Review

Authors: Katharine A Horzmann, Jennifer L Freeman

The laboratory zebrafish (Danio rerio) is now an accepted model in toxicologic research. The zebrafish model fills a niche between in vitro models and mammalian biomedical models. The developmental characteristics of the small fish are strategically being used by scientists to study topics ranging from high-throughput toxicity screens to toxicity in multi- and transgenerational studies. High-throughput technology has increased the utility of zebrafish embryonic toxicity assays in screening of chemicals and drugs for toxicity or effect. Additionally, advances in behavioral characterization and experimental methodology allow for observation of recognizable phenotypic changes after xenobiotic exposure. Future directions in zebrafish research are predicted to take advantage of CRISPR-Cas9 genome editing methods in creating models of disease and interrogating mechanisms of action with fluorescent reporters or tagged proteins. Zebrafish can also model developmental origins of health and disease and multi- and transgenerational toxicity. The zebrafish has many advantages as a toxicologic model and new methodologies and areas of study continue to expand the usefulness and application of the zebrafish.

Topics: Animals; Behavior, Animal; Embryo, Nonmammalian; Embryonic Development; High-Throughput Screening Assays; Larva; Models, Animal; Toxicology; Xenobiotics; Zebrafish

PubMed: 29471431
DOI: 10.1093/toxsci/kfy044

Authors: Ida Ferrandino

is a small tropical freshwater fish, also known as and commonly referred to as zebrafish, described for the first time in 1822 by Francis Hamilton in the Ganges River but widespread throughout the entire Great Himalayan region of Southeast Asia [...].

Topics: Zebrafish; Animals; Disease Models, Animal; Toxicology; Humans

PubMed: 39201295
DOI: 10.3390/ijms25168608

Review

Authors: Mounir Bouhifd, Thomas Hartung, Helena T Hogberg...

Metabolomics use in toxicology is rapidly increasing, particularly owing to advances in mass spectroscopy, which is widely used in the life sciences for phenotyping disease states. Toxicology has the advantage of having the disease agent, the toxicant, available for experimental induction of metabolomics changes monitored over time and dose. This review summarizes the different technologies employed and gives examples of their use in various areas of toxicology. A prominent use of metabolomics is the identification of signatures of toxicity - patterns of metabolite changes predictive of a hazard manifestation. Increasingly, such signatures indicative of a certain hazard manifestation are identified, suggesting that certain modes of action result in specific derangements of the metabolism. This might enable the deduction of underlying pathways of toxicity, which, in their entirety, form the Human Toxome, a key concept for implementing the vision of Toxicity Testing for the 21st century. This review summarizes the current state of metabolomics technologies and principles, their uses in toxicology and gives a thorough overview on metabolomics bioinformatics, pathway identification and quality assurance. In addition, this review lays out the prospects for further metabolomics application also in a regulatory context.

Topics: Animals; Data Interpretation, Statistical; Humans; Metabolic Networks and Pathways; Metabolomics; Software; Toxicology

PubMed: 23722930
DOI: 10.1002/jat.2874

Authors: A Wallace Hayes, Darlene Dixon

The 35th Annual Society of Toxicologic Pathology Symposium, held in June 2016 in San Diego, California, focused on "The Basis and Relevance of Variation in Toxicologic Responses." In order to review the basic tenants of toxicology, a "broad brush" interactive talk that gave an overview of the Cornerstones of Toxicology was presented. The presentation focused on the historical milestones and perspectives of toxicology and through many scientific graphs, data, and real-life examples covered the three basic principles of toxicology that can be summarized, as dose matters (as does timing), people differ, and things change (related to metabolism and biotransformation).

Topics: Animals; Dose-Response Relationship, Drug; History, 19th Century; History, 20th Century; History, 21st Century; History, Ancient; Humans; Pathology; Poisoning; Toxicology

PubMed: 28068892
DOI: 10.1177/0192623316675768

Review

Authors: Barry Hardy, Gordana Apic, Philip Carthew...

