Explore the vast range of titles available.

\"Recounts the gripping story of Flint's poisoned water through the people who caused it, suffered from it, and exposed it. It is a chronicle of one town, but could also be about any American city, all made precarious by the neglect of infrastructure\"-- Provided by publisher.

Advances in molecular biology and toxicology are paving the way for major improvements in the evaluation of the hazards posed by the large number of chemicals found at low levels in the environment. The National Research Council was asked by the U.S. Environmental Protection Agency to review the state of the science and create a far-reaching vision for the future of toxicity testing. The book finds that developing, improving, and validating new laboratory tools based on recent scientific advances could significantly improve our ability to understand the hazards and risks posed by chemicals. This new knowledge would lead to much more informed environmental regulations and dramatically reduce the need for animal testing because the new tests would be based on human cells and cell components. Substantial scientific efforts and resources will be required to leverage these new technologies to realize the vision, but the result will be a more efficient, informative and less costly system for assessing the hazards posed by industrial chemicals and pesticides.

When assessing the risk and hazard of a non-pharmaceutical compound, the first step is determining acute toxicity, including toxicity following inhalation. Inhalation is a major exposure route for humans, and the respiratory epithelium is the first tissue that inhaled substances directly interact with. Acute inhalation toxicity testing for regulatory purposes is currently performed only in rats and/or mice according to OECD TG403, TG436, and TG433 test guidelines. Such tests are biased by the differences in the respiratory tract architecture and function across species, making it difficult to draw conclusions on the potential hazard of inhaled compounds in humans. Research efforts have been therefore focused on developing alternative, human-relevant models, with emphasis on the creation of advanced In vitro models. To date, there is no In vitro model that has been accepted by regulatory agencies as a stand-alone replacement for inhalation toxicity testing in animals. Here, we provide a brief introduction to current OECD test guidelines for acute inhalation toxicity, the interspecies differences affecting the predictive value of such tests, and the current regulatory efforts to advance alternative approaches to animal-based inhalation toxicity studies. We then list the steps that should allow overcoming the current challenges in validating In vitro alternatives for the successful replacement of animal-based inhalation toxicity studies. These steps are inclusive and descriptive, and should be detailed when adopting in house-produced 3D cell models for inhalation tests. Hence, we provide a checklist of key parameters that should be reported in any future scientific publications for reproducibility and transparency.

As the economy grows, there is a growing emphasis on food safety. While the health benefits of chlorogenic acid (CGA) are recognized, safe dosages and potential liver cell damage from excessive CGA consumption are not well studied. This study aims to determine the safe and effective dose range of CGA and understand how it causes toxicity in hepatocyte at half-maximal inhibitory concentration (IC50). This study assessed the impact of various CGA concentrations on liver cells, examining growth, viability, toxicity, energy metabolism, and colony formation using Real-Time Cell Analysis (RTCA), CCK-8, lactate dehydrogenase (LDH) assays, and Seahorse XF96. It established CGA's IC50 for cell viability and identified differentially expressed proteins via proteomics. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted to elucidate the signaling pathways associated with the differentially expressed proteins. Further validation of the molecular mechanisms was performed using flow cytometry, Western blotting, and reverse transcription quantitative polymerase chain reaction (RT-qPCR). Finally, CGA was injected into Kunming (KM) mice via the tail vein for acute toxicity testing. In this study, 200 µM of CGA significantly reduced LDH release and increased the mitochondrial oxygen consumption rate (OCR) in hepatocytes, but it did not affect the extracellular acidification rate (ECAR). Additionally, 200 µM of CGA slightly promoted hepatocyte growth; however, at 300 μM, CGA nearly completely inhibited the clonogenic capacity of hepatocytes, and at 600 μM, it significantly impeded hepatocyte growth. The IC50 of CGA for hepatocyte activity was determined to be 613.1 µM. experiments indicated that incubation with CGA at its IC50 concentration for 96 h resulted in the arrest of L-02 cells in the S phase of the cell cycle and induced apoptosis. Further investigation revealed that the IC50 concentration of CGA, through the depletion of free iron within hepatocytes, significantly reduced the expression of iron-sulfur cluster subunits in mitochondrial complexes I-III and disrupted the oxidative-reductive homeostasis of hepatocytes, ultimately leading to hepatotoxicity. Interestingly, N-Acetyl-L-cysteine (NAC) or ferric citrate reduced hepatocyte toxicity from excessive CGA. All mice survived after receiving CGA injections at doses up to 125 mg/kg. The semi-lethal concentration (LD ) for Kunming mice was 382.28 mg/kg. These findings suggest that the antioxidant and iron-chelating properties of CGA determine its role in either liver protection or toxicity at varying concentrations, providing valuable insight for its rational dietary and clinical use.

