, strict legislation on the use of lead around the world has driven innovation in the development of strategies for recycling end-of-life products by means of environmentally friendly and cost-effective routes. Lead immobilization is a strategy to transform water-soluble lead ions into insoluble, nonbioavailable and nontransportable forms over large pH and temperature ranges and to suppress lead leakage if the devices are damaged. An ideal methodology should ensure sufficient lead-chelating capability without substantially influencing the device performance, production cost and recycling. Here we analyse chemical approaches to immobilize Pb2+ from perovskite solar cells, such as grain isolation, lead complexation, structure integration and adsorption of leaked lead, based on their feasibility to suppress lead leakage to a minimal level. We highlight the need for a standard lead-leakage test and related mathematical model to be established for the reliable evaluation of the potential environmental risk of perovskite optoelectronics.
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This review discusses topics relevant to the development of antimicrobial nanocoatings and nanoscale surface modifications for medical and dental applications. Nanomaterials have unique properties compared to their micro- and macro-scale counterparts and can be used to reduce or inhibit bacterial growth, surface colonization and biofilm development. Generally, nanocoatings exert their antimicrobial effects through biochemical reactions, production of reactive oxygen species or ionic release, while modified nanotopographies create a physically hostile surface for bacteria, killing cells via biomechanical damage. Nanocoatings may consist of metal nanoparticles including silver, copper, gold, zinc, titanium, and aluminum, while nonmetallic compounds used in nanocoatings may be carbon-based in the form of graphene or carbon nanotubes, or composed of silica or chitosan. Surface nanotopography can be modified by the inclusion of nanoprotrusions or black silicon. Two or more nanomaterials can be combined to form nanocomposites with distinct chemical or physical characteristics, allowing combination of different properties such as antimicrobial activity, biocompatibility, strength, and durability. Despite their wide range of applications in medical engineering, questions have been raised regarding potential toxicity and hazards. Current legal frameworks do not effectively regulate antimicrobial nanocoatings in matters of safety, with open questions remaining about risk analysis and occupational exposure limits not considering coating-based approaches. Bacterial resistance to nanomaterials is also a concern, especially where it may affect wider antimicrobial resistance. Nanocoatings have excellent potential for future use, but safe development of antimicrobials requires careful consideration of the "One Health" agenda, appropriate legislation, and risk assessment.
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Antiinfecciosos , Nanocompuestos , Nanotubos de Carbono , Antibacterianos/química , Nanocompuestos/química , OdontologíaRESUMEN
Mesocosms allow the simulation of environmentally relevant conditions and can be used to establish more realistic scenarios of organism exposure to nanoparticles. An indoor mesocosm experiment simulating an aquatic stream ecosystem was conducted to assess the toxicokinetics and bioaccumulation of silver sulfide nanoparticles (Ag2S NPs) and AgNO3 in the freshwater invertebrates Girardia tigrina, Physa acuta and Chironomus riparius, and determine if previous single-species tests can predict bioaccumulation in the mesocosm. Water was daily spiked at 10 µg Ag L-1. Ag concentrations in water and sediment reached values of 13.4 µg Ag L-1 and 0.30 µg Ag g-1 in the Ag2S NP exposure, and 12.8 µg Ag L-1 and 0.20 µg Ag g-1 in the AgNO3. Silver was bioaccumulated by the species from both treatments, but with approximately 1.5, 3 and 11 times higher body Ag concentrations in AgNO3 compared to Ag2S NP exposures in snails, chironomids and planarians, respectively. In the Ag2S NP exposures, the observed uptake was probably of the particulate form. This demonstrates that this more environmentally relevant Ag nanoform may be bioavailable for uptake by benthic organisms. Interspecies interactions likely occurred, namely predation (planarians fed on chironomids and snails), which somehow influenced Ag uptake/bioaccumulation, possibly by altering organisms´ foraging behaviour. Higher Ag uptake rate constants were determined for AgNO3 (0.64, 80.4 and 1.12 Lwater g-1organism day-1) than for Ag2S NPs (0.05, 2.65 and 0.32 Lwater g-1organism day-1) for planarians, snails and chironomids, respectively. Biomagnification under environmentally realistic exposure seemed to be low, although it was likely to occur in the food chain P. acuta to G. tigrina exposed to AgNO3. Single-species tests generally could not reliably predict Ag bioaccumulation in the more complex mesocosm scenario. This study provides methodologies/data to better understand exposure, toxicokinetics and bioaccumulation of Ag in complex systems, reinforcing the need to use mesocosm studies to improve the risk assessment of environmental contaminants, specifically NPs, in aquatic environments.