The field of predictive toxicology requires the development of open, public, computable, standardized toxicology vocabularies and ontologies to support the applications required by in silico, in vitro, and in vivo toxicology methods and related analysis and reporting activities. In this article we review ontology developments based on a set of perspectives showing how ontologies are being used in predictive toxicology initiatives and applications. Perspectives on resources and initiatives reviewed include OpenTox, eTOX, Pistoia Alliance, ToxWiz, Virtual Liver, EU-ADR, BEL, ToxML, and Bioclipse. We also review existing ontology developments in neighboring fields that can contribute to establishing an ontological framework for predictive toxicology. A significant set of resources is already available to provide a foundation for an ontological framework for 21st century mechanistic-based toxicology research. Ontologies such as ToxWiz provide a basis for application to toxicology investigations, whereas other ontologies under development in the biological, chemical, and biomedical communities could be incorporated in an extended future framework. OpenTox has provided a semantic web framework for the implementation of such ontologies into software applications and linked data resources. Bioclipse developers have shown the benefit of interoperability obtained through ontology by being able to link their workbench application with remote OpenTox web services. Although these developments are promising, an increased international coordination of efforts is greatly needed to develop a more unified, standardized, and open toxicology ontology framework.

Topics: Animals; Databases, Factual; Gene Expression Regulation; Humans; Toxicology; Vocabulary, Controlled

PubMed: 22562487
DOI: 10.14573/altex.2012.2.139

Authors: Lesley C Pepin, Jennie A Buchanan, Anthony F Pizon...

Topics: Adult; Curriculum; Education, Medical; Faculty, Medical; Fellowships and Scholarships; Female; Humans; Male; Middle Aged; Toxicology

PubMed: 33565003
DOI: 10.1007/s13181-021-00827-6

Review

Authors: Toshiyuki Kaji

Toxicology based on a deductive approach is called "deductive toxicology," which attempts to explain clinical and pathological findings by collecting all scientific information about the chemical substance under study and relating them to the essence of toxicity. We have introduced the method of signal toxicology into the deductive toxicology of metal and have shown that signal toxicity exists in heavy metals. Based on the results, we have proposed a new research strategy called "bioorganometallics," in which organic-inorganic hybrid molecules are used as molecular probes to analyze biological systems. This review outlines our research that has evolved from "deductive toxicology" to "bioorganometallics."

Topics: Metals, Heavy; Toxicology

PubMed: 37532572
DOI: 10.1248/yakushi.23-00103

Review

Authors: Shuyu Liu, Nuoya Yin, Francesco Faiola...

The development of stem cell biology has revolutionized regenerative medicine and its clinical applications. Another aspect through which stem cells would benefit human health is their use in toxicology. In fact, owing to their ability to differentiate into all the lineages of the human body, including germ cells, stem cells, and, in particular, pluripotent stem cells, can be utilized for the assessment, in vitro, of embryonic, developmental, reproductive, organ, and functional toxicities, relevant to human physiology, without employing live animal tests and with the possibility of high throughput applications. Thus, stem cell toxicology would tremendously assist in the toxicological evaluation of the increasing number of synthetic chemicals that we are exposed to, of which toxicity information is limited. In this review, we introduce stem cell toxicology, as an emerging branch of in vitro toxicology, which offers quick and efficient alternatives to traditional toxicology assessments. We first discuss the development of stem cell toxicology, and we then emphasize its advantages and highlight the achievements of human pluripotent stem cell-based toxicity research.

Topics: Animals; Drug-Related Side Effects and Adverse Reactions; Humans; Stem Cells; Toxicity Tests; Toxicology

PubMed: 28874109
DOI: 10.1089/scd.2017.0150

Authors: Luis M Botana, Vitor Vasconcelos

Rex Munday was a scientist working for AgResearch Ltd. in New Zealand. He was a leading figure in the area of marine toxin toxicity. His passing in July 2017 marked a loss for his family, as well as for colleagues who knew him as a dedicated professional, and a lively scientist with a great sense of humor.

Topics: History, 20th Century; History, 21st Century; Marine Toxins; New Zealand; Toxicology

PubMed: 28837074
DOI: 10.3390/toxins9090257

Authors: Marina P Sutunkova

The Special Issue "Toxicology, Nanotoxicology and Occupational Diseases" of the International Journal of Molecular Sciences includes six articles presenting the results of recent experimental studies in the fields of toxicology, nanotoxicology, and occupational health [...].

Topics: Humans; Nanostructures; Occupational Diseases; Occupational Exposure; Toxicology

PubMed: 36012476
DOI: 10.3390/ijms23169201