Environmental transport and deposition of particulate matter (PM) associated with toxic chemicals has begun to receive attention as a source of risk to pollinators. For example, dust arising from manipulations of insecticide-treated seed has potential to exert toxic effects among non-target insects. Similarly, synthetic steroid growth promoters, antibiotics and multiple insecticides and parasiticides detected in fugitive beef cattle feedyard PM may also negatively impact pollinators since many of these chemicals have been detected on wildflowers and pollinators collected near beef cattle feedyards. Therefore, there is a need to assess risk to pollinators posed by deposition of agrochemical-laden PM, both in the field and the laboratory. Unfortunately, established laboratory methods for simulating PM exposure or toxicity associated with contaminated PM are few and highly situation-specific. Herein we describe development and use of a PM circulation system that can be employed to evaluate toxicity of agrochemical-contaminated PM in the laboratory under controlled conditions. Two model organisms (honeybees (Apis mellifera) and mason bees (Osmia lignaria)) were exposed to agrochemical-free PM in the circulator system, and post-exposure mortality was compared with controls. No significant differences in mortality between exposed and control bees were observed. Next, honeybees and mason bees were exposed to PM spiked with an insecticide known to exert toxic effects to pollinators (thiamethoxam). Bees experienced significantly higher mortality when exposed to thiamethoxam-laden PM at environmentally relevant concentrations as compared to bees exposed to agrochemical-free PM. These results confirm the validity of these methods for use in controlled laboratory PM toxicity tests and offer a source of positive and negative control groups for laboratory and field experiments examining exposure of pollinators to potentially toxic agrochemical-laden PM. This method facilitates generation of more realistic toxicity data than standard contact toxicity tests when pollinator exposure scenarios involve particulate-based agrochemicals or other toxic chemicals.HighlightsA novel method for simulating pollinator exposure to particulate matter and agrochemical-laden particulate matter was developed and demonstrated.Exposure to agrochemical-free particulate matter alone does not result in significant pollinator mortality.Thiamethoxam-laden particulate matter exerted significant toxic effects on honeybees and mason bees.This method facilitates generation of realistic toxicity data when pollinator exposure scenarios involve particulate-based agrochemicals or other toxic chemicals.

Background: Cytotoxicity testing is a primary method to establish the safety of biomaterials, e.g., biocomposites. Biomaterials involve a wide range of medical materials, which are usually solid materials and are used in bone regeneration, cardiology, or dermatology. Current advancements in science and technology provide several standard cytotoxicity testing methods that are sufficiently sensitive to detect various levels of cellular toxicity, i.e., from low to high. The aim was to compare the direct and indirect methodology described in the ISO guidelines UNE-EN ISO 10993-5:2009 Part 5. Methods: Cell proliferation was measured using WST-1 assay, and cytotoxicity was measured using LDH test kit. Results: The results indicate that the molecular surface of biomaterials have impact on the cytotoxicity and proliferation profile. Based on these results, we confirm that the indirect method does not provide a clear picture of the cell condition after the exposure to the surface, and moreover, cannot provide complete results about the effects of the material. Conclusions: Comparison of both methods shows that it is pivotal to investigate biomaterials at the very early stages using both indirect and direct methods to access the influence of the released toxins and surface of the material on the cell condition.

