Recent forensic applications of enhanced chromatographic separation methods.

This study reviews the recent applications of enhanced separation methods employed in forensic analysis utilizing gas chromatography, liquid chromatography, and supercritical fluid chromatography published between 2015 to 2020, except papers previously covered in relevant review articles. Applications of enhanced chromatographic separation methods to arson investigations, environmental forensics, sexual assault investigations, drug analysis, and toxicology are discussed. Future directions for enhanced chromatographic separation methods in forensic science are also explored.

A Scaffold Free 3D Bioprinted Cartilage Model for In Vitro Toxicology.

Bioprinting has emerged as a promising method for precise spatiotemporal patterning of biological materials such as living cells, genetic materials, and proteins, which are sensitive to any other fabrication techniques. Bioprinting allows the generation of tissue constructs and models that closely mimic the anatomical and physiological attributes of a chosen tissue. In vitro toxicology assays can greatly benefit from bioprinting as drugs can be screened with higher efficiencies in a significantly reduced period. This protocol describes a method for fabricating bioprinted cartilage constructs which can be used for in vitro toxicology studies employing a scalable "tissue strand" bioprinting modality.

Nano Assessing Nano: Nanosensor-Enabled Detection of Cell Phenotypic Changes Identifies Nanoparticle Toxicological Effects at Ultra-Low Exposure Levels.

Industrial use of nanomaterials is rapidly increasing, making the effects of these materials on the environment and human health of critical concern. Standard nanotoxicity evaluation methods rely on detecting cell death or major dysfunction and will miss early signs of toxicity. In this work, the use of rapid and sensitive nanosensors that can efficiently detect subtle phenotypic changes on the cell surface following nanomaterial exposure is reported. Importantly, the method reveals significant phenotypic changes at dosages where other conventional methods show normal cellular activity. This approach holds promise in toxicological and pharmacological evaluations to ensure safer and better use of nanomaterials.

Toxicology in the Super-Resolution Era.

Light microscopy has played a central role in science for the past couple of hundred years and will continue to do so. Multiple super-resolution microscopy techniques have been in the headlines for smashing what for more than 100+ years was believed to be the limits of optical microscopy. This resolution improvement enables the visualization of molecular structures and processes on the nano scale. While certain scientific questions in toxicology can benefit from modalities within the super-resolution suite, due diligence is required for efficiency and to achieve optimal results. For a given hypothesis being tested, there are biophysical issues that need to be considered before heading down the super-resolution road. All commercially available super-resolution modalities, along with cautions and tips, will be discussed. © 2019 by John Wiley & Sons, Inc.

The Emergence of Microphysiological Systems (Organs-on-chips) as Paradigm-changing Tools for Toxicologic Pathology.

Microphysiological systems (MPS), commonly known as organs-on-chips, are a rapidly advancing technology that promises to impact many areas of medical and toxicological pathology. In this minireview, the history of MPS and its potential utility in safety assessment are described with the toxicologic pathologist in mind. Several MPS development focus areas are defined, and recent progress in the area is highlighted. MPS will likely become an important tool for the toxicologic pathologist as part of our role in the safety assessment process within the pharmaceutical, biotechnology, medical device, and cosmetic and agrichemical industries.

Medical Devices; Clinical Chemistry and Clinical Toxicology Devices; Classification of the Organophosphate Test System. Final order.

The Food and Drug Administration (FDA or we) is classifying the organophosphate test system into class II (special controls). The special controls that apply to the device type are identified in this order and will be part of the codified language for the organophosphate test system's classification. We are taking this action because we have determined that classifying the device into class II (special controls) will provide a reasonable assurance of safety and effectiveness of the device. We believe this action will also enhance patients' access to beneficial innovative devices, in part by reducing regulatory burdens.

Precision toxicology based on single cell sequencing: an evolving trend in toxicological evaluations and mechanism exploration.