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Nanopartículas del Metal , Animales , Bioacumulación , Nanopartículas del Metal/toxicidad , Ecosistema , Toxicocinética , RíosRESUMEN
The mechanisms of toxicity of engineered nanomaterials (ENMs) to the early life stages of freshwater fish, and the relative hazard compared to dissolved metals, is only partially understood. In the present study, zebrafish embryos were exposed to lethal concentrations of copper sulphate (CuSO4) or copper oxide (CuO) ENMs (primary size â¼15 nm), and then the sub-lethal effects investigated at the LC10 concentrations over 96 h. The 96 h-LC50 (mean ± 95% CI) for CuSO4 was 303 ± 14 µg Cu L-1 compared to 53 ± 9.9 mg L-1 of the whole material for CuO ENMs; with the ENMs being orders of magnitude less toxic than the metal salt. The EC50 for hatching success was 76 ± 11 µg Cu L-1 and 0.34 ± 0.78 mg L-1 for CuSO4 and CuO ENMs respectively. Failure to hatch was associated with bubbles and foam-looking perivitelline fluid (CuSO4), or particulate material smothering the chorion (CuO ENMs). In the sub-lethal exposures, about 42% of the total Cu as CuSO4 was internalised, as measured by Cu accumulation in the de-chorionated embryos, but for the ENMs exposures, nearly all (94%) of the total Cu was associated with chorion; indicating the chorion as an effective barrier to protect the embryo from the ENMs in the short term. Both forms of Cu exposure caused sodium (Na+) and calcium (Ca2+), but not magnesium (Mg2+), depletion from the embryos; and CuSO4 caused some inhibition of the sodium pump (Na+/K+-ATPase) activity. Both forms of Cu exposure caused some loss of total glutathione (tGSH) in the embryos, but without induction of superoxide dismutase (SOD) activity. In conclusion, CuSO4 was much more toxic than CuO ENMs to early life stage zebrafish, but there are subtle differences in the exposure and toxic mechanisms for each substance.
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Nanoestructuras , Contaminantes Químicos del Agua , Animales , Cobre/toxicidad , Cobre/análisis , Sulfato de Cobre/toxicidad , Pez Cebra , Nanoestructuras/toxicidad , Óxidos , Contaminantes Químicos del Agua/toxicidadRESUMEN
Biodegradable plastics have been proposed as a potential solution to plastic pollution, as they can be biodegraded into their elemental components by microbial action. However, the degradation rate of biodegradable plastics is highly variable across environments, leading to the potential for accumulation of plastic particles, chemical co-contaminants and/or degradation products. This paper reviews the toxicological effects of biodegradable plastics on species and ecosystems, and contextualises these impacts with those previously reported for conventional polymers. While the impacts of biodegradable plastics and their co-contaminants across levels of biological organisation are poorly researched compared with conventional plastics, evidence suggests that individual-level effects could be broadly similar. Where differences in the associated toxicity may arise is due to the chemical structure of biodegradable polymers which should facilitate enzymatic depolymerisation and the utilisation of the polymer carbon by the microbial community. The input of carbon can alter microbial composition, causing an enrichment of carbon-degrading bacteria and fungi, which can have wider implications for carbon and nitrogen dynamics. Furthermore, there is the potential for toxic degradation products to form during biodegradation, however understanding the environmental concentration and effects of degradation products are lacking. As global production of biodegradable polymers continues to increase, further evaluation of their ecotoxicological effects on organisms and ecosystem function are required.