Skin phototoxicity (photoirritation) is defined as an acute toxic response elicited by topically or systemically administered photoreactive chemicals after the exposure of the skin to environmental light. The in vitro reconstructed human epidermis phototoxicity test (RhE PT) is used to identify the phototoxic potential of a test chemical after topical application in reconstructed human epidermis (RhE) tissues in the presence and absence of simulated sunlight. Phototoxicity potential is evaluated by the relative reduction in viability of cells exposed to the test chemical in the presence as compared to the absence of simulated sunlight. Chemicals identified as positive in this test may be phototoxic in vivo following topical application to the skin, eyes, and other external light-exposed epithelia.

In the aim to determine neurotoxicity, new methods are being validated, including tests and test batteries comprising in vitro and in vivo approaches. Alternative test models such as the zebrafish ( Danio rerio ) embryo have received increasing attention, with minor modifications of the fish embryo toxicity test (FET; OECD TG 236) as a tool to assess behavioral endpoints related to neurotoxicity during early developmental stages. The spontaneous tail movement assay, also known as coiling assay, assesses the development of random movement into complex behavioral patterns and has proven sensitive to acetylcholine esterase inhibitors at sublethal concentrations. The present study explored the sensitivity of the assay to neurotoxicants with other modes of action (MoAs). Here, five compounds with diverse MoAs were tested at sublethal concentrations: acrylamide, carbaryl, hexachlorophene, ibuprofen, and rotenone. While carbaryl, hexachlorophene, and rotenone consistently induced severe behavioral alterations by ~ 30 h post fertilization (hpf), acrylamide and ibuprofen expressed time- and/or concentration-dependent effects. At 37–38 hpf, additional observations revealed behavioral changes during dark phases with a strict concentration-dependency. The study documented the applicability of the coiling assay to MoA-dependent behavioral alterations at sublethal concentrations, underlining its potential as a component of a neurotoxicity test battery.

Induced pluripotent stem cells (iPSCs) can be differentiated into multiple cell types in the body while maintaining proliferative capabilities. The generation of hepatocyte-like cells (HLCs) from iPSCs has resulted in a new source for liver cells. Since healthy primary human hepatocytes and hepatic cells are difficult to obtain, HLCs are gaining attention. HLCs can be obtained from a continuous, stable source while maintaining their original donor genotype, which opens new avenues into patient-specific testing and therapeutics. Studies have utilized HLCs for toxicity testing to further understand their drug metabolizing capabilities. This review focuses on advances being made to achieve hepatic functions from HLCs, their current use in hepatotoxicity testing, and their potential for future liver-related toxicity evaluations.

The embryonic zebrafish is a useful vertebrate model for assessing the effects of substances on growth and development. However, cross-laboratory developmental toxicity outcomes can vary and reported developmental defects in zebrafish may not be directly comparable between laboratories. To address these limitations for gaining broader adoption of the zebrafish model for toxicological screening, we established the Systematic Evaluation of the Application of Zebrafish in Toxicology (SEAZIT) program to investigate how experimental protocol differences can influence chemical-mediated effects on developmental toxicity (i.e., mortality and the incidence of altered phenotypes). As part of SEAZIT, three laboratories were provided a common and blinded dataset (42 substances) to evaluate substance-mediated effects on developmental toxicity in the embryonic zebrafish model. To facilitate cross-laboratory comparisons, all the raw experimental data were collected, stored in a relational database, and analyzed with a uniform data analysis pipeline. Due to variances in laboratory-specific terminology for altered phenotypes, we utilized ontology terms available from the Ontology Lookup Service (OLS) for Zebrafish Phenotype to enable additional cross-laboratory comparisons. In this manuscript, we utilized data from the first phase of screening (dose range finding, DRF) to highlight the methodology associated with the development of the database and data analysis pipeline, as well as zebrafish phenotype ontology mapping.