In this review, we introduce a new concept, precision toxicology: the mode of action of chemical- or drug-induced toxicity can be sensitively and specifically investigated by isolating a small group of cells or even a single cell with typical phenotype of interest followed by a single cell sequencing-based analysis. Precision toxicology can contribute to the better detection of subtle intracellular changes in response to exogenous substrates, and thus help researchers find solutions to control or relieve the toxicological effects that are serious threats to human health. We give examples for single cell isolation and recommend laser capture microdissection for in vivo studies and flow cytometric sorting for in vitro studies. In addition, we introduce the procedures for single cell sequencing and describe the expected application of these techniques to toxicological evaluations and mechanism exploration, which we believe will become a trend in toxicology.

Integrating Personalized Technology in Toxicology: Sensors, Smart Glass, and Social Media Applications in Toxicology Research.

Rapid proliferation of mobile technologies in social and healthcare spaces create an opportunity for advancement in research and clinical practice. The application of mobile, personalized technology in healthcare, referred to as mHealth, has not yet become routine in toxicology. However, key features of our practice environment, such as frequent need for remote evaluation, unreliable historical data from patients, and sensitive subject matter, make mHealth tools appealing solutions in comparison to traditional methods that collect retrospective or indirect data. This manuscript describes the features, uses, and costs associated with several of common sectors of mHealth research including wearable biosensors, ingestible biosensors, head-mounted devices, and social media applications. The benefits and novel challenges associated with the study and use of these applications are then discussed. Finally, opportunities for further research and integration are explored with a particular focus on toxicology-based applications.

Imaging mass spectrometry in drug development and toxicology.

During the last decades, imaging mass spectrometry has gained significant relevance in biomedical research. Recent advances in imaging mass spectrometry have paved the way for in situ studies on drug development, metabolism and toxicology. In contrast to whole-body autoradiography that images the localization of radiolabeled compounds, imaging mass spectrometry provides the possibility to simultaneously determine the discrete tissue distribution of the parent compound and its metabolites. In addition, imaging mass spectrometry features high molecular specificity and allows comprehensive, multiplexed detection and localization of hundreds of proteins, peptides and lipids directly in tissues. Toxicologists traditionally screen for adverse findings by histopathological examination. However, studies of the molecular and cellular processes underpinning toxicological and pathologic findings induced by candidate drugs or toxins are important to reach a mechanistic understanding and an effective risk assessment strategy. One of IMS strengths is the ability to directly overlay the molecular information from the mass spectrometric analysis with the tissue section and allow correlative comparisons of molecular and histologic information. Imaging mass spectrometry could therefore be a powerful tool for omics profiling of pharmacological/toxicological effects of drug candidates and toxicants in discrete tissue regions. The aim of the present review is to provide an overview of imaging mass spectrometry, with particular focus on MALDI imaging mass spectrometry, and its use in drug development and toxicology in general.

Breath biomarkers in toxicology.

Exhaled breath has joined blood and urine as a valuable resource for sampling and analyzing biomarkers in human media for assessing exposure, uptake metabolism, and elimination of toxic chemicals. This article focuses current use of exhaled gas, aerosols, and vapor in human breath, the methods for collection, and ultimately the use of the resulting data. Some advantages of breath are the noninvasive and self-administered nature of collection, the essentially inexhaustible supply, and that breath sampling does not produce potentially infectious waste such as needles, wipes, bandages, and glassware. In contrast to blood and urine, breath samples can be collected on demand in rapid succession and so allow toxicokinetic observations of uptake and elimination in any time frame. Furthermore, new technologies now allow capturing condensed breath vapor directly, or just the aerosol fraction alone, to gain access to inorganic species, lung pH, proteins and protein fragments, cellular DNA, and whole microorganisms from the pulmonary microbiome. Future applications are discussed, especially the use of isotopically labeled probes, non-targeted (discovery) analysis, cellular level toxicity testing, and ultimately assessing "crowd breath" of groups of people and the relation to dose of airborne and other environmental chemicals at the population level.

The Feasibility and Acceptability of Google Glass for Teletoxicology Consults.