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Plásticos Biodegradables , Plásticos Biodegradables/química , Ecosistema , Biodegradación Ambiental , Polímeros/química , Polímeros/metabolismo , CarbonoRESUMEN
The fate of engineered nanomaterials in ecosystems is unclear. An aquatic stream mesocosm explored the fate and bioaccumulation of silver sulfide nanoparticles (Ag2S NPs) compared to silver nitrate (AgNO3). The aims were to determine the total Ag in water, sediment and biota, and to evaluate the bioavailable fractions of silver in the sediment using a serial extraction method. The total Ag in the water column from a nominal daily dose of 10 µg L-1 of Ag for the AgNO3 or Ag2S NP treatments reached a plateau of around 13 and 12 µg L-1, respectively, by the end of the study. Similarly, the sediment of both Ag-treatments reached ~380 µg Ag kg-1, and with most of it being acid-extractable/labile. The biota accumulated 4-59 µg Ag g-1 dw, depending on the type of Ag-treatment and organism. The oligochaete worm, Lumbriculus variegatus, accumulated Ag from the Ag2S exposure over time, which was similar to the AgNO3 treatment by the end of the experiment. The planarian, Girardia tigrina, and the chironomid larva, Chironomus riparius, showed much higher Ag concentrations than the oligochaete worms; and with a clearer time-dependent statistically significant Ag accumulation relative to the untreated controls. For the pulmonate snail, Physa acuta, bioaccumulation of Ag from AgNO3 and Ag2S NP exposures was observed, but was lower from the nano treatment. The AgNO3 exposure caused appreciable Ag accumulation in the water flea, Daphnia magna, but accumulation was higher in the Ag2S NP treatment (reaching 59 µg g-1 dw). In the rainbow trout, Oncorhynchus mykiss, AgNO3, but not Ag2S NPs, caused total Ag concentrations to increase in the tissues. Overall, the study showed transfer of total Ag from the water column to the sediment, and Ag bioaccumulation in the biota, with Ag from Ag2S NP exposure generally being less bioavailable than that from AgNO3.
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Nanopartículas del Metal , Oncorhynchus mykiss , Contaminantes Químicos del Agua , Animales , Colorantes , Daphnia , Ecosistema , Metales , Ríos , Compuestos de Plata , Nitrato de Plata , SulfurosRESUMEN
There is an urgent need to apply effective, data-driven approaches to reliably predict engineered nanomaterial (ENM) toxicity. Here we introduce a predictive computational framework based on the molecular and phenotypic effects of a large panel of ENMs across multiple in vitro and in vivo models. Our methodology allows for the grouping of ENMs based on multi-omics approaches combined with robust toxicity tests. Importantly, we identify mRNA-based toxicity markers and extensively replicate them in multiple independent datasets. We find that models based on combinations of omics-derived features and material intrinsic properties display significantly improved predictive accuracy as compared to physicochemical properties alone.
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Nanoestructuras , Biomarcadores , Nanoestructuras/toxicidad , ARN Mensajero/genéticaRESUMEN
A systematic review of the use of single particle ICP-MS to analyse engineered nanomaterials (ENMs) in biological samples (plants, animals, body fluids) has highlighted that efforts have focused on a select few types of ENMs (e.g., Ag and TiO2) and there is a lack of information for some important tissues (e.g., reproductive organs, skin and fatty endocrine organs). The importance of sample storage is often overlooked but plays a critical role. Careful consideration of the ENM and matrix composition is required to select an appropriate protocol to liberate ENMs from a tissue whilst not promoting the transformation of them, or genesis of new particulates. A 'one size fits all' protocol, applicable to all possible types of ENM and biological matrices, does not seem practical. However, alkaline-based extractions would appear to show greater promise for wide applicability to animal tissues, although enzymatic approaches have a role, especially for plant tissues. There is a lack of consistency in metrics reported and how they are determined (e.g. size limit of detection, and proportions of recovery), making comparison between some studies more difficult. In order to establish standardised protocols for regulatory use, effort is needed to: develop certified reference materials, achieve international agree on nomenclature and the use of control samples, and to create a decision tree to help select the best sample preparation for the type of tissue matrix.
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The fish acute toxicity test (TG203; OECD, 2019) is frequently used and highly embedded in hazard and risk assessment globally. The test estimates the concentration of a chemical that kills 50% of the fish (LC50) over a 96 h exposure and is considered one of the most severe scientific procedures undertaken. Over the years, discussions at the Organisation for Economic Co-operation and Development (OECD) have resulted in changes to the test which reduce the number of fish used, as well as the development of a (potential) replacement test (TG236, OECD, 2013). However, refinement of the mortality endpoint with an earlier (moribundity) endpoint was not considered feasible during the Test Guideline's (TG) last update in 2019. Several stakeholders met at a UK-based workshop to discuss how TG203 can be refined, and identified two key opportunities to reduce fish suffering: (1) application of clinical signs that predict mortality and (2) shortening the test duration. However, several aspects need to be addressed before these refinements can be adopted. TG203 has required recording of major categories of sublethal clinical signs since its conception, with the option to record more detailed signs introduced in the 2019 update. However, in the absence of guidance, differences in identification, recording and reporting of clinical signs between technicians and laboratories is likely to have generated piecemeal data of varying quality. Harmonisation of reporting templates, and training in clinical sign recognition and recording are needed to standardise clinical sign data. This is critical to enable robust data-driven detection of clinical signs that predict mortality. Discussions suggested that the 96 h duration of TG203 cannot stand up to scientific scrutiny. Feedback and data from UK contract research organisations (CROs) conducting the test were that a substantial proportion of mortalities occur in the first 24 h. Refinement of TG203 by shortening the test duration would reduce suffering (and test failure rate) but requires a mechanism to correct new results to previous 96 h LC50 data. The actions needed to implement both refinement opportunities are summarised here within a roadmap. A shift in regulatory assessment, where the 96 h LC50 is a familiar base for decisions, will also be critical.
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Peces , Organización para la Cooperación y el Desarrollo Económico , Animales , Humanos , Dosificación Letal Mediana , Medición de Riesgo , Pruebas de Toxicidad AgudaRESUMEN
Toxicogenomics opens novel opportunities for hazard assessment by utilizing computational methods to map molecular events and biological processes. In this study, the transcriptomic and immunopathological changes associated with airway exposure to a total of 28 engineered nanomaterials (ENM) are investigated. The ENM are selected to have different core (Ag, Au, TiO2, CuO, nanodiamond, and multiwalled carbon nanotubes) and surface chemistries (COOH, NH2, or polyethylene glycosylation (PEG)). Additionally, ENM with variations in either size (Au) or shape (TiO2) are included. Mice are exposed to 10 µg of ENM by oropharyngeal aspiration for 4 consecutive days, followed by extensive histological/cytological analyses and transcriptomic characterization of lung tissue. The results demonstrate that transcriptomic alterations are correlated with the inflammatory cell infiltrate in the lungs. Surface modification has varying effects on the airways with amination rendering the strongest inflammatory response, while PEGylation suppresses toxicity. However, toxicological responses are also dependent on ENM core chemistry. In addition to ENM-specific transcriptional changes, a subset of 50 shared differentially expressed genes is also highlighted that cluster these ENM according to their toxicity. This study provides the largest in vivo data set currently available and as such provides valuable information to be utilized in developing predictive models for ENM toxicity.