Teletoxicology offers the potential for toxicologists to assist in providing medical care at remote locations, via remote, interactive augmented audiovisual technology. This study examined the feasibility of using Google Glass, a head-mounted device that incorporates a webcam, viewing prism, and wireless connectivity, to assess the poisoned patient by a medical toxicology consult staff. Emergency medicine residents (resident toxicology consultants) rotating on the toxicology service wore Glass during bedside evaluation of poisoned patients; Glass transmitted real-time video of patients' physical examination findings to toxicology fellows and attendings (supervisory consultants), who reviewed these findings. We evaluated the usability (e.g., quality of connectivity and video feeds) of Glass by supervisory consultants, as well as attitudes towards use of Glass. Resident toxicology consultants and supervisory consultants completed 18 consults through Glass. Toxicologists viewing the video stream found the quality of audio and visual transmission usable in 89 % of cases. Toxicologists reported their management of the patient changed after viewing the patient through Glass in 56 % of cases. Based on findings obtained through Glass, toxicologists recommended specific antidotes in six cases. Head-mounted devices like Google Glass may be effective tools for real-time teletoxicology consultation.

Cell-Based Microarrays for In Vitro Toxicology.

DNA/RNA and protein microarrays have proven their outstanding bioanalytical performance throughout the past decades, given the unprecedented level of parallelization by which molecular recognition assays can be performed and analyzed. Cell microarrays (CMAs) make use of similar construction principles. They are applied to profile a given cell population with respect to the expression of specific molecular markers and also to measure functional cell responses to drugs and chemicals. This review focuses on the use of cell-based microarrays for assessing the cytotoxicity of drugs, toxins, or chemicals in general. It also summarizes CMA construction principles with respect to the cell types that are used for such microarrays, the readout parameters to assess toxicity, and the various formats that have been established and applied. The review ends with a critical comparison of CMAs and well-established microtiter plate (MTP) approaches.

Inhalation toxicology methods: the generation and characterization of exposure atmospheres and inhalational exposures.

In this unit, the need for laboratory-based inhalation toxicology studies, the historical background on adverse health effects of airborne toxicants, and the benefits of advance planning for the building of analytic options into the study design to maximize the scientific gains to be derived from the investments in the study are outlined. The following methods are described: (1) the generation and characterization of exposure atmospheres for inhalation exposures in humans and laboratory animals; (2) the delivery and distribution into and within whole-body exposure chambers, head-only exposure chambers, face-masks, and mouthpieces or nasal catheters; (3) options for on-line functional assays during and between exposures; and (4) options for serial non-invasive assays of response. In doing so, a description beyond exposures to single agents and simple mixtures is presented, and included are methods for evaluating biological responses to complex environmental mixtures. It is also emphasized that great care should be taken in the design and execution of such studies so that the scientific returns can be maximized both initially, and in follow-up utilization of archived samples of the exposure atmospheres, excreta, and tissues collected for histology.

Indicadores de calidad en la asistencia toxicológica / Quality indicators in toxicological assistance

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Cell dispensing in low-volume range with the immediate drop-on-demand technology (I-DOT).

Handling and dosing of cells comprise the most critical step in the microfabrication of cell-based assay systems for screening and toxicity testing. Therefore, the immediate drop-on-demand technology (I-DOT) was developed to provide a flexible noncontact liquid handling system enabling dispensing of cells and liquid without the risk of cross-contamination down to a precise volume in the nanoliter range. Liquid is dispensed from a source plate within nozzles at the bottom by a short compressed air pulse that is given through a quick release valve into the well, thus exceeding the capillary pressure in the nozzle. Droplets of a defined volume can be spotted directly onto microplates or other cell culture devices. We present a study on the performance and biological impact of this technology by applying the cell line MCF-7, human fibroblasts, and human mesenchymal stem cells (hMSCs). For all cell types tested, viability after dispensing is comparable to the control and exhibits similar proliferation rates in the absence of apoptotic cells, and the differentiation potential of hMSCs is not impaired. The immediate drop-on-demand technology enables accurate cell dosage and offers promising potential for single-cell applications.

Considerations for conducting imaging studies in support of developmental toxicology studies for regulatory submission.

Preclinical imaging technologies are increasingly being applied to developmental toxicology studies in drug development to determine potential compound toxicity. Although most of these studies are conducted in a non-regulatory setting, there is interest in performing these imaging studies under applicable regulations, for example Good Laboratory Practices (GLP), to support regulatory decisions concerning drug safety. This manuscript will describe regulations and processes to consider when bringing an imaging technology into GLP compliance.