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Pulmón/efectos de los fármacos , Nanoestructuras/toxicidad , Toxicogenética/métodos , Animales , Femenino , Pulmón/metabolismo , Pulmón/patología , Ratones , Ratones Endogámicos C57BL , Modelos Animales , Nanoestructuras/química , Nanoestructuras/clasificación , TranscriptomaRESUMEN
In this study, laboratory experiments have addressed the acute toxicity of two common mycotoxins, deoxynivalenol (DON) and zearalenone (ZON), in a range of freshwater organisms (including rotifers Brachionus calyciflorus, insects Chironomus riparius (larvae), crustaceans Daphnia pulex and Thamnocephalus platyurus, cnidarians Hydra vulgaris, molluscs Lymnaea stagnalis (embryos) and Protozoa Tetrahymena thermophila). Acute EC50 values highlight crustaceans as the most sensitive organisms to DON, with T. platyurus having a 24 h EC50 of 0.14 and D. magna having a 48 h EC50 of 0.13 mg DON/L. During exposures to ZON, H. vulgaris and L. stagnalis embryos showed the highest sensitivity; mortality EC50 values were 1.1 (96 h) and 0.42 mg ZON/L (7 d), respectively. Combining these novel invertebrate toxicity results, along with recent published data for freshwater plant and fish toxicity for analysis of Species Sensitivity Distributions, provides freshwater HC5 values of 5.2 µg DON/L and 43 µg ZON/L, respectively. Using highest reported environmental concentrations and following REACH guidelines, risk ratios calculated here show the risk of ZON to freshwater organisms is low. In contrast, DON may periodically because for concern in streams subject to high agricultural run-off, likely during certain times of year where cereal crops are susceptible to higher fungal infections rates and may pose increased risks due to climate change.
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Micotoxinas , Tricotecenos , Zearalenona , Animales , Agua Dulce , Tricotecenos/toxicidad , Zearalenona/toxicidadRESUMEN
Despite considerable efforts, the properties that drive the cytotoxicity of engineered nanomaterials (ENMs) remain poorly understood. Here, the authors inverstigate a panel of 31 ENMs with different core chemistries and a variety of surface modifications using conventional in vitro assays coupled with omics-based approaches. Cytotoxicity screening and multiplex-based cytokine profiling reveals a good concordance between primary human monocyte-derived macrophages and the human monocyte-like cell line THP-1. Proteomics analysis following a low-dose exposure of cells suggests a nonspecific stress response to ENMs, while microarray-based profiling reveals significant changes in gene expression as a function of both surface modification and core chemistry. Pathway analysis highlights that the ENMs with cationic surfaces that are shown to elicit cytotoxicity downregulated DNA replication and cell cycle responses, while inflammatory responses are upregulated. These findings are validated using cell-based assays. Notably, certain small, PEGylated ENMs are found to be noncytotoxic yet they induce transcriptional responses reminiscent of viruses. In sum, using a multiparametric approach, it is shown that surface chemistry is a key determinant of cellular responses to ENMs. The data also reveal that cytotoxicity, determined by conventional in vitro assays, does not necessarily correlate with transcriptional effects of ENMs.
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The bioaccumulation potential and toxic effects of engineered nanomaterials (ENMs) to earthworms are poorly understood. Two studies were conducted following OECD TG 222 on Eisenia fetida to assess the effects of CdTe QDs with different coatings and soil ageing respectively. Earthworms were exposed to carboxylate (COOH), ammonium (NH4+), or polyethylene glycol (PEG) coated CdTe QDs, or a micron scale (bulk) CdTe material, at nominal concentrations of 50, 500 and 2000â¯mg CdTe QD kg-1 dry weight (dw) for 28 days in Lufa 2.2 soil. In the fresh soil study, earthworms accumulated similar amounts of Cd and Te in the CdTe-bulk exposures, while the accumulation of Cd was higher than Te during the exposures to CdTe QDs. However, neither the total Cd, nor Te concentrations in the earthworms, were easily explained by the extractable metal fractions in the soil or particle dissolution. There were no effects on survival, but some retardation of growth was observed at the higher doses. Inhibition of Na+/K+-ATPase activity with disturbances to tissue electrolytes, as well as tissue Cu and Mn were observed, but without depletion of total glutathione in the fresh soil experiment. Additionally, juvenile production was the most sensitive endpoint, with estimated nominal EC50 of values >2000, 108, 65, 96â¯mg CdTe kg-1 for bulk, PEG-, COOH- and NH4+-coated CdTe QDs, respectively. In the aged soil study, the accumulation of Cd and Te was higher than in the fresh soil study in all CdTe QD exposures. Survival of the adult worms was reduced in the top CdTe-COOH and -NH4+ QD exposures by 55⯱â¯5 and 60⯱â¯25%, respectively; and with decreases in growth. The nominal EC50 values for juvenile production in the aged soil were 165, 88, 78 and 63â¯mg CdTe kg-1 for bulk, PEG-, COOH- and NH4+-coated CdTe QDs, respectively. In conclusion, exposure to nanoscale CdTe QDs, regardless of coating, caused more severe toxic effects that the CdTe bulk material and the toxicity increased after soil ageing. There were some coating-mediated effects, likely due to differences in the metal content and behaviour of the materials.
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Compuestos de Cadmio/toxicidad , Oligoquetos/efectos de los fármacos , Puntos Cuánticos/toxicidad , Contaminantes del Suelo/toxicidad , Suelo/química , Telurio/toxicidad , Animales , Bioacumulación , Compuestos de Cadmio/química , Compuestos de Cadmio/metabolismo , Modelos Teóricos , Oligoquetos/metabolismo , Tamaño de la Partícula , Puntos Cuánticos/química , Puntos Cuánticos/metabolismo , Reproducción/efectos de los fármacos , Contaminantes del Suelo/química , Contaminantes del Suelo/metabolismo , Propiedades de Superficie , Telurio/química , Telurio/metabolismo , Factores de TiempoRESUMEN
Chronic dietary bioaccumulation tests with rodents are required for new substances, including engineered nanomaterials (ENMs), in order to provide information on the potential hazards to human health. However, screening tools are needed to manage the diversity of ENMs and alternative methods are desirable with respect to animal welfare. Here, an ex vivo gut sac method was used to estimate the dietary bioaccumulation potential of silver nanomaterials. The entire gastrointestinal tract (except the caecum) was removed and filled with a gut saline containing 1 mg L-1 of Ag as either AgNO3, silver nanoparticles (Ag NPs) or silver sulphide nanoparticles (Ag2S NPs), and compared to controls with no added Ag. The gut sacs were incubated for 4 h, rinsed to remove excess media, and the total Ag determined in the mucosa and muscularis. There was no detected Ag in the control treatments. Within the Ag treatments, 1.4-22% of the exposure dose was associated with the tissues and serosal saline. Within the mucosa of the AgNO3 treatment, the highest Ag concentration was associated with the intestinal regions (3639-7087 ng g-1) compared to the stomach (639 ± 128 ng g-1). This pattern was also observed in the Ag NP and Ag2S NP treatments, but there was no significant differences between any Ag treatments for the mucosa. However, differences between treatments were observed in the muscularis concentration. For example, both the Ag NP (907 ± 284 ng g -1) and Ag2S NP (1482 ± 668 ng g-1) treatments were significantly lower compared to the AgNO3 treatment (2514 ± 267 ng g-1). The duodenum demonstrated serosal accumulation in both the AgNO3 (~10 ng mL-1) and Ag NP (~3 ng mL-1) treatments. The duodenum showed some of the highest Ag accumulation with 41, 61 and 57% of the total Ag in the mucosa compared to the muscularis for the AgNO3, Ag NP and Ag2S NP treatments, respectively. In conclusion, the ex vivo gut sac method demonstrates the uptake of Ag in all Ag treatments, with the duodenum the site of highest accumulation. Based on the serosal saline accumulation, the ranked order of accumulation is AgNO3 > Ag NPs > Ag2S NPs.